Table 1.
Study and patients baseline characteristics.
| Study ID | Duration of treatment (weeks) | Reason for study discontinuation | AD stage (MMSE score for inclusion) | Study arms included in the meta-analysis | No of patients randomized, n | Age (mean ± SD), years | Male, n (%) | Female, n (%) | APOE ε4 carrier, n (%) | CDR-SOB (mean ± SD) | ADAS-Cog† (mean ± SD) | MMSE (mean ± SD) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Doody 2014 (EXPEDITION 1, NCT00905372) | 80 | N/A | Mild-to-moderate (16–26) | Solanezumab 400 mg IV Q4W | 506 | 75.0 ± 7.9 | 207 (40.9) | 299 (59.1) | 266 (57.3) (tested in a subset of 464 patients) | NR | 22.0 ± 8.0 | 21.0 ± 4.0 |
| Placebo | 506 | 74.4 ± 8.0 | 219 (43.3) | 287 (56.7) | 288 (61.3) (tested in a subset of 470 patients) | NR | 22.0 ± 9.0 | 21.0 ± 3.0 | ||||
| Doody 2014 (EXPEDITION 2, NCT00812565) | 80 | N/A | Mild-to-moderate (16–26) | Solanezumab 400 mg IV Q4W | 521 | 72.5 ± 8.0 | 238 (45.7) | 283 (54.3) | 263 (56.8) (tested in a subset of 463 patients) | NR | 24.0 ± 9.0 | 21.0 ± 3.0 |
| Placebo | 519 | 72.4 ± 7.8 | 233 (44.9) | 286 (55.1) | 281 (59.5) (tested in a subset of 472 patients) | NR | 23.0 ± 10.0 | 21.0 ± 3.0 | ||||
| Honig 2018 (EXPEDITION 3, NCT01900665) | 80 | N/A | Mild (20–26) | Solanezumab 400 mg IV Q4W | 1057 | 72.7 ± 7.8 | 457 (43.2) | 600 (56.8) | 712 (69.3) (tested in a subset of 1027 patients) | 3.9 ± 1.9 | 28.9 ± 8.3 | 22.8 ± 2.8 |
| Placebo | 1072 | 73.3 ± 8.0 | 441 (41.1) | 631 (58.9) | 685 (66.3) (tested in a subset of 1033 patients) | 3.9 ± 2.0 | 29.7 ± 8.5 | 22.6 ± 2.9 | ||||
| Sperling 2023 (A4, NCT02008357) | 240 | N/A | Prodromal AD (MMSE ≥ 25) | Solanezumab 1600 mg IV Q4W | 564 | 72.0 ± 4.7 | 235 (41.7) | 329 (58.3) | 333 (59.0) | 0.1 ± 0.2 | 28.8 ± 1.3 | |
| Placebo | 583 | 71.9 ± 5.0 | 231 (39.6) | 352 (60.4) | 342 (58.7) | 0.0 ± 0.2 | 28.8 ± 1.2 | |||||
| Salloway 2014 (Bapineuzumab 301, NCT00574132) | 78 | N/A | Mild-to-moderate (16–26) | Bapineuzumab 0.5 mg/kg IV Q13W | 337 | 73.0 ± 9.5 | 162 (48.1) | 175 (51.9) | 0 (0.0) | NR | 22.3 ± 9.6 | 21.2 ± 3.4 |
| Bapineuzumab 1.0 mg/kg IV Q13W | 329 | 73.2 ± 9.4 | 143 (43.5) | 186 (56.5) | 0 (0.0) | NR | 22.3 ± 9.9 | 21.2 ± 3.3 | ||||
| placebo | 524 | 71.8 ± 10.1 | 258 (49.2) | 266 (50.8) | 0 (0.0) | NR | 22.1 ± 10.1 | 21.3 ± 3.2 | ||||
| Salloway 2014 (Bapineuzumab 302, NCT00575055) | 78 | N/A | Mild-to-moderate (16–26) | Bapineuzumab 0.5 mg/kg IV Q13W | 673 | 72.1 ± 8.1 | 304 (45.2) | 369 (54.8) | 673 (100.0) | NR | 23.6 ± 9.5 | 20.7 ± 3.1 |
| placebo | 448 | 72.4 ± 8.3 | 196 (43.7) | 252 (56.3) | 448 (100.0) | NR | 23.9 ± 9.8 | 20.7 ± 3.2 | ||||
| Vandenberghe 2016 (Bapineuzumab 3000, NCT00667810) | 78 | Lack of clinical efficacy observed in Bapineuzumab 301 and 302 studies | Mild-to-moderate (16–26) | Bapineuzumab 0.5 mg/kg IV Q13W | 267 | 71.4 ± 9.4 | 116 (43.4) | 151 (56.6) | 0 (0.0) | NR | 23.2 (10.0) | 20.8 ± 3.2 |
| Bapineuzumab 1.0 mg/kg IV Q13W | 263 | 70.8 ± 9.7 | 113 (43.0) | 150 (57.0) | 0 (0.0) | NR | 23.5 (9.3) | 20.8 ± 3.1 | ||||
| Placebo | 344 | 69.9 ± 9.8 | 145 (42.2) | 199 (57.8) | 0 (0.0) | NR | 22.9 (10.2) | 20.8 ± 3.1 | ||||
| Vandenberghe 2016 (Bapineuzumab 3001, NCT00676143) | 78 | Lack of clinical efficacy observed in Bapineuzumab 301 and 302 studies | Mild-to-moderate (16–26) | Bapineuzumab 0.5 mg/kg IV Q13W | 654 | 71.0 ± 7.7 | 233 (35.6) | 421 (64.4) | 654 (100.0) | NR | 23.2 (8.9) | 20.9 ± 3.1 |
| Placebo | 439 | 70.3 ± 7.8 | 177 (40.3) | 262 (59.7) | 439 (100.0) | NR | 22.6 (8.9) | 21.0 ± 3.0 | ||||
| Ostrowitzki 2022 (CREAD, NCT02670083) | 105 | Futility based on interim analysis | Prodromal-to-mild (≥ 22) | Crenezumab 60 mg/kg IV Q4W | 404 | 71.0 ± 7.9 | 168 (41.6) | 236 (58.4) | 293 (72.7) | 3.9 ± 1.7 | 29.4 ± 7.6 | 23.7 ± 3.0 |
| Placebo | 409 | 70.3 ± 8.4 | 162 (39.6) | 247 (60.4) | 292 (71.7) | 3.8 ± 1.6 | 28.9 ± 7.4 | 23.4 ± 2.9 | ||||
| Ostrowitzki 2022 (CREAD2, NCT03114657) | 105 | Futility based on interim analysis | Prodromal-to-mild (≥ 22) | Crenezumab 60 mg/kg IV Q4W | 407 | 71.1 ± 7.5 | 176 (43.2) | 231 (56.8) | 271 (66.9) | 3.7 ± 1.6 | 28.8 ± 7.4 | 23.6 ± 2.8 |
| Placebo | 399 | 70.7 ± 7.9 | 174 (43.6) | 225 (56.4) | 263 (65.9) | 3.8 ± 1.6 | 28.9 ± 7.3 | 23.5 ± 2.9 | ||||
| Ostrowitzki 2017 (Scarlet RoAD, NCT01224106) | 104 | Futility based on interim analysis | Prodromal (≥ 24) | Gantenerumab 105 mg SC Q4W | 271 | 70.3 ± 7.0 | 119 (43.9) | 152 (56.1) | 151 (79.0) (tested in a subset of 191 patients) | 2.2 ± 1.0 | 23.1 ± 6.9 | 25.7 ± 2.3 |
| Gantenerumab 225 mg SC Q4W | 260 | 71.3 ± 7.1 | 108 (41.5) | 152 (58.5) | 112 (61.5) (tested in a subset of 182 patients) | 2.0 ± 0.9 | 23.0 ± 6.2 | 25.7 ± 2.2 | ||||
| Placebo | 266 | 79.5 ± 7.5 | 117 (44.0) | 149 (56.0) | 131 (70.3) (tested in a subset of 186 patients) | 2.1 ± 1.0 | 23.5 ± 7.2 | 25.7 ± 2.1 | ||||
| Voyle 2018 (Marguerite RoAD, NCT02051608) | 104 | Futility based on interim analysis | Mild (20–26) | Gantenerumab 105–225 mg SC Q4W | 192 | 69.7 ± 8.9 | 94 (49.0) | 98 (51.0) | NR | NR | NR | NR |
| Placebo | 195 | 70.1 ± 8.6 | 82 (42.1) | 113 (57.9) | NR | NR | NR | NR | ||||
| Bateman 2023 (GRADUATE I, NCT03444870) | 116 | N/A | Prodromal-to-mild (≥ 22) | Gantenerumab 510 mg SC Q2W | 499 | 61.1 ± 7.9 | 209 (41.9) | 290 (58.1) | 326 (65.3) | 3.7 ± 1.7 | 28.1 ± 7.1 | 23.5 ± 3.3 |
| placebo | 485 | 72.1 ± 7.8 | 230 (47.4) | 255 (52.6) | 328 (67.6) | 3.7 ± 1.6 | 28.1 ± 6.8 | 23.6 ± 3.0 | ||||
| Bateman 2023 (GRADUATE II, NCT03443973) | 116 | N/A | Prodromal-to-mild (≥ 22) | Gantenerumab 510 mg SC Q2W | 498 | 71.6 ± 7.8 | 210 (42.2) | 288 (57.8) | 333 (66.9) | 3.7 ± 1.6 | 28.1 ± 6.9 | 23.6 ± 3.1 |
| Placebo | 477 | 71.8 ± 7.4 | 192 (40.3) | 285 (59.7) | 321 (67.2) | 3.5 ± 1.5 | 28.2 ± 7.0 | 23.8 ± 3.2 | ||||
| Haeberlein 2022 (EMERGE, NCT02484547) | 78 | Futility based on interim analysis | Prodromal-to-mild (24–30) | Aducanumab 3 mg/kg (APOE ε4+) or 6 mg/kg (APOE ε4-) IV Q4W | 543 | 70.6 ± 7.4 | 274 (50.5) | 269 (49.5) | 362 (67.0) | 2.5 ± 1.0 | 22.5 ± 6.8 | 26.3 ± 1.7 |
| Aducanumab 6 mg/kg (APOE ε4+) or 10 mg/kg (APOE ε4-) IV Q4W | 547 | 70.6 ± 7.5 | 263 (48.1) | 284 (51.9) | 365 (67.0) | 2.5 ± 1.1 | 22.3 ± 7.1 | 26.3 ± 1.7 | ||||
| Placebo | 548 | 70.8 ± 7.4 | 258 (47.1) | 290 (52.9) | 368 (67.0) | 2.5 ± 1.0 | 21.9 ± 6.7 | 26.4 ± 1.8 | ||||
| Haeberlein 2022 (ENGAGE, NCT02477800) | 78 | Futility based on interim analysis | Prodromal-to-mild (24–30) | Aducanumab 3 mg/kg (APOE ε4+) or 6 mg/kg (APOE ε4-) IV Q4W | 547 | 70.4 ± 7.0 | 263 (48.1) | 284 (51.9) | 391 (71.0) | 2.4 ± 1.0 | 22.5 ± 6.3 | 26.4 ± 1.8 |
| Aducanumab 6 mg/kg (APOE ε4+) or 10 mg/kg (APOE ε4-) IV Q4W | 555 | 70.0 ± 7.7 | 263 (47.4) | 292 (52.6) | 378 (68.0) | 2.4 ± 1.0 | 22.4 ± 6.5 | 26.4 ± 1.8 | ||||
| Placebo | 544 | 69.8 ± 7.7 | 258 (47.3) | 286 (52.7) | 376 (69.0) | 2.4 ± 1.0 | 22.5 ± 6.6 | 26.4 ± 1.7 | ||||
| Sims 2023 (TRAILBLAZER-ALZ 2, NCT04437511) | 76 | N/A | Prodromal-to-mild AD (MMSE: 20–28) | Donanemab 1400 mg IV Q4W | 860 | 73.0 ± 6.2 | 367 (42.7) | 493 (57.3) | 598 (69.8) | 4.0 ± 2.1 | 28.7 ± 8.8 | 22.4 ± 3.8 |
| Placebo | 876 | 73.0 ± 6.2 | 373 (42.6) | 503 (57.4) | 621 (71.2) | 3.9 ± 2.1 | 29.3 ± 8.9 | 22.2 ± 3.9 | ||||
| Salloway 2022 (TRAILBLAZER-ALZ 4, NCT05108922)§ | 76 | N/A | 20–30 | Donanemab 1400 mg IV Q4W | 71 | 74.1 ± 6.9 | 33 (46.5) | 38 (53.5) | 49 (69.0) | NR | NR | 25.0 ± 2.7 |
| Aducanumab 10 mg/kg IV Q4W | 69 | 72.7 ± 6.8 | 27 (39.1) | 42 (60.9) | 49 (71.0) | NR | NR | 24.4 ± 3.0 | ||||
| van Dyck 2022 (CLARITY AD, NCT03887455) | 72 weeks | N/A | Prodromal-to-mild (24–30) | Lecanemab 10 mg/kg IV Q2W | 859 | 71.4 ± 7.9 | 416 (48.4) | 443 (51.6) | 592 (68.9) | 3.2 ± 1.3 | 24.5 ± 7.1 | 25.5 ± 2.2 |
| placebo | 875 | 71.0 ± 7.8 | 411 (47.0) | 464 (53.0) | 600 (68.6) | 3.2 ± 1.3 | 24.4 ± 7.6 | 25.6 ± 2.2 |