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• Can patients with established RA stop TNF blocker therapy?
  Paul Emery
  Published on: 21 October 2010

• Published on: 21 October 2010

  Can patients with established RA stop TNF blocker therapy?

  • Paul Emery, Arthritis Research UK Professor of Rheumatology
  • Other Contributors:
    • Benazir Saleem, Maya Buch

  Dear Editor,

  We read with interest the above publication which we found to be very informative.
  The article presents the results of a systemic literature review of patients with established rheumatoid arthritis (RA) (>2 years disease duration) treated with stable and effective disease modifying anti-rheumatic drug (DMARD) therapy, with a metaanalysis to determine the effect of therapy withdrawal...

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  Dear Editor,

  We read with interest the above publication which we found to be very informative.
  The article presents the results of a systemic literature review of patients with established rheumatoid arthritis (RA) (>2 years disease duration) treated with stable and effective disease modifying anti-rheumatic drug (DMARD) therapy, with a metaanalysis to determine the effect of therapy withdrawal vs. continuation on disease flare. We note that the authors mention 'withdrawing biological drugs after patients have achieved sustained remission is a burning question......
  Unfortunately there is a lack of primary research in this area, and as a consequence we were unable to address the question in the current systematic review. It is an area in which more primary research is needed.'
  We would, however, like to bring to the attention of the readers data published by ourselves in 2004 [1] and in last month's ARD [2], and by Brocq et al [3] and Tanaka et al [4].
  In 2004 Buch et al published long-term data from patients completing the ATTRACT study [5] in our unit. In patients with established RA on methotrexate, 100% (17/17) flared after infliximab therapy was stopped after 2 years of therapy [1].
  Our more recent data, in patients with both early and established disease (median disease duration of the established group was 10 years), demonstrated high (85%, 17 /20) flare rates in patients with established RA when tumour necrosis factor (TNF)-inhibitor therapy was stopped despite continuation of methotrexate [2].
  Prior to stopping TNF inhibitor therapy, there were no differences in neither DAS28 scores nor duration of remission; but HAQ and RAQoL scores were lower and patients had shorter disease duration in those who maintained remission. We also observed that sustained remission was associated with lower inflammation-related T cell, higher naïve T cell, and higher CD62L+ Treg frequencies when compared to patients that flared [2].
  Our flare rates post discontinuation of TNF inhibitor therapy have been confirmed by Brocq et al [3]. Patients with an average duration of RA of 11 years were withdrawn from TNF inhibitor therapy after being in DAS28-defined remission for at least 6 months. Seventy-five percent (15/20) of patients flared 12 months after the withdrawal of TNF inhibitor therapy.

  A Japanese study in which infliximab was discontinued in patients who were in sustained low disease activity (>6 months), 57% of the patients had lared 1 year after stopping therapy [4]. This better outcome may be due to the genetically different population, lower DAS28 requirement to receive infliximab and different methotrexate dosing regimes.
  We agree that more research is required but believe that there are already some useful data available for rheumatologists who may be considering withdrawing or stopping TNF inhibitor therapy. Cautious therapy reduction maybe considered [6] in patients with short disease duration and low levels of functional impairment.

  References

  [1] Buch MH, Marzo-Ortega H, Bingham SJ, et al. Long-term treatment of rheumatoid arthritis with tumour necrosis factor alpha blockade: outcome of ceasing and restarting biologicals. Rheumatology (Oxford) 2004;43(2):243-4.

  [2] Saleem B, Keen H, Goeb V et al. Patients with RA in remission on TNF blockers: when and in whom can TNF blocker therapy be stopped? Ann Rheum Dis 2010;69(9):1636-42.

  [3] Brocq O, Millasseau E, Albert C, et al. Effect of discontinuing TNF-alpha antagonist therapy in patients with remission of rheumatoid arthritis. Joint Bone Spine 2009 Apr 9.

  [4] Tanaka Y, Takeuchi T, Mimori T, et al. Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study. Ann Rheum Dis 2009;69(7):1286-91.

  [5] Maini R, St Clair EW, Breedveld F, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 1999;354(9194):1932-9.

  [6] Smolen JS, Landewé R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological diseasemodifying antirheumatic drugs. Ann Rheum Dis 2010;69(6):964-75.

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  Conflict of Interest:
  None declared.

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