MS Speaks

Rebound of Multiple Sclerosis Disease Activity Following Fingolimod Cessation

Afagh Garjani1, Esmaeil Nikfekr1, Jithin George1

1
Neurology Department, University Hospitals Leicester NHS Trust

Objective:

To describe the rebound of multiple sclerosis (MS) disease activity after cessation of fingolimod treatment.

Background:

Fingolimod is a sphingosine 1-phosphate receptor modulator which prevents lymphocyte release from lymphoid tissue. While rebound of disease activity in MS after discontinuation of natalizumab is well-known, evidence of rebound after stopping fingolimod has emerged recently. Further studies on the impact of fingolimod cessation on relapses would have implications in planning the transition between disease modifying treatments.

Design/Methods:

We retrospectively reviewed medical records of patients with MS from the University Hospitals of Leicester, United Kingdom who had fingolimod discontinued since 2013.

 In this case series, we present the clinical, laboratory, and imaging findings of five patients [who] experienced severe recurrence of MS relapses after fingolimod withdrawal which exceeded their baseline disease activity.

We reviewed the literature from PubMed database using the search term ‘fingolimod rebound’.

Results:

Five (31.2%) of the 16 patients with relapsing-remitting MS [who] stopped receiving fingolimod suffered from an unexceptionally severe clinical relapse 2 weeks to 6 months after fingolimod cessation.

The mean (SD) duration of fingolimod treatment in these female patients was 21.8 (13.9) months. In all five cases, fingolimod was discontinued for escalation to natalizumab as a result of highly active MS. All patients demonstrated substantial
new and enhancing lesions on magnetic resonance imaging (MRI). Three patients had tumefactive demyelinating lesions.

All patients received corticosteroids. One patient with encephalopathy and positive John Cunningham virus antibody required further treatment with cyclophosphamide.

Conclusions:

These cases along with similar reports in the literature highlight the need to establish a scheme for switching from fingolimod to other therapies. Further investigations that incorporate patients who have discontinued fingolimod
for reasons other than highly active MS, such as adverse effects of fingolimod or progression to secondary progressive MS, can help to identify predictors of MS rebound after fingolimod discontinuation.