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A randomized study of the efficacy and safety of 0.1% cyclosporine A cationic emulsion in treatment of moderate to severe dry eye.

ABSTRACT: PURPOSE:The SICCANOVE study aimed to compare the efficacy and safety of 0.1% cyclosporine A cationic emulsion (CsA CE) versus vehicle in patients with moderate to severe dry eye disease (DED). METHODS:In this multicenter, double-masked, parallel-group, controlled study, patients were randomized (1:1) to receive CsA CE (Ikervis®) or vehicle for 6 months. The co-primary efficacy endpoints at month 6 were mean change from baseline in corneal fluorescein staining (CFS; modified Oxford scale) and in global ocular discomfort (visual analogue scale [VAS]). RESULTS:The mean change in CFS from baseline to month 6 (CsA CE: n = 241; vehicle: n = 248) was significantly greater with CsA CE than with vehicle (-1.05 ± 0.98 and -0.82 ± 0.94, respectively; p = 0.009). Ocular discomfort improved similarly in both groups; however, the percentage of patients with ?25% improvement in VAS was significantly higher with CsA CE (50.2%) than with vehicle (41.9%; p = 0.048). In a post hoc analysis of patients with severe ocular surface damage (CFS score 4) at baseline (CsA CE: n = 43; vehicle: n = 42), the percentage of patients with improvements of ?2 grades in CFS score and ?30% in Ocular Surface Disease Index score was significantly greater with CsA CE (p = 0.003). Treatment compliance and ocular tolerability were satisfactory and as expected for CsA use. CONCLUSION:Cyclosporine A CE was well-tolerated and effectively improved signs and symptoms in patients with moderate to severe DED over 6 months, especially in patients with severe disease, who are at risk of irreversible corneal damage.

SUBMITTER: Baudouin C

PROVIDER: S-EPMC6380092 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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A randomized study of the efficacy and safety of 0.1% cyclosporine A cationic emulsion in treatment of moderate to severe dry eye.

Baudouin Christophe C Figueiredo Francisco C FC Messmer Elisabeth M EM Ismail Dahlia D Amrane Mourad M Garrigue Jean-Sébastien JS Bonini Stefano S Bonini Stefano S Leonardi Andrea A

European journal of ophthalmology 20170321 5

<h4>Purpose</h4>The SICCANOVE study aimed to compare the efficacy and safety of 0.1% cyclosporine A cationic emulsion (CsA CE) versus vehicle in patients with moderate to severe dry eye disease (DED).<h4>Methods</h4>In this multicenter, double-masked, parallel-group, controlled study, patients were randomized (1:1) to receive CsA CE (Ikervis®) or vehicle for 6 months. The co-primary efficacy endpoints at month 6 were mean change from baseline in corneal fluorescein staining (CFS; modified Oxford ...[more]

PMID: 28362054

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Project description:IntroductionThe PERSPECTIVE study evaluated, in routine clinical practice, the effectiveness, tolerability and safety of cyclosporine A (CsA) 0.1% cationic emulsion (CE) in controlling severe keratitis in adults with dry eye who remained insufficiently controlled despite artificial tear (AT) use.MethodsA prospective, multicenter, observational study was conducted at 44 ophthalmology clinics across Finland, Germany, Norway, Sweden and the UK. Adults treated with ATs for severe keratitis and dry eye received CsA 0.1% CE therapy (1 drop in both eyes at bedtime) and were followed up at weeks 4, 12 and 24 and at month 12. Primary endpoint was mean [standard deviation (SD)] change from baseline in corneal fluorescein staining (CFS; Oxford Grade Scale) at month 12 following CsA 0.1% CE initiation. Secondary endpoints examined ocular sign and symptom severity and adverse events (AEs).ResultsThe full analysis set included 472 adults (75.9% female). Mean (SD) age was 61.9 (15.41) years. Mean (SD) CFS score was significantly reduced from baseline [2.56 (1.10)] at month 12 [1.10 (SD 1.13); P < 0.0001]. CFS score reductions were statistically significant from week 4, with further incremental decreases reported at study visits through month 12 (P < 0.0001). Severity of eyelid and conjunctival erythema was significantly reduced from baseline at week 4 and maintained through month 12 (P < 0.001). Tear film breakup time increased significantly from baseline at all study visits through month 12 (P < 0.001). Ocular symptom severity was significantly reduced from baseline at all study visits through month 12 (P < 0.001). Overall, 101 treatment-related AEs were reported. Most were mild/moderate (83.6%) and resolved by month 12 (73.3%).ConclusionsIn routine clinical practice, CsA 0.1% CE provided statistically significant reductions in dry eye signs and symptoms. Improvements were seen at week 4 and maintained over 12 months. Treatment tolerability was good and consistent with previous CsA 0.1% CE clinical studies.Trial registrationEU PAS register number: EUPAS 22376.

Project description:ImportanceDry 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.ObjectiveTo 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 participantsCyclASol 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.InterventionsCyclosporine solution vs vehicle administered 2 times per day for 29 days.Main outcomes and measuresThe 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.ResultsA 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 relevanceThe 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 registrationClinicalTrials.gov Identifier: NCT04523129.

Project description:BackgroundDry eye disease (DED) is a chronic ocular surface disease that affects hundreds of millions of people worldwide. Although 0.05% cyclosporine ophthalmic emulsion (CsA OE) has long been prescribed in the U.S. for the treatment of DED, it is not commercially available in China. Our study aims to compare the efficacy and safety profile of 0.05% CsA OE versus vehicle in Chinese patients with moderate to severe DED.MethodsThis was a multicenter, randomized, double-masked, 2-parallel-arm, 3-month phase III study. Patients with moderate to severe DED were randomized to receive twice-daily 0.05% CsA OE or its vehicle, along with unpreserved hypromellose eye drops 3 times per day. Patients were followed up at day 7, 28, 56, and 84, as well as 2 weeks after the medications were discontinued for safety assessment.ResultsA total of 240 patients were randomized. The overall effective rate (OER) and efficacy index were significantly better in the CsA OE than vehicle group at all follow up times (all P < .05), and the OER of CsA OE and vehicle group at month 3 was 70.6% and 27.8%, respectively (P < .001) (primary endpoint). The patients in CsA OE group displayed a significant improvement in dry eye symptoms from day 28 and ocular surface test results from day 7 (all P < .05). The ocular surface disease index scores of 0.05% CsA OE treated patients were significantly better than those treated with vehicle control at day 56 and 84 (P = .0061 and <.001, respectively). Drug related adverse events (AEs) were recorded in 6(5%) and 3(2.5%) patients in the CsA OE and vehicle groups respectively (P = .4061) with ocular pain as the most frequently reported AEs, and it was mostly mild to moderate. There were no detrimental effects on visual acuity, intraocular pressure, or vital signs.ConclusionsTwice-daily instillation of 0.05% CsA OE was effective and well tolerated for the treatment of moderate to severe DED in Chinese population during the 3 months of the study.

Project description:BackgroundThe purpose is to perform a cost effectiveness analysis amniotic membrane vs. topical medications in the use of treating dry eye disease. A cost effectiveness analysis comparing amniotic membrane + other topical medications to topical cyclosporine A + other topical medications was evaluated using accepted decision tree modeling software.MethodsTreeAge Pro 2019 software was used to evaluate the base case costs over a one year timeframe. Sensitivity analysis was performed on those variables which had the greatest effect on choosing one therapy versus the other based on cost. Monte Carlo simulation was run 1,000 times to determine the most effective, least costly alternative. Costs were evaluated from a societal level (direct + indirect). Quality of life utility scores were evaluated using known time tradeoffs from prior studies (scale 0-1; with 1 being perfect vision).ResultsOver a one year timeframe, the base case demonstrated that amniotic membrane + topical medications was the less expensive alternative and provided for incremental utilities versus topical cyclosporine + other medications (Cost/utility: $18,275/0.78 vs. $20,740/0.74). If examining direct costs only, topical cyclosporine was the least expensive option over a one year timeframe: $4,112 vs. $10,300. Sensitivity analysis demonstrated that in order for topical cyclosporine to be the less expensive alternative the following variables would need to be: < 68 days productivity lost; < $161 productivity lost/day; > 79% of amniotic membrane implants would need to be re-implanted at month 4 (for whatever reason); > $2677 per amniotic membrane implant procedure (Medicare reimbursement rate); > 96% positive response to topical cyclosporine A at month 4; > 58% positive response to topical cyclosporine A at month 6 and; < 54% probability clinical improvement with amniotic membrane. Monte Carlo simulation demonstrated that amniotic membrane was the less costly, most effective alternative 91.5% of the time.ConclusionBased on improved outcomes using amniotic membrane, patient productivity was improved resulting in lower societal costs (less days lost from work). When considering the untoward effects of dry eye disease on societal costs, an improvement of the dry eye disease condition was accomplished most often with amniotic membrane.

Project description:PurposeTo compare the efficacy, safety, and tolerability of waterfree cyclosporine formulation (CyclASol) at 2 concentrations (0.1% and 0.05% of cyclosporine [CsA]) to vehicle when applied twice daily for 16 weeks in patients with dry eye disease (DED). An open-label Restasis (Allergan, Irvine, CA) arm was included to allow a direct comparison with an approved therapy.DesignAn exploratory phase II, multicenter, randomized, vehicle-controlled clinical trial, double-masked between CyclASol and vehicle with an open-label comparator.ParticipantsTwo hundred and seven eligible patients with a history of dry eye disease were randomized 1:1:1:1 to 1 of 4 treatment arms (CyclASol 0.05%, n = 51; CyclASol 0.1%, n = 51; vehicle, n = 52, and Restasis, n = 53).MethodsAfter a 2-week run-in period with twice-daily dosing of Systane Balance (Alcon, Fort Worth, TX), patients were randomized to the respective treatment arm and dosed twice daily for 16 weeks.Main outcome measuresThe study was set up to explore efficacy on a number of sign and symptom end points including total and subregion corneal fluorescein staining, conjunctival staining, visual analog scale (VAS) for dry eye symptoms VAS severity, and Ocular Surface Disease Index (OSDI) questionnaire.ResultsCyclASol showed a consistent reduction in corneal and conjunctival staining compared with both vehicle and Restasis over the 16-week treatment period, with an early onset of effect (at day 14). A mixed-effects model-based approach demonstrated that the CyclASol drug effect was statistically significant over vehicle (total corneal staining P < 0.1, central corneal staining P < 0.001, conjunctival staining P < 0.01). This model-based analysis suggests a significant CyclASol effect for OSDI as symptom parameter (P < 0.01). The numbers of ocular adverse events were low in all treatment groups.ConclusionsCyclASol showed efficacy, safety, and tolerability at 2 concentrations in moderate-to-severe DED. In a direct head-to-head against open-label Restasis, CyclASol was found to have an earlier onset of action, as early as after 2 weeks of treatment, in relieving the signs of DED, as measured by corneal and conjunctival staining. The central region of the cornea, an important area for visual function in dry eye sufferers, was shown to have the most benefit from treatment. Excellent safety, tolerability, and comfort profile supports this new CsA formulation as having a positive benefit-to-risk ratio.

Dataset Information

A randomized study of the efficacy and safety of 0.1% cyclosporine A cationic emulsion in treatment of moderate to severe dry eye.

Publications

A randomized study of the efficacy and safety of 0.1% cyclosporine A cationic emulsion in treatment of moderate to severe dry eye.

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