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Abstract #60538 Published in IGR 16-4
A Model-Based Dose-Response Meta-Analysis of Ocular Hypotensive Agents as a Drug Development Tool to Evaluate New Therapies in Glaucoma
Raber S; Mandema JW; Li H; Nickens DJJournal of Ocular Pharmacology and Therapeutics 2015; 31: 189-197
PURPOSE: To characterize dose and response for intraocular pressure (IOP) reduction and incidence of hyperemia using a model-based meta-analysis of IOP-lowering monotherapy studies to evaluate new ocular antihypertensive therapies for glaucoma. METHODS: Published randomized controlled trials, regulatory documents, and sponsor reports of IOP-lowering monotherapies were used to develop dose-response models to characterize efficacy (IOP change from baseline) and safety (incidence of hyperemia) profiles. RESULTS: The meta-analysis for efficacy included 31 trials with 6,516 patients receiving bimatoprost, latanoprost, travoprost, timolol, or placebo. Estimated IOP reduction with placebo was -2.01 mmHg. Maximal IOP reduction was similar among the prostaglandin analogs (estimate, -6.27 mmHg; baseline, 25 mmHg). Estimated median effective IOP-lowering dose (ED50) was 0.002%, 0.00098%, and 0.00063% daily with bimatoprost, latanoprost, and travoprost, respectively. The hyperemia (safety) analysis included 25 trials with 6,244 patients. Typical maximal estimated difference between drug and placebo was 43%, and estimated ED50 of 0.011%, 0.014%, and 0.0015% daily for bimatoprost, latanoprost, and travoprost, respectively. Latanoprost treatment was predicted to incur the lowest rate of hyperemia of the prostaglandins, for equivalent IOP reduction. CONCLUSIONS: Model-based meta-analyses for IOP reduction and incidence of hyperemia among prostaglandin analogs are well described by maximal efficacy models and can provide a useful methodology for evaluating glaucoma therapies.
1 Pfizer Inc. , San Diego, California.
Full articleClassification:
3.8 Pharmacology (Part of: 3 Laboratory methods)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
