Table 2.
Anti-TNF therapy exposure–response relationship in IBD studies regarding endoscopic and biomarker outcomes
| Drug | IBD type | Study design | No | Time point | TC (μg/mL) | Therapeutic outcome | SN | SP | PPV | NPV | Assay | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Endoscopic outcomes | ||||||||||||
| IFX | UC | Retrospective | 101 | Induction (w6) | ≥15 | Mucosal healing (w10–14) | 60 | 74 | 73 | 62 | ELISA | 31 |
| IFX | UC | Prospective | 19 | Induction (w6) | >6.6 | Endoscopic response* (w8) | 88 | 73 | ND | ND | RIA | 32 |
| IFX | UC | Retrospective | 101 | Postinduction (w14) | ≥2.1 | Mucosal healing (w10–14) | 84 | 62 | 78 | 71 | ELISA | 31 |
| IFX | CD | RCT† (SONIC) | 123 | Maintenance (w30) | ≥3 | Mucosal healing (w26) | 59 | 72 | 73 | 57 | ELISA | 13 |
| IFX | CD | Prospective | 105 | Maintenance | >1.4 | Endoscopic improvement | ND | ND | ND | ND | ELISA | 20 |
| IFX | UC | Prospective | 115 | Maintenance | >1.4 | Endoscopic improvement | ND | ND | ND | ND | ELISA | 17 |
| IFX | CD/UC | Prospective | 52 (CD: 34) | Maintenance | >0.5‡ | Mucosal healing | 89 | 80 | 83 | 87 | ELISA | 33 |
| IFX | CD/UC | Cross-sectional | 72 (CD: 49) | Maintenance | >8.3 | Mucosal healing | 71 | 73 | ND | ND | HMSA | 34 |
| IFX | CD/UC | Cross-sectional | 78 (CD: 53) | Maintenance | >5 | Mucosal healing | 39 | 85 | 70 | 62 | ELISA | 15 |
| IFX | CD | Retrospective | 45 | Maintenance | >4 | Mucosal healing | 71 | 70 | ND | ND | ELISA | 18 |
| ADM | CD/UC | Cross-sectional | 67 (CD: 58) | Maintenance | >7.1 | Mucosal healing | 32 | 85 | 51 | 72 | ELISA | 15 |
| ADM | CD/UC | Cross-sectional | 40 (CD: 22) | Maintenance | >4.9 | Mucosal healing | 66 | 85 | 88 | 51 | ELISA | 27 |
| CZP | CD | RCT† (MUSIC) | 89 | Postinduction (w8) | >23.3 | Endoscopic response and remission (w10) | ND | ND | ND | ND | ELISA | 30 |
| Biomarker outcomes | ||||||||||||
| IFX | CD/UC | Retrospective | 213 (CD: 131) | Maintenance | >3.9 | Normal FC (<250 µg/g) | 74 | 80 | ND | ND | ELISA | 19 |
| IFX | CD/UC | Retrospective | 213 (CD: 131) | Maintenance | >2.9 | CRP normalisation | 69 | 66 | ND | ND | ELISA | 19 |
| IFX | CD | Prospective | 105 | Maintenance | >1.4 | Lower CRP | ND | ND | ND | ND | ELISA | 20 |
| IFX | CD | Observational§ | 483 | Maintenance | >2.79 | Normal CRP | 77 | 52 | ND | ND | HMSA | 35 |
| IFX | CD | Prospective | 327 | Maintenance | <3 | Elevated CRP | ND | ND | ND | ND | HMSA | 22 |
| IFX | CD/UC | Cross-sectional | 78 (CD: 53) | Maintenance | >6.8 | CRP normalisation | 22 | 85 | 59 | 53 | ELISA | 15 |
| IFX | CD | Retrospective | 45 | Maintenance | >0.6 | Normal CRP (≤0.3 mg/dL) | 73 | 62 | ND | ND | ELISA | 18 |
| IFX | CD | Retrospective | 45 | Maintenance | >1.1 | Normal FC (≤300 µg/g) | 72 | 56 | ND | ND | ELISA | 18 |
| ADM | CD/UC | Cross-sectional | 67 (CD: 58) | Maintenance | >6.6 | CRP normalisation | 28 | 85 | 71 | 48 | ELISA | 15 |
| ADM | CD | Prospective | 40 | Maintenance | >5.9 | Normal CRP (≤0.3 mg/dL) | 67 | 92 | ND | ND | ELISA | 36 |
| ADM | CD | Cross-sectional | 71 | Maintenance | >5.85 | CRP normalisation | 68 | 71 | ND | ND | ELISA | 29 |
*≥1-point reduction in the endoscopic Mayo score.
†Post-hoc analysis.
‡Delta after dose intensification for SLR.
ADM, adalimumab; CD, Crohn's disease; CRP, C reactive protein; CZP, certolizumab pegol; FC, faecal calprotectin; HMSA, homogeneous mobility shift assay; IBD, inflammatory bowel disease; IFX, infliximab; ND, not defined; No, number of patients; NPV, negative predictive value; PPV, positive predictive value; RCT, randomised clinical trial; RIA, radioimmunoassay; SLR, secondary loss of response; SN, sensitivity; SP, specificity; TC, trough concentration; TNF, tumour necrosis factor; UC, ulcerative colitis; w, week.