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Published in: Systematic Reviews 1/2021

Open Access 01-12-2021 | Etanercept | Protocol

Equivalence and switching between biosimilars and reference molecules in rheumatoid arthritis: protocol for a systematic review and meta-analysis

Authors: Bruna O. Ascef, Matheus O. Almeida, Ana Cristina de Medeiros Ribeiro, Danieli C. O. Andrade, Haliton A. de Oliveira Júnior, Tiago V. Pereira, Patrícia C. de Soárez

Published in: Systematic Reviews | Issue 1/2021

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Abstract

Background

Biologic drugs such as adalimumab, etanercept, and infliximab represent major first-line and second-line treatments for rheumatoid arthritis (RA) patients. However, their high cost poses a massive burden on healthcare systems worldwide. The expiration of patents for these biologics has driven the production of biosimilar drugs, which are potentially less costly and remarkably similar, albeit not identical to the reference molecules. This paper aims to outline the protocol of a systematic review that will investigate the efficacy and safety profile of biosimilars compared to biologics (objective 1) and the impact of switching between biosimilar drugs and reference biologics on the management of RA patients (objective 2).

Methods

We will investigate the effects of any biosimilars of adalimumab, etanercept, and infliximab on RA patients. We will include randomized controlled trials (RCTs) or quasi-RCTs to assess efficacy and safety outcomes and RCTs with two- or multiple-part designs to evaluate the consequences of switching from reference biologics to biosimilar drugs (and vice-versa). Electronic searches will be performed through MEDLINE (via PubMed), EMBASE, LILACS, and CENTRAL (from inception to April 2021). Two independent reviewers will screen studies, extract data, and evaluate the risk of bias. The latter will be carried out considering specific domains from equivalence trials and switching studies. Random-effects models will be fitted to obtain summary estimates using either relative risk or standardized mean difference as a metric. The primary outcome will be the rate of treatment success according to the American College of Rheumatology 20 (ACR20), and the co-primary outcome will be the Health Assessment Questionnaire—Disability Index (HAQ-DI). Conclusions will be based on equivalence hypothesis testing using predefined margins of equivalence elicited from a group of experienced rheumatologists and prior studies. The overall certainty of the evidence will be assessed based on the GRADE system.

Discussion

The present investigation proposes a comprehensive, clinician-oriented approach to assess the equivalence and the impact of switching between biosimilars and biologics on the management of patients with RA. Our results will elucidate the efficacy, safety, immunogenicity of biosimilars, and the clinical consequences of substituting biologics with biosimilars in the management of RA.

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Appendix
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Metadata
Title
Equivalence and switching between biosimilars and reference molecules in rheumatoid arthritis: protocol for a systematic review and meta-analysis
Authors
Bruna O. Ascef
Matheus O. Almeida
Ana Cristina de Medeiros Ribeiro
Danieli C. O. Andrade
Haliton A. de Oliveira Júnior
Tiago V. Pereira
Patrícia C. de Soárez
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Systematic Reviews / Issue 1/2021
Electronic ISSN: 2046-4053
DOI
https://doi.org/10.1186/s13643-021-01754-x

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