Safety outcomes of disease-modifying therapies for relapsing–remitting multiple sclerosis: A network meta-analysis

Lucchetta, RC; Leonart, LP; Becker, J; Pontarolo, R; Fernandez-Llimós, F; Wiens, A

Safety outcomes of disease-modifying therapies for relapsing–remitting multiple sclerosis: A network meta-analysis

Lucchetta, RC Leonart, LP Becker, J Pontarolo, R Fernandez-Llimós, F

Wiens, A

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Publication Type:: Journal Article
Citation:: Multiple Sclerosis and Related Disorders, 2019, 35 pp. 7 - 15
Issue Date:: 2019-10-01

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Field	Value	Language
dc.contributor.author	Lucchetta, RC	en_US
dc.contributor.author	Leonart, LP	en_US
dc.contributor.author	Becker, J	en_US
dc.contributor.author	Pontarolo, R	en_US
dc.contributor.author	Fernandez-Llimós, F https://orcid.org/0000-0002-8529-9595	en_US
dc.contributor.author	Wiens, A	en_US
dc.date.available	2019-06-28	en_US
dc.date.issued	2019-10-01	en_US
dc.identifier.citation	Multiple Sclerosis and Related Disorders, 2019, 35 pp. 7 - 15	en_US
dc.identifier.issn	2211-0348	en_US
dc.identifier.uri	http://hdl.handle.net/10453/137469
dc.description.abstract	© 2019 Background: Randomised clinical trials (RCTs) and observational studies have reported adverse events that preclude the use of disease-modifying therapies (DMTs) in relapsing–remitting multiple sclerosis (RRMS) in the long term or in specific populations, however, little is known about the relationship between the use of DMTs and frequency of undesirable events. We aimed to conduct a systematic review and network meta-analyses (NMAs) of RCTs and observational studies to synthesise the evidence on the safety of all available DMTs for patients with RRMS. Methods: PubMed, Scopus and a manual search were performed. Bayesian NMAs of safety outcomes reported in RCTs and observational studies assessing DMTs as monotherapies were conducted. Results: Forty-seven studies were included in the systematic review. Considering all studies, 368 and 149 different safety outcomes were reported for at least one study and two studies, respectively. Considering clinical trials, 22 NMAs were conducted for 16 outcomes. Regarding geometry metrics, the median number of studies, DMTs, common comparator, strong edge, and patients were 5 (IQR 5–9), 5 (IQR 4–8), 44%, 33%, and 3998 (IQR 3380–6761). In summary, most comparisons showed similar risk of safety events for DMTs and placebo for all outcomes. Considering cohort studies, only three meta-analyses were conducted. Conclusion: Safety outcomes are poorly reported in primary studies of DMTs in RRMS, precluding the conduction of robust meta-analyses. Therefore, the current available data on safety of these drugs is not contributing to regulatory and clinical decision making, with adverse event reports underbalanced compared to efficacy outcomes.	en_US
dc.relation.ispartof	Multiple Sclerosis and Related Disorders	en_US
dc.relation.isbasedon	10.1016/j.msard.2019.06.036	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Multiple Sclerosis, Relapsing-Remitting	en_US
dc.subject.mesh	Immunologic Factors	en_US
dc.subject.mesh	Patient Safety	en_US
dc.subject.mesh	Network Meta-Analysis	en_US
dc.title	Safety outcomes of disease-modifying therapies for relapsing–remitting multiple sclerosis: A network meta-analysis	en_US
dc.type	Journal Article
utslib.citation.volume	35	en_US
utslib.for	1117 Public Health and Health Services	en_US
utslib.for	1109 Neurosciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Graduate School of Health
utslib.copyright.status	closed_access
pubs.publication-status	Published	en_US
pubs.volume	35	en_US

Abstract:

© 2019 Background: Randomised clinical trials (RCTs) and observational studies have reported adverse events that preclude the use of disease-modifying therapies (DMTs) in relapsing–remitting multiple sclerosis (RRMS) in the long term or in specific populations, however, little is known about the relationship between the use of DMTs and frequency of undesirable events. We aimed to conduct a systematic review and network meta-analyses (NMAs) of RCTs and observational studies to synthesise the evidence on the safety of all available DMTs for patients with RRMS. Methods: PubMed, Scopus and a manual search were performed. Bayesian NMAs of safety outcomes reported in RCTs and observational studies assessing DMTs as monotherapies were conducted. Results: Forty-seven studies were included in the systematic review. Considering all studies, 368 and 149 different safety outcomes were reported for at least one study and two studies, respectively. Considering clinical trials, 22 NMAs were conducted for 16 outcomes. Regarding geometry metrics, the median number of studies, DMTs, common comparator, strong edge, and patients were 5 (IQR 5–9), 5 (IQR 4–8), 44%, 33%, and 3998 (IQR 3380–6761). In summary, most comparisons showed similar risk of safety events for DMTs and placebo for all outcomes. Considering cohort studies, only three meta-analyses were conducted. Conclusion: Safety outcomes are poorly reported in primary studies of DMTs in RRMS, precluding the conduction of robust meta-analyses. Therefore, the current available data on safety of these drugs is not contributing to regulatory and clinical decision making, with adverse event reports underbalanced compared to efficacy outcomes.

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http://hdl.handle.net/10453/137469