Influence of methotrexate on gastrointestinal symptoms in patients with rheumatoid arthritis

Int J Rheum Dis. 2019 Feb;22(2):207-213. doi: 10.1111/1756-185X.13380. Epub 2018 Aug 30.

Abstract

Aim: This study aimed to determine the influence of methotrexate (MTX) on gastrointestinal (GI) symptoms in patients with rheumatoid arthritis (RA).

Methods: This cross-sectional study examined 529 consecutive patients with RA receiving oral MTX in our department between April 1 and September 30, 2017. GI symptoms were evaluated by the Gastrointestinal Symptom Rating Scale (GSRS); a score of ≥2 was considered "symptomatic." Prevalence of GI symptoms was compared between patients receiving ≤8 mg/wk (low-dose) vs >8 mg/wk (high-dose) of MTX.

Results: Of our study population, 313 (59%) received low-dose MTX at a median (interquartile range) dose of 6 (6-8) mg/wk, whereas 216 (41%) received high-dose MTX at a median dose of 12 (10-12) mg/wk. Relative to the low-dose MTX group, the high-dose MTX group exhibited a higher prevalence of reflux (32% vs 24%, P = 0.043) and abdominal pain (28% vs 18%, P = 0.007). There was no significant group-dependent difference in the prevalence of indigestion, diarrhea or constipation. Multivariate logistic regression analysis revealed that high-dose MTX (>8 mg/wk) was independently associated with reflux (odds ratio [OR]: 1.62, 95% confidence interval [CI]: 1.07-2.43) and abdominal pain (OR: 1.60, 95% CI: 1.04-2.43), and that the ORs for reflux and abdominal pain among those receiving high-dose MTX (>8 mg/wk) were similar to those using nonsteroidal anti-inflammatory drugs.

Conclusion: High-dose MTX is independently associated with the prevalence of upper GI symptoms in Japanese patients with RA.

Keywords: gastrointestinal symptoms; methotrexate; patient-reported outcomes; quality of life; rheumatoid arthritis.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Aged
  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / epidemiology
  • Cross-Sectional Studies
  • Female
  • Gastrointestinal Diseases / chemically induced*
  • Gastrointestinal Diseases / diagnosis
  • Gastrointestinal Diseases / epidemiology
  • Humans
  • Japan / epidemiology
  • Male
  • Methotrexate / administration & dosage*
  • Methotrexate / adverse effects*
  • Middle Aged
  • Prevalence
  • Quality of Life
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Methotrexate