Long-term, interventional, open-label extension study evaluating the safety of tocilizumab treatment in patients with polyarticular-course juvenile idiopathic arthritis from Poland and Russia who completed the global, international CHERISH trial

Violetta Opoka-Winiarska,Ekaterina Alexeeva,Zbigniew Żuber,Irina Nikishina,Vyacheslav Chasnyk,Grażyna Dębowska,Elżbieta Smolewska

doi:10.1007/s10067-018-4071-9

Abstract

Efficacy and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, were demonstrated in juvenile idiopathic arthritis (JIA) with polyarticular course (pJIA) in the CHERISH trial. This observational, III phase study evaluated long-term treatment of TCZ in pJIA patients was conducted by members of the Pediatric Rheumatology International Trials Organization (PRINTO) from Poland and Russia. Forty-one patients, who had completed the CHERISH core study (104 weeks), were extensionally treated with TCZ (8 mg/kg, intravenous infusion every 4 weeks). Total treatment time was from 131 to 193 weeks. The long-term safety (the primary endpoint) and efficacy were evaluated. All patients achieved ACR70 response in the core study and continued to achieve at least ACR50 response up to week 24 of this study. The safety population comprised 46.41 patient-years (PY). Rates per 100 PY of adverse (AEs) and serious events (SAEs) were 181.0 and 6.46, respectively. Pharyngitis and respiratory tract infections were the most common AEs. Except one AE (severe neutropenia), all others were classified as mild (24.4%) or moderate (29.3%). The incidence of SAEs was low (7.3%). No new safety findings were observed. The safety profile of over 2.5-year treatment with TCZ is consistent with the pre-marketing CHERISH clinical trial. Presented data and continued efficacy response support the use of TCZ in pJIA. EUDRACT No: 2011-001607-12. https://clinicaltrials.gov/ct2/show/study/NCT01575769?term=ML27783

Highlights

Juvenile idiopathic arthritis (JIA) is a clinically heterogeneous group of diseases characterized by arthritis that begins before 16 years of patient age and persists for minimum 6 weeks
The efficacy response and the consistent safety profile support the use of TCZ in pJIA
Our data demonstrate that continuing treatment over 104 to 131 weeks or longer with TCZ is safe and efficacious for the management of pJIA

Summary

Introduction

Juvenile idiopathic arthritis (JIA) is a clinically heterogeneous group of diseases characterized by arthritis that begins before 16 years of patient age and persists for minimum 6 weeks. TCZ showed safety and activity in several studies in patients with systemic and polyarticular course of JIA [5,6,7,8,9]. Efficacy and safety of TCZ were demonstrated in the global, three-part, randomized, placebo-controlled, double-blind, withdrawal, phase III clinical trial (the CHERISH study) in patients with active pJIA (rheumatoid factor-positive or rheumatoid factor-negative pJIA or persisting oligoarticular JIA) for at least 6 months and inadequate response to methotrexate (MTX) [5]. One hundred sixty-three patients, who achieved at least JIA ACR 30 responses, were enrolled into the second part of study. It was 24-week doubleblind phase with randomization 1:1 to placebo or to TCZ. European Medicines Agency has approved TCZ to treat children with pJIA in 2013

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