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JC viral load does not predict progressive multifocal leukoencephalopathy

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Detection of JC virus, an important cause of progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients, is not a good predictor of PML risk and should not be used to screen patients before initiating natalizumab treatment, scientists in Europe report.

“Anti-alpha-4 integrin therapy with natalizumab is efficacious in refractory Crohn’s disease and in multiple sclerosis, but carries an estimated 1/1000 risk of PML caused by reactivation of latent JC virus infection,” Dr. Paul Rutgeerts at Leuven University Hospital, Belgium, and his associates explain in the October issue of Gut.

To investigate the potential value of JC virus screening, the researchers used quantitative polymerase chain reaction testing and enzyme-linked immunosorbent assay to assess the seroprevalence and viral load in blood and urine specimens. Their study included 125 patients with Crohn’s disease on at least one immunomodulator treatment, 100 patients with other gastrointestinal disease not treated with immunosuppressants, and 106 healthy control subjects.

More than half the subjects were seropositive for JC virus, ranging from 52% of the healthy volunteers to 65% of the GI controls and 76% of the Crohn’s patients. Although urinary viral load was higher in the patients with Crohn’s disease, median levels still exceeded 100,000 copies/mL in the healthy controls.

The virus was detected in the blood of only two patients with Crohn’s disease.

“Identification of reliable predictors of PML risk remains a high, currently unmet need to improve the safety of natalizumab,” Dr. David B. Clifford, a neurologist at Washington University in St. Louis, remarks in an accompanying editorial. Therefore, “early detection of disease, and prompt removal of the drug, should remain the goal of clinicians.”

“However,” he adds, “due to the aggressive and often fatal nature of PML, patients must understand and accept the rare risk of disability or death from PML, opposed to the burden of Crohn’s disease when the decision to use natalizumab is entertained.”

Reference:
Gut 2008;57:1347-1349,1393-1397.