Does Gilenya (fingolimod) require a washout period when switching to another disease-modifying therapy?

Fingolimod (Gilenya) Washout Period Requirements When Switching to Another DMT

Yes, fingolimod (Gilenya) requires a washout period when switching to another disease-modifying therapy due to its prolonged pharmacodynamic effects that persist for up to 2 months after discontinuation. 1

Pharmacological Basis for Washout Period

• Fingolimod remains in the blood and continues to have pharmacodynamic effects, including decreased lymphocyte counts, for up to 2 months following the last dose 1
• Lymphocyte counts generally return to the normal range within 1-2 months of stopping therapy 1
• The FDA label specifically warns that initiating other drugs during this period warrants the same considerations needed for concomitant administration (e.g., risk of additive immunosuppressant effects) 1

Recommended Washout Period Duration

• Traditional washout period recommendation is four times a drug's terminal half-life, which is the recommended interval between therapies 2
• For switching from fingolimod to another DMT, a washout period is necessary to minimize the "immunosuppressive burden" and allow for proper pretreatment assessments 2
• Clinical trials required patients to discontinue biologic therapy for at least 3 months prior to initiating new biologic therapies 2

Risks of Inadequate Washout

• Increased risk of infections with overlapping immunosuppressive therapies 2
• Difficulty in accurately assessing baseline disease severity and performing pretreatment assessments 2
• Potential for additive immunosuppressive effects that may increase adverse event risk 1
• Risk of rebound syndrome after fingolimod discontinuation, characterized by severe neurological symptoms and development of multiple new or enhancing lesions 3

Special Considerations When Switching Therapies

• Rebound syndrome has been reported in 10.9% of patients after fingolimod discontinuation, occurring 4-16 weeks after cessation 3
• Younger age and longer washout periods have been associated with higher risk of rebound 4
• When switching specifically to anti-CD20 therapies (like rituximab or ocrelizumab), some evidence suggests that a shorter washout period (<21 days) may be safer and decrease the risk of disease reactivation compared to longer washout periods 5

Monitoring During Transition

• Monitor for signs of disease reactivation during the washout period 4, 3
• Assess lymphocyte counts to ensure recovery before initiating new therapy 1
• Maintain high vigilance for infections during the transition period 1
• Consider MRI monitoring during the transition period to detect early signs of disease reactivation 3

Practical Approach to Switching

• For most DMTs: Allow 4-8 weeks washout period after fingolimod discontinuation 2, 1
• For anti-CD20 therapies: Consider a shorter washout period (<21 days) to prevent disease reactivation 5
• In patients at high risk of rebound (younger patients, those with previously highly active disease): Consider minimal washout and close monitoring 4, 3
• Avoid overlap between fingolimod and new DMT due to risk of additive immunosuppression 2

The decision about washout duration should balance the risk of additive immunosuppression against the risk of disease reactivation, with consideration of the specific next therapy planned and individual patient risk factors for rebound disease activity.