In patients with rheumatoid arthritis (RA) refractory to methotrexate and sulfasalazine, sirukumab monotherapy (50 mg every 4 weeks or 100 mg every 2 weeks) is generally tolerable with measurable efficacy over the course of 52 weeks, according to the results of a phase 3, randomized, double-blind study (ClinicalTrials.gov identifier: NCT01689532) published in Arthritis Research & Therapy.
A total of 122 patients ≥20 years were randomly assigned to receive subcutaneously administered sirukumab 50 mg every 4 weeks (n=61) or sirukumab 100 mg every 2 weeks (n=61) for 52 weeks. After 24 weeks, all patients were permitted to take disease-modifying antirheumatic drugs (DMARDs). Safety was evaluated and efficacy assessed using American College of Rheumatology (ACR) responses, Disease Activity Score C-reactive protein (DAS28-CRP) score, and Health Assessment Questionnaire-Disability Index (HAQ-DI) score.
Of the 122 patients, a total of 99 completed the 52-week study. Adverse events were reported in 93.4% of patients, and serious adverse events were reported in 7.4% of patients. During the study period, there were no major cardiovascular adverse events, serious gastrointestinal perforations, cases of tuberculosis, or deaths reported. Grade 3 hematologic abnormalities, including leukopenia and neutropenia, were reported in 7 patients; no grade 4 hematologic abnormalities were observed.
ACR20 responses (≥20% improvement) were detected within 2 weeks in 77.0% of patients receiving sirukumab 50 mg every 4 weeks and in 72.1% of patients receiving sirukumab 100 mg every 2 weeks at 16 weeks, and were maintained through 52 weeks. In addition, ACR50/70, DAS28-CRP, and HAQ-DI responses also persisted through 52 weeks in both groups of patients.
The investigators concluded that sirukumab monotherapy at both doses was generally well tolerated, and the safety profile was independent of dosage. Treatment with sirukumab monotherapy may have the potential to be a viable new treatment option for patients with RA who are refractory to conventional synthetic or biologic DMARDs.
Takeuchi T, Yamanaka H, Harigai M, et al. Sirukumab in rheumatoid arthritis refractory to sulfasalazine or methotrexate: a randomized phase 3 safety and efficacy study in Japanese patients. Arthritis Res Ther. 2018;20(1):42.