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

Abstract

BackgroundFixed-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.MethodsIn 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.ResultsSeventy-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.ConclusionsIn 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 registrationClinicalTrials.gov: NCT01737853 (registered October 9, 2012)

Efficacy and safety of different regimens for primary open‐angle glaucoma or ocular hypertension: a systematic review and network meta‐analysis

“…2012; Garcia‐Lopez et al. 2014). Some studies showed that triple therapy provides stronger IOP lowering effect, while some studies show that it is weaker than dual therapy.…”

A Phase III Randomized Clinical Trial of a 0.5% Timolol + 0.2% Brimonidine + 2.0% Dorzolamide Fixed Combination, Preservative-Free Ophthalmic Solution vs. 0.5% Timolol + 0.2% Brimonidine + 2.0% Dorzolamide Fixed Combination in Patients with Controlled Primary Open-Angle Glaucoma

“…As mentioned above, topical therapies are often necessary to prevent the progression of glaucoma-related optic nerve damage, and here fixed combinations may be more beneficial than therapy with concomitant single agents. In accordance with this, KOF proved to be well tolerated and to have minimal harmful effects on the ocular surface [ 21 ].…”

“…In addition, the impact of tolerability on therapeutic adherence becomes a factor that contributes to the effectiveness of prolonged therapies. Previous clinical trials have demonstrated the efficacy of the triple-fixed combination KOF in treating POAG [ 17 , 21 , 22 ]. However, the preservative agent included in this formulation could potentially decrease tear film stability by altering the lipid component of the tear and perhaps produce dry eye syndrome by affecting the evaporative mechanism, producing irritation of the ocular surface [ 15 , 23 ].…”

Additive and combined glaucoma therapy: principles and practice

“…Такая предопределенность может быть связана и с высокой вероятностью нарушений режима инстилляций со стороны пациента на всех этапах лечения. Многочисленные исследования доказали, что применение группы АПГ является наиболее эффек-тивным способом медикаментозной монотерапии глаукомы в плане 24-часового контроля уровня ВГД, а различия между препаратами внутри этой группы остаются незначительными [13][14][15][16][17][18][19][20].…”

“…ст. соответственно [19]. Данные результаты были установлены при мониторировании уровня офтальмотонуса в течение 90 сут наблюдения и отличались статистической достоверностью (р < 0,001).…”