Does methotrexate help patients with rheumatoid arthritis?

This study examined the short term benefits and harms of using methotrexate (Rheumatrex, Trexall) for treating rheumatoid arthritis.

Rheumatoid arthritis is a chronic (long-term) disease that leads to inflammation of the joints. The severity of patients’ symptoms can be graded using the ACR 50 (the American College of rheumatology 50 grade). The ACR 50 grades the severity of rheumatoid arthritis based on the number of swollen joints, pain and patient disability. This scoring system can be used by researchers to determine how well a patients’ medication is working.

Methotrexate is one of the most commonly used drugs for treating rheumatoid arthritis. It can either be prescribed as a monotherapy (no other drug is given at the same time) or prescribed along with another antirheumatic drug. A number of research teams have investigated whether methotrexate monotherapy successfully relieves some of the symptoms of rheumatoid arthritis.

In this study the authors searched for any published reports that compared methotrexate used alone against a placebo (a substance with no effect on the body used as a comparison). They found 7 reports that included a total of 732 patients with rheumatoid arthritis. Patients received between 5 mg and 25 mg of methotrexate and were followed for an average of 12 to 52 months.

Benefits of methotrexate

Based on the ACR50 score, methotrexate therapy significantly improved patients’ symptoms: swollen joints, pain and disability. 23% of patients taking methotrexate had major improvements in their symptoms compared to only 8% of patients taking the placebo.

Methotrexate treatment also appeared to slow the occurrence of joint damage. X-ray analysis showed that only 4% of patients taking methotrexate had increased joint damage compared to 12% of patients who took the placebo after one year. Neither methotrexate nor placebo lead to absence of active disease.

Methotrexate use improved patient quality of life. More patients taking methotrexate rated their physical quality of life to be at least 20% better (39% of patients compared to 27% of patients taking the placebo). Slightly more patients taking methotrexate also rated their mental quality of life to be better (26% of patients compared 21% of patients taking placebo).

Harms of methotrexate

Patients taking methotrexate were twice as likely to stop taking their medication as patients receiving placebo: 16% compared to 8% stopped the treatment. Patients taking methotrexate were also 3 times more likely to experience adverse events compared to patients receiving placebo (45% compared to 15% had side effects). The most common adverse events included infections, inflammation of the mouth and lips, mouth ulcers and hair loss. There was no difference in the number of serious adverse events experienced by patients taking methotrexate compared to those taking the placebo (3% compared to 2% had a serious adverse event).

The authors concluded that methotrexate improves patients’ rheumatoid arthritis. However, higher numbers of patients taking methotrexate stopped their treatment compared to patients taking placebo.