Background. To assign genetically engineered biologic drugs, we need data on the predictors for response to therapy. Prognostic factors for the response to tocilizumab in patients with juvenile idiopathic arthritis (JIA) without systemic symptoms are poorly studied.Objective. Our aim was to reveal early predictors for the response to tocilizumab therapy in patients with JIA without systemic symptoms.Methods. A retrospective cohort study enrolled patients with JIA without systemic symptoms who received tocilizumab therapy between July 2009 and August 2017. We assessed the association between the initial demographic, clinical, and laboratory parameters in patients and the best response (according to the ACR90 criteria) to treatment after a year.Results. The study included 95 (girls 85%) patients; the mean age was 10.3 (6.0; 13.6). During the first year of therapy, 71 (75%), 55 (58%), 38 (40%), and 22 (23%) patients achieved the improvement according to ACR30/50/70/90 criteria, respectively; 22 (23%) patients reached disease inactive stage according to the Wallace criteria. When performing multivariate analysis, the following improvement predictors were revealed based on the ACR90 criteria after a year of treatment: decrease in serum C-reactive protein level during the first month of therapy [odds ratio (OR) 1.024; 95% confidence interval (CI) 1.007–1.051], decrease in disease activity score on the visual analogue scale according to the parent/patient assessment (OR 1.048; 95% CI 1.005–1.105), early onset of the disease (OR 0.38; 95% CI 0.16–0.72), persistent oligoarthritis according to the ILAR (OR 9.9; 95% CI 1.5–109.3). During the first year of tocilizumab administration, neutropenia was registered in one patient, leukopenia — in three cases, and urticaria — in one case.Conclusion. The variant of JIA, the age at the disease onset, and the disease course pattern in the first month of tocilizumab therapy are the predictors of treatment efficacy throughout the year.
Background. Immunological potency of 13-valent pneumococcal vaccine (PCV-13) in children with systemic juvenile idiopathic arthritis (SJIA) is still unstudied. Estimates of the genetically engineered biologic drugs (GEBD) effects on pneumococcal vaccination results also remain controversial.Objective. The aim of the study was to explore the PCV-13 efficacy in patients with SJIA and who is on treatment with monoclonal antibodies against interleukin 6 receptor (tocilizumab) and interleukin 8 receptor beta (canakinumab).Methods. The study included patients under the age of 18 with SJIA in remission or active form of disease vaccinated with PCV-13. The vaccine was administered in single dose of 0.5 ml intramuscularly in patients on treatment with GEBD or 3 weeks before GEBD administration for the first time (for patients with active disease). Vaccination was considered effective at achievement of the minimum protective level of antibodies to capsular polysaccharide of pneumococcus (anti-SPP IgG; ≥ 7 U/ml) or increase of anti-SPP IgG level ≥ 2 times in 4 weeks after vaccination. The anti-SPP IgG levels were measured with enzyme immunoassay.Results. The study included 53 patients (27 girls) in remission of SJIA and 25 (16 girls) in active disease. Median age was 13.3 and 10.8 years respectively. Tocilizumab/canakinumab was administrated in 43/10 and 18/7 patients respectively. Minimum significant anti-SPP IgG level and two-fold increase in anti-SPP IgG level were recorded in 49/53 (92%) and 32/53 (60%) patients with SJIA in remission, as well as in 22/25 (88%) and 18/25 (72%) patients in active disease respectively. PCV-13 immunological potency in patients with SJIA in remission and in active disease (in those who were initially administrated and who did not receive GEBD) did not differ.Conclusion. PCV-13 vaccination allows to achieve protective antibodies level in most of the patients with SJIA in children population regardless of the disease stage and the history of GEBD administration.
BackgroundA significant number of systemic juvenile idiopathic arthritis (sJIA) patients discontinue biologic disease-modifying antirheumatic drugs (bDMARDs) due to lack of efficacy or safety concerns. Studies of biologic therapy switch regimens in sJIA are required.MethodsPatients with sJIA who switched from tocilizumab (due to lack of efficacy or safety) to canakinumab (4 mg/kg every 4 weeks) and were hospitalized at the rheumatology department from August 2012 to July 2020 were included. Primary efficacy outcomes were 30% or greater improvement based on the paediatric criteria of the American College of Rheumatology (ACR30), achievement of inactive disease (JADAS-71 = 0) and clinical remission (ACR sJIA clinical inactive disease criteria). Follow-up from time first canakinumab dose administered was 12 months or the closest time point (not less than 6 and not more than 18 months). Data were extracted from electronic outpatient medical records.ResultsDuring the study period, 46 patients with sJIA switched from tocilizumab to canakinumab. Median age at baseline was 8.2 [interquartile range (IQR) 4.0–12.9] years, with the median sJIA duration being 1.8 (IQR 0.8–5.8) years; 37 (80%) patients received at least one conventional DMARD (cDMARD; oral corticosteroids, methotrexate and/or cyclosporine A). Study outcomes were followed up in 45 patients (one patient did not attend the follow-up for an unknown reason); median follow-up was 359 (IQR 282–404) days. During the follow-up, 1 patient discontinued canakinumab due to tuberculosis detection and the dose was reduced or the injection interval increased in 4 (9%) patients. In total, 27 (60%) patients continued to receive at least one cDMARD. Improvement according to the ACR30 criteria was achieved in 43 patients [96%; 95% confidence interval (CI) 85–99], inactive disease in 42 (93%; 95%CI 82–98), and remission in 37 (82%; 95% CI 69-91); after adjustment for actual time-at-risk, the rates were 83, 85 and 73 events per 100 person-years, respectively. During follow-up, 23 AEs (most frequently infections) were reported in 19/45 (42%) patients; 5/45 (11%) patients developed macrophage activation syndrome, with a favorable outcome in all cases.ConclusionsOne-year canakinumab therapy was found to be potentially effective as second-line biologic therapy after discontinuation of tocilizumab in patients with sJIA.
Background:Canakinumab (CAN) is often used as second biologics in juvenile idiopathic arthritis with active systemic features (sJIA). However, there are little information about its long-term efficacy and safety.Objectives:To evaluate the long-term effectiveness and safety of CAN as a second biologics after tocilizumab (TOC) in sJIA patients depending on the duration of the disease.Methods:Thirty-one patients were enrolled in this study: the group of early sJIA (with duration shorter than 2 years, 19 patients) and the group of late sJIA (with duration longer than 2 years, 12 patients). At the baseline, information was collected on the characteristics of the onset of the disease, previous therapy and its success. At each visit at least 1 time per year clinical and laboratory characteristics of sJIA severity were assessed. Response to therapy was assessed using the ACRPedi 30/50/70/90 criteria and the C.Wallace criteria for inactive disease (WID) and clinical remission.Results:The most common reason for withdrawal of previous TOC was secondary ineffectiveness (22 cases, 71%); in 6 cases (19.4%) allergic reaction was observed; in two cases (6.5%) primary non-effectiveness appeared; and in one case (3.2%) there was marked infusion reaction.At CAN initiation, sJIA activity was as follows: 15 (12: 23) for JADAS-71; 45 (36.5: 72) and 58 (45: 81) for physician’s and patient’s global assessment VAS; and 0.25 (0: 0.62) for the CHAQ disability index.After 12-month treatment, 22 (71%) patients reached WID: 21 on CAN therapy and 1 – after CAN withdrawal due to administrative reason and stable WID. ACR50/70/90 response was achieved by 84.2%/84.2%/64.7% patients in early arthritis group and in 83.3%/75%/75% patients in late arthritis group (p=0.792).However, 42.1% of patients with early sJIA achieved remission in the first 1.5 years without any further relapse during all the studied period and only 16.7% of patients with late arthritis (p=0.239). In multivariable analysis, it was found that age of sJIA onset (OR (2.5-97.5 CI) 0.353 (0.13 - 0.72), p=0.015), number of joints with active arthritis at sJIA onset (2.308 (1.26-5.73), p=0.025), and JADAS-71 at sJIA onset (0.664 (0.44-0.88), p=0.016) were associated with successful treatment with rapid achievement of stable remission.During the 76.7 patient-years follow-up period, 18 of 31 (58.1%) patients were able to achieve a stable clinical remission and 27 (87.1%) – WID. Two patients have achieved successfully drug-off remission. Serious adverse event (SAE) was reported in one (3.2%) patient (enteritis).Conclusion:Long-term canakinumab therapy proved to be effective and safe as a second biologics after tocilizumab for any duration of the disease. However, patients with early arthritis are more likely to quickly achieve stable remission without further relapse. Younger onset of sJIA with polyarthritis involvement and low disease activity are predictors of rapid and stable remission.Disclosure of Interests:Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Elizaveta Krekhova: None declared, Tatyana Dvoryakovskaya: None declared, Ksenia Isaeva: None declared, Aleksandra Chomakhidze: None declared, Evgeniya Chistyakova: None declared, Olga Lomakina: None declared, Rina Denisova: None declared, Anna Mamutova: None declared, Anna Fetisova: None declared, Marina Gautier: None declared, Dariya Vankova: None declared, Meyri Shingarova: None declared, Alina Alshevskaya: None declared, Andrey Moskalev: None declared, Ivan Kriulin: None declared
Background:Early-onset form of systemic juvenile idiopathic arthritis (sJIA) often presents severe disease course. Choosing the optimal therapy option as first-line treatment is necessary for rapid improvement of patients’ quality of live and prevention of further radiologic progression.Objectives:To evaluate the long-term effectiveness and safety of tociliizumab (TOC) in sJIA patients depending on the duration of the disease treated in the National Medical Research Center of Children`s health, Moscow, Russia.Methods:The study was conducted as a subanalysis of the prospective cohort study to evaluate the efficacy of biologics in children with sJIA. Analysis included sJIA patients younger than 4 years of age at the moment of TOC initiation. Patients were divided into 2 groups: with disease duration shorter than 6 month (ShorterDD group, n=35) and more than 6 month (LongerDD group, n= 19). Treatment efficacy was evaluated according to the dynamics of clinical and laboratory signs using the ACRPedi criteria. The Wallace criteria were used to evaluate whether or not remission had been achieved. Treatment safety was evaluated according to the data presented in the Adverse Event Reports.Results:TOC was first biologics in 34/35 (97.1%) patients in ShorterDD group and 18/19 (94.7%) patients in LongerDD group. Groups were comparable in terms of disease activity at TOC initiation with 100% of patients presented active systemic features. 31/35 (88.6%) patients in ShorterDD group and 17/19 (89.5%) patients in LongerDD group have median 3 (IQR 1: 6) and 5 (IQR 3: 7.5) active joints, respectively (p=0.119). JADAS-71 level was 17.14 ± 6.25 ShorterDD group and 17.36 ± 5.45 in LongerDD group (p=0.895).TOC showed high efficacy after first months of treatment with only 6/35 (17.1%) patients in ShorterDD group and 7/19 (36.8%) in LongerDD group remained with active systemic features (p=0.181). JADAS-71 level decreased to 0 points 26/35 patients (74.3%) in ShorterDD group and in 11/19 patients (57.9%) LongerDD group (p=0.237). After 3 month of treatment, WID was achieved by 27/35 patients (77.1%) in ShorterDD group and by 9/19 patients (47.4%) LongerDD group (p=0.038). ACR Pedi 50/70/90 was achieved by 88.6%/85.7%/80% of patients in ShorterDD group and by 84.2%/73.7%/68.4% of patients in LongerDD group after 1 months of treatment and in 77.1%/74.3%/74.3% and 84.2%/78.9%/68.4%, respectively, after 3 months of treatment.Conclusion:Initiation of tocilizumab treatment in sJIA patients under 4 years of age is highly effective. However, early treatment within first 6 month after disease onset had advantages in speed of reaching an inactive disease as soon as after 3 months of therapy.Disclosure of Interests:Elizaveta Krekhova: None declared, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Tatyana Dvoryakovskaya: None declared, Ksenia Isaeva: None declared, Aleksandra Chomakhidze: None declared, Evgeniya Chistyakova: None declared, Olga Lomakina: None declared, Rina Denisova: None declared, Anna Mamutova: None declared, Anna Fetisova: None declared, Marina Gautier: None declared, Dariya Vankova: None declared, Meyri Shingarova: None declared, Alina Alshevskaya: None declared, Andrey Moskalev: None declared, Ivan Kriulin: None declared
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