Three brand new studies shed light on use of natalizumab in relapsing-remitting multiple sclerosis.
Natalizumab is a highly effective therapy for relapsing-remitting multiple sclerosis. However, its efficacy in the context of other more recently available treatments needs to be assessed. Further, hampering the long-term of use of natalizumab is the association of treatment with a risk of progressive multifocal leukoencephalopathy (PML).The slides above highlight findings of 3 new studies of natalizumab.Â Â Â
A clinical trial that directly compares natalizumab with fingolimod is unlikely, but a well-performed observational study can serve as the next best thing. Using this approach, Kalincik and colleagues showed that natalizumab is better than fingolimod. Using MSBase, a large international, observational MS registry, these researchers identified patients with MS experiencing relapses or disability progression within the 6 months immediately preceding a switch to natalizumab or fingolimod. Compared were 578 patients with MS (natalizumab, n=407; fingolimod, n=171); the mean follow-up was 12 months.
A 50% relative post-switch difference in relapse hazard was seen in favor of natalizumab. Further, a 2.8-times higher rate of sustained disability regression was observed after a switch to natalizumab in comparison with fingolimod. This study suggests that in active MS during treatment with injectable disease-modifying therapies, a switch to natalizumab is more effective than a switch to fingolimod in reducing relapse rate and short-term disability.Kalincik T, Horakova D, Spelman T, et al. Switch to natalizumab vs fingolimod in active relapsing-remitting multiple sclerosis. Ann Neurol. 2015;77:425-435.
Few studies have estimated the association between natalizumab persistence and relapse-related outcomes using “real-world” data (nonâclinical trial setting). Using a US medical insurance claims database, researchers identified US patients who initiated natalizumab therapy and had at least 2 years of follow-up. Persistence was defined as no 90-day or greater gap in natalizumab therapy. Relapse was defined as an MS-related hospitalization or outpatient visit with intravenous or oral steroid claim within 7 days. The study identified 2407 natalizumab initiators who had at least 2 years of follow-up. Persistent to non-persistent treatment change was associated with a mean relapse-rate increase of 0.23.
These findings suggest that in the real-world, persistent natalizumab users who become nonpersistent have statistically significant increases in annual relapses.McQueen RB, Livingston T, Vollmer T, et al. Increased relapse activity for multiple sclerosis natalizumab users who become nonpersistent: a retrospective study. J Manag Care Spec Pharm. 2015;21:210-218.
The objective of this analysis was to examine outcomes in a large natalizumab-associated PML population. MS patients with natalizumab-associated PML identified through postmarketing surveillance were monitored for up to 24 months using a structured questionnaire completed by treating physicians. Among the 336 patients in this analysis, 76% survived. Survivors were significantly younger at diagnosis, had significantly lower EDSS scores prior to PML diagnosis, and had significantly lower cerebrospinal fluid JC viral load at the time of diagnosis.
In this analysis, nearly a quarter of patients with natalizumab-associated PML died. A younger age at diagnosis, less functional disability prior to PML diagnosis, and lower JC viral load at diagnosis appeared to predict improved survival in patients with natalizumab-associated PML.Dong-Si T, Gheuens S, Gangadharan A, et al. Predictors of survival and functional outcomes in natalizumab-associated progressive multifocal leukoencephalopathy. J Neurovirol. 2015 Mar 14. [Epub ahead of print]