Leflunomide Therapy Not Linked to Serious Hepatic Side Effects

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Leflunomide Therapy Not Linked to Serious Hepatic Side Effects

NEW YORK (Reuters Health) Jul 26 - 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 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.