Abstract
Background The efficacy of a new, extended-release (ER) formulation of memantine (28 mg, once daily) has been demonstrated previously in a 24-week, multinational, randomized, double-blind, placebo-controlled, parallel-group trial (MEM-MD-50, NCT00322153; placebo, n=335; memantine, n=342) in patients with moderate to severe Alzheimer's disease (AD) concurrently taking a cholinesterase inhibitor. The current study is a post hoc analysis, designed to explore the effects of memantine ER on combinations of outcome measures utilized in that trial. Methods Efficacy outcomes included measures of cognition (SIB), function (ADCS-ADL 19), behavior (NPI), and global status (CIBIC-Plus). For each measure, two levels of response were defined: improvement or stabilization (“no decline”; baseline-to-endpoint improvement of ≥0 points for the SIB, ADCS-ADL 19, and NPI; endpoint score ≤4 for the CIBIC-Plus) and clinically notable response (baseline-to-endpoint improvement of ≥3 points for the SIB, ADCS-ADL 19, and NPI; endpoint score ≤3 for the CIBIC-Plus). The treatment groups were compared by calculating the proportions of patients who achieved no decline or a clinically notable response on any combination of 2, 3, or all 4 efficacy measures. Data were analyzed using observed cases and Wald's test (±=0.05); numbers needed to treat (NNTs) were also calculated. Due to the exploratory nature of this analysis, no corrections for multiple comparisons were performed. Results For both response levels and all outcome combinations, proportions of responders in the memantine ER group (n=266-269) exceeded those in the placebo group (n= 271-272). The difference between proportions of memantine ER- and placebo-treated patients who experienced no decline approached statistical significance for the SIB/CIBIC-Plus combination (54.6% vs 46.1%; P =0.054, NNT=12). For clinically notable responses, memantine ER was significantly superior to placebo for the 2-measure combination of ADCS-ADL 19/NPI (21.3% vs 15.8%; P =0.042, NNT=18), and the 3-measure combinations of ADCS-ADL 19/NPI/SIB (15.4% vs 9.6%; P =0.027, NNT=17), and ADCS-ADL 19/SIB/CIBIC-Plus (12.4% vs 7.4%; P =0.030, NNT=20). Conclusions This exploratory post hoc analysis suggests that, in patients with moderate to severe AD, memantine ER may provide simultaneous benefits on multiple clinical domains, especially when improvements in cognition and function are observed, and when a response to therapy is relatively strong.