Effect of Cyclosporine Ophthalmic Solution 0.09% on Signs and Symptoms of Dry Dye Disease in Patients Inadequately Controlled on Cyclosporine Ophthalmic Emulsion 0.05%: Results from a Single-Arm, Open-Label, Phase 4 Study

Purpose: Cyclosporine ophthalmic emulsion 0.05% (CsA 0.05%) and cyclosporine ophthalmic solution 0.09% (CsA 0.09%) are approved to increase tear production in dry eye disease (DED). We investigated the effect of CsA 0.09% on DED signs and symptoms in patients whose disease was inadequately controlled on CsA 0.05%. In this Phase 4, single-arm, open-label study, adults with DED administered 1 drop of CsA 0.09% in both eyes twice daily for 12 weeks. Patients and Methods: Patients were ≥ 18 years of age with a history and clinical diagnosis of DED for ≥ 3 months, which was not adequately controlled by treatment with CsA 0.05%. The primary efficacy endpoints were mean changes from baseline in total corneal fluorescein staining (CFS) and modified Symptom Assessment iN Dry Eye (mSANDE) scores at Week 12. Secondary efficacy endpoints included mean changes from baseline in total conjunctival staining score, central CFS score, tear osmolarity, Schirmer test score, and frequency of artificial tear use at Week 12, and patient treatment preference at Week 12. Adverse events (AEs) were monitored. Results: The intent-to-treat population comprised 124 patients (mean age, 65.6 years). The mean changes from baseline in total CFS and mSANDE scores were statistically significant at Weeks 4, 8, and 12 (P < 0.0001 for all). At Week 12, statistically significant improvements from baseline were also noted for total conjunctival staining score, central CFS score, Schirmer test score, and artificial tear use frequency (P ≤ 0.0029), and 69.4% of patients preferred CsA 0.09%. Most AEs were mild. Conclusion: Treatment with CsA 0.09% elicited statistically significant improvement from baseline in DED signs and symptoms from Weeks 4 to 12 in patients inadequately controlled on CsA 0.05%. Overall, CsA 0.09% was well tolerated. The findings from this study suggest that switching from CsA 0.05% to CsA 0.09% may improve signs and symptoms in patients with DED.