title: Efficacy and safety of a selective estrogen receptor β agonist, ERB-041, in patients with rheumatoid arthritis: a 12-week, randomized, placebo-controlled, phase II study.
abstract: OBJECTIVE
  Selective estrogen receptor β (ERβ) agonists have demonstrated relevant antiinflammatory effects in different animal models. This study aimed to compare the efficacy and safety of one of these agonists, ERB-041, in subjects with rheumatoid arthritis (RA).
  
  
  METHODS
  A total of 291 patients with active RA receiving stable doses of methotrexate were randomized to receive 5, 25, or 75 mg of ERB-041 or placebo for 12 weeks. The primary end point was the American College of Rheumatology 20% improvement criteria (ACR20) at 12 weeks. Secondary end points included the ACR 50% improvement criteria (ACR50) and the ACR 70% improvement criteria (ACR70) responses, health outcomes measures, C-reactive protein (CRP) levels, and potential exposure-response relationships. Medical history, physical examination, and laboratory values were obtained at screening, baseline, and weeks 2, 4, 8, and 12.
  
  
  RESULTS
  No statistically significant difference for the ACR20 was found between the ERB-041 treatment and placebo groups (P = 0.518). Nor was a significant difference observed for ACR50 and ACR70 responses, health outcomes measures, CRP levels, and overall incidence of adverse events among all groups. Forty-four subjects (15.1%) discontinued the study and the rate of discontinuation was similar among the treatment groups. The most commonly reported treatment-emergent adverse events were headache (7.6%), nausea (6.2%), infection (4.8%), and bronchitis (4.1%). None of the adverse events was considered treatment related.
  
  
  CONCLUSIONS
  Although well tolerated and safe, ERB-041 failed to demonstrate antiinflammatory efficacy in RA patients, despite evidence of strong activity in preclinical arthritis models. These results suggest that selective ERβ agonists would not have effects on regulating inflammatory response in RA. Nevertheless, further studies are warranted to establish their efficacy in inflammatory arthritis.
authors.affiliation: Universidad Autónoma, Madrid, Spain.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Roman-Blas
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
authors.forename: Gabriel
authors.initials: G
authors.lastname: Herrero-Beaumont
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D047629:Estrogen Receptor beta / Q000819:agonists*; D005260:Female; D005500:Follow-Up Studies; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010080:Oxazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C478102:ERB 041; D047629:Estrogen Receptor beta; D010080:Oxazoles