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

Abstract

Objective: To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA).

Methods: This 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.

Results: In 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).

Conclusions: Tocilizumab 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.

Keywords: DMARDs (biologic); Juvenile Idiopathic Arthritis; Treatment.

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Figures

Figure 1

Summary of patient disposition. Part 1 treatment is indicated in parentheses. aThree patients were not included in the ITT population for part 2 because they discontinued before receiving a single dose of study drug. AE, adverse event; BW, body weight; JIA-ACR, juvenile idiopathic arthritis-American College of Rheumatology; ITT, intent-to-treat.

Figure 2

(A) JIA-ACR30/50/70/90 response rates by visit in part 1. (B) Line plot of JIA-ACR core components by week in part 1. (C) JIA-ACR30/50/70/90 improvement by treatment group at the end of part 1 at week 16. (D) Time to JIA-ACR30 flare after randomisation in the withdrawal phase (part 2); part 1 treatment is indicated in parentheses. For JIA-ACR responses (A, C), n=188. For JIA-ACR core components (B), n=182–187 for number of joints with active arthritis and number of joints with limitation of movement; n=178–184 for assessment of patient overall well-being; n=181–187 for physician global assessment of disease activity; n=182–184 for CHAQ-DI; and n=182–188 for ESR. For time to JIA-ACR30 flare (D), n=number of patients remaining in the study at each time point. aLog-rank test adjusted for stratification factors applied at randomisation in part 1 was a predefined, exploratory analysis. HR, 0.36; 95% CI 0.19 to 0.67. CHAQ-DI, Childhood Health Assessment Questionnaire-Disability Index; ESR, erythrocyte sedimentation rate; JIA-ACR, juvenile idiopathic arthritis-American College of Rheumatology; VAS, visual analogue scale.