Long-term methotrexate appears safe in arthritis

In adults who suffer from rheumatoid arthritis (RA), long-term treatment with methotrexate (MTX) appears safe, according to pooled data from 88 studies of patients with RA treated with only MTX for at least 2 years.

“Overall, although many patients experience adverse events during MTX treatment, they are generally mild and withdrawals of MTX for toxicity are less common than for other disease-modifying anti-rheumatic drugs,” Dr. C. Salliot of Hopital Cochin in Paris, France and Dr. D. van der Heijde of Leiden University Medical Center in The Netherlands conclude.

Over 12 years of treatment, the termination rate of MTX due to toxicity was less than for other commonly prescribed arthritis drugs such as sulfasalazine, gold, and D-penicillamine but higher than for hydrochloroquine, the researchers found.

Thirteen percent of patients taking MTX experienced potentially harmful spikes in liver enzymes, but only 3.7% discontinued MTX due to liver toxicity.

Data on risk of liver scarring or “fibrosis” with long-term MTX use were inconclusive. One study found a 2.7% rate of liver scarring in patients who took MTX for 4 years, but no evidence of liver damage in two other studies in which patients had repeated liver biopsies.

Long-term MTX did not appear to increase patients’ risk for infections in general or for serious infections, including herpes zoster and infectious complications of joint replacement surgery.

Of two studies that estimated patients’ risk of cardiovascular diseases during treatment, one concluded that MTX was not a risk factor and the other “even found a reduced risk” for treated patients compared to RA patients who had never received MTX, sulfasalazine, or hydrochloroquine. In fact, the researchers said, it’s possible that MTX “could provide a survival benefit by reducing cardiovascular mortality.”

There were not enough data to determine whether long-term MTX therapy increases patients’ risk of lymphoma and other malignancies, according to the authors. They add, however, that “there is no strong evidence of increased risk.”

SOURCE: Annals of the Rheumatic Diseases, June 2009.