{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:59:52Z","timestamp":1784735992517,"version":"3.55.0"},"update-to":[{"DOI":"10.12688\/f1000research.7513.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T00:00:00Z","timestamp":1462838400000}},{"DOI":"10.12688\/f1000research.7513.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T00:00:00Z","timestamp":1462838400000}}],"reference-count":6,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T00:00:00Z","timestamp":1462838400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"Many drugs have been approved by the Food and Drug Administration (FDA) since 1993 for treatment of relapsing forms of multiple sclerosis (MS). One such drug is natalizumab (Tysabri, Biogen Idec and Elan pharmaceuticals) which has enjoyed great success in the management of MS since its re-introduction in 2006. One of the complications of using natalizumab is the risk of development of progressive multifocal leukoencephalopathy (PML). To mitigate the risk of PML development, Biogen Idec initiated the TOUCH program \u2013 this strategy helps monitor the disease. Clinical vigilance remains key in the early diagnosis of PML but serological testing for the John Cunningham Virus Antibody (JCV) helps with risk stratification of PML. However, some physicians do not test for the JCV Ab and since they are not required to send such data to the company or inform the patient, one red flag for suspicion of PML is lost particularly if the patient is asymptomatic. \u00a0This undercuts the premise of the TOUCH program. In an ideal world, reporting JCV Ab status should be made mandatory since that ensures a basic tenet of the program is met \u2013 to identify patients at increased risk of developing PML and make appropriate recommendations based on that finding. Lack of requirement of reporting of this vital finding opens the door for uncertainty in assessment of risk PML development and everyone remains in the dark till it may be too late. This is unacceptable when the company created the TOUCH program specifically with intent to track PML risk in patients on natalizumab. It makes no scientific sense to let the drug be used without setting stringent criteria given the possibility of PML development.<\/ns4:p>","DOI":"10.12688\/f1000research.7513.3","type":"journal-article","created":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T05:41:29Z","timestamp":1462858889000},"page":"1450","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["The TOUCH program and natalizumab: Fundamental flaw in patient protection"],"prefix":"10.12688","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2322-503X","authenticated-orcid":false,"given":"Jagannadha","family":"Avasarala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2016,5,10]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"369-374","DOI":"10.1056\/NEJMoa051782","article-title":"Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis.","volume":"353","author":"B Kleinschmidt-DeMasters","year":"2005","journal-title":"N Engl J Med."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"375-381","DOI":"10.1056\/NEJMoa051847","article-title":"Progressive multifocal leukoencephalopathy in a patient treated with natalizumab.","volume":"353","author":"A Langer-Gould","year":"2005","journal-title":"N Engl J Med."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"362-368","DOI":"10.1056\/NEJMoa051586","article-title":"Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn\u2019s disease.","volume":"353","author":"G Van Assche","year":"2005","journal-title":"N Engl J Med."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"802-812","DOI":"10.1002\/ana.24286","article-title":"Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy.","volume":"76","author":"T Plavina","year":"2014","journal-title":"Ann Neurol."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"2240-2241","DOI":"10.1056\/NEJMc1214233","article-title":"JC viremia in natalizumab-treated patients with multiple sclerosis.","volume":"368","author":"E Major","year":"2013","journal-title":"N Engl J Med."},{"key":"ref-6","article-title":"Quarterly safety update, Biogen Idec"}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/4-1450\/v3\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/4-1450\/v3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/4-1450\/v3\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T13:15:22Z","timestamp":1544015722000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/4-1450\/v3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,10]]},"references-count":6,"URL":"https:\/\/doi.org\/10.12688\/f1000research.7513.3","relation":{},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,10]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/4-1450\/v3#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.8092.r11563, David B Clifford, Department of Neurology, Washington University in St. Louis, St Louis, MO, USA, 03 Feb 2016, version 1, 2 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/4-1450\/v1#referee-response-11563","order":0,"name":"referee-response-11563","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Jagannadha Avasarala<\/b>; \nPosted: 03 Feb 2016<\/i>; I thank Dr Clifford for his erudite observations. 1, I agree that the TOUCH program helps in early diagnosis -\n in fact, the following are explicitly stated on the touchprogram.com, thus:<\/b> Inform prescribers, infusion center healthcare providers, and patients about the risk of progressive multifocal leukoencephalopathy (PML) associated with TYSABRI including the increased risk of PML with treatment duration and prior immunosuppressant use.Warn against concurrent use with antineoplastic, immunosuppressant, or immunomodulating agents and in patients who are immunocompromised.\nPromote early diagnosis of PML<\/b> and timely discontinuation of TYSABRI in the event of suspectedFurthermore, in the important safety information section, it is clearly noted that risk factors for the development of PML include duration of therapy, prior use of immunosuppressants, \nand presence of anti-JCV antibodies.<\/b><\/i>As clinicians, we all know that 'early diagnosis' of PML includes the STRATIFY testing protocol approved by the FDA in 2012 and that test is designed specifically to assess PML risk. We also understand and know that JCV Ab negative status also carries risk of PML development but what we cannot ignore what the safety information (noted above) and STRATIFY testing are designed to do. Therefore, uncoupling the TOUCH program from testing\/reporting JCV Ab status is not only dangerous and fallacious, it runs counter to the argument that there is any 'risk stratification' being done if this simple testing is forgotten or discarded. No one can claim that JCV Ab monitoring prevents PML and nor do I state that; but assessing PML risk with STRATIFY is a fundamental principle of the test or we could discard the test altogether ! That frequent MRI testing, clinical surviellance (most critical) and patient self-reporting of new symptoms or worsening of existing symptoms is paramount to the diagnosis of PML is a well established fact, based on scientific evidence.\nIf JCV Ab testing is of such low importance, why does the TOUCH program questionnaire include this as part of their questionnaire ?<\/b> One cannot have it both ways. Either the testing is critical or we do not test it at all and shun the JCV Ab testing as well as the JCV index. Why have a test approved by the FDA (Stratify), create the TOUCH program to monitor and track PML, include JCV Ab status in the questionnaire that is generated by the company and yet reject the very idea of monitoring for PML by throwing away the JCV Ab testing ? The statement that "TOUCH program was created to help assure early diagnosis" utterly does not hold water if JCV Ab testing is not done. As pointed out in my paper, the questionnaire itself includes it ! What is the inclusion for ? It is not exactly for statistical purposes, is it ?Dr Avasarala, MD, PhD","URL":"https:\/\/f1000research.com\/articles\/4-1450\/v3#referee-comment-1794","order":1,"name":"referee-comment-1794","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Jagannadha Avasarala<\/b>; \nPosted: 03 Feb 2016<\/i>; I would also submit the following, additional comments.The TOUCH program, when it was first introduced, did not have the benefit of STRATIFY, approved in 2012. But once JCV Ab testing was FDA approved in 2012, and JCV Ab status testing was part of the TOUCH questionnaire to continue Tysabri use, it became an essential tool to monitor PML risk (in fact, the word Stratify is itself a connotation to categorize risk of PML) so how it is part of a strategy to assess PML risk and yet can be ignored at the same time does not add up. If patients are to be protected or their risk explained to them, every single tool available needs to be put to use. Simple as that.","URL":"https:\/\/f1000research.com\/articles\/4-1450\/v3#referee-comment-1795","order":2,"name":"referee-comment-1795","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.8711.r12574, Nicholas Schwab, Department of Neurology, University Hospital M\u00fcnster, M\u00fcnster, Germany, 30 Mar 2016, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/4-1450\/v2#referee-response-12574","order":3,"name":"referee-response-12574","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Jagannadha Avasarala<\/b>; \nPosted: 05 Apr 2016<\/i>; I agree with Dr Schwab regarding his revised comments. The point of my article is simple - Natalizumab continues to be used by specialists and non-specialists alike and some of them, the physicians, do NOT obtain JCV Ab titers as they are supposed to. After STRATIFY became available and FDA approved its use, in 2012, all Biogen had to do was to introduce it as one more safety measure in the TOUCH program and streamline the process. Instead, the company allows, to this day, physicians to continue to prescribe the drug sans testing or reporting of the JCV Ab status and that undercuts the principle of the TOUCH program, designed to monitor or track PML (risk assessment). Following is what the FDA said in 2012, on their website\nFDA permits marketing of first test for risk of rare brain infection in some people treated with Tysabri <\/b>Today, the U.S. Food and Drug Administration allowed marketing of the first test to help \ndetermine the risk <\/i><\/b>for a rare brain infection called progressive multifocal leukoencephalopathy (PML) in people using the drug Tysabri (natalizumab) to treat multiple sclerosis (MS) or Crohn\u2019s disease (CD).The Stratify JCV Antibody ELISA test, \nwhen used with other clinical data<\/b><\/i> from the patient, can \nhelp health care providers determine the risk for developing PML <\/b><\/i>in MS and CD patients.Dr Avasarala","URL":"https:\/\/f1000research.com\/articles\/4-1450\/v3#referee-comment-1905","order":4,"name":"referee-comment-1905","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Jagannadha Avasarala<\/b>; \nPosted: 08 Apr 2016<\/i>; Just to keep readers updated, the PML count is now 635, as of March, 2016. This is the # of\n <\/b>patients with PML who are on Tysabri for MS.Dr Avasarala","URL":"https:\/\/f1000research.com\/articles\/4-1450\/v3#referee-comment-1910","order":5,"name":"referee-comment-1910","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.8711.r13286, Michael Levy, Department of Neurology, Johns Hopkins University, Baltimore, MD, USA, 19 Apr 2016, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/4-1450\/v2#referee-response-13286","order":6,"name":"referee-response-13286","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":7,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}