“I am depersonalized by scales of dead skin. Wherever I place my body everywhere
their islets remain. We, afflicted with psoriasis, yearn for love, although capable
cause only disgust. We notice everything in the world, butwe hate our own kind.
Figuratively speaking,truethe name of this disease is humiliation.
John Updike
.
.
Currently, in many countries of the world, immunosuppressants (or immunosuppressive drugs, immunosuppressants) are used to treat psoriasis and psoriatic arthritis. These are drugs used to provide artificial immunosuppression (artificial suppression of immunity). The action of these drugs is based, in particular, on a decrease in the ability of cells to divide. Some of these funds are used mainly in transplantation, and the other part in oncology. All these drugs can be used only as prescribed by doctors and under their strict supervision, with the parallel delivery of all necessary tests.
In no case can this article be regarded as a guide to the use of this kind of therapy!
Immunosuppressants can be divided into two groups: drugs that act on the entire body as a whole, and the so-called monoclonal antibodies that act only on certain circuits of the human immune system. If the former act on the entire body and require constant monitoring when taking them at the work of such vital organs as the liver, kidneys and cardiovascular system. The latter act only on that part of the human immune system that causes psoriasis and its subsequent manifestations. When taking them, it is necessary to conduct an immunological analysis in order not to miss negative changes in the functioning of the immune system. Most monoclonal antibodies do not affect the vital organs and their work, and some of them are approved for use in diseases such as hepatitis, kidney disease and other complex diseases.
One of the most striking achievements in the pharmacotherapy of human inflammatory diseases is the creation of anticytokine drugs (syn.: biological immune response modifiers, biologics, biologic response modifiers). The main areas of development in this area include the creation of monoclonal antibodies to certain determinants of immunocompetent cells or anti-inflammatory cytokines, recombinant anti-inflammatory cytokines and natural cytokine inhibitors (soluble receptors and receptor antagonists).
Psoriasis is a chronic inflammatory immune-dependent genodermatosis transmitted by a dominant type with incomplete penetrance, characterized by an increase in the proliferative activity of keratinocytes with a violation of keratinization processes and the development of pathological processes in the skin, nails and joints.
In developed countries, 1.5-2% of the population suffers from psoriasis. The overall average incidence in the world ranges from 0.6% to 4.8%. (Harvey L, Adam M., (2004); Naldi L., 2004).
Psoriatic arthritis is a chronic inflammatory disease of the joints, spine and tendons associated with psoriasis, belongs to a group of diseases under the general name seronegative spondyloarthropathies. The prevalence of psoriatic arthritis among patients with psoriasis, according to different authors, ranges from 7 to 40%.
Skin is an immune organ
The skin has almost all types of immunocompetent and phagocytic cells, being one of the main organs of the immune system. It produces almost all known lymphokines and cytokines. Keratinocytes express histocompatibility antigens responsible for the interaction of immunocompetent cells (ICAM) and intercellular adhesion molecules (ICAM) that provide physical contact between them, and also produce a complex of interleukins (1, 2, 3 and 6).
Langerhans cells They produce interleukin-1, tumor necrosis factor, interferons and other cytokines that affect the proliferation and intercellular interaction of various immunocompetent cells. They are the main antigen-presenting cells in psoriasis.
In healthy skin and mucous membranes, the content of cell subpopulations, and, accordingly, the ratio of pro- and anti-inflammatory regulatory cytokines is balanced, which ensures an adequate immune response to antigenic irritation. Thus, the participation of the skin in all types of immune responses makes it possible to recognize and eliminate various antigens, and independently perform the function of immune surveillance.
Some aspects of etiology and pathogenesis
The development of psoriasis is based on the inherited ability of a resting population of basal keratinocytes to transform under the influence of provoking factors into a population of proliferating cells. In the process of transition of stem cells into transit ones, the latter must start differentiation or return to the pool of stem cells. A patient with psoriasis, unlike healthy people, has an innate predisposition to disrupt this process, which, under appropriate conditions, is manifested by the transition of the bulk of transit cells to a population of dividing cells. The accelerated release of these cells to the surface of the skin leads to the fact that the processes of differentiation and keratinization do not have time to go through a full cycle, as a result of which pathological incompletely keratinized corneocytes are formed. The resulting cells, on the one hand, do not have normal adhesion to each other and form easily detachable scales, on the other hand, they are immunogenic. They initiate the production of autoantibodies, which, being fixed on them together with complement, produce interleukin-1 (IL-1). Probably, IL-1 is identical to the epidermal T-lymphocyte activating factor (ETAF), which is produced by keratinocytes and activates thymic lymphocytes. IL-1 determines the chemotaxis of T-lymphocytes and, by stimulating their migration into the epidermis, is responsible for the infiltration of the epidermis by these cells with the formation of an epidermal papule. . Interleukins and interferons produced by T-lymphocytes can themselves be mediators in the processes of hyperproliferation of keratinocytes, as well as mediators of inflammation, and thus contribute to maintaining the vicious circle that determines the chronic nature of psoriasis.
Numerous studies have shown that the leading role in the pathogenesis of immune inflammation belongs to TNF-a, which behaves as an active pro-inflammatory agent, being the key in the cytokine cascade. The importance of TNF-a in the pathogenesis of psoriasis is proved by the following facts: in patients with psoriasis, the production of TNF-a by circulating lymphocytes and macrophages is increased compared to healthy people. The level of TNF-a is increased both in psoriatic plaques and in the blood serum and synovial membrane in psoriatic arthritis. At the same time, the level of TNF-a and an increase in the number of receptors for it correlate with the activity of psoriasis. A mutation in the promoter region of the TNF-a gene is associated with the onset of psoriatic arthritis at a young age. TNF-a activated IL-1, IL-6, and IL-8 stimulate chondrocytes, osteoclasts, and fibroblasts, which produce metalloproteinases (eg, MMP-1 and MMP-3), ultimately leading to bone and cartilage erosion. At the same time, there is a deficiency of regulatory Th2 cytokines IL-10 and IL-4, as well as IL-11, soluble TNF-receptor antagonists and IL-1. IL-1 also plays an important role in the development of psoriatic arthritis due to mechanisms independent of TNF-a.
Based on the currently accepted pathogenesis of psoriasis and psoriatic arthritis, the most theoretically substantiated and universal method of treatment is therapy with biological immune response modifiers (anticytokine drugs).
The strategy of anticytokine therapy for psoriasis and psoriatic arthritis includes the following directions: elimination of pathological T cells, blocking of T cell activation or their migration into tissues, immune correction to change the effects of cytokines (increase in the level of Th2 cytokines to normalize Th1 / Th2 imbalance), binding of postsecretory cytokines. When prescribing treatment for patients with psoriasis, it is necessary to take into account the stage of the disease, the area of skin lesions, the severity of the process, age, gender, the presence of concomitant diseases and contraindications to a particular treatment method or drug. At the same time, a number of applied methods of treatment affect several pathogenetic links at once. Thus, treatment tactics should be chosen individually, taking into account the dominant disorders and previous therapy.
Monoclonal antibodies to TNF-a in the treatment of psoriasis and psoria. arthritis
Theory of selection of clones F.M. Burnet gave an answer to the question why, when an antigen enters the body, it causes the synthesis of precisely those antibodies that specifically react only with it. Subsequent experiments fully confirmed the position that antibodies are formed before encountering an antigen and independently of it. In 1975 discovered a way to create identical or monoclinal antibodies (MAT). Dozens of new MATs are under development or clinical trials. As early as 2004, Janice M. Reichert of the Center for the Study of Drug Development at Tufts University suggested that 16 of them would be licensed by the FDA within three years. In 2008 the volume of MAT trade around the world amounted to about 17 billion dollars.
By molecular standards, MATs are simply giants, each of them is a complex of two heavy and two light polypeptide chains, folded in an intricate way and equipped with complex sugars. To create a MAT-based drug, scientists usually start with an antibody taken from a mouse. They then humanize the molecule by manipulating the genes encoding it to replace part or all of the protein with amino acid sequences copied from human antibodies. The names of drugs created on the basis of MAT reflect their structure and basic properties. Thus, drugs with the “-cept” ending, when interacting with their rear end, cling to the cytokine, blocking it, and, accordingly, prevent cell cooperation; preparations with the ending “- ximab” contain animal MATs and, by binding to TNF-a, block it; with the ending "-mumab" - only human (humanized) MATs with a similar mechanism of action.
The greatest experience in the use of anticytokines in dermatology has been accumulated with the use of monoclinal antibodies to TNF-a in patients with psoriasis.
The first monoclinal antibodies to TNF-i, widely introduced into clinical practice, were named infliximab (Remicade, Schering-Plough). The drug was registered in Russia for the treatment of psoriatic arthritis in April 2005, for the treatment of psoriasis in April 2006. dated November 15, 2005).
Infliximab is a chimeric monoclinal antibody consisting of a variable (Fv) region of high-affinity neutralizing mouse monoclonal antibodies to TNF-a, connected to a fragment of the human IgGI k molecule, which generally occupies 2/3 of the antibody molecule and provides its effector functions. Infliximab binds to TNF-a with high specificity, affinity and avidity, forms stable complexes with TNF-a, inhibits the biological activity of free and membrane-associated TNF-a, does not interact with lymphotoxin (TNF-b), lyses (or induces) apoptosis of TNF-a producing cells.
According to pharmacokinetic studies, the maximum plasma concentration of infliximab is proportional to the administered dose, the volume of distribution corresponds to the intravascular distribution, and the half-life is 8-12 days. With repeated administration, infliximab does not accumulate in the body, its concentration in the blood corresponds to the administered dose. Infliximab is administered intravenously at a dose of 3 mg/kg or 5 mg/kg both as monotherapy and in combination with basic drugs (methotrexate or sulfasalazine). The duration of the infusion is about two hours. Infusions are repeated after 2 weeks, after 6 weeks, then once every two months.
Infliximab is a protein drug, so it does not undergo cytochrome P450-mediated metabolism in the liver. The effectiveness of Remicade has been demonstrated in rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, juvenile idiomatic arthritis, Still's disease in adults, systemic vasculitis, Behçet's disease, polymyositis, primary Sjögren's syndrome, secondary amyloidosis. In total, according to various indications, infliximab has been used to treat about 1 million patients worldwide. The pronounced effect of infliximab in autoimmune pathology associated with the Th1 type of immune response served as the basis for studying the drug in other diseases with similar pathogenesis, namely, psoriasis and psoriatic arthritis.
Currently, the world has accumulated experience in the use of monoclinal antibodies to TNF-a in thousands of patients with psoriasis. Chaudhari et al. (2001) were the first to conduct a double-blind, placebo-controlled study evaluating the efficacy of infliximab in 33 patients with moderate to severe plaque psoriasis. Patients were randomized into three groups: placebo (n = 11), infliximab 5 mg/kg (n = 11), and infliximab 10 mg/kg (n = 11). Infusions were performed at baseline and after 2 and 6 weeks. The results were evaluated after 10 weeks in all patients who started treatment according to two criteria: the general physician assessment (PGA) and the PASI index. In the infliximab 5 Mr/kr group, 9 (82%) of 11 patients responded (good and excellent effect according to the physician), in the placebo group - 2 (10%) of 11 patients (difference 64%, 95% confidence interval 20- 89, p = 0.0089). In the infliximab 10 mg/kg group, 10 (91%) of 11 patients responded to treatment (difference from placebo 73%, 95% confidence interval 30-94, p = 0.0019). Another criterion in this study was the dynamics of the PASI index. Its decrease by 75% is considered clinically significant, therefore, an important criterion for the effectiveness of treatment is not only the average decrease in the index, but also the percentage of patients in whom it decreased by 75% or more. A decrease in PASI by 75% was observed in 9 (82%) and 8 (73%) patients who received infliximab at doses of 5 and 10 mg/kg, and only 2 (18%) patients in the placebo group. The average PASI index in the three groups decreased from 22.1, 26.6 and 20.3 to 3.8, 5.9 and 17.5, respectively (p< 0,0003). Различие между двумя группами больных, получавших активное лечение, и группой плацебо достигало статистической значимости через 2 недели (р < 0,003), а медиана времени до достижения ответа составила 4 недели в обеих группах больных, получавших инфликсимаб. Серьезных нежелательных явлений зарегистрировано не было, а переносимость инфликсимаба была хорошей.
Subsequently, convincing results indicating the high efficacy of infliximab in psoriasis were obtained during the international, multicenter, randomized, double-blind, placebo-controlled SPIRIT study, the results of which were presented by A. Gottlieb at the 12th congress of the European Association of Dermatovenereologists (EADV, 2003). The 249 patients were divided into three groups: placebo (n = 51), infliximab 3 mg/kg (n = 99) and infliximab 5 mg/kg (n = 99). The study included patients over 18 years of age with plaque psoriasis for more than 6 months. Previous systemic treatment or PUVA therapy was ineffective in them, the PASI index exceeded 12. Exclusion criteria: active or latent tuberculosis, serious infectious diseases less than 2 months before the start of treatment, lymphoproliferative diseases and/or malignancies less than 5 years before initiation of infliximab therapy.
Results were evaluated every 2 weeks for 26 weeks in all patients according to the same criteria as Chaudhari et al. (2001). Infusions were performed at baseline and after 2 and 6 weeks. It was found that the positive dynamics of rashes against the background of the first dose of infliximab occurs very quickly - within the first two weeks. The PASI index rapidly and statistically decreases by 75% during the first 4 weeks (Fig. 2). Infliximab 5 mg/kg is more effective than 3 mg/kg. The drug is well tolerated. Side effects are similar to those in the treatment of rheumatoid arthritis, Crohn's disease and ankylosing spondylitis. Upper respiratory tract infections were most frequently reported: 13.7% in the placebo group, 16.3% infliximab 3 mg/kg, and 14.1% infliximab 5 mg/kg, i.e. the difference in the incidence of side effects was unreliable. The authors proved that treatment with infliximab improves the quality of life of a patient with psoriasis.
At the 12th EADV congress (2003) Ch. Antoni reported the results of a double-blind, randomized, placebo-controlled, multicenter IMPACT study (Inflixirnab Multinational Psoriatic A>tritis Controlled Trial). The efficacy of infliximab at a dose of 5 mg/kg was evaluated in 52 patients with active psoriatic arthritis. The drug was administered initially, after 2, 6 and 14 weeks, then once every 8 weeks for 102 weeks (2 years). The normalization of the histological picture of the skin during treatment with infliximab was demonstrated, as well as a statistically significant improvement in the articular process according to the criteria of ACR (American College of Rheumatology), Clegg DO et al. and the results of magnetic resonance imaging.
Between May 2007 and to January 2009 in the clinic of skin and venereal diseases of the Military Medical Academy. CM. Kirov under observation were 10 patients with psoriasis (1 woman and 9 men), refractory to previous therapy. The age of patients is from 32 to 70 years, the duration of the disease is from 7 to 35 years. Most of the patients (9) suffered from arthropathic, 1 - from common psoriasis vulgaris. Previous therapy was ineffective in all patients: traditional "basic" treatment - in all, PUVA - 5, methotrexate - 3, raptiva - 1.
Before each infusion, the following indicators were evaluated: PASI, DLQI, data from laboratory blood tests (general clinical blood test, biochemical blood test, immunological blood test).
Infliximab was administered at a dose of 5.0 mg/kg intravenously: initially, after 2 weeks, after 6 weeks, and then once every 8 weeks.
The clinical response to treatment with infliximab was manifested already 2 weeks after the start of therapy: peeling and exudative phenomena decreased, the halo of hyperemia around papules and plaques disappeared, Voronov's pseudoatrophic rim appeared, and infiltration of elements significantly decreased. After 8 weeks, PASI decreased by 75% and DLQI by 90% in 7 patients, in 3 patients PASI and DLQI were 0 points. After 10 weeks, all patients showed normalization of the immunological parameters of the blood (both from the cellular and humoral levels of immunity). By the 24th week, clinics were observed - immunological remission in all patients who were on treatment.
The obtained results indicate that the use of infliximab in the treatment of patients with severe forms of psoriasis and psoriatic arthritis provides high clinical efficacy, favorably affects the quality of life of patients, reduces relapses and prolongs immunological remission.
.
Conclusion
.
The introduction of biological modifiers of the immune response into clinical practice has become one of the greatest achievements of medicine in the last decade. The main advantage of anticytokine drugs is their pathogenetic focus in the treatment of psoriasis. They belong to the group of so-called disease-modifying drugs. To date, it has been reliably established that infliximab (Remicade) is effective in psoriasis refractory to any other therapy. The obtained results indicate that its use of infliximab in the treatment of psoriasis and psoriatic arthritis provides high clinical efficacy, significantly improves the quality of life of patients, helps to reduce relapses, and prolongs the clinic - immunological remission.
In modern medicine, immunosuppressants are used only for severe and moderate forms of psoriasis, as well as for psoriatic arthritis. Descriptions of a number of immunosuppressants can be found on p.
For Cimzia, Cimzia (certolizumab) and Simponi/Simponi (golimumab/golimumab) are under investigation.
.
The following are descriptions of the major immunosuppressants.
.
Cyclosporine
.
The active ingredient is cyclosporine.
Commercial names: Vero-Cyclosporin; Imusporin; Consupren; Panimun Bioral; R-Immun; Sandimmun; Sandimmun-Neoral; Cycloprene; Cycloral; Cyclosporine; Cyclosporine-vero; Cyclosporine-Hexal; Ecoral.
Cyclosporine (also known as Cyclosporine A) is a potent immunosuppressant drug. It has a selective effect on T-lymphocytes, inhibits the development of cellular and humoral immunity reactions that depend on T-lymphocytes. There have been successful bone marrow and solid organ transplants (kidney, liver, heart, lung, pancreas) in humans using Cyclosporine to prevent and treat transplant rejection and graft-versus-host disease. Beneficial effects have also been demonstrated in the treatment of various conditions that are autoimmune in nature or may be considered as such (acute non-infectious uveitis, Behcet's uveitis, nephrotic syndrome and glomerulonephritis, rheumatoid arthritis, psoriasis, atopic dermatitis).
Dosage forms:
Capsules. Solution for oral administration. Concentrate for infusion.
Properties / Action:
Cyclosporine (also known as Cyclosporine A) is an immunosuppressant drug, a cyclic polypeptide consisting of 11 amino acids. Cyclosporine is a potent immunosuppressive agent that in animals increases the lifetime of allogeneic grafts of the skin, heart, kidney, pancreas, bone marrow, small intestine, and lungs. Cyclosporine has a selective effect on T-lymphocytes. Prevents the activation of lymphocytes. At the cellular level, it blocks resting lymphocytes in the G0 or G1 phases of the cell cycle and suppresses antigen-triggered production and secretion of lymphokines (including interleukin-2, T-lymphocyte growth factor) by activated T-lymphocytes. The data obtained indicate that Cyclosporine has a specific and reversible effect on lymphocytes. Cyclosporine inhibits the development of T-lymphocyte-dependent cellular and humoral immune responses, including allograft immunity, delayed-type skin hypersensitivity, allergic encephalomyelitis, Freund's adjuvant arthritis, and graft-versus-host disease (GVHD). Unlike cytostatics, Cyclosporine does not suppress hematopoiesis and does not affect the function of phagocytes. Patients receiving Cyclosporine are less susceptible to infections than patients receiving other immunosuppressive drugs. There have been successful bone marrow and solid organ transplants in humans using Cyclosporine to prevent and treat rejection and GVHD. The positive effects of Cyclosporine have also been demonstrated in the treatment of various conditions that are autoimmune in nature or may be considered as such.
Indications:
Transplantation (prevention of graft rejection, treatment of rejection, prevention and treatment of graft versus host disease): kidney, liver, heart, lung, combined cardiopulmonary transplant, pancreas; bone marrow transplantation. Autoimmune and other diseases: acute non-infectious uveitis, threatening loss of vision; uveitis of the middle or posterior part of the eye; Behcet's uveitis with recurrent inflammation and retinal involvement; nephrotic syndrome in adults and children (steroid-dependent and steroid-resistant form) due to glomerular pathology, such as minimal change nephropathy, focal and segmental glomerulosclerosis, membranous glomerulonephritis; rheumatoid arthritis with a high degree of activity (in cases where classic slow-acting antirheumatic drugs are ineffective or cannot be used); severe psoriasis, usually in cases of resistance to previous treatment; severe forms of atopic dermatitis when systemic therapy is indicated. Oral formulations may be used to induce and maintain remission, incl. caused by steroids (hydrocortisone, prednisolone, dexamethasone, betamethasone), which allows them to be canceled.
Contraindications:
individual intolerance (including history of hypersensitivity) to cyclosporine; malignant neoplasms, precancerous skin diseases; severe infectious diseases, chickenpox, Herpes zoster (risk of generalization of the process); severe impairment of kidney and liver function, liver failure, renal failure; uncontrolled arterial hypertension; hyperuricemia, hyperkalemia; pregnancy, breast-feeding (during treatment is excluded).
Experience with the use of Cyclosporine in pregnant women is limited. Data obtained from patients with transplanted organs show that, compared with conventional methods of treatment, Cyclosporine therapy does not cause an increased risk of adverse effects on the course and outcome of pregnancy. However, adequate and well-controlled studies in pregnant women have not been conducted, therefore Cyclosporine can be used during pregnancy only if the expected benefit justifies the potential risk to the fetus. Cyclosporine is excreted in breast milk. During breastfeeding, you should stop taking the drug or stop breastfeeding.
Methotrexate
.
Methotrexate Lahem
International non-proprietary name Methotrexate (Methotrexate)
Dosage form
transparent solution for injections of yellow-orange color.
Composition
METHOTREXATE Lahema 5 mg, solution for injection 1 bottle contains: Methotrexate 5 mg, sodium chloride 16.5 mg, sodium hydroxide in the amount necessary to adjust the pH, water for injection 2 ml.
METHOTREXATE Lahema 20 mg, solution for injection 1 bottle contains: Methotrexate 20 mg, sodium chloride 14 mg, sodium hydroxide in the amount necessary to adjust the pH, water for injection 2 ml.
METHOTREXATE Lahema 50 mg, solution for injection 1 bottle contains: Methotrexate 50 mg, sodium chloride 35 mg, sodium hydroxide in the amount necessary to adjust the pH, water for injection 5 ml.
METHOTREXATE Lahema 1000 mg, solution for injection 1 bottle contains: Methotrexate 1000 mg, sodium chloride 50 mg, sodium hydroxide in the amount necessary to adjust the pH, water for injection 20 ml.
Indications
trophoblastic tumors, acute leukemias (especially lymphoblastic and myeloblastic variants), neuroleukemias, non-Hodgkin's lymphomas, including lymphosarcomas, breast cancer, head and neck squamous cell carcinoma, lung cancer, skin cancer, cervical and vulvar cancer, esophageal cancer, kidney cancer, cancer bladder, testicular and ovarian germ cell tumors, penile cancer, retinoblastoma, medulloblastoma, osteogenic sarcoma and soft tissue sarcoma, Ewing's sarcoma, severe forms of psoriasis, fungal mycosis (far advanced stages), rheumatoid arthritis (with the ineffectiveness of standard therapy).
Contraindications
Methotrexate has teratogenic properties and can cause fetal death, as a result of which it is contraindicated in pregnant women. Methotrexate is excreted in breast milk, so it should not be given to women during breastfeeding. Methotrexate is contraindicated in patients with severe anemia, leukopenia, thrombocytopenia, renal or hepatic insufficiency, patients with current or recent chickenpox, patients with herpes zoster, or other infections. Methotrexate cannot be administered to patients with hypersensitivity to this drug.
Adverse reactions
Hematopoietic system: Leukopenia, neutropenia, lymphopenia (especially T-lymphocytes), thrombocytopenia, anemia. Gastrointestinal tract and liver: Anorexia, nausea, vomiting, stomatitis, gingivitis, glossitis, enteritis, diarrhea, erosive and ulcerative lesions of the gastrointestinal tract, abnormal liver function, fibrosis and cirrhosis of the liver (their likelihood is increased in patients receiving long-term continuous or daily methotrexate therapy). Nervous system: Encephalopathy, especially with the introduction of multiple doses intrathecally, as well as in patients who received radiation therapy to the skull. There are also reports of fatigue, weakness, confusion, ataxia, tremors, irritability, convulsions and coma. Acute side effects caused by intrathecal administration of methotrexate may include dizziness, blurred vision, headache, back pain, stiffness of the back of the neck, convulsions, paralysis, hemiparesis. Urinary system: Renal impairment is dose dependent. The risk of impairment is increased in patients with reduced renal function or dehydration, as well as in patients taking other nephrotoxic drugs. Renal failure is manifested by elevated levels of creatinine and hematuria. Perhaps the appearance of cystitis. Reproductive system: violation of the process of oogenesis, spermatogenesis, changes in fertility, teratogenic effects. Dermatological phenomena: Skin erythema and / or rash, urticaria, alopecia (rare), photosensitivity, furunculosis, depigmentation or hyperpigmentation, acne, skin peeling, blistering, folliculitis. Allergic reactions: Fever, chills, rash, urticaria, anaphylaxis. Organs of vision: Conjunctivitis, excessive lacrimation, cataracts, photophobia, cortical blindness (at high doses). Immune status: Immunosuppression, reduced resistance to injection diseases. Other: Malaise, osteoporosis, hyperuricemia, vasculitis. Rarely - pneumonitis, pulmonary fibrosis.
Warning and Precautions:
Methotrexate is a cytotoxic drug, so care must be taken when handling it. Dosage forms containing preservatives, in particular benzyl alcohol, must not be used for intrathecal administration and for high-dose therapy. With the introduction of high doses of Methotrexate, careful monitoring of the patient is necessary for early detection of the first signs of toxic reactions. During therapy with Methotrexate in high and high doses, it is necessary to monitor the pH of the urine: on the day of administration and in the next 2-3 days, the urine reaction should be alkaline. This is achieved by intravenous drip of a mixture consisting of 40 ml of a 4.2% sodium bicarbonate solution and 400-800 ml of an isotonic sodium chloride solution on the eve, on the day of treatment and in the next 2-3 days. Treatment with Methotrexate at elevated and high doses must be combined with enhanced hydration up to 2 liters of fluid per day. The introduction of Methotrexate at a dose of 2 g/m2 and above is carried out under the control of its concentration in the blood serum. Normal is a decrease in the content of methotrexate in the blood serum 22 hours after administration by 2 times compared with the initial level. Increasing the level of creatinine by 50% or more of the initial content and / or an increase in the level of bilirubin require intensive detoxification therapy. For the treatment of psoriasis, Methotrexate is prescribed only for patients with a severe form of the disease who are not amenable to treatment with other types of therapy. To prevent toxicity during treatment with Methotrexate, periodic blood tests, determination of the content of leukocytes and platelets, and liver and kidney function tests are necessary. With the development of diarrhea and ulcerative stomatitis, Methotrexate therapy must be interrupted, otherwise it can lead to the development of hemorrhagic enteritis and death of the patient due to intestinal perforation. In patients with impaired liver function, the period of detection of Methotrexate is increased, therefore, in such patients, therapy should be carried out with extreme caution, using reduced doses. At the moment, it is also used to reduce the amount of antibodies during cytostatic therapy with monoclonal antibodies, together with the introduction of remicade in patients with psoriasis.
Arava
.
Leflunomide: Arava; Leflunomide.
Arava is a basic antirheumatic drug. It has antiproliferative, immunosuppressive and anti-inflammatory effects. It is used as a basic remedy for the treatment of adult patients with active rheumatoid arthritis in order to reduce the symptoms of the disease and delay the development of structural damage to the joints. The clinical effect is manifested after 4-6 weeks of administration and may further increase over 4-6 months.
Latin name:
ARAVA / ARAVA.
Composition and forms of release:
Arava film-coated tablets, 30 or 100 pcs. packaged. 1 Arava tablet contains: Leflunomide 10 or 20 mg. Arava film-coated tablets, 3 pcs. packaged. 1 Arava tablet contains: Leflunomide 100 mg. Active active substance: Leflunomide / Leflunomide.
Properties / Action:
Arava is an antirheumatic and immunosuppressive drug. Belongs to the class of basic antirheumatic drugs. Arava has anti-proliferative, immunosuppressive and anti-inflammatory properties. The active metabolite of Arava (leflunomide) A771726 inhibits the enzyme dehydroorotate dehydrogenase and has an antiproliferative effect. A771726 in vitro inhibits mitogen-induced proliferation and DNA synthesis of T-lymphocytes. The antiproliferative activity of A771726 appears to be manifested at the level of pyrimidine biosynthesis, since the addition of uridine to the cell culture eliminates the inhibitory effect of the A771726 metabolite. Using radioisotope ligands, it was shown that A771726 selectively binds to the enzyme dehydroorotate dehydrogenase, which explains its ability to inhibit this enzyme and the proliferation of lymphocytes at the G1 stage. Lymphocyte proliferation is one of the key stages in the development of rheumatoid arthritis. At the same time, A771726 inhibits the expression of receptors for interleukin-2 (CB-25) and the Ki-67 and PCNA core antigens associated with the cell cycle. The therapeutic effect of Arava (leflunomide) has been shown in several experimental models of autoimmune diseases, including rheumatoid arthritis. The clinical effect of Arava usually appears after 4-6 weeks of use and may increase further over 4-6 months. Three large randomized trials, in which a total of 1839 patients participated, proved the high efficacy of Arava and a faster onset of clinical action compared to methotrexate and sulfasalazine.
Indications:
Arava is used as a basic treatment for adult patients with active rheumatoid arthritis in order to reduce the symptoms of the disease and delay the development of structural damage to the joints.
Contraindications:
individual intolerance (including history of hypersensitivity) to leflunomide or other components of the drug Arava; liver dysfunction; severe immunodeficiency (eg, AIDS); violation of bone marrow hematopoiesis; anemia, leukopenia or thrombocytopenia not associated with rheumatoid arthritis; severe uncontrolled infections; moderate or severe renal insufficiency (due to little clinical experience); severe hypoproteinemia (for example, with nephrotic syndrome); pregnancy (should be ruled out before starting treatment with Arava); women of childbearing age who do not use adequate contraception during the period of treatment with Arava and while the plasma level of the active metabolite is above 0.02 mg / l; breastfeeding period; patients under 18 years of age (since there are no data on efficacy and safety in this group of patients).
Use during pregnancy and lactation:
In experimental studies, it was found that Arava can have a fetotoxic and teratogenic effect. Arava should not be used during pregnancy and in women of childbearing age who are not using reliable contraceptives. It is necessary to make sure that there is no pregnancy before starting treatment. Patients should be informed that if pregnancy is suspected, they should immediately consult a doctor and take a pregnancy test. If the test is positive, the doctor should inform the patient about the possible risk to the fetus. Women of childbearing age should be informed that it must take 2 years after discontinuation of treatment with Arava (leflunomide) before they can become pregnant. Women who are taking Arava and want to become pregnant (or who are already pregnant) are advised to carry out a drug “washout” procedure that will quickly reduce plasma concentrations of leflunomide and its metabolite (see overdose). Next, you need to determine the concentration of the metabolite A771726 2 times with an interval of 14 days. From the moment when the concentration of the drug is fixed below 20 mcg / l until the moment of fertilization, 1.5 months should pass. It should be borne in mind that without the procedure for “washing out” the drug, a decrease in the concentration of the metabolite below 20 μg / l occurs after 2 years. Cholestyramine and activated charcoal can interfere with the absorption of estrogen and progesterone in such a way that reliable oral contraceptives do not guarantee the necessary contraception during the drug withdrawal period. It is recommended to use alternative methods of contraception. Animal studies have shown that leflunomide or its metabolites are excreted in breast milk. Therefore, if it is necessary to prescribe Arava during lactation, the issue of stopping breastfeeding should be resolved. Currently, there is no information confirming the relationship between taking Arava in men and the fetotoxic effect of the drug. Experimental studies in this direction have not been carried out. However, men treated with leflunomide should be warned of the possible fetotoxic effects of Arava and of the need to use adequate contraceptives. To reduce the risk as much as possible when planning a pregnancy, it is necessary to stop taking Arava and use the “laundering” procedure.
Side effects:
Classification of the estimated frequency of side effects of Arava: typical = 1-10% of patients; atypical = 0.1-1% of patients; rare = 0.01–0.1% of patients; very rare = 0.01% of patients or less.
From the side of the cardiovascular system: typical: increased blood pressure.
On the part of the digestive system: typical: diarrhea, nausea, vomiting, anorexia, diseases of the oral mucosa (aphthous stomatitis, ulceration of the lips), pain in the abdominal cavity, an increase in liver transaminases (ALT, less often gamma-HT), alkaline phosphatase, bilirubin; rare: hepatitis, jaundice/cholestasis; very rarely: liver failure, acute liver necrosis.
From the nervous system: typical: headache, dizziness, asthenia, paresthesia; atypical: taste disturbance, anxiety.
From the musculoskeletal system: typical: tendovaginitis; atypical: rupture of ligaments.
From the genitourinary system: the possibility of a reversible decrease in the concentration of sperm, the total number of spermatozoa and their motility cannot be ruled out.
From the side of the hematopoietic system, the lymphatic system: typical: leukopenia (leukocytes more than 2000/mkl); atypical: anemia, mild thrombocytopenia (platelets less than 100,000/µl); rare: eosinophilia, leukopenia (leukocytes less than 2000/µl), pancytopenia (possibly through an antiproliferative mechanism); very rare: agranulocytosis. Recent, concomitant or subsequent use of potentially myelotoxic agents may be associated with a greater risk of haematological effects. The risk of malignancy, especially lymphoproliferative diseases, is increased with the use of certain immunosuppressive drugs.
Infections: very rare: the development of severe infections and sepsis. Immunosuppressive drugs are known to increase susceptibility to infections. The number of possible infections (rhinitis, bronchitis and pneumonia) may increase.
Dermatological reactions: typical: increased hair loss, eczema, dry skin; atypical: Stevens-Johnson syndrome, Lyell's syndrome, erythema multiforme.
Allergic reactions: typical: mild allergic reactions, rash (including maculopapular rash), itching; atypical: urticaria; very rare: serious anaphylactic/anaphylactoid reactions.
From the side of metabolic processes: typical: weight loss (usually insignificant); atypical: hypokalemia. Mild hyperlipidemia may occur. Uric acid levels usually decrease. Laboratory data, not clinically confirmed, indicate a slight increase in the levels of lactate dehydrogenase and creatine phosphokinase in blood plasma. Atypical presentation is mild hypophosphatemia.
The active metabolite of leflunomide, A771726, has a long half-life, typically one to four weeks. If serious adverse effects occur after taking Arava (leflunomide), or if for any other reason it is necessary to quickly clear the body of A771726, then the “washout” procedure should be followed (see overdose). The procedure can be repeated according to clinical indications. If severe immunological or allergic reactions such as Stevens-Johnson syndrome or Lyell's syndrome are suspected, a complete washout procedure is required.
Special instructions and precautions:
Arava can be prescribed to patients only after a thorough medical examination.
Before starting treatment with Arava, it is necessary to be aware of the possible increase in the number of side effects in patients who have previously received other basic drugs for the treatment of rheumatoid arthritis, which have hepato- and hematotoxic effects.
The active metabolite of leflunomide, A771726, has a long half-life, typically 1 to 4 weeks. Serious adverse effects (eg, hepatotoxicity, hematotoxicity, or allergic reactions) may occur even if treatment with leflunomide is discontinued. Therefore, if such cases of toxicity occur or when switching to another basic drug (for example, methotrexate) after treatment with leflunomide, it is necessary to carry out the “washout” procedure (see overdose).
Liver reactions. Since the active metabolite of leflunomide, A771726, is protein-bound and excreted via hepatic metabolism and bile secretion, plasma levels of A771726 are expected to be elevated in patients with hypoproteinemia. Arava is contraindicated in patients with severe hypoproteinemia or hepatic impairment. Rare cases of severe liver damage, in some cases fatal, have been reported during treatment with Arava (leflunomide). Most of these cases were observed in the first six months of treatment. Although a causal relationship of these adverse events with leflunomide has not been established, and in most cases there were several additional suspicious factors, the exact implementation of recommendations for monitoring treatment is considered mandatory. ALT levels should be checked before initiating Arava therapy and then every month for the first 6 months of treatment, followed by a check every 2-3 months. The following recommendations are available for adjusting the dosing regimen or discontinuing Arava, depending on the severity and persistence of the increase in ALT levels. With a confirmed 2-3-fold excess of the upper limit of the norm of ALT, reducing the dose from 20 mg to 10 mg per day may allow you to continue taking Arava, provided that this indicator is carefully monitored. If 2-3 times the upper limit of normal ALT persists, or if there is a rise in ALT levels that exceeds the upper limit of normal more than 3 times the upper limit of normal, Arava should be discontinued and the “washout” procedure should be started. Due to possible additional hepatotoxic effects, it is recommended to refrain from drinking alcohol during treatment with Aravaya (leflunomide).
hematological reactions. A complete clinical blood count, including determination of the leukocyte count and platelet count, should be performed before starting treatment with Arava (leflunomide), as well as every 2 weeks during the first 6 months of treatment and every 8 weeks after treatment is completed. In patients with pre-existing anemia, leukopenia and / or thrombocytopenia, as well as in patients with impaired bone marrow function or at risk of developing such disorders, the risk of hematological disorders increases. If such phenomena occur, a "washout" procedure should be used to reduce the level of A771726 in the blood plasma. In case of development of serious hematological reactions, including pancytopenia, it is necessary to stop taking Arava; and any other concomitant drug that suppresses bone marrow hematopoiesis, and begin the "washing" procedure.
Combined use with other types of treatment. At present, there is no information regarding the co-administration of Arava (leflunomide) with antimalarial drugs used in rheumatology (chloroquine and hydroxychloroquine), intramuscularly or orally administered gold preparations (krizanol, auranofin), D-penicillamine, azathioprine and other immunosuppressive drugs (with the exception of methotrexate). The risk associated with the appointment of complex therapy is not known, especially with long-term treatment. Since this kind of therapy can lead to the development of additional or even synergistic toxicity (eg, hepato- or hematotoxicity), combinations of Arava with other basic drugs (eg, methotrexate) are not desirable.
Transition to other types of treatment. Because leflunomide persists in the body for a long time, switching to a different host drug (eg, methotrexate) without an appropriate washout procedure may increase the possibility of additional risk even long after the switch (eg, kinetic interaction, organotoxicity). Similarly, recent treatment with hepatotoxic or hematotoxic drugs (eg, methotrexate) may lead to an increase in the number of side effects, therefore, when starting treatment with Arava (leflunomide), it is necessary to carefully consider all the positive and negative aspects associated with taking this drug.
Skin reactions. If ulcerative stomatitis develops, Arava should be discontinued. Very rare cases of Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported in patients treated with Arava (leflunomide). In the event of skin and / or mucous reactions, it is necessary to stop taking Arava; and any other drug related to it and immediately begin the procedure of "laundering". In such cases, complete "laundering" is essential. In such cases, re-appointment of Arava is contraindicated.
Infections. It is known that drugs like Arava (leflunomide) with immunosuppressive properties make patients more susceptible to various infections. The resulting infectious diseases are usually severe and require early and intensive treatment. If a severe infectious disease occurs, it may be necessary to interrupt treatment with Arava (leflunomide) and start a “washout” procedure. Patients with tuberculin reactivity should be closely monitored because of the risk of tuberculosis reactivation. Given the long withdrawal period of Arava, it is not recommended to vaccinate with live vaccines during treatment.
Arterial pressure. Before starting treatment with Arava and periodically after its initiation, the level of blood pressure should be monitored.
Enbrel
Enbrel is a dimeric synthesized protein produced by recombinant DNA technology. Supplied in the form of 1 ml sterile disposable prefilled syringes for hypodermic injection, containing no preservative. The solution is colorless, transparent. Also available in reusable vials as a sterile white lyophilized powder, diluted with the supplied sterile bacteriostatic water. The dose of the drug also contains neutral components (mannitol, sucrose, tromethamine).
Enbrel binds to tumor necrosis factor (TNF) and blocks its interaction with TNF receptors on the cell surface. This prevents inflammation and the immune response of cells, which plays a big role in diseases such as ankylosing spondylitis, rheumatoid and psoriatic arthritis, psoriasis. The effectiveness of Enbrel in these diseases has been confirmed by clinical trials (see link). The standard use of the drug is 50 mg per week, which is divided into 2 subcutaneous injections of 25 mg. Perhaps the use of a single dose of 50 mg once a week. Clinical trials have not revealed differences in the action and effectiveness of the drug between the two indicated methods of application.
Application.
Enbrel is used to reduce clinical symptoms, delay structural changes and improve the physical condition of patients with rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, ankylosing spondylitis, psoriasis (supposed to be treated with phototherapy or systemic therapy). Can be used in conjunction with methotrexate.
Restrictions.
The drug can not be used in patients with sepsis or hypersensitivity to the components of the drug.
Warnings.
At the injection site, local effects are possible (redness, swelling, etc.), which quickly pass. Patients with cardiac disorders require special attention and observation. The effect of the drug has not been tested in patients with reduced immunity and chronic infectious diseases. Patients using Enbrel can be vaccinated without restrictions, with the exception of the use of "live" vaccines, the interaction with which has not been studied. However, it is recommended to carry out the necessary vaccination before starting the Enbrel course. If signs of the varicella virus are detected, Enbrel should be temporarily discontinued and treated with varicella zoster immunoglobulin. The use of Enbrel can lead to the production of autoantibodies, and very rarely to the development of lupus syndrome, which is eliminated by discontinuation of the drug. If such symptoms occur, treatment should be discontinued and the patient examined. Cross-action with other drugs has not been identified, but you should carefully consider the joint use of the drug with methotrexate. Serious infections were noted in 7% of patients using the drug in conjunction with the anti-arthritic drug Anakinra, neutropenia was detected in 2%.
Mutagenic activity of the drug during the studies was not revealed.
Animal studies of high doses of the drug did not reveal any effect on the fetus, however, in case of pregnancy, it is recommended to use Enbrel in case of real need due to the lack of sufficient studies. The systemic effect and penetration into milk has not been clarified, therefore it is recommended, just in case, not to use the drug during breastfeeding or to stop feeding for the period of drug use.
The specific effect of the drug, when used in patients over 65 years of age, was not detected, the effect does not differ depending on age, elderly patients require increased attention, as with other drugs.
The use of the drug in children under 4 years of age has not been studied.
Dosage.
Arthritis PA, RA - a single weekly dose of 50 mg subcutaneously. Increasing the dose to 50 mg twice a week did not give a noticeable effect, but increased the number of side effects. The use of more than 50 mg per week is not recommended. Psoriasis - starting dose of 50 mg twice a week with a break of 3-4 days for 3 months, then switching to a maintenance dose of 50 mg once a week. In children under 17 years of age, the calculation of the drug is 0.8 mg / kg of weight, but not more than 50 mg per week.
Side effects (ischemia, thrombosis, thrombophlebitis, changes in blood pressure, lymphadenopathy, bursitis, polymyositis, cholecystitis, pancreatitis, gastrointestinal hemorrhage, depression, sclerosis, worsening of psoriasis, glomerulonephropathy) were observed in patients with arthritis in the amount<5%, у пациентов с псориазом <1.5%.
.
Amevi
.
Active ingredient: Alefacept (Alefacept), immunosuppressant
Manufacturer: Biogen
Composition and form of release: 15 mg / 0.5 ml
Individual dose consisting of 1 bottle of the drug and 1 bottle of water for dilution. The package contains 1 or 4 doses.
Injection: 15 mg once a week, intramuscularly. The recommended course is 12 injections. A second course can be carried out after confirmation of a normal level of CD4 + T lymphocytes and at least a 12-week break. Mandatory control of the number of CD4 + T lymphocytes at least a week before the start of the first injection and throughout the course. At a level of less than 250 cells / μl, which persists for a month, the use of the drug must be discontinued.
Indications for use
Treatment of chronic moderate and severe psoriasis in adult patients.
Contraindications
hypersensitivity to ameviv and other components of the drug.
Side effects
While taking ameviva, hypersensitivity reactions (urticaria, angioedema) may occur. Lymphopenia, malignancy, serious infections requiring hospitalization.
Special instructions: Depending on the dose, ameviv suppresses CD4+ and CD8+ T lymphocytes. The drug should not be used in patients with below-normal CD4+ T lymphocyte levels. May increase the risk of malignant neoplasms, infectious diseases and manifestations of chronic latent infections. Ameviv should not be used in known chronic infections or in the presence of infectious symptoms. New infections occurring during or after the end of the course should be carefully monitored. If signs of infection develop, the use of Ameviv should be discontinued. Patients should not receive any other immunosuppressive therapy or phototherapy to avoid excessive immunosuppression. The repeated use of ameviv in combination with other immunosuppressive methods has not been studied. The efficacy of vaccines and live vaccines has not been studied in patients.
Pregnancy and lactation
It is necessary to notify the doctor about pregnancy during the use of ameviva or within 8 weeks after the end of the course. When breastfeeding, you should choose in order of importance - cessation of feeding or discontinuation of the drug. Amevi should be used with extreme caution in the elderly. The drug is not intended for children.
Remicade
COMPOSITION
Active substance: infliximab (infliximab).
Excipients: sucrose, polysorbate 80, sodium dihydrogen phosphate, sodium hydrogen phosphate.
Description
Lyophilizate in the form of a dense mass of white color without signs of melting, not containing foreign inclusions.
PHARMACOTHERAPEUTIC GROUP
Selective immunosuppressants. ATX code: L04AA12.
Biological properties
Remicade is a chimeric compound based on hybrid mouse and human IgG1 monoclonal antibodies. Remicade has a high affinity for tumor necrosis factor alpha (TNFa), which is a cytokine with a wide range of biological activities, including mediating the inflammatory response and participating in immune system responses. It is clear that TNFa plays a role in the development of autoimmune and inflammatory diseases. Remicade quickly binds and forms a stable compound with both forms (soluble and transmembrane) of human tumor necrosis factor alpha, while reducing the functional activity of TNF-a.
The specificity of Remicade for TNFa is confirmed by its inability to neutralize the cytotoxic effect of alpha lymphotoxin (LTa or TNFb), a cytokine that can bind to the same receptors as TNFa.
INDICATIONS FOR USE
Rheumatoid arthritis. Treatment of patients with active rheumatoid arthritis who have failed previous treatment with disease-modifying antirheumatic drugs (DMARDs), including methotrexate, and treatment of patients with severe progressive active rheumatoid arthritis who have not previously been treated with methotrexate or other disease-modifying antirheumatic drugs. Treatment is carried out in combination with methotrexate. Combined treatment with Remicade and methotrexate can reduce the symptoms of the disease, improve the functional state and slow the progression of joint damage.
Crohn's disease. Treatment of patients suffering from active, severe Crohn's disease, including those with fistula formation, who do not have sufficient effect from standard therapy (or have contraindications to its implementation), including corticosteroids and / or immunosuppressants (in the fistulous form - antibiotics, immunosuppressants and drainage). Treatment with Remicade helps to reduce the symptoms of the disease, achieve and maintain remission, heal the mucous membranes and close fistulas, reduce the number of fistulas, and improve the quality of life of patients.
Ulcerative colitis. Treatment of patients suffering from ulcerative colitis in whom traditional therapy has not been effective enough. Treatment with Remicade helps to heal the intestinal mucosa, reduce symptoms of the disease, reduce the dose or cancel glucocorticosteroids, reduce the need for inpatient treatment, establish and maintain remission, and improve the quality of life of patients.
Ankylosing spondylitis. Treatment of patients suffering from ankylosing spondylitis with severe axial symptoms and laboratory signs of inflammatory activity who have not responded to standard therapy. Treatment with Remicade allows to achieve a reduction in the symptoms of the disease and an improvement in the functional activity of the joints.
Psoriatic arthritis. In combination with methotrexate, treatment of patients with progressive active psoriatic arthritis in whom previous treatment with disease-modifying antirheumatic drugs (DMARDs) was ineffective. Treatment with Remicade makes it possible to achieve a reduction in the symptoms of arthritis and an improvement in the functional activity of patients, as well as a decrease in the severity of psoriasis according to the PASI index (takes into account the area of skin lesions and the severity of symptoms).
Psoriasis. Treatment of patients with severe psoriasis subject to systemic therapy, as well as patients with moderate psoriasis with ineffectiveness or contraindications to PUFA therapy. Treatment with Remicade leads to a decrease in inflammation in the epidermis and normalization of the differentiation process of keratinocytes.
Contraindications
Hypersensitivity reactions to infliximab, other mouse proteins, as well as to any of the inactive components of the drug.
Severe infectious process, such as sepsis, abscess, tuberculosis, or other opportunistic infection.
Heart failure - severe or moderate.
Pregnancy and breastfeeding.
Age less than 18 years.
Side effect
In clinical studies, adverse reactions were observed in approximately 60% of patients receiving Remicade and 40% of patients receiving placebo.
Table 1 lists the relatively common (frequency >1:100<1:10), нечастые (>1:1000 <1:100) и редкие (>1:10000 <1:1000) побочные реакции, выявленные при проведении клинических испытаний. Большая часть из них протекала в легкой и среднетяжелой форме. Наиболее частыми побочными реакциями и наиболее частыми причинами для прекращения лечения были инфузионные реакции: одышка, крапивница, головная боль.
infusion reactions. As such, when conducting clinical trials, any adverse reactions that occurred during the infusion or within 1-2 hours after it were considered. In clinical trials, the incidence of infusion reactions with Remicade was about 20% and about 10% in the comparison group (placebo). Approximately 3% of patients were forced to stop treatment due to the development of infusion reactions, while in all patients the reactions were reversible (with or without drug therapy).
Anaphylactoid reactions, including pharyngeal/laryngeal edema and marked bronchospasm, have been reported in post-marketing experience with Remicade.
Delayed type hypersensitivity reactions. In a clinical trial involving 41 patients who were re-treated with Remicade 2-4 years after the previous dose, 10 patients experienced side effects that developed 3-12 days after the second infusion. In 6 patients these reactions were severe. Symptoms included myalgia and/or arthralgia accompanied by fever and/or rash. Some patients also reported itching, swelling of the face, lips or hands, dysphagia, urticaria, sore throat and/or headache. In all cases, medications were able to achieve improvement or disappearance of symptoms. In clinical studies and post-marketing use, these events were observed infrequently with repeated administration of Remicade at intervals of less than 1 year after the previous administration. In clinical studies, arthralgia, myalgia, fever and rash were noted in 1% of patients with psoriasis at the beginning of the course of treatment with Remicade.
infectious complications. In clinical studies, the addition of an infection that required treatment was observed in 35% of patients treated with Remicade therapy and in 22% of patients treated with placebo. However, serious infectious complications, such as pneumonia, were noted in 5% of patients in both groups - those who received Remicade and those who received placebo. In clinical studies, 1% of patients with psoriasis after maintenance treatment with Remicade for 24 weeks developed serious infectious complications, while in the control group (placebo) serious infectious complications were noted. In post-marketing practice, infectious complications were the most common serious side effects, in some cases with a fatal outcome. Approximately 50% of all fatal outcomes were associated with infectious complications. Cases of tuberculosis have been reported, including miliary tuberculosis and tuberculosis with extrapulmonary localization, in some cases with a fatal outcome.
Malignant neoplasms and lymphoproliferative diseases. In clinical studies, cases of the appearance or recurrence of a malignant neoplasm have been noted. The incidence of lymphoma in patients treated with Remicade was higher than the expected incidence of this disease in the general population. The frequency of other forms of malignancy in patients treated with Remicade did not exceed, and in the control group of patients was lower than the expected frequency in the general population. The potential role of anti-TNF therapy in the development of malignancies is not known.
Cardiovascular insufficiency. In phase II clinical trials of Remicade in patients with moderate to severe cardiovascular insufficiency, an increase in mortality was noted due to an increase in cardiovascular insufficiency during Remicade therapy, especially when using an increased dose of 10 mg / kg (two times the maximum recommended therapeutic dose).
There have also been post-marketing reports of worsening CVD with Remicade, with or without additional factors. In addition, there have been rare reports of newly diagnosed cardiovascular insufficiency, including in patients who had no previous cardiovascular disease. Some of these patients were under 50 years of age.
Changes in the liver and biliary tract. In post-marketing practice, there have been very rare reports of jaundice and non-infectious hepatitis, in some cases showing signs of autoimmune hepatitis, in patients treated with Remicade. There have been isolated cases of liver failure, which led to the need for a liver transplant or a fatal outcome. A causal relationship between the development of these phenomena and treatment with Remicade has not been established. As with the use of other immunosuppressants, cases of exacerbation of hepatitis B in patients who are chronic virus carriers (having a positive reaction to HBsAg) have been observed with the use of Remicade.
In clinical studies, patients treated with Remicade showed a mild or moderate increase in ALS and AST levels without the development of severe liver damage. An increase in aminotransferases (ALT to a greater extent than AST) was noted more often in the group of patients treated with Remicade than in the control group. This has been observed both when Remicade was used alone and when it was used in combination with other immunosuppressants. In most cases, the increase in aminotransferases was transient, however, in a small number of patients, this increase was more prolonged. In general, elevations in ALT and AST levels were asymptomatic, with decreases or returns to baseline regardless of whether Remicade treatment was continued or discontinued, or concomitant therapy changed. An increase in ALT to a level equal to or greater than 5 times the upper limit of normal was observed in 1% of patients treated with Remicade.
SPECIAL INSTRUCTIONS
Remicade, when administered, can cause the development of acute allergic reactions (immediate type) and delayed-type allergic reactions. The time of development of these reactions is different. Acute infusion reactions may develop immediately or within a few hours after administration. For early detection of a possible acute reaction to the administration of Remicade, the patient should be carefully observed during and for at least 1-2 hours after the infusion of the drug. If an acute infusion reaction occurs, the administration of the drug should be stopped immediately. Equipment and medicines for emergency treatment (adrenaline, antihistamines, glucocorticosteroids, ventilators) should be prepared in advance for immediate use if necessary.
To prevent mild and transient infusion reactions, the patient may be given antihistamines, hydrocortisone and/or paracetamol before starting the infusion.
Some patients may develop antibodies to Remicade, which is associated with more frequent infusion reactions. A small proportion of infusion reactions were serious allergic reactions. In patients suffering from Crohn's disease, the relationship between the formation of antibodies and a reduction in the duration of the effect of treatment was noted. With the concomitant use of immunosuppressants, a lower incidence of antibodies to infliximab and a decrease in the frequency of infusion reactions were noted. The effect of the use of immunosuppressants in patients treated episodically was more complete than in patients on maintenance treatment. Patients who stop taking immunosuppressant drugs before or during treatment with Remicade are more at risk of developing these antibodies. The presence of antibodies in serum cannot always be determined. With the development of severe reactions, symptomatic therapy should be carried out, and further use of Remicade should be excluded.
In clinical studies with one or more doses of infliximab ranging from 1 to 20 mg/kg, antibodies to infliximab were detected in 14% of patients treated with any immunosuppressant and in 24% of patients who did not receive immunosuppressants. Among patients with rheumatoid arthritis who received the recommended treatment regimen (repeated doses of infliximab and methotrexate), 8% had antibodies to infliximab. Among patients with Crohn's disease who are on maintenance therapy, antibodies to infliximab were detected in 6-13%. The incidence of antibodies to infliximab was 2-3 times higher in patients treated episodically. Due to the limitations of the method of determination, a negative result did not allow us to exclude the presence of antibodies to infliximab. In some patients with high titers of antibodies to infliximab, there was a decrease in the effectiveness of treatment. In clinical studies in patients with psoriasis after induction therapy with Remicade and subsequent maintenance therapy with an 8-week interval, antibodies were detected in approximately 20% of cases.
Delayed-type hypersensitivity reactions were observed with a high frequency (25%) in Crohn's disease after the appointment of repeated treatment 2-4 years after the primary. They were characterized by the development of myalgia and/or arthralgia with fever and/or rash. Some patients also developed itching, swelling of the face, lips, hands, dysphagia, urticaria, inflammation of the pharynx, and headache. Patients should be warned that if these symptoms develop, they should immediately consult a doctor. When re-appointing Remicade after a long break in treatment, it is necessary to be vigilant about the appearance of a delayed-type hypersensitivity reaction in the patient.
Tumor necrosis factor alpha (TNFa) is an inflammatory mediator and modulator of cellular immunity. In patients treated with Remicade, opportunistic infections were noted, which developed, presumably, as a result of a violation of the body's defense mechanisms against infections. It should be borne in mind that suppression of TNFa may also mask symptoms of infection, such as fever.
When conducting clinical studies using various anti-TNF agents, there was a more frequent development of lymphoma in patients receiving an anti-TNF agent than in patients in the control group. In clinical studies with Remicade in rheumatoid arthritis, Crohn's disease, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis, the occurrence of lymphoma has been reported rarely, although more frequently than might be expected in the general population. Patients with rheumatoid arthritis or Crohn's disease, especially in the active form or with long-term use of immunosuppressants, have an increased (up to several times), compared with the general population, the risk of developing lymphoma, even in the absence of therapy with TNF blockers. When conducting clinical studies with the use of various anti-TNF agents, it was also noted that the development of other forms of malignant neoplasms (not lymphoma) in patients receiving an anti-TNF agent was also more frequent than in patients in the control group. The frequency of these forms of malignancy in patients treated with Remicade did not exceed, and in the control group of patients was lower than the expected frequency in the general population. In clinical studies investigating the use of Remicade for a possible new indication - COPD (severe and moderate) - in patients who smoked (or former smokers), the incidence of neoplasms was higher in the Remicade group than in the control group. The potential role of anti-TNF therapy in the development of malignancies is not known. Special care should be taken when prescribing Remicade to patients with a history of indications of malignant neoplasms, or when deciding whether to continue treatment with Remicade, in patients with newly diagnosed malignant neoplasms.
Before starting treatment with Remicade, the patient should be carefully examined for both active and latent tuberculosis. The examination should include a thorough history taking, including the need to find out whether the patient had tuberculosis in the past, whether there were contacts with patients with tuberculosis. In addition, it is necessary to evaluate the feasibility of screening tests (chest x-ray, tuberculin test). It should be borne in mind that in severely ill patients and patients with immunosuppression, a false-negative tuberculin test can be obtained. If an active tuberculosis process is suspected, treatment should be discontinued until a diagnosis is made and, if necessary, appropriate treatment is initiated. When latent tuberculosis is detected, measures should be taken to prevent the activation of the process, and the benefit/risk ratio should be assessed before deciding whether to prescribe Remicade to this patient.
During treatment and after its completion, the patient should be carefully monitored for signs of a possible infection. Since the elimination of Remicade occurs within 6 months, the patient during this period should be constantly under the supervision of a physician. Treatment with Remicade should be discontinued if the patient develops a severe infection, including tuberculosis, sepsis, or pneumonia.
The patient should be informed that he will need to see a doctor in case of symptoms of a possible tuberculosis process, such as persistent cough, weight loss, slightly elevated body temperature, during treatment with Remicade or after it has ended.
Patients with Crohn's disease with acute purulent fistulas should not begin treatment with Remicade until another possible source of infection, especially an abscess, has been identified and eliminated.
There are only limited data on the safety of surgical interventions in patients treated with Remicade. Patients receiving Remicade who require surgery should be carefully evaluated for infection and, if necessary, treated appropriately.
In clinical trials, combination treatment with etanercept (another anti-TNFa agent) and anakinra has been associated with severe infectious complications, with no therapeutic benefit compared with etanercept alone. Given the nature of the side effects noted with combination therapy with anakinra and etanercept, one would expect the same effects to occur with combination therapy with anakinra and some other anti-TNFa agent. For this reason, combination treatment with infliximab and anakinra is not recommended.
At present, there is no information on how patients receiving anti-TNF therapy respond to vaccination with live vaccines or secondary transmission of infection with live vaccines. It is recommended not to use live vaccines in such patients.
In rare cases, the relative deficiency of TNFa caused by anti-TNF therapy can initiate the development of an autoimmune process in genetically predisposed patients. If the patient develops symptoms resembling lupus syndrome (persistent rash, fever, joint pain, fatigue) and DNA antibodies are detected, treatment with Remicade should be discontinued.
According to clinical studies, approximately half of the number of patients treated with infliximab, and approximately 1/5 of the number of patients treated with placebo, who did not have antinuclear antibodies (ANA) before treatment, began to detect antinuclear antibodies during treatment. Antibodies to double-stranded native DNA (anti-dsDNA) began to be detected in approximately 17% of patients receiving infliximab, and were not detected in patients receiving placebo. At the final examination, 57% of patients treated with infliximab had antibodies to double-stranded DNA. However, reports of the development of lupus or lupus syndrome remained infrequent.
The use of infliximab and other anti-TNF agents has been associated with rare cases of optic neuritis, epileptic seizures, the onset or exacerbation of clinical and radiographic symptoms of demyelinating diseases, including multiple sclerosis. The benefit/risk of Remicade should be carefully weighed when administered to patients with pre-existing or recent onset CNS demyelinating disease.
Patients with moderately severe circulatory failure should be carefully monitored. In the event of an increase in symptoms of circulatory failure, Remicade should be discontinued.
Patients with evidence of liver dysfunction should be evaluated for liver damage. In the event of jaundice or an increase in ALT activity above 5 times the upper limit of normal, Remicade should be discontinued and a thorough investigation of the disorder should be carried out.
Chronic hepatitis B virus carriers should be appropriately screened before using Remicade and closely monitored during treatment for possible exacerbation of hepatitis B.
The treatment of Remicade in children and adolescents up to and including 17 years of age with rheumatoid arthritis or Crohn's disease has not been studied. Remicade should not be used in this age group until appropriate data are available on the safety and efficacy of Remicade.
Special studies on the use of Remicade in the elderly, as well as in persons with liver and kidney diseases, have not been conducted.
Remicade is not recommended during pregnancy as it may interfere with the development of the fetal immune system. Women of childbearing age should use reliable methods of contraception during treatment with Remicade and for at least 6 months after its termination.
It is not known if Remicade is excreted in milk. In this regard, when prescribing Remicade, breastfeeding should be stopped. Breastfeeding is allowed no earlier than 6 months after the end of treatment.
There is limited experience demonstrating the safety of Remicade treatment in patients undergoing arthroplasty.
.
Humira
.
The active substance is adalimumab.
Solution for s / c injection opalescent, slightly colored. 1 syringe 40 mg
Excipients: mannitol, citric acid monohydrate, sodium citrate, disodium hydrogen phosphate dihydrate, sodium dihydrogen phosphate dihydrate, sodium chloride, polysorbate 80, water for injection, sodium hydroxide.
Clinico-pharmacological group: Selective immunosuppressant. Monoclonal antibodies to TNF
solution for s / c injection 40 mg / 0.8 ml: syringes 1 or 2 - LS-002422, 10.09.08
Indications
moderate and severe active rheumatoid arthritis (as monotherapy or in combination with methotrexate or other basic anti-inflammatory drugs);
active psoriatic arthritis (as monotherapy or in combination with methotrexate or other basic anti-inflammatory drugs);
active ankylosing spondylitis.
Side effect
Below are Humira's safety data from placebo-controlled clinical trials.
Clinical and laboratory adverse events, the association of which with adalimumab was at least possible, distributed by system and frequency: very often (> 1/10); often (>1/100, ≤1/10); infrequently (> 1/1000, ≤1/100).
Infections: very often - infection of the upper respiratory tract; often - lower respiratory tract infection (including pneumonia and bronchitis), urinary tract infection, herpes infection (including herpes simplex and herpes zoster), influenza, superficial fungal infection (including skin and nail lesions); infrequently - sepsis, joint and wound infections, abscess, skin infection (including impetigo), hair follicle infection (including boils and carbuncles), paronychia, pustular rash, tooth and periodontal infection, ear infection, gastroenteritis, oral and pharyngeal candidiasis, vaginal infections (including fungal), viral infection.
Neoplasms: infrequently - skin papilloma.
From the hemopoietic system: often - anemia, lymphopenia; infrequently - leukopenia, leukocytosis, lymphadenopathy, neutropenia, thrombocytopenia.
From the immune system: infrequently - hypersensitivity reactions, seasonal allergies.
From the side of metabolism: infrequently - hypercholesterolemia, hyperuricemia, anorexia, loss of appetite, hyperglycemia, weight gain or decrease.
From the side of the central nervous system and peripheral nervous system: often - headache, dizziness, paresthesia; infrequently - depression, anxiety disorders (including nervousness and agitation), insomnia, confusion, taste perversion, migraine, drowsiness, fainting, neuralgia, tremor, neuropathy.
From the sensory organs: infrequently - conjunctivitis, blepharitis, pain, redness, dry eyes, swelling of the eyelid, glaucoma, pain, congestion and ringing in the ears.
From the side of the cardiovascular system: often - arterial hypertension; infrequently - hot flashes, hematomas, tachycardia, palpitations.
From the respiratory system: often - cough, sore throat, nasal congestion; infrequently - shortness of breath, asthma, dysphonia, pulmonary crepitus, ulceration of the nasal mucosa, swelling of the upper respiratory tract, redness of the throat.
From the digestive system: often - nausea, abdominal pain, diarrhea, dyspepsia, ulceration of the oral mucosa, increased activity of liver enzymes (including ALT and AST), alkaline phosphatase; infrequently - vomiting, flatulence, constipation, gastroesophageal reflux, dysphagia, gastritis, colitis, hemorrhoids, hemorrhoidal bleeding, vesicular rash in the oral cavity, toothache, dry mouth, gingivitis, ulceration of the tongue, stomatitis (including aphthous)
Dermatological reactions: often - rash (including erythematous and itchy), pruritus, hair loss; infrequently - macular or papular rash, dry skin, sweating, night sweats, eczema, dermatitis, psoriasis, urticaria, ecchymosis, purpura, acne, skin ulcers, angioedema, changes in the nail plate, photosensitivity reactions, skin peeling, rheumatoid nodules.
From the musculoskeletal system: infrequently - arthralgia, pain in the extremities, pain in the back and shoulder girdle, muscle cramps, myalgia, swelling of the joints, synovitis, bursitis, tendinitis.
From the genitourinary system: infrequently - hematuria, dysuria, nocturia, pollakiuria, pain in the kidneys, menorrhagia
On the part of the body as a whole: often - increased fatigue (including asthenia), flu-like syndrome; infrequently - fever, feeling hot, chills, chest pain, worsening wound healing.
Local reactions: very often - pain, swelling, hyperemia, itching at the injection site.
On the part of laboratory parameters: infrequently - an increase in the level of triglycerides, CPK, LDH, urea and creatinine in the blood, an increase in APTT, a decrease in the level of potassium in the blood, the formation of autoantibodies, the appearance of protein in the urine.
Contraindications
infectious diseases, including tuberculosis;
pregnancy;
lactation period (breastfeeding);
children and adolescents up to 16 years of age;
hypersensitivity to adalimumab or any of its auxiliary components.
With caution, the drug should be prescribed for demyelinating diseases.
In experimental animal studies at doses up to 100 mg/kg, there were no signs of a damaging effect of adalimumab on the fetus. However, in adequate controlled studies in pregnant women, the drug has not been studied. Animal studies do not always predict the effect on humans, so during pregnancy, Humira should be used only if clearly necessary.
Women of childbearing age should avoid conception while taking Humira.
The effects of Humira on labor and delivery are not known.
There is no information on the excretion of adalimumab in breast milk or its absorption after oral administration. Many medicinal substances and immunoglobulins pass into breast milk. Given the risk of developing serious adverse reactions in the newborn, it is advisable to stop breastfeeding or discontinue the drug, taking into account its importance to the mother.
special instructions
Serious infections, rare cases of tuberculosis and opportunistic infections have been observed during treatment with anti-TNF monoclonal antibodies, including Humira, incl. with a lethal outcome. In many cases, serious infectious processes developed in patients receiving concomitant immunosuppressive therapy. Rheumatoid arthritis itself predisposes to the development of infectious complications.
Humira should not be administered to patients with active infections, incl. chronic or focal. Treatment can only be started after infection control has been achieved.
As with other anti-TNF monoclonal antibodies, monitor for signs of infections, including tuberculosis, before, during, and after Humira therapy.
If a new infection develops during Humira therapy, patients should be closely monitored. In severe cases, treatment with Humira should be discontinued. It can only be resumed after infection control has been achieved.
Caution should be exercised when discussing the use of Humira in patients with a history of recurrent infections or diseases predisposing to the development of infectious complications.
The use of monoclonal antibodies to TNF may be accompanied by reactivation of the hepatitis B virus (HBV) in infected patients - carriers of this virus. Several cases of death due to reactivation of the hepatitis B virus have been described with the use of TNF blockers. In most cases, HBV activation was observed in patients receiving concomitant immunosuppressive therapy in addition to TNF blockers. Patients at risk for hepatitis B should be carefully screened for HBV before anti-TNF monoclonal antibodies are given. The use of TNF blockers in HBV carriers should be considered based on the potential risk to the patient. If a carrier of HBV is prescribed therapy with anti-TNF monoclonal antibodies, the patient should be closely monitored throughout the course of therapy and several months after its completion. If hepatitis B virus reactivation occurs during the use of Humira, treatment with Humira should be discontinued and effective antiviral therapy initiated.
Therapy with monoclonal antibodies to TNF, including Humira, in rare cases was accompanied by the appearance or exacerbation of clinical and / or radiographic manifestations of demyelinating diseases. Physicians should exercise caution when prescribing Humira to patients with demyelinating diseases of the central nervous system.
In controlled studies, the incidence of malignant tumors, including lymphoma, was higher in patients treated with anti-TNF monoclonal antibodies than in patients in control groups. The total number of patients treated with placebo and the duration of follow-up were less than the number and duration of follow-up of patients treated with TNF blockers. In addition, the risk of developing lymphoma is increased in patients with rheumatoid arthritis, accompanied by chronic highly active inflammation, which makes it difficult to assess its risk during treatment. In long-term clinical studies of Humira, the incidence of malignant neoplasms corresponded to this indicator in patients of the same age, gender and race in the general population. However, the data available to date are insufficient to rule out a possible risk of developing lymphoma or other malignant tumors during anti-TNF monoclonal antibody therapy.
Clinical studies did not include patients with a history of malignant tumors, and Humira therapy was discontinued if a tumor developed. Accordingly, special care must be taken when considering treatment with Humira in such patients.
In clinical studies, serious allergic reactions with the use of Humira were rare. In clinical practice, very rare cases of serious allergic reactions (including anaphylactic reactions) have been reported after the administration of Humira. If anaphylaxis or other severe allergic reaction develops, Humira therapy should be discontinued immediately and appropriate treatment instituted.
The needle cap of the injection syringe contains latex, which can cause severe allergic reactions in patients with latex hypersensitivity.
Tuberculosis has been reported in clinical trials with Humira and other similar drugs. They were observed with the use of the drug in any doses, however, the frequency of reactivation of tuberculosis increased mainly when Humira was administered at doses exceeding the recommended ones. Fungal and other types of opportunistic infections have been described in patients taking Humira. Some of these infections, including tuberculosis, have been fatal.
Before starting treatment with Humira, all patients should be screened to rule out active and inactive (latent) tuberculosis. It is necessary to collect a detailed medical history, incl. find out the presence of contacts with patients with active tuberculosis and clarify whether immunosuppressive therapy has been and/or is being carried out. Screening tests (eg, chest x-ray and tuberculin test) should be performed. The possibility of false-negative tuberculin tests should be taken into account, especially in critically ill and immunocompromised patients.
If active TB is diagnosed, treatment with Humira should not be started.
In case of latent tuberculosis, preventive anti-tuberculosis treatment should be carried out before starting treatment with Humira.
Patients should be informed about the need to consult a doctor if there are signs of tuberculosis infection (persistent cough, weight loss, low-grade fever).
Rare cases of pancytopenia, including aplastic anemia, have been described during treatment with TNF blockers. When Humira was prescribed, adverse events from the hematopoietic system, including clinically significant cytopenias (thrombocytopenia, leukopenia), were recorded infrequently. Their connection to Humira remains unclear. Patients should seek immediate medical attention if they develop symptoms of a blood disorder (eg, persistent fever, bruising, bleeding, pallor) during treatment with Humira. In patients with severe blood changes, consideration should be given to discontinuing Humira.
In clinical studies, concomitant use of anakinra and the TNF blocker etanercept has been associated with serious infections with no additional clinical benefit compared with etanercept alone. Given the nature of the adverse events that have developed in combination therapy with anakinra and etanercept, similar effects can be expected in the treatment of anakinra in combination with other TNF blockers. Therefore, combination therapy with adalimumab and anakinra is not recommended.
In a study of 64 patients treated with Humira, there were no signs of inhibition of delayed-type hypersensitivity reactions, decreased immunoglobulin levels, or changes in the number of effector T cells, B cells and NK cells, monocytes/macrophages, and neutrophils.
Patients receiving Humira may be vaccinated (with the exception of live vaccines). There is no information on the possibility of infection during vaccination with live vaccines during treatment with Humira.
Humira has not been specifically studied in patients with chronic heart failure, however, in clinical studies of another TNF antagonist, an increase in the rate of progression of chronic heart failure and the development of its new cases was noted. Cases of worsening heart failure have also been described in patients treated with Humira. Humira should be used with caution and under close medical supervision in patients with heart failure.
Humira therapy may be accompanied by the formation of autoantibodies. The effect of long-term use of Humira on the development of autoimmune diseases is not known. Humira should be discontinued if the patient develops signs of a lupus-like syndrome during treatment.
There is no information about the effect of Humira on the results of laboratory tests.
Safety and efficacy in older and younger patients generally do not differ. However, hypersensitivity to the drug in some elderly patients cannot be ruled out.
Pediatric use
The safety and efficacy of Humira in children have not been studied.
Raptiva
.
CFG: Monoclonal antibodies
Release form, composition and packaging
Lyophilisate for the preparation of a solution for s / c administration in the form of a mass of white or white with a yellowish tint. 1 vial
efalizumab 125 mg
Excipients: sucrose, L-histidine hydrochloride monohydrate, L-histidine, polysorbate 20.
Solvent: water d / i - 1.3 ml.
Glass vials (1) complete with a solvent (glass syringes - 1), a sterile needle for the preparation of solution (1) and a sterile needle for injection (1) - packs of cardboard.
Glass vials (4) complete with a solvent (glass syringes - 4), sterile needles for the preparation of solution (4) and sterile needles for injection (4) - packs of cardboard.
Clinico-pharmacological group: Immunosuppressant. Recombinant humanized monoclonal antibodies (IgG1)
lyophilisate for preparation. r-ra d / p / c injection 125 mg: vial. 1 or 4 per set with solvent in syringes and needles. — LS-002323, 08.12.06
Indications
treatment of moderate to severe psoriasis (plaque psoriasis) in adults.
Side effect
Flu-like symptoms: 43% mild or moderate headache, fever, chills, nausea, muscle pain. The severity of these symptoms is dose-dependent.
When conducting multicenter placebo-controlled clinical trials, these reactions were observed 20% more often than in the placebo group, the duration of therapy was 12 weeks. Symptoms were observed more often after the first injection, almost 2 times less often after the second injection, and were comparable in frequency with the placebo group. The predominant symptom was headache. Only in 5% of cases these symptoms were regarded as severe, in less than 1% they became the reason for discontinuation of the drug.
On the part of the hematopoietic system: 50% - asymptomatic lymphocytosis (2.5-3.5 times higher than ULN). The number of lymphocytes returned to baseline after cessation of therapy. Less commonly, a slight increase in the absolute number of neutrophils and eosinophils.
On the part of the blood coagulation system: 0.3% - thrombocytopenia (less than 52x109 cells / l), which may be accompanied by ecchymosis, spontaneous hemorrhages, bleeding from the mucous membranes.
From the side of the liver: 3.5% - increased activity of alkaline phosphatase; 1.7% - increase in ALT activity. The value of these indicators returned to baseline after cessation of therapy.
Allergic reactions: 8.3% (2.8% more often than in the placebo group) - urticaria, skin rash.
Other: The incidence of malignant tumors was approximately the same in the groups treated with Raptiva (1.8/100 patient-years) and in the placebo groups (1.6/100 patient-years).
Contraindications
malignant neoplasms;
severe infectious diseases (including sepsis, tuberculosis, hepatitis B, hepatitis C).
Use during pregnancy and lactation
Raptiva is not recommended for use during pregnancy.
There are no data on teratogenic effects or negative effects on the reproductive system.
Women of childbearing age receiving Raptiva are advised to use reliable methods of contraception.
It is not known whether efalizumab is excreted in breast milk. Since immunoglobulins usually pass into breast milk, if necessary, the use of the drug during lactation, breastfeeding should be discontinued.
Application for violations of liver function
There is no experience of using the drug in patients with hepatic insufficiency.
Application for violations of kidney function
There is no experience of using the drug in patients with renal insufficiency.
special instructions
Raptiva, like other therapeutic agents for systemic use in psoriasis, may reduce the effectiveness of the immune response against infectious agents. It has not been established what effect Raptiva therapy has on the development and treatment of acute and / or chronic infectious diseases. If the patient has developed a serious infectious disease, the drug should be discontinued.
During clinical trials, it was noted that during the first 12 weeks of therapy, serious infectious diseases were observed in 0.4% of cases in the group receiving Raptiva and in 0.1% of cases in the placebo group; for the entire study period, infectious diseases were observed in 1.09% of patients.
It was noted that the interruption of the course of treatment without substitution therapy may be accompanied by a significant deterioration in the course of psoriasis. The resumption of the course stabilized the skin process and led to a decrease in the frequency of relapses of the disease.
Raptiva should not be given in combination with other immunosuppressive therapy.
Against the background of Raptiva therapy, an exacerbation of the course of psoriasis or psoriatic arthritis is possible. In this case, it is recommended to stop using the drug.
When the drug is discontinued, it is necessary to monitor the patient's condition and, in case of relapse, to prescribe an effective treatment.
There were no differences in the effectiveness of Raptiva therapy in elderly and young patients. Since the elderly are more likely to develop infectious diseases, therapy should be carried out with extreme caution.
During the course of treatment with efalizumab, it is not recommended to vaccinate with live vaccines.
Approximately 6.3% of patients treated with efalizumab developed specific anti-antibodies to efalizumab. Anti-antibodies did not have any significant effect on pharmacodynamic and pharmacokinetic parameters. There was also no visible effect on the efficacy and safety of the drug.
If symptoms of thrombocytopenia appear, efalizumab should be discontinued immediately, the platelet count should be determined, and appropriate symptomatic therapy initiated promptly.
If allergic reactions occur, Raptiva should be discontinued immediately.
Clinical experience with Raptiva has not confirmed an increased risk of developing malignancies compared with the general population. If a neoplasm is found in a patient during the course of treatment, the drug should be discontinued.
The patient should be warned that if any side effects occur, the attending physician should be informed.
Clinical studies of the efficacy and safety of the drug in patients with impaired renal and hepatic function have not been conducted. Treatment of patients in this group should be carried out with extreme caution.
There is no experience of using the drug in patients with renal or hepatic insufficiency.
Pediatric use
Data on the use of Raptiva in patients under 18 years of age are not available. Therefore, the drug should not be used in pediatrics until more information is available.
Influence on the ability to drive vehicles and control mechanisms
Special clinical studies to study the effect of Raptiva on the ability to drive vehicles and work with mechanisms have not been conducted. Given the mechanisms of pharmacological action of efalizumab, it is unlikely that Raptiva can affect this ability.
According to the latest data, Raptiva is being withdrawn from sale by the manufacturer, and at the beginning of this year, the use of this drug in the Russian Federation was suspended due to the occurrence of a brain infection in patients ....
To the attention of those using or planning to use the drug Raptiva (Raptiva, efalizumab)!
The drug was withdrawn from sale in 2009-2010 by the manufacturer from the markets of America and Europe due to an increased risk of developing multifocal leukoencephalopathy caused by a virus that affects the central nervous system. Prescriptions were discontinued over a year ago. Appropriate warnings have been issued by the FDA and EMEA. In this regard, it is possible for unscrupulous sellers to distribute “remnants” of the drug in countries that are not in the FDA or EMEA area.
Be careful!
.
Stelara
Psoriasis and immunity are inextricably linked, because the disease occurs due to malfunctions in the immune system. Under the influence of provoking factors, antibodies begin to be produced that contribute to the development of the inflammatory process, accompanied by redness and peeling. Measures aimed at suppressing immune responses help to cope with psoriasis.
How to boost immunity
It is possible to raise immunity in psoriasis with the help of drugs that have a regulatory effect on the immune system. Additionally, special diets and folk recipes are used.
Medicines for the normalization of the immune system are divided into:
- Immunostimulants of general action. Change the way the immune system functions. Drugs negatively affect the state of internal organs, so they should be used as directed by a doctor.
- Selective immunomodulators. The composition of the drugs includes those that have a directed effect on some parts of the immune system, provoking the onset of symptoms of psoriasis. Before using drugs, an immunogram is prescribed to help detect pathological changes. Selective drugs do not have a negative effect on the body.
- Immunosuppressants. Suppress the activity of the immune system, reducing the intensity of autoimmune reactions. They make the body susceptible to infectious diseases, so they should be used with caution.
List of effective immunomodulators
Conducting immunotherapy for psoriasis involves the use of immunomodulators of the old and new generations. The latter are expensive, but they have a milder effect on the body.
Efalizumab
The drug contains modified monoclonal antibodies obtained from Chinese hamster ovaries. Efalizumab inhibits the activity of T-lymphocytes, reducing the intensity of autoimmune reactions. Under the influence of the drug, the severity of psoriasis symptoms decreases, signs of inflammation disappear, and the general condition of the skin improves.
The remedy is prescribed for psoriasis vulgaris of moderate and severe course. The solution is injected subcutaneously, a single dose is 0.7 mg/kg. Injections are given once a week, the dose is gradually increased until the onset of a therapeutic effect. Treated for at least 3 months. When using the drug, the following side effects may occur:
- febrile syndrome (fever, aching muscles and joints, headache);
- local reactions (itching and redness of the skin, pain at the injection site);
- allergic reactions (urticaria, angioedema, anaphylactic shock);
- decrease in the number of leukocytes, platelets and lymphocytes;
- generalized bacterial, viral or fungal infections;
- increased activity of liver enzymes;
- the appearance of benign and malignant neoplasms.
Efalizumab is not used for:
- severe chronic infections (sepsis, tuberculosis, hepatitis);
- oncological diseases;
- childhood;
- pregnancy and lactation;
- administration of live virus vaccines;
- acute renal and hepatic failure.
Contains a synthetic peptide that:
- has immunosuppressive properties;
- suppresses humoral and cellular reactions;
- reduces the number of lymphocytes in the blood;
- slows down the production of helpers and suppressors;
- prevents the division of T-cells;
- does not have a toxic effect on the body.
The drug is used to treat psoriatic lesions of the skin and joints in children and adults. 1-2 ml of the solution is injected into the gluteal muscle. The therapy lasts 7-10 days, after which they take a break. After 2 days, treatment is resumed according to the scheme drawn up by the doctor. During therapy, the following undesirable effects occur:
- decrease in the number of leukocytes;
- allergic reactions in the form of skin rashes, itching and urticaria;
- exacerbation of chronic bacterial, fungal and viral infections.
Thymodepressin is not prescribed for:
- taking immunostimulants;
- acute form of infectious diseases;
- the presence of malignant tumors;
- intractable hypertension;
- individual intolerance to the drug;
The immunosuppressor belongs to the cytostatics of the group of synthetic chloroethylamines. It suppresses the activity of dividing and resting immune cells, inhibits the proliferation of T-lymphocytes, reducing the cellular and humoral reactivity of the immune system. Cyclosporine does not affect the functioning of the hematopoietic system, it is injected.
A single dose for psoriasis is calculated taking into account the severity of the course of the disease and the individual characteristics of the organism. The therapeutic course lasts no more than 3 months, after which a break is taken. Cyclosporine may cause the following side effects:
The drug is contraindicated in:
- low levels of platelets and white blood cells;
- anemia;
- severe depletion of the body;
- oncological diseases;
- hypertension;
- acute infections;
- pregnancy and breastfeeding;
- severe diseases of the cardiovascular and excretory systems.
Methotrexate
Refers to drugs that inhibit cell division. Against the background of treatment with Methotrexate, the severity of manifestations of psoriasis decreases. The drug masks some molecules, which makes the skin cells inaccessible to the immune system. The inflammatory process leading to the occurrence of redness, itching and peeling does not develop. The drug is prescribed for common psoriatic lesions, pustular or atypical form of the disease, psoriatic erythroderma. The drug is also effective.
Designed for intravenous and intramuscular administration. Injections are given 1-2 times a week. The average single dose is 25-30 mg. The therapeutic course lasts a month. During treatment, the following undesirable consequences may develop:
- nausea and vomiting;
- allergic reactions;
- headaches;
- itchy skin rashes;
- inflammation of the middle ear, hearing loss;
- inflammatory processes in the lungs;
- dysfunction of the liver, kidneys and bone marrow;
- digestive disorders (flatulence, loose stools);
- changes in the composition of the blood;
- ulceration of the mucous membranes of the oral cavity;
- trophic ulcers of the legs;
- hemorrhagic complications;
- violation of the menstrual cycle;
- inflammation of the bladder.
The list of contraindications includes:
- pregnancy and lactation;
- severe liver and kidney disease;
- ulcerative lesions of the stomach or large intestine;
- diseases of the hematopoietic system.
Arava is a new generation of immunosuppressive drugs used to treat autoimmune skin lesions. The active substance (leflunomide) has anti-inflammatory, immunomodulatory and antiproliferative properties. The drug is available in the form of tablets that are taken once a day. The therapeutic course lasts 4-6 months. Side effects of Arava include:
- increased blood pressure;
- signs of damage to the digestive system (ulcerative stomatitis, nausea and vomiting, loose stools, stomach pain, changes in taste perception);
- pneumonia;
- weight loss;
- inflammation and rupture of the tendons;
- erythematous rashes;
- focal alopecia;
- the transition of psoriasis to a pustular form;
- allergic reactions in the form of rhinitis, urticaria and eczema;
- severe infectious diseases;
- increased activity of hepatic transaminases;
- changes in the composition of the blood;
- increased risk of developing malignant neoplasms.
An immunosuppressant is contraindicated in:
- allergic reactions to the components of the drug;
- immunodeficiency states;
- anemia;
- dysfunction of the hematopoietic system;
- severe liver failure;
- pregnancy and breastfeeding.
Timalin
The drug is produced on the basis of an extract of the thymus of cattle. It is produced in the form of a lyophilisate, from which a solution for intramuscular injections is prepared. The drug accelerates healing, prevents the accumulation of immunoglobulin in the skin, reduces the negative impact of the environment on the body.
The only contraindication to the use of Timalin is individual intolerance. Injections are made 1 time per day for a week. If the signs of psoriasis persist, a second course is carried out after a one-month break.
Enbrel
The drug reduces the reactivity of the immune system, eliminating the main signs of psoriasis. Used for:
- treatment of psoriatic arthritis;
- inability to use Methotrexate and Cyclosporine;
- treatment of psoriasis in children older than 8 years (with intolerance to phototherapy).
Enbrel is available as a lyophilisate for the preparation of a solution that is injected subcutaneously. The recommended single dose is 25 mg. The drug is administered 2 times a week for 6-8 months. The drug may cause the following side effects:
- pneumonia;
- septicemia;
- change in the qualitative and quantitative composition of the blood;
- allergic and anaphylactic reactions;
- convulsive syndrome;
- damage to the optic nerve;
- autoimmune liver damage;
- congestive heart failure;
- systemic vasculitis;
- malignant tumors of the skin;
- subcutaneous hemorrhages;
- internal bleeding.
The drug is not used for generalized infections, pregnancy and lactation, cancer.
Other Ways to Boost Immunity
Proper nutrition helps to increase the chances of psoriasis going into remission. Foods that can provoke an allergic reaction are excluded from the diet:
- chocolate and confectionery;
- smoked meats and sausages;
- citrus;
- salted and pickled vegetables.
Fruits and vegetables with a neutral taste, fermented milk products, sea fish, buckwheat porridge are useful for psoriasis. Products must be boiled, stewed or steamed.
The use of folk remedies
Helps to normalize the functioning of the immune system:
- Decoction of bay leaf. 7-8 small sheets pour 400 ml of boiling water, cook over low heat for 10 minutes. The agent is cooled, filtered and taken 100 ml 3 times a day. The course of treatment is a week.
- Collection of chamomile, tricolor violet, St. John's wort and lingonberry leaves. The ingredients are mixed in equal proportions, 1 tbsp. l. the mixture is poured with 200 ml of boiling water, insisted for half an hour, after which 1 tbsp is added. l. pharmacy extract of eleutherococcus. The tool is taken in the morning at 0.5 tbsp.
Precautionary measures
When treating with immunomodulators, you need to consider:
- the need for constant monitoring of blood composition and the state of internal organs;
- the possibility of deterioration of the condition of the skin with prolonged use of drugs;
- a high probability of an exacerbation of the disease within six months after the start of treatment (psoriasis in this case has a severe course);
- high risk of developing infectious diseases.
Conclusion
For the treatment of psoriasis, drugs that suppress immune responses are used. They must be taken with caution, because drugs in this group have a large number of side effects.
Immunomodulators in psoriasis help to strengthen the body's resistance to the disease. Based on, dermatologists must prescribe them as part of the complex treatment of this autoimmune pathology. In medical practice, many drugs are used to strengthen the immune system. For success and patients it is useful to learn about the features of these drugs.
Types and purpose of immunomodulators
For more than a decade, immunomodulators have shown themselves to be effective boosters of immunity to combat psoriasis.
The drugs are divided into 2 groups:
- immunostimulants that accelerate and enhance the immune response;
- immunosuppressants that reduce the speed and strength of the immune response.
In psoriatic pathologies, immunosuppressants are prescribed, which stabilize the patient's condition and relieve the autoimmune inflammatory process. A number of these compounds help to suppress the production of antibodies and regression of the manifestations of clinical cases of the disease.
Systemic immunosuppressants
Immunomodulators of this category act on the entire immune system as a whole. These include:
- . The drug inhibits the reproduction of epidermal cells. A powerful drug is used if other medicines are powerless in the treatment of psoriasis and cannot positively affect the patient's immunity. Methotrexate is used both in tablets and in the form of injections.
- Cyclosporine. The drug inhibits the activity of T-lymphocytes and relieves the autoimmune inflammatory process. The drug does not have a long-term effect on the blood picture. The medicine is usually prescribed.
- Potent drugs Cyclosporine and Methotrexate are prohibited in a number of diseases, including thrombocytopenia, liver and kidney dysfunction, ulcers.
- Individual intolerance to the drug.
- and breastfeeding.
- Immunodeficiency.
These are not all contraindications to the use of immunomodulators. To prescribe an effective and safe medication, data on the patient's immunity status are needed, so only the attending physician can choose the right immunomodulator. The use of the drug in the presence of contraindications may cause or addiction.
Interesting! A dermatologist gives a free referral for tests and helps to navigate the whole variety of pharmaceutical names.
The effectiveness of therapy with immunomodulators
By following all the doctor's prescriptions and prescriptions, you can achieve increased immunity and softening. As practice has shown, if the patient responsibly follows the recommendations of a dermatologist, then complex therapy with the inclusion of immunomodulators increases the likelihood of remission by an average of 50–60%.
Psoriasis is one of the most common dermatoses, but it has not yet been precisely clarified. One of the popular theories links the development of dermatosis with a malfunction of the immune system. This is the reason for the use of immunomodulators in psoriasis.
Autoimmune theory of the origin of psoriasis
The skin is one of the main organs of the human immune system and has all types of phagocytic and immunocompetent cells. In a normal state, the cells of the immune system of the skin and mucous membranes, as well as the number of pro-inflammatory and anti-inflammatory cytokines, are balanced, which ensures an adequate immune response to irritation. The development of psoriasis is associated with the excessive activity of certain immune cells, which leads to a violation of the desquamation of the skin. In this disease, immunity disorders are found both at the cellular and humoral levels.
In addition to the skin, joints and internal organs are involved in the pathological process. Small joints are affected more often than large ones. Today, medicine offers many drugs to eliminate the symptoms of the disease. In recent decades, the widespread use of immunomodulators in psoriasis has begun. These drugs prevent the reproduction of immune cells, thereby exerting a depressing effect on the immune system. This leads to a significant mitigation of the symptoms of the disease.
What are immunomodulators
In a broad sense, the term "immunomodulators" is used to refer to natural or synthetic substances that have a regulatory effect on the immune system. In accordance with the nature of their effect on immunity, drugs are divided into immunostimulating and immunosuppressive.
Immunosuppressants are used in autoimmune diseases, inflammation, allergies, transplantation to suppress the activity of lymphoid cells. There are several main groups of immunosuppressants: 
- Hormonal preparations.
- Cytostatics.
- Anti-Rhesus immunoglobulins and anti-lymphocyte immunoglobulins.
- monoclonal antibodies.
- Some antibiotics.
Their immunomodulatory activity is associated with the ability to inhibit hematopoiesis (hematopoiesis), interact with proteins involved in the immune response, inhibit the production of nucleotides, etc.
Immunomodulators are obtained from plant and animal tissues through biosynthesis, using genetic engineering and chemical synthesis methods.
Immunomodulators for the treatment of psoriasis
Today, in many countries of the world, immunosuppressants are used to treat autoimmune diseases. Their action is based mainly on artificial suppression of immunity, suppression of the ability of cells to divide. Some of these tools are used in transplantology, others in oncology.
The use of immunomodulators in psoriasis began relatively recently. The drugs are divided into two groups:
Currently, immunomodulators are indicated for use in severe or moderate psoriasis, as well as in psoriatic arthritis.
In the complex treatment of psoriasis, these drugs can only be used as directed by a doctor who selects a specific remedy, develops an individual treatment regimen, and also includes other medications or physiotherapy. The search for the most suitable immunomodulator for each case can take quite a long time, since its tolerability and toxicity are preliminarily calculated. The duration of the course averages from 4 weeks to six months.
The use of immunosuppressants: arguments against
Over the past 20-25 years, these drugs have become an important part of the treatment of psoriasis. Their use allows you to reduce the dose of corticosteroids and get a more pronounced clinical effect. However, we should not forget about the reverse side of the coin: the drugs in this group have a number of disadvantages. The main ones are:
Due to these factors, many experts consider the use of immunosuppressants appropriate only for severe types of psoriasis and in case of ineffectiveness of others.
Overview of immunomodulators for psoriasis
The drug is an immunosuppressant and cytostatic, belongs to the group of synthetic chlorethylamines. It suppresses proliferating and resting immunocompetent cells, inhibits the functioning of T-lymphocytes, as a result, the humoral and cellular response decreases. Does not affect the function of hematopoiesis. In most cases, it is used in the form of injections.
Cyclosporine is used for psoriasis, psoriatic arthritis, a number of other autoimmune and rheumatic diseases, and for oncological diseases. 
Application
The dosage is determined individually and adjusted according to the clinical effect and the degree of toxic effects. In psoriasis, the drug is prescribed at a rate of 2.5 mg per 1 kg of body weight per day. In case of a severe clinical picture, a double dose can be used. If there is no effect within 6 weeks, the drug should be discontinued. For maintenance therapy, the minimum effective dose should be no more than 5 mg per 1 kg.
The duration of the course is no more than 12 weeks. Treatment is carried out intermittently due to possible negative effects on the kidneys.
Side effects
The main problems with the use of Cyclosporine are:
- kidney damage;
- increased blood pressure;
- increased likelihood of developing infectious and neoplastic diseases (mainly in the case of large doses of the drug);
- pancytopenia;
- alopecia (partial or complete);
- hypertrichosis;
- irritation of the mucous membranes of the digestive tract;
- heaviness in the epigastric region;
- dysuric phenomena;
- hematuria;
- weakness;
- blurred vision;
- dizziness;
- nausea, sometimes with vomiting;
- tremor;
- convulsive seizures;
- paresthesia;
- anorexia;
- anemia
- hyperkalemia;
- thrombocytopenia;
- reversible forms of amenorrhea and dysmenorrhea.
A warning
Patients treated with ciclosporin should have their blood tested twice a week because ciclosporin is not indicated for white blood cells below 3500 cells per cubic meter. mm and a platelet level of less than 100,000 cells per µl. Strict observance of a dosage and time of reception of means is necessary. Close contact with infectious patients should be avoided.
Contraindications
These include:
- thrombocytopenia;
- leukopenia;
- anemia;
- cachexia;
- bone marrow hypoplasia;
- severe pathologies of the heart, kidneys, liver;
- oncological diseases;
- hypersensitivity to components;
- arterial hypertension;
- acute eye infections (when applied topically);
- pregnancy;
- lactation period;
- age up to 1 year.
Reviews
There are not very many reviews on the use of this immunomodulator in psoriasis. Patients generally note a significant number of undesirable effects, which may be due to excess dosage or duration of treatment. Many patients point to the mitigation of the symptoms of psoriasis, but some users note that the effect was temporary: after improvement, they experienced an exacerbation of the disease. Almost all patients mention the high cost of the drug.
Price
The price of this immunomodulator depends on the dose and form of release and can vary from 2300 rubles for 10 capsules of 25 mg to 9900 rubles for 10 capsules of 100 mg.
The drug was developed as an anticancer agent. It was soon noticed that when it was taken, the severity of psoriatic rashes was significantly reduced. Today Methotrexate is used to treat severe forms of psoriasis and other autoimmune diseases. Taking large doses of the drug leads to blocking the synthesis of DNA and RNA and prevents the reproduction of cells - in particular, tumor cells. However, in the treatment of psoriasis, a much lower dose of the drug is used than in oncological diseases (about 100 times). 
Experts believe that Methotrexate acts in a different way in autoimmune pathologies. According to one theory, it masks certain molecules so that immune cells cannot detect them. Without these molecules, cells do not accumulate on the skin and do not provoke inflammation, leading to the formation of plaques.
Application
This immunomodulator is prescribed for lesions of more than 20% of the skin area, as well as for the development of atypical and pustular varieties of psoriasis, psoriatic arthritis and erythroderma. The drug is also effective in case of damage to the nails.
It is applied:
- Three times a week orally, 2.5 mg with an interval of 12 hours. The duration of the course is 4-5 weeks.
- Intravenously and intramuscularly. The dose is 10-30 mg once a week. The duration of treatment is 5 weeks.
Side effects
- Nausea.
- Headaches.
- Skin reactions.
- Allergic rashes.
- Otitis.
- Damage to the tissues of the liver, kidneys and bone marrow.
- Lung diseases.
- Gastrointestinal disorders.
- Stomatitis.
- Gingivitis.
- Pharyngitis.
- Pyoderma.
- Leg ulcers.
- hemorrhagic syndrome.
- Anemia.
- thrombocytopenia.
- Leukocytopenia.
- Violation of the menstrual cycle.
- Cystitis.
- Miscarriage.
- Congenital defects of the fetus.
Contraindications
These include:
- dysfunction of the liver and kidneys;
- peptic ulcer;
- bone marrow diseases;
- pregnancy, pregnancy planning;
- lactation.
Reviews
Patients emphasize the effectiveness of the drug, a significant reduction in the number of plaques, but only during the period of treatment with Methotrexate. Many are afraid to take it because of the high risk of damage to the liver and kidneys.
Price
The immunomodulator can be bought at the following prices:
tablets of 2.5 mg - 250-300 rubles;
tablets of 10 mg (50 pcs.) - 450-600 rubles;
injection solution in 50 mg ampoules (5 pcs.) - 2500-5000 rubles.
Refers to drugs of selective action used in severe and moderate forms of psoriasis. Studies show that this immunosuppressant is effective when the body is resistant to other treatments. The drug improves the quality of life of patients, prolongs remission, reduces the risk of relapse. 
Application
Infliximab is used for psoriasis and progressive psoriatic arthritis in case of involvement of at least 5 joints. Patients are prescribed intravenous injections using an infusion system of 3-5 mg / kg. The maximum injection rate is 2 ml per minute. Often used in combination with Methotrexate.
Side effects
Nervous system and sense organs:
- headaches;
- dizziness;
- fatigue;
- depression;
- amnesia;
- sleep disturbance;
- confusion;
- keratitis;
- conjunctivitis;
- meningitis;
- paresthesia;
- neuropathy.
Cardiovascular system and blood:
- heart failure;
- arrhythmia;
- increase or decrease in blood pressure;
- bradycardia;
- vasospasm;
- thrombophlebitis;
- anemia;
- thrombocytopenic purpura;
- lymphocytosis.
Respiratory system:
- pneumonia;
- bronchitis;
- sinusitis;
- pulmonary edema;
- dyspnea.
Gastrointestinal tract:
- nausea;
- indigestion;
- gastroesophageal reflux;
- liver dysfunction;
- cholecystitis;
- pancreatitis;
- hepatitis;
- gastrointestinal bleeding;
- bowel perforation
Urogenital system:
- vaginitis;
- swelling;
- urinary tract infections.
- dryness;
- violation of pigmentation;
- cyanosis;
- sweating;
- rosacea;
- seborrhea;
- allergic reactions;
- alopecia;
- vasculitis;
- erythema.
Other side effects:
- myalgia;
- arthralgia;
- fever;
- pain in the chest, abdomen, back.
Contraindications
- Hypersensitivity to components (including mouse proteins).
- Severe infections: tuberculosis, sepsis, abscess.
- Age up to 18 years.
- Pregnancy.
- breastfeeding period.
Reviews
Most patients leave positive feedback about this immunomodulator, emphasizing the achievement of long-term remission even in severe forms of psoriasis. Negative reviews are mainly associated with the occurrence of side effects. Patients often mention fatigue, headaches, nausea. Many are also not satisfied with the price of the drug.
Price
This is quite an expensive drug. One bottle of Infliximab costs from 24,000 to 50,000 rubles.
The drug is a humanized recombinant monoclonal antibody derived from Chinese hamster ovary cells. It suppresses activated T-lymphocytes, influencing immunological processes, helps to reduce the severity of clinical manifestations of psoriasis, reduce symptoms of inflammation and improve skin condition.
Application
The remedy is prescribed for plaque form of psoriasis of severe and moderate degree. Efalizumab is administered subcutaneously, periodically changing the injection site. The solution is prepared immediately before use. The initial dose is 0.7 mg/kg. The following injections are carried out once a week, the dose of the administered drug is increased to 1 mg / kg. The therapy lasts 12 weeks.
In the presence of positive dynamics, treatment is continued. If after a 12-week course there is no noticeable clinical effect, therapy should be discontinued.
Side effects
- Flu-like syndrome: cold symptoms, headache, nausea, myalgia.
- Reactions at the injection site: redness, allergic rashes, urticaria.
- Lymphocytosis and leukocytosis.
- thrombocytopenia.
- severe infections.
- On the part of the liver: increased levels of alkaline phosphatase and hepatic transaminases.
- Neoplasms of a benign and malignant nature.
A warning
Since the drug belongs to immunosuppressants, in the treatment of psoriasis in patients with recurrent or chronic infectious diseases, a serious infectious disease may develop.
During the use of Efalizumab, constant monitoring of the number of platelets and leukocytes is necessary.
Contraindications
- Hypersensitivity to the drug.
- Severe infectious diseases: tuberculosis, sepsis, hepatitis B, C.
- Malignant neoplasms.
- Vaccination with live bacteria.
- The patient's age is up to 18 years.
- Pregnancy.
- Lactation.
The drug is used with caution in hepatic, renal failure and in the treatment of elderly patients.
Reviews
Due to the high risk of developing serious infectious diseases, including progressive multifocal leukoencephalopathy (PML), the FDA does not recommend starting treatment of new patients with this drug. If the patient is already on Raptiva, they should be closely monitored for neurological signs suggestive of PML. With a patient continuing treatment with the drug, discuss options for alternative therapy.
It is a peptide of synthetic origin, consisting of glutamic acid and tryptophan. It has immunosuppressive properties, inhibits the reactions of cellular and humoral immunity. Helps to reduce the number of lymphocytes in the composition of peripheral blood, proportionally reduces the levels of suppressors and helpers, inhibits the proliferation of T-cells. The immunomodulator does not have toxicity, it is quite effective at a low dosage. It can be used in the treatment of psoriasis and to prevent the recurrence of the disease in adults and children. 
Application
1-2 ml of the drug is administered intramuscularly. The duration of the course is 7-10 days, after which a 2-day break is necessary. After that, the therapy is repeated in a similar way. Depending on the severity of symptoms, 3-5 cycles are carried out.
Intranasal administration of the spray is advisable for the prophylactic use of the drug, during maintenance therapy and in the treatment of children. 1 or 2 doses are administered into each nasal passage. The duration of the course is 7-10 days. After a 14-day break, the course can be repeated.
With generalized psoriatic erythroderma, intramuscular injection of a solution (2 ml each) is indicated for 2 weeks, after which they switch to the use of a spray and medium doses of glucocorticosteroids.
Side effects
- As a result of the repeated course, a decrease in the number of leukocytes is not excluded.
- Allergic reactions are possible.
A warning
In the event of unforeseen adverse reactions, you should consult a specialist.
The drug is not prescribed simultaneously with immunostimulants.
Contraindications
- Acute phase of infectious and viral diseases.
- uncontrolled hypertension.
- Individual intolerance to the drug.
- Pregnancy.
- breastfeeding period.
by Harius in Treatment // 0 Comments
Injections for psoriasis show the best result of the entire set of drugs aimed at combating the disease. Along with ointments, creams, shampoos, they can quickly affect the course of the pathology, relieve its symptoms. As a rule, they are prescribed for moderate and severe degrees of complexity of the disease, and only in cases where local and general treatment has not given the desired result.
Injections for psoriasis, depending on the active ingredient in their composition, are divided into the following categories:
- Immunosuppressants.
- Antihistamines.
- Glucocorticosteroids.
- Hepatoprotective agents.
- monoclonal bodies.
Which injections for psoriasis are preferable to use depends on the characteristics of the course of the disease, its stage and form.
Immunomodulators
These drugs perform a regulatory function. They normalize metabolism in tissues and cells. Immunomodulatory injections for psoriasis have anti-inflammatory, desensitizing, hemostimulating properties.
After the use of injections, the metabolism in tissues and cells is regulated, the disease proceeds in a milder form, and the duration of remission increases. The patient feels much better as the symptoms of psoriasis go away. The standard course of therapy lasts from 10 days to a month. Injections are contraindicated for pregnant women, nursing mothers, people with individual drug intolerance.
"Pyrogenal" 
It belongs to the group of bacterial origin of liposaccharides. It is isolated from Pseudomonas aeruginosa or microorganisms that provoke typhoid fever. Injections for psoriasis are given daily or every 1-3 days. During treatment, up to 30 injections are performed. After a 3-month break, therapy can be repeated.
"Thymodepressin"
Reduces the activity of cellular and humoral immunity. For psoriasis, use weekly courses with a 2-day break. Depending on the complexity of the course of the disease, 3-5 courses are carried out.
The drug is able to restore immunological reactivity, normalizes the volume of lymphocytes. Used in the complex therapy of psoriasis and other pathologies in which there is a decrease in cellular immunity. It is an effective bio- and immunostimulator. Injected into muscle tissue daily. In some cases, injections are performed every other day. The course reaches 30 days.
"Polyoxidonium" 
The tool increases a person's resistance to infections. The drug has immunomodulatory properties, directly affects phagocytic cells, stimulates the formation of antibodies.
An effective immunomodulator that has a cytoprotective effect. The drug modulates processes inside cells, affects thiol metabolism, which affects the regulation of genetic processes and metabolism. The drug increases the effectiveness of phototherapy. Injections of "Glutoxim" can reduce the toxic effect of "Methotrexate" on the liver and circulatory system, which allows its full use. The course of treatment for psoriasis includes 25 injections.
Immunosuppressants
New immunosuppressants give a good result due to the inclusion in the composition of monoclonal bodies. For the treatment of psoriasis, it is enough to perform several intramuscular injections. Often an obstacle to the use of immunosuppressants is their high cost. The second disadvantage of medications is the suppression of the immune system as a result of their work, which can cause other serious diseases.
Preparations of this group cannot be used in case of individual non-acceptance of their composition by the body, with complex infectious pathologies, oncological diseases. It is forbidden to give injections to children under the age of majority, during pregnancy and lactation.
"Thymodepressin" 
The properties of the drug are based on a decrease in humoral and cellular immunity, a decrease in the activity of lymphocytes. The drug is prescribed for autoimmune pathologies, both independently and as part of complex therapy. Get rid of psoriasis with the help of "Timodepressin" will not work. It is used as part of the complex treatment of the disease. To improve the patient's condition, intramuscular or subcutaneous injections are prescribed in a volume of 2 ml. Treatment may consist of 2-5 week courses, between which they take a break for 2 days.
Hepatoprotectors
Medicines in this group are the safest. They have practically no contraindications. Designed primarily for cleansing the body, in particular the liver. Hepatoprotectors remove toxins well, have antioxidant, regenerating and detoxifying properties. The standard course of therapy includes 10-15 injections.
An effective hepatoprotective agent, the active substance of which is ademetionine. The medication has the following effect: 
- antioxidant;
- regenerating;
- neuroprotective;
- cholekinetic;
- choleretic;
- detoxification;
- antifibrosing.
At the initial stage of treatment, intramuscular or intravenous injections are performed, after which they switch to taking pills. The daily dosage varies from 5 to 12 mg per 1 kg of body weight.
The active element of the drug is ademetionine. "Heptor" refers to antidepressant hepatoprotective drugs. It has a detoxifying, cholekinetic, antifibrosing, antioxidant effect. The tool replenishes the deficiency in the body of ademetionine and accelerates its production. Injected into a vein or muscle. The first 2-3 weeks shows the use of 0.4 - 0.8 mg. Switching to tablets is possible.
Antihistamines
The purpose of antihistamines is to:
- sedative;
- antipruritic;
- anticholinergic;
- decongestant;
- local anesthetic;
- antiserotonin;
- antispastic action.
Antihistamines are prescribed for allergic manifestations of psoriasis.
"Tavegil" 
The drug relieves allergies, itching, reduces vascular permeability, stops exudation. It also shows sedative and anticholinergic effects. Use injections for psoriasis twice a day, 2 ml. For prevention, "Tavegil" is injected into a vein by drip.
"Chloropyramine"
Effective blocker of histamine receptors. Facilitates the course and prevents allergies, facilitates its manifestations. The tool relieves itching and soothes, creates a hypnotic effect. The drug has a moderate antispasmodic and anticholinergic activity. Adults and children are shown the introduction of a 2% solution 2-3 times a day. The dosage varies from 6.25 to 12.5 mg.
"Methotrexate"
An antitumor agent related to antimetabolite drugs, folic acid antagonists. It inhibits the reproduction of purine nucleotides and thymidylate, resists cell division and growth, as well as tissue proliferation, which is observed in psoriasis.
Due to the risk of complications, the use of Methotrexate is justified for large psoriatic lesions occupying more than 20% of the body surface. The drug is prescribed for developing arthritis in psoriasis, erythroderma, nail lesions, pustules, as well as for atypical forms of the disease, which cannot be eliminated through photochemotherapy and local preparations.
There are several options for using methotrexate for psoriasis. More effective is the administration of the drug once a week with exacerbations of the disease at a dosage of 10-30 mg.
"Calcium gluconate"
The drug is widely used in the complex treatment of psoriasis. Injections can strengthen blood vessels, relieve inflammation, swelling and itching on the skin. Dermatologists confirm the effectiveness of the drug in all forms of the disease, especially with manifestations of weeping and unbearable itching, in the presence of affected areas on the legs, in the folds of the body.
"Calcium Gluconate" has the following properties:
- anti-allergic;
- desensitizing;
- anti-inflammatory;
- detoxification;
- reduces the permeability of blood vessels and cell membranes.
The use of the drug is contraindicated in hyperkalemia, thrombophlebitis, hypercoagulability, arterial hypertension. For psoriasis, injections into muscle tissue or a vein of a 10% form of gluconate are performed. Adult patients are shown the introduction of 5-10 ml of a solution from 1 to 3 times a day or every other day. The dosage for children depends on age and can reach 5 ml. Introduce "Calcium Gluconate" to children every 2 to 3 days.
The medicine is well tolerated by patients. It reduces the severity of psoriasis symptoms, relieves itching and swelling, improves sleep, eliminates nervousness and irritability.
"Sodium thiosulfate"
The drug binds toxic substances that are excreted from the body with urine. This allows you to bring the enzyme system back to normal. Also, the medication improves the condition of the nervous system, has a positive effect on vascular permeability. With psoriasis, Unitol injections are used on an outpatient basis to relieve intoxication. To do this, you need to perform 10 injections into the muscle tissue, per day - 1 injection. Do not use the remedy for liver dysfunction and hypertension.
Glucocorticosteroid drugs
This group of medicines is characterized by anti-inflammatory, immunosuppressive and anti-allergic effects. Glucocorticosteroids can only be used if other therapies have failed. Since they are addictive, they should be used for a short period. During the year, no more than 3 - 5 injections are performed. You can not prescribe injections to pregnant women, patients with endocrine system disorders, during lactation.
It has anti-allergic, anti-rheumatic and anti-inflammatory properties.
An effective remedy for psoriasis with the following properties: 
- immunosuppressive;
- antidote;
- desensitizing;
- antishock;
- anti-inflammatory;
- improves metabolism.
In addition, the drug shows a pronounced glucocorticosteroid effect with a low mineralocorticoid activity. The active ingredients are: betamethasone phosphate and sodium dipropionate.
Doctors are ambivalent about the need to use the drug "Diprospan" for psoriasis. Some experts point to the high effectiveness of the drug for psoriasis, others talk about multiple side effects during therapy. At the same time, there is a high probability of an exacerbation of the disease, as well as its flow into a complex hormone-dependent form.
Injections from psoriasis "Diprospan" instructions for use prescribe to be done intramuscularly. As a rule, the course of treatment includes the implementation of 3 injections, between which a 14-day interval is observed.
It is forbidden to use the product when:
- diabetes
- glaucoma;
- complicated hypertension;
- pregnancy;
- mental illness;
- tuberculosis;
- various types of infections;
- stomach ulcer.
With long-term therapy, Diprospan injections, reviews indicate this, can cause side effects in the form of: disorders of the nervous system, gastrointestinal tract, metabolism.
"Dexamethasone"
Hormonal drug that suppresses the action of hyaluronidase, collagenase. The drug reduces vascular permeability, regulates the formation of cartilage and bone tissue, and normalizes the activity of cell membranes. The tool stops proliferation and relieves inflammation. 
Reviews of physicians point to the anti-shock, anti-allergic, immunosuppressive and anti-inflammatory effects of the drug. For therapy, droppers or injections of "Dexamethasone" are prescribed, which helps patients with psoriasis. The medicine is used for 4 days, injecting the solution 3-4 times a day. The dosage varies from 4 to 20 mg.
Reviews and instructions for use "Dexamethasone" warn of multiple contraindications and side effects. In the treatment of psoriasis, there may be a deterioration in the state of the cardiac and vascular systems, metabolism, immunity, stomach, intestines, endocrine system, and skin.
Monoclonal antibodies
A new drug for psoriasis, according to Indian pharmacists, is an effective and safe drug. The drug significantly improves the patient's condition, increases the duration of the remission period. The drug is intended for intravenous administration. Therapy is carried out for 6 months.
The agent is an absolute analogue of human monoclonal bodies. The active ingredient is ustekinumab. The work of the Stellara drug, which improves the patient's condition with psoriasis, is to block the reproduction and activity of proteins that provoke the development of the disease. 
After using the product, the symptoms of psoriasis are significantly reduced, including hyperplasia and proliferation of skin cells. The best result can be achieved in the treatment of moderate and severe forms of plaque psoriasis. The drug "Stellara" instructions for use allow for use by adult patients.
The dosage is 45 mg of solution. The second injection is performed in a month. Then injections are given every 3 months. With a patient's body weight above 100 kg, the dosage is increased by 2 times. If there is no result after 6 months of treatment, the use of the medication is stopped.
The drug has a selective immunosuppressive effect. It is represented by humanized monoclonal antibodies. It is used for the treatment of complex and moderate forms of psoriasis in adult patients.
Selective immunosuppressant, often used in conjunction with methotrexate. The drug is prescribed for chronic forms of psoriatic arthritis and plaque psoriasis. Injections are performed under the skin in the abdomen or in the thigh area 1 time in 2 weeks. The second injection is given after a week break. The course of treatment is 3 months.
"Remicade" 
The drug is a complex of human and mouse monoclonal antibodies. It is used in the treatment of complex forms of psoriasis in adult patients. Assign a remedy in extreme cases in the absence of a result from the use of other medicines. Injections are made by drip into a vein. The initial dosage includes 5 mg/kg of solution. The second injection is performed after 2 weeks, the third - after a month. Then injections are done every 1.5 - 2 months. Treatment is combined with the drug "Methotrexate".
Patient reviews indicate a positive result after 3 months of using the product. Significantly improves the condition of psoriatic arthritis, reduces inflammation and returns to normal differentiation of keratocytes.
How to give injections for psoriasis: rules for conducting
Injections of drugs against psoriasis give a quick and stable result, allow you to achieve a long-term remission. When using injections, you need to remember a number of rules:
- Injections for psoriasis are prescribed only in extreme cases, with the ineffectiveness of local and general treatment. As a rule, indications for use are complex forms of the disease, including psoriatic arthritis.
- Injections should be carried out only under the supervision of a specialist. This is insurance against unforeseen complications, when the patient may need immediate medical attention.
- When performing injections, it is necessary to strictly adhere to the recommendations of the instructions for use, the indicated dosage and the therapy regimen.
The success of psoriasis treatment depends on an integrated approach to therapy. In addition to injections, it is recommended to use ointments, creams, physiotherapy procedures. The success of therapy also depends on a positive mood. Injections for psoriasis patient reviews are recommended to be carried out in a hospital, as they can cause side effects.
Biological therapy of psoriasis and psoriatic arthritis. XV All-Russian Congress of Dermatovenereologists and Cosmetologists. Janssen satellite symposium
- KEY WORDS: psoriasis, arthritis, ustekinumab, etanercept, adalimumab
Latest news on biological therapy for psoriasis and psoriatic arthritis: focus on ustekinumab (IL-12/23)
The evolution of biological therapy is on the way to improve the effectiveness and safety of drugs, as well as the convenience of their use by the patient. These drugs include ustekinumab, which is a human monoclonal antibody that blocks the biological activity of interleukins (IL) 12 and 23. Professor Luis PUIG (Hospital de la Santa Creu i Sant Pau, Barcelona, Spain) drew the audience's attention to the latest data from international clinical trials of efficacy and safety of ustekinumab in psoriasis and psoriatic arthritis.
An important advantage of a biological preparation, according to the professor, is the duration of the therapeutic effect. The PSOLAR international prospective study examined the safety profile and duration of use (resistance) of therapy in patients with psoriasis and psoriatic arthritis 1, 2 (Fig. 1).
Ustekinumab was the most stable therapy compared to infliximab (p = 0.0014), adalimumab (p 3 ). This is also demonstrated by the data of the PSOLAR study: ustekinumab therapy stability was statistically higher than that of TNF-alpha blockers in patients with psoriasis and psoriatic arthritis. A similar trend was observed in a subgroup of naive psoriatic arthritis patients, as well as in psoriatic arthritis patients who had previously used biologics.
The ability to extrapolate the results of the above studies into real clinical practice was demonstrated by L. Puig using his own cohort study as an example. 428 patients from two medical institutions took part in it. Patients received a total of 703 courses of therapy: 231 courses with adalimumab, 248 with etanercept, 140 with ustekinumab, and 84 courses with infliximab. “We tried to analyze whether there are differences between the drugs, as well as the reasons for the different data on the resistance of therapy with these drugs,” the speaker explained.
Many patients had concomitant diseases: arterial hypertension (30.9%), diabetes mellitus (16.5%), dyslipidemia (28.1%). More than 35% of the participants suffered from psoriatic arthritis. More than half had not previously received biological therapy, in 76% of cases they were prescribed a combination therapy - a biologic drug with methotrexate. Biological preparations were used in accordance with the instructions for use. At the same time, it was possible to adjust the dose depending on the clinical response (Psoriasis Area Severity Index (PASI) 75 or 90).
At week 16 of therapy, PASI-75 was achieved by 60% of patients, and PASI-90 by 41%. The median duration of drug use averaged 31 months. The data obtained at the two institutions were equivalent. The maximum follow-up period was four years.
The results of the study confirmed that against the background of therapy with ustekinumab, a long-term clinical effect is achieved and adherence to treatment is increased (compared to other biological drugs). Thus, by the end of the follow-up, out of 77% of patients who started treatment with ustekinumab, 60% continued to take it (against 42% of patients taking infliximab, 34% of patients taking adalimumab and 30% of patients taking etanercept).
Next, Professor L. Puig analyzed the safety profile of ustekinumab. He noted that the PSOLAR register assessed the incidence of cardiovascular risks, infectious complications and oncological diseases against the background of the use of biological and non-biological drugs. The mean CV event rate for all drugs was 0.33 per 100 patient-years. Men's sex, advanced age, smoking 4 are named among the factors that increase this risk.
The use of biological agents may increase the risk of severe infections. These studies showed that the highest incidence of infections was observed with infliximab (2.49) and adalimumab (1.97), and the lowest with ustekinumab (0.83 cases per 100 patient-years) (Fig. 2) 5 . Predictors for the development of severe infections are older age, diabetes, a history of other infectious diseases, and smoking.
The results of the study did not reveal a significant trend towards an increase in the incidence of malignant neoplasms. Thus, the incidence of malignant neoplasms in patients treated with ustekinumab was comparable to that in the general population (Fig. 3) 6 .
The Phase III CADMUS 7 study evaluated the safety and efficacy of ustekinumab versus placebo in the treatment of patients 12 to 18 years of age with psoriasis who had more than 2% skin area affected. For patients weighing less than 60 kg, half the standard dose of ustekinumab or 0.75 mg/kg was prescribed, from 60 to 100 kg - 45 mg, over 100 kg - at a dose of 90 mg (in accordance with the instructions for use).
At week 12, PASI-75 response was observed in 78.4% of patients receiving half the standard dose of the drug, in 80.6% of patients at doses of 45 mg and 90 mg, and in 10.8% of patients receiving placebo. The response according to PASI-90 criteria was higher in the ustekinumab treatment groups - in 54.1 and 61.1% of patients versus 5.4% of patients in the placebo group (Fig. 4). PASI-100 was achieved in 38.9% of patients taking ustekinumab at standard doses.
The resulting effect persisted until the 52nd week of therapy. No new adverse events in children during therapy with ustekinumab were noted.
Italian researchers have found that the effectiveness of the clinical response to therapy with an IL-12/23 inhibitor can be affected by the presence of the HLA-C06 antigen. It has been proven that it is patients with a positive HLA-C06 antigen that achieved a response according to the PASI-90/100 criteria during treatment with ustekinumab 8 .
In summary, Professor L. Puig noted that ustekinumab has a good safety profile, no decrease in efficacy with long-term use, and higher compliance compared to other biological drugs.
Personalized treatment of psoriasis with biologics: case studies
In the second report, L. Puig presented his own data on the use of ustekinumab. He noted that achieving a response is an indicator of the success of therapy. Before choosing a treatment strategy, you should carefully examine the patient, assess the area of skin lesions, the condition of the joints, clarify the presence of concomitant pathology, the fact of smoking, taking medications.
Clinical case 1. Man, 53 years old. The patient has high blood pressure, type 2 diabetes mellitus, psoriasis vulgaris since the age of 36 plus a family history of psoriasis, psoriatic arthritis since the age of 42. He received several courses of ultraviolet phototherapy (2006, 2008, 2009, 2011) and high-dose methotrexate (15–20 mg/week). Recently, the condition of the skin has worsened and the manifestations of psoriasis (PASI-16) have worsened, the area of the lesion was at least 26%. The overall assessment of the patient's condition by a doctor (Physician Global Assessment - PGA) - 4 points.
Ultrasound examination (ultrasound) showed a thickening of the carotid artery wall, which gave grounds to classify the patient at risk for stroke and myocardial infarction (14% risk according to the REGICOR scale).
In such patients, the choice of a biological preparation should be approached especially carefully. Cyclosporine, for example, increases the risk of serious cardiovascular events. TNF-alpha inhibitors are believed to reduce the risk of developing cardiovascular disease, while ustekinumab does not increase it, although further research in this direction is required.
Infliximab and ustekinumab demonstrate high clinical efficacy, however, infliximab, unlike ustekinumab, can increase body weight, which is undesirable for patients with diabetes mellitus. According to Professor L. Puig, the most justified in this case is the appointment of ustekinumab or adalimumab.
Clinical case 2. Woman, 41 years old. She has been suffering from plaque psoriasis for 20 years. She was treated with efalizumab at a dose of 1 mg/kg. After a short improvement (PASI-12) developed psoriatic arthritis. The patient was prescribed methotrexate at a dose of 20 mg once a week. After a month of treatment, the condition worsened - PASI-30.
In this case, infliximab and ustekinumab can be considered the most preferred drugs, which contribute to a rapid and significant improvement in the condition. Since the risk of developing infections is lower with ustekinumab (compared to infliximab and adalimumab), the choice was made in its favor. “This patient was prescribed ustekinumab at the standard dose. A fairly good answer was received,” the professor stated.
Thus, the choice of biological therapy for psoriasis and psoriatic arthritis should be based on an individual approach to the patient. It is a personalized approach that allows achieving significant improvement and stable remission of the disease.
Interleukin 12, 23 inhibitor - new goals and possibilities for the treatment of psoriasis, psoriatic arthritis
According to the Associate Professor of the Department of Dermatovenereology with the clinic of the First St. Petersburg State Medical University named after I.I. acad. I.P. Pavlov (St. Petersburg State Medical University named after academician I.P. Pavlov), Head of the Center for Therapy with Genetically Engineered Biological Drugs, Ph.D. Marianna Mikhailovna KHOBEISH, in patients with severe psoriasis and psoriatic arthritis, the risk of death is 50% higher, while in half of the cases it is due to cardiovascular disorders 9 .
Usually, patients with moderate and severe psoriasis, psoriatic arthritis are prescribed basic anti-inflammatory drugs - methotrexate, cyclosporine A, synthetic retinoids, sulfasalazine, systemic photochemotherapy. With varying effectiveness, these immunosuppressive agents and methods are not without side effects, in particular, increased atherogenic risk and induction of hypertension. As a result, there are limitations in application. That is why, when prescribing therapy, one should take into account not only the severity of psoriasis, psoriatic arthritis, but also the comorbid background.
According to the conclusions of the expert group of the European Consensus on the Treatment of Moderate and Severe Psoriasis (Delphic Consensus 2010), systemic immunosuppressive therapy, including genetically engineered biological drugs, is indicated:
with moderate and severe (including "problem") psoriasis;
active progressive damage to the musculoskeletal system in the presence of unfavorable prognosis factors;
the presence of comorbid diseases.
It has been proven that pathogenetic therapy of psoriasis and psoriatic arthritis with genetically engineered biological agents reduces the risk of developing comorbid diseases, in particular, metabolic syndrome 10 , insulin resistance, and type 2 diabetes mellitus.
For adequate control of psoriasis, it is necessary to block the activity of TNF-alpha, a pro-inflammatory cytokine, or the biological activity of IL-12, -23 and -17, which play a key role in the pathogenesis of psoriasis. According to M.M. Hobeish, inhibitors of individual ILs are distinguished by a highly specific, more selective nature of their effect on the immunopathogenetic cascade. Currently, dermatologists have at their disposal only one representative of IL inhibitors - ustekinumab (an IL-12/23 inhibitor). The drug is included in the list of vital and essential drugs (VED) and medical and economic standards for the treatment of psoriasis.
The use of biological preparations (genetically engineered monoclonal antibodies) makes it possible to achieve a significant or complete resolution of the disease, prevent destructive changes in the joints in patients with psoriatic arthritis, and provide control over systemic inflammation.
According to the Federal Clinical Guidelines for the Diagnosis and Treatment of Psoriatic Arthritis (2013), in peripheral arthritis, spondylitis, enthesitis, and dactylitis with moderate or severe activity and the presence of poor prognosis factors, TNF-alpha inhibitors or the drug ustekinumab are prescribed (grade of recommendation A). If one TNF-alpha inhibitor fails, the patient is transferred to treatment with another TNF-alpha inhibitor or monoclonal antibodies to IL-12/23 (ustekinumab).
At the Center for Therapy with Genetically Engineered Biological Preparations at the Department of Dermatovenereology, St. Petersburg State Medical University. acad. I.P. Pavlova has accumulated successful experience in the use of ustekinumab in patients with psoriasis and psoriatic arthritis. MM. Hobeish cited two clinical cases as an example.
Clinical case 1. Patient K., 23 years old, disabled person of the second group. She has been observed at the Department of Dermatovenereology since 2009, where she complained of widespread skin lesions, severe pain and significant limitation of range of motion, morning stiffness in the area of small and large joints, psoriatic lesions of the nail plates. Sick of psoriasis for over 17 years. Family history is aggravated (psoriasis in the mother). Over the past seven years, there has been an aggravation of the skin process, a tendency to universalize psoriasis vulgaris, pain in the thoracic and lumbar spine, knee joints, interphalangeal and metacarpophalangeal joints of the hands, metatarsophalangeal and interphalangeal joints of the legs.
Repeatedly treated in hospitals. On the recommendation of a rheumatologist, she received sulfasalazine (about nine months), cyclosporine (more than six months), methotrexate at a dose of 20–25 mg/week for a year and a half. Severe pain in the area of the affected joints persisted, so the patient was constantly taking non-steroidal anti-inflammatory drugs (NSAIDs) at a high dose (200 mg/day).
The ongoing therapy did not give a positive effect, it was noted that new joints were involved in the pathological process. At the same time, there were side effects. So, as a result of long-term use of methotrexate, the level of transaminases increased three times from the initial level, after each dose of the drug, severe nausea and vomiting were noted. On admission to the clinic, body temperature 38–39 °C, generalized lymphadenopathy, universal large plaque psoriasis (skin area > 10%, PASI-58), active progressive psoriatic arthritis with an active acute phase reaction (erythrocyte sedimentation rate - 67–69 mm/h ).
Treatment: The patient was prescribed infliximab therapy. After three injections of the drug, the skin process was practically resolved, the indicators of the acute phase reaction decreased, pain and stiffness of the joints decreased. However, the next injection of the drug was accompanied by an infusion reaction, a decrease in the time of the effective period of drug action was noted, a high level of antibodies to it (> 100) was detected.
The patient was switched to ustekinumab 45 mg. Already after four weeks of therapy, a positive effect on the skin (PASI-50), a decrease in the intensity of pain in the area of small joints of the hands and feet, a decrease in the number of swollen joints, and an increase in the range of motion were noted. At the eighth week of ustekinumab therapy, there was almost complete cleansing of the skin (PASI-90), a decrease in the activity of psoriatic arthritis according to the criteria of the American College of Rheumatology (ACR) by 20%. By the 12th week, a high response to PASI-90 and a trend towards a decrease in the inflammatory process in the joints (ACR 50) remained.
After five years of treatment with ustekinumab, patient K. has no skin lesion (PASI-0), virtually no joint pain, no morning stiffness, slight periarticular edema over the left knee joint, in the area of the small joints of the feet (ACR 70), the need for NSAIDs are rare, serological remission, no radiographic progression. The patient is now getting married and planning a pregnancy. “The advantage of ustekinumab is that in the case of a planned pregnancy or planned surgery, treatment can be paused without a significant loss of effect when therapy is resumed,” the speaker clarified.
Clinical case 2. Patient C. Diagnosis: widespread psoriasis vulgaris (skin area > 10%, PASI-14), progressive psoriatic arthritis, type 2 diabetes mellitus, second-degree obesity, second-degree arterial hypertension, second- or third-degree cardiovascular insufficiency.
Treatment: took ustekinumab at the standard dose of 45 mg subcutaneously. The effectiveness of the prescribed therapy was noted already at the eighth week: PASI-50, ACR 20. After two years of therapy, almost complete cleansing of the skin (PASI-90) and a significant improvement in psoriatic arthritis (ACR 90) were recorded. “Any instability in relation to cardiovascular insufficiency in the patient during therapy with ustekinumab was not observed. Of course, this drug is preferable in patients with cardiovascular risk,” explained M.M. Hobeish. Ustekinumab is registered in the USA, Europe, Russia. In December 2014, it was included in the list of vital drugs, as well as in the draft Russian standards for providing medical care to patients with psoriasis and psoriatic arthritis. The Federal Guidelines for the Treatment of Psoriasis and Psoriatic Arthritis list ustekinumab as a first-line drug along with TNF-alpha inhibitors. In May 2015, ustekinumab was recommended by the Russian Ministry of Health for use in children with severe psoriasis from the age of 12.
Concluding the speech, M.M. Hobeisch focused the attention of the symposium participants on the fact that ustekinumab has won the highest award in the pharmaceutical industry, the Prix Galien Award, three times (in 2010, 2011 and 2012). At the same time, its new mechanism of action, significant efficacy and dosing regimen were especially noted.
Summarizing the materials presented by the speakers, the chairman of the symposium, head of the department of dermatovenereology with the clinic of the St. Petersburg State Medical University. acad. I.P. Pavlova, Doctor of Medical Sciences, Professor Evgeny Vladislavovich SOKOLOVSKII emphasized that the introduction of ustekinumab in the treatment of psoriasis and psoriatic arthritis opens up new prospects for such patients. Ustekinumab is a highly effective biologic with a good safety profile. It allows success even after previous failure or intolerance to the TNF-alpha inhibitors, methotrexate. It is also important that ustekinumab has a high compliance. All this suggests that the use of ustekinumab will provide stable clinical remission in a significant proportion of patients.
Immunomodulators against psoriasis: due to what they are effective
Recent studies in the field of psoriasis therapy pay close attention to the possibilities of drugs that can affect the immune system. Usually these are low molecular weight compounds that have anti-inflammatory, anxiolytic, antioxidant properties and at the same time are able to influence the activity of leukocyte cells. A number of such drugs affect the functional metabolic activity of macrophages, inhibit the production of tumor necrosis factor (TNF-a), interleukins and other pro-inflammatory cytokines. Another property of immunomodulatory drugs that is valuable in the fight against psoriasis is that they can inhibit the production of reactive oxygen species by macrophages, creating obstacles to the development of oxidative stress, which often becomes a characteristic feature of psoriasis. Thanks to immunomodulators, the functional state of macrophages is normalized, which leads to a decrease in the level of autoaggression in the skin, while the functions of G-lymphocytes are restored and the effectiveness of the fight against psoriasis is significantly increased.
Clinical Study
Regarding the action of immunomodulatory drugs and their effectiveness in psoriasis, the following study was conducted.
Treatment. The main group included 19 patients who, along with traditional dermatological treatment, received an immunomodulator in the form of a suppository in a course of 15 every other day. Patients in the control group (18 people) received aevit, calcium preparations and topical salicylic ointment.
Results. The assessment was carried out one month after the start of therapy based on a clinical examination and using the PASI scale: no change - the index does not change or deviates slightly, improvement - the index decreases by 50%, significant improvement - the index is lower by more than 85%, remission stage - complete disappearance of manifestations of psoriasis on the skin.
The results of the study showed that in the complex treatment group, where patients took immunomodulators simultaneously with dermatological prescriptions, the frequency of favorable outcomes was significantly higher.
Laboratory data showed that immunomodulators reduced the production of such an active pro-inflammatory cytokine as skin necrosis factor TNF-a, and normalized the functional activity of T-lymphocytes.
To date, in the treatment of psoriasis, drugs such as lycopene, thymalin, cycloferon, thymodepressin, xymedon, cyclosporine, polyoxidonium, and galavit have demonstrated their effectiveness.
The researchers also note the absolute importance of the antioxidant and anti-anxiety effects of immunomodulators, point out that when prescribing drugs against psoriasis, it is necessary to take into account the close contact of the immune and nervous systems, their direct connection with the skin, which can significantly increase the effectiveness of psoriasis treatment.
What are the best pills for psoriasis?
Tablets for psoriasis are prescribed taking into account the history, age, stage of the disease, the prevalence of rashes, the presence of concomitant pathology and contraindications in each case. Treatment of psoriasis with pills is aimed at suppressing the increased reproduction of skin cells and eliminating inflammation.
Psoriasis treatment - pills
Treatment of psoriasis with medications has the following goals:
- Relief of manifestations of exacerbation of the disease. There are three scenarios for the development of events:
- significant improvement - reverse development of 75% of plaques and more;
- improvement - regression of 50-70% of rashes;
- stabilization - stopping the appearance of a new rash.
- Improving the quality of life of the patient.
Exacerbation of the disease of mild forms is treated with antihistamines, detoxification solutions, anti-inflammatory tablets and local ointments. The approach to the treatment of moderate, severe common forms is the use of retinoids, PUVA treatment, cytostatics, hormonal drugs, immunosuppressants. Vitamins and sedatives are used in all variants of the course of the disease.
During treatment, mistakes are often made that lead to stable forms of the disease and their transition to severe disabling variants.
The most common mistakes in therapy:
- The simultaneous use of tablets that are toxic to the liver, such as retinoids and cytostatics, is not recommended.
- With the simultaneous use of cytostatics and immunosuppressors, a pronounced suppression of immunity is observed.
- Hormonal pills for mild psoriasis are not prescribed due to the possibility of transforming the disease into a severe form.
Hormonal pills
The use of hormonal tablets is due to the powerful anti-inflammatory focus of corticosteroid drugs. Hormones are prescribed during exacerbation of the disease in its exudative form, with erythroderma, arthropathy. This indicates the development of addiction to glucocorticoids, which requires careful analysis when prescribing drugs.
The longer the patient does not take hormonal pills for psoriasis, the more favorable the course of the disease is predicted in the future.
Hormonal pills have the following effect:
- inhibit skin inflammation;
- narrow the vessels of the dermis, suppressing their increased permeability;
- reduce swelling;
- relieve joint pain.
The most commonly used hormonal good remedy for psoriasis - Prednisolone, Triamcinolone, Polcortolon, Metipred - quickly stops inflammation, itching, but shortens the remission for several months or years.
There are many analogues of synthetic corticosteroids, these include: Celeston, Kenakort, Kenalog, Berlikort, Lemod, Decadron, Urbazon and others.
Russian drugs for psoriasis of a hormonal nature - Benacort, Cortisone are characterized by high efficiency, lower cost compared to imported medicines.
Uncontrolled and prolonged use of hormonal pills can lead to Itsenko-Cushing's syndrome. Against the background of psoriasis, the syndrome is much more severe. The disease is characterized by damage to the adrenal glands, manifested by obesity, hypertension, decreased immunity, and often leads to disability.
Side effects of antihistamines
Immunomodulators and immunosuppressants
Types of disease of generalized forms (erythroderma, exudative common psoriasis, arthropathy) are often resistant to treatment with hormonal pills and retinoids. In such cases, doctors prescribe immunosuppressants.
Among the drugs that suppress the immune system, Cyclosporine is widely used, as well as Azathioprine, Leflunomide, Maisept, Revlimid.
Mechanism of action of immunosuppressants:
- artificial suppression of immunity;
- suppression of cell division;
- a pronounced decrease in immune inflammation.
The best medicine for psoriasis, suppressing immunity, such as Cyclosporine, allows patients with severe, generalized forms of the disease to get rid of excruciating pain in the joints, itching of the skin and its inflammatory edema. Some types of the disease occur with a pronounced autoimmune component, so it is impossible to do without immunosuppressants.
Particular care must be taken by patients with impaired renal function, liver, with an increase in uric acid, hyperkalemia.
During treatment with immunosuppressants, blood creatinine and blood pressure are subject to constant monitoring.
Cytostatics
The appointment of cytostatic drugs - substances that stop cell division - is approached with extreme caution. Cytostatics are used to treat psoriasis with its persistent course, the presence of contraindications to other serious drugs.
The psoriasis drug Methotrexate is the most commonly prescribed drug for the treatment of erythroderma and the arthropathic form of the disease.
Methotrexate is taken once a week, and with a severe form of the disease - 3 times a week. Duration of admission - 3-5 weeks.
Methotrexate exhibits severe toxicity, therefore, during treatment, blood and urine parameters are constantly monitored. Determine the level of erythrocytes, platelets, leukocytes, hemoglobin, creatinine, urea, total protein, enzymes, urine parameters.
The appointment of retinoid tablets is justified in case of a common form, erythroderma, plaque form, arthropathy, lesions of the scalp. Drugs inhibit cell reproduction, normalize keratinization.
Aromatic retinoids or vitamin A derivatives are tablets that help with psoriasis of any localization quickly, effectively and without serious consequences. The most commonly used drugs are acitretin (Neotigazon). The course of treatment is 2 - 3 months.
Tablets for psoriasis of the scalp in the form of retinoids in combination with phototherapy, ointments effectively cope with plaque damage to the scalp.
Peculiarities. Women taking retinoids should use contraception for 2 years after taking the pills due to the accumulation of these drugs and their negative effect on the fetus.
Taking retinoid tablets is accompanied by reversible side effects that depend on the dose of the drug.
Side effects include:
- cracked dryness of the mucous membranes of the mouth and lips;
- conjunctivitis;
- temporary increase in the level of liver enzymes and blood lipids.
If the tablets are taken for more than a year, pain in the bones and muscles may occur.
Vitamins and dietary supplements
Among the vitamins for the treatment of psoriasis, doctors prescribe vitamins of group B, ascorutin, vitamin D, A and C. These drugs are effective during remission for the prevention of exacerbations, as they increase the body's resistance, and during exacerbation they help to enhance the effect of essential drugs and neutralize side effects from potent drugs. medicines.
Dietary supplements or homeopathic remedies in the treatment of psoriasis have a number of advantages:
- Normalization of self-regulation mechanisms.
- Wide spectrum of action.
- Safety due to herbal natural composition.
- Lack of addiction.
- No contraindications.
The most popular dietary supplements for psoriasis are manufacturers such as Heel, Deutsche Homeopathie Union, Edas, Loma Lux.
Dietary supplements, like tablets for psoriasis and other skin diseases, are widely used among patients, and the most effective and popular are Lecithin, Rekitsen, colloidal silver, Essentiale, Psorilen.
Sedatives
Stress is one of the triggers for exacerbating the disease and maintaining it in an active form. Emotional instability is inherent in almost all patients with psoriasis. Therefore, the therapy block of any form and type of illness includes sedatives - mint, motherwort, valerian, St. John's wort, as well as psychotropic and antidepressant drugs - Diazepam, Afobazole, Azafen, Coaxil and others.
Antihistamine pills for itching
Itching accompanies psoriasis of all types and forms, so antihistamines are part of the main therapeutic block.
In the foci of psoriatic plaques, a large number of immune cells are concentrated, including mast cells - basophils, the granules of which contain histamine. Itching is initiated precisely by histamine, and the tablets are aimed at blocking the skin receptors for histamine. By blocking them, drugs suppress painful sensations and swelling.
The best remedy for psoriasis, aimed at eliminating itching, is one that lasts at least 8 hours, and such tablets include Clemastin, Loratadin, Mebhydrolin, Chloropyramine.
The most effective pills for psoriasis
The best remedy for psoriasis is a combination of photochemotherapy with topical treatment with ointments and pills. PUVA therapy or photochemotherapy is the effect of ultraviolet rays on the affected skin, while the patient takes special pills - photosensitizers, with which ultraviolet in the skin will interact. At the same time, plaques are treated with ointments, depending on the severity of the process (naftalan ointments, salicylic, ichthyol, hormonal). As part of systemic therapy, patients take retinoids, anti-inflammatory pills (hormonal or non-hormonal). This combination of methods is the most effective and effective in the treatment of exacerbations of psoriasis.
Forms of the disease that affect the scalp often occur with a pronounced inflammatory process. Therefore, tablets for psoriasis on the head should contain hormones to quickly stop itching and exudation.
Notifications In which country is it better to get higher education
How to open a medical center
Raising the housing tax at times will soon seem "flowers"
How to start a flower business
Business for a girl from scratch: the best ideas and approximate calculations