Assessing PML risk under immunotherapy: if all you have is a hammer, everything looks like a nail

Recently, three progressive multifocal leukoencephalopathy (PML) cases have been reported in multiple sclerosis (MS) patients, two treated with fingolimod (Gilenya, Novartis), the third with dimethyl fumarate (Tecfidera, Biogen). Because our immunotherapeutic arsenal in MS and other diseases is increasing, and because PML is a very serious health risk, it is of interest to the clinical community to show how we can assess this risk in a statistically sound way. The null-hypothesis for this analysis was that there is no elevated risk for PML in patients treated with one of these recent drugs, compared to the incidence in the general population. We conclude that the null hypothesis cannot be refuted.