Evaluation of Patients Treated with Natalizumab for Progressive Multifocal Leukoencephalopathy

Yousry, Tarek; Major, Eugene O.; Ryschkewitsch, Caroline F.; Fahle, Gary A.; Fischer, Steven H.; Hou, Jean; Curfman, Blanche; Miszkiel, Katherine; Mueller-Lenke, Nicole; Sánchez, Esther; Barkhof, Frederik; Radue, Ernst‐Wilhelm; Jäger, Hans Rolf; Clifford, David B.

doi:10.1056/nejmoa054693

Cited by 718 publications

(402 citation statements)

References 13 publications

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“…A subsequent retrospective review of 3,417 patients who had received natalizumab found no cases of detectable JCV DNA in the cerebrospinal fluid and only 1 possible case of PML, which was unconfirmed due to lack of followup data; the estimated risk of PML in patients treated with natalizumab was 1 case per 1,000 patients in 18 months (71). The mechanisms underlying the involvement of natalizumab in the pathogenesis of PML remain unclear at present.…”

Section: Polyomavirusmentioning

confidence: 99%

Viral infection and reactivation in autoimmune disease

Chakravarty

2008

Arthritis & Rheumatism

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Section: Polyomavirusmentioning

confidence: 99%

Viral infection and reactivation in autoimmune disease

Chakravarty

2008

Arthritis & Rheumatism

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“…Immune reconstitution as an effective approach to control of PML has been further established by the important experience of treating PML associated with natalizumab therapy in the setting of multiple sclerosis. Natalizumab-associated PML emerged in 2005 when this effective integrin inhibitor was found to increase vastly the risk of developing PML in a population that had previously never seen this complication [57][58][59][60]. Rapid immune reconstitution can be accomplished by using plasma exchange to speed drug clearance and allowing access to the brain for the existing immune response.…”

Section: Progressive Multifocal Leukencephalopathymentioning

confidence: 99%

Clinical Trials in Neurovirology: Successes, Challenges, and Pitfalls

Haubenberger

Clifford

2016

Neurotherapeutics

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Clinical trials in neurovirology illustrate the special challenges confronting investigators planning to study these conditions, as well as the contributions of successful trials in establishing appropriate management for these devastating diseases. This article reviews key examples of progress in neurovirology that have been spurred by clinical trials, emphasizing human herpes virus encephalitis, HIV, and JC virus. Clinical trials in the setting of neurovirological diseases are characterized by specific challenges, which may include small sample sizes, clinical presentations from life-threatening conditions to chronic courses of disease, regional and temporally restricted outbreaks scenarios, and the unavailability of validated diagnostic tests that can be rapidly deployed at the bedside. This review aims to highlight these methodological challenges and pitfalls in designing and executing clinical neurovirology trials, as well as to outline innovative trial designs, which could be useful in addressing common challenges.

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“…Subsequently, evaluation of another patient who died in a trial for the treatment of Crohn's disease confirmed a third case of PML. With a known denominator of approximately 3,000 patients who received the drug during clinical trials to treat MS or Crohn's disease it was possible to estimate a rate of PML in patients who received natazilumab of approximately 1/1,000 (16,17). Because of the small number of PML cases it was not possible to definitively determine the relative contribution to risk by concomitant treatment with IFN β-1a or other immunosuppressive drugs.…”

Section: Natalizumab and Progressive Multifocal Leukoencephalopathy (mentioning

confidence: 99%

Informatic Tools and Approaches in Postmarketing Pharmacovigilance Used by FDA

Weaver

Willy

Avigan

2008

AAPS J

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Abstract. The safety profile of newly approved drugs and therapeutic biologics is less well developed by pre-marketing clinical testing than is the efficacy profile. The full safety profile of an approved product is established during years of clinical use. For nearly 40 years, the FDA has relied on the voluntary reporting of adverse events by healthcare practitioners and patients to help establish the safety of marketed products. Epidemiologic studies, including case series, secular trends, case-control and cohort studies, are used to supplement the investigation of a safety signal. Ideally, active surveillance systems would supplement the identification and exploration of safety signals. The FDA has implemented a number of initiatives to help identify safety problems with drugs and continues to evaluate their efforts.

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Evaluation of Patients Treated with Natalizumab for Progressive Multifocal Leukoencephalopathy

Abstract: Background Progressive multifocal leukoencephalopathy (PML) was reported to have developed in three patients treated with natalizumab. We conducted an evaluation to determine whether PML had developed in any other treated patients.

Cited by 718 publications

References 13 publications

Viral infection and reactivation in autoimmune disease

Viral infection and reactivation in autoimmune disease

Clinical Trials in Neurovirology: Successes, Challenges, and Pitfalls

Informatic Tools and Approaches in Postmarketing Pharmacovigilance Used by FDA

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