Statistical analysis of PML incidences of natalizu

Authors: Denise Campagnolo Qunming Dong Lily Lee PeiRan Ho Diogo Amarante Harold Koendgen

Publish Date: 2016/10/11

Volume: 22, Issue: 6, Pages: 880-881

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Abstract

In January 2012 the presence of John Cunningham virus JCV antibodies was incorporated into the US prescribing information for Tysabri® natalizumab as a third independent risk factor for progressive multifocal leukoencephalopathy PML development in natalizumabtreated patients Tysabri 2016 The assay used to detect the presence of JCV antibodies Stratify JCV® DxSelect™ Focus Diagnostics Cypress CA USA reports a binary output of positive or negative Additional research described in 2013 Plavina et al 2013 and published in 2014 Plavina et al 2014 demonstrated that JCV index values could further stratify PML risk in natalizumabtreated antiJCV antibody positive patients without prior exposure to immunosuppressantsThe estimated US incidence of PML risk table Tysabri 2016 helps to inform health care providers HCPs and their patients about PML risk on natalizumab treatment It is based on three identified risk factors the presence of antiJCV antibodies the duration of treatment especially beyond 2 years and prior treatment with an immunosuppressant Benefit/risk assessment is complex and varies among HCPs and patients The algorithm exists to assist HCPs in risk stratification of PML based on the established risk factors On the assumption that risk stratification has altered patient management the outcome of potentially changing behavior can only be assessed retrospectively and after a significant period of timeDr Werner has reported Werner and Huang 2016 that in the nearly 4 years since the antibody test became available as a means of risk stratification there has been only a modest reduction in the incidence of PML arising from natalizumab treatment based on data from February 2011 to January 2016Incidence of PML in natalizumabtreated patients from 2009 to 2016 Piecewise regression analysis incorporating changing points was employed to identify the optimal break point and to estimate the slopes Statistical testing shows a twopiece regression is significantly better than onepiece regression whereas threepiece regression does not give a significantly better fit for the data than twopiece regression CI confidence intervalWhile it is not possible to assign causal relationships for the slope reduction a significant reduction in PML incidence rise is observed beginning in September 2013 and continuing through June 2016 Further investigation may elucidate factors that have influenced this change over time in PML incidenceOpen Access This article is distributed under the terms of the Creative Commons Attribution 40 International License http//creativecommonsorg/licenses/by/40/ which permits unrestricted use distribution and reproduction in any medium provided you give appropriate credit to the original authors and the source provide a link to the Creative Commons license and indicate if changes were made

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