REBOUND SYNDROME FOLLOWING FINGOLIMOD DISCONTINUATION IN MULTIPLE SCLEROSIS

Abstract

Objectives: Fingolimod is the first oral medication approved for relapsing-remitting multiple sclerosis therapy. In contrast to the thorough description of the rebound effect of natalizumab, data about a possible disease re-activation and development of tumefactive lesions after fingolimod discontinuation results only from case reports and small case series. Methods: We present a case with disease reactivation, based on clinical and radiological evidence, 4 months after fingolimod withdrawal. We also reviewed the relevant literature to evaluate clinical characteristics of similar cases that were available. Results: A 31-year-old woman, diagnosed with RRMS, discontinued fingolimod treatment due to nodular lymphoid hyperplasia of the stomach. Four months after fingolimod cessation, the patient experienced neurological worsening with gait disturbances, numbness and weakness in her right extremities. Brain-MRI showed substantial increase in the number, volume and activity of pre-existing MS lesions. The severity of clinical worsening and of radiological exacerbation largely exceeded the disease activity during prior fingolimod treatment. Literature review disclosed a total of 46 similar cases that presented with rebound phenomenon following fingolimod discontinuation, with the elapsed time ranging between 4 and 16 weeks. The majority of the cases were responsive to steroid treatment. Conclusions: Cessation of fingolimod may result in rebound effect in patients with relapsing multiple sclerosis, whichmay cause substantial clinical deterioration and neuroimaging exacerbation of disease activity. Despite the increasing number of published case reports, the exact prevalence or precipitating factors remain unknown. Large prospective or population-based studies are needed to accurately describe this phenomenon and identify optimal therapeutic management.