Dataset Information

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

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.

Systematic review registration

PROSPERO CRD42019137152 and CRD42019137155.

SUBMITTER: Ascef BO

PROVIDER: S-EPMC8286602 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Total glucosides of paeony (TGP) is a natural plant extract, which is widely used in China for treating rheumatoid arthritis (RA). Many relevant randomised controlled trials (RCTs) of TGP for RA are available, but they have not been systematically reviewed. This systematic review aims to examine the effectiveness and safety of TGP in patients with RA.We will search for RCTs of TGP in the treatment of RA, performed up until February 2016, in PubMed, Embase, Cochrane Central Register of Controlled Trials, and four Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Database and Chinese Scientific Journal Database). Trial registers and reference lists of retrieved articles will also be searched to identify potential articles. RCTs comparing TGP with placebo, no treatment, or disease-modifying antirheumatic drugs for patients with RA will be retrieved. The primary outcomes will be disease improvement and disease remission. The secondary outcomes will be surrogate outcomes, symptoms, adverse effects, and quality of life. Two reviewers will independently extract data on participants, interventions, comparisons, outcomes, etc. The methodological quality of each included study will be evaluated using the Cochrane risk of bias tool, and the strength of evidence on prespecified outcomes will be assessed in accordance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Review Manager 5.3 software will be used for data analyses. Meta-analyses will be performed if the data are sufficiently homogeneous, both statistically and clinically. Possible publication bias will also be checked using funnel plots once the number of included studies is sufficient.Ethics approval is not required, as this study will not involve patients. The results of this study will be submitted to a peer-reviewed journal for publication, to inform both clinical practice and further research.CRD42015026345.