Epidemiology

Leflunomide therapy not linked to serious hepatic side effects

Last Updated: 2004-07-26 11:43:45 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Treatment with leflunomide, a newer disease-modifying antirheumatic drug (DMARD), does not increase the risk of adverse hepatic events compared with methotrexate, an older DMARD with a well-established safety profile, new research shows.

In contrast, the findings suggest that the biologic DMARDs, namely etanercept and infliximab, do increase the risk of hepatic adverse events, according to the report in the July 15th issue of The American Journal of Medicine.

After leflunomide was introduced in 1998, case reports surfaced linking the drug with serious and, sometimes, fatal liver toxicity. Still, the risk attributable to the drug was unclear because many of the patients were also taking agents with known hepatotoxic effects or had compromised liver function at baseline.

To investigate, Dr. Samy Suissa, from the Royal Victoria Hospital in Montreal, and colleagues analyzed data from 41,885 patients who received a DMARD prescription for rheumatoid arthritis between September 1998 and December 2001.

In addition, to leflunomide, methotrexate, and the biologic DMARDs, the researchers evaluated the safety of traditional DMARDs, which included hydroxychloroquine, sulfasalazine, auranofin, and cyclosporine, among several others.

In the entire cohort, 25 cases of serious hepatic events occurred, yielding a rate of 4.9 events per 10,000 patients per year. Similarly, 411 nonserious hepatic events were observed for a rate of 80.0 per 10,000 patients per year.

Treatment with leflunomide or the traditional DMARDs did not increase the risk of serious or nonserious adverse hepatic events. Use of the biologic DMARDs, by contrast, was associated with 5.5- and 1.5-fold increased risks of serious and nonserious events, respectively.

The results suggest that leflunomide is not linked to an excess risk of hepatic side effects compared with methotrexate, the authors state.

Numerous reports of liver failure in biologic DMARD users have been made to the US Food and Drug Administration, they point out. "Future studies should carefully assess whether this risk is real or whether these newest drugs are being given to patients with more severe disease or who are at greater risk for hepatic toxicity."

Am J Med 2004;117:87-92.