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The Place of Memantine in the Treatment of Alzheimer’s Disease: a Number Needed to Treat Analysis. Livingston G. and Kartona C. International Journal of Geriatric Psychiatry 2004; 19:919–925. Numbers Needed to Treat.
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The Place of Memantine in the Treatment of Alzheimer’s Disease: a Number Needed to Treat Analysis Livingston G. and Kartona C. International Journal of Geriatric Psychiatry 2004;19:919–925
Numbers Needed to Treat • The NNT is the number of patients who need to be treated with the treatment in question, compared to another treatment (often placebo) for one patient to gain a specified benefit • The NNT is a clinically useful measure of treatment effect • NNTs depend on the definition of benefit
Numbers Needed to Treat: Calculation Definition of response e.g. Improvement and stabilisation on SIB scale • Calculate % of patients under memantine and under placebo, • e.g. 50% and 25% 1 NNT = = 2 50% – 25%
NNTs for AD Drugs • Livingston and Katona used the NNT approach to define whether the effects of reported trials of AChE-I and of Memantine are clinically relevant • Compared the NNTs for Memantine to the NNTs for Galantamine where there are the same or similar endpoints in terms of definitions of response • Earlier analyzed NNTs of Donepezil and Rivastigmine are shown for comparison Livingston and Katona 2000 and 2004
Single domain Responder for Memantine OC analysis; Response = improvement or stabilization Memantine Placebo Responder (%) Responder (%) NNT CIBIC-Plus 59 40 6 SIB 38 23 7 ADCS-ADL1934 20 8 Reisberg et al., 2003 Livingston and Katona 2004
Other NNTs for Memantine LOCF analysis Memantine Placebo Responder (%) Responder (%) NNT Improvement or stabilisation in 11 6 18CIBIC-Plus and SIB and ADL Improvement or stabilisation in 29 10 6CIBIC-Plus and SIB or ADL Improvement or stabilisation in 21 6 7CIBIC-Plus and SIB Improvement in 11 2 11CIBIC-Plus and SIB Reisberg et al., 2003; EPAR 2000
NNTs for Memantine in Severe Dementia OC analysis Memantine Placebo Responder (%) Responder (%) NNT BGP-D 69 38 4improvement 15% CGI-C 77 43 3final score 4 Responder analysis 64 27 3both above Winblad and Poritis 1999 Livingston and Katona 2004
NNTs for Galantamine Galantamine Placebo Responder (%) Responder (%) NNT CIBIC-Plus 62 50 9no deterioration ADAS-cog 63 41 5improvement 4 Wilcock et al., 2000 Livingston and Katona 2004
NNTs for Donepezil Donepezil Placebo Responder (%) Responder (%) NNT ADAS-cog 81 58 5no deterioration ADAS-cog 53 27 4improvement ≥ 4 ADAS-cog 25 8 6improvement ≥ 7 CIBIC-Plus score 25 11 8improvement ≥ 3 CIBIC-Plus score 75 55 5deterioration ≥ 5 Rogers et al., 1998 Livingston and Katona 2000
NNTs for Rivastigmine Rivastigmine Placebo Responder (%) Responder (%) NNT ADAS-cog improvement ≥ 4*24 16 13 CIBIC-Plus improvement*37 20 6 PDS (ADL) 29 19 10improvement 10%* ADAS-cog no deterioration**54 27 4 CIBIC-Plus improvement**24 16 12.5 PDS (ADL) 25 15 10improvement 10%** * Rosler et al., ** Corey-Bloom et al. Livingston and Katona 2000
Conclusions Memantine: • NNTs for memantine are comparable with NNTs of AChEIs Memantine is efficacious on cognitive and non cognitive domains • Memantine treatment shows a clinically significant benefit in moderate to severe AD Livingston and Katona 2000 and 2004