Memantine With Cholinesterase Inhibitors Maintains Improvements of Psychiatric Symptoms vs Cholinesterase Inhibitors Alone: Post Hoc Analyses From 3 Randomized, Double-blind, Placebo-controlled Studies in Patients With Alzheimer’s Disease (P6.177)

Objective: To evaluate Neuropsychiatric Index (NPI) maintenance of response from weeks 12–24 between patients receiving memantine/ChEI vs placebo/ChEI.

Background: Neuropsychiatric symptoms, as measured by the NPI, impact daily function and quality of life, hasten time to institutionalization, and increase healthcare costs in patients with AD. Memantine significantly improves NPI scores vs placebo in moderate-to-severe AD. Maintenance of response represents a meaningful treatment benefit and symptom stabilization.

Design/Methods: Post hoc analyses used pooled data from moderate to severe (baseline MMSE ≤19)patients (N=1121) in 3 randomized, double-blind, placebo-controlled studies (MEM-MD-02 [Tariot et al, JAMA 2004], MEM-MD-50 [Grossberg et al, CNS Drugs 2013], and MEM-MD-12 [Porsteinsson et al, Curr Alzheimer Res 2008]). To characterize NPI responder rates, evenly spaced change from baseline score groups (≤0, ≤−3, ≤−6, ≤−9, ≤−12) were identified. Maintenance of response was defined as total NPI score change at week 12 (earliest pooled timepoint) that was maintained through week 24 (endpoint). The percentages of patients who maintained response were compared between patients receiving memantine/ChEI or placebo/ChEI using Fisher’s exact test with observed case.

Results: Pooled data showed that greater proportions of moderate-to-severe patients treated with memantine/ChEI maintained improvements on total NPI from weeks 12–24 compared with placebo/ChEI patients. For memantine/ChEI-treated vs PBO/ChEI-treated patients, 23.4% vs 18.2% maintained improvements of 6 points or more (P=0.0332); 17.0% vs 11.5% maintained improvements of 9 points or more (P=0.0103); 13.3% vs 7.7% maintained improvements of 12 points or more (P=0.0024).

Conclusions: The combination of memantine added to ChEI resulted in improvements on total NPI that were sustained over weeks 12–24 of treatment in this OC analysis, which may represent clinically meaningful improvements for patients with moderate-to-severe AD with neuropsychiatric symptoms. For clinicians, the ability to characterize treatment effects of combination therapy over time may be useful in identifying treatment options and setting patient and caregiver expectations.

Study Supported by: Allergan plc

Disclosure: Dr. Cummings has nothing to disclose. Dr. Grossberg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Grossberg has served as a consultant for Acadia, Allergan, Avanir, Axovant, GE, Genentech, Lundbeck, Novartis, Otsuka, Roche, and Takeda, and for the Speaker’s Bureau for Acadia. Dr. Grossberg has received research support from Dr. Grossberg has received research support and funds from Cognoptix, Janssen, and NIH. Dr. Porsteinsson has nothing to disclose. Dr. Hendrix has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pentara Corporation employee. Dr. Ellison has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pentara Corporation employee. Dr. Kerolous has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan employee.