A Case of Severe Multiple Sclerosis Reactivation Following Fingolimod Cessation

Background: The risk of immune reconstitution inflammatory syndrome (IRIS) post Natilizumab (NAT) discontinuation is well known. In fact, it has been shown that disease breakthrough occurs approximately 12 weeks after NAT cessation^1. Such data is not yet available regarding the risk of rebound with other therapies. It is important to elucidate the optimal wash out period when switching from one DMD to another in order to mitigate risk of opportunistic infections, such as PML, and preventing MS disease breakthrough. Fingolimod (FGD) is considered to be a potent oral therapy for MS, with multiple reported cases of disease rebound post FGD discontinuation due to the abrupt rise in previously sequestered lymphocytes.

Objectives: Here we report the case of a young woman who experienced severe consecutive clinical relapses with profound MRI activity, following FGD discontinuation.

Methods: Case History

Results: A 36 year-old woman with a history of RRMS was started on FGD in April 2011 after previously having been on IFN-β 1a. Her baseline lymphocyte count(LC) on FGD was 400. In 05/2015, she stopped FGD in order to conceive. Approximately 3 months later, she experienced at least two clinical relapses, each refractory to treatment with IV steroids. In 10/2015, she restarted FGD but remained symptomatic and was subsequently admitted for plasma exchange(PLEX). Her symptoms persisted post PLEX and repeat MRI studies revealed innumerable enhancing lesions throughout the brain, cervical and thoracic spine. At this time, her LC's were around 500. The patient was readmitted and treated with Rituximab. The patient was transferred to an inpatient rehabilitation facility, where she currently remains.

Conclusions: The severity of rebound in this case highlights the need to better understand the consequence of lymphocyte redistribution, the rate of immune recovery, and factors involved in immune regulation.

1. Fox R, Kappos L, Cree B, et al., eds. Effects of a 24-week natalizumab treatment interruption on clinical and radiologic parameters of multiple sclerosis disease activity: the RESTORE study. 5th Joint Triennial Congress of the European and Americas Committees for Treatment an d Research in Multiple Sclerosis, 2011;19–22 October, Amsterdam, The Netherlands.