Newer disease-modifying antirheumatic drugs and the risk of serious hepatic adverse events in patients with rheumatoid arthritis.

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Am J Med. 2004 Jul 15;117(2):87-92.

Newer disease-modifying antirheumatic drugs and the risk of serious

hepatic adverse events in patients with rheumatoid arthritis.

Suissa S, Ernst P, Hudson M, Bitton A, Kezouh A.

Division of Clinical Epidemiology (SS, PE, MH, AK), McGill University

Health Centre, Montreal, Canada.

BACKGROUND: Spontaneous cases of hepatic adverse events have been

reported in patients with rheumatoid arthritis who were being treated with

leflunomide, one of the newer disease-modifying antirheumatic drugs

(DMARDs). We assessed the risk of hepatic events associated with the use of

leflunomide and other DMARDs. METHODS: Two cohorts comprising 41,885

patients with rheumatoid arthritis who had been dispensed a DMARD between

September 1, 1998, and December 31, 2001, were formed using claims

databases. Follow-up was from the first dispensing date to the occurrence of

a serious or nonserious hepatic event. A nested case-control approach was

used to estimate adjusted rate ratios of hepatic events associated with

DMARDs dispensed during the prior year, as compared with methotrexate

monotherapy. RESULTS: There were 25 cases of serious hepatic events (rate,

4.9 per 10,000 per year) and 411 nonserious hepatic events (rate, 80.0 per

10,000 per year). There was no increase in the rate of serious hepatic

events with either leflunomide (rate ratio [RR] = 0.9; 95% confidence

interval [CI]: 0.2 to 4.9) or traditional DMARDs (RR = 2.3; 95% CI: 0.8 to

6.5). However, the rate was increased with biologic DMARDs (RR = 5.5; 95%

CI: 1.2 to 24.6). The rate of nonserious hepatic events was also increased

with biologic DMARDs (RR = 1.5; 95% CI: 1.0 to 2.3), but not with

leflunomide (RR = 0.9; 95% CI: 0.7 to 1.3) and traditional DMARDs (RR = 1.1;

95% CI: 0.8 to 1.4). CONCLUSIONS: We found no evidence of an excess risk of

serious or nonserious hepatic events with the use of leflunomide as compared

with methotrexate. Still, the increased risk observed with the new biologic

DMARDs should be investigated further.

PMID: 15234643 [PubMed - as supplied by publisher]