Beyond First-Line: Natalizumab vs Fingolimod for Relapsing-Remitting Multiple Sclerosis

Before discontinuing a particular therapy due to suboptimal response, however, it is important to confirm that the patient has been compliant with taking it, Patricia K. Coyle, MD, a neurology professor and director of the MS Comprehensive Care Center at Stony Brook University Medical Center in New York, told Neurology Advisor. Once adherence has been addressed, “efficacy of the drug now moves to a more important consideration, as the patient has declared themselves to have more active disease than usual, favoring use of a high efficacy DMT.” Pros and cons of the various alternatives must be weighed for each patient based on a range of personal factors.

Natalizumab: Efficacy with a Risk

Natalizumab is highly effective and generally well-tolerated, and the “fact that natalizumab is infused affords observed administration and may lead to higher medication adherence,” Thomas P. Leist, MD, PhD, director of the Comprehensive Multiple Sclerosis Clinical Center at Thomas Jefferson University in Philadelphia, told Neurology Advisor.

A major downside of natalizumab, however, is its associated risk of progressive multifocal leukoencephalopathy (PML). Testing for JC virus antibodies can help physicians stratify a patient’s risk of PML while on natalizumab therapy, and “recently it has been suggested that less frequent infusions or potentially weight-based dosing may also help to control risk even in individuals who test positive for JC antibody,” though more research on these approaches is needed. While JC antibody testing is an important tool, a significant number of patients who test negative still harbor the virus, and some have been found to subsequently convert to positive status, noted Dr Leist, who has co-authored a significant body of research on MS therapies.3,4,5

Fingolimod: A Foe to Comorbidities

Advantages of fingolimod include high efficacy and tolerability and the convenience of oral therapy with a low risk of PML, said Dr Coyle, who has also studied MS treatment extensively.3,4,5 Some negative points to consider include “the inconvenience of extensive pretreatment testing and first dose observation, and the fact that coexisting morbidity — significant cardiac or pulmonary disease, diabetes, uveitis — is a relative contraindication to therapy.”