title: Treatment carryover impacts on effectiveness of intraocular pressure lowering agents, estimated by a discrete event simulation model.
abstract: OBJECTIVE
  To compare the effectiveness of two treatment sequences, latanoprost-latanoprost timolol fixed combination (L-LT) versus travoprost-travoprost timolol fixed combination (T-TT), in the treatment of open-angle glaucoma (OAG) or ocular hypertension (OHT).
  
  
  METHODS
  A discrete event simulation (DES) model was constructed. Patients with either OAG or OHT were treated first-line with a prostaglandin, either latanoprost or travoprost. In case of treatment failure, patients were switched to the specific prostaglandin-timolol sequence LT or TT. Failure was defined as intraocular pressure higher than or equal to 18 mmHg at two visits. Time to failure was estimated from two randomized clinical trials. Log-rank tests were computed. Linear functions after log-log transformation were used to model time to failure. The time horizon of the model was 60 months. Outcomes included treatment failure and disease progression. Sensitivity analyses were performed.
  
  
  RESULTS
  Latanoprost treatment resulted in more treatment failures than travoprost (p<0.01), and LT more than TT (p<0.01). At 60 months, the probability of starting a third treatment line was 39.2% with L-LT versus 29.9% with T-TT. On average, L-LT patients developed 0.55 new visual field defects versus 0.48 for T-TT patients. The probability of no disease progression at 60 months was 61.4% with L-LT and 65.5% with T-TT.
  
  
  CONCLUSIONS
  Based on randomized clinical trial results and using a DES model, the T-TT sequence was more effective at avoiding starting a third line treatment than the L-LT sequence. T-TT treated patients developed less glaucoma progression.
authors.affiliation: Hopital Edouard Herriot, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: Denis
authors.forename: C
authors.initials: C
authors.lastname: Le Pen
authors.forename: D
authors.initials: D
authors.lastname: Umuhire
authors.forename: G
authors.initials: G
authors.lastname: Berdeaux
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003008:Cloprostenol / Q000031:analogs & derivatives / Q000627:therapeutic use; D003198:Computer Simulation; D018450:Disease Progression; D004338:Drug Combinations; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009798:Ocular Hypertension / Q000188:drug therapy; D011336:Probability; D011461:Prostaglandins F, Synthetic / Q000627:therapeutic use; D013999:Timolol / Q000627:therapeutic use; D014065:Tonometry, Ocular; D000069557:Travoprost; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; D011461:Prostaglandins F, Synthetic; D003008:Cloprostenol; D000077338:Latanoprost; D013999:Timolol; D000069557:Travoprost