Feb 10, 2009
Tysabri Update: New Published Papers Explore its Benefits, and New Case of PML Reported
Two newly published papers explore aspects of how Tysabri® (natalizumab, Biogen Idec, Inc and Elan Pharmaceuticals) impacts relapsing multiple sclerosis. One, an investigator-initiated study that has been following individuals after they stopped using Tysabri after a median of 30 doses, found that after 14 months there were no signs of a rebound of increased disease activity after the drug’s cessation. The other study looks back at MRIs and clinical measures of disease activity gathered during the course of one of the phase 3 clinical trials that led to the drug’s approval, and finds that over two years, 37% of those on Tysabri were free of MRI or clinically detected disease activity, versus only 7% of those on inactive placebo during the trial.
Details: No Rebound in Those Who Stopped Taking Tysabri After Extended Exposure
A paper appearing in the February 3, 2009 issue of Neurology (2009;72:396-401) describes follow-up studies in 23 individuals who had taken Tysabri largely in the context of phase 3 clinical trials (the AFFIRM and SENTINEL trials), and who had been administered a median of 30 monthly doses before stopping the drug. Some previous studies had suggested that stopping Tysabri could bring about a rebound of increased MS activity, while another previous study had not found evidence of rebound.
To address the question of disease activity after cessation of Tysabri, Olaf Stuve, MD, PhD (VA North Texas Health Care System, Dallas) and collaborators conducted an investigator-initiated study (not funded by the drug’s sponsor) evaluating immune activity in the blood and spinal fluid, relapse rates and disease progression, and MRI scans 14 months after the cessation of Tysabri. They found that at 14 months, most were stable, with no new clinical disease activity, MRI activity or immune activity. In an accompanying editorial, Drs. Nicoline Schiess and Peter Calabresi comment that, based on this and previous studies, stopping Tysabri after extended dosing may not cause rebound, whereas stopping the drug after only a few doses may indeed cause disease worsening.
Details: Disease Activity Remitted in Significant Proportion of Patients on Tysabri During Clinical Trial
In a study funded by Biogen Idec, Eva Havrdova, MD, PhD (Charles University in Prague, Czech Republic) and collaborators evaluated data gathered during the course of the AFFIRM phase 3 clinical trial of Tysabri in relapsing-remitting MS, one of two phase 3 trials that led to the drug’s marketing approval. In the original two-year study, the drug significantly reduced relapse rates by 68% over placebo, and reduced the risk for disability progression and MRI activity, and improved quality of life measures.
In this post-hoc analysis, published early online on February 9, 2009 in Lancet Neurology, the investigators looked back at the serial MRI scans and clinical measures of disease activity and disability. They found that, of 596 people on active therapy, 64% were free of clinical disease activity, compared to 39% of the 311 people taking inactive placebo. In addition, 58% of those on Tysabri, versus 14% of those on placebo, were free of MRI-detected disease activity. Using both measures of disease activity together, 37% of those on Tysabri were free of disease activity, versus 7% of those on placebo.
Monitoring for PML
The FDA prescribing information about Tysabri includes a black box warning about the risk of progressive multifocal leukoencephalopathy (PML), a viral infection of the brain that usually leads to death or severe disability. The typical symptoms associated with PML progress over days to weeks, and can include clumsiness and progressive weakness on one side of the body, disturbances of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. Changes of this kind should be reported immediately to one’s physician. Although the absolute risk for PML in patients treated with Tysabri cannot be precisely determined, the frequency of PML to date remains less than the one-in-one thousand risk that was estimated at the time of Tysabri’s re-approval in 2006.
Read the latest post-marketing safety warnings provided by the FDA
Tysabri is a registered trademark of Biogen Idec and Elan.