Collarette Elimination and Demodex Mite Eradication with Topical Lotilaner Ophthalmic Solution, 0.25%

Abstract

Purpose: To evaluate the efficacy of topical lotilaner ophthalmic solution, 0.25%, in patients with Demodex blepharitis. Methods: Eighteen adults with Demodex blepharitis, defined as >10 collarettes on the upper lid and/or mite density of ‡1.5 mites per lash (upper and lower), were treated bid for 42 days with the topical lotilaner ophthalmic solution, 0.25%. Contact lens wear, artificial eyelashes, and lid structural abnormalities were among the exclusion criteria. No other antibacterial, antiparasitic, or anti-inflammatory treatment or lid hygiene products were permitted. One eye of each patient was selected for analysis and assessed on day 7, 14, 28, and 42. Collarettes were graded at each visit, and mite density was evaluated by microscopy at each visit except day 7. Outcome measures were collarette elimination (£2 lashes with collarettes) and mite eradication (0 mites). Drop tolerability, adverse events, visual acuity, and slit-lamp biomicroscopy were assessed. Results: Collarette elimination was achieved in 13/18 participants (72.2%) by day 42. Mean collarette grade (upper lid) declined from 3.56 -0.17 to 0.28 -0.11. Mite eradication was achieved in 14/18 participants (77.8%) by day 42. Mean mite density decreased from 2.63 -0.39 to 0.12 -0.08 mites/lash. Participants reported good tolerability. Adverse events were mild and transient and did not result in treatment discontinuation. Conclusion: Six weeks of at-home topical therapy with the lotilaner ophthalmic solution, 0.25%, was effective in eliminating the most common objective signs of Demodex blepharitis, with a collarette elimination rate of 72% and mite eradication in 78% of eyes by day 42. ISRCTN registration #: 24398865

Lotilaner Ophthalmic Solution, 0.25%, for the Treatment of Demodex Blepharitis: Results of a Prospective, Randomized, Vehicle-Controlled, Double-Masked, Pivotal Trial (Saturn-1)

“…The collarette grading scale shown in Figure 1 was used in a previous phase 2a study 33 and was based on the groupings and/or scales used by Gao et al and Hosseini et al 22 , 39 The collarette grading scale used is a nonlinear scale with grades 2 to 4 representing much higher levels of Demodex infestation. For example, an improvement in the collarette grade from grade 3 to grade 1 can reflect a 90% reduction in the number of collarettes per lid.…”

“…34 , 35 Statistically significant reductions in collarette grade and mite density were reported, and the improvement observed during the treatment period was maintained for at least 2 months after treatment cessation. In the next 2 clinical trials, Io (n = 18) and Europa (n = 54), a longer treatment duration of 6 weeks was evaluated 33 , 36 where the additional treatment improved the outcomes. This study with 6 weeks of treatment in 421 patients confirms the findings of the previous Phase 2 studies.…”

“…12,29,30,49,50 Before this phase 2b/3 study, the study drug, topical lotilaner ophthalmic solution, 0.25%, has been extensively evaluated in several phase 2 clinical trials. [33][34][35][36] In the first 2 clinical trials, Mars (single-arm pilot study, n = 15) and Jupiter (vehicle-controlled study, n = 60), patients with Demodex blepharitis were treated with lotilaner ophthalmic solution, 0.25%, for 4 weeks and followed for an additional 2 months after treatment cessation. 34,35 Statistically significant reductions in collarette grade and mite density were reported, and the improvement observed during the treatment period was maintained for at least 2 months after treatment cessation.…”

“…31 Lotilaner is a well-characterized, highly lipophilic, antiparasitic agent that paralyzes and eradicates Demodex mites by selectively inhibiting parasite-specific g-aminobutyric acid chloride channels. 32 The safety and efficacy of lotilaner ophthalmic solution, 0.25% (TP-03, Tarsus Pharmaceuticals Inc, Irvine CA), has been evaluated previously in humans in 2 single-arm 33,34 and 2 vehicle-controlled phase 2 studies with sample sizes ranging from 15 to 60 patients. 35,36 In these studies, lotilaner ophthalmic solution, 0.25%, was found to be well-tolerated, safe, and effective in reducing collarettes and mite density after 28-day or 42-day treatment regimens, with 42-day treatment yielding greater improvements in collarette grade and Demodex density.…”

Delphi Panel Consensus Regarding Current Clinical Practice Management Options for Demodex blepharitis

“…Prior to the live meeting, 3 articles related to Demodex blepharitis treatment were sent to the panel as pre-reading material. [35][36][37] The articles chosen for distribution were published since the prior Delphi panel and had a focus on treatment and management of Demodex blepharitis. A video conference was then held to discuss aspects of DB management.…”