Table 4.
Anti-TNF therapy immunogenicity–therapeutic outcomes relationship in IBD
| Drug | IBD type | Study type | No | Time point | ADA | Therapeutic outcome | Method | Ref. |
|---|---|---|---|---|---|---|---|---|
| Clinical efficacy | ||||||||
| IFX | CD/UC | Retrospective | 90 (CD: 64) | Induction and maintenance* | Detectable | Treatment failure and discontinuation | HMSA | 11 |
| IFX | CD/UC | Retrospective | 90 (CD: 64) | Induction and maintenance* | >9.1 U/mL | Failure of dose intensification after SLR | HMSA | 11 |
| IFX | CD/UC | Retrospective | 128 (CD: 105) | Induction after drug holiday | Undetectable | Short-term clinical response | HMSA | 63 |
| IFX | CD | Prospective | 125 | Maintenance | >8 μg/mL-eq | Shorter clinical response | ELISA | 23 |
| IFX | CD/UC | Cross-sectional (paediatric) | 134 (CD: 114) | Maintenance | >12 U/mL | Surgery | HMSA | 56 |
| ADM | CD | Retrospective | 130 | Maintenance | Detectable | Treatment discontinuation | ELISA | 26 |
| ADM | CD | Retrospective | 30 | Maintenance | Detectable† | No clinical response | RIA | 57 |
| ADM | CD | Cross-sectional | 118 | Maintenance | Detectable‡ | Active disease | ELISA | 29 |
| Endoscopic and biomarker outcomes | ||||||||
| IFX | UC | Prospective | 19 | Induction | Detectable | No endoscopic response | HMSA | 32 |
| IFX | UC | Retrospective | 101 | Induction (w6) | Detectable | No mucosal healing | ELISA§ | 31 |
| IFX | CD | Retrospective | 45 | Maintenance | Detectable | No mucosal healing | ELISA | 18 |
| IFX | CD/UC | Cross-sectional | 78 (CD: 53) | Maintenance | Undetectable | Mucosal healing | ELISA | 15 |
| IFX | CD | Prospective | 327 | Maintenance | Detectable | CRP >5 mg/L | HMSA | 22 |
| IFX | CD | Observational¶ | 483 | Maintenance | Detectable | CRP >5 mg/L | HMSA | 35 |
| ADM | CD | Prospective | 40 | Maintenance | Detectable | Higher CRP and ESR | ELISA | 36 |
| Loss of response | ||||||||
| IFX | CD/UC | Prospective | 125 (CD: 98) | Induction and maintenance | Detectable | SLR | ELISA | 52 |
| IFX | CD/UC | Case–control | 62 (CD: 51) | Maintenance | Detectable | SLR | ELISA | 58 |
| IFX | CD | Prospective | 53 | Maintenance | Detectable** | SLR | ELISA | 53 |
| IFX | CD/UC | Prospective | 93 (CD: 59) | Maintenance (w22) | Detectable stable ATI†† | SLR | ELISA | 12 |
| IFX | CD | Retrospective | 33 | Maintenance | Detectable | SLR | RIA | 59 |
| IFX | CD | Retrospective (paediatric) | 28 | Maintenance | Detectable | SLR | ELISA | 60 |
| IFX | CD | Retrospective | 106 | Maintenance | Detectable‡‡ | SLR | RIA | 14 |
| ADM | CD | Retrospective | 148 | Maintenance | Detectable | SLR§§ | HMSA | 25 |
| ADM | CD/UC | Retrospective | 72 (CD: 53) | Maintenance | Detectable | SLR§§ | RIA | 61 |
| ADM | CD/UC | Retrospective | 57 (CD: 42) | Maintenance | Detectable | SLR | RIA | 28 |
*Ever had a positive ATI.
†>12 U⁄mL.
‡≥3 μg/mL-eq.
§Recently developed drug-tolerant assay.
**IFX level ≤1.4.
††Two consecutive ATI >20 ng/mL.
‡‡>10 U/mL.
§§Drug discontinuation.
ADA, antidrug antibody; ADM, adalimumab; ATI, antibodies to infliximab; CD, Crohn's disease; CRP, C reactive protein; eq, equivalent; ESR, erythrocyte sedimentation rate; HMSA, homogeneous mobility shift assay; IBD, inflammatory bowel disease; IFX, infliximab; No, number of patients; RIA, Radio-immunoassay; SLR, secondary loss of response; U, units; UC, ulcerative colitis.