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

Br J Ophthalmol. 2019 Jan;103(1):125-131. doi: 10.1136/bjophthalmol-2017-311801. Epub 2018 Mar 15.

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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cyclosporine / adverse effects
  • Cyclosporine / therapeutic use*
  • Double-Blind Method
  • Dry Eye Syndromes / drug therapy*
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Logistic Models
  • Male
  • Middle Aged
  • Ophthalmic Solutions
  • Visual Acuity

Substances

  • Immunosuppressive Agents
  • Ophthalmic Solutions
  • Cyclosporine