Objective To assess the safety and efficacy of secukinumab, a fully human monoclonal anti-interleukin-17A antibody, in patients with rheumatoid arthritis (RA).
Methods Patients (n=237) with inadequate response to methotrexate were randomly assigned to receive monthly subcutaneous injections of secukinumab 25 mg, 75 mg, 150 mg, 300 mg or placebo. The primary endpoint was the American College of Rheumatology 20% response (ACR20) at week 16.
Results Demographics and baseline characteristics were comparable across all treatment groups. The primary efficacy endpoint was not achieved: the proportion of ACR20 responders at week 16 with secukinumab 25–300 mg was 36.0–53.7% versus placebo (34%). Disease activity score in 28 joints (DAS28)–C-reactive protein (CRP) was a secondary endpoint and clinically relevant decreases with secukinumab 75–300 mg were reported versus placebo. Serum high sensitivity CRP levels at week 16 were significantly reduced with secukinumab 75 mg, 150 mg and 300 mg doses versus placebo. The safety profile of secukinumab was consistent with that seen with other biological agents. Most adverse events (AE) were mild to moderate in severity. Infections were slightly more frequent with secukinumab than placebo. Six serious AE were reported: secukinumab 75 mg (one), secukinumab 300 mg (four) and placebo (one).
Conclusions ACR20 response rates differed between secukinumab 75 mg, 150 mg and 300 mg doses and placebo; however, the primary efficacy endpoint was not achieved. Greater decreases in DAS28 were observed with secukinumab 75 mg, 150 mg and 300 mg than placebo. There were no unexpected safety signals and no specific organ-related toxicities. Further trials with secukinumab in the treatment of RA are warranted.
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Funding The study was financially supported by an unrestricted grant from Novartis Pharma AG, Basel, Switzerland.
Competing interests MCG has received grant research support and consulting fees from Novartis; JAA has received speaker fees, consulting fees and/or Honiara from Abbott, Amgen, Takeda, UCB and Wyeth/Pfizer; PD, JS, ED, VM, S-HL, CEC, HK and TI have nothing to disclose; HBR is an employee of Novartis; SH and SM are employees of Novartis and own stocks or stock options in Novartis.
Patient consent Obtained.
Ethics approval Regulatory and ethical review board approvals from competent authorities in each country were obtained for the study protocol.
Provenance and peer review Not commissioned; externally peer reviewed.
ClinicalTrials.gov identifier NCT00928512.