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Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients: results of a 1-year follow-up study from the CERERRA collaboration
  1. Katerina Chatzidionysiou1,
  2. Elisabeth Lie2,
  3. Evgeny Nasonov3,
  4. Galina Lukina3,
  5. Merete Lund Hetland4,
  6. Ulrik Tarp5,
  7. Piet L C M van Riel6,
  8. Dan C Nordström7,
  9. Juan Gomez-Reino8,
  10. Karel Pavelka9,
  11. Matija Tomsic10,
  12. Tore K Kvien2,
  13. Ronald F van Vollenhoven1,
  14. Cem Gabay11
  1. 1Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
  2. 2Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  3. 3ARBITER, Institute of Rheumatology, Moscow, Russia
  4. 4DANBIO, Department of Rheumatology, Copenhagen University Hospital, Glostrup, Copenhagen, Denmark
  5. 5Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark
  6. 6Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  7. 7Department of Medicine, ROB-FIN Helsinki University Central Hospital, Helsinki, Finland
  8. 8Hospital Clinico University De Santiago, Santiago, Spain
  9. 9Institute of Rheumatology, Charles University, Prague, Czech Republic
  10. 10University Medical Center, Ljubljana, Slovenia
  11. 11Department of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland
  1. Correspondence to Professor Cem Gabay, Department of Rheumatology, University Hospitals of Geneva, 26 Avenue Beau-Séjour, 1211 Geneva 14, Switzerland; cem.gabay{at} for the SCQM Registry


Objectives To compare the effectiveness and safety of rituximab alone or in combination with either methotrexate or leflunomide.

Methods 10 European registries submitted anonymised datasets with baseline, 3, 6, 9 and 12-month clinical data from patients who started rituximab.

Results 1195 patients were treated with rituximab plus methotrexate, 177 with rituximab plus leflunomide and 505 with rituximab alone. Significantly more patients achieved a European League Against Rheumatism good response at 6 months when treated with rituximab plus leflunomide (29.1%) compared with rituximab plus methotrexate (21.1%) and rituximab alone (19.3%; p=0.02 and p=0.01, respectively). Similar results were observed at 12 months. Adverse events occurred in 10.2%, 13.2% and 13.9% of patients on rituximab plus leflunomide, rituximab plus methotrexate and rituximab alone, respectively.

Conclusions Leflunomide is an effective and safe alternative to methotrexate as concomitant treatment with rituximab. Slightly better results were obtained by the combination of rituximab and leflunomide than rituximab and methotrexate, raising the possibility of a synergistic effect of leflunomide and rituximab.

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  • Funding The study was funded by industry (Roche).

  • Competing interests None.

  • Ethics approval The study was approved by different ethics committees in the different countries involved.

  • Provenance and peer review Not commissioned; externally peer reviewed.