Efficacy and safety of follitropin alpha biosimilars compared to their reference product: a Meta-analysis

Abstract

Aim

Recently published multicentre, randomized phase III studies suggested the therapeutic equivalence of biosimilar follitropin alpha medicaments compared to the reference product. The aim of this meta-analysis is to pool the results of the three phase III trials in order to provide an overall analysis about the clinical bioequivalence between biosimilars and the originator.

Methods

The studies included in the analysis were pooled together in order to estimate the log odds ratio (OR) for binary outcomes and the weighted mean difference (WMD) for continuous outcomes along with the corresponding 95% confidence intervals (CI) by using a random effects model. The heterogeneity between the studies was evaluated with the Higgins and Chi-square tests.

Results

No differences were found in term of number of oocytes retrieved at ovum pick-up, the primary endpoint recommended by the European Medicines Agency. No statistical differences were also found for biochemical pregnancy rate, take home baby rate, total follitropin alpha dose, duration of stimulation, and OHSS risk. A significantly higher clinical pregnancy rate (p = .03) was observed in the originator group in comparison to the biosimilar follitropin alpha.

Conclusion

Biosimilar follitropin alpha medicaments resulted comparable in comparison to the reference product with respect to the number of oocytes retrieved, that is the primary endpoint recommended by the European Medicines Agency .Further study is needed to evaluate the therapeutic bioequivalence between follitropin alpha biosimilar and the reference medication with respect to secondary endpoints.

摘要

目的：最近发表的多中心、随机的III期研究表明, 与参照药物相比, 促卵泡素α生物仿制药的疗效相同。这项荟萃分析的目的是汇集三个III期临床试验的结果, 以提供关于生物仿制药和原药之间临床生物等效性的全面分析。方法：采用随机效应模型, 将纳入分析的研究汇集在一起, 估计二元结果的对数优势比(OR)和连续结果的加权平均差值(WMD)以及相应的95%可信区间(CI)。研究之间的异质性用Higgins和卡方检验进行评估。结果：在欧洲药品管理局推荐的主要终点--取卵时取卵的数量方面没有发现差异。在生化妊娠率、带回家的婴儿比率、总促卵泡素α剂量、刺激持续时间和OHSS风险方面也没有统计学差异。与促卵泡素α的生物仿制药相比, 原药组的临床妊娠率明显更高(p=.03)。结论：与欧洲药品管理局推荐的主要终点相比, 促卵泡素α的生物仿制药在获取卵子的数量方面与其参照药物具有可比性, 就次级终点而言, 促卵泡素α生物仿制药与其参照药物的治疗生物等效性还需要进一步的研究。

Keywords:

• Follitropin alpha
• follitropin alpha biosimilars
• controlled ovarian stimulation
• therapeutic bioequivalence
• assisted reproductive technology

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

All the authors contributed toward the construction of the study. MCB and GMT performed the search and collected data. SF and MDM collected data and performed statistical analyses. All authors contributed to manuscript drafting and critical discussion of the manuscript. All authors read and approved the manuscript.