Ascef Bruna O, Almeida Matheus O, de Medeiros Ribeiro Ana Cristina, Andrade Danieli C O, de Oliveira Júnior Haliton A, Pereira Tiago V, de Soárez Patrícia C
Programa de Pós-Graduação em Saúde Coletiva, Departamento de Medicina Preventiva, Faculdade de Medicina - FMUSP, Universidade de São Paulo, São Paulo, SP, Brazil.
Programa de Pós-Graduação em Fisioterapia, Universidade Ibirapuera, São Paulo, SP, Brazil.
Syst Rev. 2021 Jul 17;10(1):205. doi: 10.1186/s13643-021-01754-x.
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).
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.
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.
PROSPERO CRD42019137152 and CRD42019137155.
阿达木单抗、依那西普和英夫利昔单抗等生物药物是类风湿关节炎（RA）患者主要的一线和二线治疗药物。然而，其高昂的成本给全球医疗系统带来了巨大负担。这些生物制剂专利的到期推动了生物类似药的生产，生物类似药成本可能更低，且与参照药物分子极为相似，尽管并非完全相同。本文旨在概述一项系统评价的方案，该评价将调查生物类似药与生物制剂相比的疗效和安全性概况（目标1）以及生物类似药与参照生物制剂之间的转换对RA患者管理的影响（目标2）。
我们将调查阿达木单抗、依那西普和英夫利昔单抗的任何生物类似药对RA患者的影响。我们将纳入随机对照试验（RCT）或准RCT以评估疗效和安全性结局，并纳入具有两部分或多部分设计的RCT以评估从参照生物制剂转换为生物类似药（反之亦然）的后果。将通过MEDLINE（通过PubMed）、EMBASE、LILACS和CENTRAL（从创刊至2021年4月）进行电子检索。两名独立的评审员将筛选研究、提取数据并评估偏倚风险。将根据等效性试验和转换研究的特定领域进行评估。将采用随机效应模型，以相对风险或标准化均数差作为指标来获得汇总估计值。主要结局将是根据美国风湿病学会20（ACR20）标准的治疗成功率，共同主要结局将是健康评估问卷残疾指数（HAQ-DI）。结论将基于使用从一组经验丰富的风湿病学家和先前研究中得出的预定义等效界值进行的等效性假设检验。将根据GRADE系统评估证据的总体确定性。
本研究提出了一种全面的、以临床医生为导向的方法，以评估生物类似药与生物制剂之间的等效性以及转换对RA患者管理的影响。我们的结果将阐明生物类似药在RA管理中的疗效、安全性、免疫原性，以及用生物类似药替代生物制剂的临床后果。
PROSPERO CRD42019137152和CRD42019137155。
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