Efficacy and safety of tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (SJIA): tender 52-week data

Abstract

BACKGROUND: Treatment options for sJIA, a disease associated with substantial morbidity and mortality, are limited. Excessive IL-6 production has been implicated in several manifestations of sJIA. Tocilizumab (TCZ), an IL-6 receptor inhibitor, improved arthritis and systemic symptoms of sJIA in a Japanese, placebo-controlled, withdrawal-design phase 3 trial in patients with sJIA refractory to conventional treatment. OBJECTIVE: To determine the efficacy and safety of TCZ in the 12-wk, double-blind, placebo-controlled, parallel-group part of the global 3-part, 5-yr, phase 3, multicentre study in patients with active sJIA. METHODS: Patients aged 2-17 yrs with active sJIA for >6 months and inadequate response to systemic corticosteroids (CS) and NSAIDs were randomised 2:1 to TCZ (8 mg/kg if body weight >30 kg; 12 mg/kg if <30 kg) or placebo (control) administered every 2 wks for 12 wks. CS tapering was permitted at wks 6 and 8 in patients with JIA ACR70 response, erythrocyte sedimentation rate <20 mm/h and no fever. Stable doses of NSAIDs and methotrexate were continued and could be altered or discontinued only for safety reasons. Patients who qualified for escape received standard-of-care rescue therapy; they were offered open-label TCZ every 2 wks and considered non-responders. The primary efficacy end point was proportion of patients attaining JIA ACR30 response at wk 12 and no fever (no temperature >237.5degreeC in preceding 7 days). RESULTS: The intent-to-treat population comprised 112 patients. Baseline characteristics were similar between arms (Table). By wk 12, 1 control (3%) and 2 TCZ patients (3%) withdrew, and more control than TCZ patients required rescue therapy (54% vs 3%). Significantly more TCZ than control patients (85.3% [64/75] vs 24.3% [9/37]; p<0.0001) attained the primary efficacy end point. JIA ACR70 and ACR90 responses were significantly (p<0.0001) greater in TCZ than control patients (Table). Among patients with fever, rash or anaemia at baseline, significantly more TCZ than control patients were afebrile, had no rash or had normal haemoglobin levels, respectively, at wk 12 (p<0.0008) (Table). Mean percentage decrease from baseline to wk 12 in the number of joints with active arthritis was significantly greater in TCZ than control patients (70.6% vs 37.2%; p=0.0012). Moreover, a significantly greater mean decrease from baseline to wk 12 in CHAQ-DI score occurred in TCZ than control patients (0.9 vs 0.2; p=0.0029). Furthermore, of patients who were receiving oral CS at baseline, a significantly greater proportion of TCZ than control patients (24.3% [17/70] vs 3.2% [1/31]; p=0.028) achieved JIA ACR70 response at wk 6 or 8, allowing them to reduce their CS dose by >20% without subsequent JIA ACR30 flare or occurrence of systemic symptoms. Four serious adverse events were reported in 3 patients, all in the TCZ group (angio-oedema and urticaria in 1 patient, bacterial arthritis and varicella infection); all resolved without sequelae. CONCLUSIONS: Results from this first global phase 3 study demonstrate that TCZ is highly effective and generally well tolerated in the short-term (12-wk) treatment of patients with sJIA.