In this week's issue of the Lancet Neurology, glatiramer acetate, known as Copaxone(R), was subjected to an independent review. The systematic review, called a Cochrane Review, performed by Dr. Luca Munari and colleagues, challenges the claims of benefit from previous industry- based publications.
A convincing benefit on disability and an effect on the proportion of patients free from acute flare-ups of the disease during treatment could not be demonstrated, "Glatiramer acetate is now routinely prescribed for MS and it is the fastest-growing product in its market. However our systematic review of all randomized controlled trials of glatiramer acetate found little support for use of the drug in patients with MS," notes Dr. Luca Munari of Italy's Azienda Ospedaliera Niguarda Ca' Granda.
These efficacy-challenging observations might come as a surprise for many Copaxone users. Most Canadian MS patients and prescribers are unaware of these early concerns about Copaxone's efficacy even though the FDA, the U.S. government agency which reviewed the product license application in 1996, was concerned about "data dredging" in the sponsor's own data analysis. The agency conceded then that the treatment had a very slim treatment effect, but approved the drug.
Cochrane Reviews are now being applied to the new drugs being used to treat multiple sclerosis. Given that Canadian neurologists prescribed $150 million worth of these new treatments last year, it is imperative that those without a financial stake scrutinize treatment claims.
"Canadian health care dollars are precious. We must continue to scrutinize treatment claims from the pharmaceutical industry and continue to design clinical studies, which improve upon from the missteps of previous studies," says Dr. George Rice, Neurologist and Director of the MS Clinic at London Health Sciences Hospital in London, Ontario. The Cochrane Collaboration attempts to distill a true sense of worth from all published and unpublished clinical trials of a given agent or intervention, despite industry claims. The approach is simply to obtain all published observations, to adjudicate trial methodology and quality and to perform statistical analyses of aggregate outcomes. The Cochrane organization is not-for-profit and is designed to provide realistic expectations of what drugs might do, for patients, prescribers and payers. Application of rigid methodology in Cochrane views generally leads to more sobering interpretation of treatment claims.
Beta-Interferons are widely used in the treatment of early, relapsing forms of multiple sclerosis. The Cochrane Collaboration scrutinized these clinical trials in a publication in Lancet last year. A consistent benefit on attacks and disability progression was identified for two years for which data were available. Concerns were raised about the relatively short duration of clinical experimentation justifying use of this kind of treatment in a disease, which is 40 or 50 years for most patients. Concerns were also raised about methodological problems across most of the studies reviewed, particularly the application of rigid intention to treat analyses.