- Use of Biomarker has Potential to Advance Personalized Treatment for MS Patients -
“By identifying these risk factors and incorporating them into our risk
stratification algorithm, we bring the advantages of personalized
medicine to MS,” said
About the Research
Researchers used data from clinical studies, post-marketing sources, and an independent Swedish registry to estimate the incidence of PML among TYSABRI-treated patients. Data as of
Blood samples from 5,896 MS patients who participated in three clinical studies - AFFIRM , STRATIFY-1, and the U.S. arm of the TYSABRI Global Observational Program in Safety [TYGRIS] study - as well as blood samples from patients included in the Swedish Multiple Sclerosis registry, were tested for anti-JCV antibodies.
In addition, data from 54 TYSABRI-treated patients who developed PML and had blood samples collected six to 187 months before they were diagnosed with PML were tested for anti-JCV antibodies; all samples tested positive for anti-JCV antibodies.
Data on prior IS use were not available for all patients taking TYSABRI. Therefore, the proportion of prior IS use within the global TYGRIS studies (U.S. and Rest of World) were used to estimate prior IS use in the overall TYSABRI-treated population.
The risk of PML increased with longer duration of TYSABRI treatment, with the greatest increase observed after two years of therapy. Data beyond four years of therapy were limited.
Prior IS use was more common in patients who developed PML (34.5%) compared to patients in the global TYGRIS study (20.3%), indicating that prior IS use was associated with an increased risk of PML.
The prevalence of anti-JCV antibodies in the general MS population was 54.9 percent (95% confidence interval [CI], 53.7 – 56.2) and differed from the 100 percent anti-JCV antibody positivity observed in the 54 MS patients who developed PML and had known pre-PML anti-JCV antibody status. Because all 54 MS patients with known pre-PML anti-JCV antibody status tested positive, a sensitivity analysis assuming one hypothetical anti-JCV antibody negative PML patient was used to estimate the PML risk in antibody negative patients.
Anti-JCV antibody status, combined with prior IS use and TYSABRI treatment duration were used to stratify patients at lower or higher risk for the development of PML. There was an approximately 120-fold difference between patients in the lowest and highest risk groups. Patients who were anti-JCV antibody negative were at the lowest risk for PML with an estimated risk of 0.09 cases or fewer per 1,000 patients (95% CI, 0 to 0.48).
The highest risk of PML was found in patients who had received 25 to 48 months of TYSABRI treatment, had been treated with an IS therapy before TYSABRI treatment was initiated, and were positive for anti-JCV antibodies. The PML incidence in this group was estimated to be 11.1 cases per 1,000 patients (95% CI, 8.3 to 14.5).
The authors concluded that data from prospective studies are needed to further characterize these risks.
“Although TYSABRI has proven efficacy, the risk of PML has been a cause
of concern for patients," said
About the Risk Stratification
The TYSABRI U.S. label and EU Summary of Product Characteristics were updated to add anti-JCV antibody status as a risk factor for PML. In addition to prior IS therapy and duration of TYSABRI therapy, anti-JCV antibody status is the third factor in the risk stratification model developed by
At the time of this analysis (
TYSABRI is approved in more than 65 countries. TYSABRI is approved in
TYSABRI has advanced the treatment of MS patients with its established
efficacy. Data from the Phase 3 AFFIRM trial, which was published in the
TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain, which usually leads to death or severe disability. Infection by the JC virus (JCV) is required for the development of PML and patients who are anti-JCV antibody positive have a higher risk of developing PML. Factors that increase the risk of PML are presence of anti-JCV antibodies, prior immunosuppressant use, and longer TYSABRI treatment duration. Patients who have all three risk factors have the highest risk of developing PML. Other serious adverse events that have occurred in TYSABRI-treated patients include hypersensitivity reactions (e.g., anaphylaxis) and infections, including opportunistic and other atypical infections. Clinically significant liver injury has also been reported in the post-marketing setting. A list of adverse events can be found in the full TYSABRI product labeling for each country where it is approved.
TYSABRI is marketed and distributed by
Through cutting-edge science and medicine,
Jeff Boyle, + 1 781 464 3260
Benjamin Strain, +1 781 464 2442
Niamh Lyons, +353 1 709 4176
Chris Burns, +1 800 252 3526
David Marshall, + 353 1 709 4444