Drug-Induced Progressive Multifocal Leukoencephalopathy: A Comprehensive Analysis of the WHO Adverse Drug Reaction Database

Abstract

We report a possible association between several drugs and PML that has not been previously described. In addition, we have confirmed previously reported signals in a number of drugs. We highlight the need for follow-up by regulatory agencies.

Drug-induced progressive multifocal leukoencephalopathy: a case/noncase study in the French pharmacovigilance database

“…PML is not mentioned in the French SPC for all the other drugs ( Table ). Our results are consistent with data reported in the literature , except for oxaliplatin not evidenced in the WHO ADR database . All these drugs have been associated with other concomitant cytotoxic agents or immunosuppressive drugs, except for one case with fludarabine in a hematological patient (lymphoma).…”

“…PML is not mentioned in the French SPC and has not been clearly reported in the literature, except for prednisone administered as an immunosuppressant in SLE patients developing PML . This result is consistent with reported data using the ROR measure to detect safety signals focusing on PML . In our study, glucocorticoids were administered as co‐medications in hematological patients and in solid organ transplant patients or in autoimmune diseases.…”

“…Finally, we showed that many different times to the onset of drug‐induced PML are observed ( Table ). These data, not studied by Melis et al in the WHO database , are important for two reasons: (i) a long‐term use of these drugs could increase the risk of PML and (ii) a long time to onset after stopping some drugs is possible.…”

Progressive multifocal leukoencephalopathy in a lung transplant recipient

“…Two of the 13 cases previously described also specified basiliximab as part of their induction immunosuppression regimen (Table 1). 7,10 While there are limited data in the literature regarding the risk of PML associated with basiliximab, one analysis of the World Health Organization adverse drug reaction database provided evidence for a potential association between basiliximab and PML 20 . Additional research is needed to understand if there is a defined association.…”

Progressive multi-focal leucoencephalopathy – driven from rarity to clinical mainstream by iatrogenic immunodeficiency

“…There is a single report of PML in a patient with myelofibrosis receiving Ruxolitinib, an inhibitor of Janus kinase (JAK)‐1 and JAK‐2 kinases , while recent analysis of the World Health Organization's adverse drug reaction database reveals a newly emergent signal for PML in association with muromonab (anti‐CD3) and basiliximab (anti‐CD25) . Because inhibition of the therapeutic targets of these agents suggests some biological plausibility for the development of opportunistic infection, the results of enhanced pharmacovigilance initiatives will be required in order to assess the risk of PML with these drugs.…”