Topical ocular 0.1% cyclosporine A cationic emulsion in dry eye disease patients with severe keratitis: experience through the French early-access program

Abstract

PurposeThe objective of this study was to report the evaluation of efficacy and safety of cyclosporine A cationic emulsion (CsA CE) 0.1% for the treatment of severe keratitis in adults with dry eye disease (DED) in a French early-access program.MethodsPatients with DED and severe keratitis (corneal fluorescein staining [CFS] score of 3–5 on the Oxford scale and/or the presence of corneal lesions [filaments or ulcers]) were enrolled in a compassionate use program (Authorization for Temporary Use [ATU]) for once-daily CsA CE, which was approved by French health authorities prior to its registration. Efficacy and safety at 1, 3, 6, and 12-month follow-up visits were evaluated.ResultsThe ATU cohort (n=1,212; mean age =60.5 years; 79.5% female; 98.1% with severe keratitis; 74.5% with corneal lesions) consisted of 601 CsA-naïve patients and 611 patients treated previously with other CsA formulations. The primary DED etiology was Sjögren’s syndrome (48.7%). Clinical benefit could be discerned among 548 evaluable patients from months 1 to 12: keratitis improvement, 44.8% at month 1 and 42.1% at month 12; keratitis stabilization, 47.2% and 45.7%, respectively; symptom improvement, 47.2% and 48.6%; and symptom stabilization, 44.8% and 45.0%. Corneal clearing (CFS score =0) increased from 4.8% (month 1) to 11.4% (month 12). No unexpected safety concerns were identified; instillation site pain (10.2%) and eye irritation (7.8%) were the most common adverse events.ConclusionThe French ATU cohort provides supportive data on the clinical benefit of CsA CE in improving/stabilizing symptoms and corneal damage in DED patients with severe keratitis in real-world clinical practice.

Management of inflammation in dry eye disease: Recommendations from a European panel of experts

“…Data have showed that an initial response to CsA may be evident within the first month of treatment, demonstrated by measurable improvements in DED signs and symptoms. 43,[55][56][57][58][59][60][61][62]82 Furthermore, in the real-world setting, a statistically significant improvement (P < 0.0001) in the severity of CFS was reported at Week 4 in patients treated with topical CsA, which was maintained until Month 12. 83 It is recommended that the outcome measures used in clinical trials for DED should be selected carefully depending on the treatment being assessed, because the sensitivity of markers or signs differ considerably depending on the tested therapy and its mechanism of action.…”

“…Initial responses to CsA treatment may be evident within the first month of therapy, demonstrated by improvements in some signs and symptoms of DED, but are typically seen after 6-8 weeks. [41][42][43][55][56][57][58][59][60][61][62] These responses are usually maintained or further improved after 3-6 months of treatment. [41][42][43]55,56,[59][60][61][62][63][64] Administration of ATs 15-20 min before and/or after administration of CsA leads to significant improvements in the symptoms of burning, stinging and irritation previously experienced with CsA instillation.…”

“…[41][42][43][55][56][57][58][59][60][61][62] These responses are usually maintained or further improved after 3-6 months of treatment. [41][42][43]55,56,[59][60][61][62][63][64] Administration of ATs 15-20 min before and/or after administration of CsA leads to significant improvements in the symptoms of burning, stinging and irritation previously experienced with CsA instillation. 65…”

Impact of Attrition, Intercellular Shear in Dry Eye Disease: When Cells are Challenged and Neurons are Triggered

“…Its presence in human corneal epithelium is very important, as TSG-6, a multifunctional protein [ 91 ], has anti-inflammatory effects and appears to be capable of downregulating inflammatory response [ 92 ]. The external application of TSG-6 in the treatment of dry eye has shown promising effects [ 13 ], as well as the application of immunomodulators such as ICAM-1 inhibitors [ 93 , 94 , 95 , 96 , 97 ] and Cyclosporin-A [ 98 , 99 , 100 , 101 , 102 ].…”

Wenn Tränenersatzmittel nicht mehr ausreichen: die Bedeutung von Entzündungsprozessen beim Trockenen Auge. Praktische Aspekte einer antientzündlichen Therapie des Trockenen Auges

“…Bei den vorbehandelten Gruppen fand sich 12 Monate nach dem Therapiewechsel auf das kationische CsA 0,1 % eine Stabilisierung der subjektiven Symptome bei 46 % und eine Verbesserung bei 49 % der Patienten. Bei Patienten, die von einer Apothekenrezeptur auf CsA 0,1 % umgestellt wurden, zeigte sich bei 50 % eine Stabilisierung der Symptomatik und bei 50 % der Patienten eine Verbesserung [83]. Da jedoch keine direkten Vergleichsstudien der einzelnen Formulierungen von CsA vorliegen, sind derzeit keine Aussagen zu Unterschieden hinsichtlich der Wirksamkeit und der lokalen Verträglichkeit zwischen den einzelnen Formulierungen und Dosierungen von CsA möglich.…”