Table 1:
Summary of findings
| Outcome | Studies (N) | Participants (N) | Risk of Bias | Inconsistency | Indirectness | Imprecision | Reporting bias | Pooled RR (95% CI, p) | Quality |
|---|---|---|---|---|---|---|---|---|---|
| Comparison: Infliximab combination therapy vs. infliximab monotherapy | |||||||||
| ADA formation (all studies) | 13 | 1825 | High | Low | No indirectness | 405 events | None | 0.52 (0.44, 0.62; p<0.001) | ⊕⊕⊕⊕ High |
| ADA formation (randomized to monotherapy or combination therapy) | 3 | 413 | Low | No | No indirectness | 40 events | None | 0.13 (0.05, 0.33; p<0.001) | ⊕⊕⊕⊝ Moderate1 |
| ADA formation (observational data) | 10 | 1412 | High | No | No indirectness | 365 events | None | 0.59 (0.49, 0.71; p<0.001) | ⊕⊕⊕⊕ High |
| ADA formation (induction treatment) | 3 | 352 | High | No | No indirectness | 197 events | None | 0.57 (0.47, 0.70; p<0.001) | ⊕⊕⊕⊝ Moderate1 |
| ADA formation (maintenance treatment) | 10 | 1473 | High | Moderate | No indirectness | 208 events | None | 0.47 (0.35, 0.63; p<0.001) | ⊕⊕⊕⊝ Moderate1 |
| ADA formation (CD patients) | 10 | 1471 | High | Low | No indirectness | 378 events | None | 0.52 (0.44, 0.62; p<0.001) | ⊕⊕⊕⊕ High |
| ADA formation (UC patients) | 1 | 68 | Low | Not applicable | Not applicable | 8 events | None | 0.12 (0.02, 0.92; p=0.04) | ⊕⊕⊝⊝ Low2 |
| ADA formation (IBD patients) | 2 | 286 | High | No | No indirectness | 19 events | None | 0.83 (0.34, 2.03; p=0.68) | ⊕⊕⊝⊝ Low2 |
| ADA formation (Thiopurines only) | 4 | 491 | High | Moderate | No indirectness | 108 events | None | 0.50 (0.37, 0.67; p<0.001) | ⊕⊕⊕⊝ Moderate1 |
| ADA formation (MTX only) | 2 | 235 | High | Moderate | No indirectness | 81 events | None | 0.51 (0.36. 0.72; p<0.001) | ⊕⊕⊕⊝ Moderate1 |
| ADA formation (Corticosteroids only) | 2 | 477 | Low | Low | No indirectness | 89 events | None | 0.80 (0.53, 1.22; p=0.30) | ⊕⊕⊕⊝ Moderate1 |
| ADA formation (Drug sensitive assays) | 11 | 1561 | High | Low | No indirectness | 342 events | None | 0.49 (0.41, 0.60; p<0.001) | ⊕⊕⊕⊕ High |
| ADA formation (Drug tolerant assays) | 2 | 264 | High | High | No indirectness | 63 events | None | 0.67 (0.44, 1.04; p=0.07) | ⊕⊕⊝⊝ Low3 |
| Comparison: Infliximab ADA positive vs ADA undetectable | |||||||||
| Clinical response | 7 | 1127 | High | No | No indirectness | 573 events | None | 0.75 (0.61, 0.91; p=0.004) | ⊕⊕⊕⊕ High |
| Infusion reactions | 5 | 1242 | Low | Moderate | No indirectness | 230 events | None | 2.36 (1.85, 3.01; p<0.001) | ⊕⊕⊕⊝ Moderate1 |
| Comparison: Adalimumab combination therapy vs. adalimumab monotherapy | |||||||||
| ADA formation (all data) | 5 | 698 | Low | No | No indirectness | 38 events | None | 0.34 (0.16, 0.75; p=0.007) | ⊕⊕⊕⊝ Moderate1 |
| ADA formation (maintenance treatment) | 4 | 539 | Low | No | No indirectness | 38 events | None | 0.31 (0.14, 0.69; p=0.004) | ⊕⊕⊕⊝ Moderate1 |
| Comparison: Golimumab combination therapy vs. golimumab monotherapy | |||||||||
| ADA formation | 1 | 1103 | Low | Not applicable | Not applicable | 32 events | None | 0.29 (0.10, 0.83; p=0.02) | ⊕⊕⊕⊝ Moderate |
| Comparison: Golimumab ADA positive vs ADA undetectable | |||||||||
| Clinical response (week 6) | 1 | 720 | Low | Not applicable | Not applicable | 374 events | None | 1.26 (0.91, 1.75; p=0.17) | ⊕⊕⊕⊕ High |
| Clinical response (week 54) | 1 | 263 | Low | Not applicable | Not applicable | 146 events | None | 0.51 (0.16, 1.65; p=0.26) | ⊕⊕⊕⊝ Moderate1 |
| Clinical remission (week 6) | 1 | 720 | Low | Not applicable | Not applicable | 135 events | None | 1.35 (0.62, 2.92; p=0.45) | ⊕⊕⊕⊝ Moderate1 |
| Clinical remission (week 54) | 1 | 263 | Low | Not applicable | Not applicable | 77 events | None | 0.48 (0.08, 2.98; p=0.43) | ⊕⊕⊕⊝ Moderate1 |
| Mucosal healing (week 6) | 1 | 720 | Low | Not applicable | Not applicable | 316 events | None | 1.26 (0.84, 1.89; p=0.26) | ⊕⊕⊕⊕ High |
| Mucosal healing (week 54) | 1 | 263 | Low | Not applicable | Not applicable | 127 events | None | 0.59 (0.18, 1.90; p=0.37) | ⊕⊕⊕⊝ Moderate1 |
| Comparison: Certolizumab pegol combination therapy vs. certolizumab pegol monotherapy | |||||||||
| ADA formation (all data) | 2 | 1139 | Low | Low | No indirectness | 43 events | None | 0.30 (0.14, 0.67; p=0.003) | ⊕⊕⊕⊝ Moderate1 |
| Comparison: Ustekinumab combination therapy vs. ustekinumab monotherapy | |||||||||
| ADA formation (all data) | 2 | 917 | Low | Low | No indirectness | 50 events | None | 0.59 (0.30, 1.18; p<0.13) | ⊕⊕⊕⊝ Moderate1 |
| Comparison: Natalizumab combination therapy vs. natalizumab monotherapy | |||||||||
| ADA formation (all data) | 3 | 763 | Low | No | No indirectness | 70 events | None | 0.17 (0.08, 0.38; p<0.001) | ⊕⊕⊕⊝ Moderate1 |
1
Downgraded 1 level due to sparse data
2
Downgraded 2 levels due to sparse data
3
Downgraded 2 levels due to sparse data & high heterogeneity
ADA: anti-drug antibodies; IBD: inflammatory bowel disease; CD: Crohn’s disease; UC: ulcerative colitis; MTX: methotrexate.