Efficacy and tolerability of fixed-combination bimatoprost/timolol versus fixed-combination dorzolamide/brimonidine/timolol in patients with primary open-angle glaucoma or ocular hypertension: a multicenter, prospective, crossover study

Alfonso García-López, José A Paczka, Jesús Jiménez-Román, Curt Hartleben, Alfonso García-López, José A Paczka, Jesús Jiménez-Román, Curt Hartleben

Abstract

Background: Fixed-combination ocular hypotensives have multiple advantages, but triple-therapy dorzolamide/brimonidine/timolol (dorz/brim/tim) is only available in Latin and South America, and information on its relative efficacy is limited. This study compares the efficacy and tolerability of fixed-combination bimatoprost/timolol (bim/tim) and dorz/brim/tim in Mexican patients with primary open-angle glaucoma or ocular hypertension.

Methods: In this investigator-masked, crossover study, patients with unmet target intraocular pressure (IOP) on once-daily bim/tim or twice-daily dorz/brim/tim received the opposite medication for 3 months before returning to their pre-baseline medication for 3 months. IOP was evaluated before and after morning instillation at months 2, 3, 5 and 6. Primary endpoints were mean IOP change and Ocular Surface Disease Index© (OSDI) score at each visit. The intent-to-treat population was the a priori analysis population, but due to the number of discontinuations, the per-protocol and intent-to-treat populations were used for the primary efficacy and sensitivity analyses, respectively.

Results: Seventy-eight and 56 patients were included in the intent-to-treat and per-protocol populations, respectively. At month 3, statistically significant IOP reductions from baseline were observed in the bim/tim (P < 0.01) and dorz/brim/tim (P < 0.0001) groups, regardless of assessment time. At month 6, patients returned to bim/tim exhibited no significant IOP increase (regardless of assessment time), but patients returned to dorz/brim/tim exhibited a statistically significant IOP increase (P < 0.001) when assessed before instillation of study treatment. Results were similar in both intent-to-treat and per-protocol analysis populations. In the per-protocol analysis, 70% of patients on bim/tim at month 3 had an IOP <14 mm Hg, which declined to 58% (P = 0.0061) at month 6 (ie, after 3 months of dorz/brim/tim treatment). In patients receiving dorz/brim/tim at month 3, 38% had an IOP <14 mm Hg, which remained comparable after return to bim/tim. OSDI scores and incidence of adverse events were similar in both groups.

Conclusions: In this first direct comparison of the efficacy of dorz/brim/tim and bim/tim, patients switched from dorz/brim/tim to bim/tim demonstrated improved/lower IOP; when returned to dorz/brim/tim, IOP increased to levels seen at study initiation, suggesting that once-daily bim/tim may have greater IOP-lowering efficacy. Both bim/tim and dorz/brim/tim were well tolerated with minimal ocular surface damage.

Trial registration: ClinicalTrials.gov: NCT01737853 (registered October 9, 2012).

Figures

Figure 1
Figure 1
Study design. No assessments were performed at months 1 and 4. Bim/tim, bimatoprost 0.03% and timolol maleate 0.5%; dorz/brim/tim, dorzolamide 2%, brimonidine 0.2%, and timolol maleate 0.5%; IOP, intraocular pressure.
Figure 2
Figure 2
Mean IOP at baseline, month 2, and month 3 following the baseline crossover (ITT population). A. Mean IOP ± SD in Group 1. B. Mean IOP ± SD in Group 2. Bim/tim, bimatoprost 0.03% and timolol maleate 0.5%; dorz/brim/tim, dorzolamide 2%, brimonidine 0.2%, and timolol maleate 0.5%; IOP, intraocular pressure; ITT, intent-to-treat; SD, standard deviation.
Figure 3
Figure 3
Mean IOP at months 3, 5 and 6 following the 3-month crossover (ITT population). A. Mean IOP ± SD in Group 1. B. Mean IOP ± SD in Group 2. Bim/tim, bimatoprost 0.03% and timolol maleate 0.5%; dorz/brim/tim, dorzolamide 2%, brimonidine 0.2%, and timolol maleate 0.5%; IOP, intraocular pressure; ITT, intent-to-treat; SD, standard deviation.
Figure 4
Figure 4
Mean OSDI scores over the course of the study (n = 78). The change in OSDI score (± SE) over time was not statistically significant in either group (P > 0.1). Bim/tim, bimatoprost 0.03% and timolol maleate 0.5%; dorz/brim/tim, dorzolamide 2%, brimonidine 0.2%, and timolol maleate 0.5%; OSDI, Ocular Surface Disease Index; SE, standard error.

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Pre-publication history
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