Maximum Medical Therapy: Brinzolamide/Brimonidine And Travoprost/Timolol Fixed-Dose Combinations In Glaucoma And Ocular Hypertension (original) (raw)
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Journal of Ophthalmology, 2017
Objective. To evaluate the efficacy and safety of triple fixed-combination bimatoprost 0.01%/brimonidine 0.15%/timolol 0.5% (TFC) versus dual fixed-combination brimonidine 0.2%/timolol 0.5% (DFC) in primary open-angle glaucoma and ocular hypertension. Methods. Patients with intraocular pressure (IOP) ≥23 and ≤34 mmHg were randomized to twice-daily TFC or DFC. The primary variable is the change in worse eye mean IOP from baseline at week 12 (modified intent-to-treat (mITT) population). Secondary endpoints are mean IOP and mean change from baseline at weeks 1, 2, 4, 8, and 12 (mITT population). TFC superiority was demonstrated if the primary variable favored TFC (p ≤ 0 05). Sensitivity analyses were conducted, and safety was assessed at all visits. Results. TFC (n = 93) provided greater IOP reductions from baseline than DFC (n = 97) at week 12 (treatment difference, 0.85 mmHg; p = 0 028) and all other visits. TFC was also superior to DFC in patients with high baseline IOP (i.e., IOP ≥ 25 mmHg; p ≤ 0 011). Conjunctival hyperemia, ocular irritation, and dry eye were reported more often with TFC (p ≤ 0 016); however, discontinuations for ocular adverse events were similar between treatments. Conclusions. TFC demonstrated IOP-lowering benefits that outweigh the risk of predominantly mild ocular side effects, which may be particularly relevant in patients who require greater IOP lowering to prevent/delay disease progression. This trial is registered with ClinicalTrials.gov registry number: NCT01241240.
Clinical Ophthalmology, 2013
The aim of this study was to evaluate the safety and efficacy of a fixed combination of bimatoprost 0.03% and timolol (BTFC) in a clinical setting, in a large sample of patients with primary open-angle glaucoma or ocular hypertension and insufficient intraocular pressure (IOP) lowering on prior therapy. Methods: Patient data were combined (n = 5556) from five multicenter, observational, noncontrolled, open-label studies throughout Europe. Patients were identified from 830 sites in Austria, France, Germany, The Netherlands, and Switzerland. Assessments were made at baseline, 6 weeks (in Austrian, German and Swiss centers), and 12 weeks in all centers. Results: BTFC lowered mean IOP from baseline by 5.4 mmHg over the 12-week duration of the studies (P , 0.0001). At study entry, 92.9% of patients were receiving another ocular hypotensive medication. In patients with no previous treatment (n = 311), BTFC reduced IOP by −9.1 mmHg, corresponding to a reduction from baseline of 36.4% (P , 0.0001). In patients receiving prior therapy of a prostaglandin analog, a β-blocker, or a fixed combination, BTFC reduced IOP by a further 24.5%, 25.9%, and 21.4%, respectively. The majority of patients (90.3%) reported no adverse events. The most common adverse events were conjunctival hyperemia (3.2%) and eye irritation (2.8%). BTFC was rated as "good" or "very good" by 92.5% of physicians and 88.0% of patients. Most patients (96.3%) were equally or more compliant with BTFC than with their previous treatment. Conclusion: In routine clinical practice, BTFC achieved consistent IOP lowering in both previously treated and untreated patients with primary open-angle glaucoma or ocular hypertension. BTFC was associated with significant IOP reductions, good tolerability, and good compliance.
Ophthalmology, 2007
Three-month randomized, parallel-group, double-masked, multicenter clinical trial. Participants: Patients with primary open-angle glaucoma, exfoliation glaucoma, or ocular hypertension with intraocular pressure (IOP) Ͼ 18 mmHg on monotherapy with travoprost (N ϭ 163). Methods: Patients were randomized to receive adjunctive therapy with twice-daily brimonidine (N ϭ 79) or twice-daily brinzolamide (N ϭ 84). Treatment efficacy was assessed after 1 and 3 months of combination therapy. Intraocular pressure was measured at 8 AM, noon, and 4 PM at baseline (on travoprost monotherapy) and after 3 months of combination therapy. Mean diurnal IOP was defined as the average of the IOP measurements at these 3 time points. Adverse events were recorded at each visit. Main Outcome Measure: Difference between treatment groups in mean diurnal IOP at month 3, adjusted for difference in baseline IOP, using analysis of covariance. Results: Mean diurnal IOPs (Ϯ standard error of the mean) at baseline were 21.7Ϯ0.33 mmHg in the brimonidine group and 21.1Ϯ0.29 mmHg in the brinzolamide group (P ϭ 0.16). Mean diurnal IOPs at month 3 were 19.6Ϯ0.41 mmHg in the brimonidine group and 18.4Ϯ0.33 mm Hg in the brinzolamide group (P ϭ 0.019). At month 3, mean diurnal IOPs, adjusted for difference in baseline IOP, were 19.3Ϯ0.27 in the brimonidine group and 18.6Ϯ0.25 in the brinzolamide group (P ϭ 0.035). Conclusions: The combination of travoprost and brinzolamide was statistically significantly more efficacious than the combination of travoprost and brimonidine in lowering IOP. The clinical significance of this difference is uncertain.
Journal of Ocular Pharmacology and Therapeutics, 2011
Purpose: To investigate the intraocular pressure (IOP) lowering effect of bimatoprost (BIM) 0.03% and the potential additional effect of the BIM 0.03%/timolol 0.5% fixed combination (BTFC) in eyes with ocular hypertension, primary open-angle glaucoma, or exfoliation glaucoma. Methods: Following an appropriate washout period that varied with previous medication, participants with ocular hypertension, primary open-angle glaucoma, or exfoliation glaucoma were treated with evening-dosed BIM for 5 weeks. They were then given evening-dosed BTFC for another 5 weeks. One randomly selected eye was evaluated. Goldmann applanation tonometry was performed by the same investigator at 8 a.m., 12 noon, 4 p.m., and 8 p.m. at baseline and at the end of each treatment period. Results: Thirty-three participants completed the study. Three patients discontinued because of local adverse effects during the BIM treatment period. The mean diurnal IOP (mean AE SD) at baseline, on BIM, and on BTFC were 24.8 AE 5.4, 17.3 AE 3.5, and 14.9 AE 3.1 mmHg, respectively (repeated measures analysis of variance, P < 0.001 for all pairwise comparisons). The individual time-point IOP values showed similar significant reductions. The percentage of IOP reduction from baseline was 30.2% for BIM and 39.9% for the BTFC. The mean AE SD diurnal fluctuation at baseline was 6.8 AE 3.2 mmHg, which decreased to 4.0 AE 3.1 and 2.9 AE 1.4 mmHg on BIM and BTFC, respectively (P < 0.05 for both treatments versus baseline). Conclusions: Both BIM 0.03% and the BTFC were effective in lowering IOP in eyes with ocular hypertension and open-angle glaucoma. However, the fixed combination provided an additional statistically significant reduction in IOP compared with BIM 0.03%.
Brinzolamide/Brimonidine Fixed Combination: Simplifying Glaucoma Treatment Regimens
Ophthalmology and Therapy
Introduction: To simplify the medical treatment of glaucoma for patients on multiple drops by introducing brinzolamide/brimonidine tartrate fixed combination (BBFC) ophthalmic suspension 1%/0.2% (SIMBRINZA Ò ; Alcon Laboratories, Inc., Fort Worth, TX, USA) to the drop regimen and to establish its efficacy. To demonstrate that fixed combination (FC) therapies are associated with improvements in treatment adherence and persistence with reduced exposure to preservative-related ocular surface problems. Methods: Retrospective study: 76 patients were identified as taking BBFC following a switch in treatment regimen. Intraocular pressure (IOP) prior to and 2-17.5 months (average 5.4 months) after the introduction of BBFC was measured. The change in the average number of bottles used per eye was recorded. The rate of adverse effects (AEs) of BBFC was recorded. A two-tailed paired sample t test was used to compare IOP prior to and after the introduction of BBFC for each eye. Results: Mean change in IOP after BBFC introduction BBFC:-2.76 mmHg (p \ 0.0001). BBFC intolerance: 13%. On average there was a 0.24 reduction in the number of bottles of IOPlowering medication used per eye (p \ 0.0064). Conclusion: A switch to BBFC in the drop regimen is associated with a significant drop in IOP with reduced drop burden. Instead of a third IOP-lowering medication and bottle, a practitioner should consider using BBFC ? prostaglandin analogue/FC drop for effective IOP control, reduced drop burden, reduced preservative load and increased likelihood of adherence. This study promotes the concept that any treatment should principally be assessed from the patients' perspective and quality of life.
Eye, 2016
Purpose To determine whether intraocular pressure (IOP) lowering with fixed-combination brinzolamide/brimonidine (BBFC) adjunctive to a prostaglandin analog (PGA) was superior to that of vehicle+PGA in patients with open-angle glaucoma or ocular hypertension who were inadequately controlled with PGA monotherapy Methods This 6-week, multicenter, randomized, double-masked, parallel-group trial was conducted at 30 clinical sites in the United States between October 2013 and May 2014. Eligible patients were adults with open-angle glaucoma or ocular hypertension and with mean IOP ≥ 21 and o32 mm Hg, whereas receiving an open-label PGA (latanoprost, bimatoprost, or travoprost). Patients instilled a PGA once-daily in a run-in phase before randomization to masked BBFC or vehicle adjunctive treatment. Masked treatments were instilled 3 times daily for 6 weeks, and patients continued once-daily use of their PGA. The primary efficacy end point was the between-group difference in mean diurnal IOP (average of 0800, 1000, 1500, and 1700 hours time points) at week 6. Results At week 6, mean diurnal IOP with BBFC+PGA was lower than with vehicle +PGA (17.1 ± 0.4 mm Hg vs 20.5 ± 0.4 mm Hg; between-group difference, − 3.4 ± 0.5 mm Hg; Po0.0001; 95% confidence interval, − 4.5 to − 2.4 mm Hg). BBFC+PGA reduced mean diurnal IOP by 5.7 mm Hg (25%) from the baseline IOP achieved with PGA monotherapy. Conclusions Therapy with BBFC produced an additive IOP-lowering effect compared with a PGA alone or in conjunction with vehicle. BBFC may provide an effective treatment option for patients receiving PGA monotherapy who require additional IOP reduction.
British Journal of Ophthalmology, 2004
Purpose: To compare the intraocular pressure (IOP) reducing effect and safety of fixed combination (FC) latanoprost/ timolol with unfixed combination (UFC) brimonidine/timolol in patients with increased IOP. Methods: In this 6 month, randomised, evaluator masked, parallel group European study, patients with glaucoma or ocular hypertension and IOP >21 mm Hg on monotherapy or .16 mm Hg on dual therapy received either FC latanoprost/timolol at 8:00AM or UFC brimonidine/timolol at 8:00AM and 8:00PM. The primary outcome was the difference from baseline to month 6 in mean diurnal IOP reduction. Results: 325 of 334 randomised patients were included in intent to treat analyses (FC latanoprost/timolol, 163; UFC brimonidine/timolol, 162). Baseline diurnal IOP levels were similar: FC latanoprost/timolol, 26.4 (SD 2.7) mm Hg; UFC brimonidine/timolol, 26.5 (SD 2.8) mm Hg (p = 0.851). At month 6, levels were 16.9 (SD 2.8) mm Hg in FC latanoprost/timolol patients and 18.2 (SD 3.1) mm Hg in UFC brimonidine/timolol patients (p,0.001). No adverse events were reported by 76.4% and 75.5% of patients receiving FC latanoprost/timolol versus UFC brimonidine/ timolol, respectively. Larger proportions of brimonidine/ timolol treated patients reported study medication related adverse events (18.6% v 7.3%) and discontinued study participation because of this (10.8% v 1.8%). Conclusion: Fixed combination latanoprost/timolol administered once daily is both more effective and better tolerated than twice daily dosing with UFC brimonidine/timolol. T opical hypotensive medication is considered the treatment of choice in the initial management of increased intraocular pressure (IOP) in patients with glaucoma. 1 2 Target IOP levels are not always achieved with the use of one agent, however, and many patients require combination therapy. Several new and effective IOP lowering drugs have additive effects when used in combination with the b adrenergic receptor antagonist timolol. Latanoprost, the only prostaglandin analogue indicated for first line use as an ocular hypotensive in Europe and the United States, lowers IOP levels by increasing uveoscleral outflow with little or no effect on aqueous humour production, 7 8 while b blockers are believed to reduce aqueous humour formation. The concomitant administration of latanoprost and timolol produces an additive IOP reducing effect. 10 11 Because complex, multidrug regimens can reduce patient compliance, 12 13 a fixed formulation of latanoprost 0.005% and timolol 0.5% has been made available. Once daily administration of this combination is well tolerated and reduces IOP more effectively than either individual component alone in patients with open angle glaucoma and ocular hypertension. 5 14 15