title: 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: 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.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01737853 (registered October 9, 2012).
authors.affiliation: Fundación Hospital de Nuestra Señora de la Luz, Ezequiel Montes #135 C,P, 06030 Del, Cuauhtémoc, México City, D,F,, México. alfonsogarl@mac.com.
authors.forename: Alfonso
authors.initials: A
authors.lastname: García-López
authors.forename: José A
authors.initials: JA
authors.lastname: Paczka
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Román
authors.forename: Curt
authors.initials: C
authors.lastname: Hartleben
mesh_terms: D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069580:Bimatoprost; D000068438:Brimonidine Tartrate; D002940:Circadian Rhythm; D003008:Cloprostenol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy / Q000503:physiopathology; D009883:Ophthalmic Solutions; D011446:Prospective Studies; D011810:Quinoxalines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013999:Timolol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014065:Tonometry, Ocular; D016896:Treatment Outcome
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D004338:Drug Combinations; D009883:Ophthalmic Solutions; D011810:Quinoxalines; D013449:Sulfonamides; D013876:Thiophenes; D003008:Cloprostenol; D000068438:Brimonidine Tartrate; D013999:Timolol; C062765:dorzolamide; D000069580:Bimatoprost