By Lily Jung, MD, FAAN, Swedish Neuroscience Institute, Seattle, WA
Biogen Idec notified physicians on Thursday, July 31, that two new cases of progressive multifocal leukoencephalopathy (PML) have been identified in multiple sclerosis patients receiving natalizumab (Tysabri) in the European Union. Close clinical surveillance associated with the drug allowed for the identification of the two new cases reported.
The identification of three cases of PML soon after the drug was initially released resulted in natalizumab being voluntarily removed from the market in 2005. The FDA approved its re-release in 2006 on the condition that a risk map be implemented involving close monitoring of the drug and its clinical indications.
In these earlier cases of PML, two MS patients had been treated with natalizumab and interferon-beta 1-a, while a Crohn's patient had received natalizumab after having received immunosuppressive therapies in the past. No patients who had been treated with natalizumab alone had been identified as having PML. As a result of this, an FDA physician advisory panel had recommended that natalizumab be used as monotherapy for MS patients. Natalizumab was re-released in June 2006 with the TOUCH program in place to monitor patients while on therapy. Of particular concern for neurologists at this time is that one of the newly diagnosed PML cases had not previously received immunosuppressive therapies and had no known risk factors for immunocompromise.
At the AAN Annual Meeting in April, Biogen Idec released safety data showing that over thirty-two thousand patients had received the drug worldwide, with more than thirteen thousand having been on the drug longer than 12 months, and 6,600 having been on treatment for over 18 months, with no new cases of PML identified. This resulted in a change of perception that the risk of developing PML with natalizumab was one-in-a-thousand to one-in-ten-thousand.
At this time, no recommendations around the management of patients who are currently on natalizumab therapy have been made. In Thursday's phone conference with MS neurologists, Al Sandrock, MD, PhD, of Biogen Idec stated that it was due to clinical vigilance that the two cases in the EU were diagnosed definitively. He also noted that, as always, the risks and benefits of natalizumab therapy should be carefully discussed with patients prior to initiating or continuing therapy.
Search for abstracts presented at the 2008 AAN Annual Meeting that address treatment with natalizumab.
Within the past 24 months, Dr. Jung has received personal compensation as a consultant for the Speaker's Bureau of Biogen, as well as from Glaxo Smith Kline, Chromos, and VLST Corporation. She has also served as an expert witness for medical liability, personal injury, and felony cases, and has received support for clinical research from Novartis and Biogen.