However, the observed effects do not reach the minimal clinically important difference of 3.5 to 4 points for ADAS-Cog and 1 to 2 points in CDR-SB and therefore might not be clinically meaningful for patients or caregivers, but the outcomes may not be best for evaluating progression of the disease. The certainty of evidence was downgraded due to imprecision; there was a high number of incomplete outcome data, and the confidence intervals were wide.
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias [Table «Additional comments for included studies...»2. Additional comments] |
|---|---|---|---|---|---|
| SR=systematic review; MA=meta-analysis; MCI= mild cognitive impairment; ADAS-Cog= Alzheimer's Disease Assessment Scale–Cognitive Subscale-11 to 14 items; CDR-SB=Clinical Dementia Rating–Sum Boxes scale | |||||
| «Ebell MH, Barry HC, Baduni K, ym. Clinically Impor...»1 | SR/MA | Adults with MCI or mild Alzheimer disease. Mean age ~70–75 years, mixed sex. Recruited from outpatient memory clinics in North America, Europe, and Asia. | Intervention: Anti-amyloid monoclonal antibodies (donanemab or lecanemab) administered intravenously every 2 or 4 weeks. Comparison: Placebo. | Cognitive outcomes: 1.ADAS-Cog (11–14 item versions). 2.CDR-SB |
Low |
| Reference | Comments |
|---|---|
| «Ebell MH, Barry HC, Baduni K, ym. Clinically Impor...»1 | Trials enrolled adults with cognitive impairment, Alzheimer disease of any severity, or high risk for Alzheimer disease, and had to report at least 1 patient-oriented benefit or harm after a minimum of 1 year. There were no limits by year or language. Trials reporting the results of only a single infusion and phase 1 trials were excluded, as well as trials or trial arms using doses lower than those used in phase 3 trials or ultimately approved by the FDA. |
Results
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Mean (SD) I | Mean (SD) C | Mean difference (95% CI); SMD (95%CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to inconsistency and imprecision. I=intervention; SD=Standard deviation; C=comparison; CI=confidence interval; SMD=Standardized mean difference. |
|||||
| «Ebell MH, Barry HC, Baduni K, ym. Clinically Impor...»1 (Mintun 2021; Sims 2023) | Donanemab: 2 RCTs; total n=1993 (991/1002) |
18–19 months | 2.9 (7.54) and 5.46 (8.20) | 4.77 (7.41) and 6.79 (7.99) | −1.41 points (−2.11 to −0.70); –0.18 (–0.26 to –0.09) |
| «Ebell MH, Barry HC, Baduni K, ym. Clinically Impor...»1 (Swanson 2021; Van Dyck 2023) | Lecanemab: 2 RCTs; total n=2621 (1264/1357) |
18 months | 2.59 (10.00) and 4.14 (17.59) | 4.90 (9.50) and 5.58 (17.75) | −1.8 points (−3.1 to −0.52); –0.11 (–0.19 to –0.02) |
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Mean (SD) I | Mean (SD) C | Mean difference (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to imprecision I= intervention; C=comparison; CI=confidence interval |
|||||
| «Ebell MH, Barry HC, Baduni K, ym. Clinically Impor...»1 (Mintun 2021; Sims 2023) | Donanemab: 2 RCTs; total n=1993 (991/1002) |
18–19 months | 1.22 (2.01) and 1.66 (2.61) | 1.58 (2.00) and 2.33 (2.56) | −0.59 points ( −0.86 to −0.33 |
| «Ebell MH, Barry HC, Baduni K, ym. Clinically Impor...»1 Swanson 2021; Van Dyck 2023) | Lecanebab: 2 RCTs; total n=2621 (1264/1357) |
18 months | 1.10 (2.63) and 1.21 (4.69) | 1.50 (2.47) and 1.66 (5.47) | −0.43 (−0.78 to −0.07) |