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Extended report
Treatment strategies in patients with rheumatoid arthritis for whom methotrexate monotherapy has failed: data from the NOR-DMARD register
  1. Elisabeth Lie1,
  2. Désirée van der Heijde1,2,
  3. Till Uhlig1,
  4. Knut Mikkelsen3,
  5. Synøve Kalstad4,
  6. Cecilie Kaufmann5,
  7. Erik Rødevand6,
  8. Tore K Kvien1
  1. 1Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  2. 2Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3Department of Rheumatology Lillehammer Hospital for Rheumatic Diseases, Lillehammer, Norway
  4. 4Department of Rheumatology, University Hospital Northern Norway, Tromsø, Norway
  5. 5Department of Rheumatology, Buskerud Central Hospital, Drammen, Norway
  6. 6Department of Rheumatology, St Olavs Hospital, Trondheim, Norway
  1. Correspondence to Dr Elisabeth Lie, Department of Rheumatology, Diakonhjemmet Hospital, PO Box 23 Vinderen, N-0319 Oslo, Norway; elisabeth_lie{at}


Objectives To compare the effectiveness of adding synthetic disease-modifying antirheumatic drugs (sDMARDs) versus tumour necrosis factor α inhibitors (TNFi) to methotrexate (MTX) in patients with rheumatoid arthritis (RA) who were MTX inadequate responders (IR). Second, to examine outcomes in patients receiving MTX+TNFi for whom the MTX+sDMARD combination had also failed.

Methods Patients with RA (disease duration ≤ 5 years, MTX IR and naïve to other DMARDs) starting treatment with MTX+TNFi or MTX+sDMARDs were included. From the latter group a subgroup of patients who went on to receive MTX+TNFi was identified.

Results Patients receiving MTX+TNFi (n=98) and MTX+sDMARDs (n=129) had similar baseline disease activity when starting combination therapy (mean Disease Activity Score 28 (DAS28) = 4.90 and 4.96, respectively). Three- and 6-month effectiveness and 2-year drug survival were better for MTX+TNFi than for MTX+sDMARDs: mean ∆DAS28 was −1.61 versus −0.85 after 3 months (p<0.001) and −1.91 versus −1.03 after 6 months (p=0.01); DAS28<2.6 was reached by 29.0% versus 11.6% after 3 and 34.5% versus 12.9% after 6 months. Effectiveness was somewhat better with triple therapy than other MTX+sDMARD combinations but was generally inferior compared with MTX+TNFi. For the patients who received MTX+TNFi as a third step after MTX+sDMARDs had failed (n=38) there was a tendency towards lower remission rates, worse disease activity states and inferior drug survival compared with patients who received MTX+TNFi directly after the failure of MTX.

Conclusions Effectiveness was better for MTX+TNFi than for MTX+sDMARDs. Patients who started MTX+TNFi after two synthetic DMARD regimens had failed had a tendency to less favourable disease states after 3 months than patients who switched directly from MTX to MTX+TNFi.

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  • Funding The work was supported by Eastern Norway Regional Health Authority. The Norwegian Disease-Modifying Antirheumatic Drug study has received unrestricted grant support from Abbott, Amgen, Wyeth, Aventis, MSD, Schering-Plough/Centocor, BristolMyers Squibb, UCB, Roche and the Norwegian Directorate for Health and Social Affairs.

  • Competing interests The NOR-DMARD register is financially supported by pharmaceutical companies but the sponsors are not involved in the analyses and presentation of data. Most of the authors have received speaker and/or consultancy honoraria from companies marketing biological DMARDs.

  • Ethics approval This study was conducted with the approval of the regional ethics committee and by the Data Inspectorate. Patients gave written informed consent before participation.

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