Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial

Abstract

ObjectiveTo evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA).MethodsThis three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) <30 kg; 8 mg/kg for BW ≥30 kg). At week 16, patients with ≥JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab.ResultsIn part 1, 188 patients received tocilizumab (<30 kg: 10 mg/kg (n=35) or 8 mg/kg (n=34); ≥30 kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: −0.21; 95% CI −0.35 to −0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY).ConclusionsTocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis.Trial registration number:NCT00988221.

The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation

“…Studies included (n = 4) (described by 9 full papers and 12 conference abstracts) [65][66][67] ) and one RCT evaluated tocilizumab [68][69][70][71][72][73][74][75][76] (the CHERISH trial). For the sake of brevity, generally only the key reference for each RCT is cited in the main text of this report.…”

Administration of TNF- Inhibitors for Rheumatoid Arthritis Therapy. Comments to the Results of a Meta-Analysis of Randomized Trials by N. Graudal et al.: Final or Thought Provoking Conclusions?

“…Также в соответствии с рекоменда-циями EULAR (2013) по лечению ревматоидного артрита терапия ГИБП может применяться уже через 6 мес при неэффективности или непереносимости метотрексата или других небиологических БМПП при наличии небла-гоприятных факторов риска [7]. Практически во всех рандомизированных контролируемых исследованиях эффективности и безопасности ГИБП в лечении ювениль-ного идиопатического артрита комбинированная терапия является критерием исключения из соображений безо-пасности [8,9], и потому имеется не так много данных, позволяющих проводить сопоставительный анализ. Тем не менее, в реальной клинической практике, особенно в «добиологическую эру», детские ревматологи часто при-бегали к комбинированной терапии, и первые пациенты, получавшие ГИБП, были именно дети, которые лечились небиологическими БМПП [10].…”

Distinct Cytokine Profiles in Patients with Oligoarticular Juvenile Idiopathic Arthritis after &lt;i&gt;in&lt;/i&gt; &lt;i&gt;Vitro&lt;/i&gt; Blockade of T Cells by Cyclosporine and Abatacept

“…Up to 30% of pJIA patients still show signs of active disease although these patients may respond to methotrexate or biologics approved for pJIA [31] [32]. The study of Brunner et al allowed the conclusions that treatment with IL-6 inhibitor tocilizumab provides safe, sustained and clinically meaningful improvement for patients with pJIA [33].…”