Monday, May 12
One-half of Brazilian patients with multiple sclerosis using TYSABRI are DNA-JC virus positive
Objective Tysabri (Natalizumab) is a new and efficient treatment for multiple sclerosis (MS). The risk of developing progressive multifocal leukoencephalopathy (PML) during the use of this drug has created the need for better comprehension of JC virus (JCV) infection.RESULTS
Results were obtained from investigations on JCV-DNA viremia in 168 patients undergoing MS treatment with natalizumab. The patients were from 17 MS units in nine Brazilian states. These 168 patients on natalizumab had experienced therapeutic failure with interferon beta and/or glatiramer acetate. The patients’ previous therapeutic failure most frequently was in relation to both of the aforementioned immunomodulatory drugs.
These patients comprised 111 females and 57 males. They had an average age of 41.2±10.8 years. The JCV-DNA was detectable in 86 (51.2%) patients. There was no correlation between JCV-DNA positivity and gender, age, or treatment duration. The average length of natalizumab use was 11.2±6.2 months (range, 1–44 months). Previous use of immunosuppressive drugs was observed in 24% of the 168 patients. In considering only the patients who were positive for JCV-DNA, 22 patients had used immunosuppressive drugs before the prescription of natalizumab (i.e. 25.6% of the JCV-DNA-positive patients). No cases of PML were observed in these patients. All doctors participating in this study were aware of the risks of PML in relation to the JCV and to the previous use of immunosuppressive drugs.
The present study is very relevant since only two previous papers have reported JCV serology among MS patients undergoing treatment with natalizumab. The published reports show that 51% to 58.8% of these patients are seropositive for the JCV 7 , 8 . The results from this Brazilian population showed a similar prevalence: approximately one-half of the patients with MS receiving natalizumab were positive for JCV-DNA. The prevalence of JCV in patients with MS in France, Germany, and Brazil is considerably less than the 80% suggested by other authors 5 . However, different methods were used to assess JCV in the various studies. Other countries should follow soon with the publication of their data to help assess the worldwide prevalence of JCV in MS patients requiring treatment with natalizumab. In understanding the serum anti-JCV status of MS patients, clinicians also need to know that this result underestimates infection levels since the false negative rates have been calculated as high as 37% 9 . This additional fact, recently reported in the literature, states that a negative JCV antibody result should not be conflated with absence of JCV infection 9 . In fact, there are reports of PML caused by the JCV in natalizumab-treated patients with negative JCV test results 10 .
Brazilian neurologists are well aware of the risks for patients who are JCV-DNA-positive and have used immunosuppressive drugs in the past. With the patient’s agreement, they are nonetheless prescribing natalizumab in patients who have had therapeutic failure with immunomodulatory drugs. It is imperative that continuous medical education programs and pharmacovigilance databases are maintained in Brazil since the use of natalizumab has become more frequent 11.
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