For the second year in a row the Food and Drug Administration (FDA) has revised the label of natalizumab (Tysabri), an immune modulator used to treat relapsing forms of multiple sclerosis and moderately-to-severely active Crohn's disease. The changes emphasize the risk of the rare but serious brain infection known as progressive multifocal leukoencephalopathy (PML).

Natalizumab works by preventing the migration of leukocytes from the bloodstream into other parts of the body, thereby preventing the immune cells from causing damage. Leukocyte levels in the bloodstream will rise as a result of this inhibition. PML is a brain infection caused by the John Cunningham (JC) virus, a common virus acquired by most people in their childhood. The JC virus appears to be dormant until something, such as a weakened immune system, reactivates it. The symptoms of PML are varied and can progress quickly (over days) or more slowly (over weeks). The progression of deficits "can lead to death or severe disability over weeks or months," according to an FDA Drug Safety Communication released on April 22. Symptoms include "progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation, leading to confusion and personality changes."

The revised label now lists the prior use of immunosuppressants (mitoxantrone [Novantrone], azathioprine [Azasan, Imuran], methotrexate [Rheumatrex, Trexall], cyclophosphamide [Cytoxan], mycophenolate [CellCept, Myfortic]) as a risk factor for developing PML; previously the label warned only of the simultaneous use of any of these agents with natalizumab. Additionally, the new warnings indicate that the risk is dosage dependent: receiving 24 or more infusions of natalizumab increases the risk of PML.

Natalizumab was already available only through a restricted prescribing program known as the Tysabri Outreach: Unified Commitment to Health (TOUCH) program, which was designed to mitigate risks to patients, including the risks related to PML. The drug will continue to be available through the TOUCH program.

Nurses caring for patients prescribed natalizumab should confirm, prior to administration of the first dose, that the patient hasn't previously taken a drug that suppresses the immune system. Education should include teaching patients to recognize the symptoms of PML. If any of the symptoms is noted or reported by the patient, nurses should immediately withhold the drug and notify the prescriber. Nurses should also be aware of the risk of a rare but serious inflammatory response, immune reconstitution inflammatory syndrome (IRIS), that can occur when patients with PML stop taking natalizumab.