Table 2. Primary and Secondary Outcomes for CREAD.
| Variablea | Placebo | Crenezumab | Mean difference (95% CI) | ||
|---|---|---|---|---|---|
| No. | Mean change from baseline at week 105 (95% CI) | No. | Mean change from baseline at week 105 (95% CI) | ||
| CDR-SB scoreb | 88 | 3.42 (2.90 to 3.93) | 86 | 3.59 (3.07 to 4.11) | −0.17 (−0.86 to 0.53) |
| CDR-GS score | 88 | 0.55 (0.44 to 0.66) | 86 | 0.50 (0.39 to 0.61) | 0.05 (−0.10 to 0.20) |
| MMSE score | 90 | −4.63 (−5.37 to −3.89) | 87 | −4.96 (−5.72 to −4.21) | 0.33 (−0.62 to 1.29) |
| ADAS-Cog11 score | 86 | 8.43 (6.94 to 9.92) | 80 | 8.53 (7.01 to 10.05) | −0.10 (−2.08 to 1.88) |
| ADAS-Cog13 score | 86 | 9.55 (7.94 to 11.17) | 80 | 9.82 (8.16 to 11.47) | −0.26 (−2.39 to 1.87) |
| ADCS-ADL | 90 | −11.51 (−13.92 to −9.10) | 88 | −13.39 (−15.83 to −10.94) | 1.88 (−1.43 to 5.18) |
| ADCS-iADL subscore | 90 | −9.22 (−11.12 to −7.31) | 88 | −10.44 (−12.37 to −8.51) | 1.22 (−1.35 to 3.79) |
| NPI-Q total severity score | 84 | 1.02 (−0.09 to 2.12) | 87 | 1.55 (0.45 to 2.64) | −0.53 (−1.95 to 0.90) |
| Patient QoL-AD total score | 90 | −1.69 (−2.67 to –0.70) | 86 | −2.08 (−3.09 to −1.07) | 0.40 (–0.81 to 1.60) |
| ZCI-AD total score | 86 | 22.72 (12.62 to 32.82) | 87 | 24.11 (14.07 to 34.15) | −1.39 (−13.64 to 10.86) |
| Patient EQ-5D VAS score | 89 | −4.54 (–7.94 to –1.13) | 87 | −6.35 (–9.82 to −2.89) | 1.82 (−2.64 to 6.27) |
| Caregiver EQ-5D VAS total score | 89 | −3.16 (−6.53 to 0.21) | 88 | −4.09 (−7.48 to −0.71) | 0.94 (−3.45 to 5.32) |
Abbreviations: ADAS-Cog13, Alzheimer’s Disease Assessment Scale 13; ADAS-Cog11, Alzheimer’s Disease Assessment Scale 11; ADCS-ADL, Alzheimer’s Disease Cooperative Study–Activities of Daily Living; ADCS-iADL, Alzheimer’s Disease Cooperative Study–Activities of Daily Living Instrumental Subscale; CDR-GS, Clinical Dementia Rating Scale–Global score; CREAD, A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy and Safety Study of Crenezumab in Patients With Prodromal to Mild Alzheimer’s Disease; MMSE, Mini-Mental State Examination; NPI-Q, Neuropsychiatric Inventory Questionnaire; QoL-AD, Quality of Life–Alzheimer Dementia; VAS, visual analogue scale; ZCI-AD, Zarit Caregiver Interview for Alzheimer Disease scale.
Analyses conducted using mixed model for repeated measures in the modified intent-to-treat analysis. Secondary efficacy measures included cognition assessed by ADAS-Cog11 (score range 0 to 70); ADAS-Cog13 (score range 0 to 85), in which higher scores indicate greater impairment9,10; MMSE (score range 0 to 30), with lower scores indicating more severe impairment11; dementia severity assessed by CDR-GS (score range 0 to 3), with higher score indicating more severe dementia13; function assessed by ADCS-ADL (score range 0 to 78); and the instrumental subscale of ADCS-ADL (score range 0 to 56),12 where lower scores indicate worse functioning. Behavioral disturbances were assessed with NPI-Q (severity score range from 0 to 36), where higher scores indicate more severe symptoms,14 The impact of crenezumab on quality of life and caregiver burden was measured using QoL-AD scale,15 ZCI-AD scale16,17 (modified from the original Zarit Burden Interview), and EQ-5D VAS score for patients and caregivers.17,18