Wednesday, 2 April 2003

This presentation is part of : Poster Session 1

Consistently Small “Number-Needed-to-Treat” (NNT) in Galantamine Treated Patients with “Advanced Moderate” Alzheimer’s Disease

Susanne Schwalen, European Medical Affairs Neurology, Janssen-Cilag, Neuss, Germany, Gerry Hammond, European Medical Afairs, Janssen-Cilag, Buckinghamshire, United Kingdom, and Michael Davidson, Sheba Medical Center, Tel Aviv, Israel.

Introduction: Galantamine, a drug with unique nicotinic receptor modulating properties has shown its potential for the treatment of Alzheimer’s disease (AD) in controlled clinical trials with consistently high efficacy in all evaluated domains. Subgroup-analyses of pooled patients’ data from placebo-controlled trials demonstrated significant improvements with galantamine irrespective of gender, age or disease severity.

Objective: In order to assess the therapeutic value in one of these post-hoc subsets, a "Number-Needed-to-Treat" (NNT) analysis was performed on the pooled data of patients with “advanced moderate” AD from three large-scale Phase III studies of 5-6 months.

Design: A total of 705 patients received galantamine 24 mg whereof N=178 with baseline ADAS-cog scores >30 and N=86 with baseline MMSE scores £14 were included into the NNT analyses.

Materials and Methods: The NNT analyses were based on “responders” in ADAS-cog (with improvements ³0, ³4 and ³7 points) and on patients ‘improved or unchanged’ according to the Clinician’s Interview-Based Impression of Change plus caregiver input (CIBIC-plus). The galantamine treated groups were then compared to the matched placebo groups (N=183 and N=101, respectively) and the NNT was calculated according to the following formula: NNT=1/(proportion benefiting from active intervention - proportion benefiting from control). For the same intervention it is generally accepted that “the lower the NNT the more effective the drug”. NNT 4 for an ADAS-cog improvement ³4 would mean that one out of four patients respond to the treatment with an improvement of ³4 points. The 95% confidence intervals were added to estimate the range of variability. Furthermore the NNT values of the advanced moderate population in the galantamine clinical trials were put in relation to the NNT values of commonly used anticonvulsants with 50% seizure reduction defining “responders”.

Results: The patients were equally distributed for baseline characteristics such as mean ADAS-cog, MMSE, gender and age. In patients with baseline ADAS-cog scores >30 the NNT is 3 for ADAS-cog improvement of ³0 points, 4 for ADAS-cog improvements of ³4 and ³7 points and 5 for CIBIC-plus “improved or unchanged”. In patients with baseline MMSE £14 the NNT is 3 for patients with ADAS-cog improvements ³0 and ³4 points, 5 for those with ADAS-cog improvement ³7 points and 4 for the group with CIBIC-plus “improved or unchanged”. All corresponding CIs were small. The NNT values of the anticonvulsants lamotrigine and gabapentine were calculated as 8 and 9, respectively.

Conclusion: These consistently small NNT data and the likewise consistently small confidence intervals for cognitive and global outcome in both subgroups of advanced moderate AD patients strengthen the conclusion that galantamine treatment is very effective. The AD treatment with galantamine has NNTs that are in line with other treatments accepted as effective in other CNS disorders such as epilepsy supporting the appropriateness of treating AD patients.

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