PML Risk Increases With Repeated Natalizumab Infusions: FDA

Susan Jeffrey

Disclosures

February 05, 2010

February 5, 2010 — The US Food and Drug Administration (FDA) today notified healthcare professionals and patients that the risk of developing progressive multifocal leukoencephalopathy (PML) increases with the number of infusions in patients treated with natalizumab (Tysabri).

"This new safety information, based on reports of 31 confirmed cases of PML received by the FDA as of January 21, 2010, will now be included in the Tysabri drug label and patient Medication Guide," the FDA communication notes.

Information about cases of immune reconstitution inflammatory syndrome (IRIS) in patients who developed PML and discontinued natalizumab treatment has also been added to the drug label, the update notes.

"Based on the available information, FDA believes that the clinical benefits of Tysabri continue to outweigh the potential risks," the announcement adds. "Revisions to drug label and patient Medication Guide, with the continued use of the TOUCH Prescribing Program, are intended to maximize the safe use of Tysabri and the identification of new PML cases."

Natalizumab is approved for the treatment of relapsing-remitting multiple sclerosis (MS) and moderately to severely active Crohn's disease. It is generally recommended for patients who have had an inadequate response to or are unable to tolerate other MS therapies.

Since July 2006, when marketing for natalizumab resumed subsequent to suspension in February 2005 after the first cases of PML surfaced, there have been 31 confirmed cases of PML in patients taking the drug, the announcement notes, including 10 cases in the United States. All patients were receiving treatment as monotherapy for MS; no cases have been seen in Crohn's disease patients, although in the United States, the only country where it has been approved for this indication, these constitute less than 2% of natalizumab-treated patients.

The overall worldwide cumulative rate of PML in patients who have received 1 or more infusions is 0.5 cases per 1000 patients. "Since Tysabri's remarketing in the US, there have been no cases of PML in patients treated with Tysabri for less than 12 months," the FDA announcement notes.

The overall worldwide cumulative rate of PML in patients who have received at least 24 infusions is 1.3 cases of PML per 1000 patients. In the United States, the cumulative rate of PML in patients who have received at least 24 infusions is 0.8 per 1000 patients. Outside the United States, the cumulative rate in patients who have received at least 24 infusions is 1.9 per 1000 patients.

"Relatively few patients have received 36 infusions or more, either in clinical trials or since marketing resumption; therefore, the magnitude of the risk of PML and other adverse events in patients who have received 36 infusions or more is not able to be well characterized," the announcement notes.

More information is available on the FDA's Web site.

Adverse events related to natalizumab should be communicated to the FDA's MedWatch program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.

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