title: Efficacy of a preservative-free formulation of fixed-combination bimatoprost and timolol (Ganfort PF) in treatment-naïve patients vs previously treated patients.
abstract: OBJECTIVE
  To evaluate, using subgroup analysis, the effect of treatment status on the intraocular pressure (IOP)-lowering efficacy of a preservative-free formulation of fixed-combination bimatoprost 0.03%/timolol 0.5% (FCBT PF).
  
  
  METHODS
  A primary, multicenter, randomized, double-masked, 12-week study compared the efficacy and safety of FCBT PF with preserved FCBT (Ganfort(®)) in 561 patients diagnosed with glaucoma or ocular hypertension. For this analysis, eligible patients were treatment-naïve or had inadequate IOP lowering and underwent a washout of previous treatment. IOP (8 am, 10 am, and 4 pm) was measured at baseline and weeks 2, 6, and 12. Subgroup analysis of the FCBT PF arm assessed changes in average eye IOP from baseline in treatment-naïve vs previously treated patients. To evaluate the effect of treatment status at baseline (treatment-naïve vs previously treated) on IOP reduction in the FCBT PF treatment group, an analysis of covariance model was used with treatment status and investigator as fixed effects, and baseline average eye IOP, age, glaucoma diagnosis, and baseline average eye corneal thickness as covariates. P-values and the 95% confidence intervals were determined using the model.
  
  
  RESULTS
  In the FCBT PF arm, IOP mean changes from baseline ranged from -8.7 mmHg to -9.8 mmHg in treatment-naïve patients (N=50), compared with -7.3 mmHg to -8.5 mmHg in previously treated patients (N=228). Baseline IOP, age, glaucoma diagnosis, and corneal thickness significantly affected IOP reduction in the FCBT PF group. Adjusting for these covariates, FCBT PF had a greater IOP-lowering effect (0.8-1.7 mmHg) in treatment-naïve patients than previously treated patients, which was statistically significant (P≤0.05) at seven of nine time points.
  
  
  CONCLUSIONS
  In this subgroup analysis, FCBT PF reduced IOP more effectively in treatment-naïve than in previously treated patients possibly due, in part, to altered responsiveness or tachyphylaxis that has been associated with prior ocular hypotensive agent treatment.
authors.affiliation: Western Eye Hospital, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: M Francesca
authors.initials: MF
authors.lastname: Cordeiro
authors.affiliation: Discipline of Ophthalmology, University of Sydney, Sydney, NSW, Australia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Goldberg
authors.affiliation: Allergan, Inc., Irvine, CA, USA.
authors.forename: Rhett
authors.initials: R
authors.lastname: Schiffman
authors.affiliation: Allergan, Inc., Irvine, CA, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Bernstein
authors.affiliation: Allergan, Inc., Irvine, CA, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Bejanian
keywords: benzalkonium chloride; bimatoprost; glaucoma; intraocular pressure; ocular hypertension; timolol