Side effects of methotrexate therapy in patients with rheumatoid arthritis

Introduction: Methotrexate is widely used as the most common disease-modifying anti-rheumatoid drug (DMARD) and is known as the first line treatment for rheumatoid arthritis (RA). Objectives: To assess the side effects of methotrexate in Iranian patients with RA and to compare them with the known side effects from previous studies. Patients and Methods: We conducted a cross-sectional study of 300 patients who fulfilled the EULAR 2010 criteria of RA. The following data were recruited from patients’ profiles; age, body mass index (BMI), duration of treatment with methotrexate, initiating dose, maximum dose and current dose of methotrexate, history of fatty liver disease or hepatitis B and concomitant use of sulfasalazine, leflunomide or hydroxychloroquine. Results: In 149 out of 300 patients (49.66%), Methotrexate therapy was stopped or tapered due to side effects including nausea (23%), flu-like symptoms (8%), hepatotoxicity (12%) and hair loss (6%). The patients with hepatotoxicity had a higher duration of treatment with methotrexate (10.35 compared with 5.83; P<0.001) and also the higher initiating dose of methotrexate (12.91 compared with 12.17; P=0.010). All of the RASS (rheumatoid arthritis severity scale) indexes including disease activity, functional impairment, and physical damage are related to the presence of hepatotoxicity (P<0.001). Conclusion: Methotrexate is an excellent and effective agent for the treatment of RA and its potential side effects during the treatment are dependent on the methotrexate dosage, the level of anti-citrullinated protein antibody (ACPA) and anti-MCV antibodies and concomitant use of other drugs such as leflunomide.