Abstract

OBJECTIVE: To evaluate long-term safety and efficacy of sarilumab over 5 years in patients with RA refractory to TNF inhibitors (TNFi).METHODS: Patients in the 24-week randomized controlled trial (RCT) TARGET (NCT01709578) whoreceived double-blind placebo or sarilumab 150 or 200mg every 2 weeks (q2w), plus conventionalsynthetic DMARDs (csDMARDs), were eligible to receive open-label sarilumab 200mg q2w pluscsDMARDs in the open-label extension (OLE), EXTEND (NCT01146652). OLE dose reduction to 150mg q2w was permitted per investigators' judgement or protocol-mandated safety concerns. Safety and efficacy were assessed through treatment-emergent adverse events (AEs), laboratoryabnormalities and clinical disease activity scores. All statistics are descriptive.RESULTS: Of 546 patients, 454 (83%) were treated with sarilumab in the OLE. Cumulative observation period was 1654.8 patient-years (PY; n = 521); 268 patients (51%) had =4 years' exposure. Incidencerates per 100 PY of AEs, AEs leading to discontinuation, infection and serious infection were 160.4, 8.1, 57.8 and 3.9, respectively. Neutropenia was the most common AE (15.3 per 100 PY). Absoluteneutrophil count <1000 cells/mm3 (Grade 3/4 neutropenia) was observed in 74 patients (14.2%) and normalized on treatment in 48. Clinical efficacy was sustained through 5 years' follow-up. Efficacy was similar for patients with 1 and >1 TNFi failure, and between patients who either remained on 200mg or reduced to 150mg.CONCLUSION: In patients with RA refractory to TNFi, sarilumab's long-term term safety profile was consistent with previous clinical studies and post-marketing reports. Efficacy was sustained over 5years.

View details for DOI 10.1093/rheumatology/keab355

View details for PubMedID 33871596