Table 1.
Anti-TNF therapy exposure–response relationship in IBD studies regarding clinical efficacy
| Drug | IBD type | Study design | No | Time point | TC (μg/mL) | Therapeutic outcome | SN | SP | PPV | NPV | Assay | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| IFX | UC | RCT* | 82 | Induction (w2) | >21.3 | Clinical remission (w14) | 61 | 69 | 72 | 58 | ELISA | 6 |
| IFX | UC | RCT* (ACT-1 and 2) | 446 | Induction (w6) | >22 | Clinical response (w8) | 60 | 62 | 78 | 41 | ELISA | 7 |
| IFX | UC | RCT* (ACT-1 and 2) | 377 | Postinduction (w14) | >5.1 | Clinical response (w30) | 66 | 63 | 74 | 54 | ELISA | 7 |
| IFX | UC | Retrospective | 112 | Postinduction (w14) | >2.5 | Absence of clinical relapse† | 81 | 75 | ND | ND | ELISA | 8 |
| IFX | CD | RCT* (ACCENT-1) | 284 | Postinduction (w14) | >3.5 | Sustained clinical response (w54) | 64 | 78 | 56 | 83 | ELISA | 9 |
| IFX | UC | RCT* (ACT-1 and 2) | 158 | Postinduction (w14) | >3.5 | Clinical response (w54) | 82 | 50 | 63 | 72 | ELISA | 7 |
| IFX | CD | Prospective | 84 | Postinduction (w14 or w22) | >3 | Sustained clinical response | 70 | 62 | 41 | 84 | ELISA | 10 |
| IFX | CD/UC | Prospective | 93 (CD: 59) | Maintenance (w22) | ≤5.5 | SLR | 25 | 84 | ND | ND | ELISA | 12 |
| IFX | UC | RCT* (ACT-1 and 2) | 377 | Maintenance (w30) | >3.7 | Clinical response (w30) | 65 | 71 | 82 | 51 | ELISA | 7 |
| IFX | UC | RCT* (ACT-1 and 2) | 158 | Maintenance (w30) | >2.4 | Clinical response (w54) | 86 | 62 | 76 | 77 | ELISA | 7 |
| IFX | CD | RCT* (SONIC) | 203 | Maintenance (w30) | ≥3 | CS-free remission (w50) | 50 | 65 | 69 | 46 | ELISA | 13 |
| IFX | UC | RCT* (ACT-1 and 2) | 158 | Maintenance (w54) | >1.7 | Clinical response (w54) | 89 | 64 | 83 | 74 | ELISA | 7 |
| IFX | CD | Retrospective | 69 | Maintenance | <0.5 | SLR | 86 | 85 | ND | ND | RIA | 14 |
| IFX | UC | Retrospective | 13 | Maintenance | <0.8 | SLR | 75 | 100 | ND | ND | RIA | 14 |
| IFX | CD/UC | Retrospective | 213 (CD: 131) | Maintenance | >2.1 | Clinical remission | 78 | 76 | ND | ND | ELISA | 19 |
| IFX | CD | Prospective | 105 | Maintenance | >1.4 | Clinical remission | ND | ND | ND | ND | ELISA | 20 |
| IFX | UC | Prospective | 115 | Maintenance | >1.4 | Clinical remission | ND | ND | ND | ND | ELISA | 17 |
| IFX | UC | Prospective | 46 | Maintenance | >6.26 | Clinical remission | 50 | 88 | NA | NA | ELISA | 21 |
| IFX | CD | Prospective | 61 | Maintenance | >2.18 | Clinical remission | 67 | 79 | NA | NA | ELISA | 21 |
| ADM | UC | Retrospective | 73 | Postinduction (w4) | >4.58 | Clinical response (w12) | 80 | 56 | 85 | 47 | ELISA | 24 |
| ADM | UC | Retrospective | 73 | Postinduction (w4) | >7 | Clinical response (w52) | 80 | 69 | 43 | 92 | ELISA | 24 |
| ADM | CD | Retrospective | 148 | Postinduction (w4) | <5 | Drug discontinuation | ND | ND | ND | ND | HMSA | 25 |
| ADM | CD/UC | Cross-sectional | 40 (CD: 22) | Maintenance | >4.85 | Clinical remission | 81 | 67 | 84 | 57 | ELISA | 27 |
| ADM | CD/UC | Retrospective | 57 (CD: 42) | Maintenance | <6.85 | SLR | 69 | 69 | 58 | 78 | RIA | 28 |
| ADM | CD | Cross-section | 71 | Maintenance | >5.85 | Clinical remission | 68 | 71 | ND | ND | ELISA | 29 |
*Post-hoc analysis.
†Within 6 months of baseline.
ACT, Active Ulcerative Colitis Trial; ADM, adalimumab; CD, Crohn's disease; CS, corticosteroids; HMSA, homogeneous mobility shift assay; IBD, inflammatory bowel disease; IFX, infliximab; NA, not applicable; 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; SONIC, study of biologic and immunomodulator naive patients in Crohn's disease; SN, sensitivity; SP, specificity; TC, trough concentration; TNF, tumour necrosis factor; UC, ulcerative colitis; w, week.