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Methotrexate reduces withdrawal rates of TNF inhibitors due to ineffectiveness in rheumatoid arthritis but only in patients who are seropositive
  1. Mandy Greenwood1,
  2. Muhammad Shipa1,
  3. Su-Ann Yeoh1,
  4. Euthalia Roussou2,
  5. Dev Mukerjee3,
  6. Michael R Ehrenstein1
  1. 1 Centre for Rheumatology, UCL, London, UK
  2. 2 Rheumatology Department, Barking Havering and Redbridge University Hospitals NHS Trust, Romford, Essex, UK
  3. 3 Rheumatology Department, North Middlesex University Hospital NHS Trust, London, UK
  1. Correspondence to Professor Michael R Ehrenstein, Centre for Rheumatology, UCL, London WC1E 6JF, UK; m.ehrenstein{at}

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The benefits of coprescribing methotrexate (MTX) with tumour necrosis factor (TNF)-inhibitors are well documented in rheumatoid arthritis (RA), though rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) status have not always been taken into account.1 Increasing doubt about the value of combination MTX and anti-TNF therapy in psoriatic arthritis2 3 led us to evaluate whether MTX reduced withdrawal rates due to ineffectiveness of anti-TNF therapy equally in seropositive and seronegative RA. Treatment durations for adalimumab or etanercept were analysed for 301 patients with RA using retrospective, real-world data from a single centre. All had started adalimumab or etanercept as a first-line biologic from 2003 onwards. Rates of ineffectiveness-related withdrawal during the first 5 years of anti-TNF therapy were analysed using Kaplan-Meier and Cox regression, with comparison of rates with respect to concomitant MTX at anti-TNF initiation. Fifty-two withdrawals for adverse events and 10 for other reasons constituted censored cases as did 136 still on anti-TNF at 5 years and 60 …

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  • Handling editor Josef S Smolen

  • Twitter @MikeEhrenstein

  • Contributors MG and MRE were involved in the design of the study and data interpretation and wrote the manuscript. MG performed the research and collected and analysed the data. MS, S-AY, ER and DM collected, verified and analysed the validation cohort. All authors reviewed and approved the manuscript’s content before submission.

  • Funding MG (and MRE in part) are supported by the University College London Hospital Biomedical Research Centre (BRC420).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

  • Patient consent for publication Not required.

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