Karel Pavelka1, Yun Chon1, Richard Newmark1, Shao-Lee Lin1, Scott Baumgartner1, Ngozi Erondu2. 1. From the Institute of Rheumatology, Prague, Czech Republic; and Amgen Inc., Thousand Oaks, California, USA.K. Pavelka, MD, PhD, Institute of Rheumatology; Y. Chon, PhD; R. Newmark, PhD, Amgen Inc.; S.L. Lin, MD, PhD; S. Baumgartner, MD, formerly employed by Amgen Inc.; N. Erondu, MD, PhD, Amgen Inc. 2. From the Institute of Rheumatology, Prague, Czech Republic; and Amgen Inc., Thousand Oaks, California, USA.K. Pavelka, MD, PhD, Institute of Rheumatology; Y. Chon, PhD; R. Newmark, PhD, Amgen Inc.; S.L. Lin, MD, PhD; S. Baumgartner, MD, formerly employed by Amgen Inc.; N. Erondu, MD, PhD, Amgen Inc. nerondu@amgen.com.
Abstract
OBJECTIVE: To evaluate the efficacy and safety of brodalumab, a human monoclonal antibody inhibitor of the interleukin 17 receptor, in subjects with rheumatoid arthritis (RA). METHODS:Patients (n = 252) with inadequate response tomethotrexate (MTX) were randomized to receive subcutaneous injections of brodalumab (70 mg, 140 mg, or 210 mg) or placebo. The primary endpoint was the American College of Rheumatology 50% response (ACR50) at Week 12. RESULTS: Demographics and baseline characteristics were generally balanced among treatment groups. At Week 12, ACR50 occurred in 16% (70 mg), 16% (140 mg), 10% (210 mg), and 13% (placebo; all nonsignificant vs placebo) of subjects. No significant treatment effects were observed for the secondary endpoints, including ACR20, ACR70, and Disease Activity Score in 28 joints. Incidences of all adverse events (AE), including serious AE (SAE), were similar across treatment groups. A total of 7 subjects reported SAE during the study (2 in the placebo group and 5 in the brodalumab groups), none of which was treatment related. There was 1 death (cardiopulmonary failure) ∼1 week after the last dose in the 140 mg group. CONCLUSION: Our study failed to find evidence of meaningful clinical efficacy with brodalumab treatment in subjects with RA who had an inadequate response to MTX. These preliminary results do not support further evaluation of brodalumab as a treatment for RA. Clinicaltrials.gov number: NCT00950989.
RCT Entities:
OBJECTIVE: To evaluate the efficacy and safety of brodalumab, a human monoclonal antibody inhibitor of the interleukin 17 receptor, in subjects with rheumatoid arthritis (RA). METHODS:Patients (n = 252) with inadequate response to methotrexate (MTX) were randomized to receive subcutaneous injections of brodalumab (70 mg, 140 mg, or 210 mg) or placebo. The primary endpoint was the American College of Rheumatology 50% response (ACR50) at Week 12. RESULTS: Demographics and baseline characteristics were generally balanced among treatment groups. At Week 12, ACR50 occurred in 16% (70 mg), 16% (140 mg), 10% (210 mg), and 13% (placebo; all nonsignificant vs placebo) of subjects. No significant treatment effects were observed for the secondary endpoints, including ACR20, ACR70, and Disease Activity Score in 28 joints. Incidences of all adverse events (AE), including serious AE (SAE), were similar across treatment groups. A total of 7 subjects reported SAE during the study (2 in the placebo group and 5 in the brodalumab groups), none of which was treatment related. There was 1 death (cardiopulmonary failure) ∼1 week after the last dose in the 140 mg group. CONCLUSION: Our study failed to find evidence of meaningful clinical efficacy with brodalumab treatment in subjects with RA who had an inadequate response to MTX. These preliminary results do not support further evaluation of brodalumab as a treatment for RA. Clinicaltrials.gov number: NCT00950989.