Treatment with the rheumatoid arthritis drug Arava (known generically as leflunomide) does not increase the risk of liver side effects compared with methotrexate, an older drug with a well-established safety profile, new research shows.

Both drugs are member of a group called disease-modifying antirheumatic drugs or DMARDs.

In contrast, the findings suggest that the new “biologic” DMARDs, namely Enbrel (etanercept) and Remicade (infliximab), do carry an increased risk of liver side effects, according to the report in The American Journal of Medicine.

After Arava was introduced in 1998, case reports surfaced linking the drug with serious - sometimes fatal - liver side effects. Still, the risk attributable to the drug was unclear because many of the patients were also taking agents with known liver effects or had damaged livers to begin with.

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

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

Overall, 25 people experienced serious liver side effects and 411 experienced non-serious side effects.

Treatment with Arava or the traditional DMARDs did not increase the risk of serious or non-serious hepatitic side effects. Use of the biologic DMARDs did increase the risk of serious and non-serious events by 5.5- and 1.5-fold, respectively.

The results suggest that Arava is not linked to an excess risk of liver 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.”

SOURCE: American Journal of Medicine, July 15, 2004.