Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study
- Mark C Genovese1,
- Patrick Durez2,
- Hanno B Richards3,
- Jerzy Supronik4,
- Eva Dokoupilova5,
- Vadim Mazurov6,
- Jacob A Aelion7,
- Sang-Heon Lee8,
- Christine E Codding9,
- Herbert Kellner10,
- Takashi Ikawa11,
- Sophie Hugot3,
- Shephard Mpofu3
- 1Department of Rheumatology, Stanford University, Palo Alto, California, USA
- 2Université Catholique de Louvain, Brussels, Belgium
- 3Novartis Pharma AG, Basel, Switzerland
- 4NZOZ Centrum Medyczne Artur Racewicz, Bialystok, Poland
- 5Medical Plus, Uherske Hradiste, Czech Republic
- 6St. Petersburg State Medical Academy of Postgraduate Education, St Petersburg, Russia
- 7The Arthritis Clinic, Jackson, Tennessee, USA
- 8Konkuk University Medical Center, Seoul, Republic of Korea
- 9Health Research of Oklahoma, Oklahoma City, Oklahoma, USA
- 10Department of Rheumatology, Hospital Neuwittelsbach, Munich, Germany
- 11Konan Yamate Clinic, Kobe, Hyogo, Japan
- Correspondence to Dr Mark C Genovese, Division of Immunology and Rheumatology, Stanford University, 1000 Welch RD #203, Palo Alto, CA 94304, USA;
- Received 28 February 2012
- Accepted 20 May 2012
- Published Online First 23 June 2012
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.