Understanding What Is the Washout Period for Tysabri?

October 10, 2025 •

4 min read

According to MyMSTeam, the general guideline for a Tysabri (natalizumab) washout period is typically one to three months when switching to another disease-modifying therapy. Determining the optimal length of this period requires a careful balance between managing the risk of a rare brain infection called progressive multifocal leukoencephalopathy (PML) and preventing a relapse of the underlying condition.

Quick Summary

The optimal washout period for Tysabri varies based on the next treatment and patient risk factors, typically ranging from a few weeks to several months. This critical transitional phase is designed to mitigate the risks of both progressive multifocal leukoencephalopathy and disease rebound while switching therapies.

Key Points

Duration Varies by Target Therapy: The typical Tysabri washout is 1-3 months, but the specific length depends heavily on the next medication.
Risk of Disease Reactivation: Longer washout periods are associated with a higher risk of MS disease rebound, with increased relapses and MRI activity.
PML Risk Management: The washout period is crucial for managing the risk of Progressive Multifocal Leukoencephalopathy (PML), and monitoring for symptoms must continue for at least six months after the last dose.
Shorter Washouts Can Reduce Relapse Risk: For some therapies, such as fingolimod, shorter washouts (e.g., 4 weeks) have been shown to provide better protection against disease activity compared to longer ones.
Individualized Medical Decisions: The optimal washout period is a personalized strategy developed with a neurologist, balancing PML risk, disease rebound, and specific patient factors.
Careful Monitoring is Essential: Close medical supervision, including regular check-ups and brain MRIs, is required throughout the transition period.
Other Factors to Consider: JCV antibody status, prior disease history, and pregnancy planning all play a role in determining the appropriate washout strategy.

What is a Washout Period for Tysabri?

In medicine, a washout period is the time between discontinuing one medication and starting another. For Tysabri (natalizumab), this period is crucial because of its potent mechanism and associated risks. Tysabri works by blocking certain white blood cells from entering the brain and spinal cord, which helps reduce the inflammation that causes damage in multiple sclerosis (MS) and Crohn's disease. While highly effective, this mechanism increases the risk of a rare but serious brain infection called progressive multifocal leukoencephalopathy (PML).

A washout period is necessary for several reasons:

To reduce PML risk: Allowing Tysabri to clear from the body before starting another immunosuppressant or immunomodulatory therapy can reduce the additive risk of PML.
To minimize drug interactions: It prevents potential overlapping effects and side effects from two different medications.
To prepare for new therapy: It gives the body time to clear Tysabri, which can be measured through specific assays, and prepares the immune system for the new treatment approach.

Factors Influencing the Length of the Tysabri Washout Period

The length of a Tysabri washout period is not one-size-fits-all and should always be determined in consultation with a neurologist. Several factors influence this decision:

The Next Therapy: The drug being switched to is the most significant factor. Newer, more potent therapies with a different mechanism of action may require different washout strategies.
JCV Antibody Status: The risk of PML is significantly higher in patients who test positive for the John Cunningham (JC) virus and have been on Tysabri for more than two years. This risk profile heavily influences the decision to switch and the approach to the washout period.
Risk of Disease Reactivation: A primary concern with stopping Tysabri is the potential for disease rebound, which can lead to severe relapses. The longer the washout, the higher the risk of disease activity returning.
Clinical Stability: A patient's history of disease activity before and during Tysabri treatment can predict the risk of relapse during the transition period.
Pregnancy Planning: Washout is also necessary for women planning a pregnancy, with a recommended two to three-month period to minimize fetal exposure.

Washout Considerations for Common DMT Switches

The optimal Tysabri washout period varies depending on the subsequent therapy. While longer washouts seem to reduce the risk of "carryover" PML, they increase the risk of disease reactivation. Newer evidence suggests that shorter washouts, especially to highly effective treatments, may be preferable for minimizing relapse risk.

Tysabri Washout Comparison


Feature	Switching to Fingolimod (Gilenya)	Switching to Ocrelizumab (Ocrevus)	Switching to Dimethyl Fumarate (Tecfidera)
Recommended Washout Period	4 to 8 weeks, with some studies favoring shorter durations	4 to 12 weeks	1 month or less, especially if discontinuing due to PML risk
Primary Goal	Minimize disease rebound and MRI activity.	Minimize PML risk, especially with history of JCV exposure.	Reduce disease flare-ups during the transition period.
Washout Risk	Increased relapse risk with longer washouts (>8 weeks).	Potential for "carryover" PML if washout is too short.	Higher relapse risk if washout is >90 days.
Evidence	Strong evidence supporting shorter washouts (e.g., 4 weeks) over longer ones (e.g., 8-16 weeks).	Smaller studies suggest safety and stability with transitions, but larger studies are still needed.	Real-world data suggests similar outcomes to clinical trials with shorter washouts.

Risks Associated with the Tysabri Washout

The transition period after discontinuing Tysabri is a delicate time that requires close medical supervision. The primary risks include:

Progressive Multifocal Leukoencephalopathy (PML): The risk of developing PML, which is caused by the JC virus, does not end immediately after stopping Tysabri. There is a small risk of "carryover" PML, especially if the subsequent therapy is also an immunosuppressant. Patients must be monitored for PML symptoms for at least six months after their last infusion.
Disease Reactivation or Rebound: For many patients, especially those who had high disease activity before starting Tysabri, stopping the medication can lead to a significant increase in relapses and MRI lesion activity. This can be particularly severe in the two to six months following discontinuation. The goal of a well-managed washout is to minimize this rebound effect.
Uncertainty with Newer Agents: While there is more experience with older switching strategies, data on transitions to newer monoclonal antibodies like ocrelizumab or other oral medications is still accumulating. The most appropriate washout period may still be a subject of ongoing research and clinical experience.

The Physician's Role in Managing the Washout Period

A neurologist plays a central role in managing the washout process. This involves:

Risk Assessment: Evaluating the patient's individual risk factors, including JCV antibody status, prior treatment history, and overall disease activity.
Developing a Transition Strategy: Choosing the most appropriate next therapy and determining the length of the washout period based on the best available evidence.
Intensive Monitoring: Scheduling regular check-ins, monitoring blood counts, and performing brain MRIs to look for signs of disease activity or PML.
Patient Education: Ensuring the patient understands the risks involved, the signs and symptoms to look for, and the importance of adhering to the monitoring plan.

Conclusion

The Tysabri washout period is a necessary and complex component of switching therapies for multiple sclerosis or Crohn's disease. The optimal duration is a careful, individualized balance between the risks of PML and disease reactivation. While general guidelines suggest a one to three-month window, evidence supports shorter washouts, especially when switching to another highly effective therapy, to minimize the risk of a disease rebound. Any decision regarding discontinuation and the subsequent washout period must be made in close consultation with a qualified healthcare professional who can weigh the specific risks and benefits for each patient. Careful planning and intensive monitoring are crucial for a safe and effective transition.

Disclaimer: This article provides general information and should not be considered medical advice. Always consult with a qualified healthcare provider for any health concerns or before making decisions about your treatment.

Frequently Asked Questions

A washout period is necessary after stopping Tysabri to reduce the risk of Progressive Multifocal Leukoencephalopathy (PML) from overlapping immunosuppressant effects and to minimize the risk of a disease rebound or relapse while transitioning to a new medication.

There is no single fixed duration for the washout period, as it varies depending on the next therapy and individual risk factors. General guidelines often suggest one to three months, but specific transitions, like switching to fingolimod, may involve shorter, more strategic washouts.

The risk of relapse or disease rebound can increase during the washout period, particularly if the gap between therapies is longer. Studies have shown that longer washouts can lead to more relapses and MRI disease activity compared to shorter washouts.

Evidence suggests that a shorter washout period, such as four weeks, is generally safer and more effective at preventing disease reactivation when switching from Tysabri to fingolimod (Gilenya), compared to longer periods like eight or sixteen weeks.

Yes, a washout period is typically recommended when switching from Tysabri to Ocrevus (ocrelizumab), with an ideal duration of 4 to 12 weeks to mitigate the risk of overlapping immunosuppression and PML carryover.

'Carryover' PML refers to the risk of developing the infection even after stopping Tysabri, potentially influenced by the lingering effects of the drug and the start of a new immunosuppressant. The washout period aims to reduce this risk by allowing Tysabri to clear from the body before the new drug is introduced.

Patients should be closely monitored by their healthcare provider with regular check-ups, potentially including brain MRIs, to detect any signs of disease reactivation or symptoms suggestive of PML. This monitoring is crucial and typically continues for at least six months.