Comparison of seven cyclosporine A formulations for dry eye disease: A systematic review and network meta-analysis

Abstract

Background: Dry eye disease is a common ocular surface disease affecting tens of millions of people worldwide. It is characterized by an unstable tear film and increasing prevalence. Different commercial formulations of cyclosporine A for dry eye have been approved, however, it is still unclear whether the differences in formulations of these products will make a difference in clinical efficacy and safety.Methods: Randomized controlled trials of commercial cyclosporine A formulation for dry eye disease were searched in Pubmed, EMBASE, Scopus, and Cochrane controlled trials registries and Web of Science from inception till 1 December 2021. Independent literature screening, data extraction, quality evaluation, and the study in line with quality standards were analyzed by using Stata16.0 software. The study is registered with PROSPERO under the number CRD42022301423. Code and data for this study is publicly available (https://github.com/DongYangGao/Dongyang.github.io.git).Results: 21 randomized clinical trials with a total of 4,107 participants were included in this study. Restasis® (OR-4.82, 95% CI-6.18 to 3.45, SUCRA 77.2%) was the most effective commercial formulation for reducing OSDI, Zirun® (SUCRA 73.9%) performed better in improving Schirmer’s test. TJ Cyporin® (SUCRA 65.3%) ranked first in terms of improving tear film break-up time. For treatment-emergent adverse events incidence, Clacier® was close to placebo. The risk of reporting bias is considered low.Conclusion: In the comparison of outcomes included in this study, the optimal order of various commercial cyclosporine A formulations is different, so it is difficult to select the optimal formula. Appropriate commercial formulations should be selected according to patients’ conditions in clinical practice.

NLRP3 Inflammasome as a Potential Therapeutic Target in Dry Eye Disease

“…The release of free surfactants from the breakdown of the emulsion may also cause irritation to the ocular surface [ 124 ]. Several new commercialised formulations have been developed to address challenges with user tolerance and low bioavailability of cyclosporin A in the form of Restasis ® (Allergan, an AbbVie company, Madison, NJ, USA), including Ikervis ® (Santen Pharmaceuticals Co., Ltd., Osaka, Japan) and Vevye ® (Novaliq GmbH, Heidelberg, Germany) [ 125 ].…”

Updates on Biodegradable Formulations for Ocular Drug Delivery

“…Topical CsA is an effective treatment for DED for its anti-inflammatory properties, with several FDA-approved non-biodegradable formulations available, such as Restasis ® (CsA 0.05%, Allergan Inc, Irvine, CA, USA), Ikervis ® (CsA 1 mg/mL, Santen Pharmaceutical, Osaka, Japan), and Cequa ® (CsA 0.09%, Sun Pharma, Cranbury, NJ, USA) [ 91 , 108 , 109 ]. In the past decade, biodegradable drug delivery systems have been studied to enhance the therapeutic effect of CsA ( Table 1 ).…”

Biodegradable Polymer-Based Drug-Delivery Systems for Ocular Diseases

“…Topical CsA, a fungal metabolite, has gained attention due to its anti-inflammatory characteristics, which presumably stem from its capability to inhibit T-cell activation through interleukin-2. Several FDA-approved CsA-based eye drop formulations such as Restasis ® , Ikervis ® , Cequa ® , and CyclASol ® have proven effective in alleviating symptoms and signs related to DED [ 155 , 217 , 218 ]. Significant efforts have been dedicated in recent times to leverage biodegradable DDSs to enhance the therapeutic efficacy of CsA.…”