Dataset Information

One-Year Efficacy and Safety of 0.1% Cyclosporine a Cationic Emulsion in the Treatment of Severe Dry Eye Disease.

ABSTRACT: PURPOSE:The SANSIKA study evaluated the efficacy/safety of 0.1% (1 mg/mL) cyclosporine A cationic emulsion (CsA CE) for treating dry eye disease (DED) with severe keratitis. The double-masked phase demonstrated that CsA CE was effective in reducing corneal damage and ocular surface inflammation, and was well-tolerated over 6 months. Here we report efficacy and safety findings of SANSIKA's open-label extension (OLE). METHODS:In this multicenter, double-masked, phase III study, patients with severe DED (corneal fluorescein staining [CFS] grade 4, modified Oxford scale) were randomized to once-daily CsA CE (Ikervis®) or its vehicle for 6 months, followed by 6-month open-label, once-daily CsA CE (CsA CE/CsA CE and vehicle/CsA CE groups). RESULTS:A total of 177 patients completed the OLE. Efficacy results reiterated the double-masked phase: CsA CE reduced CFS score and human leukocyte antigen-antigen D related expression, improved corneal clearing, and produced continuous improvements in global symptom scores (ocular surface disease index [OSDI], visual analogue scale). The CFS-OSDI response rates (?2 CFS points, ?30% OSDI improvement vs baseline) at 12 vs 6 months were 39.1% vs 28.6%, respectively, for CsA CE/CsA CE and 38.0% vs 23.1% for vehicle/CsA CE. Cyclosporine A CE's safety profile was similar to the initial 6 months. The most common treatment-related treatment-emergent adverse event was instillation site pain (7.8%, CsA CE/CsA CE group; 19.0%, vehicle/CsA CE group). No unexpected safety signals were observed; systemic CsA levels were undetectable/negligible in all patients except 2 previously treated with systemic CsA. CONCLUSIONS:In this 12-month study, once-daily CsA CE was well-tolerated and showed reductions in ocular surface inflammation and improvements in signs/symptoms in DED patients with severe keratitis.

SUBMITTER: Baudouin C

PROVIDER: S-EPMC6380090 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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One-Year Efficacy and Safety of 0.1% Cyclosporine a Cationic Emulsion in the Treatment of Severe Dry Eye Disease.

Baudouin Christophe C de la Maza Maite Sainz MS Amrane Mourad M Garrigue Jean-Sébastien JS Ismail Dahlia D Figueiredo Francisco C FC Leonardi Andrea A

European journal of ophthalmology 20171101 6

<h4>Purpose</h4>The SANSIKA study evaluated the efficacy/safety of 0.1% (1 mg/mL) cyclosporine A cationic emulsion (CsA CE) for treating dry eye disease (DED) with severe keratitis. The double-masked phase demonstrated that CsA CE was effective in reducing corneal damage and ocular surface inflammation, and was well-tolerated over 6 months. Here we report efficacy and safety findings of SANSIKA's open-label extension (OLE).<h4>Methods</h4>In this multicenter, double-masked, phase III study, pati ...[more]

PMID: 28708219

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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:Purpose:Preservative-free cationic emulsion-based artificial tears (ATs) or drug vehicles are innovative eye drop formulations with tear film stabilization and drug delivery properties, and valuable in vivo anti-inflammatory and wound healing properties. These ATs have recently reached the market as ATs for the management of dry eye disease (DED) symptoms (i.e., Cationorm) or as a drug vehicle for cyclosporine (Ikervis). The aim of the present study was to explore the mechanism of action underlying the intrinsic anti-inflammatory and wound-healing efficacies harbored by the cationic emulsions of cetalkonium chloride (CE-CKC). Methods:The anti-inflammatory activity of two CE-CKC (0.002% and 0.005% CKC) emulsions was evaluated by assessing the expression of proinflammatory genes and the secretion of various markers in the following human cell types stressed by different agents: peripheral blood mononuclear cells (PBMCs; stimulation with anti-CD3/anti-CD28 or lipopolysaccharide (LPS)), CD4+ T lymphocytes (TCD4; stimulation with anti-CD3/anti-CD28), and a human corneal epithelial cell line (HCE-2; stimulation with LPS). The cells were incubated for 30 min with a 10% dilution of CE-CKC emulsions and then cultured without the emulsions for 24 h or 72 h in the presence of the various challenging agents. The supernatant was collected, and the secreted markers quantitated with flow cytometry or an enzyme-linked immunosorbent assay (ELISA). Gene expression of inflammatory markers was evaluated only in the PBMCs and HCE-2 cells stimulated with LPS. The in vitro protein kinase C (PKC) binding assay for IC50 determination was performed using standard procedures. Results:The CE-CKC emulsions decreased inflammatory gene expression in LPS-stimulated PBMCs (IFN-?, IL-17A, CXCL-9, and TNF?) and LPS-stimulated HCE-2 cells (THBS1 and CCL2). Both CE-CKC emulsions inhibited the secretion of IL-17 (from anti-CD3/anti-CD28-stimulated TCD4), TNF?, IFN-?, and IL-2 (from anti-CD3-/anti-CD28-stimulated PBMCs), and IL-6 and IL-8 (from LPS-stimulated HCE-2). The in vitro PKC binding assay revealed that CKC, the cationic agent, is a specific PKC? inhibitor. In addition, tyloxapol, another excipient, showed some anti-inflammatory activity on IL-6 and IL-8 in the LPS-stimulated HCE-2 cells. Conclusions:This study indicates that the CE-CKC emulsions are able to directly modulate the secretion and expression of proinflammatory cytokines and chemokines. The results also suggest that CKC and tyloxapol are pharmacologically active excipients with potentially beneficial effects in vivo. These data shed new light on the efficacy observed on the DED signs of these CE-CKC emulsions in clinical trials.

Project description:Background: The 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.Methods: TreeAge 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).Results: Over 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.Conclusion: Based 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.

Dataset Information

One-Year Efficacy and Safety of 0.1% Cyclosporine a Cationic Emulsion in the Treatment of Severe Dry Eye Disease.

Publications

One-Year Efficacy and Safety of 0.1% Cyclosporine a Cationic Emulsion in the Treatment of Severe Dry Eye Disease.

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