Matching-adjusted indirect comparison of acoltremon ophthalmic solution 0.003% and cyclosporine 0.05% ophthalmic emulsion for increased tear production in patients with dry eye disease

Aim: Dry eye disease (DED) is a chronic, multifactorial condition arising through loss of tear film and ocular surface homeostasis. Treatment aims to restore natural tear production and normalize ocular surface homeostasis. Several prescription medications are available in the US that increase tear production in patients with DED. In the absence of head-to-head trials, this study employed a matching-adjusted indirect comparison (MAIC) approach to estimate the comparative tear production efficacy of acoltremon 0.003% and cyclosporine 0.05% for the treatment of DED. Materials & methods: MAICs were conducted for the key outcome of categorized Schirmer test score (STS), where higher values indicate greater tear production. Patient data were available for acoltremon 0.003% (from COMET-2 and COMET-3 trials) and summary level data for cyclosporine 0.05%. Populations were matched on clinically relevant variables including age, race, sex and anesthetized categorized STS. The primary analysis compared mean change from baseline (CFB) categorized STS at day 90. An exploratory analysis investigated earlier onset of tear production (day 14) attributed to acoltremon 0.003% compared with the earliest available data (Day 90) for cyclosporine 0.05%. Results: After all adjustments, a greater mean CFB categorized STS was observed for acoltremon 0.003% compared with cyclosporine 0.05% (mean difference MD: 1.62 categories, 95% CI: 1.42–1.83, p < 0.001) at day 90. The exploratory analysis also demonstrated a greater mean CFB categorized STS for day 14 acoltremon 0.003% compared with day 90 cyclosporine 0.05% (MD: 1.62 categories, 95% CI: 1.42–1.82, p < 0.001). Conclusion: Our findings suggest that acoltremon 0.003% may provide a greater increase in tear production relative to cyclosporine 0,05% at day 90, with exploratory findings suggesting similar results at day 14. As this was an unanchored MAIC, results may be influenced by residual confounding from unmeasured differences between trials.