Authors: Julian Borchardt
We show that the quarterly updates about the risk of PML during natalizumab therapy, while in principle helpful, underestimate the real incidences systematically and significantly. Calculating the PML incidences using an appropriate method and on realistic assumptions, we obtain estimates that are up to 80% higher. In fact, with the recent paper [Plavina et al 2014], our approximate incidences are up to ten times as high. The present article describes the shortcomings of the methods used in [Bloomgren et al 2012] and by Plavina et al for computing incidences, and demonstrates how to properly estimate the true (prospective) risk of developing PML during natalizumab treatment. One application is that the newest data concerning the advances in risk-mitigation through the extension of dosing intervals, although characterised as not quite statistically significant, are in fact significant. Lastly, we discuss why the established risk-stratification algorithms, even on assessing the PML incidences correctly, are no longer state-of-the-art; in the light of all the progress that has been made so far, already today it is possible to reliably identify over 95% of patients in whom (a personalised regimen of) natalizumab should be very safe.
Comments: 45 Pages. Parts of this manuscript have been published in Multiple Sclerosis and Related Disorders (Vol. 8, pp. 145-150, 2016, doi:10.1016/j.msard.2016.03.005). The complete PDF can be downloaded for free from http://authors.elsevier.com/a/1TQWn7skoepyJK
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