A Network Meta-Analysis of Efficacy and Evaluation of Safety of Subcutaneous Pegylated Interferon Beta-1a versus Other Injectable Therapies for the Treatment of Relapsing-Remitting Multiple Sclerosis

PLOS ONE, Dec 2019

Subcutaneous pegylated interferon beta-1a (peginterferon beta-1a [PEG-IFN]) 125 μg every two or four weeks has been studied in relapsing-remitting multiple sclerosis (RRMS) patients in the pivotal Phase 3 ADVANCE trial. In the absence of direct comparative evidence, a network meta-analysis (NMA) was conducted to provide an indirect assessment of the relative efficacy, safety, and tolerability of PEG-IFN versus other injectable RRMS therapies. Systematic searches were conducted in MEDLINE, Embase, and the Cochrane Library, and conference proceedings from relevant annual symposia were hand-searched. Included studies were randomized controlled trials evaluating ≥1 first-line treatments including interferon beta-1a 30, 44, and 22 μg, interferon beta-1b, and glatiramer acetate in patients with RRMS. Studies were included based on a pre-specified protocol and extracted by a team of independent reviewers and information scientists, utilizing criteria from NICE and IQWiG. In line with ADVANCE findings, NMA results support that PEG-IFN every 2 weeks significantly reduced annualized relapse rate, and 3- and 6-month confirmed disability progression (CDP) versus placebo. There was numerical trend favoring PEG-IFN every 2 weeks versus other IFNs assessed for annualized relapse rate, and versus all other injectables for 3- and 6-month CDP (6-month CDP was significantly reduced versus IFN beta-1a 30 μg). The safety and tolerability profile of PEG-IFN beta-1a 125 μg every 2 weeks was consistent with that of other evaluated treatments. Study limitations for the NMA include variant definitions of relapse and other systematic differences across trials, assumptions that populations were sufficiently similar, and inability to perform NMA of adverse events. With similar efficacy compared to other RRMS treatments in terms of annualized relapse rate and 3- and 6-month CDP, a promising safety profile, and up to 93% reduction in number of injections (which may improve adherence), PEG-IFN every 2 weeks offers a valuable alternative treatment option for patients with RRMS.

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A Network Meta-Analysis of Efficacy and Evaluation of Safety of Subcutaneous Pegylated Interferon Beta-1a versus Other Injectable Therapies for the Treatment of Relapsing-Remitting Multiple Sclerosis

June A Network Meta-Analysis of Efficacy and Evaluation of Safety of Subcutaneous Pegylated Interferon Beta-1a versus Other Injectable Therapies for the Treatment of Relapsing-Remitting Multiple Sclerosis Keith Tolley 0 1 Michael Hutchinson 0 1 Xiaojun You 0 1 Ping Wang 0 1 Bjoern Sperling 0 1 Ankush Taneja 0 1 Mohammed Kashif Siddiqui 0 1 Elizabeth Kinter 0 1 0 1 Tolley Health Economics Ltd. , Buxton , United Kingdom , 2 St. Vincent's University Hospital , Dublin, Ireland , 3 Biogen Idec Inc. , Cambridge, MA , United States of America, 4 HERON Commercialization-A Parexel Company , Chandigarh , India 1 Academic Editor: Maarten Postma, Groningen Research Institute of Pharmacy , NETHERLANDS Subcutaneous pegylated interferon beta-1a (peginterferon beta-1a [PEG-IFN]) 125 μg every two or four weeks has been studied in relapsing-remitting multiple sclerosis (RRMS) patients in the pivotal Phase 3 ADVANCE trial. In the absence of direct comparative evidence, a network meta-analysis (NMA) was conducted to provide an indirect assessment of the relative efficacy, safety, and tolerability of PEG-IFN versus other injectable RRMS therapies. Systematic searches were conducted in MEDLINE, Embase, and the Cochrane Library, and conference proceedings from relevant annual symposia were hand-searched. Included studies were randomized controlled trials evaluating 1 first-line treatments including interferon beta-1a 30, 44, and 22 μg, interferon beta-1b, and glatiramer acetate in patients with RRMS. Studies were included based on a pre-specified protocol and extracted by a team of independent reviewers and information scientists, utilizing criteria from NICE and IQWiG. In line with ADVANCE findings, NMA results support that PEG-IFN every 2 weeks significantly reduced annualized relapse rate, and 3- and 6-month confirmed disability progression (CDP) versus placebo. There was numerical trend favoring PEG-IFN every 2 weeks versus other IFNs assessed for annualized relapse rate, and versus all other injectables for 3- and 6-month CDP (6-month CDP was significantly reduced versus IFN beta-1a 30 μg). The safety and tolerability profile of PEG-IFN beta-1a 125 μg every 2 weeks was consistent with that of other evaluated treatments. Study limitations for the NMA include variant definitions of relapse and other systematic differences across trials, assumptions that populations were sufficiently similar, and inability to perform NMA of adverse events. With similar efficacy compared to other RRMS treatments in terms of annualized relapse rate and 3- and 6-month CDP, a promising safety profile, and up to 93% reduction in number of injections (which may improve adherence), PEG-IFN every 2 weeks offers a valuable alternative treatment option for patients with RRMS. - Funding: This study was sponsored by Biogen Idec Inc. (Cambridge, MA, USA). XY, PW, BS, and EK are employees of Biogen Idec Inc., and were involved in conception and design of the work, data acquisition, analysis and interpretation, critical revision of the manuscript for important intellectual content, and final approval of the version to be published. MKS and AT are employees of HERON, a company that received funding from Biogen Idec to conduct this study. KT receives consulting fees from Biogen Idec Inc. KT is employed by Tolley Health Economics Ltd., Buxton, UK, a commercial company. KT has no other relevant declarations relating to employment, consultancy, patents, products in development or marketed products. MH receives speaker bureau fees from Bayer Schering, Biogen Idec Inc., Merck Serono, and Novartis. There were no restrictions on sharing of data and/or materials. These interests did not alter the authors' adherence to PLOS ONE policies on sharing data and materials. Competing Interests: The authors' have read the journal's policy and the authors of this manuscript have the following competing interests: MKS and AT are employees of HERON, a company that received funding from Biogen Idec to conduct this study. KT receives consulting fees from Biogen Idec Inc. MH receives speaker bureau fees from Bayer Schering, Biogen Idec Inc., Merck Serono, and Novartis. XY, PW, BS, and EK are employees of Biogen Idec Inc. These interests did not alter the authors' adherence to PLOS ONE policies on sharing data and materials. Multiple sclerosis (MS) is a chronic, neuro-inflammatory and neurodegenerative autoimmune disorder affecting the central nervous system (CNS) characterized clinically by recurring episodes of neurological symptoms and increasing disability over time. More than 2.1 million people are affected by MS worldwide with approximately 400,000 cases reported in the United States (US) and 600,000 cases in the European Union [1]. About 85% of patients present with relapsing forms of MS, while the other 15% present with steady progressive disability (primary progressive MS) [2,3]. Current management of relapsing-remitting MS (RRMS) involves the use of disease-modifying (...truncated)


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Keith Tolley, Michael Hutchinson, Xiaojun You, Ping Wang, Bjoern Sperling, Ankush Taneja, Mohammed Kashif Siddiqui, Elizabeth Kinter. A Network Meta-Analysis of Efficacy and Evaluation of Safety of Subcutaneous Pegylated Interferon Beta-1a versus Other Injectable Therapies for the Treatment of Relapsing-Remitting Multiple Sclerosis, PLOS ONE, 2015, Volume 10, Issue 6, DOI: 10.1371/journal.pone.0127960