Tysabri (natalizumab) is a monoclonal antibody used to treat relapsing forms of multiple sclerosis (MS) and moderate-to-severe Crohn's disease. By modifying the immune system, it can effectively manage these conditions, but it also carries a risk of serious infections, including the rare but deadly brain infection, progressive multifocal leukoencephalopathy (PML). The potential for interaction with other medications is significant and requires careful management under a healthcare provider's supervision.
The Most Serious Interactions: Immunosuppressants and TNF Blockers
Combining Tysabri with other immunosuppressive or immunomodulating agents is strongly advised against, as it significantly elevates the risk of severe infections, including PML. Both Tysabri and these other drugs weaken the immune system, leading to a cumulative effect that compromises the body's ability to fight off infections. This combination is a major risk factor for developing PML.
Immunosuppressants
These medications are designed to reduce immune system activity and include a variety of drugs used for autoimmune conditions and to prevent organ transplant rejection. Tysabri should not be co-administered with these drugs.
- Azathioprine (Azasan, Imuran): Used for Crohn's disease and other autoimmune conditions.
- Methotrexate (Trexall): Common for rheumatoid arthritis, certain cancers, and Crohn's disease.
- Cyclosporine (Gengraf, Neoral): Prescribed to prevent organ rejection and for other immune conditions.
- Mycophenolate mofetil (CellCept): Used to prevent organ transplant rejection.
- Mitoxantrone: Used for certain types of MS and cancer.
TNF-alpha Blockers
These medications block tumor necrosis factor (TNF), a substance that causes inflammation, and are used for conditions like Crohn's disease. Combining them with Tysabri is contraindicated.
- Adalimumab (Humira): A common TNF blocker.
- Infliximab (Remicade): Another TNF-alpha inhibitor used for Crohn's disease.
- Etanercept (Enbrel): Used for various autoimmune conditions.
Tysabri and Corticosteroids
Long-term use of corticosteroids, often used to manage inflammation in MS and Crohn's disease, can also suppress the immune system. Taking Tysabri with chronic oral corticosteroids further increases the risk of infection, including PML. Therefore, careful management is essential.
- Tapering Protocol: For patients with Crohn's disease beginning Tysabri while on chronic oral corticosteroids, a steroid tapering protocol should be initiated. If the patient cannot be weaned off steroids within six months, Tysabri should be discontinued.
- Examples: Common corticosteroids include prednisone (Rayos), methylprednisolone (Medrol), and dexamethasone.
Other Interactions with Tysabri
Live Vaccines
Since Tysabri can reduce immune system activity, patients should avoid live vaccines, as they contain a weakened form of the virus or bacteria and may cause an infection. Examples include the nasal spray flu vaccine, measles, mumps, rubella (MMR), and yellow fever vaccines.
Other Biologic and Immunomodulatory Therapies
Many other therapies can have additive immune-suppressing effects when combined with Tysabri, heightening infection risks. These include:
- Fingolimod (Gilenya): Used for MS, carries its own immunosuppressive risks.
- Ozanimod (Zeposia): An MS drug with a similar risk profile.
- Ocrelizumab (Ocrevus): Another MS treatment that can increase immunosuppression.
- Chemotherapy and radiation therapy: These treatments significantly suppress the immune system and should be disclosed to your doctor.
Understanding the Risk of PML
Progressive multifocal leukoencephalopathy (PML) is a severe viral infection of the brain caused by the JC virus. While rare, its risk is a primary concern with Tysabri. Key risk factors include:
- JCV Antibody Status: Patients who test positive for anti-JCV antibodies have a significantly higher risk.
- Duration of Tysabri Use: The risk increases with longer treatment, especially beyond two years.
- Prior Immunosuppressant Use: Previous use of potent immunosuppressants is a known risk factor.
To manage this risk, Tysabri is available only through a restricted program called TOUCH, which involves regular monitoring.
Comparing Risks: Tysabri Alone vs. Combination Therapy
| Factor | Tysabri as Monotherapy | Tysabri with Other Immunosuppressants/TNF Blockers |
|---|---|---|
| Infection Risk | Elevated compared to general population. | Significantly higher due to additive immunosuppressive effects. |
| PML Risk | Present, with risk factors like JCV antibody status and duration. | Substantially increased, particularly with prior immunosuppressant use. |
| Recommended Use | Standard of care for relapsing forms of MS and moderate-to-severe Crohn's disease. | Contraindicated for concomitant use. |
| Steroid Co-use | Requires careful tapering protocol during treatment initiation. | Avoided due to enhanced infection risk; alternatives or dose adjustments are necessary. |
What Should Patients Do?
Patients must be proactive and communicate thoroughly with their healthcare team to avoid dangerous drug interactions. Always disclose your full medical history and a complete list of all medications, including over-the-counter drugs, vitamins, and herbal supplements. Your doctor will carefully weigh the risks and benefits of Tysabri based on your individual risk factors and determine the safest course of action.
In some cases, if you have been on other immunosuppressants, your doctor may require a washout period before starting Tysabri. It is also crucial to report any new or unusual symptoms to your doctor immediately, especially those suggesting a serious infection or PML, which could include weakness, changes in vision, or confusion. The FDA provides important safety information for patients and providers regarding PML risk, which can be found in drug safety communications from the FDA.
Conclusion
While Tysabri offers significant therapeutic benefits for certain autoimmune conditions, its immunosuppressive nature demands careful consideration of potential drug interactions. The combination of Tysabri with other immunosuppressants, TNF-alpha blockers, or chronic corticosteroids is associated with a markedly higher risk of serious infections, including PML. Open and honest communication with your healthcare provider is the most effective way to manage these risks and ensure the safe and effective use of this medication. Do not start, stop, or change any medication dosage without first consulting your doctor.
