title: A study to evaluate the safety, tolerability, and efficacy of brodalumab in subjects with rheumatoid arthritis and an inadequate response to methotrexate.
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 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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Karel
authors: K
authors: Pavelka
authors: 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.
authors: Yun
authors: Y
authors: Chon
authors: 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.
authors: Richard
authors: R
authors: Newmark
authors: 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.
authors: Shao-Lee
authors: SL
authors: Lin
authors: 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.
authors: Scott
authors: S
authors: Baumgartner
authors: 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.
authors: Ngozi
authors: N
authors: Erondu
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D020714:Maximum Tolerated Dose; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D015999:Multivariate Analysis; D010147:Pain Measurement; D011446:Prospective Studies; D019233:Retreatment / Q000379:methods; D018570:Risk Assessment; D012720:Severity of Illness Index; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C571216:brodalumab; D008727:Methotrexate
keywords: BRODALUMAB; INTERLEUKIN 17; PHASE 2; RANDOMIZED CONTROLLED TRIAL; RHEUMATOID ARTHRITIS