Background: This analysis aimed to identify an operational, clinically relevant definition of response achieved in short-term clinical trials to support the identification of patients with Alzheimer's disease (AD) who would benefit most from long-term galantamine therapy.
Methods: Data were analyzed from 6 randomized placebo-controlled trials of up to 6 months' duration, which included patients with mild to moderate AD receiving maintenance doses of galantamine 16-24 mg/day, and from 12 open-label extensions (galantamine 24 mg/day maintenance therapy). Assessments included changes from baseline in the 11-item AD Assessment Scale-Cognitive subscale (ADAS-Cog 11).
Results: Pooled analysis of the 5-6 month trial data showed that at the trial endpoint (2-5 months after reaching maintenance doses), the proportions of galantamine- (n=1,173) versus placebo-treated patients (n=801) with probable AD categorized according to "improved", "stable" or "non-rapid decline" criteria, were 45.8% versus 27.2%, 59.5% versus 37.1%, and 87.6% versus 69.7%, respectively (observed cases analysis), whilst changes in ADAS-Cog 11 scores versus baseline were -4.9, -4.7 and -2.9 points, respectively, for "improved", "stable" and "non-rapid decline" galantamine-treated patients (-1.5 points for galantamine recipients overall). "Improved" or "stable" galantamine-treated patients displayed mean improvement in ADAS-Cog 11 scores over baseline until 18 months after starting treatment, and attenuated deterioration thereafter; for galantamine-treated patients exhibiting "non-rapid decline", mean ADAS-Cog 11 score returned to baseline after approximately 12 months.
Conclusions: Patients who demonstrate improvement, stability, or limited cognitive decline 2-5 months after reaching maintenance doses of galantamine are more likely to experience continued benefit from long-term galantamine therapy.