Abstract
Introduction: 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. Conclusion: 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.
