Stronger association of drug-induced progressive multifocal leukoencephalopathy (PML) with biological immunomodulating agents

Eur J Clin Pharmacol. 2010 Feb;66(2):199-206. doi: 10.1007/s00228-009-0739-z. Epub 2009 Oct 17.

Abstract

Aim: The aim of the present study was to collect and compare cases of drug-induced PML in order to contribute to the debate about the role of the underlying diseases and/or drug immunosuppression in PML occurrence.

Methods: We searched for drug-induced PML cases in two international spontaneous adverse drug reaction (ADR) report databases, FDA-AERS and WHO-VigiBase. From MEDLINE, we retrieved case reports and case series containing the MESH term "leukoencephalopathy, progressive multifocal/chemically induced". In order to assess the PML-drug relationship, we analysed drug-reaction pairs in terms of the patients' underlying diseases and co-suspected drugs.

Results: Overall, 214 cases in FDA-AERS, 118 in WHO-VigiBase and 140 in MEDLINE were collected. Therapeutic groups more frequently involved in PML cases were monoclonal antibodies (MAbs), conventional immunosuppressive drugs and anti-HIV drugs. The most frequent underlying diseases were lymphoproliferative diseases (28%), autoimmune disorders (20%) and transplants (10%). MAbs were more often reported in cases where they were the only suspected drugs, whereas for the other therapeutic groups, concomitant drugs were reported.

Conclusions: We found a strong relationship between PML and MAbs, especially when used in autoimmune diseases. PML is becoming a crucial issue of MAbs, since they can cause severe ADRs through the imbalance of the immune system. Based on these results, patients treated with MAbs should be carefully monitored for early signs and symptoms of PML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adverse Drug Reaction Reporting Systems
  • Alemtuzumab
  • Anti-HIV Agents / adverse effects
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antibodies, Neoplasm / adverse effects
  • Autoimmune Diseases / complications
  • Autoimmune Diseases / drug therapy
  • Biological Products / adverse effects*
  • Biological Products / classification
  • Biological Therapy / adverse effects
  • Female
  • Humans
  • Immunologic Factors / adverse effects*
  • Immunomodulation
  • Immunosuppressive Agents / adverse effects
  • Leukoencephalopathy, Progressive Multifocal / chemically induced*
  • Leukoencephalopathy, Progressive Multifocal / complications
  • Lymphoproliferative Disorders / complications
  • Lymphoproliferative Disorders / drug therapy
  • Male
  • Product Surveillance, Postmarketing / statistics & numerical data*
  • Retrospective Studies
  • Rituximab
  • Transplantation

Substances

  • Anti-HIV Agents
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antibodies, Neoplasm
  • Biological Products
  • Immunologic Factors
  • Immunosuppressive Agents
  • Alemtuzumab
  • Rituximab