Memantine ER With an AChEI Improves Individual SIB Scores Compared With AChEI Alone: Post Hoc Analyses From a Randomized, Double-blind, Placebo-controlled Study (P6.173)

Objective: To examine Severe Impairment Battery (SIB) score changes (improvement or worsening) of ≥5, ≥10, and ≥15 points for patients with moderate to severe Alzheimer’s disease (AD) receiving memantine ER (MemER)/cholinesterase inhibitors (ChEI) vs placebo (PBO)/ChEI.

Background: Rigorous phase 3 studies demonstrated memantine efficacy, in combination with ChEI, on cognition, function, and global outcomes in patients with moderate-to-severe AD. In a randomized, double-blind, PBO-controlled study (NCT00322153, MemER/ChEI treatment significantly improved SIB scores vs PBO/ChEI, with a PBO-adjusted mean difference of 2.6 points at week 24.

Design/Methods: Post hoc analyses examined SIB baseline-to-endpoint (week 24) score changes in patients receiving an ChEI randomized to MemER (28 mg/day) or PBO. SIB score changes were examined in 5-point increments (eg, absolute changes of 1–5, 6–10, 11–15). “Improvement/decline” was noted at 5-point changes; “notable improvement/decline” at 10-point changes; and “remarkable improvement/decline” at 15-point changes.

Results: Of 676 patients (safety population), 541 had SIB scores at baseline and week 24 (n=270 MemER/ChEI; n=271 PBO/ChEI). At week 24, 40% of MemER/ChEI patients experienced a ≥5-point SIB improvement vs 31% of PBO/ChEI patients. More MemER/ChEI patients had notable improvements of ≥10 points vs PBO/ChEI patients (23% vs 13%); twice as many had remarkable improvements (≥15 points) with MemER/ChEI vs PBO/ChEI (14% vs 7%). Fewer MemER/ChEI patients declined by ≥5 points vs PBO/ChEI (19% vs 24%), with similar results at declines of ≥10 (10% vs 13%) and ≥15 (6% vs 7%).

Conclusions: Compared with PBO/ChEI, more MemER/ChEI-treated patients experienced improvements of ≥5, ≥10 and ≥15 points on the SIB, all greater than the PBO-adjusted mean of 2.6 points; fewer MemER/ChEI-patients experienced a decline in cognition. As no disease-modifying AD treatments are available, these data reaffirm the efficacy of combination therapy with MemER/ChEI on cognition and support its use in patients with moderate to severe AD.

Study Supported by: Allergan plc

Disclosure: 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. Kramer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan employee. 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.