Background: Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA). Usually uveitis developed during first two years after arthritis occurred [1]. In the previous studies was shown the shorter time interval between arthritis and uveitis the severe uveitis course was observed [2]. Information about course of uveitis developed before arthritis is scarce. Objectives: We aimed to evaluate the clinical features and therapy of JIA-associated uveitis, which developed before and after joint manifestation. Methods: In the retrospective study 191 pediatric autoimmune uveitis included. The onset age ranged from 1 to 17 years. We evaluated differences in clinical, laboratorial and treatment differences between groups, i) where uveitis developed before (n=58) and ii) after (n=133) arthritis. Chronic autoimmune uveitis without joint manifestations was excluded. Results: Uveitits before arthritis developed in 58 (30.4%) cases. Patients whom uveitis developed before arthritis had were elder and characterized equal gender involvement, rare ANA positivity, and rare use of immunosupression, e.g. corticosteroids, biologics and methotrexate, due to treatment by ophthalmologist predominantly. Patients developed uveitis before arthritis received biologics earlier due to severity of uveitis (LogRank test, p=0.016, HR=1.97 (95%CI: 1.3; 3.1, p=0.004). Data are in the Table 1 and Figure 1. Conclusion: Patients with JIA associated uveitis with initial ocular presentation demonstrated more severe course and delayed diagnostics and treatment due to lack of contacts with pediatric rheumatologist. Cooperation between ophthalmologist and pediatric rheumatologist is strictly required in all cases with chronic anterior uveitis. Table 1. Table 1. Parameter Uveitis before arthritis (n=58) Uveitis after arthritis (n=133) p Sex, female 32 (55,2) 97 (72,9) 0.016 Onset age, years 6.7 (4.6; 10.2) 3.2 (2; 6.1) 0.000001 JIA category Oligoarthritis 41 (70.7) 84 (63.6) 0.174 Polyarthritis 9 (15.5) 36 (27.3) Enthesytis-related arthritis 8 (13.8) 12 (9.1) Type of uveitis Anterior 44 (75.9) 111 (84.1) 0.315 Peripheral 3 (5.2) 2 (1.5) Posterior 3 (5.2) 3 (2.3) Panuveitis 8 (13.8) 16 (12.1) Unilateral uveitis, n (%) 19 (32.8) 48 (36.1) 0.632 ANA posititivity, n (%) 25/54 (46.3) 72/110 (65.5) 0.019 HLA B27 positivity, n (%) 8/35 (22.9) 13/62 (21.0) 0.828 Methotrexate, n (%) 3 (5.2) 57/132 (43.2) 0.0000001 Systemic corticosteroids, n (%) 3 (5.2) 44/131 (33.6) 0.00003 Biologic, n (%) 26 (44.8) 88 (66.2) 0.006 ESR, mm/h 19.0 (4.0; 25.0) 23 (15.0; 32.0) 0.095 CRP, mg/l 97.0 (0.1; 107.5) 8.1 (0.9; 57.4) 0.493 Time between arthritis and uveitis, years 2.7 (0.9; 4.3) 4.0 (2.0; 7.1) 0.016 Time before biologic, years 2.5 (0.9; 3.5) 1.3 (0.5; 5.0) 0.462 This work supported by the Russian Foundation for Basic Research (grant № 18-515-57001). References: [1]Verazza S, et al. Pediatr Rheumatol Online J 2008;6(Suppl 1):77. [2]Zannin ME, et al. Acta Ophthalmol 2012;90:91-5. Disclosure of Interests: None declared Figure 1.
Systemic corticosteroids are continued to be administered in juvenile idiopathic arthritis (JIA) patients, especially in systemic JIA (sJIA), despite the ability of biologic therapy. One of the complications of long-term CS treatment is delayed hip arthritis development with risk of secondary hip osteoarthritis formation and total hip arthroplasty (THA).We compared different types of hip joint lesions in JIA, especially, secondary hip osteoarthritis development and THA rates in systemic and non-systemic JIA, and evaluate systemic corticosteroids contribution to those complications.The study included 753 JIA patients. They were divided into 2 groups: patients with sJIA and non-systemic JIA (nsJIA). Clinical and demographic characteristics, CS treatment regimens were compared. Results. Hip arthritis was found equally often in both groups, but both secondary hip osteoarthritis (19% vs 5,3%) and THA (8.6% vs 1.6%) prevailed in the sJIA. Patients with sJIA had delayed hip involvement (57.9% vs 30.6%; p=0.019), earlier secondary hip osteoarthritis development (4.5 vs 5.1 years after the JIA onset) with younger age of secondary hip osteoarthritis achievement (13.7 vs 15.2 years; р=0.045), they also had higher inflammatory activity, greater systemic corticosteroids administration (94.8% vs 56.1%; р=0.0000001) and higher cumulative systemic corticosteroids dose (3085 mg vs 2000 mg; p=0,005). More than half patients (56.1%) with nsJIA had systemic corticosteroids treatment and impaired calcium-phosphorus metabolism. Conclusion. Systemic corticosteroid treatment and delayed hip involvement are independent predictors of secondary hip osteoarthritis in all JIA categories. Calcium and phosphate metabolism disturbances are additional predictor for secondary hip osteoarthritis in non-systemic JIA categories
JAK-inhibitors are small molecules blocking the JAK-STAT pathway that have proven effective in the treatment of different immune-mediated diseases in adults and juvenile idiopathic arthritis (JIA).To evaluate the safety and efficacy of tofacitinib in children with different rheumatic diseases.We extracted information from 24 children with the following diagnosis: JIA (n = 15), undifferentiated systemic autoinflammatory diseases (SAIDs) (n = 7), and juvenile dermatomyositis (JDM) (n = 2) who have been treated with tofacitinib for a period of longer than 6 months. The treatment outcomes were classified according to the opinion of the attending physicians as having a complete response (CR), i.e., the absence of disease activity, or a partial response (PR)-a significant improvement of symptoms and disease activity, or no response (NR)-no changes in disease activity.CR was achieved in 10/24 patients; 7/15 among JIA patients, 1/2 among JDM patients, 4/7 among SAID patients, and PR in 5/15 of JIA, 1/2 of JDM, and 3/7 of SAID patients. Three non-responders with JIA discontinued tofacitinib. Corticosteroids were successfully tapered off in 11/14 patients and discontinued in 2/14 patients. Four patients had side effects not requiring treatment discontinuation: liver enzyme elevation (n = 2), hypercholesterolemia (n = 1), lymphadenitis (n = 1).JAK-inhibitors are effective new therapies for the treatment of multiple immune-mediated diseases. Our experience has shown the best results in patients with JIA and JIA-associated alopecia, and type I interferonopathies. More data from randomized controlled clinical trials are needed to use JAK-inhibitors safely in pediatric rheumatic diseases.
Background: While efficacy of tofacitinib (TOF) has been proven in many adult immune-mediated conditions, the information on its’ safety and efficacy in the pediatric population is limited. Objectives: to evaluate the safety and efficacy of TOF in children with immune-mediated diseases. Methods: from 23 children whom TOF has been initiated, 17 children with treatment duration of > 6 months were extracted including 16 girls and 1 boy with the following diagnosis: JIA (n=10), autoinflammatory diseases (AID) (n=5) and juvenile dermatomyositis (JDM) (n=2) due to impossibility to taper corticosteroids (CS) or previous biologic treatment failed. The treatment outcome was classified according to the opinion of the attending physicians as complete response (CR) i.e., the absence of disease activity, partial response (PR) – a significant improvement of symptoms and disease activity or no response (NR) - no changes in disease activity. Results: Mean duration of TOF treatment was 25.4±18.9 months. TOF was used as monotherapy in 3 cases, in combination with methotrexate (MTX) in 6, and in combination with other biologics in 3 children: tocilizumab (n=2) and canakinumab (n=1). Nine patients received CS. (Table 1). In two JIA patients with alopecia TOF induced intensive hair growth and controlled joint inflammation. 9 patients had CR: AID (n=3), JIA (n=4) and JDM(n=1): 7 patients had PR and 1 was NR. 13 patients had a previous history of several subsequent failed biologic: 4 biologics (n=1), 3 biologics (n=6), 2 biologics (n=1), 1 biologic (n=5). TOF treatment allowed discontinuation of CS in patient#6 and reducing the CS in 8/10 patients from 0.4 ±0.27 mg/kg to 0.15±0.1 mg/kg in 3.7±3.4 times: in 2 cases the tapering of steroids failed (Figure 1). 4 patients had side effects not requiring treatment discontinuation: liver enzymes elevation (n=2), hypercholesterolemia (n=1), lymphadenitis (n=1). In pt#6 after achievement of the remission the TOF dosage was decreased up to 2 times and tocilizumab intervals were increased up to 6 weeks. Table 1. # Diagnosis Indication Previous biologics Current treat-ment TOF, dose, mg/kg Duration of TOF treatment, months Genetic variants detected Efficacy 1 AID Severe inflamma-tion, aortitis, colitis INX, TCZ, ADA CS, TOF 0.5 7 NOD2 c.2578G>A (p.A860T); NOD2 c.2722G>C (p.G908R) ADA2 c.927G>A (p.M309I) PR 2 JDM recurrent skin rash CS, TOF, MTX 0.5 5 PR 3 JDM skin involvement, ulceration CS, MTX, TOF 0.7 7 NLRP12c.154G>A (p.G52S) CR 4 AID, IFP skin rash, recurrent inflammation, failure to thrive CAN, TCZ CS, TOF, CAN 0.5 32 RNASEH2B c.916dupA (p.I309Nfs*7) CR 5 JIA, poly severe arthritis ETA,TCZ, ADA TOF,TCZ 0.27 22 PR 6 soJIA resistant to CS and biologic systemic inflammation, arthritis TCZ, ABC, CAN TOF, TCZ 0.4 23 PR 7 JIA, poly (RF+) alopecia Severe arthritis, lung involvement, alopecia ETA, ABC, TCZ, ADA TOF, MTX, CS 0.3 37 IL1RN c.10G>C (p.A4P); NLRP3 c.2113C>A (p.Q705L); MEFV c.1105C>T (p.P369S) CR 8 IFP, CANDLE- like recurrent inflammation, digital ischemia, ulcers, CS-dependency ETA, RTX, CAN TOF, CS 0.25 43 MDA5 NLRP3 CR 9 AID, IFP systemic inflammation, ulcers ETA TOF, CS 0.5 13 СR 10 JIA, ERA arthritis ETA TOF, MTX 0.2 44 CR 11 JIA, poly arthritis ABC, ETA TOF, MTX 0.25 38 CR 12 JIA, poly Arthritis, alopecia ETA TOF 0.15 31 PR 13 soJIA + MAS systemic inflammation, arthritis TCZ, CAN, ETA TOF, CS 0.5 38 NR 14 JIA, poly arthritis INX, ETA, ADA, TCZ TOF, MTX 0.2 24 PR 15 AID Systemic inflammation, CS-dependency TCZ TOF,CS 0.5 21 STAT3, c1343A>C PR 16 JIA, ERA arthritis ETA TOF 0.25 21 PR 17 JIA, poly arthritis ADA, TCZ, ETA TOF 0.15 39 СR Figure 1. Conclusion: Tofacitinib is a promising agent in treating pediatric rheumatic diseases. In our study the best results were in AID patients with rare alleles in interferon pathway genes, patients with arthritis and alopecia and in children with JDM. Future studies are needed to identify clear indications for treatment with JAK-inhibitors. Acknowledgements: This work was supported by the RSF grant №20-45-01005. Disclosure of Interests: None declared.
Systemic lupus erythematosus (SLE) is an immunopathological disease characterized by various systemic malfunction and a prognosis for unfavorable outcomes. In the current standards of treatment for SLE the biological therapy is not included in the first line of therapy. The data from previous studies do not allow drawing a clear conclusion about the benefits of using biological therapy. The purpose of this research was to study the outcomes of SLE therapy using the rituximab biosimilar BCD020 compared with the standard non-biological therapy. Materials and methods used: a single-center cohort retrospective study of 79 medical records of children aged 0 to 18 y/o suffering from SLE were analyzed: 19 received rituximab as part of multicomponent therapy in the first 6 months from the onset of the disease, the remaining 60 received standard non-biological therapy. Damage to organs and systems, laboratory data, doses of corticosteroid therapy and disease activity were assessed using the SELENA-SLEDAI tool at the time of initiation of therapy and one year after. Results: higher degree of disease activity involving the central nervous system and kidneys was noted in the group of children receiving rituximab therapy. No statistically significant difference between the data of the two groups, including disease activity, was noted in 12 months after the start of the therapy. There was a statistically significantly more pronounced decrease in the SLEDAI activity index after a year in the group of children who received rituximab (p=0.001) compared to children who did not receive it. During rituximab therapy, infectious complications were noted in 3 cases, including the development of meningitis; and a single patient had developed with bicytopenia. Conclusion: rituximab was used in children with higher disease activity, with involvement of organs and systems whose damage leads to an unfavorable prognosis (CNS and renal damage). Rituximab can be considered as an option in the treatment of severe variants of SLE with a poor prognosis due to its ability to more intensively arrest disease activity compared to standard non-biological therapy.
BACKGROUND: Juvenile idiopathic arthritis is the most common rheumatic disease in children. A frequent extra-articular manifestation of juvenile idiopathic arthritis is uveitis, which is a serious clinical diagnostic problem in routine pediatric practice. Among the known risk factors for uveitis are the early age of the juvenile idiopathic arthritis onset, oligoarticular subtype, seropositivity by antinuclear factor.
AIM: to evaluate the influence of presence of uveitis on the course of juvenile idiopathic arthritis.
MATERIALS AND METHODS: A single-center retrospective study included 520 patients with uveitis. The analysis was carried out among patients who developed (n = 116) and did not develop (n = 404) uveitis. The minimum follow-up period was 2 years, for patients who did not develop uveitis.
RESULTS: Uveitis was diagnosed in 116 (22.3%) children with juvenile idiopathic arthritis. Most often, uveitis occurred in patients with oligoarthritis and psoriatic arthritis. When comparing the features of the articular status of patients with juvenile idiopathic arthritis who developed and did not develop uveitis, a lower frequency of involvement of the cervical spine, temporomandibular, shoulder, elbow, wrist, proximal and distal interphalangeal joints, hip, talus-heel joint, as well as a smaller number of active joints in children with uveitis was found. Patients with uveitis received methotrexate therapy more often, cumulative doses of corticosteroids were lower, the frequency of prescribing genetically engineered biological drugs was approximately the same in both groups. Remission of arthritis was achieved more often, but the proportion of children who developed an exacerbation was higher. When calculating the risk factors of uveitis by binary logistic regression, it was found that the main predictors of uveitis were oligoarthritis, the number of active joints 8, seropositivity by antinuclear factor and recurrent course of arthritis. The difference in the frequency of achieving remission may be due to more aggressive systemic therapy in the presence of uveitis.
CONCLUSIONS: Children with uveitis have a more severe course of juvenile idiopathic arthritis and may require more aggressive immuno-suppressive therapy. Further studies are required to determine the prognostic role of uveitis in the course and outcomes of juvenile idiopathic arthritis.
Background: Patients with juvenile idiopathic arthritis (JIA) may have lower protective levels of anti-vaccine antibodies due to high inflammatory activity, interrupted or incomplete vaccination schedule, and due to using of immune-modulating drugs, e.g. systemic corticosteroids (CS), methotrexate (MTX) and biologics. Objectives: The aim of our study was to find the predictors of low levels of anti-vaccine antibodies in patients with JIA. Methods: In the present study were included data 170 JIA (55 boys and 115 girls) aged from 2 to 17 years, who received scheduled vaccination before the age of 2 years and before JIA onset against measles, parotitis, hepatitis B, diphtheria and rubella. In all patients the Ig G anti-vaccine antibodies levels were detected with ELISA. In each patient we evaluate the type of the disease (oligoarthritis - 73, polyarthritis - 61, systemic-16 and enthesitis-related arthritis - 20), onset age, presence of uveitis, duration of JIA, treatment with corticosteroids (CS), methotrexate (MTX) and biologics. Data presented with median and 25%-75%. Results: The main demographic characteristics: age of inclusion in the study 11.4 (7.6-14.8) years, disease onset – 6.0 (3.7-9.0) years, disease duration – 3.8 (1.9-6.5) years. Treatment with CS was in 43 (25.3%), MTX in 154 (90,6%) and biologics 82 (48.2%) patients, among them 53 had TNFa-inhibitors. More than 1 biologic consequently received 16/82 (19.5%) patients. Protective levels of anti-measles antibodies was in 98 (57,6%) of all JIA population, anti-parotitis – 136 (80.0%), anti-hepatitis B – 85 (50.0%), anti-diphtheria – 88 (51,7%), anti-rubella – 167 (98.8%). Data of vaccination status and anti-vaccine antibodies levels in the table. In univariate and multivariate regression analysis the main risk factors for anti-measles antibodies levels were MTX using (p=0.045), more than 1 biologics (p=0.0004); for anti-hepatitis B – MTX (p=0.03), for anti-diphtheria antibodies: onset age (p=0.0002), JIA duration (p=0.00007), number vaccine doses (p=0.02), more than 1 biologics (p=0.01); combined treatment with biologics and other drugs (MTX or CS). Parameter No treatment (n=14) MTT, only (n=74) Biologics±MTT ±CS (n=82) P # anti-measels vaccine doses 2.0 (2.0; 2.0) 2.0 (1.0; 2.0) 2.0 (1.0; 2.0) 0.19 Anti-measels IgG, Me/ml 0.28 (0.1; 0.6) 0.4 (0.1-0.7) 0.17 (0.0; 0.29) 0.0002 Protective anti-measels IgG level, n (%) 8 (57) 50 (68) 40 (49) 0.06 # anti-parotitis vaccine doses 2.0 (2.0; 2.0) 2.0 (1.0; 2.0) 2.0 (1.0; 2.0) 0.19 Anti-parotitis IgG, Me/ml 2.0 (1.2; 4.3) 2.8 (1.3; 5.6) 2.5 (1.0; 5.1) 0.47 Protective anti-parotitis IgG level, n (%) 12 (86) 62 (84) 62 (76) 0.38 # anti-diphtheria vaccine doses 5.0 (4.0; 5.0) 4.0 (4.0; 5.0) 5.0 (4.0; 5.0) 0.39 Anti-diphtheria IgG, Me/ml 0.17 (0.0; 1.2) 0.18 (0.0; 0.4) 0.1 (0.0; 0.2) 0.18 Protective anti-diphtheria IgG level, n (%) 9 (64) 42 (57) 37 (45) 0.22 # anti-hepatitis B vaccine doses 3.0 (3.0; 3.0) 3.0 (3.0; 3.0) 3.0 (3.0; 3.0) 0.91 Anti-hepatitis B IgG, Me/ml 0.56 (0.0; 7.5) 11.4 (0.3; 44.8) 10.0 (0.0; 44.1) 0.08 Protective anti-hepatitis B IgG level, n (%) 3 (21) 40 (54) 42 (51) 0.08 # anti-rubella vaccine doses 2.0 (2.0; 2.0) 2.0 (1.0; 2.0) 2.0 (1.0; 2.0) 0.19 Anti-rubella IgG, Me/ml 121.8 (70.0; 200.0) 95.6 (53.3; 198.2) 56.4 (37.0; 100.1) 0.008 Protective anti-rubella IgG level, n (%) 14 (100) 73 (100) 80 (98) 0.34 Conclusion: MTX, biologics and JIA durations are factors influenced on anti-vaccine antibody level. It is necessary to regularly check the levels of anti-vaccine antibodies, especially anti-measels and anti-diphtheria for creation of the individual vaccination plan for JIA patients, treated with MTX and biologics. Disclosure of Interests: None declared
Background/Objectives: Cervical spine arthritis (CSA) in children with juvenile idiopathic arthritis (JIA) can lead to clinically significant and irreversible functional impairment. Our study aimed to evaluate the features of the JIA disease course in children with CSA. Methods: In the retrospective cohort study, the data from medical charts of children with JIA (n = 753) who corresponded to the ILAR criteria and were treated from 2007 to 2016 were included. CSA was diagnosed by clinical manifestations (pain and limited range of motion) with radiological confirmation in the available cases. Results: CSA had 101 JIA patients (13.4%), predominantly with polyarticular (48%, OR = 1.8 (1.2; 2.7), p < 0.001) and systemic (18.9%, OR = 3.6 [2.0; 6.6], p < 0.001) JIA categories. CSA was associated with longer disease duration, higher inflammatory activity, a higher number of active joints, a lower probability of achieving remission (HR = 1.33 (95% CI: 1.01; 1.76, p = 0.04)), and a higher probability of being treated with biologics (HR = 1.78 (95% CI: 1.22; 2.59, p = 0.002)). Patients with temporomandibular arthritis (OR = 10.4 [5.4; 19.8], p < 0.001) and shoulder arthritis (OR = 14.1 [7.5; 26.3], p < 0.001) had the highest risk of having CSA. Conclusions: CSA was an independent predictor of treatment with biologics and failure to achieve remission. Identified predictors can help to find the group of patients with higher suspicion for whom the functional tests and MRI are required to not miss the CSA. A radiology assessment of CSA should be performed as far as possible in children, unless there are risks of general anesthesia for younger patients.
Background: Macrophage activation syndrome (MAS) is a severe life-threatening complication of the systemic-onset juvenile idiopathic arthritis (soJIA). The treatment options included high-dose of the corticosteroids (CS), cyclosporine A (CsA), intravenous immunoglobulin (IVIG) and biologics, predominantly IL-1 antagonist – anakinra. In Russia anakinra has not approved yet, so canakinumab (CAN) is a single anti-IL-1 option, available in Russia. Objectives: To evaluate the safety and efficacy of canakinumab in patients with severe MAS in soJIA, who failed the previous treatment. Methods: In the retrospective case series study were included 9 soJIA patients (4 boys and 5 girls) with severe MAS, resistant to combination of high-dose CS, IVIG and CsA. Results: All patients had a MAS during the onset of JIA. The main clinical features of disease onset included: fever 9 (100%), active arthritis 5 (56%), pleuritis 7 (78%), pericarditis – 5 (56%), peritonitis 2 (22%), rash 6 (67%), hepatomegaly 9 (100%), splenomegaly 9 (100%), lymphadenopathy 7 (78%), bleeding 4 (44%), CNS involvement – 3 (33%). Initial treatment included high doses CS 8 (89%), oral CS 9 (100%), methotrexate 5 (56%), tocilizumab 4 (44%), and canakinumab 5 (56%), CsA 4 (44%), IVIG 6 (67%). TCZ was discontinued due to infusion reaction (n=2), TCZ inefficacy (n=3) and presence of MAS in all patients (n=5). In children whom TCZ was switched on CAN we used the standard dose of CAN 4 mg/kg, but if MAS occurred on the CAN we temporally increased the doses since 8 to 25 mg/kg (300 mg). In all cases MAS episodes were successfully resolved during CAN treatment. In 5 (56%) MAS had repeated course during the CAN which lead to temporally increasing the doses of CAN (pt3, pt5, pt8, pt 9) or required to increase immunosupression with abatacept or tofacitinib. Three patients with repeated MAS developed interstitial lung disease (ILD). Two patients who successfully resolved MAS after CAN had relapses of arthritis and switched CAN to TCZ. ID Sex JIA onset, y Repeated MAS Initial biologic MAS on CAN Experience of increased CAN doses Outcomes Current treatment 1 F 7.7 N TCZ N N Remission CAN 2 F 11.5 N CAN N N soJIA flare, ILD TCZ 3 F 7.9 Y CAN Y Y Remission CAN 4 F 3.4 N TCZ N Y Remission, ILD CAN, CS, MMF 5 M 0.8 Y TCZ Y Y Remission, ILD CAN, abatacept, CsA, CS 6 M 14.2 Y CAN N N Remission TCZ 7 M 1.1 Y CAN N N Remission N 8 М 1.3 N CAN Y Y Remission CAN every 12 months 9 F 9.1 N TCZ Y Y Minimal disease activity CAN, tofacitinib Footnotes: CAN – canakinumab, CS – corticosteroids, CsA – cyclosporine A, ID – identification, ILD – interstitial lung disease, F – females, M – males, N- no, TCZ – tocilizumab, Y – yes. Conclusion: Canakinumab is an effective rescue treatment either soJIA either MAS. In patients with MAS developed on CAN required the temporal increasing of the doses. Funding statement: This work was supported by the Russian Foundation for Basic Research (grant № 18-515-57001). Disclosure of Interests: None declared
TNF-α inhibitors are used in the treatment of non-systemic variants of juvenile idiopathic arthritis (JIA) in case of ineffectiveness or intolerance to methotrexate. Despite 20 years of experience of using of etanercept in pediatric rheumatology, a long-term study of the efficacy and safety of the drug in real clinical practice remains necessary. Objective of the study: to study the efficacy and safety of etanercept for treatment of various non-systemic JIA subtypes in real clinical practice. Materials and methods of research: data from the case histories of 375 patients (242 girls and 133 boys) with articular forms of JIA for 2010–2020 were included in a retrospective, open, uncontrolled, nonrandomized, continuous multicenter cohort study. The age of debut was 6.3 (2.9; 10.7) years. Demographic characteristics, subtypes of arthritis, indicators of laboratory activity of inflammation, and outcomes were estimated: achievement of remission, exacerbation, and switching from etanercept to another genetically engineered biological drug (GEBD) were assessed. Results: remission was recorded in 78.9% on average after 6 months. The factors that determine the likelihood of achieving remission were the absence of previous therapy with GEBD (p=0.001) and compliance with therapy – OR=2.5 (95% CI: 1.3; 4.7), p=0.006. Exacerbations were recorded in 29.5% and were associated with the presence of the HLA B27 antigen – OR=2.6 (95% CI: 1.1; 6.0), p=0.028, antinuclear factor seropositivity (p=0.060). Change of etanercept to another GEBD was made in 17.4% of children and was associated with a failure to achieve remission – OR=7.7 (95% CI: 4.0–14.3), p=0.000001, with previous exacerbations – OR=14,8 (5.3; 41.2), p=0.0000001 and the development of de novo uveitis – OR=2.4 (95% CI: 1.1–5.3), p=0.038. The arthritis subtype and the presence of concomitant methotrexate therapy did not significantly affect treatment outcomes. Conclusion: achievement of remission, compliance with therapy, history of previous therapy with GEBD, exacerbation of JIA and development of de novo uveitis determined the main outcomes of etanercept therapy. The JIA subtype, as well as concomitant therapy with methotrexate, did not significantly affect the outcomes of the disease, which makes it possible to consider etanercept therapy a very effective and safe method of treating JIA as a genetically engineered first-line therapy of any variants of articular forms of JIA, even in monotherapy with ineffectiveness or intolerance to methotrexate.
