Influence of methotrexate on gastrointestinal symptoms in patients with rheumatoid arthritis

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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.

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