Donepezil, rivastigmine, galantamine and memantine for ...

More documents

Recommendations

Info

68 Clinical effectiveness TABLE 35 ADAS-cog for donepezil versus rivastigmine Fuschillo et al. 68 Mean ± SD score Donepezil 5 mg/day (n = 16) Rivastigmine 1.5–9 mg/day (n = 11) Treatment difference between groups 39.4 ± 6.6 (baseline 43.0 ± 7.6) 36.5 ± 5.7 (baseline 40.3 ± 6.7) Not reported Wilkinson et al. 69 Mean ± SEM change from baseline Donepezil 5 mg/day (n = 50) Rivastigmine 3–12 mg/day (n = 37) Treatment difference between groups (95% CI) –0.90 ± 0.56 –1.05 ± 0.67 –0.15 (–1.85 to 1.55) TABLE 36 MMSE for donepezil versus rivastigmine Fuschillo et al. 68 Mean ± SD score Donepezil 5 mg/day (n = 16) Rivastigmine 1.5–9 mg/day (n = 11) Treatment difference between groups 14.9 ± 4.4 (baseline 13.7 ± 3.4) 16.0 ± 3.6 (baseline 13.2 ± 3.3) Not reported Wilkinson et al. 69 Mean ± SEM change from baseline Donepezil 5 mg/day (n = 51) Rivastigmine 3–12 mg/day (n = 39) Treatment difference between groups (95% CI) 0.71 ± 0.44 1.20 ± 0.52 0.49 (–0.82 to 1.81) the included studies 69,70 state that an ITT analysis was undertaken; however, the methods used do not meet the definition of ITT and therefore these studies are categorised as inadequate on this quality criterion. Two studies give details of the numbers of and reasons for withdrawals from the study. 69,70 Assessment of effectiveness: donepezil versus rivastigmine Cognitive outcomes ADAS-cog Both RCTs report the ADAS-cog and the results are given in Table 35. The study by Fuschillo and colleagues 68 reported the mean ADAS-cog score at endpoint, whereas that by Wilkinson and colleagues 69 reported the mean change from baseline. To aid interpretation, the baseline ADAS-cog for the Fuschillo and colleagues study has been added to Table 35 (in parentheses). On the ADAS-cog a negative mean change indicates a clinical improvement. Both included studies show comparable improvements on the ADAS-cog in the donepezil-treated and the rivastigmine-treated participants, but statistical comparisons are not reported for either study. MMSE Both RCTs report the MMSE and results are given in Table 36. The Fuschillo and colleagues 68 study reported the mean MMSE score at endpoint, whereas the Wilkinson and colleagues 69 study reported the mean change from baseline. To aid interpretation, the baseline MMSE score for the Fuschillo and colleagues study has been added to Table 36 (in parentheses). On the MMSE a positive mean change indicates a clinical improvement. Both included studies show improvements on the MMSE in the donepeziltreated and the rivastigmine-treated participants. In both studies the difference from baseline in the rivastigmine groups can be observed to be greater than that of the donepezil group, but statistical comparisons are not reported for either study. Functional outcomes PSMS The Physical Self-Maintenance Scale (PSMS) was used in one included trial. 68 On this scale, which measures ADLs, a decreased change in score indicates improvement. At 30 weeks the mean PSMS in the donepezil-treated group was 9.1 (baseline 9.2) and in the rivastigmine-treated
TABLE 37 Adverse events for donepezil versus rivastigmine group 11.0 (baseline 11.5). Statistical analyses were within-group rather than between-group comparisons. Compliance Wilkinson and colleagues 69 assessed compliance between those given donepezil and those given rivastigmine. Those defined as reaching the maximum daily dose at some time during the study were 98.2% in the donepezil group and 60% in the rivastigmine group. Those defined as remaining at the maximum dose until study completion or the final visit were 87.5% in the donepezil group and 47.3% in the rivastigmine group. These differences were not tested for statistical significance. Adverse events Various event rates for selected adverse events were reported in the included trials and can be seen in Table 37. The most commonly reported adverse events related to the gastrointestinal system, including nausea, vomiting and diarrhoea. Rates of adverse events were generally higher in the rivastigmine-treated participants than in the donepezil-treated participants, but no statistical comparisons between the treatment groups were reported. Adverse events were generally mild to moderate in severity; however, four participants in the rivastigmine group of the Wilkinson and © Queen’s Printer and Controller of HMSO 2006. All rights reserved. colleagues 69 study reported a severe treatmentrelated digestive system adverse event compared with none in the donepezil group. Fuschillo and colleagues 68 reported no withdrawals due to adverse events in either study group. In the Wilkinson and colleagues 69 study 10.7% of donepezil-treated participants and 21.8% of rivastigmine-treated participants withdrew owing to the onset of adverse events. Withdrawals unrelated to adverse events were reported in the Wilkinson and colleagues 69 study, where more patients withdrew or died in the rivastigmine group than the donepezil group, but this was not tested for statistical significance. Data relating to withdrawals are given in Appendix 10. Summary Health Technology Assessment 2006; Vol. 10: No. 1 Fuschillo et al. 68 % occurrence Donepezil 5 mg/day (n = 16 ) Rivastigmine 1.5–9 mg/day (n = 11) Nausea 8 15 Vomiting 5 10 Dizziness 10 15 Diarrhoea 8 10 Abdominal pain 5 8 Headache 8 10 Wilkinson et al. 69 Treatment-emergent AEs occurring in ≥ 5% of participants and more than twice as frequently in either treatment group (all causalities). No. (%) Donepezil 5 mg/day (n = 56) Rivastigmine 3–12 mg/day (n = 55) Nausea 6 (10.7) 23 (41.8) Vomiting 4 (7.1) 13 (23.6) Headache 4 (7.1) 10 (18.2) Anorexia 1 (1.8) 5 (9.1) Abnormal dreams 4 (7.1) 1 (1.8) Back pain 4 (7.1) 0 Somnolence 1 (1.8) 3 (5.5) Urinary tract infection 3 (5.4) 0 Proportion experiencing 42.9% 58.2% ≥ 1 treatment-related advance event ● Two studies compared treatment with donepezil with treatment with rivastigmine. The methodological quality and the quality of reporting in the studies was generally poor and one study had a small sample size. One study was funded by the manufacturers of donepezil. ● On measures of cognitive ability, general trends suggest that treatment with rivastigmine (1.5–12 mg/day) leads to more improvement than treatment with 5 mg/day donepezil; however, these trends are small, are not tested for statistical significance and may also reflect the differences in the doses given. 69
Page 1 and 2:
Health Technology Assessment 2006;
Page 3 and 4:
The clinical and cost-effectiveness
Page 5 and 6:
Objectives: To provide an update re
Page 7 and 8:
List of abbreviations .............
Page 9 and 10:
AChEI acetylcholinesterase inhibito
Page 11 and 12:
Epidemiology and background Alzheim
Page 13:
Galantamine Five published economic
Page 17 and 18:
Description of underlying health pr
Page 19 and 20:
TABLE 1 Estimated prevalence of AD
Page 21 and 22:
as one component of their care. A n
Page 23 and 24:
The a priori methods used for syste
Page 25:
Data synthesis Data were synthesise
Page 28 and 29:
14 Clinical effectiveness TABLE 3 C
Page 30 and 31:
16 Clinical effectiveness TABLE 3 C
Page 32 and 33: 18 Clinical effectiveness particula
Page 34 and 35: 20 Clinical effectiveness Compariso
Page 36 and 37: 22 Clinical effectiveness TABLE 6 M
Page 38 and 39: 24 Clinical effectiveness donepezil
Page 46 and 47: 32 Clinical effectiveness DAD The D
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
Page 60 and 61: 46 Clinical effectiveness Summary:
Page 62 and 63: 48 Clinical effectiveness differenc
Page 66 and 67: 52 Clinical effectiveness This appe
Page 76 and 77: 62 Clinical effectiveness placebo [
Page 80 and 81: 66 Clinical effectiveness (24 mg/da
Page 84 and 85: 70 Clinical effectiveness ● One R
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
Page 98 and 99: 84 TABLE 49 Economic analysis Outli
Page 100 and 101: 86 Economic analysis The UK study r
Page 102 and 103: 88 Economic analysis The AD2000 stu
Page 104 and 105: 90 Economic analysis term). Where w
Page 106 and 107: 92 Economic analysis published econ
Page 108 and 109: 94 Economic analysis Fenn and Gray
Page 110 and 111: 96 Economic analysis one another. W
Page 112 and 113: 98 Economic analysis outcomes: (1)
Page 114 and 115: 100 Economic analysis respond to ga
Page 116 and 117: 102 Economic analysis donepezil, ri
Page 118 and 119: 104 Economic analysis of this study
Page 120 and 121: 106 Economic analysis independent,
Page 122 and 123: 108 Economic analysis classificatio
Page 124 and 125: 110 Economic analysis survey studie
Page 126 and 127: 112 Economic analysis vascular deme
Page 128 and 129: 114 Economic analysis Livingston an
Page 130 and 131: 116 Economic analysis sensitive to
Page 132 and 133:
118 Economic analysis Neumann and c
Page 134 and 135:
120 Economic analysis The model str
Page 136 and 137:
122 Economic analysis CEA, given th
Page 138 and 139:
124 Economic analysis TABLE 70 Key
Page 140 and 141:
126 Economic analysis TABLE 73 Prof
Page 142 and 143:
128 Economic analysis Probability o
Page 144 and 145:
130 Economic analysis Results are s
Page 146 and 147:
132 Economic analysis 4. The model
Page 148 and 149:
134 Economic analysis perspective e
Page 150 and 151:
136 Economic analysis indicating th
Page 153:
Ongoing research, with relevance to
Page 157:
The increasing numbers of the very
Page 160 and 161:
146 Discussion and conclusions dose
Page 162 and 163:
148 Discussion and conclusions effo
Page 164 and 165:
150 Discussion and conclusions Stre
Page 167 and 168:
1. Clegg A, Bryant J, Nicholson T,
Page 169 and 170:
placebo-controlled study of donepez
Page 171 and 172:
94. Brooks E, Deal L. The effect of
Page 173 and 174:
of memantine in patients with moder
Page 175:
This version of HTA monograph volum
Page 179 and 180:
376 Health Technology Assessment Pr
Page 181:
378 Health Technology Assessment Pr
show all

Donepezil, rivastigmine, galantamine and memantine for ...

Create successful ePaper yourself

Delete template?

Save as template?