Vedolizumab clearance (CL) outperforms serum trough concentrations in predicting therapeutic outcomes in Crohn's disease. Higher CL was significantly associated with reduced remission rates, supporting CL as a pharmacokinetic marker for optimizing vedolizumab therapy.

Abstract Background In clinical practice, vedolizumab (VDZ) is often considered a slow acting agent in Crohn’s disease (CD). However, a post-hoc analysis of the GEMINI trials revealed, that patients previously exposed to anti-TNF therapy already experienced less diarrhoea and abdominal pain already after respectively 2 and 4 weeks of VDZ treatment.1,2 We evaluated the rapidity of clinical and endoscopic benefit of VDZ treatment in the prospective, open-label LOVE-CD trial conducted in Belgium, the Netherlands and Hungary.3 Methods In the LOVE-CD trial, early and late CD patients with moderate-severe active CD (Crohn’s Disease Activity Index [CDAI] 220-450 and presence of ulcers at baseline endoscopy) received intravenous VDZ over a 52-week period. Early CD was defined as a diagnosis <24 months (treatment-naïve or prior corticosteroid and/or immunomodulator use), and late CD >24 months with prior anti-TNF exposure (and corticosteroids and/or immunomodulator use). Corticosteroids were tapered mandatorily and had to be discontinued by week 26. At every study visit, clinical remission (defined as a CDAI ≤150) and steroid-free clinical remission (no corticosteroids and CDAI ≤150) were calculated. At baseline, week 26 and week 52 an endoscopy was performed with independent scoring. Endoscopic response was defined as a reduction in SES-CD score of ≥50% compared to baseline. Missing data were imputed as non-responders. Results In total, 86 early CD patients and 174 late CD patients were included in the LOVE-CD trial. Baseline median CDAI and SES-CD were similar between the early and late group (255 [IQR 236-287] vs. 259 [235-315] and 9 [6-17] vs. 12 [7-17], resp.). Patients in the early group were younger and had evidently shorter disease duration compared to the late CD group (median age 30 [24-45] vs 36 [28-48] years old, median disease duration 0 [IQR 0-1] vs 11 [6-16] years, resp.). From week 6 onward, clinical remission was reached in a significantly higher proportion of early CD than late CD patients. At week 14, more than half of patients with early CD were in clinical remission, compared to 31% in the late CD group (p<0.001) (Table 1). Week 14 corticosteroid free clinical remission results were comparable (47.7% vs 27.6%, p=0.001) (Figure 1A). The proportion of patients with an endoscopic response was significantly higher in the early CD group compared to the late CD group at week 26 (64% vs 34.5%, p<0.001) and at week 52 (57% vs 35.6%, p=0.001) (Figure 1B). No new safety signals were observed. Conclusion Vedolizumab induced (steroid-free) clinical remission and endoscopic response more often in early than in late CD. Based on these observations, vedolizumab may be considered as a potential first line treatment for CD patients. References 1.Sandborn, et al. (2013). Vedolizumab as induction and maintenance therapy for Crohn's disease. The New England journal of medicine, 369(8), 711–721. https://doi.org/10.1056/NEJMoa1215739 2.Feagan, et al. (2019). Rapid Response to Vedolizumab Therapy in Biologic-Naive Patients With Inflammatory Bowel Diseases. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 17(1), 130–138.e7. https://doi.org/10.1016/j.cgh.2018.05.026 3.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.

Abstract Background Up to 40% of patients with acute severe ulcerative colitis (ASUC) do not respond to infliximab (IFX)(1). Insufficient drug exposure with low IFX serum concentrations is associated with non-response (1, 2). We investigated whether personalised TDM-driven induction dosing of IFX was superior to standard dosing. Methods In this prospective open-label, multi-centre randomised controlled trial (Netherlands, Norway and Ireland), hospitalised adult IFX-naïve and steroid-refractory ASUC patients were randomised 1:1 to standard (SD) or personalised dosing of IFX (PD). After an initial 5 mg/kg IFX infusion, SD consisted of 5 mg/kg IFX at week 2 and 6. In the PD group, additional 5 mg/kg IFX infusions were administered guided by a Bayesian pharmacokinetic algorithm (iDose) aiming at IFX serum concentrations >28 ug/mL from day 0-28 and >15 ug/mL from day 29-42 (measured with Quantum Blue IFX rapid test). After day 42, all patients received 5 mg/kg IFX maintenance every 8 weeks until day 182, with escalation at physician’s discretion. The primary composite endpoint was clinical and endoscopic response at day 42 (Lichtiger score <10 and ≥3 points decrease from baseline and UCEIS ≥2 points decrease with double central endoscopy read and adjudication). Key secondary endpoints included day 42 clinical response, day 42 endoscopic response, day 182 clinical remission (Lichtiger score ≤3), day 182 endoscopic remission (UCEIS ≤1 on all components), and safety (SAEs). Endoscopies were performed at baseline, day 42 and 182. Results 48 patients were included and received study treatment (23 PD/25 SD), 31 of whom completed treatment through week 26 (19 PD/12 SD). Median cumulative IFX dose until day 42 was 18.41 mg/kg [14.77, 20.27] for PD vs 13.79 mg/kg [10.38, 14.82] for SD (Table 1). The primary composite endpoint of clinical and endoscopic response at day 42 was not met (13/23 (56.5%) in PD vs 11/25 (44.0%) in SD; p=0.564) (Figure 1). PD showed a higher day 42 clinical response vs SD (21/23 (91.3%) vs 16/25 (64.0%); p=0.039), Day 42 endoscopic response was observed in 13/23 (56.5%) in PD and 11/25 (44.0%) in SD (p=0.564). Numerically more patients on PD had day 182 clinical remission (14/23 (60.9%) vs 9/25 (36.0%); p=0.148) and endoscopic remission (15/23 (65.2%) vs 9/25 (36.0%); p=0.082) compared to SD. SAEs occurred in 3/23 (13.0%) of patients on PD vs 5/25 (20.0%) of patients on SD (p=0.703) and included infection (2/23 (8.7%) vs 1/25 (4.0%)), thromboembolic event (0 vs 1/25 (4.0%)), colectomy (1/23 (4.4%) vs 2/25 (8.0%)), and death (0 vs 1/25 (4.0%)). Following an interim analysis, the trial was discontinued based on futility. Conclusion Personalised dosing of infliximab was not superior to standard dosing in acute severe ulcerative colitis. References 1.Seow CH, Newman A, Irwin SP, Steinhart AH, Silverberg MS, Greenberg GR. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut. 2010;59(1):49-54. 2.Papamichael K, Van Stappen T, Vande Casteele N, Gils A, Billiet T, Tops S, et al. Infliximab Concentration Thresholds During Induction Therapy Are Associated With Short-term Mucosal Healing in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol. 2016;14(4):543-9.

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 <24 months and late CD as diagnosis >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 <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<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.

Abstract Background Achieving deep remission, encompassing clinical, endoscopic, and biological remission, is a long-term goal in Crohn's disease [CD] according to the STRIDE-2 guidelines. The role of histological remission in CD remains unclear. We evaluated the efficacy of vedolizumab [VDZ] for inducing histo-endoscopic remission in early versus late CD in the prospective, open-label LOVE-CD trial conducted in Belgium, the Netherlands and Hungary. Methods In the LOVE-CD trial, patients with moderate-to-severe disease (Crohn’s Disease Activity Index 220-450 and presence of ulcers at baseline endoscopy) received intravenous vedolizumab over a 52-week period. Early CD was defined as a diagnosis <24 months (treatment-naive or history of corticosteroid and/or immunomodulator use), and late CD as a diagnosis >24 months with prior anti-TNF exposure. Ileocolonoscopies were performed at three timepoints (baseline, week 26, week 52) during which biopsies were systematically collected in the terminal ileum and colon. Both the endoscopies and biopsies were centrally scored by experienced readers for the simple endoscopic score for Crohn's disease [SES-CD], Robarts’ histopathology index [RHI], and Geboes score [GS]. Endoscopic remission, histo-endoscopic mucosal improvement [HEMI], and histo-endoscopic mucosal remission [HEMR] were defined as SES-CD <4, GS ≤3B.1, and GS <2B.1 respectively. The association between histologic and endoscopic scores was studied with Spearman’s correlation coefficient. Intention-to-treat analysis with non-responder imputation was used to handle missing data. Results Of the 260 patients included in LOVE-CD (Table), 440 biopsies (336 colon, 114 ileum) from 179 patients at week 26, and 435 biopsies (323 colon, 112 ileum) from 177 patients at week 52 were analysed. There was a strong correlation between the endoscopic and histological assessment (colon r 0.69, ileum r 0.64, total r 0.64, p<0.001). Patients with early CD were more likely to achieve histological remission than patients with late CD at week 52 (38.4 % vs. 14.9%, p=0.00004). Endoscopic and histological healing rates at week 26 (endoscopic remission 36.9%, HEMI 30.4%, HEMR 24.2%) and week 52 (endoscopic remission 35%, HEMI 30%, HEMR 22.7%) were comparable. When looking at disease location, histological remission rates in the colon and ileum did not significantly differ (35.2% vs. 27.8%, p=0.15). Conclusion Vedolizumab was more efficient at inducing histo-endoscopic remission in early CD as compared to late CD, with most of the histo-endoscopic healing occurring during the first 26 weeks. Histo-endoscopic healing rates under vedolizumab were comparable in colonic and ileal disease. Histological scores (RHI, GS) are also applicable for the evaluation of ileal and colonic CD.

Abstract Background 5-aminosalicylic acid (5-ASA), the cornerstone treatment for ulcerative colitis (UC), can impact thiopurine S-methyltransferase (TPMT) activity and thiopurine metabolism. We performed a post-hoc analysis of OPTIC, a randomised prospective controlled trial comparing mercaptopurine (MP) to placebo while continuing 5-ASA treatment in UC, to provide insight into the influence of different 5-ASA preparations on 6-thioguaninenucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) levels. Methods UC patients with active disease, despite ≥2 g/day 5-ASA treatment, received remission induction therapy with corticosteroids and conjunctively started weight-based MP therapy (1-1.5 mg/kg of bodyweight). For this analysis, the initial TDM measurement, using the Dervieux method, at week 6 was selected to exclude subsequent time points where dose adjustments were made. Different 5-ASA preparations were used, including time-dependent release (Pentasa® 4 g/day), Multi-Matrix (MMX) (Mezavant® 2.4, 3.6 or 4.8 g/day) and pH-dependent release (Salofalk® 3 or 4 g/day). Associations between 6-TGN and 6-MMP levels and 5-ASA preparations were analysed. Results In total, 29 patients started MP treatment, 27 patients reached the initial TDM measurement (41% female, median age 46 years [IQR 26-58], median disease duration 6 years [IQR 1-14]). Median 5-ASA dose was 4 g/day (IQR 3-4), the majority was treated with MMX 5-ASA (13/27), followed by time-dependent release 5-ASA (9/27) and pH-dependent release 5-ASA (5/27). Distribution of MP dose, body weight and age were similar across the different 5-ASA groups. At week 6, patients using an MMX 5-ASA formulation were more likely to have toxic 6-MMP concentrations (>5700 pmol/8×108 RBC), but not 6-TGN levels, compared to time-dependent release formulation users (91% vs 38%, P=0.041) as well as an unfavourable 6-MMP/6-TGN ratio (P=0.024). This effect was not dose-dependent. Median 6-MMP levels at week 6 varied statistically significantly between the different 5-ASA preparations: i.e. MMX 5-ASA showed the highest and time-dependent release 5-ASA the lowest 6-MMP level (19000 [IQR 10519-31000] vs 3950 pmol/8×108 RBC [IQR 2200-31000], resp., P=0.026, Figure 1). MP treatment persistence up to week 52 differed numerically between different 5-ASA preparations (MMX: 46%, time-dependent release: 78%, pH-dependent release: 60%), while no differences in hepatotoxicity or leukopenia were seen between 5-ASA formulations. Conclusion In UC patients receiving MP treatment, concomitant use of MMX 5-ASA was associated with higher toxic 6-MMP concentrations accompanied with an unfavourable 6-MMP/6-TGN ratio compared to time-dependent release 5-ASA leading to higher MP discontinuation rates.

Abstract Background OPTIC was a prospective placebo-controlled trial investigating therapeutic drug monitoring (TDM)-based mercaptopurine (MP) therapy in ulcerative colitis (UC). Although the primary endpoint (corticosteroid-free clinical remission and endoscopic improvement at week 52) favoured patients with TDM-based MP therapy over placebo, drug-related adverse events were frequent and drop-out rates high. This post-hoc analysis was carried out to show the therapeutic implications of proactive TDM of MP. Methods UC patients with active disease, despite ≥2 g/day mesalamine, underwent remission induction treatment with corticosteroids and initiated weight-based MP therapy (1-1.5 mg/kg). TDM based optimisations were performed at week 6, 12, 18, 24, 36 and 52 using the Dervieux method, unblinded non-including thiopurine expert physicians (DA, MD and AB) provided dosing advice according to a predefined algorithm, aiming for 6-TGN levels of 600-1200 pmol/8×108 RBC and 6-MMP of <5700 pmol/8×108 RBC. Associations between 6-TGN and 6-MMP levels, MP dose and thiopurine S-methyltransferase (TPMT) polymorphisms were explored. Results In total, 29 patients initiated MP treatment (41% female, median age 46 yrs [IQR 26-58], median disease duration 6 yrs [IQR 1-14]). TPMT heterozygosity was found in 4/29 patients (3/4 TPMT*3A, 1/4 TPMT*3C). TDM dose adjustments were required in 22/29 patients: 14/29 started allopurinol and decreased MP dose, 5/29 discontinued MP before the first TDM assessment, 2/29 continued MP at the initial dose up until week 52 and the remaining underwent MP dose adjustments. Most adjustments (71%) were made at week 6, thereafter 6-MMP levels stabilised, while 6-TGN concentrations remained stable (Figure 1). TPMT variant carriers had a higher median 6-TGN concentration compared to non-carriers (1700 [IQR 1625-1850] vs 539 pmol/8×108 RBC [IQR 355-953], P<0.001) and more likely to have leukopenia (P=0.025). Two TPMT heterozygous patients achieved the primary endpoint with dose reductions, two discontinued due to myelotoxicity or hepatotoxicity. Until week 52, 16/29 patients completed the trial, 14/29 reached the endpoint with a median 6-TGN of 585 pmol/8×108 RBC (IQR 428-745) and 6-MMP of 268 pmol/8×108 RBC (IQR 110-1257). MP dose correlated with 6-MMP but not with 6-TGN levels. Independently of allopurinol co-prescription, the initial median weight-based MP dose of 100 mg (IQR 75-125) decreased significantly to 50 mg (IQR 25-100, P=0.041). Conclusion Most patients underwent TDM optimisation of MP, half of the patients initiated allopurinol with decreased MP dose. TPMT heterozygosity led to supratherapeutic 6-TGN concentrations and adverse events. Weight-based initial MP dose may need reconsideration.

Abstract Background Endoscopic healing is an important treatment goal in Crohn’s disease (CD). Vedolizumab (VDZ) was shown to induce endoscopic healing after 6 months in a significantly greater proportion of pts with early CD than in those with late CD (>2 years)(UEGW 2022). We investigated whether further endoscopic healing could be attained with 6 more months of VDZ treatment in those pts with no SES-CD worsening at month 6 compared to baseline. Methods Pts in the LOVE-CD study received standard doses of VDZ and had ileocolonoscopies at baseline, w26 and 52. We studied the kinetics of endoscopic improvement during continued VDZ treatment. Endoscopies were scored by independent readers. So far, 157 pts completed the LOVE-CD trial with available central reading results. We here report the results of 76 pts (48%) who had stable endoscopic diseases or any degree of endoscopic improvement at w26 with 3 centrally read endoscopy scores (baseline, w26 and 52) available at present. VDZ serum conc were also measured and correlated to endoscopic improvement. Results We studied 76 pts (mean age 36.7, 51 (67%) female, median baseline SES-CD 10 (range 3-30) who reached w52 and had no SES-CD worsening at w26. We identified 3 endoscopic improvement patterns: 1) 24 pts (32%, 12 early, 12 late CD) with median baseline SES-CD 7.5 (range 3-21) had a SES-CD score of 0 at w26. Three of these pts had again mild lesions at w52 (SES-CD 1-4), the rest maintained SES-CD=0 at w52 (endoscopic healing); 2) 20 pts (26%, 6 early, 14 late CD) with median baseline SES-CD 8 (range 3-27) had a SES-CD of 1-3 at w26 (endoscopic remission defined as SES-CD<4). At w52, 10/20 had a score of 0, 7/20 the same score as at w26 and only 3/20 a higher score; 3) 32 pts (42%, 5 early, 27 late CD) with median baseline SES-CD 14 (range 5-30) had no endoscopic remission at w26 (SES-CD >4) with a drop to median SES-CD 7 (range 5-20) at w26 and further to median SES-CD 5 (range 0-15) at w52. Figure 1 shows the evolution of the SES-CD. The mean VDZ serum conc was (1) 19.36 mg/l at w26 and 22.23 mg/l at w52 in the group with endoscopic healing, (2) 19.52 mg/l at w26 and 21.69 mg/l at w52 in the group with endoscopic remission, and (3) 17.38 mg/l at w26 and 20.09 mg/l at w52 in the group without endoscopic healing or remission. Conclusion In this subset of LOVE-CD pts with endoscopic improvement or unchanged SES-CD at w26, the majority of pts (44/76) reached endoscopic remission (SES-CD<4). Overall, endoscopic improvement in this subgroup of responders by SES-CD score was a median of 7 (range -1 to 25) SES-CD points between w0 and w26 and a median of 0 (range -10 to +15) SES-CD points between w26 and w52. The degree of endoscopic improvement beyond month 6 was unrelated to VDZ serum conc.

Abstract Background To date, the association between vedolizumab (VDZ) serum concentrations and histological remission in ulcerative colitis (UC) has not been studied prospectively. VDZ serum concentrations could potentially offer additional guidance for predicting histological remission. We studied the relationship between VDZ serum concentrations and histological remission in a prospective study. Methods LOVE-UC was a multicentre international (Belgium, the Netherlands, and Hungary) open label prospective study in patients with moderately to severely active UC treated with VDZ. VDZ serum concentrations were measured at trough prior to every infusion. Endoscopy was performed at baseline, week 26 and 52. Biopsies from the most severely affected area and endoscopy videos were scored by blinded central readers. Histological remission was defined as a Robarts Histopathology Index <3 without neutrophils. Patients who did not undergo histological assessment were regarded as not having reached histological remission. Endoscopic remission was defined as a Mayo endoscopic sub-score 0. Results A total of 121 patients (61 male, 62 with prior exposure to tumour necrosis factor antagonists, mean total Mayo score at baseline of 9) received at least one infusion of VDZ. At week 26, 37.2% (45/121) patients were in histological remission, 38.8% (47/121) were in histological remission at week 52. The corresponding rates of combined histological and endoscopic remission were 19.8% (24/121) and 20.7% (25/121), respectively. Median VDZ serum concentrations were numerically higher at all time points in patients who achieved histological remission at week 26 than in those who did not (Table 1). Concentration thresholds (sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve) of 32.5 mg/L (66%, 68%, 54%, 74%, 0.681) at week 6 and 12.5 mg/L (76%, 60%, 61%, 70%, 0.724) at week 22 were associated with histological remission at week 26. Higher proportions of patients achieved histological remission at week 26 in higher VDZ serum concentration quartiles (Figure 1). Conclusion VDZ serum concentrations were positively associated with histological remission in UC, although the predictive value of serum concentrations for subsequent histological remission was modest.

Abstract Background Crohn’s disease (CD) is a chronic, immune-mediated inflammatory condition of the intestine, for which the majority of patients still needs to undergo surgical resection. Following the most common intervention ileocolonic resection, the vast majority of patients suffers from recurrence of CD in the neoterminal ileum. Endoscopic lesions usually precede symptoms in the first months after resection and predict the severity of the further disease course. No treatments have been approved for recurrence-prevention of CD. REPREVIO is a prospective placebo-controlled randomized trial investigating the preventive effect of vedolizumab, an anti-integrin antibody, on recurrence of CD. Methods Following ileocolonic resection, patients were treated with vedolizumab (300 mg IV at week 0,8,16 and 24) or PLC (1:1) at 12 sites in the Netherlands, France, Italy and Spain. Treatment was initiated within 4 weeks following ileocolonic resection with anastomosis. Six months following surgery, patients underwent ileocolonoscopy for assessment of recurrent lesions. Video recordings were centrally scored using the modified Rutgeerts’ score by 2 readers with adjudication in case of disagreement. The primary endpoint was endoscopic recurrence (ER) of CD (non-parametric); secondary endpoints were the proportion of patients with ER >i2a and clinical recurrence. Adverse events were recorded. Results 95 pts were screened and 80 randomized. All patients have reached month 6 and the videos are being analysed. We will receive the results of all statistical analysis in December, 2022. Conclusion The efficacy of vedolizumab postoperative recurrence-prevention treatment was studied in the REPREVIO study.

Vedolizumab (VDZ) is an anti-α4β7 integrin registered for treatment of moderate to severe Crohn's disease (CD). Prospective data on mucosal healing in CD and the association with VDZ serum concentrations are lacking. We report a first analysis of the ongoing LOVE-CD trial (NCT02646683). Patients with moderate–severe CD based on Crohn's Disease Activity Index (CDAI) 220–450 and the presence of ulcers at baseline endoscopy received 300 mg VDZ at Week 0, 2, and 6 with additional w10 infusion in the absence of clinical response, followed by 300 mg VDZ every 8w. CDAI, C-reactive protein (CRP) and VDZ concentrations were measured before every infusion. Endoscopies were performed at baseline and w26 and scored with the Simple Endoscopic Score for CD (SES-CD). Clinical remission was defined as CDAI<150, endoscopic remission as SES-CD ≤3 and endoscopic response as SES-CD reduction ≥50% compared with baseline. Quartile analysis was performed in the per protocol population (patients who reached w26 and had two endoscopies). A total of 110 CD (70% female) patients were included, with median ([interquartile range, IQR]) age 36 years [28–46], median disease duration 12 years [6–16]. All patients had failed conventional therapy and 88% failed prior anti-TNF therapy. Median baseline SES-CD was 11 [7–17], median CDAI 263 [238–313], median CRP: 9 [4-22]. At week 26, 76 patients (69%) were still on VDZ and 74/76 patients underwent w26 endoscopy. Endoscopic response was observed in 43/110 (39%), endoscopic remission in 33/110 patients (30%) and clinical remission in 37/110 patients (34%). Patients with endoscopic response at w26 had higher median VDZ concentrations compared with endoscopic non-responders at w6, 10, 14, and 22 (Table 1). Higher proportions of patients achieved endoscopic remission at w26 with higher VDZ quartiles compared with lower quartiles at w6, 10, and 22 (Figure 1). CRP concentrations were inversely correlated with VDZ concentrations (p-value =.001). Vedolizumab serum concentrations (μg/ml). Vedolizumab serum concentrations (μg/ml). Vedolizumab quartiles and endoscopic remission at week 26. This is the first prospective trial showing endoscopic response and remission rates with VDZ in CD. VDZ concentrations were significantly higher in patients with an endoscopic response compared with non-responders. The study was support provided by Takeda.