Tolerance and Adherence to Cationic 0.1% Cyclosporine in Ocular Graft-versus-Host Disease

Abstract

Introduction: Anti-inflammatory, topical therapy of severe keratitis in dry eye disease (DED) and ocular graft-versus-host disease (oGvHD) includes steroids, cyclosporine (Cs), and others. In Germany, a commercial product containing 0.1% Cs in a cationic formulation is available since 2015. Objective: The aim of this study was to present real-life data using cationic 0.1% Cs in oGvHD patients. Methods: This was a retrospective study of 26 oGvHD and 41 DED patients with corneal staining of at least Oxford grade III. Parameters analyzed were Ocular Surface Disease Index, corneal staining, intraocular pressure, tear film break-up time, Schirmer, and visual acuity. In addition, it was evaluated how different Cs formulations were tolerated. Results: Corneal staining improved significantly in 1 eye in DED but not in oGvHD. In DED, cationic 0.1% Cs was not tolerated by 32% of the patients, in contrast to 0.05% Cs in castor oil not tolerated by 47% and liposomal 0.05% Cs by 63%. In oGvHD patients, cationic 0.1% Cs was not tolerated by 62%, 0.05% Cs in castor oil by 33%, and liposomal 0.05% Cs by 39% of the patients. Conclusions: This study demonstrates differences between the tolerance of different Cs formulations depending on the underlying cause of severe keratitis. Cationic 0.1% Cs is considerably less tolerated in oGvHD, and its use should be considered with care.

Real-World Effectiveness, Tolerability and Safety of Cyclosporine A 0.1% Cationic Emulsion in Severe Keratitis and Dry Eye Treatment

“…Eye pain and irritation were the most frequently reported treatment-related AEs in the current study, and this is also true for previously published randomized trials [ 20 – 24 , 27 ]. While previous studies highlight that some populations may experience tolerability issues (particularly discomfort/pain at the site of instillation), just 31 participants (6.6% of the FAS) withdrew from the PERSPECTIVE study due to poor local tolerance, which was also slightly lower than the proportion withdrawing due to ocular treatment-related AEs in the SANISKA/SICCANOVE pooled analysis (9.3%) [ 20 , 32 – 34 ].…”

“…This resulted in the inclusion of a heterogenous study population, which is reflective of routine clinical practice but may present challenges when comparing treatment outcomes against those from randomized trials examining CsA 0.1% CE use in a homogenous and stringently selected group [ 21 – 24 ]. Nonetheless, as demonstrated in previously published retrospective and observational analyses, real-world studies enable factors such as treatment tolerance to be examined at a practical level to improve understanding regarding those patients who may be best suited to CsA 0.1% CE therapy as well as those who would benefit from a different approach [ 25 , 32 , 34 ]. In accordance with usual clinical practice in the real-world setting, patients were allowed to continue AT therapy throughout the study, which could have contributed to the healing of the corneal surface and the therapeutic effect observed with CsA 0.1% CE treatment.…”

“…While CsA 0.1% CE has been shown to be generally well tolerated in clinical studies, some retrospective analysis and pre-clinical data indicate that tolerance may be reduced/low in certain populations (e.g. ocular graft vs. host disease), with pain/irritation at the site of installation being the main adverse event (AE) and reason for discontinuation reported [ 20 – 24 , 28 , 32 – 34 ].…”

Recent advances in ocular graft-versus-host disease

“…Among these, cationic 0.1% CSA is considerably less tolerated. Common intolerable symptoms include burning sensations, redness, conjunctival and lid swelling, and itching ( 94 ). Tacrolimus, with a mechanism of action similar to that of cyclosporine, is more effective than CSA ( 95 ).…”

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

“…Most commonly used symptom parameters 41,42,[55][56][57][58][59][60][61][62]74,82,88,89,92 Least commonly used symptom parameters 41,42,55,56,58,62,88,89 Most commonly used sign parameters 41,42,[55][56][57][58][59][60][61][62][63][64]72,74,82,88,89,92 Least commonly used sign parameters 41,42,[55][56][57][58]62,89 Although studies have shown that the majority of patients and physicians (60-80%) are satisfied overall with topical CsA in DED, 95,…”