Maximum Medical Therapy: Brinzolamide/Brimonidine And Travoprost/Timolol Fixed-Dose Combinations In Glaucoma And Ocular Hypertension

Abstract

Introduction

Maximal medical therapy (MMT) is the use of ≥3 classes of topical anti-glaucoma agents to achieve maximal intraocular pressure (IOP) reduction while minimizing adverse effects and compliance challenges.

Purpose

To evaluate the additive IOP-lowering effect of twice-daily brinzolamide 1%/brimonidine 0.2% fixed-dose combination (BBFC) used adjunctively with once daily travoprost 0.004%/timolol 0.5% fixed-dose combination (TTFC) in patients with open-angle glaucoma (OAG)/ocular hypertension (OHT).

Methods

In this phase IV, double-masked study, patients on TTFC for ≥28 days, aged ≥18 years, with mean IOP ≥19 and ≤28 mmHg in at least 1 eye were randomized to receive BBFC+TTFC (n=67) or vehicle+TTFC (n=67) for 6 weeks. The primary endpoint was mean change in diurnal IOP from baseline (BL, averaged over 09:00 and 11:00) at Week 6.

Results

The study was terminated prematurely due to recruitment challenges. BL mean IOP was similar in both groups (BBFC+TTFC: 21.6±1.78 mmHg; vehicle+TTFC: 21.8±1.90 mmHg). Mean change in diurnal IOP from BL at Week 6 was greater with BBFC+TTFC (−4.25 mmHg, 95% confidence interval [CI]: −4.7, −3.8) than with vehicle+TTFC (−2.11 mmHg, 95% CI: −2.6, −1.6, treatment difference, −2.15 mmHg (95% CI: −2.8, −1.5; P<0.001). Ocular adverse events (AEs) were reported in 11.9% of patients given BBFC+TTFC and 7.5% of patients given vehicle+TTFC. The AE with highest frequency was punctate keratitis (3%) in the BBFC+TTFC group; eye irritation (3%) in the vehicle+TTFC group.

Conclusion

BBFC+TTFC as MMT demonstrated clinically relevant and statistically significant reductions in mean diurnal IOP in patients with OAG/OHT. AEs were consistent with known safety profiles of individual medications.

Keywords:

• brinzolamide/brimonidine fixed-dose combination
• travoprost/timolol fixed-dose combination
• open-angle glaucoma
• ocular hypertension
• IOP
• maximal medical therapy

Data Sharing Statement

The datasets generated during the current study are not publicly available due to ethical considerations but are available from the corresponding author on reasonable request.

Acknowledgments

The medical writing support and editorial assistance during the development of the manuscript was provided by Indumathy Pinnamaneni and Swati Bhandari (Novartis Healthcare Pvt. Ltd., Hyderabad, India). Dr Oddone’s work for this study was partly supported by the Italian Ministry of Health and by Fondazione Roma. The study was supported by Novartis Pharma AG, Basel and is registered with ClinicalTrials.gov as NCT02730871. The results of this study have been presented at: Lu et al Poster presented at the 34th Asia-Pacific Academy of Ophthalmology Congress, Bangkok, Thailand (6–9 March, 2019) and Lerner et al Poster presented at the 8th World Glaucoma Congress, Melbourne, Australia (27–30 March, 2019).

Disclosure

Fabian Lerner reports grants/research support/speaker fees from Allergan, Glaukos, Iridex, Novartis/Alcon. Francesco Oddone reports personal fees from Allergan, Centervue, Glaucoom and Omikron Italia, honoraria from Centervue, Glaucoom Omikron Italia and Santen, and unrestricted grants from Allergan and Omikron Italia. Ana Sanseau reports Honoraria and Consultation fees from Novartis, Alcon, Poen, Baush & Lomb, Speaker’s bureau: Novartis. Merce Guarro reports grants/research support from Novartis, Alcon, and Santen. Antonia Ridolfi and Doug Hubatsch are both employees of Novartis. The authors report no other conflicts of interest in this work.