Risk factors for oral methotrexate failure in patients with inflammatory polyarthritis: Results from a UK prospective cohort study

James Bluett, Jamie Sergeant, Alex J MacGregor, Jacqueline R. Chipping, Tarnya Marshall, Deborah Symmons, Suzanne Verstappen

Research output: Contribution to journalArticlepeer-review


Oral methotrexate (MTX) is the first-line therapy for patients with rheumatoid arthritis (RA). However, approximately one quarter of patients discontinue MTX within 12 months. MTX failure, defined as MTX cessation or the addition of another anti-rheumatic drug, is usually due adverse event(s) and/or inefficacy. The aims of this study were to evaluate the rate and predictors of oral MTX failure.
Subjects were recruited from the Norfolk Arthritis Register (NOAR), a primary care based inception cohort of patients with early inflammatory polyarthritis (IP). Subjects were eligible if they commenced MTX as their first DMARD and were recruited between 2000-2008. Patient-reported reasons for MTX failure were recorded and categorised as adverse event, inefficacy or other. The addition of a second DMARD during the study period was categorised as failure due to inefficacy. Cox proportional hazards regression models were used to assess potential predictors of MTX failure, accounting for competing risks.
431 patients were eligible. The probability of patients remaining on MTX at two years was 82%. Competing risk analysis revealed that earlier MTX failure due to inefficacy was associated with rheumatoid factor (RF) positivity, younger age at symptom onset and higher baseline disease activity (DAS-28). MTX cessation due to an adverse event was less likely in the RF positive cohort.
RF positive inflammatory polyarthritis patients who are younger with higher baseline disease activity have an increased risk of MTX failure due to inefficacy. Such patients may require combination therapy as first line
Original languageEnglish
Article number50
JournalArthritis Research and Therapy
Early online date20 Mar 2018
Publication statusPublished - 2018


  • Methotrexate
  • medication persistence
  • competing risk analysis
  • arthritis
  • treatment failure

Research Beacons, Institutes and Platforms

  • Manchester Institute for Collaborative Research on Ageing


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