Reuters Health Information (2004-03-05): Hepatic injury with the beta-interferons for MS more common than thought
Hepatic injury with the beta-interferons for MS more common than thought
Last Updated: 2004-03-05 17:08:19 -0400 (Reuters Health)
NEW YORK (Reuters Health) - A greater proportion of patients receiving a beta-interferon for multiple sclerosis develop elevated aminotransferase levels than were reported in clinical trials leading up to approval of these agents.
That's according to a postmarketing study in which researchers took a look back at biochemical liver tests of 844 MS patients prescribed one of the three commercially available beta-interferons in British Columbia, Canada, between 1995 and 2001.
Overall, 36.9% of patients developed new elevations of alanine aminotransferase (ALT), Dr. Helen L. Tremlett from the University of British Columbia in Vancouver and colleagues report in the February 24th issue of Neurology.
All of the beta-interferons -- subcutaneous IFN-beta-1a and IFN-beta-1b (IM), and intramuscular IFN-beta-1a -- caused elevated aminotransferase levels compared with pretreatment levels (p<0.005) and, as mentioned, the incidence aminotransferase elevation was substantially "higher than reported in clinical trials," the team notes.
For example, 11% of patients had mild or moderate ALT elevations in a pivotal trial of IFN-beta-1b compared with 38.9% in the current study and 37.5% in another postmarketing study published recently.
Likewise, in a pre-approval IFN-beta-1a (SC) trial, 19.6% and 27% of patients treated with low and high doses, respectively, experienced ALT increases, compared with 33.6% and 38.0% in the current study.
"No evidence of liver enzyme elevations" was reported in a pivotal trial of IFN-beta-1a (IM), whereas in the current study 23.0% developed de novo ALT elevations, the team reports.
As Dr. Tremlett's team notes in their report, the postmarketing experience prompted a Food and Drug Administration MedWatch warning in March 2003 of "hepatic injury including elevated serum hepatic enzyme levels, some of which have been severe."
The team was unable to identify predictors of IFN-beta-induced liver injury. They suggest "regular monitoring of the liver tests, particularly during the first year of treatment," emphasizing, however, that a "balance should be found because frequent testing can cause anxiety, pain, inconvenience, and is not without cost."