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Research Article
14 May 2026

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

Authors: Stephen Pflugfelder https://orcid.org/0000-0002-9341-3482 [email protected], Tony Okoro https://orcid.org/0009-0007-6522-2199, Margaret Ainslie-Garcia https://orcid.org/0000-0002-5678-1227, Anja Haltner https://orcid.org/0000-0002-9829-7791, Emily K Prentiss https://orcid.org/0009-0008-6314-5908, Elizabeth M Salvo-Halloran https://orcid.org/0000-0002-1850-9855, Nikethana Srikanth https://orcid.org/0009-0005-4548-8374, Michelle Senchyna https://orcid.org/0009-0000-8909-6843, and Esen K AkpekAuthor Info & Affiliations
Volume 15, Number 6
https://doi.org/10.57264/cer-2026-0032
PDFFormats

Abstract

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.

Plain language summary

A statistical comparison of two prescription eye drops (acoltremon 0.003% and cyclosporine 0.05%) for increasing tear production in patients with eye disease.

What is the article about?

Dry eye disease (DED) is generally associated with a deficiency in the quantity and/or quality of tears. We compared how well acoltremon 0.003% and cyclosporine 0.05% increase tear production in adults with DED.

What was the methodology used?

As there are no direct comparison trials between acoltremon 0.003% and cyclosporine 0.05%, we used a matching-adjusted indirect comparison approach using patient-level data for acoltremon 0.003% and published population data for cyclosporine 0.05%. This method reweights individual patient data from the acoltremon 0.003% trials to match published summary cyclosporine 0.05% data. This ensures the two groups are as similar as possible for a fair comparison. A categorized Schirmer test score was used as a measure of tear production, and we considered the average difference in the change from baseline in categorized Schirmer’s test result at day 90 for each treatment as the main end point in this analysis.

What were the results?

Our results suggest that after 90 days on the therapies, patients using acoltremon 0.003% had significantly greater tear production than patients using cyclosporine 0.05%, with a mean difference of 1.62 categories for the Schirmer test score.

Why is this important?

These results support acoltremon 0.003% as a valuable treatment option for the signs and symptoms of DED.

Supplementary Material

File (supplementary data.docx)

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