Responder analysis of a randomized comparison of the 13.3 mg/24 h and 9.5 mg/24 h rivastigmine patch

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.

Trial registration: Clinicaltrials.gov identifier: NCT00506415; registered July 20, 2007.

Figures

Figure 1

Responder analyses for the individual assessment scales. (A) Compared with the 9.5 mg/24 h patch, the 13.3 mg/24 h patch was associated with a significantly higher proportion of patients with ≥4 point improvement on the ADAS-cog at both weeks 24 and 48. *P <0.05, 13.3 mg/24 h versus 9.5 mg/24 h patch. (B) Compared with the 9.5 mg/24 h patch, the 13.3 mg/24 h patch was associated with a significantly higher proportion of patients who showed no decline on the ADCS-IADL at Week 24. *P <0.05, 13.3 mg/24 h versus 9.5 mg/24 h patch. ADAS-cog, Alzheimer’s Disease Assessment Scale–cognitive subscale; ADCS-IADL, Instrumental domain of the Alzheimer’s Disease Cooperation Study–Activities of Daily Living scale.