Introduction

Inflammatory bowel diseases (IBD) are chronic gastrointestinal diseases that include ulcerative colitis (UC) and Crohn's disease (CD). IBD is a major public health concern, affecting approximately 6 million people globally (2). Although more common in industrialized countries, the prevalence of IBD is rising in emerging countries as a result of lifestyle changes. Unfortunately, there is no official data on the occurrence of IBD in Montenegro, either for children or adults. Vedolizumab is a humanized monoclonal antibody that selectively targets α4β7 integrin and was approved for the treatment of adult patients with moderately to severely active UC and CD. The effects of therapeutic drug monitoring or a target serum concentration for vedolizumab are not fully established at this time. It is assumed that higher serum concentrations of vedolizumab lead to a higher probability of clinical response or remission.

Aims & Methods

The aim of the study was to investigate the relationship between vedolizumab serum concentrations (measured at week 6th after beginning of treatment) and clinical and endoscopic responses in IBD patients (evaluated at week 14th). The trial included 22 biologic-naive IBD patients (15 - UC, 7- CD), who received vedolizumab as a first-line treatment. We evaluated endoscopic scores (Mayo Score for UC and Simple Endoscopic Score (SES) for CD) as well as the clinical disease activity scores (Ulcerative Colitis Disease Activity Index (CDAI), Partial Mayo Score (PMS) for UC, and Harvey Bradshaw Index (HBI) for CD). Endoscopic response was defined as a 50% decrease in SES-CD score from the baseline value and Mayo endoscopy subscores of 0 or 1 were considered satisfactory. Clinical remission was defined as an HBI < 5, Mayo Score ≤ 2, and no individual subscore > 1. Clinical response was defined as a decrease in HBI ≥ 3, a decrease in Mayo Score ≥ 30%, and ≥ 3 points from the induction baseline, with a rectal bleeding subscore of 0 or 1.

Results

In the 14th week of therapy, a statistically significant clinical and endoscopic response was achieved, surpassing the overall response of patients with UC and CD (p<0.001). Furthermore, a statistically significant reduction in individual clinical scores (CDAI, HBI, and PMS) was observed in the 14th week of drug application (p=0.004; p=0.026, p=0.005, respectively). The endoscopic response was statistically significant in patients with UC (Mayo endoscopic score, p=0.003) in the 14th week, but not in patients with CD (p=0.176).
The difference in vedolizumab concentration was statistically significant between patients who achieved an endoscopic response in the 14th week and those who did not (p=0.02). Additionally, the difference in drug concentration was close to statistical significance (p=0.088) between patients with UC (28.6±13.6) and CD (21±9.7).
In biologic-naïve IBD patients, a vedolizumab serum concentration of 25.6 mcg/mL or greater at week 6th demonstrated a sensitivity of 88.9% and a specificity of 100% in predicting an endoscopic response at week 14th.

Conclusion

Early determination of vedolizumab serum concentration in biologic-naive IBD patients, primarily UC, can be a promising predictor of endoscopic improvement in these patients.

References

1. Osterman MT, Rosario M, Lasch K, et al. Vedolizumab exposure levels and clinical outcomes in ulcerative colitis: determining the potential for dose optimisation. Aliment Pharmacol Ther. 2019;49(4):408-418
2. Sandborn WJ, Feagan BG, Rutgeerts P, et al; for the GEMINI 2 Study Group. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013a;369(8):711-721
3. Dreesen E, Verstockt B, Bian S, et al. Evidence to support monitoring of vedolizumab trough concentrations in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2018;16(12):1937-1946
4. Liefferinckx C, Minsart C, Cremer A, et al. Early vedolizumab trough levels at induction in inflammatory bowel disease patients with treatment failure during maintenance. Eur J Gastroenterol Hepatol. 2019;31(4):478-485
5. Scribano ML. Vedolizumab for inflammatory bowel disease: From randomized controlled trials to real-life evidence. World J Gastroenterol. 2018;24(23):2457-2467

Disclosure

This abstract was presented at the 1^st International Congress of Gastroenterohepatologists of Montenegro, held from June 9-11, 2023 in Budva, Montenegro

Introduction

As the therapeutic armamentarium for inflammatory bowel diseases (IBD) is rapidly expanding, it is of increasing importance to optimize treatment sequencing. However, head-to-head trials comparing efficacy of vedolizumab (VDZ) in bio-naïve versus bio-experienced patients are scarce.

Aims & Methods

Aim: To compare the effectiveness of VDZ in bio-naïve versus bio-experienced patients with IBD in a real world setting.
Methods: A retrospective monocentric study was performed in IBD patients treated with VDZ at a Belgian University Hospital, from January 2018 to June 2021 with follow-up until December 2021. Primary endpoints considering efficacy after induction and after 1 year of therapy were: clinical response (CRp) and remission (CRm), biochemical response (BRp) and remission (BRm) and endoscopic response (ERp) and remission (ERm). Secondary endpoint was treatment survival during follow-up. For assessment of risk factors influencing efficacy and treatment survival, a multivariate logistic regression and Cox regression model (CRM) were applied.

Results

A total of 84 patients were treated with VDZ, 42 bio-naïve and 42 bio-experienced. At baseline, significantly more bio-experienced patients had prior intestinal resection (IR) (40.5% (17/42) vs. 16.7% (7/42), P=0.016), used an immunomodulator (IMM) (35.7% (15/42) vs. 16.7% (7/42), P=0.047) and had a longer disease duration (12.5 vs. 3.5 years, P<0.001). Bio-naïve patients had more moderate to severe comorbidities (21.4% (9/42) vs. 2.4% (1/42), P=0.007). After VDZ induction, CRp rate was higher in bio-naïve patients (60.9% (39/42) vs 39.1% (25/42), P<0.001). Multiple logistic regression analyses revealed that bio-naïve patients had a higher chance reaching CRp (aOR 14.69, 95%CI [3.12-69.14], P<0.001)(table). CRm was reached in 35.7% bio-naïve and 19% bio-experienced patients (P=0.087). No significant difference in BRp (P=0.932) or BRm (P=0.730) rate was found . A significantly higher ERp rate was seen in bio-naïve patients (90.3% (28/31) vs. 66.7% (18/27), P=0.027). Multiple logistic regression analyses showed a trend towards higher ERp rate in bio-naïve patients (aOR 4.65, [0.99-21.84], P= 0.051)(table). No significant difference was seen for ERm (32.3 % (10/31) vs. 11.1% (3/27), P=0.054). After 1 year of VDZ, CRp was significantly higher in bio-naïve patients (82.9% (34/41) vs. 62.5% (25/40), P=0.039). Multiple logistic regression analyses showed no significant difference between both groups. Univariate analyses showed significantly higher CRm rate in bio-naïve patients (70.7% (29/41) vs. 37.5% (15/40), P=0.003). After adjustment for age, disease duration, IMM use and prior IR, this difference was no longer significant. Patients without prior IR had significantly higher odds of reaching CRm (aOR 4.33,[1.13-16.59], P=0.032). No significant difference was seen for BRp (P=0.443) and BRm (P=0.313), nor for ERp (P=0.184) or ERm (P=0.061) in univariate analyses. Cox regression analysis showed significantly longer treatment survival in bio-naïve patients (aHR 2.32, [1.03-5.23], P=0.043).

Conclusion

In this tertiary real-world cohort of patients treated with VDZ, overall, a better efficacy was seen in bio-naïve compared to bio-experienced patients.

Disclosure

No conflict of interest

Introduction

Usability of subcutaneous vedolizumab (SC VDZ) in inflammatory bowel diseases (IBD, ulcerative colitis [UC], Crohn’s disease [CD]) have proved via clinical trials, while real-world data collection is ongoing. Experiences of Central-European population and assessment of patient’s perspectives are lacking.

Aims & Methods

Our study aimed to evaluate the real-world efficacy, safety and patient’s preferences of SC VDZ maintenance treatment after switching from intravenous (IV) formulation in a Hungarian IBD cohort. In this prospective, multicenter cohort study, IBD patients on maintenance IV VDZ treatment were enrolled, who switched to SC administration. Baseline was the day of the switch, while 52-week follow-up was set. Clinical and demographic data were collected, while serum VDZ level and CRP was measured at baseline and at w52. A non-validated questionary was filled by patients who were on drug at w12 recording patient’ satisfaction. Primary outcome was the drug survival rate at one year, while secondary outcomes were change in corticosteroid-free clinical (CSFR, based on physicians’ global assessment score PGA<1), and biochemical remission (BR, 5 mg/l³CRP) rates to w52, safety issues and patients’ preferences and change in serum drug levels.

Results

In total, 37 IBD patients were followed (15 CD and 22 UC, male/female ratio 45.9 %, median age 42.0 [IQR 34-49] years). In CD group, 66.7% were in CSFR and 60 % in BR, while in UC group 63.6% were in CSFR and 68.2 % in BR (p=0.55 and p=0.61). Overall, 29.7 % of patients ceased SC VDZ treatment after a median of 20 (IQR 6-26) weeks. Cessation was due to secondary response losing in 3/6 and 4/5 patients in CD and UC group. In case of 2 and one patients, SC treatment was terminated due to local reactions. One patient was fear of needle. Severe adverse event did not occur. Factors associated with discontinuation did not identify. The mean serum VDZ level has higher at w52 compared to baseline in CD and UC patients (CD: 8.9 ±6.9 to 30.6 ±17.8 ug/mL, p = 0.047; UC: 13.6±13.8 to 33.6±17.6 ug/mL, p = 0.001), while disease activity was stable. 84 % of the patients who filled the questionnaire were satisfied with injection, while only one patient found it difficult to inject.

Conclusion

Transition from IV to SC maintenance VDZ treatment is effective at one year, the overall survival rate is high presumably due to the elevated serum drug levels. Severe safety issue did not raise. Satisfaction of switched patients is high, which may improve treatment adherence and save resources.

Disclosure

K.F. has received speaker’s honoraria from AbbVie, Janssen, Ferring, Takeda, and Goodwill Pharma. T.M. has received speaker’s honoraria from MSD, AbbVie, Egis, Goodwill Pharma, Takeda, Pfizer, Janssen, Sandoz, MundiPharma, Phytotec, Roche, Fresenius, and Teva. ​Remaining authors have no conflict of interest to declare.

Introduction

Biological drugs has revolutionized the management of inflammatory bowel disease (IBD). However, its use has led to a significant increase in cost that has strained health systems. Biosimilars will reduce cost related to treatment, allowing access to a greater proportion of patients. However, data on the efficacy and safety of the various adalimumab (ADA) biosimilars in IBD patients “naive” to biologics remains scarce.

Aims & Methods

We performed an observational cohort study in 8 Spanish hospitals located in Galicia. All patients with IBD naïve to biologics who started ADA biosimilar between November 2018 and January 2022 for control of their disease were enrolled. The primary endpoints were efficacy defined as clinical remission at week 8 and long term efficacy defined as persistence on drug treatment at the end of follow-up. The other co-primary endpoint was to determine the incidence of adverse events that lead to suspension or discontinuation of the drug or hospitalization of the patient.

Results

383 patients (95 CU; 283 CD) with a median age of 47.0 (34.0-59.3) years and a median disease duration of 3.4 (0.8-10.0) years before starting treatment were included. After induction (at 8 weeks) 63.8 % of patients were in clinical remission and 85.3 % achieved clinical response. At this time of follow-up, 14 patients (4.9 %) discontinued treatment mainly due to primary non-response (PNR) (57.1 %) and adverse events (42.9 %). In total, 114 patients discontinued treatment during follow-up. The main reasons for stopping therapy were adverse events (26.3 %), PNR (30.7 %) and secondary loss of response (43.0 %). Clinical remission was maintained in 78.4 % of patients, after a median follow-up of 18 (12-24) months. Drug persistence shown by Kaplan-Meier survival curves were significantly higher in CD patients (p = 0.012) and in the group of patients treated with immunomodulators (IMM) (p = 0.001). Additionally, the rates of clinical remission and clinical response were higher in CD patients and in IMM-treated patients (Table 1). Adalimumab levels were also measured during follow-up, showing a median of 10.4 (6.7-13.0) μg/mL. Significantly, drug persistence was higher in patients with post-induction ADA levels ≥ 7 μg/mL (p = 0.002). Regarding treatment safety in this population, adverse events that required treatment suspension or discontinuation were reported in 30 patients.

Table 1. Comparison of the clinical effectiveness at the end of follow-up between EC vs. UC patients and IMM vs. non-IMM treated patients.

Conclusion

ADA biosimilars in usual clinical practice are safe and effective in inducing and maintaining remission in Galician patients with IBD. Drug persistence was significantly higher in patients with CD, treated with IMM and with post-induction ADA levels ≥ 7 μg/mL.

Introduction

The therapeutic armamentarium for inflammatory bowel disease (IBD) is rapidly increasing recent years with newer therapies such as vedolizumab (VDZ). Their effectiveness has already been demonstrated against placebo, but head-to-head trials compared to tumour necrosis factor alpha inhibitors (anti-TNF) are scarce.

Aims & Methods

Aim: To compare the effectiveness of VDZ versus anti-TNF in bio-naïve IBD patients in a real world setting.
Methods: A retrospective monocentric study was performed in IBD patients treated with VDZ and anti-TNF at a Belgian University Hospital, from January 2018 to June 2021 with follow-up until December 2021. Primary endpoints considering efficacy after induction and after 1 year of therapy were: clinical response (CRp) and remission (CRm), biochemical response (BRp) and remission (BRm) and endoscopic response (ERp) and remission (ERm). Secondary endpoint was treatment survival during follow-up. For assessment of risk factors influencing efficacy and treatment survival, a multivariate logistic regression and Cox regression model were applied. Propensity scores for VDZ vs. anti-TNF were weighted for age at start biological, IBD type, perianal disease activity, disease duration and previous IBD-related intestinal resection.

Results

In total, 42 patients received VDZ and 57 anti-TNF. At baseline, the VDZ group had an older median age (38 vs. 31 years, P=0.024), longer disease duration (P=0.017) and more moderate to severe comorbidities (21.4% (9/42) vs. 0% (0/57), P<0.001). In the anti-TNF group, percentage of CD patients was higher (77.2% (44/57) vs. 57.1% (24/42),P=0.034), patients had more upper GI, penetrating or stricturing disease (P=0.013 for location and P=0.004 for behavior), perianal disease (P=0.034) and used more immunomodulators (IMM) during treatment (52.6% (30/57) vs. 16.7% (7/42), P<0.001). After treatment induction, CRp (P=0.311) and CRm (P=0.216) rate was not significantly different. The anti-TNF group had a significantly higher BRp rate compared to the VDZ group (87.8% (43/49) vs. (23/34), P=0.026). After adjusting for propensity score, age, IBD type, systemic corticosteroid (CS) or IMM use, the higher rate of BRp remained (aOR 3.83 [1.01-14.60], P=0.049). Similar results were found for BRm (87.8% (43/49) vs. 67.6% (23/34), P=0.026). After adjustment for the same confounders, the higher rate of BRm in the anti-TNF group remained (aOR 3.83 [1.01-14.60], P=0.049). No significant difference was seen for ERp (P=1.000) and ERm (P=0.338). After 1 year, univariate analysis showed no significant difference for CRp (P=0.736) and CRm (P=0.404), nor for BRp (P=0.907) and BRm (0.890) or for ERp (P=0.163) and ERm (P=0.533). Treatment survival using Cox regression model with adjustment for propensity and IMM or CS use, showed no significant longer treatment duration for anti-TNF compared to VDZ (aHR 0.947 [0.36-2.49], P=0.913).

Conclusion

In this tertiary real-world cohort of bio-naïve patients with IBD, anti-TNF and VDZ showed a similar efficacy, with an advantage of anti-TNF regarding onset of action.

Introduction

Symptomatic luminal stricture in Crohn’s Disease (CD) occurs in up to 20% of patients at the diagnosis and in more than 50% during their lifetime. A considerable percentage of patients often require further surgery for post-operative CD recurrence, with a consequent increased burden of short bowel syndrome. In this scenario, combining biological therapy with endoscopic balloon dilation (EBD) could potentially reduce this risk.

Aims & Methods

Our study aimed to evaluate the efficacy of EBD combined with biologic therapy in symptomatic gastrointestinal strictures in CD patients. We conducted a retrospective study including consecutive CD patients who underwent EBD for low gastrointestinal strictures from December 2015 until November 2022 at our tertiary IBD Center. Subsequent subocclusive/occlusive episodes, the need for steroids, and surgery due to CD stenosis were evaluated during a follow-up period of 6, 12 months, and 24 months.

Results

A total of 52 patients treated with EBD with an overall number of 55 strictures were included. The mean age was 46,8 (18-77) years. The median of disease duration was 9 (0-42) years. Among the total of 55 studied strictures: 14 (25%) in patients with active smoking, 21 (38%) with increased CRP values at the time of dilation, 43 (78%) had evidence of moderate or severe endoscopic disease activity with ulcerative lesions at stricture site. Anastomotic strictures accounted for 26 (47%) of all 55 strictures. The remaining 29 (53%) were de novo stricture: 8 (15%) ileal, 11 (20%) at ileocecal valve, 4 (7%) colonic, and 6 (11%) anal . Forty-two patients (76%) were under biologic therapy at the time of EBD and 2 (4%) started after EBD. EBD technical success was reported in 60% of the procedures, and no adverse events were recorded. After 6 months from EBD, at univariate analysis, increased CRP at the time of dilation resulted in a risk factor for the need for steroids (OR 14,63, IC 2,690 to 71,50; p-value = 0,0006, Table 2). Concomitant biological therapy, active smoke, and the presence of ulcerative lesions did not show a significant correlation with considered outcomes. After 12 and 24 months from EBD, concomitant biological therapy resulted in being a protective factor for surgery (OR 0,06; IC 0,005 to 0,502; p-value=0,0047), while subocclusive and occlusive events were less frequent in anastomotic strictures than ileal stenosis (OR 0,07; IC 0,005 to 0,651; p-value=0,0152).

Conclusion

In patients with CD undergoing EBD for intestinal CD stricture, concomitant biological therapy reduces the risk of surgery for CD stenosis recurrence. Further prospective and controlled studies are underway to confirm these observations.

Disclosure

Antonio Gasbarrini reports personal fees for consultancy for Eisai S.r.l., 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, Sinergie S.r.l. Board MRGE, and Sanofi S.p.A, personal fees for acting as a speaker for Takeda S.p.A, AbbVie, and Sandoz S.p.A, and personal fees for acting on advisory boards
for VSL3 and Eisai. Daniela Pugliese received speaker fees from AbbVie, MSD, Takeda and Janssen, Pfizer; advisory board fees from Pfizer. Franco Scaldaferri i: advisory board for Abbvie, Janssen, MSD, Sanofi and Takeda; All the other authors have no conflict of interest to declare

Introduction

Aim: To report on the efficacy and safety of elective switching from intravenously (IV) to subcutaneously (SC) administered Vedolizumab in Inflammatory Bowel Disease (IBD) patients in clinical remission.

Aims & Methods

Retrospective analysis of IBD patients in clinical remission who were receiving Vedolizumab IV for treatment of their disease in a single tertiary center and were switched to SC, based on their physician’s choice. The primary endpoint was disease deterioration during the follow-up period, according to the disease specific composite measures. In CD, clinical remission was defined as Crohn's Disease Activity Index (CDAI) <150 and in UC as Simple Clinical Colitis Activity Index (SCCAI) <2.

Results

Between December 2023 and February 2025, 86 patients (Crohn’s disease = 17, Ulcerative colitis = 69) were consulted in order to switch from IV to SC vedolizumab administration. Five patients (5,8%) did not want to change and therefore, 81 patients (94,2%) were finally switched. All patients were in clinical remission. After a mean (SD) follow up period of 8 (4) months, 9 patients (11,1%) experienced worsening of their disease, and were either switched back to IV VDZ (n=4, 4,9%) or to another agent (n=5, 6,2%). The remaining 72 patients (88,8%) showed favorable response, none of them requested an unscheduled visit, or developed an adverse event (clinical or laboratory) or needed escalation of treatment.

Conclusion

Elective switching from IV to SC Vedolizumab seems to be an effective and safe approach in real-world every day clinical practice in IBD patients in clinical remission.