Tysabri: an Introduction
Tysabri (natalizumab), approved by the FDA for the treatment of MS in 2004, offered MS patients a treatment option beyond the interferons and Copaxone for the first time. Tysabri is given as a monthly infusion and works by preventing immune cells in the bloodstream from entering the brain.
The efficacy of Tysabri in controlling (though not entirely eliminating) the relapses of MS is beyond question. In the two most important studies of Tysabri (the SENTINAL and AFFIRM trials), Tysabri showed a powerful ability to control disease activity in MS.
In the AFFIRM trial, Tysabri reduced relapses by a whopping 68 percent compared to placebo, and its ability to prevent new lesions on MRI was even more impressive.
In the SENTINAL study, a combination of Tysabri and Avonex were compared against Avonex alone, and there were no study subjects who received placebo. Again, the results showed a significant benefit to the use of Tysabri.
Over half of the patients taking the Tysabri/Avonex combination had no relapses at the conclusion on the 2-year study, while only one third of the patients on Avonex alone were without relapses after two years. Certainly these numbers are impressive, and I don’t think any MS neurologist would say that their experience deviates significantly from the impressive results reported in these studies.
Yet, in 2005, the medication was removed from the market by the FDA. This is because Tysabri, unlike any of the interferons or Copaxone, has been associated with a disabling and even fatal side effect, known as progressive multifocal leukoencephalopathy (PML). PML is a viral infection of the brain caused by the JC virus. This virus was discovered in 1971 and is named after John Cunningham, the first patient in whom it was recognized. It is a very common virus, and about 75 percent of people in the United States have evidence of being infected with it. It is generally a harmless virus, and as far as we know has nothing to do with MS. It remained an essentially unknown entity until the AIDS epidemic started in the early 1980s. In patients with suppressed immune systems, it can cause the devastating, fatal infection known as PML. In PML, the virus infects oligodendrocytes, the cells in the brain that make myelin which is the substance that is destroyed in MS. Patients with PML can have widespread demyelination throughout the brain, and in patients with AIDS, the disease is almost always fatal.
In 2006, Tysabri was reintroduced into the market and the pharmaceutical company introduced a strict monitoring program for patients receiving the medication, known as the TOUCH program. It was hoped that giving Tysabri alone, rather than in combination with Avonex, would eliminate this risk. Unfortunately, this has not turned out to be the case, and as of May 2011, there have been 124 reported cases of PML in MS Tysabri patients, and 23 patients have died. Those who have survived the illness, suffer a range of disability, from mild impairment to significant disability.
Overall, the risk of developing PML is about 1:1,000. This is a small risk to be sure, but far from trivial. The use of Tysabri in patients with MS is one of the most controversial and difficult decisions faced by patients and doctors alike. Still, there is little doubt that the outlook for MS patients is brighter even with such difficult decisions.
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