To assess clinical and MRI disease activity in MS patients after cessation of fingolimod in a real- world setting and characterize those with rebound disease activity. 

Fingolimod was approved for multiple sclerosis (MS) in 2010. In late 2018, the FDA alerted prescribers about the risk of rebound disease activity after stopping fingolimod based on 35 cases with significant clinical and MRI disease activity 2-24 weeks after treatment discontinuation. Patient characteristics and treatment specifics were not provided. In this study, we evaluate the cohort of an academic MS specialty center regarding the occurrence of disease activity after discontinuation of fingolimod to explore the phenomenon of rebound disease activity.    

We retrospectively analyzed patients treated with fingolimod since November 2010 at our center to evaluate for inflammatory clinical/radiographic disease activity after stopping fingolimod.  

49.3% (108/219) of patients treated in our center discontinued fingolimod after 939.9 days (mean,  range 18-2813), most commonly for worsening MS (n=40), safety concerns (n=21), infections (n=9) or skin cancer (n=4).  Twenty-one patients stopped more than once, usually for incompliance or pregnancy.

Most patients (65.4%) transitioned to other disease-modifying treatments (DMT) within 6 months (mean 44.1 days, range 0-180).  18/108 had clinical/radiological relapse within the first six months. Rebound disease activity, defined as highly inflammatory clinical and/or disease activity uncharacteristic for the patients’ disease course, was seen in 6/108 patients 15.3 weeks (mean, range 10-24) after discontinuation. Two patients required hospitalization and plasmapheresis, one underwent brain biopsy. The washout period ranged 3-30 days.

A potential risk of rebound disease activity after discontinuation of fingolimod has been recently reported.  We describe 6 patients with severe reactivation and rebound disease activity after stopping fingolimod. Specifics of our cases will be presented.  Case series like this may help identify risk factors for individual patients and strategies to reduce the risk of rebound activity.