Two New Cases of PML Reported in Patients Taking Tysabri
August 5, 2008
Two new cases of progressive multifocal leukoencephalopathy (PML), which is an often-fatal viral infection of the brain, have been reported in patients taking Tysabri® (natalizumab) for the long-term treatment of MS. These two cases were reported to the United States Food and Drug Administration (FDA) on July 31, 2008. These are the first cases to be reported since the drug's re-release in June 2006.
MSAA Chief Medical Officer Jack Burks, MD, participated in a phone conference with other medical professionals regarding this new development. According to Dr. Burks, "I have been told that both of these cases occurred within the first two years of beginning treatment with Tysabri. The first patient has received five plasma exchange (PE) therapy treatments to help remove Tysabri from the body, and is now at home, reported to be in clinically stable condition. The second patient, who is also in stable condition, is at the hospital and is receiving PE treatments. Both individuals reside in Europe."
Tysabri had received early approval in November 2004, but was voluntarily taken off of the market in February 2005 after two people were found to have developed progressive PML. These two patients had been given the combination of Tysabri along with Avonex® (interferon beta-1a) in an MS trial for more than two years. One patient died and the other survived but is disabled. A third patient who had been treated with Tysabri earlier in an open-label Crohn's disease clinical trial and died, was diagnosed with PML postmortem.
Tysabri is now approved as a monotherapy, which means that it should not be combined with any other drug designed to modify or suppress the immune system. The distribution of Tysabri is regulated by a Risk Management Plan known as the TOUCH (Tysabri Outreach: Unified Commitment to Health) Prescribing Program.
The TOUCH Prescribing Program is directed to prescribers (physicians), infusion centers, pharmacies, and patients considering Tysabri. It includes several documents that provide information, guidelines, checklists, and authorizations, as well as forms for enrollment, questionnaires, and status reports, all aimed at increasing awareness and safety.
Dr. Burk continues, "The fact that both cases were picked up early is a good indication that doctors are taking the precautions very seriously. Both patients being 'stable' clinically is a hopeful sign, but we must wait to see what happens next.
"The decision to initiate or continue treatment with Tysabri is between the patient and doctor, unless the FDA intervenes. As an organization dedicated to enriching the quality of life for everyone affected by MS, MSAA's job is to reinforce the TOUCH program and encourage Tysabri patients to report their symptoms to their doctor, as indicated."
Tysabri's prescribing information states, "Healthcare professionals should monitor patients on Tysabri for any new sign or symptom suggestive of PML. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. The progression of deficits usually leads to death or severe disability over weeks or months. Withhold Tysabri dosing immediately at the first sign or symptom suggestive of PML. For diagnosis, an evaluation including a gadolinium-enhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended."
Marketed by Biogen Idec and Elan Corporation, Tysabri is the first humanized monoclonal antibody to be approved for the treatment of MS. It works by inhibiting the action of adhesion molecules on the surface of immune cells, and therefore prevents damaging immune cells from crossing the blood-brain barrier from the bloodstream and entering the brain and spinal cord. Tysabri is administered via intravenous infusions every four weeks in a TOUCH Program infusion center. At this time, nearly 31,800 patients are on the drug worldwide.
Individuals with questions may speak with an MSAA consultant by calling (800) 532-7667 between the hours of 8:30 am and 7 pm (ET) Mondays through Thursdays, and between 8:30 am and 5 pm (ET) on Fridays. Spanish-speaking individuals may contact a bi-lingual consultant between 9:00 am and 5 pm on weekdays by dialing extension 108.
All media inquires should be addressed to Amanda Bednar, MSAA Public Relations Manager, at (800) 532-7667, extension 122 or via email: abednar@msassociation.org.
Information summarized by Susan Wells Courtney, MSAA Senior Writer and Creative Director
Reviewed by Dr. Jack Burks, MSAA Chief Medical Officer
