Search in the Abstract Database

Abstracts Search 2018

DOP048 Vedolizumab levels during induction are associated with long-term clinical and endoscopic remission in patients with inflammatory bowel disease

A. Yarur1*, A. Bruss1, C. Fox1, P. Beniwal-Patel1, A. Patel1, B. Berens1, S. Naik2, D. Stein1

1Medical College of Wisconsin, Gastroenterology and Hepatology, Milwaukee, USA, 2Prometheus Laboratories, San Diego, USA

Background

Cross-sectional serum vedolizumab (VDZ) levels (SVL) have been associated with disease activity in Crohn’s disease (CD) or ulcerative colitis (UC) but the role of therapeutic drug monitoring (TDM) early in the course of therapy is unknown. The aim of this study was to assess the association of serum vedolizumab (VDZ) levels (SVL) during induction and remission in CD and UC after 52 weeks (52w) of therapy. We also sought to assess predictive variables associated with SVL through the first 22w of therapy.

Methods

Prospective cohort study including patients with active UC and CD starting standard therapy with VDZ. Predictive variables included demographics, pre-infusion SVL measured using a validated drug-tolerant assay at weeks 2, 6, 14 and 22 (Anser® VDZ), C-reactive protein (CRP), albumin level, feacal calprotectin (FC), Harvey–Bradshaw index (HBI) in CD and Mayo Clinical Score (MCS) in UC, Simple endoscopic score-CD (SES-CD) in CD and Mayo endoscopic score (MES) in UC. Primary outcome was deep remission at 52W, defined as HBI<5 (in CD)/MCS<3 (in UC), and SES-CD≤2 (in CD) or MES≤1 (in UC). Secondary outcome was discontinuation of VDZ due to non-response.

Results

Of the 53 patients in the study population, 28 (53%) had UC. Twenty-one (40%) achieved deep remission by week 52. These patients had higher SVL at weeks 2, 6, 14 and 22 of therapy vs. those that did not, but only the differences at Weeks 2 and 6 achieved statistical significance (Figure 1).

Figure 1. Differences in Vedolizumab Levels at Several Time-points Between those that did and did not achieve remission by week 52 of therapy (*) Statistically significant.

Nineteen (36%) patients discontinued VDZ due to non-response. Differences between those that were and were not in deep remission at week 52 are shown in Table 1.

Table 1. Differences between patients that did and did not achieve remission at week 52 (*) Statistically significant.

Did not achieve deep remissionAchieved deep remissionp valueBaseline SES-CD score (in CD patients) [median (IQR)]10 (3–16)5 (4–7)0.04*Baseline endoscopic Mayo score (in UC patients) [median (IQR)]2.5 (2–3)2 (2–3)0.34Steroid dependent at week 30 [n (%)]16 (50)3 (14.3)<0.0001*Naïve to biologics [n (%)]7 (22)10 (47.6)0.049*Vedolizumab levels week 2 [mean in g/ml (SD)]21 (6)25 (5)0.011*Vedolizumab levels week 6 [mean in g/ml (SD)]18 (8)23 (7)0.021*Vedolizumab levels week 14 [mean in g/ml (SD)]10 (8)12 (7)0.311Vedolizumab levels week 22 [mean in g/ml (SD)]8 (8)11 (8)0.27Baseline Albumin [mean in mg/ml (SD)]3.9 (0.4)4.3 (0.09)0.049*

Patients that started VDZ on combination therapy with an immunomodulator did not have significantly higher SVL at any time-point when compared with those who did not (p > 0.05 for all). There was a positive, significant correlation between baseline albumin levels and SVL at week 6 (rho: 0.4, p = 0.003) and positive but not significant correlation and SVL at week 2 (rho: 0.2, p = 0.09). Furthermore, there was a significant negative correlation between baseline FC and SVL at week 2 (rho: −0.5, p < 0.001) and week 6 (rho: −0.33, p = 0.03).

Conclusion

Vedolizumab levels at induction are associated with achievement of remission at 52w of therapy. While interventional studies are needed, the use of early TDM in patients on VDZ may improve outcomes.