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Gradual tapering TNF inhibitors versus conventional synthetic DMARDs after achieving controlled disease in patients with rheumatoid arthritis: first-year results of the randomised controlled TARA study
  1. Elise van Mulligen1,
  2. Pascal Hendrik Pieter de Jong1,
  3. Tjallingius Martijn Kuijper2,
  4. Myrthe van der Ven1,
  5. Cathelijne Appels3,
  6. Casper Bijkerk4,
  7. Joop B Harbers5,
  8. Yael de Man6,
  9. T H Esmeralda Molenaar7,
  10. Ilja Tchetverikov8,
  11. Yvonne P M Goekoop-Ruiterman9,
  12. Jende van Zeben10,
  13. Johanna M W Hazes1,
  14. Angelique E A M Weel2,
  15. Jolanda J Luime1
  1. 1 Rheumatology, Erasmus Medical Centre, Rotterdam, The Netherlands
  2. 2 Rheumatology, Maasstad Ziekenhuis, Rotterdam, The Netherlands
  3. 3 Rheumatology, Amphia ziekenhuis, Breda, The Netherlands
  4. 4 Rheumatology, Reinier de Graaf Gasthuis, Delft, The Netherlands
  5. 5 Rheumatology, Franciscus ziekenhuis, Roosendaal, The Netherlands
  6. 6 Rheumatology, Sint Antonius Ziekenhuis, Utrecht, The Netherlands
  7. 7 Rheumatology, Groene Hart Ziekenhuis, Gouda, The Netherlands
  8. 8 Rheumatology, Albert Schweitzer Ziekenhuis, Dordrecht, The Netherlands
  9. 9 Rheumatology, Haga Ziekenhuis, The Hague, The Netherlands
  10. 10 Rheumatology, Franciscus Gasthuis, Rotterdam, The Netherlands
  1. Correspondence to Elise van Mulligen, Rheumatology, Erasmus MC, Rotterdam 3015, Netherlands; elise.vanmulligen{at}


Objectives The aim of this study is to evaluate the effectiveness of two tapering strategies after achieving controlled disease in patients with rheumatoid arthritis (RA), during 1 year of follow-up.

Methods In this multicentre single-blinded (research nurses) randomised controlled trial, patients with RA were included who achieved controlled disease, defined as a Disease Activity Score (DAS) ≤ 2.4 and a Swollen Joint Count (SJC) ≤ 1, treated with both a conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and a TNF inhibitor. Eligible patients were randomised into gradual tapering csDMARDs or TNF inhibitors. Medication was tapered if the RA was still under control, by cutting the dosage into half, a quarter and thereafter it was stopped. Primary outcome was proportion of patients with a disease flare, defined as DAS > 2.4 and/or SJC > 1. Secondary outcomes were DAS, European Quality of Life-5 Dimensions (EQ5D) and functional ability (Health Assessment Questionnaire Disability Index [HAQ-DI]) after 1 year and over time.

Results A total of 189 patients were randomly assigned to tapering csDMARDs (n = 94) or tapering anti-TNF (n = 95). The cumulative flare rates in the csDMARD and anti-TNF tapering group were, respectively, 33 % (95% CI,24% to 43 %) and 43 % (95% CI, 33% to 53 % (p = 0.17). Mean DAS, HAQ-DI and EQ-5D did not differ between tapering groups after 1 year and over time.

Conclusion Up to 9 months, flare rates of tapering csDMARDs or TNF inhibitors were similar. After 1 year, a non-significant difference was found of 10 % favouring csDMARD tapering. Tapering TNF inhibitors was, therefore, not superior to tapering csDMARDs. From a societal perspective, it would be sensible to taper the TNF inhibitor first, because of possible cost reductions and less long-term side effects.

Trial registration number NTR2754

  • drug withdrawal
  • tapering
  • csdmards
  • anti-tnf therapy
  • rheumatoid arthritis

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  • Handling editor Josef S Smolen

  • Correction notice This article has been corrected since it first published online. The open access licence type has been amended.

  • Contributors All authors contributed to the conception or design of the study; or the acquisition, analysis or interpretation of data; drafting or revision of the manuscript; and final approval of the manuscript for publication.

  • Funding The study was supported by an unrestricted grant from ZonMW.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Ethics approval Medical ethics committees of each participating centre approved the protocol.

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

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