Table 2. Clinical Outcomes From Baseline to 76 Weeks in the Low/Medium Tau and Combined Populations.
| Outcomea | Group | Donanemab | Placebo | LSM difference vs placebo (95% CI) | P value vs placebo | Slowing of clinical progression, % (95% CI)b | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Mean (SD) | LSM change (95% CI) | Mean (SD) | LSM change | |||||||
| Baseline | 76 Weeks | Baseline | 76 Weeks | |||||||
| iADRS | Low/medium tau | n = 533 | n = 418 | n = 560 | n = 444 | |||||
| NCS2c | 105.92 (13.72) | 101.31 (18.23) | −6.02 (−7.01 to −5.03) | 105.95 (13.42) | 98.88 (17.95) | −9.27 (−10.23 to −8.31) | 3.25 (1.88 to 4.62) | <.001 | 35.1 (19.90 to 50.23) | |
| MMRMd | 105.92 (13.72) | 101.31 (18.23) | −5.81 (−6.90 to −4.71) | 105.95 (13.42) | 98.88 (17.96) | −9.61 (−10.67 to −8.56) | 3.80 (2.36 to 5.25) | <.001 | 39.6 (23.93 to 55.22) | |
| Combined | n = 775 | n = 583 | n = 824 | n = 653 | ||||||
| NCS2c | 104.55 (13.90) | 96.98 (20.87) | −10.19 (−11.22 to −9.16) | 103.82 (13.88) | 93.82 (20.38) | −13.11 (−14.10 to −12.13) | 2.92 (1.51 to 4.33) | <.001 | 22.3 (11.38 to 33.15) | |
| MMRMd | 104.55 (13.90) | 96.98 (20.87) | −10.19 (−11.27 to −9.11) | 103.82 (13.88) | 93.82 (20.38) | −13.22 (−14.27 to −12.18) | 3.03 (1.60 to 4.47) | <.001 | 22.9 (11.96 to 33.92) | |
| CDR-SB | Low/medium tau | n = 546 | n = 424 | n = 569 | n = 459 | |||||
| NCS2 | 3.72 (2.09) | 4.64 (2.90) | 1.16 (0.97 to 1.35) | 3.64 (1.99) | 5.13 (2.93) | 1.84 (1.65 to 2.02) | −0.68 (−0.94 to −0.42) | <.001 | 37.0 (22.26 to 51.75) | |
| MMRMc,d | 3.72 (2.09) | 4.64 (2.90) | 1.20 (1.00 to 1.41) | 3.64 (1.99) | 5.13 (2.93) | 1.88 (1.68 to 2.08) | −0.67 (−0.95 to −0.40) | <.001 | 36.0 (20.76 to 51.15) | |
| Combined | n = 794 | n = 598 | n = 838 | n = 672 | ||||||
| NCS2 | 3.92 (2.06) | 5.25 (3.21) | 1.66 (1.48 to 1.83) | 3.89 (2.03) | 5.80 (3.22) | 2.33 (2.16 to 2.50) | −0.67 (−0.92 to −0.43) | <.001 | 28.9 (18.26 to 39.53) | |
| MMRMc,d | 3.92 (2.06) | 5.25 (3.21) | 1.72 (1.53 to 1.91) | 3.89 (2.03) | 5.80 (3.22) | 2.42 (2.24 to 2.60) | −0.70 (−0.95 to −0.45) | <.001 | 28.9 (18.41 to 39.44) | |
| ADCS-iADL | Low/medium tau | n = 535 | n = 420 | n = 562 | n = 451 | |||||
| NCS2c | 48.20 (7.88) | 46.12 (10.26) | −2.76 (−3.42 to −2.10) | 48.56 (7.70) | 45.10 (9.82) | −4.59 (−5.23 to −3.95) | 1.83 (0.91 to 2.75) | <.001 | 39.9 (19.15 to 60.58) | |
| MMRMd | 48.20 (7.88) | 46.12 (10.26) | −2.66 (−3.39 to −1.94) | 48.56 (7.70) | 45.10 (9.82) | −4.66 (−5.36 to −3.96) | 2.00 (1.04 to 2.96) | <.001 | 42.9 (21.39 to 64.44) | |
| Combined | n = 780 | n = 591 | n = 826 | n = 661 | ||||||
| NCS2c | 47.96 (7.85) | 44.53 (11.06) | −4.42 (−5.05 to −3.80) | 47.98 (7.70) | 43.30 (10.61) | −6.13 (−6.72 to −5.53) | 1.70 (0.84 to 2.57) | <.001 | 27.8 (13.48 to 42.13) | |
| MMRMd | 47.96 (7.85) | 44.53 (11.06) | −4.57 (−5.24 to −3.90) | 47.98 (7.70) | 43.30 (10.61) | −6.32 (−6.97 to −5.67) | 1.75 (0.86 to 2.64) | <.001 | 27.7 (13.37 to 42.00) | |
| ADAS-Cog13 | Low/medium tau | n = 550 | n = 431 | n = 570 | n = 460 | |||||
| NCS2c | 27.41 (8.44) | 29.77 (10.65) | 3.17 (2.64 to 3.69) | 27.60 (8.21) | 31.17 (10.37) | 4.69 (4.18 to 5.20) | −1.52 (−2.25 to −0.79) | <.001 | 32.4 (16.55 to 48.35) | |
| MMRMd | 27.41 (8.44) | 29.77 (10.65) | 3.16 (2.54 to 3.77) | 27.60 (8.21) | 31.17 (10.37) | 4.88 (4.28 to 5.47) | −1.72 (−2.53 to −0.92) | <.001 | 35.3 (18.27 to 52.33) | |
| Combined | n = 797 | n = 607 | n = 841 | n = 677 | ||||||
| NCS2c | 28.53 (8.78) | 32.72 (12.44) | 5.46 (4.91 to 6.01) | 29.16 (8.85) | 34.53 (12.00) | 6.79 (6.26 to 7.32) | −1.33 (−2.09 to −0.57) | <.001 | 19.5 (8.23 to 30.83) | |
| MMRMd | 28.53 (8.78) | 32.72 (12.44) | 5.70 (5.10 to 6.30) | 29.16 (8.85) | 34.53 (12.00) | 7.05 (6.47 to 7.63) | −1.35 (−2.14 to −0.57) | <.001 | 19.2 (7.99 to 30.38) | |
| MMSE | Low/medium tau | n = 549 | n = 429 | n = 573 | n = 465 | |||||
| NCS2 | 23.11 (3.64) | 22.00 (4.90) | −1.61 (−1.89 to −1.33) | 22.88 (3.74) | 21.30 (4.82) | −2.09 (−2.36 to −1.81) | 0.48 (0.09 to 0.87) | .02 | 22.9 (4.04 to 41.84) | |
| MMRMd | 23.11 (3.64) | 22.00 (4.90) | −1.58 (−1.91 to −1.25) | 22.88 (3.74) | 21.30 (4.82) | −2.15 (−2.47 to −1.83) | 0.57 (0.13 to 1.00) | .01 | 26.4 (5.88 to 47.01) | |
| Combined | n = 796 | n = 600 | n = 841 | n = 679 | ||||||
| NCS2 | 22.52 (3.84) | 20.71 (5.52) | −2.47 (−2.73 to −2.20) | 22.20 (3.90) | 19.79 (5.51) | −2.94 (−3.20 to −2.69) | 0.47 (0.10 to 0.84) | .01 | 16.1 (3.49 to 28.67) | |
| MMRMd | 22.52 (3.84) | 20.71 (5.52) | −2.75 (−3.05 to −2.44) | 22.20 (3.90) | 19.79 (5.51) | −3.22 (−3.51 to −2.93) | 0.48 (0.08 to 0.87) | .02 | 14.8 (2.46 to 27.06) | |
Abbreviations: ADAS-Cog13, 13-item cognitive subscale of the Alzheimer Disease Assessment Scale; ADCS-iADL, Alzheimer Disease Cooperative Study—Instrumental Activities of Daily Living; CDR-SB, sum of boxes of the Clinical Dementia Rating Scale; iADRS, Integrated Alzheimer Disease Rating Scale; MMRM, mixed models for repeated measures; MMSE, Mini-Mental State Examination; NCS2, natural cubic spline with 2 degrees of freedom.
Clinical outcomes were scored as follows: ADAS-Cog13 scores range from 0 to 85, with higher scores indicating greater overall cognition deficit; ADCS-iADL range from 0 to 59, with lower scores indicating greater impairment in daily function; CDR-SB range from 0 to 18, with higher scores indicating greater clinical impairment; iADRS range from 0 to 144, with lower scores indicating greater impairment; and MMSE range from 0 to 30, with lower scores indicating greater level of impairment.
The percentage of slowing of clinical progression was calculated by dividing the least-squares mean change from baseline treatment differences at 76 weeks by the least-squares mean change from baseline with placebo at 76 weeks and multiplying by 100. The CI is estimated using the Delta method.
Gated outcome.
For MMRM analyses, 95% CIs for least-squares mean changes were calculated with the normal approximation method.