Hepatic and hematological adverse effects of long-term low-dose methotrexate therapy in rheumatoid arthritis: An observational study

Indian J Pharmacol. 2016 Sep-Oct;48(5):591-594. doi: 10.4103/0253-7613.190761.


Objectives: Methotrexate (MTX) is the most commonly used cost-effective disease-modifying antirheumatoid drug (DMARD). Its main dose-limiting adverse effects are hepatic and hematopoietic. This cross-sectional, observational study evaluated the prevalence of hepatic and hematological adverse effects with long-term low-dose MTX therapy.

Materials and methods: Rheumatoid arthritis (RA) patients taking ≤15 mg/week MTX for at least 2 years were enrolled from the rheumatology outpatient department. Demographic, disease, drug treatment profiles, and hematological and hepatic enzyme levels were noted.

Results: Of the 204 patients enrolled, the frequency of raised alanine transaminase level (≥3-fold rise above the upper limit of normal) was 6.37% (95% confidence interval of 3.76-10.59) including two biopsy-proven hepatic fibrosis cases. About 5.4% had severe anemia (<8 g/dl) and 4.4% had leukopenia.

Conclusion: Long-term low-dose MTX is safe in RA patients in the Indian population. The patterns of adverse effects were similar to those documented in earlier studies. However, our study results suggest that disease duration, cumulative MTX dose, concomitant DMARD intake are not risk factors associated with hepatic or hematological adverse effects.

Keywords: Adverse effects; hematological; hepatotoxicity; methotrexate; rheumatoid arthritis.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Anemia / chemically induced
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / pathology
  • Female
  • Humans
  • Leukopenia / chemically induced
  • Liver / drug effects
  • Liver / pathology
  • Liver Cirrhosis / chemically induced
  • Male
  • Methotrexate / adverse effects*
  • Middle Aged
  • Thrombocytopenia / chemically induced
  • Young Adult


  • Antirheumatic Agents
  • Alanine Transaminase
  • Methotrexate