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Ann Rheum Dis 73:1508-1514 doi:10.1136/annrheumdis-2013-203480
  • Clinical and epidemiological research
  • Extended report

Evaluation of low-dose rituximab for the retreatment of patients with active rheumatoid arthritis: a non-inferiority randomised controlled trial

  1. Maxime Dougados7
  1. 1Department of Rheumatology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Paris Sud, Université Paris Sud, INSERM U1012, Le Kremlin—Bicêtre, France
  2. 2Roche, Boulogne Billancourt, France
  3. 3Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
  4. 4Department of Rheumatology, Hôpital Lapeyronie, Université Montpellier I, Montpellier, France
  5. 5Department of Rheumatology, Hôpital Universitaire de Rouen, Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Rouen, France
  6. 6Department of Rheumatology, Hôpital Lyon-sud, Pierre-Bénite, France
  7. 7Department of Rheumatology, Hôpital Cochin, Rene Descartes University, Paris, France
  1. Correspondence to Dr X Mariette, Rhumatologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, 78 rue du général Leclerc, Le Kremlin Bicêtre 94275, France; xavier.mariette{at}bct.aphp.fr
  • Accepted 5 May 2013
  • Published Online First 30 May 2013

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.

ClinicalTrials.gov registration number: NCT01126541.