Sarilumab in Polyarticular-Course Juvenile Idiopathic Arthritis: Dose-Finding and One-Year Analysis of a Phase 2b, Open-Label, Multicenter Study

Abstract

Objective: This study assessed sarilumab in treating patients with polyarticular-course juvenile idiopathic arthritis (pcJIA).

Methods: This phase 2b, open-label study (NCT02776735) consisted of three sequential parts (each with a core-treatment and extension-phase). During part 1, three doses were assessed in two weight groups (Group A/B: ≥30-60 kg/≥10-<30 kg) to select the optimal dose with regards to pharmacokinetics, safety and efficacy to evaluate in latter parts. During the extension-phase of part 1, patients initially assigned to the selected optimal dose continued on this dose; the remaining patients were switched to this selected dose. Patients in parts 2 and 3 received the selected dose from baseline. The primary endpoint was pharmacokinetic exposure (AUC_{0- Շ}, C_max, C_trough). Safety and efficacy were assessed.

Results: Mean age of treated patients (n=101; 76.2% female) was 9.4 years. Of the evaluated doses in part 1, dose 2 (Group A/B: 3.0/4.0 mg/kg every 2 weeks [q2w]) was selected. In patients receiving selected dose from baseline (n=73), C_max, AUC_0-14days and C_trough at steady-state in Group A/B were 27.1/40.4 mg/L, 276/395 day*mg/L, and 9.57/14.4 mg/L respectively. At Week 48, JIA-ACR 30/50/70/90 rates were 100%/100%/93.8%/76.6%. Adverse events were reported in 70/73 (95.9%) patients. Twenty-seven (37%) patients experienced grade 3/4 neutropenia; with no associated infections. No death occurred.

Conclusion: In pcJIA patients receiving the selected dose from baseline, pharmacokinetic exposure was comparable to a dose of 200mg q2w for adults with rheumatoid arthritis. Clinically relevant improvements were observed in disease activity, with safety being consistent with the known profile of sarilumab.