THURSDAY, June 9, 2005 (HealthDay News) -- Detailed reports shed new light on why three patients who were treated with the biologic drug Tysabri for either multiple sclerosis or Crohn's disease developed severe brain infections.
In three scientific briefs and two editorials released Thursday by the New England Journal of Medicine, the specifics of each case are laid out and analyzed by experts in the field. The journal released the package early after a possible fourth case was reported last week. Two of the first three patients have died.
"This is the first time we've had a peer-reviewed report of the information provided by the company to the public," said Dr. John R. Richert, vice president for research and clinical programs for the Multiple Sclerosis Society. "It is the first time we have been able to peruse details of the cases."
Although the news of the infections first came as a blow to those in the MS community, Richert noted that some of the details in these case reports leave open the possibility that Tysabri might one day return to the market if screening methods are found to detect which patients might be susceptible to the brain infection.
In November 2004, natalizumab (Tysabri) was approved for the treatment of multiple sclerosis (MS) and Crohn's disease, both conditions in which the body's immune system attacks it own tissue. But last February, Elan Corp. and Biogen Idec Inc., which marketed the drug, voluntarily withdrew it after reports that three patients taking it had developed progressive multifocal leukoencephalopathy (PML), a degenerative brain infection that often is fatal.
The journal reports provide "two major pieces of information we have not had before," Richert said. "One is that in one case, when they looked at blood samples that were serially obtained during the trial [of the drug], the JC virus that causes PML was detected in the blood serum before the onset of symptoms. That raises the possibility that diagnosis of this infection may be possible much earlier than we have thought in people at risk."
The second fact reported in the journal is that "one of the patients who was very, very ill from PML survived and experienced a significant recovery of neurological function," Richert said. "That person does have some significant neurological defects, but has experienced significant improvement. Until this time, we really weren't certain whether PML would be uniformly fatal or whether by stopping the drug and instituting appropriate antiviral therapy we could prevent death and effect clinical improvement."
But it will be a long time, if ever, before Tysabri is allowed back on the market, Richert acknowledged. One unresolved issue is whether the fourth patient who took the drug actually developed PML, since it is a difficult infection to diagnose accurately.
"That fourth case is up in the air," Richert said. "The question of whether that person had PML is still being evaluated."
The first reports of PML in people taking the drug "were certainly a setback," Richert said. "But the information that is newly available with these new reports is actually more encouraging news. There is still a reasonable possibility that Tysabri will eventually be approved for coming back on the market."
That possibility would be welcomed by those with either MS or Crohn's disease. FDA approval was given after carefully controlled studies showed the drug slowed progression of the conditions as no other medication had been able to do.
However, there is a strong cautionary note in the reports, said Dr. Igor J. Koralnik, an associate professor of neurology at Harvard Medical School, and co-author of one of the accompanying editorials.
Tysabri is a monoclonal antibody, engineered to attach itself to white blood cells called lymphocytes and prevent them from entering the brain, where they do the damage that causes the disabling symptoms of MS.
That same approach is being used by biomedical researchers to attack a number of other conditions, some rare but also some as widespread as asthma, Koralnik said, and so "we need to learn from this unexpected tragedy and try to get enough information to prevent it from happening again by understanding the mechanisms and monitoring for this feature."
As his editorial states, the case reports "force us to reconsider the potential risks associated with inhibition of lymphocyte trafficking. Bad things may happen when rescuers are turned back at the gates."
More information
A detailed account of multiple sclerosis and Tysabri is available from the FDA.
