title: Evaluation of low-dose rituximab for the retreatment of patients with active rheumatoid arthritis: a non-inferiority randomised controlled trial.
abstract: BACKGROUND
  The licensed dose of rituximab in rheumatoid arthritis (RA) is two doses of 1000 mg given 2 weeks apart. A lower dose has never been specifically studied in patients with an inadequate response to anti-tumour necrosis factor (TNF) agents.
  
  
  OBJECTIVE
  To compare the efficacy and safety of rituximab repeat treatment with two doses (1000 mg×1 and 1000 mg×2) following initial treatment with 1000 mg×2.
  
  
  METHODS
  We set up an open-label, prospective, multicentre, non-inferiority study comprising a non-controlled period (24 weeks) followed by a randomised controlled period (weeks 24-104) in patients with RA and an inadequate response to anti-TNF agents. All patients received one course of rituximab (1000 mg×2) with methotrexate. At week 24, patients achieving a EULAR response (moderate or good) were randomised to rituximab retreatment at 1000 mg×1 (Arm A) or 1000 mg×2 (Arm B). The primary objective measure was disease activity in 28 joints C-reactive protein (DAS28-CRP) area under the curve (AUC) over 104 weeks with a non-inferiority margin defined by 20% (444) of the mean DAS28-CRP AUC (mean±SD 2218±967) of the reference data.
  
  
  RESULTS
  The intent-to-treat and per-protocol (PP) populations comprised 143 (A/B: 70/73) and 100 (A/B: 51/49) patients, respectively. The adjusted mean difference in DAS28-CRP AUC (PP) was 51.4 (95% CI -131.2 to 234), demonstrating non-inferiority between arms A and B. The overall rituximab safety profile was similar with both retreatment regimens.
  
  
  CONCLUSIONS
  Following a clinical response to a first course of rituximab in RA at the licensed dose of 1000 mg×2, retreatment with rituximab at 1000 mg×1 results in efficacy outcomes that are non-inferior to those achieved with retreatment at 1000 mg×2.
  
  
  BACKGROUND
  NCT01126541.
authors.affiliation: Department of Rheumatology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Paris Sud, Université Paris Sud, INSERM U1012, Le Kremlin-Bicêtre, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Roche, Boulogne Billancourt, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Rouanet
authors.affiliation: Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.affiliation: Department of Rheumatology, Hôpital Lapeyronie, Université Montpellier I, Montpellier, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Combe
authors.affiliation: Department of Rheumatology, Hôpital Universitaire de Rouen, Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Rouen, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Le Loët
authors.affiliation: Department of Rheumatology, Hôpital Lyon-sud, Pierre-Bénite, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Tebib
authors.affiliation: Roche, Boulogne Billancourt, France.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Jourdan
authors.affiliation: Department of Rheumatology, Hôpital Cochin, Rene Descartes University, Paris, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015415:Biomarkers; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000517:prevention & control; D011446:Prospective Studies; D019233:Retreatment / Q000379:methods; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D015415:Biomarkers; D000069283:Rituximab
keywords: B cells; Rheumatoid Arthritis; Treatment