Influence of methotrexate on gastrointestinal symptoms in patients with rheumatoid arthritis

• Published in: International journal of rheumatic diseases 2019-02, Vol.22 (2), p.207-213
• Main Authors: Asai, Shuji, Nagai, Kaoru, Takahashi, Nobunori, Watanabe, Tatsuo, Matsumoto, Takuya, Asai, Nobuyuki, Sobue, Yasumori, Ishiguro, Naoki, Kojima, Toshihisa
• Format: Article
• Language: English
• Subjects: Abdomen; Administration, Oral; Aged; Antirheumatic Agents - administration & dosage; Antirheumatic Agents - adverse effects; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - epidemiology; Constipation; Cross-Sectional Studies; Diarrhea; Female; Gastrointestinal Diseases - chemically induced; Gastrointestinal Diseases - diagnosis; Gastrointestinal Diseases - epidemiology; gastrointestinal symptoms; Health risk assessment; Humans; Inflammation; Japan - epidemiology; Male; Methotrexate; Methotrexate - administration & dosage; Methotrexate - adverse effects; Middle Aged; Pain; patient‐reported outcomes; Population studies; Prevalence; Quality of Life; Rheumatoid arthritis; Risk Factors; Time Factors; Treatment Outcome
• ISSN: 1756-1841; 1756-185X
• DOI: 10.1111/1756-185X.13380

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.