Galantamine Provides Sustained Benefits in Patients with ‘Advanced Moderate’ Alzheimer’s Disease for at Least 12 Months

Abstract

Galantamine (Reminyl^®), a novel agent with a dual mode of action, modulates nicotinic acetylcholine receptors and inhibits acetylcholinesterase. Galantamine has consistently demonstrated a broad range of beneficial effects and has shown sustained benefits in cognitive and functional abilities for at least 12 months in patients with mild-to-moderate Alzheimer’s disease (AD). As pivotal studies demonstrating the efficacy of cholinergic drugs were designed to exclude patients with severer AD, many patients with the advanced stage of this condition are currently not treated due to the lack of demonstrated efficacy in clinical trials. We aimed to investigate whether there was any evidence for the benefits of galantamine in patients with severer disease, by performing a post hoc analysis using data extracted from the population of the two long-term galantamine studies. We evaluated the efficacy of galantamine in patients with ‘advanced moderate’ AD. ‘Advanced moderate’ patients were those with baseline Mini Mental State Examination (MMSE) scores ≤14 or Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS-cog) scores >30. These patients were compared with matched controls who received placebo in a different historical study. Cognitive abilities (assessed using the ADAS-cog scale) of ‘advanced moderate’ AD patients receiving galantamine for 12 months were maintained at baseline levels after 12 months, and significantly improved over those of placebo patients (p < 0.001). Of the ‘advanced moderate’ patients receiving galantamine, 51% with baseline ADAS-cog of >30 maintained or improved their ADAS-cog scores over baseline values, compared with 13% receiving placebo (p < 0.001). In the subgroup of ‘advanced moderate’ patients with baseline MMSE ≤14, 48% of those receiving galantamine and 4% of those receiving placebo maintained or improved their ADAS-cog scores at 12 months (p = 0.001). In both subgroups, the treatment difference (galantamine vs. historical placebo) amounted to approximately 10 points on the ADAS-cog scale. Functional abilities, as assessed using the Disability Assessment for Dementia scale, remained significantly superior in galantamine-treated patients compared with historical placebo-treated patients at 12 months (p < 0.001). In conclusion, galantamine offered sustained efficacy to patients with ‘advanced moderate’ AD, confirming the benefits seen in published studies of patients with mild-to-moderate AD. This drug has potential for broader use in clinical practice.