Background
Methods
Literature search strategy
Eligibility criteria and study selection
Data extraction
Risk of bias assessment
Data synthesis
Results
Study ID | Study Design | Population | Sample size in each group | Finding | |
---|---|---|---|---|---|
Bapineuzumab | Placebo | ||||
Salloway et al., 2009 [13] | - Phase II, randomized in a ratio of 8:7, double- blinded. - Patients received 6 infusions of bapineuzumab or placebo, 13 weeks apart. Final assessment occurred at 78 weeks. | • Patients aged from 50 to 85 years. • Met criteria for AD and had MRI findings, consistent with AD. • Mini-Mental State Examination (MMSE) score of 16 to 26. • Rosen Modified Hachinski Ischemic score < 4. • Participants were excluded from the study if they had a clinically significant neurological (other than AD) or systemic disease. | 124 patients were allocated in 1 of 4 sequential dose cohorts (0.15, 0.5, 1.0, or 2.0 mg/kg). | 110 patients were allocated to Placebo group. | No significant treatment differences were found in the primary efficacy analysis. However, exploratory analyses showed potential differences on cognitive and functional outcomes in study completers and APOE- 4 non-carriers. |
Salloway et al., 2014 (Carriers) [16] | - Phase IIIa, randomized in a ratio of 3:2, double blinded. - Patients received 6 infusions of bapineuzumab or placebo, 13 weeks apart. Final assessment occurred at 78 weeks. | • Patients aged from 50 to 88 years. • Met criteria for AD and had MRI findings, consistent with AD. • Carriers of the apolipoprotein E (APOE) ε4 allele • Mini–Mental State Examination (MMSE) of 16 to 26. • Score on the Hachinski Ischemic scale of 4 or lower. • Participants were excluded from the study if they had a clinically significant neurological (other than AD) or systemic disease. | 658 patients were allocated to bapineuzumab 0.5 mg per kg group. | 432 patients were allocated to placebo group. | No differences between bapineuzumab and placebo in terms of change from baseline in the ADAS-cog11 and DAD scores (P = 0.80 and 0.34 respectively). Therefore, Bapineuzumab did not improve the clinical outcomes in AD patients. |
Salloway et al., 2014 (Non-carriers) [16] | - Phase IIIb, randomized 3:3:4, double blinded. - Patients received 6 infusions of bapineuzumab or placebo, 13 weeks apart. Final assessment occurred at 78 weeks. | • Patients aged from 50 to 88 years. • Met criteria for AD and had MRI findings, consistent with AD. • Non-Carriers of the apolipoprotein E (APOE) ε4 allele • Mini–Mental State Examination (MMSE) of 16 to 26. • Score on the Hachinski Ischemic scale of 4 or lower. • Participants were excluded from the study if they had a clinically significant neurological (other than AD) or systemic disease. | 621 patients were allocated to bapineuzumab groups. - Bapineuzumab 0.5 mg per kg: 337 - Bapineuzumab 1.0 mg per kg: 307 | 524 patients were allocated to placebo group. | No differences were found between bapineuzumab (Both doses) and placebo groups in terms of change from baseline in the ADAS-cog11 and DAD scores (P = 0.64 and 0.07 respectively). Therefore, bapineuzumab did not improve the clinical outcomes in patients with AD. |
Black et al., 2010 [15] | - Phase II, randomized, third-party unblinded. - Patients received bapineuzumab or placebo with dose escalation every 10 weeks. Final assessment occurred at 52 weeks. | • Patients aged from 50 to 88 years. • Met criteria for AD and had MRI findings, consistent with AD. • Mini-Mental State Examination (MMSE) score of 14 to 26. • Rosen Modified Hachinski Ischemic score ≤ 4. • Participants were excluded from the study if they had a clinically significant neurological (other than AD) or systemic disease. | 22 patients were allocated to bapineuzumab groups. - Bapineuzumab 0.5 mg/kg: 6 - Bapineuzumab 1.5 mg/kg: 6 - Bapineuzumab 5 mg/kg: 10 | 8 patients were allocated to placebo group. | MMSE scores improved at lower doses of bapineuzumab (0.5 and 1.5 mg/kg) compared to placebo, but not with the highest dose (5 mg/kg). Moreover, The 5 mg/kg dose was significantly associated with MRI amyloid abnormalities that resolved over time. |
Arai et al., 2015 [17] | - Phase I, randomized, double- blinded. - Patients received one infusion of the study drug or placebo. Final assessment occurred at 52 weeks. | • Patients aged from 50 to 85 years. • Met criteria for AD and had MRI findings, consistent with AD. • Mini-Mental State Examination (MMSE) score of 14 to 26. • Rosen Modified Hachinski Ischemic score ≤ 4. • Participants were excluded from the study if they had a clinically significant neurological (other than AD) or systemic disease. | 24 patients were equally allocated to 4 dose cohorts (0.15, 0.5, 1, or 2 mg/kg). | 8 patients were allocated to placebo group. | Plasma β-amyloid levels increased with increasing doses of bapineuzumab. Bapineuzumab was well tolerated at all doses in Japanese patients with mild to moderate AD. |
Rinne et al., 2010 [14] | - Phase II, randomized, double- blinded. - Patients received 6 infusions of bapineuzumab or placebo, 13 weeks apart. Final assessment occurred at 78 weeks. | • Patients aged from 50 to 85 years. • Met criteria for AD and had MRI findings, consistent with AD. • Mini-Mental State Examination (MMSE) score of 18 to 26. • Rosen Modified Hachinski Ischemic score ≤ 4. • Participants had amyloid-B loads in the range expected for patients with Alzheimer’s disease, defined as 11C–PiB PET retention ratios relative to the cerebellum of 1 to 5 or more in at least three brain regions among the anterior cingulate, posterior cingulate, frontal, temporal, and parietal cortices. • Participants were excluded from the study if they had a clinically significant neurological (other than AD) or systemic disease. | 19 patients were allocated to 1 of 3 sequential dose cohorts (0.5, 1.0, 2.0 mg/kg). | 7 patients were allocated to placebo group. | Treatment with bapineuzumab for 78 weeks reduced cortical carbon-11-labelled Pittsburgh compound B (C-PiB) retention, compared to placebo. Adverse events were typically mild to moderate in severity and transient in duration. |
Study ID | Drug | N | Age (Mean ± SD) | Sex (male) n (%) | Race (White) n | MMSE score (Mean ± SD) | AChEI or memantineuse, n (%) |
APOE ε4 status carrier no. (%) | ADAS-cog score (Mean ± SD) | DAD score (Mean ± SD) |
---|---|---|---|---|---|---|---|---|---|---|
SSalloway et al., 2009 [13] | Placebo | 107 | 67.9 ± 8.8 | 43 (40.2) | 102 (95.3) | 20.7 ± 3.1 | 103 (96.3) | 74 (69.8) | ….. | …. |
Bapineuzumab | 122 | 70.1 ± 9.6 | 661 (50.0) | 118 (96.7) | 20.9 ± 3.2 | 116 (95.1) | 72 (60.5) | ….. | ….. | |
Black et al., 2010 [15] | Placebo | 8 | 69.8 ± 10.7 | 11 (12.5) | 5 (62.5) | 20.8 | ..... | ..... | ..... | ..... |
Bapineuzumab 0.5 mg/kg | 6 | 74.67 ± 5.65 | 33 (50) | 4 (66.67) | 21.8 | ..... | ..... | ..... | ..... | |
Rinne et al., 2010 [14] | Placebo | 7 | 70 ± 8·81 | 33 (43) | 7 (100) | 22·29 ± 2·69 | 7 (100) | 5 (71) | 19·19 ± 5·27 | 93·78 ± 8·24 |
Bapineuzumab | 19 | 67·26 ± 8·60 | 311 (57.9) | 19 (100) | 21·00 ± 2·33 | 19 (100) | 12 (63) | 22·26 ± 7·65 | 84·38 ± 11·95 | |
Salloway et al., 2014 (Carrier) [16] | Placebo | 432 | 72.3 ± 8.4 | 190 (44) | 420 (97.2) | 20.7 ± 3.2 | 400 (92.6) | 432 (100) | 23.9 ± 9.5 | 79.4 ± 18.9 |
Bapineuzumab 0.5 mg/kg | 658 | 72.0 ± 8.0 | 300 (45.6) | 624 (94.8) | 20.8 ± 3.1 | 606 (92.1) | 658 (100) | 23.5 ± 9.4 | 80.9 ± 17.3 | |
Salloway et al., 2014 (Non-Carrier) [16] | Placebo | 493 | 71.9 ± 10.1 | 245 (49.7) | 469 (95.1) | 21.2 ± 3.2 | 442 (89.7) | 493 (100) | 23.5 ± 9.4 | 80.5 ± 19.2 |
Bapineuzumab 0.5 mg/kg | 314 | 73.1 ± 9.3 | 149 (47.5) | 298 (94.9) | 21.2 ± 3.4 | 281 (89.5) | 314 (100) | 22.4 ± 9.7 | 80.0 ± 18.1 | |
Bapineuzumab 1 mg/kg | 307 | 73.5 ± 9.1 | 132 (42.9) | 292 (95.1) | 21.2 ± 3.3 | 278 (90.6) | 307 (100) | 22.2 ± 10 | 80.4 ± 18.8 | |
Arai et al., 2015 [17] | Placebo | 8 | 68.8 ± 8.9 | 4 (50) | ..... | 20.6 ± 3.0 | ..... | ..... | ..... | ..... |
Bapineuzumab 0.5 mg/kg | 6 | 72.2 ± 8.4 | 5 (83.3) | ..... | 21.0 ± 3.6 | ..... | ..... | ..... | ..... | |
Bapineuzumab 1 mg/kg | 6 | 72.2 ± 10.9 | 3 (50) | ..... | 21.0 ± 4.6 | ..... | ..... | ..... | ..... |