Aim : to assess efficacy and safety of «changeover» to the second genetically engineered biological agent (GEBA) in patients with juvenile idiopathic arthritis (JIA) with resistance or intolerability to the first GEBA. Patients and methods : the results of retrospective observational research of efficacy and safety of «changeover» to the second GEBA in 136 patients with various variants of JIA aged from 1 to 17 years old with primary resistance, partial effect or loss of efficacy to other biological agents are shown in this article. Among those 41 patient have systemic and 95 — JIA without extra-articular involvement. In 32 patients with JIA without extra-articular involvement the efficacy and safety of etanercept were assessed; in 63 — of adalimumab; in 22 patients with JIA and active extra-articular involvement — of tocilizumab, in 5 — of rituximab; in 14 patients with JIA without extra-articular involvement and active arthritis — of tumor necrosis factor (TNF) α inhibitors — adalimumab and etanercept. JIA was diagnosed according to the ILAR criteria. Results : in 6 and 12 months of treatment with the second GEBA inactive stage of disease / remission was detected in 65 and 84% of patients, respectively. In 13/22 patients with JIA and insufficient efficacy of rituximab remission was achieved in 24 weeks of follow-up after switching to the treatment with interleukin (IL) 6 receptors inhibitor, in 2/5 patients with resistance to tocilizumab — after switching to rituximab. In a year of treatment with etanercept as the second GEBA non-active stage / remission was induced in 100% of children with JIA without extra-articular involvement, in 85% — after switching to adalimumab, and in 100% of patients with JIA without extra-articular involvement — after administration of anti-TNF α-therapy. Conclusions : changeover to the second GEBA in patients with primary and secondary resistance or intolerability to the first GEBA allowed achieving of remission of systemic manifestations in patients with JIA and contributed to almost complete restoration of function in the joints in patients with JIA without extra-articular involvement and articular forms of JIA. Along with its high clinical efficacy the second GEBA was characterized by good tolerability and comparable safety profile.

The article presents a case of successful use of an interleukin-1 monoclonal antibody drug (canakinumab) for severe systemic juvenile idiopathic arthritis refractory to treatment with classic immunosuppressants and genetically engineered biopharmaceuticals with a different mode of action. Canakinumab treatment shortly provided reduction in clinical and laboratory parameters of the disease activity, life quality improvement, development of an inactive disease stage and allowed reducing the prednisolone dose by 90% and avoiding intravenous and intraarticular administration of glucocorticoids.

This article presents a case of severe course of polyarticular juvenile idiopathic arthritis. Active articular syndrome, high laboratory parameters of disease activity, severe incompetence were observed in a child by the therapy initiation. Successful use of intramuscular methotrexate in the dose of 15 mg/m2 of body surface per week is described. Exudative articular alterations, arthralgiae, morning stiffness duration reduced as early as one month after the therapy initiation in a child. Acute inflammatory articular alterations cut off, range of motions recovered completely in 4 out of the 6 affected joints, laboratory parameters of disease activity reduced and normalized (ESR and CRP), inactive disease stage was registered after 6 months of treatment. We did not observe any undesirable phenomena in the setting of methotrexate therapy.

The case of early debut and heavy course of juvenile idiopathic arthritis in the patient at the age of 1 year and 8 months, associated with uveitis refractory to the therapy by methotrexate and nonsteroid antiinflammatory preparations is presented. The given clinical example shows high therapeutic efficiency of the adalimumab. To the 8th week of treatment inflammatory changes in conjunctiva were stopped, to the 12th week the stage of inactive illness was registered, i.e. the patient had no inflammatory changes in joints, uveitis activity signs, increase of laboratory indicators of illness activity. Duration of remission of articulate syndrome and uveitis made 9 months.

Aim: to carry out a retrospective analysis of efficacy and safety of tocilizumab treatment in children with severe resistant forms of systemic juvenile idiopathic arthritis. Patients and methods: 75 patients (35 girls and 40 boys) aged 8,8 (6; 12) years old with severe systemic juvenile idiopathic arthritis resistant to routine immunosuppressive therapy were included to the study. The mean duration of the disease before tocilizumab administration was 3,2 (1,9; 5,2) years. The diagnose was made based on the ILAR criteria. All patients were performed standard clinical and laboratory examination. The efficacy of treatment was assessed according to the pediatric criteria for improvement of the American College of Rheumatology. The frequency of achievement of non-active stage and medicinal remission of the disease were considered to be the target characteristics of the treatment efficacy. Results: in 6 months of treatment non-active stage of the disease was recorded in 64% of patients, in 12 months — in 73% of patients. Undesirable effects were represented by mild and moderate infections as well as changes in certain laboratory indexes: leucopenia, granulocytopenia, increased transaminase activity. Conclusions: tocilizumab is a highly effective drug in treatment of patients with the most severe systemic form of juvenile arthritis resistant to steroids, methotrexate, cyclosporine, as well as combined immunosuppressive therapy and anti-TNF and anti-B cell therapy.

Aim : to assess efficacy and safety of rituximab treatment in children with systemic juvenile idiopathic arthritis under prolonged follow-up. Patients and methods: results of treatment of 60 children (33 girls and 27 boys) with systemic variant of juvenile idiopathic arthritis being followed-up in rheumatology department of the Federal State Institution «Scientific Centre of Children Health» of RAMS (FSI «SCCH» RAMS) were analyzed. The mean age of children was 8,7 years. The mean duration of disease course at the moment of first rituximab administration was 5,3 years. At the beginning of rituximab therapy all children had active articular syndrome, severe systemic manifestations and significantly increased laboratory markers of activity. As the signs of improvement the authors used pediatric criteria of the American College of Rheumatology. The treatment was approved by the local ethic committee of the FSI «SCCH» RAMS; the patients’ representatives and patients older than 14 years old had signed informed agreement. Results: remission was induced in 26 of 60 (43%) patients: in 9 of them after the 1 st course of treatment, in 8 — after the 2 nd , in 6 — after the 3d and in 3 — after the 4 th . The maximal duration of remission was 5 years 4 months, minimal — 6 months. Other genetically engineered drugs were administered to 34 (57%) of the patients: due to the primary inefficiency in 15, secondary inefficiency — in 10; due to partial inefficiency — in 9 children. The drug was well-tolerated in most of the patients. Undesirable effects were represented by transfusional reactions to the rituximab infusion, infections with different severity and granulocytopenia. Conclusions: rituximab has high efficiency in patients with severe systemic variant of juvenile idiopathic arthritis. The drug induced remission in patients who had been considered almost incurable, with low status of physical and social adaptation.

The article offers successful application of a preparation of human monoclonal antibodies to tumor necrosis factor (TNF) α – adalimumab – in the setting of a severe course of juvenile idiopathic arthritis characterized by inefficiency of the standard antirheumatic therapy and secondary resistance to chimeric antibodies to TNF α. Adalimumab treatment secured overcoming of the secondary infliximab inefficiency, rapid disease activity decrease, peripheral joints’ function recovery and the patient’s functional activity increase in a short space of time. The drug averted the patient’s steadily progressing incapacitation and induced the clinical-laboratory disease remission development.

Aim: to assess efficacy and safety of abatacept usage in children and adolescents with polyarticular juvenile idiopathic arthritis without systemic manifestations. Patients and methods: 15 patients aged 13 (11; 14,5) years old were included into the study; the mean duration of disease course was 4 (3; 5) years. The disease was diagnosed based on the ILAR criteria. All the patients were performed routine clinical and laboratory examination. Efficacy of treatment was assessed according to the pediatric criteria for improvement of the American College of Rheumatology (ACRpedi). Target characteristics of treatment efficacy were: the number of patients with 30/50/70/90% improvement according to the ACRpedi criteria during first 4 months from the therapy administration, and then – every 2 months; percentage of non-active stage and remission achievement. Results: in 4 months after beginning of treatment improvement according to the ACRpedi 30/50 criteria was observed in 60/30% of patients; in 6 months according to the ACRpedi 30/50/70 criteria — in 80/40/40%, respectively; in 12 months according to the ACRpedi 70 criteria — in 80% of patients. Non-active stage of disease in 6 and 12 months was confirmed in 6/15 (30%) and 10/15 (60%) of patients, respectively. Remission was confirmed in 10/15 (60%) of children in 12 months of therapy. Side effects were observed in 6/15 (40%) of children and were mild. Three patients had relapses of Herpes labialis infection, 3 other had acute respiratory tract infections. Conclusions: abatacept is effective for treatment of polyarticular juvenile idiopathic arthritis, resistant to steroids, methotrexate and combined immunosuppressive treatment.

A history case of a patient with psoriatic arthritis, characterized by severe disease course, systemic symptoms, significantly increased laboratory markers, polyarticular syndrome, typical skin and nails changes, rapid development of patient’s disability and low quality of his and his family life is presented in this article. The authors showed high efficacy of treatment with biological agent — etanercept. In 3 months of treatment non-active stage of disease was achieved, in 9 months — clinical and laboratory remission, not only of the articular syndrome, but also of the extra-articular and dermatological manifestations and laboratory markers of the activity.

Aim: to assess efficacy and safety of hypodermic methotrexate injections in children aged from 1,5 to 16 years old with juvenile idiopathic arthritis (JIA) without extra-articular manifestations. Patients and methods: the results of treatment of 104 patients with JIA without systemic manifestations (61 girls and 43 boys) aged 5,0 (1,5–16) years old being followed-up in the rheumatology department of FSFI «SCCH» of RAMS were analyzed. The mean duration of the disease at the moment of methotrexate first administration was 6 months. Efficacy of methotrexate therapy was assessed according to the pediatric criteria for improvement of the American College of Rheumatology. The percentage of non-active stage and medicinal remission achievement were considered to be the target characteristics of therapy efficacy. Results: 61 patients (59%) were maintained in the study during 1 year. In 12 months of treatment remission according to C. Wallace criteria was induced in 39 of 104 (38%) children. In 22 (21%) of patients who failed to achieve remission in 1 year of treatment, 70% improvement was observed. Side effects were found in 45 (43%) of children: mild and moderate — in 33 (32%), severe — in 12 (12%) of patients. In 9 patients methotrexate was withdrawn due to intolerance of the drug. These patients as well as 34 children with resistance to performed treatment were administered genetically engineered biological agents. Conclusions: hypodermic injections of methotrexate are highly efficient in patients with JIA without extra-articular manifestations. Early administration at the dose of 15 mg/m2 of body surface as well as appropriate selection of administration form induced remission and allowed to prevent of disability development in 38% of children.

Aim: to assess efficacy and safety of rituximab treatment in children with systemic juvenile idiopathic arthritis under prolonged follow-up. Patients and methods: results of treatment of 60 children (33 girls and 27 boys) with systemic variant of juvenile idiopathic arthritis being followed-up in rheumatology department of the Federal State Institution «Scientific Centre of Children Health» of RAMS (FSI «SCCH» RAMS) were analyzed. The mean age of children was 8,7 years. The mean duration of disease course at the moment of first rituximab administration was 5,3 years. At the beginning of rituximab therapy all children had active articular syndrome, severe systemic manifestations and significantly increased laboratory markers of activity. As the signs of improvement the authors used pediatric criteria of the American College of Rheumatology. The treatment was approved by the local ethic committee of the FSI «SCCH» RAMS; the patients’ representatives and patients older than 14 years old had signed informed agreement. Results: remission was induced in 26 of 60 (43%) patients: in 9 of them after the 1st course of treatment, in 8 — after the 2nd, in 6 — after the 3d and in 3 — after the 4th. The maximal duration of remission was 5 years 4 months, minimal — 6 months. Other genetically engineered drugs were administered to 34 (57%) of the patients: due to the primary inefficiency in 15, secondary inefficiency — in 10; due to partial inefficiency — in 9 children. The drug was well-tolerated in most of the patients. Undesirable effects were represented by transfusional reactions to the rituximab infusion, infections with different severity and granulocytopenia. Conclusions: rituximab has high efficiency in patients with severe systemic variant of juvenile idiopathic arthritis. The drug induced remission in patients who had been considered almost incurable, with low status of physical and social adaptation.

PURPOSE:To evaluate the safety and efficiency of adalimumab in children with severe refractory JIA with primary inefficiency, partial effect or loss of the effectiveness of other biologicals.PATIENTS AND METHODS:The article presents the results of the retrospective observational study of the efficacy and safety of adalimumab in 68 patients aged 10 (3, 17) years with various embodiments of JIA, with the primary inefficiency or partial or loss of the effectiveness of other biologicals. JIA diagnosis established on the basis of criteria ILAR (International League of Associations for Rheumatology).RESULTS:Efficacy was assessed during 1 year in 68 and 2 years--in 56 patients . At the 24th week we observed the improvement by criteria AKR 30, 50.70 in 100, 91 and 74% of patients, respectively, and at the 52th week--in 100, 96 and 90%, respectively. Inactive disease status was recorded in 55.8, 66.1 and 98.2% of study participants after 6 months, 1 and 2 years, respectively. Remission was achieved in 55.8 and 96.4% of patients after 1 and 2 years of observation, respectively.CONCLUSIONS:Adalimumab was effective and well tolerated by patients with primary inefficiency, partial and loss of efficiency of other biologicals. In clinical practice, patients with non-systemic JIA transition to the second TNF-alpha blocker can restore the biological effect of the first drug without increasing the frequency of infectious AEs.

Aim : to assess efficacy and safety of hypodermic methotrexate injections in children aged from 1,5 to 16 years old with juvenile idiopathic arthritis (JIA) without extra-articular manifestations. Patients and methods : the results of treatment of 104 patients with JIA without systemic manifestations (61 girls and 43 boys) aged 5,0 (1,5–16) years old being followed-up in the rheumatology department of FSFI «SCCH» of RAMS were analyzed. The mean duration of the disease at the moment of methotrexate first administration was 6 months. Efficacy of methotrexate therapy was assessed according to the pediatric criteria for improvement of the American College of Rheumatology. The percentage of non-active stage and medicinal remission achievement were considered to be the target characteristics of therapy efficacy. Results : 61 patients (59%) were maintained in the study during 1 year. In 12 months of treatment remission according to C. Wallace criteria was induced in 39 of 104 (38%) children. In 22 (21%) of patients who failed to achieve remission in 1 year of treatment, 70% improvement was observed. Side effects were found in 45 (43%) of children: mild and moderate — in 33 (32%), severe — in 12 (12%) of patients. In 9 patients methotrexate was withdrawn due to intolerance of the drug. These patients as well as 34 children with resistance to performed treatment were administered genetically engineered biological agents. Conclusions : hypodermic injections of methotrexate are highly efficient in patients with JIA without extra-articular manifestations. Early administration at the dose of 15 mg/m 2 of body surface as well as appropriate selection of administration form induced remission and allowed to prevent of disability development in 38% of children.

Management protocol for patients with juvenile arthritis was developed with the assistance of the workers from the two largest educational scientific research institutions — Scientific Centre of Children Health and I.M. Sechenov First Moscow Medical State University. The authors summarized international and their own long-term clinical experience and showed the modern data on etiology, pathogenesis, diagnostics and treatment of juvenile arthritis.

A history case of systemic juvenile idiopathic arthritis with early onset and severe clinical case, resistant to treatment with standard immunosuppressive agents is represented in the article. This case demonstrates high clinical efficacy of adalimumab in a patient with severe course of systemic juvenile idiopathic arthritis, prolonged remission of extra-articular involvement and persistent polyarthritis. By the 4th week of the treatment inflammatory changes in the joints had arrested, range of motions had widened, laboratory markers of activity had normalized and non-active stage of the disease had been established. The duration of the remission of articular syndrome was 2 years, no relapses were observed during the follow-up period.

The article contains results of the study of efficacy and safety of adalimumab treatment given to 110 patients with juvenile idiopathic arthritis (JIA) and arthritis with eye-lesions, refractory to classical immunosuppressive treatment. Follow up period was from 3 monthsto 1 year long. The dosage regimen was as follows — 1 subcutaneous injection of Adalimumab 40 mg once in 2 weeks. Against the background of treatment with anti-TNF agents clinical remission, decrease and normalization of lab parameters of the disease activity, lower degree of disability, quality of life increase in 100 patients (90%), decrease in uveitis activity (N = 9, 18.75%), and remission of uveitis (N=39, 81.25%) were achieved. During the follow up period there were no adverse events that lead to drug withdrawal. Thereby, Adalimumab treatment is pathogenetically justified, effective and safe for patients with JIA and uveitis.