Gilenya (Fingolimod) & Multiple Sclerosis Relapse

The U.S. Food and Drug Administration (FDA) initiated this study in the Sentinel System to evaluate potential rebound of multiple sclerosis (MS) disease activity following discontinuation of fingolimod hydrochloride, particularly in the context of pregnancy planning. Fingolimod hydrochloride is used to treat relapsing forms of MS, a chronic autoimmune condition characterized by episodic neurological relapses. While MS therapies are effective in reducing relapse rates and delaying progression, discontinuation—especially when abrupt—has been associated with a rebound phenomenon, where disease activity returns in a more severe form.

This feasibility analysis specifically aimed to estimate MS relapse frequency and rate as the primary indicators of disease activity, and to compare the performance of MS relapse algorithms found in the literature. We assessed four cohorts: prevalent MS-fingolimod hydrochloride-exposed, incident MS-fingolimod hydrochloride-exposed, prevalent MS-fingolimod hydrochloride-never exposed, and incident MS-fingolimod hydrochloride-never exposed. Five algorithms were used to identify MS relapse. Between September 21, 2010, to January 31, 2018, the total number of patients exposed to fingolimod hydrochloride was 7,589 prevalent MS patients and 1,039 incident MS patients. The total number of fingolimod hydrochloride-never exposed members was 216,429 prevalent MS patients and 133,567 incident MS patients. MS relapse rates varied by algorithm, such that algorithms that included diagnoses in outpatient settings captured more MS relapses than algorithms that included diagnoses in inpatient settings alone. The findings were intended to inform regulatory decision-making and clinical guidance on the safe discontinuation of fingolimod, particularly for women planning pregnancy where interruption of treatment may be necessary.

Ultimately, the FDA did not pursue further analyses, as a related regulatory action—label change to add “severe increase in disability after stopping GILENYA” to the Warnings and Precautions—had been taken.