Does Tysabri (Natalizumab) require a washout period when switching to or from another disease-modifying therapy?

Tysabri Washout Requirements When Switching Therapies

When switching FROM Tysabri (natalizumab) to another disease-modifying therapy, a washout period is generally recommended but should be minimized to 4-12 weeks maximum to prevent disease rebound, while switching TO Tysabri requires consideration of prior immunosuppressive therapy clearance. 1, 2

Switching FROM Tysabri to Another DMT

Optimal Washout Duration

• The ideal washout period when discontinuing Tysabri is 4-12 weeks, as washout periods exceeding 12 weeks are associated with significantly increased disease activity 2
• Unexpectedly, the shortest washout periods (0-30 days) show the highest disease activity rates (44.2%), while moderate washout periods of 31-60 days demonstrate the lowest disease activity (18.6%) 3
• Washout periods of 31-60 days provide the optimal balance, showing significantly decreased odds of disease activity (OR 0.241) compared to immediate switching 3

Critical Risks of Prolonged Washout

• Longer washout times are a modifiable risk factor that predicts higher relapse risk when switching from Tysabri 1
• Patients who switch to oral therapies after ≥2 years on Tysabri have twice the relapse risk (HR 2.18), and those switching to injectable therapies have three times the risk (HR 3.02) compared to continuing Tysabri 1
• Disease rebound or reactivation is a significant concern when discontinuing Tysabri, particularly with prolonged washout periods 4, 2

Switching TO Tysabri from Other Therapies

Prior Immunosuppressant Considerations

• When switching TO Tysabri from immunosuppressive medications, the traditional recommendation is a washout period of four times the drug's terminal half-life to minimize immunosuppressive burden 5
• For biologic therapies specifically, clinical trials required discontinuation for at least 3 months prior to initiating new biologic therapies 5
• Patients must not be immunocompromised when initiating Tysabri, as this increases PML risk, particularly in those previously receiving immunosuppressants 6

Fingolimod-Specific Washout

• When switching from fingolimod to Tysabri, a washout period of four times fingolimod's terminal half-life is recommended to allow proper pretreatment assessments and minimize immunosuppressive burden 7
• Clinical trials required patients to discontinue biologic therapy for at least 3 months before initiating new biologics 7

Practical Management Algorithm

When Discontinuing Tysabri:

1. Target a 31-60 day washout period before initiating the next DMT 3
2. Avoid washout periods <30 days (highest disease activity) or >12 weeks (increased relapse risk) 3, 2
3. Consider that shorter Tysabri treatment duration predicts higher relapse risk after switching 1
4. Monitor closely during the transition period for signs of disease reactivation 2

When Initiating Tysabri:

1. Ensure adequate clearance of prior immunosuppressants (4× terminal half-life) 5
2. For prior biologic therapy, consider 3-month washout 5
3. Verify patient is not immunocompromised before starting Tysabri 6
4. Complete pretreatment assessments including JCV antibody status 5, 4

Important Caveats

• The concept of "no washout" used in some clinical practice may not be optimal, as the data show 0-30 day washout periods have paradoxically worse outcomes than 31-60 day periods 3
• Overlapping immunosuppressive therapies should be avoided when switching between biologics due to increased infection risk 5
• The risk of PML increases with Tysabri treatment duration beyond 24 months, which may influence decisions about continuing versus switching 8
• Stopping Tysabri altogether without transitioning to another therapy is inappropriate for most patients due to high relapse/rebound rates 2