title: A randomised phase II study evaluating the efficacy and safety of subcutaneously administered ustekinumab and guselkumab in patients with active rheumatoid arthritis despite treatment with methotrexate.
abstract: OBJECTIVE
  Interleukin (IL)-12 and IL-23 have been implicated in the pathogenesis of rheumatoid arthritis (RA). The safety and efficacy of ustekinumab, a human monoclonal anti-IL-12/23 p40 antibody, and guselkumab, a human monoclonal anti-IL-23 antibody, were evaluated in adults with active RA despite methotrexate (MTX) therapy.
  
  
  METHODS
  Patients were randomly assigned (1:1:1:1:1) to receive placebo at weeks 0, 4 and every 8 weeks (n=55), ustekinumab 90 mg at weeks 0, 4 and every 8 weeks (n=55), ustekinumab 90 mg at weeks 0, 4 and every 12 weeks (n=55), guselkumab 50 mg at weeks 0, 4 and every 8 weeks (n=55), or guselkumab 200 mg at weeks 0, 4 and every 8 weeks (n=54) through week 28; all patients continued a stable dose of MTX (10-25 mg/week). The primary end point was the proportion of patients with at least a 20% improvement in the American College of Rheumatology criteria (ACR 20) at week 28. Safety was monitored through week 48.
  
  
  RESULTS
  At week 28, there were no statistically significant differences in the proportions of patients achieving an ACR 20 response between the combined ustekinumab group (53.6%) or the combined guselkumab group (41.3%) compared with placebo (40.0%) (p=0.101 and p=0.877, respectively). Through week 48, the proportions of patients with at least one adverse event (AE) were comparable among the treatment groups. Infections were the most common type of AE.
  
  
  CONCLUSIONS
  Treatment with ustekinumab or guselkumab did not significantly reduce the signs and symptoms of RA. No new safety findings were observed with either treatment.
  
  
  BACKGROUND
  NCT01645280.
authors.affiliation: Medical University of Vienna and Hietzing Hospital, Vienna, Austria.
authors.forename: Josef S
authors.identifier: http://orcid.org/0000-0002-8899-9087
authors.initials: JS
authors.lastname: Smolen
authors.affiliation: Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Agarwal
authors.affiliation: Leningrad Region Clinical Hospital, Saint Petersburg, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Ilivanova
authors.affiliation: Janssen Research & Development, LLC, La Jolla, California, USA.
authors.forename: Xie Lillian
authors.initials: XL
authors.lastname: Xu
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Ivo
authors.initials: I
authors.lastname: Nnane
authors.affiliation: Janssen Research & Development, LLC, La Jolla, California, USA.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Radziszewski
authors.affiliation: Janssen Research & Development, LLC, La Jolla, California, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Greenspan
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Beutler
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Baker
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D019233:Retreatment; D012720:Severity of Illness Index; D017211:Treatment Failure; D000069549:Ustekinumab / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C000588857:guselkumab; D000069549:Ustekinumab; D008727:Methotrexate
keywords: Disease Activity; Methotrexate; Rheumatoid Arthritis; Treatment