Page 49 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

Table 8: Key questions and summary of the evidence
Quality of Conclusion
Key Question
Evidence
Key Question 1: Poor to fair No double-blind head-to-head trial compared one AD drug
Efficacy / Effectiveness to another. Three open-label head-to-head trials
compared the efficacy of one AD medication to another;
two trials compared donepezil to galantamine and one trial
compared donepezil to rivastigmine. Evidence for the
comparison of donepezil with galantamine is mixed. In one
52-week trial, donepezil and galantamine did not differ in
stabilizing symptoms or improving behavior and functional
status. In a shorter trial (12 weeks), donepezil was
superior to galantamine in its effects on cognition,
functional status, and caregiver and clinician satisfaction.
The comparison of donepezil to rivastigmine is limited to a
single 12-week trial; similar improvements in cognitive
scores were reported for both drugs, although clinician and
caregiver satisfaction ratings were significantly better for
donepezil. Both trials that reported significant differences
were funded by the manufacturer of donepezil while the
trial reporting no differences was funded by the
manufacturer of galantamine.

Evidence of general efficacy for donepezil, galantamine,
rivastigmine, tacrine, and memantine is fair; 1 placebo-
controlled effectiveness trial, 22 efficacy trials, and 8
systematic reviews support modest effects on symptom
stabilization, behavior, and functional status as measured
by various scales. Although some trials did not support
statistically significant differences between active treatment
and placebo on all outcome measures, most trials yielded
data supporting modest improvement or a slower rate of
decline in measures of cognition and global assessment.
Fewer data supported differences in measures of behavior,
functioning, rate of institutionalization, or caregiver burden.

Although evidence of general efficacy is fair, evidence of
effectiveness is poor. We identified only one trial
considered to demonstrate effectiveness.

Key Question 2: Poor We did not identify any study that directly compared the
Time to Effect time to effect or time required to assess the clinical
response of one AD drug compared to another. Placebo-
controlled trials are too heterogeneous with respect to
study design, outcomes assessment, and populations to
allow any inferences about the comparative time to effect
or time required to assess clinical response.

Key Question 3: Poor to Fair Head-to-head trials did not present differences in adverse
Adverse events events between donepezil and galantamine, and donepezil
and rivastigmine. Indirect evidence from placebo-controlled
trials indicates a substantially higher risk of hepatotoxicity
for tacrine than for donepezil, galantamine, rivastigmine,
and memantine.

Key Question 4: Poor We did not identify any study specifically designed to
Subgroups compare the effect of donepezil, galantamine, rivastigmine,
tacrine, or memantine in one subgroup of patients

Alzheimer's Drugs Page 49 of 205