Cargando…
Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial
IMPORTANCE: 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 tolerabili...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Medical Association
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10080403/ https://www.ncbi.nlm.nih.gov/pubmed/37022717 http://dx.doi.org/10.1001/jamaophthalmol.2023.0709 |
_version_ | 1785020914907217920 |
---|---|
author | Akpek, Esen K. Wirta, David L. Downing, Johnathon E. Tauber, Joseph Sheppard, John D. Ciolino, Joseph B. Meides, Alice S. Krösser, Sonja |
author_facet | Akpek, Esen K. Wirta, David L. Downing, Johnathon E. Tauber, Joseph Sheppard, John D. Ciolino, Joseph B. Meides, Alice S. Krösser, Sonja |
author_sort | Akpek, Esen K. |
collection | PubMed |
description | IMPORTANCE: 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 < .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 |
format | Online Article Text |
id | pubmed-10080403 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Medical Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-100804032023-04-08 Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial Akpek, Esen K. Wirta, David L. Downing, Johnathon E. Tauber, Joseph Sheppard, John D. Ciolino, Joseph B. Meides, Alice S. Krösser, Sonja JAMA Ophthalmol Original Investigation IMPORTANCE: 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 < .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 American Medical Association 2023-04-06 2023-05 /pmc/articles/PMC10080403/ /pubmed/37022717 http://dx.doi.org/10.1001/jamaophthalmol.2023.0709 Text en Copyright 2023 Akpek EK et al. JAMA Ophthalmology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the CC-BY-NC-ND License. |
spellingShingle | Original Investigation Akpek, Esen K. Wirta, David L. Downing, Johnathon E. Tauber, Joseph Sheppard, John D. Ciolino, Joseph B. Meides, Alice S. Krösser, Sonja Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial |
title | Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial |
title_full | Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial |
title_fullStr | Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial |
title_full_unstemmed | Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial |
title_short | Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial |
title_sort | efficacy and safety of a water-free topical cyclosporine, 0.1%, solution for the treatment of moderate to severe dry eye disease: the essence-2 randomized clinical trial |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10080403/ https://www.ncbi.nlm.nih.gov/pubmed/37022717 http://dx.doi.org/10.1001/jamaophthalmol.2023.0709 |
work_keys_str_mv | AT akpekesenk efficacyandsafetyofawaterfreetopicalcyclosporine01solutionforthetreatmentofmoderatetoseveredryeyediseasetheessence2randomizedclinicaltrial AT wirtadavidl efficacyandsafetyofawaterfreetopicalcyclosporine01solutionforthetreatmentofmoderatetoseveredryeyediseasetheessence2randomizedclinicaltrial AT downingjohnathone efficacyandsafetyofawaterfreetopicalcyclosporine01solutionforthetreatmentofmoderatetoseveredryeyediseasetheessence2randomizedclinicaltrial AT tauberjoseph efficacyandsafetyofawaterfreetopicalcyclosporine01solutionforthetreatmentofmoderatetoseveredryeyediseasetheessence2randomizedclinicaltrial AT sheppardjohnd efficacyandsafetyofawaterfreetopicalcyclosporine01solutionforthetreatmentofmoderatetoseveredryeyediseasetheessence2randomizedclinicaltrial AT ciolinojosephb efficacyandsafetyofawaterfreetopicalcyclosporine01solutionforthetreatmentofmoderatetoseveredryeyediseasetheessence2randomizedclinicaltrial AT meidesalices efficacyandsafetyofawaterfreetopicalcyclosporine01solutionforthetreatmentofmoderatetoseveredryeyediseasetheessence2randomizedclinicaltrial AT krossersonja efficacyandsafetyofawaterfreetopicalcyclosporine01solutionforthetreatmentofmoderatetoseveredryeyediseasetheessence2randomizedclinicaltrial |