JagannadhaAvasarala, Associate Professor of Neurology, Greenville Health System & U of South Carolina School of Medicine[email protected]
Submitted February 16, 2016
The findings by Schwab et al. that a high JC virus (JCV) seroconversion and rising JCV index values were associated with natalizumab (Tysabri) use in patients with multiple sclerosis (MS) are worrisome. [1]
The TOUCH (Tysabri Outreach: Unified Commitment to Health program) program, created in 2006, is a risk minimization plan for progressive multifocal leukoencephalopathy (PML); it was developed by Biogen Idec, intended to ensure physicians and patients understand the benefits and potential risks associated with the use of Tysabri, particularly the risk of PML. Under the TOUCH program, every patient who receives Tysabri is closely monitored for PML and other serious opportunistic infections. However, as noted in my recent article, [2] the TOUCH program has failed in protecting patients as testing for JCV antibody is not mandatory, allowing physicians to continue Tysabri use despite not checking the JCV antibody status.
JCV antibody positive status is a risk factor for developing PML, but a negative JCV antibody status does not confer protection against PML development either. Since JCV antibody positive status implies higher risk of PML development, checking JCV antibody status must be made mandatory in the TOUCH program.
In Biogen's defense, when the TOUCH program was originally instituted, there was no JCV antibody testing and the test (Stratify JCV Antibody ELISA test) developed to check for JCV antibody status was not approved by the FDA until January 2012. With this approval, testing should have been made mandatory, but instead it remains optional. Physicians who continue prescribing the drug without testing for JCV antibody status are jeopardizing patient safety. At a minimum, withholding the drug when JCV antibody testing status is not reported to Biogen would alert the physician to test for JCV antibody status. Of course, physicians must be aware of prior immunosuppressant drug use as well as how long the patient had been on Tysabri, since both factors also figure in PML risk assessment.
The latest PML count is 614, as of December 2015, per the quarterly report by Biogen. [3] What if one of these cases was due to failure of checking for JCV antibody status? Also, why are raw data not publicly available on these 614 PML cases along with their JCV antibody status?
1. Schwab N, Schneider-Hohendorf T, Pignolet B, et al. Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values. Neurol Neuroimmunol Neuroinflamm Epub 2016 Jan 27.
2. Avasarala J. The TOUCH program and natalizumab: Fundamental flaw in patient protection [version 1; referees: 1 approved with reservations]. F1000Research 2015;4:1450.
3. Biogen medical information. Available at: https://medinfo.biogenidec.com. Accessed December 10, 2015.
For disclosures, please contact the editorial office at [email protected].
The findings by Schwab et al. that a high JC virus (JCV) seroconversion and rising JCV index values were associated with natalizumab (Tysabri) use in patients with multiple sclerosis (MS) are worrisome. [1]
The TOUCH (Tysabri Outreach: Unified Commitment to Health program) program, created in 2006, is a risk minimization plan for progressive multifocal leukoencephalopathy (PML); it was developed by Biogen Idec, intended to ensure physicians and patients understand the benefits and potential risks associated with the use of Tysabri, particularly the risk of PML. Under the TOUCH program, every patient who receives Tysabri is closely monitored for PML and other serious opportunistic infections. However, as noted in my recent article, [2] the TOUCH program has failed in protecting patients as testing for JCV antibody is not mandatory, allowing physicians to continue Tysabri use despite not checking the JCV antibody status. JCV antibody positive status is a risk factor for developing PML, but a negative JCV antibody status does not confer protection against PML development either. Since JCV antibody positive status implies higher risk of PML development, checking JCV antibody status must be made mandatory in the TOUCH program. In Biogen's defense, when the TOUCH program was originally instituted, there was no JCV antibody testing and the test (Stratify JCV Antibody ELISA test) developed to check for JCV antibody status was not approved by the FDA until January 2012. With this approval, testing should have been made mandatory, but instead it remains optional. Physicians who continue prescribing the drug without testing for JCV antibody status are jeopardizing patient safety. At a minimum, withholding the drug when JCV antibody testing status is not reported to Biogen would alert the physician to test for JCV antibody status. Of course, physicians must be aware of prior immunosuppressant drug use as well as how long the patient had been on Tysabri, since both factors also figure in PML risk assessment.
The latest PML count is 614, as of December 2015, per the quarterly report by Biogen. [3] What if one of these cases was due to failure of checking for JCV antibody status? Also, why are raw data not publicly available on these 614 PML cases along with their JCV antibody status?
1. Schwab N, Schneider-Hohendorf T, Pignolet B, et al. Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values. Neurol Neuroimmunol Neuroinflamm Epub 2016 Jan 27.
2. Avasarala J. The TOUCH program and natalizumab: Fundamental flaw in patient protection [version 1; referees: 1 approved with reservations]. F1000Research 2015;4:1450.
3. Biogen medical information. Available at: https://medinfo.biogenidec.com. Accessed December 10, 2015.
For disclosures, please contact the editorial office at [email protected].