Research Activities, January 2014
Biological drug offers multiple sclerosis patients fewer relapses and improved quality of life, despite some risks
A new study of three disease-modifying therapies (DMTs) approved by the U.S. Food and Drug Administration (FDA) for use in patients with relapsing-remitting multiple sclerosis (RRMS) finds that natalizumab reduces the number of relapses and increases the patients' quality-adjusted life years (QALYs) when compared with a commonly prescribed DMT, (glatiramer acetate [GA]). Fingolimod, an oral DMT approved by the FDA in 2010, was also compared to the other two DMTs.
The study took into account that natalizumab is associated with a risk of a virus-related brain disease, progressive multifocal leukoencephalopathy (PML). PML is an often fatal brain disease caused by reactivation of a common human virus (polyomavirus JC, also known as JC virus), which is found in 70–90 percent of the world population. The reactivated virus can cross the blood-brain barrier to cause progressive inflammation of the brain and damage to myelinated nerve fibers. The researchers undertook the study because randomized clinical trials typically follow patients for 1–2 years, and do not allow comparison of the average long-term (20-year) risks and benefits for each drug.
To simulate 20-year outcomes of PML and other risks, benefits, and QALYs, the researchers used published data on the natural history of RRMS in patients without antibodies to JC virus, as well as treatment effects in such patients for each drug (from clinical trials)—on disease progression and relapse rates, PML risks, and utility preference scores. In comparing the model's 20-year outcomes for the three drugs pairwise, the researchers estimated that compared to GA, natalizumab resulted in 4.6 fewer relapses, 0.6 more years of disability-free time, 0.0165 cases of PML per patient treated, and an incremental 1.2 QALYs gained.
Compared with fingolimod, Natalizumab resulted in 1.7 fewer relapses, 0.1 more years of disability-free time, 0.0165 more cases of PML per patient treated, and a gain of 0.4 QALYs. The comparison against fingolimod did not result in statistical significance. These findings suggest that, on average, the benefits of natalizumab outweigh its risks when compared with the other two DMTs. The study was funded in part by AHRQ (HS19464).
More details are in "Comparative effectiveness of early natalizumab treatment in JC virus-negative relapsing-remitting multiple sclerosis," by Jonathan D. Campbell, Ph.D., R. Brett McQueen, Ph.D., Augusto Miravalle, M.D., and others in the April 2013 American Journal of Managed Care 19(4), pp. 278-285.