Репозиторий Университета

© 2019 The Journal of Rheumatology. All rights reserved. Objective. To determine whether neutropenia is associated with increased risk for infection in patients with systemic juvenile idiopathic arthritis (sJIA) and polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ). Methods. Data up to Week 104 from 2 phase III trials of intravenous TCZ in sJIA (n = 112; ClinicalTrials.gov, NCT00642460) and pcJIA (n = 188; ClinicalTrials.gov, NCT00988221) were pooled. Worst common toxicity criteria grade and lowest observed absolute neutrophil count (ANC) were identified for each patient. Associations between patient characteristics and lowest observed ANC were tested using univariate regression analysis. Infection and serious infection rates per 100 patient-years (PY) in periods associated with grades 1/2 and 3/4 neutrophil counts were compared with rates associated with normal neutrophil counts. Results.ANC decreased to grade ≥ 3 in 25.0% and 5.9% of sJIA and pcJIA patients, respectively, and decreases were transient. Young age (p = 0.047) and methotrexate use (p = 0.012) were positively associated with neutropenia in patients with sJIA but not in patients with pcJIA. The rate of serious infections in patients with sJIA (10.9/100 PY; 95% CI 6.8-16.5) tended to be higher than in patients with pcJIA (5.2/100 PY; 95% CI 3-8.5). No increase in rates of serious or nonserious infections was observed during periods of neutropenia in either trial. Conclusion. Patients with JIA treated with TCZ experienced transient neutropenia that was not associated with an increased number of infections.

Copyright © 2018. All rights reserved. Objective: Evaluate growth in patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ) for up to 2 years in a phase III trial. Methods: Patients with pcJIA lasting at least 6 months and inadequate response to methotrexate received open-label TCZ intravenously every 4 weeks (randomly assigned to 8 or 10 mg/kg if they weighed < 30 kg; received 8 mg/kg if they weighed ≥ 30 kg) for 16 weeks. Patients with JIA American College of Rheumatology 30 response at Week 16 were randomly assigned to TCZ or placebo for 24 weeks, with an open-label extension through Week 104. Mean ± SD height velocity (cm/yr) and World Health Organization (WHO) height SD score (SDS) were measured in patients receiving ≥ 1 dose of TCZ who did not receive growth hormone and in patients whose baseline Tanner stage was ≤ 3. Results: The study included 187 of 188 patients (99.5%) with mean WHO height SDS -0.5 ± 1.2, which was unrelated to age or disease duration (Spearman rank correlations r = 0.08 and r = -0.12, respectively). There were 123 patients at Tanner stage ≤ 3 at baseline, among whom 103 completed the study with 2 years of height SDS data. Mean height SDS increased from baseline to year 2 (+0.40, p < 0.0001). In 74 of 103 patients (72%), height SDS was greater than at baseline, and mean height velocity was 6.7 ± 2.0 cm/year. Conclusion. Among patients with pcJIA at Tanner stage ≤ 3 at baseline, 72% (74/103) had increased height SDS at the end of the study.

© 2018, Pediatria Ltd.. All rights reserved. Therapy with genetically engineered biological preparations (GEBP) significantly improved the prognosis and quality of life of patients with juvenile idiopathic arthritis (JIA). However, primary or secondary in efficiency, the development of undesirable phenomena require switching to another GEBP. Objective of the research – to determine optimal GEBP preparations when selecting and switching therapy based on the analysis of prescribed GEBP in real practice, depending on the clinical version of the JIA and the presence of uveitis. Materials and methods: the study included 322 patients with JIA on GEBP therapy, observed in the Pediatric Rheumatology Department of Children's Clinical Hospital of the I.M. Sechenov First Moscow State Medical University from Jan. 1, 2015 to Dec. 31, 2017. Retrospective, continuous observational clinical study. Of 322 patients, 70 (21,74%) had systemic JIA, 155 patients (48,14%) had polyarterial seronegative for rheumatoid factor (RF–) variant of JIA, 9 patients (2,8%) – polyarticular seropositive for rheumatoid factor RF+) variant of JIA, 55 patients (17,08%) – oligoarticular (persistent and spreading) variant of JIA, 26 patients (8,07%) – enthesitis (juvenile spondylitis), 7 patients (2,17%) – psoriatic variant of JIA. Results: as the first biological preparation were prescribed: etanercept to 177 (54,97%) patients; adalimumab to 51 (15,84%); tocilizumab to 44 (13,66%); abatacept to 39 (12,11%); infliximab to 11 (3,42%) patients. Transition to the second line of biological therapy was performed in 51 patients (in 15,8% of cases), on the third line of therapy in 13 patients (in 4,04% of cases), on the fourth line in 3 patients (in 0,93% of cases). As the second-line GEBP adelimumab was prescribed in 22 cases (43,14%), tocilizumab in 13 (25,49%), etanercept in 11 (21,57%), abatacept in 5 (9,8%). GEBP inefficiency was the reason for switching to the second line in 32 cases (9,9%). Of these, secondary inefficiency in 22 cases (6,8%); primary inefficiency – in 4 (1,3%), low efficiency – in 6 (1,9%), development/exacerbation of uveitis – in 7 patients (2,2%), in 6 cases (1,9%) due to insufficient compliance, drug shortage in the community, etc. Adverse effects caused switching in 5 patients (1,6%), incl. in 4 children – infusion reactions, in one – tuberculosis. Analysis of GEBP choice depending on the disease form and the presence of uveitis, was performed in 3 groups. Group 1 (n=70) consisted of patients with systemic JIA. Group 2 (n=53) included patients with articular form of JIA and concomitant uveitis. Group 3 (n=199) included patients with articular form of JIA without concomitant uveitis. Patients with systemic JIA as the first-line GEBP tocilizumab was prescribed significantly more often – to 38 patients out of 70 (54,29±5,96%) than etanercept – to 19 patients (27,14±10,19%) (t=2, 3, p<0,05), and other drugs in total (infliximab, abatacept, adalimumab) – to 13 (18,57±10,88%) (t=2,9, p<0,05). Switching to GEBP second line in this group was performed in 20 patients (28,57%). Tocilizumab was the final choice drug (after 3 years of follow-up) at the time of samples collection in 50 patients (71,43%) with systemic JIA. In patients with articular forms of JIA and concomitant uveitis as the first-line GEBP, adalimumab was prescribed significantly more often – in 34 of 53 cases (64,15±8,23%) than other drugs (abatacept, etanercept, infliximab) in total – 19 of 53 cases (35,85±11,01%) (t=2,06, p<0,05). Adalimumab was the drug final choice at the time of sample collection for 43 (81,13%) patients with JIA and uveitis. Most patients with articular form without uveitis received etanercept as first-line GEBP, 150 of 199 (75,38±3,54%), and etanercept prescription frequency was significantly higher than that of other drugs (abatacept, adalimumab, tocilizumab, infliximab) in total – 49 of 199 (24,62±6,19%) (t=7,1, p<0,01). In this group, the switching frequency was the smallest and amounted only 8,54%. The number of patients who received etanercept at the end of the study actually remained unchanged – 148 patients (74,37%).