Adverse effects of low dose methotrexate in rheumatoid arthritis patients. A hospital-based study

OBJECTIVE: To evaluate the side effects of methotrexate (MTX) in rheumatoid arthritis (RA) patients and to evaluate the possible predisposing variables.

METHODS: A retrospective analysis conducted for all patients diagnosed with RA and treated with MTX over 3-years (January 2006 to December 2008) at King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia. Frequency of MTX side effects and the predictive variables were recorded and analyzed statistically.

RESULTS: Out of 116 RA patients, 71 patients used MTX. The most frequent side effect was gastrointestinal (GIT) disturbance in 31%, followed by central nervous system symptoms in 18%, hepatotoxicity in 14%, stomatitis and alopecia in 10% each, macrocytosis 7%, fever, malar rash and pancytopenia in 4%, and MTX-induced lung injury with increase in the size of rheumatoid nodule in 1% of patients. By Logistic regression analysis, renal impairment was the most significant variable increasing the risk of the side effects (OR=7.14, p<0.05). Other associated variables were male-gender, non-Saudi nationality, smoking, steroids use, hypoalbuminemia, and the presence of extra-articular manifestations.

CONCLUSION: Methotrexate is the most commonly drug used in the treatment of RA. Gastrointestinal disturbances were the most common side effect while lung involvement was the least. The impact of each clinical variable on MTX side effects requires paying more attention on the disease management as not all variables can be considered as risk factors.