Fingolimod Cessation and Disease Reactivation in Multiple Sclerosis

Fingolimod is an oral sphingosine-1-phosphate receptor modulator widely used to reduce relapse frequency and new lesion formation in relapsing-remitting multiple sclerosis. By sequestering lymphocytes in lymphoid tissues, fingolimod limits their entry into the central nervous system. However, following treatment cessation, a rebound phenomenon characterised by the sudden return or worsening of inflammatory activity may occur. This reactivation can present clinically as severe relapses, radiologically as new or enlarging lesions, and in some cases as immune reconstitution inflammatory syndrome. Risk factors for disease reactivation include younger age at treatment initiation, prolonged fingolimod exposure, low lymphocyte counts at discontinuation and a history of active disease during therapy. The global challenge lies in balancing washout duration against prompt initiation of alternative disease-modifying therapies to mitigate re-emerging inflammation and prevent permanent disability.

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Fingolimod Cessation and Disease Reactivation in Multiple Sclerosis publication trend

The graph below shows the total number of articles in fingolimod cessation and disease reactivation in multiple sclerosis across all publications each year (not limited to Nature Index journals).

Technical terms

Fingolimod: An oral sphingosine-1-phosphate receptor modulator used to prevent lymphocyte egress from lymphoid tissues in relapsing‐remitting multiple sclerosis.

Disease-modifying therapy (DMT): A treatment aimed at altering the underlying course of multiple sclerosis by reducing relapses and delaying disability progression.

Rebound disease activity: A pronounced increase in clinical or radiological disease activity that occurs after stopping an immunomodulatory treatment.

T2 lesion: A hyperintense area on T2-weighted MRI scans indicating regions of inflammation, demyelination or oedema in the central nervous system.

Washout period: The interval between discontinuing one therapy and initiating another, during which drug levels decline to minimise overlapping immunosuppression.

References

1. Risk of T2 lesions when discontinuing fingolimod: a nationwide predictive and comparative study. Brain Communications (2023).
2. Frequency and risk factors of rebound after fingolimod discontinuation – A retrospective study. Multiple Sclerosis and Related Disorders (2023).
3. Neurological update: treatment escalation in multiple sclerosis patients refractory to fingolimod—potentials and risks of subsequent highly active agents. Journal of Neurology (2022).