Efficacy and Safety of PEGylated Interferons for Relapsing-Remitting Multiple Sclerosis in Adult Patients: Results of Matching-Adjusted Indirect Comparison

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Abstract

Introduction. Beta interferons are effective and safe agents for the treatment of relapsing-remitting multiple sclerosis (RRMS). PEGylated interferons have been developed in order to increase patient adherence. Direct comparisons of the efficacy and safety of PEGylated interferons have not yet been conducted.

Our objective was to evaluate the efficacy and safety of SamPEG-IFN-β1a versus PEG-IFN-β1a in adult patients with RRMS.

Materials and methods. We conducted a systematic search of randomized clinical trials (RCTs) using the PubMed, Embase and eLIBRARY.RU databases. Efficacy was assessed based on the proportion of patients with disease relapses and the annualized relapse rate (ARR) during the 1st and the 2nd years of treatment. Safety was assessed by the number of patients with adverse events (AEs), serious AEs (SAEs), and any AEs that led to the treatment discontinuation. We conducted pairwise matching-adjusted indirect comparison (MAIC) to assess comparative efficacy of PEGylated IFNs. To evaluate the efficacy, hypotheses of non-inferiority of SamPEG-IFN-β1a to PEG-IFN-β1a and superiority of SamPEG-IFN-β1a over PEG-IFN-β1a were tested.

Results. Based on results of the systematic review, four articles were selected wherein the results of phase 3 clinical trial of PEG-IFN-β1a and phase 2–3 clinical trial of SamPEG-IFN-β1a were described. In PEG-IFN-β1a group (n = 512) the agent was administered once every 2 weeks, in SamPEGIFN-β1a group (n = 114) the agent was administered at a dose of 240 μg. The analysis results confirmed the hypothesis of SamPEG-IFN-β1a non-inferiority to PEG-IFN-β1a in efficacy, while SamPEG-IFN-β1a superiority over PEG-IFN-β1a in efficacy was not confirmed. The hypothesis of SamPEG-IFN-β1a superiority over PEG-IFN-β1a in safety was also confirmed based on a significantly lower incidence of SAEs and any AEs that led to treatment discontinuation.

Conclusions. The proportion of patients with relapses and the ARR in 1 year and in 2 years of therapy indicates that SamPEG-IFN-β1a is non-inferior to PEG-IFN-β1a in efficacy. SamPEG-IFN-B1a demonstrated a more favourable safety profile than PEG-IFN-B1a as showing less odds of SAEs and AEs leading to treatment discontinuation.

About the authors

Taras O. Simaniv

Research Center of Neurology

Author for correspondence.
Email: simaniv@neurology.ru
ORCID iD: 0000-0001-7256-2668

Cand. Sci. (Med.), senior researcher, 6th Neurological department, Institute of Clinical and Preventive Neurology

Russian Federation, Moscow

Maria N. Zakharova

Research Center of Neurology

Email: simaniv@neurology.ru
ORCID iD: 0000-0002-1072-9968

D. Sci. (Med.), principal researcher, Head, 6th Neurological department, Institute of Clinical and Preventive Neurology

Russian Federation, Moscow

Kirill V. Sapozhnikov

Kirov Military Medical Academy

Email: simaniv@neurology.ru
ORCID iD: 0000-0002-2476-7666

Cand. Sci. (Med.), lecturer, Department of automated medical systems

Russian Federation, Saint Petersburg

Daria G. Tolkacheva

North-West Institute of Management, Russian Presidential Academy of National Economy and Public Administration

Email: simaniv@neurology.ru
ORCID iD: 0000-0002-6314-4218

independent expert of research projects, Project office

Russian Federation, Saint Petersburg

Valeria D. Sokolova

Monash University

Email: simaniv@neurology.ru
ORCID iD: 0000-0001-7335-4852

researcher, Health Economics Group School of Public Health and Preventive Medicine

Australia, Melbourne

Natalia A. Sableva

North-West Institute of Management, Russian Presidential Academy of National Economy and Public Administration

Email: simaniv@neurology.ru
ORCID iD: 0000-0002-5809-9221

independent expert of research projects, Project office

Russian Federation, Saint Petersburg

Olga N. Mironenko

North-West Institute of Management, Russian Presidential Academy of National Economy and Public Administration

Email: simaniv@neurology.ru
ORCID iD: 0000-0001-8952-8386

Cand. Sci. (Econ.), independent expert of research projects, Project office

Russian Federation, Saint Petersburg

Taras V. Khimich

North-West Institute of Management, Russian Presidential Academy of National Economy and Public Administration

Email: simaniv@neurology.ru
ORCID iD: 0000-0003-2482-2108

independent expert of research projects, Project office

Russian Federation, Saint Petersburg

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Supplementary files

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1. JATS XML
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2. Appendix 3. Results of risk-of-bias assessment, modified sample including all the patients who received at least 1 dose of the treatment
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3. Fig. 1. SamPEG-IFN-β1a vs PEG-IFN-β1a: odds ratio for relapses of multiple sclerosis.

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4. Fig. 2. SamPEG-IFN-β1a vs PEG-IFN-β1a: annualized relapse rate. IRR — incidence rate ratio.

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5. Fig. 3. SamPEG-IFN-β1a vs PEG-IFN-β1a: odds ratio for various categories of adverse events. *Statistically significant difference.

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6. Appendix 1. Search strategy
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7. Appendix 2. Overview of search results
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8. Appendix 3. Results of risk-of-bias assessment, modified sample including all the patients who received at least 1 dose of the treatment
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Copyright (c) 2024 Simaniv T.O., Zakharova M.N., Sapozhnikov K.V., Tolkacheva D.G., Sokolova V.D., Sableva N.A., Mironenko O.N., Khimich T.V.

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