In:
JAMA Ophthalmology, American Medical Association (AMA), Vol. 141, No. 5 ( 2023-05-01), p. 459-
Abstract:
Dry eye disease (DED) is a common public health problem with significant impact on vision-related quality of life and well-being of patients. Medications with rapid onset of action and a good tolerability profile remain an unmet need. Objective To assess efficacy, safety, and tolerability of a water-free cyclosporine ophthalmic solution, 0.1% (CyclASol [Novaliq GmbH]), applied twice daily in DED compared with vehicle. Design, Setting, and Participants CyclASol for the Treatment of Signs and Symptoms of Dry Eye Disease (ESSENCE-2) was a phase 3, multicenter, randomized, double-masked, vehicle-controlled clinical study conducted from December 5, 2020, to October 8, 2021. Following a 14-day run-in period with an artificial tear administered 2 times per day, eligible participants were randomly assigned 1:1 to the treatment groups. Patients with moderate to severe DED were included in the study. Interventions Cyclosporine solution vs vehicle administered 2 times per day for 29 days. Main Outcomes and Measures The primary end points were changes from baseline in total corneal fluorescein staining (tCFS; 0-15 National Eye Institute scale) and in dryness score (0-100 visual analog scale) at day 29. Conjunctival staining, central corneal fluorescein staining, and tCFS responders were also assessed. Results A total of 834 study participants were randomly assigned to cyclosporine (423 [50.7%]) or vehicle (411 [49.3%] ) groups at 27 sites. Participants had a mean (SD) age of 57.1 (15.8) years, and 609 (73.0%) were female individuals. The majority of participants self-identified in the following race categories: 79 Asian (9.5 %), 108 Black (12.9%), and 635 White (76.1%). Participants treated with cyclosporine solution had greater improvement in tCFS (−4.0 grades) than the vehicle group (−3.6 grades) at day 29 (change [∆] = −0.4; 95% CI, −0.8 to 0; P = .03). The dryness score showed treatment benefits from baseline in both groups: −12.2 points for cyclosporine and −13.6 points for vehicle (∆ = 1.4; 95% CI, −1.8 to 4.6; P = .38). In the cyclosporine group, 293 participants (71.6%) achieved clinically meaningful reductions of 3 grades or higher in tCFS vs 236 (59.7%) in the vehicle group (∆ = 12.6%; 95% CI, 6.0%-19.3%; P & amp;lt; .001). These responders showed greater improvement in symptoms at day 29 including dryness (∆ = −4.6; 95% CI, −8.0 to −1.2; P = .007) and blurred vision (Δ = −3.5; 95% CI, −6.6 to −4.0; P = .03) compared with nonresponders. Conclusions and Relevance The ESSENCE-2 trial confirmed that treatment with a water-free cyclosporine solution, 0.1%, results in early therapeutic effects on the ocular surface compared with vehicle. The responder analyses suggest that the effect is clinically meaningful in 71.6% of participants in the cyclosporine group. Trial Registration ClinicalTrials.gov Identifier: NCT04523129
Type of Medium:
Online Resource
ISSN:
2168-6165
DOI:
10.1001/jamaophthalmol.2023.0709
Language:
English
Publisher:
American Medical Association (AMA)
Publication Date:
2023
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