Abstract
IntroductionOPtimizing 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.MethodsUsing 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.ResultsOverall, 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.ConclusionMore 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.Trial registrationClinicaltrials.gov identifier: NCT00506415; registered July 20, 2007.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-014-0088-8) contains supplementary material, which is available to authorized users.
Highlights
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
Study population In total, 265 patients randomized to the 13.3 mg/24 h patch and 271 patients randomized to the 9.5 mg/24 h patch met the criteria for inclusion in the ITT-DB population and were included in the present analysis
Response on the ADAS-cog and Alzheimer’s Disease Cooperative Study (ADCS)-IADL when analyzed separately A significantly greater proportion of patients receiving the 13.3 mg/24 h compared with the 9.5 mg/24 h patch demonstrated ≥4 points improvement on the ADAS-cog
Summary
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. The Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog) [3] is the standard neuropsychological measure in trials involving patients with mild-to-moderate AD [4,5]. It is important that functional decline is measured to assess the ability to perform clinically meaningful activities of daily living (ADL). The criterion usually applied for a ‘responder’ is a four-point or more improvement on the ADAS-cog [8], as this is generally accepted to represent a clinically relevant change on an individual basis in patients with mild-to-moderate AD [9]. For a population of patients who, without treatment, display continuous decline, achieving any improvement or temporary stability on the ADAS-cog and other assessments may represent a significant therapeutic benefit. It is important to identify factors that may influence the likelihood of receiving a benefit from treatment, as patients may vary in their response to treatment according to their clinical characteristics [10,11]
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