Efficacy and safety of 0.1% ciclosporin A cationic emulsion in dry eye disease: a pooled analysis of two double-masked, randomised, vehicle-controlled phase III clinical studies

Abstract

Background/aim: To assess the treatment effect of 0.1% ciclosporin A cationic emulsion (CsA CE) versus vehicle on signs/symptoms of dry eye disease (DED) in various subgroups (moderate-to-severe DED/severe DED/Sjögren's syndrome (SS)/SS with severe DED).

Methods: Pooled data were analysed from two similar phase III studies: SICCANOVE (moderate-to-severe DED) and SANSIKA (severe DED with severe keratitis). In both studies, patients aged ≥18 years received CsA CE 0.1% (n=395) or vehicle (n=339) once daily for 6 months. A composite responder efficacy endpoint (corneal fluorescein staining-Ocular Surface Disease Index (CFS-OSDI) at month 6) was used to evaluate the efficacy of CsA CE in alleviating signs/symptoms of DED (response defined as improvement of ≥2 grades in CFS and ≥30% in OSDI (baseline to month 6)). Human leucocyte antigen-DR (HLA-DR) conjunctival expression was used as a biomarker of ocular surface inflammation.

Results: CsA CE-treated patients were significantly more likely to be CFS-OSDI responders than vehicle-treated patients in the overall (OR 1.66, 95% CI 1.11 to 2.50; P=0.015), severe DED (1.80, 1.04 to 3.19; P=0.038) and SS with severe DED (3.37, 1.20 to 11.19; P=0.030) populations. The difference was not significant for CsA CE versus vehicle for the overall Sjögren's population (OR 1.77, CI 0.89 to 3.66; P=0.109). CsA CE also significantly reduced median HLA-DR expression versus vehicle at 6 months (P=0.002).

Conclusion: Pooled phase III data indicate CsA CE produced significant improvement in signs/symptoms versus vehicle in patients with moderate-to-severe DED (especially in those with severe keratitis), including patients with SS with severe DED.

Keywords: ocular surface; tears; treatment medical.

Conflict of interest statement

Competing interests: AL is a consultant for, or has received a research grant from, Allergan, Alcon, MediVis, Santen, SIFI and Théa and was an investigator in the SICCANOVE and SANSIKA studies. EMM is a consultant for, or has received speaker honoraria from, Alcon Pharma GmbH, Dompé, Pharm-Allergan GmbH, Santen GmbH, Shire, Théa Pharma GmbH, TRB Chemedica AG, Ursapharm and VISUfarma and was an investigator in the SICCANOVE study. ML is a consultant for, or has received a research grant from, Alcon, Allergan, Bausch & Lomb, Dompé, Santen and Théa and was an investigator in the SICCANOVE and SANSIKA studies. MA is an employee of Santen SAS. J-SG is an employee of Santen SAS. DI is an employee of Santen SAS. MS-d-l-M is a consultant for Santen and was an investigator in the SICCANOVE and SANSIKA studies. FCF is a consultant for, or has received a research grant from, Allergan, Théa and Santen and was an investigator in the SICCANOVE and SANSIKA studies. CB is a consultant for, or has received a research grant from, Alcon, Allergan, Santen and Théa and was a clinical investigator in the SICCANOVE and SANSIKA studies.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

CFS–OSDI responder rates in the pooled analysis. *Statistically significant difference for CsA CE versus vehicle (P

Figure 2

Pooled analysis and individual study results for the effect of CsA CE in improving both signs and symptoms (assessed by CFS–OSDI responder rate) in (A) all patients, (B) patients with severe DED, (C) all patients with SS and (D) patients with SS and severe DED at baseline. A response was defined as improvement of ≥2 grades in CFS and ≥30% in OSDI. CFS, corneal fluorescein staining; CsA CE, 0.1% (1 mg/mL) ciclosporin A in a cationic emulsion; DED, dry eye disease; FAS, full analysis set; OSDI, Ocular Surface Disease Index; SS, Sjögren’s syndrome.

Figure 3

Change from baseline in CFS score at month 6 by patient subgroup in the pooled analysis (n=629). Green boxes represent the estimate of the difference between groups (least-squares means). Horizontal lines are 95% confidence limits. CFS, corneal fluorescein staining; CL, confidence limit; CsA CE, 0.1% (1 mg/mL) ciclosporin A in a cationic emulsion; LCL, lower confidence limit; UCL, upper confidence limit; VEH, vehicle.

Figure 4

Pooled analysis of the relationship between CFS score and HLA-DR expression (as assessed by impression cytology). AUF, arbitrary units of fluorescence; CFS, corneal fluorescein staining; CsA CE, 0.1% (1 mg/mL) ciclosporin A in a cationic emulsion; HLA-DR, human leucocyte antigen-DR.