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Evaluation of Patients Treated With Natalizumab Finds no new Cases of Progressive Multifocal Leukoencephalopathy
Natalizumab, an immune system-modifying drug, was approved by the U.S. Food and Drug Administration in November 2004 to treat relapsing-remitting MS. Studies have shown that it can substantially reduce the frequency of relapses in that disease. However, the drug was withdrawn from the market and from clinical trials in February 2005 after the manufacturer identified 2 cases of PML in MS patients who had received the drug. A person with Crohn's disease who had received natalizumab was also diagnosed with PML. The current study was conducted to determine whether other people treated with natalizumab were at risk of PML. Symptoms of PML include mental deterioration, problems with vision, speech, balance, and movement, and, in most cases, coma and death.
"This was an important opportunity for NIH to use its specialized expertise in cooperation with the private sector to address a pressing and unanticipated risk of a devastating disorder," said NIH Director Elias A. Zerhouni, M.D.
A total of 44 patients were referred to the IAC because of clinical findings of possible PML, abnormalities on MRI, or a high blood level of JC virus. None of them had detectable JC virus DNA in the cerebrospinal fluid. Only the three previously reported cases of PML were confirmed. The data suggested that the risk of PML associated with natalizumab was approximately 1 in 1000 among these patients, who had been treated with natalizumab for an average of 17.9 months.
The study did not formally include patients who were treated with natalizumab outside of clinical trials. However, since PML is a very severe disease, it is likely that any PML in other patients who received natalizumab would have been diagnosed, the researchers say.
The results of this study are important not only for natalizumab, but also for similar drugs that are now in development, says Dr. Major. "Even under close evaluation, PML remains a rare disease. But as we alter the immune system, we need to understand what unintended effects it might have. This experience tells us that we need to understand more about how the JC virus causes disease in order to find ways to intervene." In the future, it might be possible to monitor people given natalizumab and similar drugs for activation of the JC virus in order to prevent PML, he adds.
The NINDS is a component of the NIH within the Department of Health and Human Services and is the nation's primary supporter of biomedical research on the brain and nervous system.
---------------------------------------------------- * Yousry TA, Major EO, Ryschkewitsch C, Fahle G, Fischer S, Hou J, Curfman B, Miszkiel K, Mueller-Lenke N, Sanchez E, Barkhof F, Radue E-W, Jäger HR, Clifford DB. "Evaluation of Patients Treated with Natalizumab for Progressive Multifocal Leukoencephalopathy." "New England Journal of Medicine", March 2, 2006, vol. 354, no. 9, pp. 26-35.
Source: The National Institutes of Health