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

  • Pharmacoepidemiology and Prescription
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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.

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Acknowledgements

The authors are indebted to the national centres who contributed data. The opinions and conclusions, however, are not necessarily those of the various centres nor of the WHO.

Conflict of interest

None of the authors have any potential conflict of interest with commercial parties.

Funding

This study was funded with institutional funds from the Emilia-Romagna Region and from the University of Bologna (RFO).

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Authors and Affiliations

  1. Department of Pharmacology, University of Bologna, Via Irnerio, 48, 40126, Bologna, Italy

    Carlo Piccinni, Chiara Sacripanti, Elisabetta Poluzzi, Domenico Motola & Nicola Montanaro

  2. Clinical Pharmacology Unit, University of Verona, P.le Ludovico Antonio Scuro, 10, 37134, Verona, Italy

    Lara Magro, Ugo Moretti & Anita Conforti

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  1. Carlo Piccinni
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  2. Chiara Sacripanti
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  4. Domenico Motola
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  8. Nicola Montanaro
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Correspondence to Nicola Montanaro.

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Piccinni, C., Sacripanti, C., Poluzzi, E. et al. Stronger association of drug-induced progressive multifocal leukoencephalopathy (PML) with biological immunomodulating agents. Eur J Clin Pharmacol 66, 199–206 (2010). https://doi.org/10.1007/s00228-009-0739-z

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  • DOI: https://doi.org/10.1007/s00228-009-0739-z

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