Sarilumab in Polyarticular-Course Juvenile Idiopathic Arthritis: Dose-Finding and 1-Year Analysis of a Phase 2b, Open-Label, Multicenter Study.
prospective_cohort · Level II
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- Also identified by DOI 10.1002/acr.25692.
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Abstract
This study assessed sarilumab in treating patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). 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 to <30 kg) to select the optimal dose with regard to pharmacokinetics, safety and efficacy were evaluated 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 (area under the serum concentration versus time curve during a dose interval Շ of 2 weeks [AUC<sub>0-Շ</sub>], maximum serum concentration observed [C<sub>max</sub>], and concentrations observed before treatment administration during repeated dosing [C<sub>trough</sub>]). Safety and efficacy were assessed. The 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 the selected dose from baseline (n = 73), C<sub>max</sub>, AUC<sub>0-14 days</sub> and C<sub>trough</sub> 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, the JIA-American College of Rheumatology 30%, 50%, 70%, and 90% improvement criteria rates were 100%, 100%, 93.8%, and 76.6%, respectively. Adverse events were reported in 70 of 73 patients (95.9%). Twenty-seven patients (37%) experienced grade 3/4 neutropenia; there were no associated infections. No deaths occurred. In patients with pcJIA receiving the selected dose from baseline, pharmacokinetic exposure was comparable to a dose of 200 mg q2w for adults with rheumatoid arthritis. Clinically relevant improvements were observed in disease activity, with safety being consistent with the known profile of sarilumab.