Comparative Efficacy and Safety of Biosimilars and Reference Biologics for Treatment of Non-Infectious Uveitis
Authors: Tina Felfeli1 Natalie Kozlowski2, Felicia Tai3, Jorge R. Georgakopoulos4, Elizabeth Uleryk, Rafael N. Miranda5, 6. 1Temerty Faculty of Medicine, University of Toronto, 2Division of Ophthalmology, McMaster University, 3University of Toronto, 4E/M Uleryk Consulting, 5Toronto Health Economics and Technology Assessment (THETA) Collaborative, University Health Network, 6Department of Ophthalmology and Vision Sciences, University of Toronto.
Author Disclosures: N. Kozlowski: None. F. Tai: None. J.R. Georgakopoulos: None. E. Uleryk: None. R.N. Miranda: None. T. Felfeli: None.
Abstract Body:
Purpose: Systemic biologics have high clinical value in the management of non-infectious uveitis (NIU). The high cost and recent expiry of patents of biologics has prompted the development of similar versions of drugs, termed biosimilars. The bioequivalence of biosimilars has allowed for omission of rigorous clinical trials, hindering clarity in their risk of safety and efficacy when switching from reference biologics to biosimilars in systemic diseases including NIU. The study aims to compare the efficacy and safety of reference biologics and their biosimilars in the treatment of NIU.
Study Design: Systematic review and meta-analysis.
Methods: A comprehensive search of the literature was conducted in Ovid MEDLINE, Ovid EMBASE and Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from inception until October 7, 2021 (PROSPERO protocol #: CRD42021283386). Eligible studies included adults or pediatrics with NIU, and any type of biosimilar or biologic. Risk of bias and quality of evidence within studies was assessed using ROBINS-I and GRADE, respectively. A meta-analysis with random-effects models using the Mantel-Haenszel method was performed and a p-value of <0.05 was considered statistically significant.
Results: Overall, 5,450 studies were reviewed, 9 of which met the inclusion criteria. This included a total of 243 patients with NIU with an average age of 41.4 years. Of the 9 studies, 7 were retrospective and 2 were prospective. A meta-analysis comparing biosimilars to reference biologics was conducted, where the relative risk of treatment recurrence for biosimilars was 0.711 (p=0.357); the mean difference in final logMAR visual acuity between biosimilar and reference biologics was -0.036 (p=0.6616), and; the mean difference in glucocorticoid-sparing effect of biosimilar to reference biologics was -7.153 mg/day (p=0.142). In terms of safety outcomes, the risk ratio of ophthalmic, minor systemic, and major systemic adverse events was 1.025 (p=0.974), 1.282 (p=0.418), and 1.241 (p=0.739), respectively. The risk ratio for drug discontinuation due to lack of efficacy, adverse events and other reasons was 2.606 (p=0.194), 1.223 (p=0.717) and 1.450 (p=0.688), respectively. With regards to quality assessment, the majority of studies received a rating of “serious” risk due to biases from confounding, as well as a GRADE assessment of “low” quality due to the risk of bias present.
Conclusions: There is low quality evidence available, which suggests biosimilars are statistically comparable in terms of efficacy and safety to their reference biologics in treating NIU.
