title: Responder analysis of a randomized comparison of the 13.3 mg/24 h and 9.5 mg/24 h rivastigmine patch.
abstract: BACKGROUND
  OPtimizing Transdermal Exelon In Mild-to-moderate Alzheimer's disease (OPTIMA) was a randomized, double-blind comparison of 13.3 mg/24 h versus 9.5 mg/24 h rivastigmine patch in patients with mild-to-moderate Alzheimer's disease who declined despite open-label treatment with 9.5 mg/24 h patch. Over 48 weeks of double-blind treatment, high-dose patch produced greater functional and cognitive benefits compared with 9.5 mg/24 h patch.
  
  
  METHODS
  Using OPTIMA data, a post-hoc responder analysis was performed to firstly, compare the proportion of patients demonstrating improvement or absence of decline with 13.3 mg/24 h versus 9.5 mg/24 h patch; and secondly, identify predictors of improvement or absence of decline. 'Improvers' were patients who improved on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) by ≥4 points from baseline, and did not decline on the instrumental domain of the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-IADL). 'Non-decliners' were patients who did not decline on either scale.
  
  
  RESULTS
  Overall, 265 patients randomized to 13.3 mg/24 h and 271 to 9.5 mg/24 h patch met the criteria for inclusion in the intention-to-treat population and were included in the analyses. Significantly more patients were 'improvers' with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Weeks 24 (44 (16.6%) versus 19 (7.0%); P < 0.001) and 48 (21 (7.9%) versus 10 (3.7%); P = 0.023). A significantly greater proportion of patients were 'non-decliners' with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Week 24 (71 (26.8%) versus 44 (16.2%); P = 0.002). At Week 48, there was a trend in favor of 13.3 mg/24 h patch. Functional and cognitive assessment scores at double-blind baseline did not consistently predict effects at Weeks 24 or 48.
  
  
  CONCLUSIONS
  More patients with mild-to-moderate Alzheimer's disease who are titrated to 13.3 mg/24 h rivastigmine patch at time of decline are 'improvers' or 'non-decliners' i.e. show responses on cognition and activities of daily living compared with patients remaining on 9.5 mg/24 h patch.
  
  
  BACKGROUND
  Clinicaltrials.gov identifier: NCT00506415; registered July 20, 2007.
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, ICN, Hospital Clínic i Universitari, IDIBAPS, Villarroel 170, Barcelona, 08036 Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Molinuevo
authors.affiliation: Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Frölich
authors.affiliation: Department of Neurology & Psychiatry, School of Medicine, St Louis University, St Louis, MO USA.
authors.forename: George T
authors.initials: GT
authors.lastname: Grossberg
authors.affiliation: Center for Cognitive Neurology, New York University Langone School of Medicine, New York, NY USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Galvin
authors.affiliation: Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV USA ; Cleveland Clinic Lou Ruvo Center for Brain Health, Cleveland, OH USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Cummings
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Tillmann
authors.initials: T
authors.lastname: Krahnke
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Strohmaier