Clinical Ophthalmology (Dec 2019)
Maximum Medical Therapy: Brinzolamide/Brimonidine And Travoprost/Timolol Fixed-Dose Combinations In Glaucoma And Ocular Hypertension
Abstract
S Fabián Lerner,1 Francesco Oddone,2 Da-Wen Lu,3 Ana Sanseau,4 Merce Guarro,5 Antonia Ridolfi,6 Douglas Hubatsch7 1Consultorio Oftalmológico Dr. Fabian Lerner And Facultad de Ciencias Médicas, Universidad Favaloro, Buenos Aires, Argentina; 2Glaucoma Research Unit, IRCCS – Fondazione Bietti, Rome, Italy; 3Department of Ophthalmology, Tri-Service General Hospital, Taipei, Taiwan, Republic of China; 4Instituto de la Visión, Ciudad de Buenos Aires, Argentina; 5Vallès Oftalmologia Recerca-OMIQ and Ophthalmology Department, Hospital de Granollers, Barcelona, Spain; 6Novartis Pharma S.A.S, Paris, France; 7Novartis Pharmaceutical Corporation, Fort Worth, TX, USACorrespondence: S Fabián LernerConsultorio Oftalmológico Dr. Fabián Lerner, Facultad de Ciencias Médicas, Universidad Favaloro, Marcelo T. De Alvear 2010, 2A, Buenos Aires C1122AAF, ArgentinaTel +54 11 4961-9258Email [email protected]: 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
