Efficacy of Anti-Alzheimer’S (AD) Drugs in Cognitive Improvement: A Network Meta-Analysis (NMA) of Randomized Controlled Trials (RCTS)

OBJECTIVES: To assess the effect of different drugs on the cognitive impairment in AD by conducting an NMA of RCTs.

METHODS: MEDLINE and EMBASE were searched to identify English language publications of RCTs that compared anti AD drugs with placebo and reported ADAS-Cog, MMSE, or CDR-SOB scores. Studies that did not report AD diagnostic criteria including NINCDS-ADRDA criteria, the IWG-2 criteria, or the ATN framework were excluded. Studies that included patients with mild cognitive impairment (MCI) or preclinical AD, non-pharmacological treatments, or assessed dose titration were also excluded. Standardized mean difference (SMD) in change from baseline between treatment and placebo were pooled in an NMA using R package netmeta, results of random effects model are presented here.

RESULTS: Of 339 records obtained from searches, 15 met the inclusion criteria. The highest change in ADAS-Cog score (vs placebo) was obtained with Sodium oligomannate (GV-971) (150mg), followed by Masitinib (4.5mg/kg/day), and Donepezil (5mg/day); SMD [95% CI]: -2.15 [-3.37; -0.93], -2.15 [-3.61; -0.69], -2.12 [-3.77; -0.47]. The highest change in MMSE score (vs placebo) was obtained with Semagacestat (140mg/day); SMD [95% CI]: -0.90 [-1.75; -0.05]. None of the treatments had statistically significant SMD vs placebo for CDR-SOB.

CONCLUSIONS: Sodium oligomannate (GV-971) (150mg) showed highest improvement in ADAS-Cog score vs placebo, only Semagacestat (140mg/day) showed statistically significant SMD in MMSE score vs placebo, and none of the treatments showed improvement in CSD-SOB score. Although, lecanemab has recently been approved by USFDA for MCI and mild AD, the effect sizes were not significantly different from placebo.