Side Effects of Methotrexate Treatment in Patients With Rheumatoid Arthritis

Background. Methotrexte (MTX) is the most commonly prescribed disease-modifying anti-rheumatic drug. However, toxicity is an important drawback of MTX therapy. Objectives. The objective of this study was to determine the long-term safety of low-dose MTX in the treatment of rheumatoid arthritis (RA) and to evaluate the spectrum, severity, and frequency of adverse effects in clinical practice. Material and Methods. One hundred forty patients with RA (119 women, 21 men) treated with MTX who were hospitalized in rheumatology departments or were rheumatologists' outpatients between 2002 and 2007 were included in the observation group. Patients who had been taking MTX for at least 6 months or had developed adverse reactions earlier were analyzed. The median age of the RA patients was 54 years. The duration of RA ranged from 0.3-35 years and the median dose of MTX used was 15 mg/week. Results. One hundred five patients had a complete laboratory evaluation and clinical examination. Adverse effects (AEs) occurred in 54 patients (51.4%), but only 20 (19%) of the patients discontinued MTX permanently. Five stopped MTX therapy temporarily and four had a lower dose of MTX but did not stop the treatment completely. The median time after onset was six months. During the study the most common adverse events were gastrointestinal symptoms in 33 patients (31%). In this patient population the most common side effects leading to MTX withdrawal were hepatotoxicity and pulmonary and hematological toxicity. The potential risk factors for AEs were age > 65 yr and polypharmacy. Conclusion. Side effects were often observed in the group of patients treated with MTX, but they rather rarely caused cessation of therapy. The side effects occurred more often in older patients. Most gastrointestinal symptoms decreased after dividing the dose and after changing from oral to parenteral administration (Adv Clin Exp Med 2008, 17,4,387-394).