title: Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)).
abstract: OBJECTIVE
  This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment.
  
  
  METHODS
  Patients with active disease on stable MTX (10-25 mg/week) were randomised to rituximab 2 x 500 mg (n=168), rituximab 2 x 1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) > or =2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2 x 500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48.
  
  
  RESULTS
  At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2 x 500 mg) + MTX, rituximab (2 x 1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48.
  
  
  CONCLUSIONS
  Rituximab (at 2 x 500 mg and 2 x 1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses.
authors.affiliation: Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds. p.emery@leeds.ac.uk [corrected]
authors.forename: P
authors.initials: P
authors.lastname: Emery
authors.forename: A
authors.initials: A
authors.lastname: Deodhar
authors.forename: W F
authors.initials: WF
authors.lastname: Rigby
authors.forename: J D
authors.initials: JD
authors.lastname: Isaacs
authors.forename: B
authors.initials: B
authors.lastname: Combe
authors.forename: A J
authors.initials: AJ
authors.lastname: Racewicz
authors.forename: K
authors.initials: K
authors.lastname: Latinis
authors.forename: C
authors.initials: C
authors.lastname: Abud-Mendoza
authors.forename: L J
authors.initials: LJ
authors.lastname: Szczepanski
authors.forename: R A
authors.initials: RA
authors.lastname: Roschmann
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.forename: G K
authors.initials: GK
authors.lastname: Armstrong
authors.forename: W
authors.initials: W
authors.lastname: Douglass
authors.forename: H
authors.initials: H
authors.lastname: Tyrrell
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D000069283:Rituximab; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D000069283:Rituximab; D008727:Methotrexate