By Wayne Kuznar
Chicago, IL—Routine screening for replicating JC polyomavirus (JCPyV) or serum antibodies does not seem to be warranted in rheumatic patients treated with rituximab (Rituxan).
JCPyV is a DNA virus that causes progressive multifocal leukoencephalopathy (PML), which is a demyelinating disease of the brain. Rituximab treatment has been identified as a risk factor for the development of PML caused by JCPyV infection, and this risk has been quantified at approximately 1 of 30,000. (Natalizumab treatment is also a risk factor with the risk quantified at 1.5 of 1000.) Reactivation of persistent JCPyV infection is thought to be responsible for the development of PML.
In a study conducted by Jens Verheyen, MD, National Reference Center for Papilloma and Polyoma Viruses, Institute of Virology, University of Cologne, Germany, and colleagues, patterns of JCPyV infections were scrutinized in 65 patients with rheumatic diseases, all of whom were treated with at least 1 cycle of rituximab. No patient showed any neurologic symptoms during the course of the study.
Blood samples were analyzed for JCPyV in all patients, and antibodies for JCPyV were analyzed in the urine in a subset. Samples were taken before and after at least 1 cycle of rituximab in 21 patients (baseline group); in 44 patients, all samples were collected during ongoing treatment (rituximab treatment group).
In the baseline group, JCPyV DNA was detected in 33% of samples. In the rituximab treatment group, 43% of urine samples were positive at the beginning, and only 1 switch from negative to positive occurred during the observation period. These percentages are similar to those in healthy individuals tested for the prevalence of JCPyV in the urine in previous studies when adjusted for the older age of patients in this current analysis, noted Dr Verheyen.
Therefore, “rituximab treatment did not seem to influence the shedding of JCPyV in the urine of patients with rheumatic disease,” Dr Verheyen said.
Using a JCPyV assay, JCPyV antibodies in the blood were detected in 79.6% of 54 patients tested. “Interestingly, the amount of antibodies detected was significantly higher in patients shedding JCPyV in the urine,” he said. By comparison, using the same assay, the prevalence of JCPyV antibodies in healthy individuals aged 50 to 70 years is 43% to 68%, respectively, based on reports in the literature, which suggest that treatment with rituximab did not significantly influence the detection rates of JCPyV antibodies in patients with rheumatic diseases.
“Even though we analyzed multiple blood samples, we were only able to detect JCPyV DNA in the blood samples of 2 [of 65] patients [3%]; in 1 patient, we were able to analyze another blood sample, and this was negative 1 month later,” Dr Verheyen pointed out. In patients treated with natalizumab, the rate of JCPyV in the blood has ranged from 0.3% to 63%, and the rate of transient viremia has been 2% to 7%.
At the moment, high- and low-risk groups cannot be sufficiently distinguished through the use of screening for JCPyV in patients treated with rituximab, concluded Dr Verheyen.
Editor’s Note:
In January 2012, the Food and Drug Administration (FDA) approved the first test for assessing the risk of multifocal leukoencephalopathy in patients treated with natalizumab. The Stratify JCV Antibody ELISA test screens for the presence of antibodies to JCPyV. According to the FDA, a total of 201 cases of PML have been reported among approximately 96,582 patients treated with natalizumab through January 4, 2012. |