Table 1.
Exposure–efficacy relationship of vedolizumab in inflammatory bowel disease
| Reference | Design | Number of patients | Main outcome parameter | Key findings | Other findings | ||
|---|---|---|---|---|---|---|---|
| Clinical trials | |||||||
| Rosario et al. (2017) [9] | Clinical trial (post-hoc analysis) | 681 (UC); 850 (CD) | Vedolizumab TL and clinical remission statusa at week 6 | Median (IQR) TL at week 6: clinical remission (UC) | 34.7 (31.7–36.6) | P-value: not stated | TL at week 6 < 17 (UC) and < 16 (CD): clinical remission rates similar to placebo |
| Median (IQR) TL at week 6: no clinical remission (UC) | 23.7 (22.0–24.8) | ||||||
| Median (IQR) TL at week 6: clinical remission (CD) | 26.8 (24.9–30.1) | P-value: not stated | |||||
| Median (IQR) TL at week 6: no clinical remission (CD) | 23.5 (22.4–24.8) | ||||||
| Osterman et al. (2019) [10] | Clinical trial (post-hoc analysis); propensity-score-based case-matching analysis | 693 (UC) | Target vedolizumab TL for clinical response/remissionb, adjusted for confounding factors on drug clearance | Target TL at different timepoints for clinical response/remission | Week 6 was the earliest time point at which TL was consistently associated with clinical response and remission at week 14 and week 52 | ||
| Week 6 | > 37.1 | ||||||
| Week 14 | > 18.4 | ||||||
| Maintenance | > 12.7 | ||||||
| Real-world cohorts | |||||||
| Williet et al. (2017) [11] | Prospective, observational; multicentric | 16 (UC); 31 (CD) | Association between vedolizumab TL at week 0–6 and need for additional dosing in first 6 months | Cut-off TL associated with the need for additional dosing in first 6 months | |||
| Week 2 | < 24.5 | AUROC 0.62 | |||||
| Week 6 | < 18.5 | AUROC 0.72 | |||||
| Al-Bawardy et al. (2018) [12] | Retrospective, cross-sectional; single-centre | 53 (UC); 106 (CD); 12 (IBDU) | Vedolizumab TL and mucosal healingc | Median (IQR) TL and mucosal healing | 13.7 (10–32.9) | P = 0.64 | |
| Median (IQR) TL and no mucosal healing | 16.1 (7.7–27.6) | ||||||
| Dreesen et al. (2018) [13] | Retrospective, observational; single-centre | 66 (UC); 113 (CD) | Vedolizumab TL and clinical/biological/endoscopic effectiveness endpointsd at week 14 (UC) and week 22 (CD) | Cut-off TL associated with effectiveness at week 14/22 (UC/CD) | |||
| Week 2 | > 30 | P < 0.05 | |||||
| Week 6 | > 24 | P < 0.05 | |||||
| Week 14 | > 14 | P < 0.05 | |||||
| Yacoub et al. (2018) [14] | Prospective, observational; multicentric | 43 (UC); 39 (CD) | Vedolizumab TL during induction (weeks 2, 6, 14) and mucosal healinge within 1 year | Median (IQR) TL and mucosal healing within 1 year | TL at week 6 > 18 was the only independent variable associated with mucosal healing within 1 year (AUROC: 0.735) | ||
| Week 2 | 27 (23.6–33.8) | P = 0.845 | |||||
| Week 6 | 26.8 (21.4–40.4) | P = 0.035 | |||||
| Week 14 | 16 (8–21) | P = 0.241 | |||||
| Median (IQR) TL and no mucosal healing within 1 year | |||||||
| Week 2 | 27.8 (18.1–34.5) | P = 0.845 | |||||
| Week 6 | 15.1 (13.4–23.5) | P = 0.035 | |||||
| Week 14 | 6.3 (4.5–15) | P = 0.241 | |||||
| Ungaro et al. (2019) [15] | Prospective, cross-sectional; multicentric | 116 (UC); 142 (CD) | Vedolizumab TL and corticosteroid-free clinical and biochemical remission during maintenance therapyf | Median (IQR) TL and steroid-free clinical and biochemical remission | 12.7 (8.4–19.4) | P = 0.002 | Patients with TL > 11.5 were 2.4 times more likely to be in corticosteroid-free clinical and biochemical remission |
| Median (IQR) TL and no steroid-free clinical and biochemical remission | 10.1 (5.9–15.2) | ||||||
| Pouillon et al. (2019) [16] | Retrospective, cross-sectional; single-centre | 31g (UC) | Vedolizumab TL and histological healingh | Median (IQR) TL and histological healing | 31.5 (25–49.1) | P = 0.02 | TL > 25 was most optimal to predict histological healing (AUROC: 0.62) |
| Median (IQR) TL and no histological healing | 15 (9–26.6) | ||||||
| Yarur et al. (2019) [17] | Prospective, observational; single-centre | 30 (UC); 25 (CD) | Vedolizumab TL during induction (weeks 2, 6, 14) and steroid-free endoscopic remission at week 52i | Median (IQR) TL and steroid-free endoscopic remission at week 52 | |||
| Week 2 | 24.8 (23–28) | P = 0.005 | |||||
| Week 6 | 25 (17–28) | P = 0.016 | |||||
| Week 14 | 11 (7–17) | P = 0.42 | |||||
| Median (IQR) TL and no steroid-free endoscopic remission at week 52 | |||||||
| Week 2 | 20 (18–25) | P = 0.005 | |||||
| Week 6 | 17.3 (10–24) | P = 0.016 | |||||
| Week 14 | 8 (6–14) | P = 0.42 | |||||
AUROC area under the receiver operating curve, CD Crohn’s disease, IBDu indeterminate inflammatory bowel disease, IQR interquartile range, TL trough level (expressed in μg/mL), UC ulcerative colitis
aComplete Mayo score of ≤2 points AND no individual subscore > 1 point (UC) OR CD activity score of ≤150 points
bClinical response: reduction in complete or partial Mayo score of ≥3 points and ≥ 30% from baseline, AND a decrease of ≥1 point on the rectal bleeding subscore, OR an absolute rectal bleeding subscore ≤1; clinical remission: complete Mayo score of ≤2 points, AND no individual subscore > 1 point (UC)
cAbsence of ulcers (CD) OR Mayo endoscopic subscore ≤1 (UC)
dClinical effectiveness: physician global assessment; biological effectiveness: C-reactive protein level < 5 mg/L; endoscopic effectiveness: absence of ulcers (CD) OR Mayo endoscopic subscore ≤1 (UC)
eAbsence of significant intestinal inflammation on magnetic resonance imaging, AND/OR absence of ulcers (CD), OR Mayo endoscopic subscore ≤1 (UC)
fHarvey Bradshaw Index < 5 (CD), OR partial Mayo score < 2 (UC), AND C-reactive protein level < 5 mg/L, AND no oral corticosteroid use in prior four weeks
gThirty-five histological samples from 31 patients
hNancy histological index ≤1
iSimple endoscopic score < 2 (CD), OR Mayo endoscopic subscore ≤1 (UC) while off steroids