Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study

Rheumatology (Oxford). 2022 Oct 6;61(10):3930-3938. doi: 10.1093/rheumatology/keab917.


Objectives: To estimate prevalence rates and identify baseline predictors of adverse events (AEs) over the first year of treatment in patients with RA starting MTX.

Methods: Data came from the UK Rheumatoid Arthritis Medication Study (RAMS), a prospective cohort of patients with RA starting MTX. This analysis included patients aged ≥18 years with physician diagnosed RA and symptom duration ≤2 years, who were commencing MTX for the first time. AEs were recorded by interviewing patients at 6- and 12-month follow-up visits. The period prevalence rates of AEs are reported for 0-6 months, 6-12 months and 0-12 months of follow-up. The associations between baseline characteristics and AEs were assessed using multivariable logistic regression.

Results: A total of 1069 patients were included in the analysis. Overall, 77.5% experienced at least one AE. The most commonly reported AEs were: gastrointestinal (42.0%), neurological (28.6%), mucocutaneous (26.0%), pulmonary (20.9%), elevated alanine transaminase (18.0%) and haematological AEs (5.6%). Factors associated with increased odds of AEs were: women vs men (gastrointestinal, mucocutaneous, neurological) and alcohol consumption (nausea, alopecia, mucocutaneous). Older age, higher estimated glomerular filtration rate and alcohol consumption were associated with less reporting of haematological AEs.

Conclusions: AEs were common among patients over the first year of MTX, although most were not serious. Knowledge of the rates and factors associated with AE occurrence are valuable when communicating risks prior to commencing MTX. This can help patients make informed decisions whether to start MTX, potentially increasing adherence to treatment.

Keywords: DMARDs; adverse events; methotrexate; prognostic factors; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase
  • Animals
  • Antirheumatic Agents* / adverse effects
  • Arthritis, Rheumatoid* / chemically induced
  • Arthritis, Rheumatoid* / drug therapy
  • Drug Therapy, Combination
  • Female
  • Male
  • Methotrexate / adverse effects
  • Prospective Studies
  • Sheep
  • Treatment Outcome
  • United Kingdom / epidemiology


  • Antirheumatic Agents
  • Alanine Transaminase
  • Methotrexate