Donepezil, rivastigmine, galantamine and memantine for ...

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58 Clinical effectiveness Comparison: Outcome: Study Raskind 2000 gal Wilcock 2000 gal 07 Galantamine ADAS-cog change from baseline 02 Galantamine 32 at 6 months Treatment n 197 217 Mean (SD) –1.40 (6.20) –0.80 (6.30) Total (95% CI) Test for heterogeneity 2 414 = 0.05, df = 1, p = 0.82 Test for overall effect z = 7.62, p < 0.00001 Control n 207 215 Figure 13). Similarly, the fixed-effect models for 24–32 mg/day compared with placebo [WMD –1.65 (95% CI: –2.43 to –0.87)] and for 32 mg/day galantamine compared with placebo [WMD –3.29 (95% CI: –4.14 to –2.45)] favoured galantamine at 6 months follow-up (Figures 14 and 15). Use of the random effects models resulted in limited change to the outcomes of the meta-analysis and none of the models were affected by heterogeneity. Cognitive responders on ADAS-cog Three RCTs reported the proportion of participants who were responders to treatment with at least a 4-point improvement on the ADAScog scale (Table 27). Rockwood and colleagues 62 reported that a higher proportion of participants on galantamine 24–32 mg/day were responders to treatment compared with those on placebo (difference 6.3%). Wilcock and colleagues 64 noted that statistically significantly more participants on galantamine 24 mg/day (difference 14%) and 32 mg/day (difference 17%) were considered to be responders to treatment on ADAS-cog compared with participants receiving placebo. Similar differences in the proportion of responders to treatment were found by Tariot and colleagues with statistically significantly more participants on 16 mg/day (difference 16%) and 24 mg/day (difference 17.4%) achieving a 4-point or more improvement on ADAS-cog/11 scale compared with participants on placebo. 63 Summary: galantamine appears to confer a statistically significant benefit to participants compared with placebo on the cognitive outcome ADAS-cog. Global outcome measures CIBIC-plus Five published [commercial/academic confidential information removed] RCTs assessed the clinical Mean (SD) 2.00 (6.50) 2.40 (6.00) FIGURE 15 ADAS-cog change from baseline with galantamine 32 mg WMD (95% CI fixed) Weight % 46.7 53.3 WMD (95% CI fixed) –3.40 (–4.64 to –2.16) –3.20 (–4.36 to –2.04) 422 100.0 –3.29 (–4.14 to –2.45) –10 –5 0 5 10 Favours treatment Favours control effectiveness of galantamine using the CIBIC-plus outcome measure, reporting either the proportion of participants within each category 61,62,64,66 or the proportion of responders (Table 28). 63 A comparison of 24–32 mg/day galantamine with placebo by Rockwood and colleagues 62 found that a greater proportion of participants receiving galantamine improved on the CIBIC-plus scale compared with those on placebo, with statistically significantly more reporting a minimal (difference 4.1%) or moderate (difference 2.0%) improvement. In contrast, statistically significantly more participants in the placebo group experienced minimal (difference 11.7%) or moderate (difference 4.1%) worsening of their condition compared with those in the galantamine group. Wilkinson and colleagues 66 reported similar differences, with participants receiving 24–32 mg/day galantamine reporting statistically significant benefit on the CIBIC-plus outcome measure compared with participants on placebo. Statistically significant differences were also identified by Raskind and colleagues 61 and Wilcock and colleagues 64 when comparing the doses of 24 and 32 mg/day galantamine with placebo. Raskind and colleagues 61 reported that statistically significantly more participants receiving either 24 or 32 mg/day galantamine showed marked, moderate or minimal improvement on CIBIC-plus compared with placebo. In addition, statistically significantly more placebo participants worsened minimally, moderately or markedly than participants on either 24 or 32 mg/day galantamine. Comparison between the two doses of galantamine showed slight benefit for those participants receiving 24 mg/day, although the differences were not statistically significant. Although Wilcock and colleagues 64 found comparable benefits for participants receiving 24 and 32 mg/day
TABLE 27 ADAS-cog: responders for galantamine Rockwood et al. 62 © Queen’s Printer and Controller of HMSO 2006. All rights reserved. Health Technology Assessment 2006; Vol. 10: No. 1 No. (%) ADAS-cog/11 responders ≥ 4 points improvement Galantamine 24–32 mg/day (n = 258) Placebo (n = 123) p-Value vs placebo 73 (28.3) 27 (22.0) ns Wilcock et al. 64 1. Galantamine 2. Galantamine 3. Placebo (n = 215) Treatment difference 24 mg/day (n = 220) 32 mg/day (n = 217) (95% CI), p-Value vs placebo No. (%) with ≥ 0 points improvement 138 (63) 130 (60) 88 (41) 1. 21.5 (12.0 to 31.0) p < 0.001 2. 19.5 (10.0 to 29.0) p < 0.001 No. (%) with ≥ 4 points improvement 64 (29) 70 (32) 32 (15) 1. 14.0 (6.0 to 22.0) p < 0.001 2. 17.0 (9.0 to 25.0) p < 0.001 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 = 255) (n = 126) (n = 253) (n = 253) ADAS-cog/11 responders ≥ 4 points improvement (%) Not reported 35.6 37.0 19.6 1. p < 0.001 2. p < 0.001 Proportion participants, on ADAS-cog, improved ≥ 7 points relative to baseline (%) Not reported 15.9 22.3 7.6 1. p < 0.01 2. p < 0.01 TABLE 28 CIBIC-plus for galantamine: all n (%) unless stated otherwise Rockwood et al. 62 Galantamine 24–32 mg/day (n = 248) Placebo (n = 124) p-Value vs placebo 1 = markedly improved 1 (0.4) 1 = markedly improved 0 (0) 2 = moderately improved 7 (2.8)** 2 = moderately improved 1 (0.8) **p < 0.01 3 = minimally improved 56 (22.6)** 3 = minimally improved 23 (18.5) **p < 0.01 4 = no change 132 (53.2)** 4 = no change 54 (43.5) **p < 0.01 5 = minimally worsened 43 (17.3)** 5 = minimally worsened 36 (29.0) **p < 0.01 6 = moderately worsened 8 (3.2)** 6 = moderately worsened 9 (7.3) **p < 0.01 7 = markedly worsened 1 (0.4) 7 = markedly worsened 1 (0.8) Wilkinson et al. 66 Galantamine 24–32 mg/day (n = 240) Placebo (n = 123) p-Value vs placebo 1 = markedly improved 0.4 1 = markedly improved 0 2 = moderately improved 2.9 2 = moderately improved 0.8 3 = minimally improved 22.1 3 = minimally improved 18.7 Overall p < 0.01 4 = no change 55.4 4 = no change 43.1 5 = minimally worsened 16.7 5 = minimally worsened 29.3 6 = moderately worsened 2.5 6 = moderately worsened 7.3 7 = markedly worsened 0 7 = markedly worsened 0.8 continued 59
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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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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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