Our thoughts are with the patients and families in Europe who recently developed PML (Progressive Multifocal Leukoencephalopathy) on Natalizumab (Tysabri®).
When Tysabri® was being developed a few years ago, there was a lot of hope in the MS Community about the idea of a non injectable disease modifying agent for the prevention of relapses (and hopefully disability). Since the first MS disease modifying medication was approved in 1993, there have been a total of four injectable medicines (Avonex®, Betaseron®, Copaxone® and Rebif®) FDA approved for the treatment of Relapsing-Remitting MS (RRMS); and there is a growing trend of “injection fatigue” (a desire for moving away from injectables towards oral or IV medicines). This is seen in the development and clinical trials of multiple new oral medicines and IV medicines. Tysabri® allowed just such a hope when it was released in November 2005, and there were predictions that tens to hundred of thousands of MS patients would switch or start up with this monthly infusion.
Then a few months later, in February 2006, it was discovered that three people (two with MS and one with Crohn’s disease) who had been on Tysabri® developed PML (Progressive Multifocal Leukoencephalopathy). PML had never been seen in MS patients before, and is an infection of the brain seen in patients who are immunosuppressed (cancer and HIV mostly). Then two MS patients had been on a combination of Tysabri® and Avonex® (weekly interferon beta 1a in to the muscle) and so after Tysabri® was voluntarily taken off the market and rereleased with the blessing of the FDA in June 2006, a new surveillance program (called TOUCH) was started and patients were not allowed to be on combination medicine with Tysabri®.
The feeling in the MS community was that PML might happen again, but its risk in people taking Tysabri® alone (not in combination with the injectables) is unknown and so thousands of patients worldwide were placed on Tysabri® as a second-line medicine. Soon after the second anniversary of Tysabri® being available again, however, two people on Tysabri® alone were found to have developed PML. On July 31, 2008 Biogen Idec (the makers of Tysabri® in conjection with Elan) reported that a patient in Germany and in Germany tested positive for the JC virus (the virus responsible for PML) in their cerebrospinal fluid. Plasmapheresis (a technique to clean out chemicals in the blood, similar in some ways to hemodialysis) had already been completed in one patient, and he was already back at home, and the other patient was being started on plasmapheresis (also called plasma exchange).
So what does this mean to the MS community?
This reinforces the importance in considering the risks and benefits of MS medications. Despite the annoyance for some of injecting medicines under the skin (Betaseron®, Copaxone® and Rebif®) or into the muscle (Avonex®), we should realize and recognize the long-term safety of these “older” medicines. While we continue to strive for better and more convenient medicines for MS, we should also weigh the potential benefits and risks of various forms of treatment.
So what does this mean for the future of Tysabri?
The regulatory agencies, including the FDA and the European medication agencies, have not instituted new regulations as of yet, but of course the package insert for Tysabri® will be changed to include these new cases of PML. At our MS Center, we have called all our patients on Tysabri® and discussed this new information with them so that they remain fully informed.
Staying informed is the best way of managing your MS so that you can remain the center of the MS Team in M*STAR (MS Team Approach Rule).
Disclosure: Dr. Kantor has received financial support from Biogen Idec in the past.
Published On: August 08, 2008