Evidence map›Paper›PMID 26507833›Full record

ArticleCNS drugs2015

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

Mauro Melis, Chiara Biagi, Lars Småbrekke, Francesco Nonino, Elena Buccellato, Monia Donati, Alberto Vaccheri, Domenico Motola

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In one paragraph

Article in CNS drugs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 13 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Mauro MelisUnit of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, via Irnerio 48, 40126, Bologna, Italy.
Chiara BiagiUnit of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, via Irnerio 48, 40126, Bologna, Italy.
Lars SmåbrekkeDepartment of Pharmacy, UiT-The Arctic University of Norway, Tromsø, Norway.
Francesco NoninoMedicines and Medical Devices Area - Health and Social Policies Directorate, Emilia-Romagna Region, via Aldo Moro 21, 40127, Bologna, Italy.
Elena BuccellatoUnit of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, via Irnerio 48, 40126, Bologna, Italy.
Monia DonatiUnit of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, via Irnerio 48, 40126, Bologna, Italy.
Alberto VaccheriUnit of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, via Irnerio 48, 40126, Bologna, Italy.
Domenico MotolaUnit of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, via Irnerio 48, 40126, Bologna, Italy. domenico.motola@unibo.it.
University of Bologna · ITRegione Emilia-RomagnaUiT The Arctic University of Norway · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo identify safety signals concerning the association between the use of various drug classes and the onset of progressive multifocal leukoencephalopathy (PML).

methodsAll reports containing suspected or interacting PML-related or leukoencephalopathy-related drugs, held in the World Health Organization spontaneous individual case safety reports database as at 1 September 2014, were retrieved. We identified safety signals by analysing the drug-reaction pairs, using the reporting odds ratio as a measure of disproportionality. A safety signal was defined if a drug was reported more than twice in PML cases with a reporting odds ratio >2 and a lower 95 % confidence limit >1.

resultsWe retrieved 2452 reports associated with PML (N = 1612), leukoencephalopathy (N = 835) or both (N = 5), corresponding to 343 different drugs. PML was reported similarly in male and female adults (18-64 years), and almost 30 % of the cases had a fatal outcome. The most frequent Anatomical Therapeutic Chemical (ATC) classification groups concerned antineoplastic agents (23.5 %), antivirals for systemic use (10.1 %) or immunostimulants (4.6 %). Significant disproportionality was found for 88 drugs in the overall analysis (of cases with 'progressive multifocal leukoencephalopathy' or 'leukoencephalopathy' as the Preferred Term), and a new safety signal was identified for 59 active substances (e.g. muromonab-CD3, basiliximab and antithymocyte Ig), as no information on a possible risk of PML was acknowledged in their Summary of Product Characteristics documents. Some safety signals were confirmed also after sensitivity analysis adjustment for several confounding factors (underlying diseases and considering only 'progressive multifocal leukoencephalopathy' as the Preferred Term).

conclusionWe 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.

Indexed as

AdolescentAdultAgedChildChild, PreschoolDatabases, PharmaceuticalDrug-Related Side Effects and Adverse ReactionsFemaleHumansInfantInfant, NewbornLeukoencephalopathy, Progressive MultifocalMaleMiddle AgedWorld Health OrganizationYoung Adult

Identifiers

PMID26507833
OpenAlexW2198766546

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.