Donepezil, rivastigmine, galantamine and memantine for ...

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62 Clinical effectiveness placebo [OR 1.43 (95% CI: 0.98 to 2.08)] favoured galantamine at 6 months follow-up. Use of the random effects models resulted in limited change to the outcomes of the metaanalysis and none of the models were affected by heterogeneity. Summary: in individual studies higher proportions of participants on galantamine improved on CIBIC-plus and CGIC compared with participants on placebo, who were likely to deteriorate. When studies were pooled, no statistical significance is noted between treatment groups and placebo. Function DAD Three RCTs assessed changes from baseline on the DAD scale (Table 29). 62,64,66 The DAD scale assesses basic and instrumental activities of daily living, initiation, planning and organisation, performance and leisure, scoring people between 0 and 100. Rockwood and colleagues 62 noted that participants in the 24–32 mg/day galantamine group deteriorated statistically significantly less than those in the placebo group (difference 4.1 points). Similarly, Wilkinson and colleagues 66 reported a statistically significantly smaller deterioration on the DAD scale for participants in the 24–32 mg/day galantamine group compared with placebo (difference 4.8 points). Wilcock and colleagues 64 noted a slower deterioration in DAD scores for participants receiving 24 mg/day (difference 2.8 points) or 32 mg/day (difference 3.5 points) galantamine compared with placebo, statistically significantly so for the group receiving 32 mg/day. TABLE 29 DAD for galantamine: all mean (SEM) change from baseline Rockwood et al. 62 ADL Tariot and colleagues 63 reported mean (SEM) changes from baseline on the Alzheimer’s Disease Cooperative Study Activities of Daily Living inventory (ADCS/ADL) for participants receiving 8, 16 and 24 mg/day galantamine and placebo. This outcome measure assesses daily activities in participants, such as using household appliances, choosing clothes to wear, bathing and toileting. Although all participants had deteriorated over the 5 months’ duration of the study, it was statistically significantly less for those receiving 16 mg/day [–0.7 (SEM 0.5), p < 0.001] and 24 mg/day [–1.5 (SEM 0.6), p < 0.01] than placebo [–3.8 (SEM 0.6)]. [Commercial/academic confidential information removed] PDS Wilkinson and Murray 65 assessed differences in the proportion of participants who were classified as either much improved, improved, no change, worse or much worse on the PDS-1, which is a measure of activities of daily living. Although participants receiving either 18, 24 or 36 mg/day galantamine were less likely to be worse/much worse compared with participants on placebo and that participants receiving either 18 or 24 mg/day were more likely to have improved/much improved compared with participants on placebo or 36 mg/day galantamine, the differences were not statistically significant. Summary: participants receiving galantamine appeared to suffer less deterioration compared with those on placebo, statistically significantly for doses between 16 and 32 mg/day on the DAD and ADL scales. Galantamine 24–32 mg/day (n = 261) Placebo (n = 125) p-Value vs placebo –1.2 (0.83) –5.3 (1.17) p < 0.01 Wilkinson et al. 66 Galantamine 24–32 mg/day (n = 239) Placebo (n = 120) p-Value vs placebo –0.4 (0.76) –5.2 (1.18) p < 0.001 Wilcock et al. 64 1. Galantamine 24 mg/day 2. Galantamine 3. Placebo (n = 210) Treatment difference (n = 212) 32 mg/day (n = 214) (95% CI), p-value vs placebo –3.2 (1.02) –2.5 (1.07) –6.0 (1.08) 1. 2.8 (–0.6 to 6.1) p = 0.1 2. 3.4 (0.1 to 6.7) p < 0.05
Behaviour and mood NPI Two published 62,63,67 [commercial/academic confidential information removed] RCTs examined mean (SEM) changes from baseline for NPI and can be seen in Table 30. Rockwood and colleagues 62 reported that participants in the 24–32 mg/day arm experienced an improvement on the NPI scale whereas participants on placebo worsened (difference 0.9), but this difference did not reach statistical significance. Tariot and colleagues 63,67 found some improvement on the NPI scale for participants receiving 16 mg/day and no change compared with baseline for those receiving 24 mg/day. Participants receiving 8 mg/day galantamine or placebo experienced deterioration on the NPI scale. Differences in the change in mean NPI score between placebo and the 16 mg/day (difference 2.1) and 24 mg/day (difference 2.0) galantamine groups were statistically significant. [Commercial/academic confidential information removed] Summary: higher doses of galantamine were associated with a statistically significant slowing in the TABLE 30 NPI for galantamine: all mean (SEM) change from baseline Rockwood et al. 62 © Queen’s Printer and Controller of HMSO 2006. All rights reserved. Health Technology Assessment 2006; Vol. 10: No. 1 deterioration of participants condition on NPI compared with placebo in one trial. In two trials the slowing of deterioration was not statistically significantly different between those treated with galantamine and those treated with placebo. Adverse events All six published [commercial/academic confidential information removed] RCTs reported adverse events affecting the different patient groups, 61–66 focusing on the proportion of participants suffering a particular event (see Table 31). It was evident that participants receiving galantamine suffered between 2 and 27% more adverse events than those on placebo, with differences tending to reflect a dose–response effect. Nausea affected between 6% (8 mg/day) and 44% (32 mg/day) of galantamine participants compared with between 3 and 13% of placebo participants. Similarly, a higher proportion of participants in the RCTs on galantamine suffered from vomiting (difference range 1–18%), dizziness (difference range 0–10%), anorexia (difference range 3–14%) than participants on placebo. As a consequence, withdrawals due to adverse events Galantamine 24–32 mg/day (n = 261) Placebo (n = 125) p-Value vs placebo –0.4 (0.65) 0.5 (0.64) ns Tariot et al. 63,67 1. Galantamine 2. Galantamine 3. Galantamine 4. Placebo p-Value vs placebo 8 mg/day 16 mg/day 24 mg/day (n = 262) (n = 129) (n = 255) (n = 253) 2.3 (1.0) –0.1 (0.7) 0.0 (0.8) 2.0 (0.7) 2. p < 0.05 3. p < 0.05 [Commercial/academic confidential information removed] TABLE 31 Adverse events for galantamine (note that p-values are not reported unless stated) Rockwood et al. 62 No. (%) of adverse events occurring at least 5% more with galantamine than placebo Galantamine 24–32 mg/day (n = 261) Placebo (n = 125) Nausea 84 (32.2) 14 (11.2) Dizziness 39 (14.9) 5 (4.0) Vomiting 38 (14.6) 5 (4.0) Anorexia 31 (11.9) 3 (2.4) Somnolence 20 (7.7) 1 (0.8) Abdominal pain 18 (6.9) 2 (1.6) Agitation 16 (6.1) 1 (0.8) Any adverse event 225 (86.2) 79 (63.2) continued 63
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Health Technology Assessment 2006;
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The clinical and cost-effectiveness
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Objectives: To provide an update re
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List of abbreviations .............
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AChEI acetylcholinesterase inhibito
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Epidemiology and background Alzheim
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Galantamine Five published economic
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Description of underlying health pr
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TABLE 1 Estimated prevalence of AD
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as one component of their care. A n
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The a priori methods used for syste
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Page 28 and 29: 14 Clinical effectiveness TABLE 3 C
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Page 38 and 39: 24 Clinical effectiveness donepezil
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Page 48 and 49: 34 Clinical effectiveness clinical
Page 50 and 51: 36 Clinical effectiveness TABLE 10
Page 54 and 55: 40 Clinical effectiveness statistic
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Page 62 and 63: 48 Clinical effectiveness differenc
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Page 86 and 87: 72 Clinical effectiveness by the pa
Page 92 and 93: 78 Clinical effectiveness donepezil
Page 94 and 95: 80 Evidence from systematic reviews
Page 96 and 97: 82 Economic analysis TABLE 48 Chara
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Page 100 and 101: 86 Economic analysis The UK study r
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112 Economic analysis vascular deme
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114 Economic analysis Livingston an
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116 Economic analysis sensitive to
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118 Economic analysis Neumann and c
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120 Economic analysis The model str
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122 Economic analysis CEA, given th
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124 Economic analysis TABLE 70 Key
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126 Economic analysis TABLE 73 Prof
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128 Economic analysis Probability o
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130 Economic analysis Results are s
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132 Economic analysis 4. The model
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134 Economic analysis perspective e
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136 Economic analysis indicating th
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Ongoing research, with relevance to
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The increasing numbers of the very
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146 Discussion and conclusions dose
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148 Discussion and conclusions effo
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150 Discussion and conclusions Stre
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1. Clegg A, Bryant J, Nicholson T,
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placebo-controlled study of donepez
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94. Brooks E, Deal L. The effect of
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of memantine in patients with moder
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This version of HTA monograph volum
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376 Health Technology Assessment Pr
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378 Health Technology Assessment Pr
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