A Systematic Review and Mixed Treatment Comparison of Pharmaceutical Interventions for Multiple Sclerosis
Abstract Background Since 2010, 27 mixed-treatment comparisons (MTCs) of disease-modifying therapies (DMTs) for multiple sclerosis have been published. However, there has been continued evolution in the field of MTCs. Additionally, limitations in methodological approach and reporting transparency, e...
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Adis, Springer Healthcare
2020-09-01
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Series: | Neurology and Therapy |
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Online Access: | https://doi.org/10.1007/s40120-020-00212-5 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gavin Giovannoni Shona Lang Robert Wolff Steven Duffy Robert Hyde Elizabeth Kinter Craig Wakeford Maria Pia Sormani Jos Kleijnen |
spellingShingle |
Gavin Giovannoni Shona Lang Robert Wolff Steven Duffy Robert Hyde Elizabeth Kinter Craig Wakeford Maria Pia Sormani Jos Kleijnen A Systematic Review and Mixed Treatment Comparison of Pharmaceutical Interventions for Multiple Sclerosis Neurology and Therapy Disease-modifying therapies Meta-analysis Mixed treatment comparison Multiple sclerosis Relapsing–remitting multiple sclerosis |
author_facet |
Gavin Giovannoni Shona Lang Robert Wolff Steven Duffy Robert Hyde Elizabeth Kinter Craig Wakeford Maria Pia Sormani Jos Kleijnen |
author_sort |
Gavin Giovannoni |
title |
A Systematic Review and Mixed Treatment Comparison of Pharmaceutical Interventions for Multiple Sclerosis |
title_short |
A Systematic Review and Mixed Treatment Comparison of Pharmaceutical Interventions for Multiple Sclerosis |
title_full |
A Systematic Review and Mixed Treatment Comparison of Pharmaceutical Interventions for Multiple Sclerosis |
title_fullStr |
A Systematic Review and Mixed Treatment Comparison of Pharmaceutical Interventions for Multiple Sclerosis |
title_full_unstemmed |
A Systematic Review and Mixed Treatment Comparison of Pharmaceutical Interventions for Multiple Sclerosis |
title_sort |
systematic review and mixed treatment comparison of pharmaceutical interventions for multiple sclerosis |
publisher |
Adis, Springer Healthcare |
series |
Neurology and Therapy |
issn |
2193-8253 2193-6536 |
publishDate |
2020-09-01 |
description |
Abstract Background Since 2010, 27 mixed-treatment comparisons (MTCs) of disease-modifying therapies (DMTs) for multiple sclerosis have been published. However, there has been continued evolution in the field of MTCs. Additionally, limitations in methodological approach and reporting transparency, even in the most recent publications, makes interpretation and comparison of existing studies difficult. Objectives The objectives of this study are twofold: (1) to estimate the efficacy and safety of DMTs at European Commission-approved doses compared with placebo in adults with relapsing–remitting multiple sclerosis (RRMS) using MTC, and (2) to identify and address methodological challenges when performing MTC in RRMS, thereby creating a baseline for comparisons with future treatments. Methods Searches were completed in 14 databases, including MEDLINE, Embase, CENTRAL, CDSR and DARE, from inception to June 2018 to identify published or unpublished prospective, randomised controlled trials of all European Union-approved DMTs or DMTs expected to be approved in the near future in RRMS or rapidly-evolving severe RRMS. No language or date restrictions were applied. Studies were included in the MTC if they were judged to have sufficiently similar characteristics, based on the following: patient age; proportion of male participants; Expanded Disability Status Scale (EDSS) score; duration of disease; number of relapses prior to enrolment and proportion of previously treated patients. Background information from the included studies, as well as effect size and confidence intervals (where relevant) of defined outcomes were extracted. Reporting of the MTC was consistent with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) network meta-analysis guidelines. Results In total, 33 studies were included in the MTC. Annualised relapse rate (ARR 28 trials) was significantly reduced in all treatments compared with placebo. Alemtuzumab had the highest probability (63%) of being the most effective treatment in terms of ARR compared with placebo (rate ratio [RR] 0.28, 95% credible interval [CrI] 0.21–0.38), followed by natalizumab (30% probability; RR 0.32, 95% CrI 0.23–0.43). The risk of 3- and 6-month confirmed disability progression (CDP3M, 13 trials; CDP6M, 14 trials) were similar; CDP6M was significantly reduced for alemtuzumab (hazard ratio [HR] 0.365; 95% CrI 0.165–0.725), ocrelizumab (HR 0.405, 95% CrI 0.188–0.853) and natalizumab (HR 0.459, 95% CrI 0.252–0.840) relative to placebo. There were no significant differences in the odds of serious adverse events (SAEs, 6 trials) between any treatment and placebo. The results of the MTC were limited by the lack of studies reporting direct comparisons between the included treatments and by heterogeneous reporting of key outcome data. Conclusions Meta-analyses confirmed the benefit of all DMTs in terms of relapse rate compared with placebo with a comparable rate of SAEs for the DMTs that could be included in the network. The rigor and transparency of reporting in this study provide a benchmark for comparisons with future new agents. |
topic |
Disease-modifying therapies Meta-analysis Mixed treatment comparison Multiple sclerosis Relapsing–remitting multiple sclerosis |
url |
https://doi.org/10.1007/s40120-020-00212-5 |
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doaj-fb99c4a74e28457887e4c79f3516fdb62021-10-03T11:03:41ZengAdis, Springer HealthcareNeurology and Therapy2193-82532193-65362020-09-019235937410.1007/s40120-020-00212-5A Systematic Review and Mixed Treatment Comparison of Pharmaceutical Interventions for Multiple SclerosisGavin Giovannoni0Shona Lang1Robert Wolff2Steven Duffy3Robert Hyde4Elizabeth Kinter5Craig Wakeford6Maria Pia Sormani7Jos Kleijnen8Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of LondonKleijnen Systematic Reviews LtdKleijnen Systematic Reviews LtdKleijnen Systematic Reviews LtdBiogenBiogenBiogenDepartment of Health Sciences, University of GenoaSchool for Public Health and Primary Care (CAPHRI), Maastricht UniversityAbstract Background Since 2010, 27 mixed-treatment comparisons (MTCs) of disease-modifying therapies (DMTs) for multiple sclerosis have been published. However, there has been continued evolution in the field of MTCs. Additionally, limitations in methodological approach and reporting transparency, even in the most recent publications, makes interpretation and comparison of existing studies difficult. Objectives The objectives of this study are twofold: (1) to estimate the efficacy and safety of DMTs at European Commission-approved doses compared with placebo in adults with relapsing–remitting multiple sclerosis (RRMS) using MTC, and (2) to identify and address methodological challenges when performing MTC in RRMS, thereby creating a baseline for comparisons with future treatments. Methods Searches were completed in 14 databases, including MEDLINE, Embase, CENTRAL, CDSR and DARE, from inception to June 2018 to identify published or unpublished prospective, randomised controlled trials of all European Union-approved DMTs or DMTs expected to be approved in the near future in RRMS or rapidly-evolving severe RRMS. No language or date restrictions were applied. Studies were included in the MTC if they were judged to have sufficiently similar characteristics, based on the following: patient age; proportion of male participants; Expanded Disability Status Scale (EDSS) score; duration of disease; number of relapses prior to enrolment and proportion of previously treated patients. Background information from the included studies, as well as effect size and confidence intervals (where relevant) of defined outcomes were extracted. Reporting of the MTC was consistent with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) network meta-analysis guidelines. Results In total, 33 studies were included in the MTC. Annualised relapse rate (ARR 28 trials) was significantly reduced in all treatments compared with placebo. Alemtuzumab had the highest probability (63%) of being the most effective treatment in terms of ARR compared with placebo (rate ratio [RR] 0.28, 95% credible interval [CrI] 0.21–0.38), followed by natalizumab (30% probability; RR 0.32, 95% CrI 0.23–0.43). The risk of 3- and 6-month confirmed disability progression (CDP3M, 13 trials; CDP6M, 14 trials) were similar; CDP6M was significantly reduced for alemtuzumab (hazard ratio [HR] 0.365; 95% CrI 0.165–0.725), ocrelizumab (HR 0.405, 95% CrI 0.188–0.853) and natalizumab (HR 0.459, 95% CrI 0.252–0.840) relative to placebo. There were no significant differences in the odds of serious adverse events (SAEs, 6 trials) between any treatment and placebo. The results of the MTC were limited by the lack of studies reporting direct comparisons between the included treatments and by heterogeneous reporting of key outcome data. Conclusions Meta-analyses confirmed the benefit of all DMTs in terms of relapse rate compared with placebo with a comparable rate of SAEs for the DMTs that could be included in the network. The rigor and transparency of reporting in this study provide a benchmark for comparisons with future new agents.https://doi.org/10.1007/s40120-020-00212-5Disease-modifying therapiesMeta-analysisMixed treatment comparisonMultiple sclerosisRelapsing–remitting multiple sclerosis |