OP09 Dose intensification of vedolizumab is not effective in inducing endoscopic response in Crohn’s disease patients with endoscopic primary non-response
Authors: Oldenburg L , Baert F , Bossuyt P , Hoentjen F , Clasquin E , Molnar T , Löwenberg M , Vermeire S , D'Haens G 
Published: January 2025

Abstract

Background
Dose intensification of anti-α4β7 integrin vedolizumab (VDZ) in Crohn’s Disease (CD) patients with secondary loss of response has been reported to be effective. However, data on effectiveness of this intervention in primary non-responders is often inconsistent and retrospectively collected.1 Our aim was to investigate the effect of vedolizumab dose intensification in endoscopic non-responders after 26 weeks of standard dosing on both clinical and endoscopic remission at week 52.

Methods
In the LOVE-CD trial, early and late CD patients with moderate-severe disease activity (Crohn’s Disease Activity Index (CDAI) 220-450) and presence of ulcers at baseline endoscopy were treated with VDZ for 52 weeks.2 Early CD was defined as diagnosis &lt;24 months and late CD as diagnosis &gt;24 months and previous exposure to anti-TNF. All patients received standard doses of vedolizumab (300 mg at week 0,2 and 6 and further every 8 weeks with an additional dose at week 10 in case of clinical non-response) and underwent an endoscopy at week 0, 26 and 52. Corticosteroids were mandatorily tapered and had to be discontinued by week 26. Halfway the trial, after 130 patients (50%) had been included, the study protocol was amended by introducing dose intensification from 300 mg IV every 8 weeks to every 4 week in patients without endoscopic response (DSES-CD drop &lt;50%) at week 26. The primary outcome was deep remission, defined as clinical (CDAI ≤150) and endoscopic remission (SES-CD ≤3) at week 52.

Results
In LOVE-CD, eighty-two patients (31.5%) were endoscopic non-responders at week 26 (44 prior to and 38 after the dose intensification amendment). Four patients in the dose intensification group were excluded from analysis due to missing week 52 endoscopy data. Apart from previous biological exposure (90.0% vs 73.5% in the dose intensification and standard dosing group, resp.), baseline characteristics were similar between the dose intensification and continued standard dosing groups (median SES-CD at baseline 11 (IQR 7-17) vs 13 (IQR 8-18) resp.). At week 52, the dose-intensified group had significantly higher VDZ serum concentrations at trough (mean 46.4 vs 16.3 ug/ml, p&lt;0.001). However, there was no significant difference in endoscopic remission, clinical remission and deep remission rates at week 52 between the two groups (table 1). No significant differences in severe adverse events were observed between both groups (9.7% vs 13.6%, p=0.344).

Conclusion
In the LOVE-CD trial, dose intensification of vedolizumab in endoscopic non-responders with Crohn’s Disease after 6 months of standard dosing was not effective.

References
1.Samaan, et al. (2019). Effectiveness of vedolizumab dose intensification to achieve inflammatory bowel disease control in cases of suboptimal response. Frontline gastroenterology, 11(3), 188-193. https://doi.org/10.1136/flgastro-2019-101259
2.D’Haens et al (2024). Vedolizumab treatment is more effective and safer in early versus late Crohn’s Disease: final results of the LOVE-CD trial. United European Gastroenterology Week, OP 2677.