bluuebunny/crossref_metadata_2025 huggingface dataset:
P734 Super-responders in patients with moderate-to-severe Crohn’s disease treated with subcutaneous infliximab maintenance therapy: A post hoc analysis of the LIBERTY-CD study
Authors: Schreiber S W , Sands B E , Hanauer S B , Danese S , Loftus Jr E V , Jeong A L , Kim D H , Lee Y N , Colombel J F
Published: January 2024

Background

The LIBERTY-CD study demonstrated a broad level of benefit for subcutaneous (SC) infliximab (IFX) maintenance therapy compared with placebo in patients (pts) with moderate-to-severe active Crohn’s disease (CD) who responded to intravenous IFX induction. Characterising subgroups of pts with different levels of response could help to better position SC IFX therapy.

Methods

This was a post hoc analysis of 231 pts from the CT-P13 SC arm of the randomised, parallel-group, placebo-controlled LIBERTY-CD study (NCT03945019). Unsupervised group-based trajectory modelling (GBTM) was conducted to deconvolute cohort-level data into response trajectories. Longitudinal patient reported outcomes (PRO-2: abdominal pain and stool frequency) were used to investigate whether pts who received SC IFX maintenance therapy cluster into response trajectories. Efficacy endpoints (clinical remission, endoscopic response and remission, corticosteroid-free remission and comprehensive disease control [CDC] rate) were analysed and compared between different trajectories. Trough levels of IFX (TLI) were evaluated by trajectory throughout the treatment period. Baseline characteristics were analysed in a descriptive manner to explore predictors for super-response.

Results

Four distinct trajectories were clearly separated and stabilised around Week (W) 10–14 (Figure): rapid and sustained improvement (super-responders, n=61), rapid, but slightly less drastic than super-responders, then sustained improvement (fast responders, n=56), gradual then sustained improvement (slow responders, n=63) and partial improvement during the maintenance phase (limited responders, n=51). Super-responders had the highest rates of W54 clinical remission (73.8%; p=0.002), endoscopic response (63.9%; p=0.009), corticosteroid-free remission (63.6%; p=0.007), endoscopic remission (42.6%; p=0.094) and CDC (37.7%; p=0.013) among trajectories (Table). Super-responders also maintained the highest TLI from W10 throughout the maintenance period. Super-responders showed a trend towards lower baseline body weight, body mass index and oral corticosteroid use, but higher Crohn’s Disease Activity Index score and prior biologic/Janus kinase inhibitor use compared to other trajectories.

Conclusion

Distinct subpopulations with different levels of responses were detected by GBTM using data from a large group of pts with moderate-to-severe active CD who were treated with SC IFX for 1 year. Super-responders with rapid and sustained improvements during SC IFX therapy had a higher likelihood of achieving desirable long-term outcomes, with substantial individual benefit (CDC). Baseline characteristics and TLI were associated with super-response.
P748 Place of thiopurine monotherapy in the treatment of Crohn's Disease in the era of biologic therapies: results of a long-term tertiary single-center experience
Authors: Aouroud H , Aouroud M , Lairani F E , Nacir O , Ait errami A , Oubaha S , Samlani Z , Krati K
Published: January 2024

Background

Crohn's disease (CD) is a chronic and disabling immune-mediated disease of the digestive tract, and immunosuppressive drugs are a cornerstone in the therapeutic approach, particularly purine analogues which are widely used in the treatment of CD as an agent to maintain remission. Despite their widespread use, adverse effects are frequent and lead to discontinuation of treatment in a significant proportion of patients so the increasing use of anti-TNFα biologics may have had an impact on the use of thiopurines. We present a long-term retrospective experience from a tertiary hospital center aimed at studying the evolution of thiopurine monotherapy use in the era of biologics, based on current therapeutic goals and safety standards.

Methods

We performed a retrospective analysis of all Crohn's disease patients followed up in our hepato-gastroenterology department who received AZA monotherapy at the standard dose (2-2.5 mg/kg/d) or 6-MP (1-1.5 mg/kg/d) at any time during their follow-up between January 2016 and June 2023 and who were still being followed up at that time. Patients who had received prior or concomitant biological treatment were excluded from the analysis. Various socio-demographic and phenotypic data were collected. Failure was defined as discontinuation of treatment due to lack of efficacy or AE. Statistical analysis was performed using SPSS2.0 software. Statistical significance was set at p < 0.05.

Results

A total of 383 patients were included: 46.5% were men and the mean age was 31 years (range 17-65). Median follow-up was 66 months. Indications for thiopurine monotherapy were cortico-dependence (306 patients, 80%) or prevention of postoperative recurrence (77 patients, 20%). Overall, 147 patients (38%) failed. The observational study of our patients showed that 74 patients (18.4%) discontinued AZA due to an adverse event (most of which occurred during the first month of treatment), 73 (19%) due to lack of efficacy. Among the main indications for AZA we note: prevention of postoperative recurrence, male gender gave better results than steroid dependence (p =0.001); perianal fistulization of CD and grecal localization gave worse results (p = 0.002).

Conclusion

In our experience, a significant proportion of CD patients on thiopurine monotherapy failed. Although IS monotherapy remains useful for CD in the era of biologics, current clinical practice is moving towards anti-TNFα biologics in an increasing proportion of patients.
P764 Darvastrocel in Treatment of 152 Patients with Perianal Crohn's Disease - Observational Study
Authors: Serclova Z , Tremerova A , Ryska O , Zuskova P , Lengalova M , Vlkova K
Published: January 2024

Background

Complex perianal fistulas significantly affect quality of life and treatment costs in patient with Crohn's disease (CD). Application of adult allogeneic expanded adipose-derived mesenchymal stem cells (Darvastrocel, Takeda Pharmaceuticals) represents novel treatment modality for this challenging condition.

The aim of this study was to examine the long-term effects of Darvastrocel (DVS) in patients with complex perianal fistula associated with Crohn’s disease.

Methods

The study was conducted at two Czech medical facilities (NH Hospital, Horovice and ISCARE, Prague). All consecutive CD patients with complex perianal fistula (up to 2 internal and 3 external openings) treated by the same team with DVS between August 2019 and July 2023 were enrolled into the study and followed prospectively. All fistulas persist despite previous biologic and surgical treatment. The technique of DVS application was based on the ADMIRE CD study protocol and was in accordance with SPC. Fistula tract was curetted, internal opening closed and leak test performed under GA. DVS was applied below the internal opening and along the fistula tract subsequently. Perianal area was then assessed at week 3, month 3 and 6 and then every year postoperatively.

Results

In total, 152 patients (53.9% male, 46.1% female) with median age of 36.6 (20-72) years were enrolled (tab. 1). Primary success rate detected within the period of 19.8 (4.2-50.2) months after application was 80.3% (122 patients). Fistula recurred in 9 patients (at the site of original fistula in 6 and in a new location in 3 cases), resulting in a sustained healing rate of 74.3% (113 patients) observed within average of 27.2 months. The Perianal Crohn's Disease Index was significantly lower 3, 6, and 12 months after application in the healed compared to failed group - 1 (0-9), 0 (0-8) and 0 (0-9) vs. 7 (1-13, 8 (0-12) and 6 (0-12), p<0.005. Postoperatively, 48 patients (31.6%) were prescribed antibiotics due to inflammatory changes in perianal area. Out of 122 healed patients 31 (25.4%) received antibiotics for 17 (5-37) days, while 17 (56,6%) patients with treatment failure were treated for 16 (7-70) days.

Conclusion

This real-life study showed that Darvastrocel is highly effective in treatment of complex perianal Crohn’s disease resistant to conservative and surgical management. Moreover, for some patients (anal stricture, chronic changes in anorectum) this may be the only available therapeutic option. Intermittent antibiotic treatment did not affect long-term outcomes. We consider clinical response (crucial for the patient's quality of life) sufficient for predicting sustained long term remission.
P776 A Prospective, Multicenter, Single-arm, Observational Study to Evaluate the Safety and Effectiveness of Vedolizumab in Real-world Clinical Practice in China: Interim Analysis of Safety results
Authors: Zheng C , Chen B , Yu J , Wang X , Li L , Hu Y , Xie L , Liu M , Chen M
Published: January 2024

Background

Crohn's disease (CD) and ulcerative colitis (UC) are categorized as inflammatory bowel disease [IBD] usually treated by corticosteroids, immunomodulators and biologics, etc. Vedolizumab, a gut-selective α4β7 integrin antibody, has been approved in China for IBD patients who are intolerant /lost response to conventional therapies or TNF-α inhibitors. Of late, there is a paucity of data on the safety and effectiveness of vedolizumab in real-world clinical practice in China. This study evaluates the safety and effectiveness of vedolizumab in adult patients with UC or CD Here, we present the first interim analysis.

Methods

In this multicenter, single arm, prospective, observational, real-world study (NCT04872491), adults (aged >18 years) with UC or CD were administered intravenous vedolizumab 300 mg at week 0, 2, 6, and thereafter every 8 weeks. Incidence of adverse events (AEs), serious AEs (SAEs), Treatment-related AEs (TRAEs) and AEs of special interest (AESIs) were the primary endpoints Patients with administration of at least 1 dose of VDZ were included and observed 18 weeks after completion of the study or early termination, up to maximum of 72 weeks. AESIs included infections, malignancies, infusion-related reactions, and hypersensitivity. The secondary endpoints included the effectiveness of vedolizumab in terms of clinical response, clinical remission and endoscopic remission assessed at week 14 and week 54 after vedolizumab initiation.

Results

A total of 307 patients (UC, n=245; CD, n=62) with a median age of 41 years (range: 18-86) were included in the interim analysis. Median duration was 883 days (UC: 1035 days; CD: 731 days) and 105 days (UC: 107 days; CD: 99 days) for IBD and vedolizumab exposure, respectively. A total of 105 (34.20%) patients (UC: 35.92%; CD: 27.42%) developed 225 AEs and the most frequent AEs were infections and infestations (16.61%) followed by gastrointestinal disorders (GID) (14.66%) and general disorders (GD) (4.56%). Colitis and pyeria were the most common GID and GD, respectively occurred in 7(2.28%) patients each (Table 1).

Forty-one TRAEs were observed and ten AEs lead to study discontinuation. Total 13 AESIs and 34 SAEs were reported and at least one AESI was reported in 10 patients. No deaths were reported during the study (Table 2).

A total of 79.19% (118/149) and 34.48% (10/29) patients with UC and CD respectively, achieved clinical response at week 14 (±4 weeks). Clinical remission and endoscopic remission was achieved by 2/2 and 1/1 patients with UC, respectively at week 54 (±4 weeks).

Conclusion

Vedolizumab demonstrated favorable safety profile and treatment effectiveness among Chinese adult patients with UC or CD in real-world clinical practice.
P778 The association of drugs and clinical relapse in patients with microscopic colitis. A retrospective observational study
Authors: Karling P , Bjurström O
Published: January 2024

Background

Smoking, the use of non-steroidal anti-inflammatory drugs (NSAID) acetylsalicylic acid (ASA), proton pump inhibitors, serotonin reuptake inhibitors (SSRI) and statins has been associated with microscopic colitis (MC). We aimed to study if these factors were associated with a higher risk of clinical relapse in patients diagnosed with MC.

Methods

All patients with a histological verified diagnosis of MC at our clinic between the years 2006-2022 were identified. Baseline factors and drugs prescribed before and after diagnosis were registered. Risk factors influence on the odds of having a prescription of oral budesonide and the odds of having a second course of budesonide (clinical relapse) were studied retrospectively.

Results

Patients with MC (n=183) with a mean age of 62.3 years (SD 13.3 years) were followed for median 5 years (25th-75th percentile 4-10 years) after diagnosis. One-hundred and thirty-eight patients (75%) had at least one prescription of budesonide after diagnosis and 90 patients (49%) had at least one clinical relapse treated with budesonide. The time to clinical relpase in patients with at least one course of budesonide are shown in Figure below. Patients who had been prescribed NSAIDs within one year before clinical relapse had higher odds for clinical relapse (OR 2.88, 95% CI 1.11-7.43) but there was no increased risk for clinical relapse for the use of ASA (OR 0.99, 95% CI 0.43-2.33), PPIs (OR 1.06, 95% CI 0.53-2.14), SSRI (OR 1.29, 0.59-2.80) or statins (OR 0.93, 95% CI 0.46-1.89). No association was seen for being a smoker and/or being prescribed NSAID, ASA, PPI, SSRI and statins at baseline and the odds of having a prescription of oral budesonide within one year after diagnosis.

Conclusion

The risk of a clinical relapse are associated with the use of NSAIDs but not with the use of ASA, PPIs, SSRIs and statins. We suggest that patients with MC use NSAID with caution.
P780 Persistence of Health-related Quality of life decline in IBD patients after the COVID-19 outbreak
Authors: Herrera De Guise C M , Mayorga Ayala L F , Serra Ruiz X , Robles Alonso V , Céspedes Martínez E , Casellas F , Pérez Martínez Z , Oller Jimenez E , Borruel Sainz N
Published: January 2024

Background

Inflammatory bowel disease (IBD) affects many aspects of a patient’s life and impairs their health-related quality of life (HRQoL). We previously showed that there was a negative impact of the COVID-19 outbreak on the HRQoL of IBD patients in remission. This study aimed to assess if IBD patients in stable, clinical remission could recover their pre-outbreak HRQoL once the global emergency for COVID-19 ended. We also compared their self-perceived stress scores during and after the outbreak.

Methods

We carried out a prospective, observational study on IBD patients with biological treatment and stable clinical remission who had participated in the previous study. Patients filled in the IBDQ9 and the Perceived Stress Scale (PSS) electronically. The results of the IBDQ9 pre-, during, and post-COVID-19 outbreak were compared to determine any changes. PSS scores during and after the outbreak were also compared.

Results

Ninety-three patients in clinical remission were included, with a median age of 43 years; 40% were female, and 78% had Crohn’s disease. Median pre-COVID-19 IBDQ9 was 54 (50-59) and decreased to 50 (46-58) during the outbreak, and post-outbreak was 49 (44-56) (p<0.01). PSS score improved after the outbreak, with a median value of 10 (8-18) during the outbreak and a score of 14 (9-19) after the pandemic. There was a significant negative correlation between the PSS (during the outbreak) and post-outbreak IBDQ9 (r=-0.76, p<0.001). Regression analysis showed that the PSS score during the outbreak was independently associated with a lower post-outbreak IBDQ-9 (p<0.05).

Conclusion

During the COVID-19 pandemic, there was a negative impact on the HRQoL of IBD patients in remission that persists after the outbreak, with higher self-perceived stress scores during the pandemic associated with a lower post-outbreak QoL. The results of this study underscore the long-term impact that unexpected situations can have on IBD patient's HRQoL. Unforeseen circumstances are mostly non-predictable, as the COVID-19 outbreak has shown, and measures to provide high-quality health care, including access to mental care, will hopefully be implemented for IBD patient care.
P782 Comparison of accelerated and standard infliximab induction regimens in Acute Severe Ulcerative Colitis using propensity score: A retrospective multicenter study in a Chinese cohort
Authors: Liu X , Li H , Tian F , Xie Y , Zhang X , Zhi M , Zhang M , Song X , Guo H , Li X , Liang J , Shen J , Li Y
Published: January 2024

Background

The optimal regimen of infliximab salvage in acute severe ulcerative colitis (ASUC) patients remains controversial. This retrospective multicenter study aimed to compare accelerated and standard infliximab induction in a Chinese cohort of ASUC patients, and to explore risk factors associated with poor prognosis.

Methods

Data were collected retrospectively from steroid-refractory ASUC patients who received infliximab induction as rescue therapy at seven tertiary centers across China. Accelerated infliximab induction was defined as receiving two doses of infliximab on or before day 13 and/or receiving intensified doses of ≥ 7.5 mg/kg. Outcomes including colectomy and clinical remission (Mayo score ≤ 2 and every subscore ≤ 1 at day 14) rates were compared using propensity score adjustment for potential confounders. The variables in propensity score model was determined by logistic regression analysis for accelerated induction.

Results

A total of 76 patients were included: 29 received standard induction and 47 received accelerated induction. The overall disease severity was significantly higher in patients of accelerated group (Table). The 30-day colectomy rates did not differ between two groups (4.3% vs. 0%, P=0.522). However, the accelerated group had a higher 90-day colectomy rate (17.8% vs. 0%, P=0.019) and lower clinical remission rate (27.7% vs. 65.5%, P=0.001). (Figure. A) After adjusting with propensity score and institution, there was no significant difference in colectomy (P=0.20) or no clinical remission (P=0.48) hazards. Dose-effect curves plotted by restricted cubic splines (adjusted for propensity score and institution) showed decreased colectomy hazard with higher cumulative infliximab dosage within 5 days, while no improvement was observed for increasing cumulative infliximab dosage within 28 days. (Figure. B) Multivariate logistic regression analyses revealed female gender (OR=7.69, 95%CI: 1.96-33.33) and C-reactive protein (CRP) >10 mg/L at infliximab initiation (OR=5.00, 95%CI: 1.27-24.34) as independent risk factors for no clinical remission. (Figure. C)

Conclusion

After adjusting for confounders, there were no significant differences in colectomy or clinical remission rates between accelerated and standard infliximab induction among steroid-refractory ASUC patients. Elevated CRP at infliximab initiation indicated more intensive treatment or earlier surgery to be considered. And it would be better to give early intensified dosage within 5 days if needed.
P785 Obesity in the response to biological treatments in Inflammatory Bowel Disease patients
Authors: Cabrerizo Mengotti M , Agudo Fernández S , Castaño Milla C
Published: January 2024

Background

Obesity rates in patients with IBD reach up to 40%. Several authors suggest that obese patients have worse response rates to treatments. The aim of the study is to determine whether body mass index (BMI) influences the response to biological therapies in IBD. Secondly, other risk factors will be analyzed, and response rates to different biological treatments will be compared.

Methods

A retrospective cohort study of patients with IBD on biologic drugs under treatment between February 2013 and September 2022 is presented. Patients were recruited from IBD consultation of a tertiary center (Hospital Rey Juan Carlos, Madrid). Inclusion criteria included being under biologic treatment due to IBD and being näive to these therapies. The follow-up of these patients were carried out from February 2013 to September 2022.

The main objective of the study is to determine if BMI influences the response to biological treatment in patients with IBD. As secondary objectives we will try to find the existence of other risk factors for loss of response and between different treatments.

Treatment failure was defined as: need of dose increase, switch or swap to another biological treatment, clinical deterioration (measured by clinical indexes), use of systemic corticosteroid therapy, hospitalization, endoscopic inflammatory activity or surgical complications.

The percentage loss of response was estimated using Kaplan-Meier curves, and factors influencing long-term response were studied using Cox regression.

Results

A total of 135 patients were included in the study, (mean age of 46.3 years), 59.3% male, 25.9% smokers, with a mean BMI of 26.1 kg/m2 (18.5% with BMI>30 kg/m2). In the study, 60% received infliximab and 45.9% received combined immunosuppressive therapy. Treatment failure was 59.1% in the non-obese and 80% in the obese (p=0.051). There were no differences in long-term response rates according to biologic treatments or disease subtypes. The only predictor factor for long-term response was combined treatment with immunosuppressants (p=0.037).

Conclusion

Obesity is not associated with a higher treatment failure rate in patients with IBD undergoing biological therapy. Combined treatment with immunosuppressants acts as a long-term response factor.
P796 Comparative Effectiveness of First-Line Infliximab and Vedolizumab in Patients with Early Ulcerative Colitis
Authors: Rozenfeld Hemed A , Cohen N A , Green O , Hirsch A , Thurm T , Ron Y , Fishman S , Leibovitzh H , Maharshak N
Published: January 2024

Background

Despite the increasing armamentarium of advanced therapies for the treatment of ulcerative colitis (UC), data comparing the effectiveness of biologics in early disease are scarce. We aimed to categorize selection of patients and assess the effectiveness, therapeutic persistence and safety of biologics used to treat early UC in a bio-naïve patient cohort.

Methods

This single-center, retrospective study included all bio-naïve UC patients who commenced advanced therapy within two years of diagnosis between 2012-2023. We collected demographic, clinical, and laboratory data. Clinical disease activity was assessed using the Simple Clinical Colitis Activity Index; clinical response was defined as a decrease of ≥ 3 points from baseline and clinical remission defined as an SCCAI of ≤2

Results

Out of the 1117 patients with UC who were treated at our center during the study period, 46 bio-naïve patients (mean age 36.7 years (±17)) were treated with either infliximab (IFX) or vedolizumab (VDZ), within 2 years from diagnosis. IFX was the first biologic in 19 (41%) patients and VDZ in 27 (58%) patients. At therapy initiation, 38 (82%) patients were receiving corticosteroids and 7 (15%) concomitant immunomodulators (Table 1). Patients treated with IFX had significantly lower hemoglobin (10.4 (IQR 8.5-11.3) vs 12.1 (IQR 10.8-13.9) g/dL, p=0.007) and albumin (3 (IQR 2.8-3.8) vs. 3.8 (IQR 3.4-4.2) g/dL, p=0.01) and significantly higher C-reactive protein (CRP) (48.5 (IQR 9-119) vs. 2.5 (IQR 2-3) mg/L, p<0.001) compared with patients starting VDZ.

Following induction (week 14) clinical response and remission rates were similar in both treatment groups (IFX: 73% and 63%; VDZ: 74% and 67%, respectively; p=0.75). At week 52, clinical response and remission rates were similar in both treatment groups (IFX: 50% for both; VDZ: 50% for both, p=n/s). Corticosteroid (CS)-free remission rates amongst patients receiving CS at baseline (17 patients IFX and 21 patient VDZ) at week 52 were similar in both groups (IFX: 58% vs VDZ 57%, p=n/s). Treatment persistence over 2 years of follow-up was similar between IFX and VDZ (Figure 1). Safety profiles were similar in both treatment groups with no new signals noted.

Conclusion

In these real-world data in patients with early and bio-naïve UC, first line IFX was used in more severe baseline disease as highlighted by lower albumin and hemoglobin levels and higher CRP at baseline. Despite this, IFX showed equal effectiveness in induction and long-term maintenance and showed similar treatment persistence compared with VDZ.
P801 Umbrella review of effectiveness of digital technologies for the management of Inflammatory Bowel Disease
Authors: Gasparetto M , Narula P , Wong C , Ashton J , Kammermeier J , Pierik M , Kopylov U , Arebi N
Published: January 2024

Background

The use of digital technology is increasing significantly world wide, with 67% of the global population (5.1 billion people) having subscribed to mobile internet services in 2018 [1]. Clinical trials assessing commercially available health tools are sparse, with limited evidence-based outcome data. Systematic reviews of the randomized clinical trials (RCTs) on digital health technology in inflammatory bowel disease (IBD) performed so far, provide mixed results from highly heterogeneous studies. This umbrella review aims to investigate the effectiveness of digital health technology for the care of patients with IBD, to identify research gaps and highlight areas where future work should focus on.

Methods

The following databases were searched for systematic reviews published from 2012 to August 2022: PubMed and Medline via OVID, Embase via Ovid, Cochrane Library and Prospero database of systematic reviews, CINAHL via EBSCO, PsycINFO via Ovid, AMED (Allied and Complementary Medicine database) via Ovid. Electronic search results were downloaded into the “Covidence” software and screened by two reviewers independently by titles and abstracts according to the inclusion and exclusion criteria. Standardised extraction forms were established in Microsoft EXCEL. The methodological quality assessment of the included reviews was performed using AMSTAR 2.0. [2]

Results

The literature search identified 65 studies that were uploaded on the “Covidence” software for title and abstract screening. Three duplicates were removed. Of the 62 papers remaining, 32 were excluded based on title and abstract screening. The full text of the remaining 30 was analysed, with a resulting selection of 8 systematic reviews (four including meta-analyses) deemed relevant to this umbrella review. The RCTs on digital health technology in IBD conducted so far have identified aspects of IBD care that appear to benefit from the use of digital technology, including the patients’ satisfaction, their quality of life and quality of care, their adherence to medications and a reduced number of hospital attendances. Existing trials have not, however, been able to prove a direct benefit of using technology to achieve or maintain clinical remission (Table 1).

Conclusion

Telemedicine should be regarded as an important adjuvant to routine clinical practice. Future larger trials with longer follow-up and defined interventions and outcomes have the potential to address unanswered questions in this area and to identify the patients with IBD who would most benefit from telemedicine so that these approaches can be tailored to specific groups.

References:

[1] Agarwal K, del Hoyo F. J Med Internet Res 2019.

[2] Shea BJ, Reeves BC, Wells G. BMJ 2017, 358, j40.
P809 VARIETY BEACH: Real-world treatment patterns for vedolizumab intravenous and subcutaneous maintenance dosing observed over 1 year in studies from Belgium, Austria and Switzerland
Authors: Novacek G , Hrúz P , Högenauer C , Louis E , Vavricka S R , Moschen A R , Biedermann L , Mächler C , Stemberger B , Van Gassen G , Baert F
Published: January 2024

Background

Vedolizumab (VDZ) is approved for moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD) as intravenous (IV) or subcutaneous (SC) formulations. Real-world data on VDZ treatment patterns in patients (pts) with inflammatory bowel disease (IBD) comparing VDZ IV or SC maintenance are still scarce.

Methods

Three prospective, non-interventional, observational studies following an umbrella protocol enrolled pts in Belgium (NCT04959851), Austria (NCT04890262) and Switzerland (NCT04989907) from Aug 2021 to Jun 2022. Adults initiating VDZ IV induction per the product label or continuing VDZ IV maintenance with the option to switch to SC administration, were eligible. The primary endpoint was VDZ treatment persistence at 1 year. Administration route, dosing frequency, reasons for regimen change and safety endpoints were also assessed. Non- responder imputation was applied for pts discontinuing treatment, discontinuing the study or lost to follow-up. A descriptive analysis was performed.

Results

Of 377 pts enrolled, 373 (UC=218, CD=155) were included in this interim analysis. At enrolment, 287 (77%) (UC=159, CD=128) already received VDZ IV maintenance for median 2.8 (0–12.6) years and 86 (23%) (UC=59, CD=27) started VDZ induction (baseline pt characteristics summarized in Table 1). For pts enrolled on VDZ IV maintenance, 12 discontinued vedolizumab, 34 discontinued the study and 14 were lost to follow-up; resulting in a VDZ persistence rate at 1 year of 79% (227/287). Of pts in this cohort persistent on VDZ at 1 year (n=227; UC=124, CD=103), 39% (88/227) switched from VDZ IV maintenance to SC during the study. For pts initiating VDZ induction, 10 discontinued VDZ, 16 discontinued the study and 3 were lost to follow-up; resulting in a VDZ treatment persistence of 66% (57/86). Of pts from this cohort persistent on VDZ at 1 year (n=57; UC=43, CD=14), 56% (32/57) switched to VDZ SC during the study (Figure 1). Overall, the most common reasons for administration route changes were pt decision 98/161 (61%; UC=56%, CD=67%), end of induction (planned switch: 10%; UC=14%, CD=5%) and disease adequately controlled (6%; UC=7%, CD=3%). Adverse events (AEs) occurred in 48 pts (13%) (UC=20, CD=28) and serious AEs in 6 pts (2%) (UC=3: Budd-Chiari syndrome, death cause unknown, UC worsening; CD=3: bronchopneumonia, gastroenteritis, recurrent urinary tract infection).

Conclusion

Real-world data from prospective observational studies in Belgium, Austria and Switzerland reported high persistence of VDZ IV and SC maintenance treatment over 1 year. Decisions on route of administration change were most frequently driven by patients. Safety results were consistent with the known safety profile of VDZ.
P819 Postoperative prophylaxis prevents surgical and severe endoscopic recurrence after primary ileocecal resection in CD patients
Authors: ten Bokkel Huinink S , Bak M , Beelen E , Erler N , Hoentjen F , Bodelier A , Dijkstra G , Romberg-Camps M , de Boer N , Stassen L , van der Meulen-de Jong A , West R , van der Woude C J , van Ruler O , de Vries A
Published: January 2024

Background

Prophylactic medication following ileocecal resection (ICR) is recommended in patients with Crohn’s disease (CD), particularly in patients at increased risk of recurrence. This study aimed to evaluate the effect of prophylactic medication on long-term prognosis.

Methods

A retrospective cohort study was performed in patients with CD who underwent a primary ICR. Patients were divided into two groups: prophylaxis (i.e. initiation of prophylactic medication<12 weeks following ICR) versus no prophylaxis. The primary and secondary outcomes were surgical recurrence and severe endoscopic recurrence (modified Rutgeerts score ≥ i3). To compare the outcomes between both groups, inverse propensity score-weighted comparison was used to adjust for confounding and selection bias. The survival and association between prophylaxis and both outcomes were assessed with Kaplan-Meier analyses and Cox proportional hazard models.

Results

811 patients underwent an ICR [median follow-up 5.8 years (IQR 2.5 – 10.7)](Table 1). Prophylaxis was initiated in 297/811 [37%] patients. In 364/514 [71%] patients without prophylaxis, medication was started after median follow-up 15 months [IQR 7.2 – 46.5]. Cumulative rates of surgical and endoscopic recurrence at 1, 2, 5 and 10 years were significantly lower in patients with prophylaxis versus no prophylaxis [1%, 3%, 9% and 19%, vs. 3%, 4%, 11% and 23%, p < 0.05] and [4%, 8%, 15% and 27% vs. 10%, 16%, 25% and 40%, p < 0.01]. Propensity-scored weighted analysis showed that patients treated with prophylaxis were less likely to experience surgical recurrence [aOR 0.52; 95% CI 0.33 – 0.82] and severe endoscopic recurrence[aOR 0.53; 95% CI 0.35 – 0.81]. In multivariable analysis, prophylaxis was identified as protective factor for surgical [aHR 0.67, 95% CI 0.45 – 0.99] and severe endoscopic recurrence [aHR 0.54, 95% CI 0.37 – 0.78] (Table 2).

Conclusion

Surgical and severe endoscopic recurrence up to 10 years following primary ICR are significantly reduced in patients with CD who received prophylaxis as compared to no prophylaxis. Prophylaxis was associated with the prevention of surgical and severe endoscopic recurrence.
P848 Risankizumab Effectiveness in Ustekinumab-naïve and Ustekinumab-experienced Patients with Crohn’s Disease- Real-world Data from a Large Tertiary Center
Authors: Zinger A , Choi D , Choi N , Fear E , Fine Z , Cohen R D , Dalal S R , Krugliak Cleveland N , Pekow J , Rubin D T
Published: January 2024

Background

Risankizumab and ustekinumab are both IL23 inhibitors approved for treating moderate to severe Crohn’s disease (CD). They are distinguished by the fact that ustekinumab targets p40, the shared subunit of both IL23 and IL12, while risankizumab targets the p19 subunit and thus selectively inhibits IL23. The effectiveness of risankizumab in ustekinumab-experienced patients is of particular interest due to similar mechanisms of action. We present a large long-term real-world experience with risankizumab in ustekinumab-naïve and ustekinumab-experienced patients with CD.

Methods

We prospectively followed patients with CD treated with risankizumab in our center and documented their disease activity score at weeks 2, 4, 8, 12, 26, and 52 after treatment initiation. Patients treated for active luminal disease, defined as HBI≥5, fecal calprotectin≥250, or evidence of active disease per ileocolonoscopy or imaging were included. Patients who stopped treatment due to ineffectiveness or intolerance were counted as non-responders for the purpose of remission-rate calculation at each time point.

Results

102 patients with CD with active luminal disease were treated with risankizumab and had at least 12 weeks of follow-up. Of them 46 (45%) were ustekinumab-naïve, and 56 (55%) were ustekinumab-experienced. The ustekinumab-experienced patients had longer disease duration and higher rates of prior bowel resection and exposure to multiple advanced therapies (Table 1). The baseline median HBI was higher in the ustekinumab-experienced group. Both groups had a continuous downward trend throughout the follow-up period (Figure 1A). At week 12, 74% (34/46) of the ustekinumab-naïve and 55% (31/56) of the ustekinumab-experienced patients achieved steroid-free clinical remission (SFCR) (P=0.06). At week 26, SFCR rates were 76% (25/33) and 60% (21/35) in ustekinumab naïve and experienced patients respectively (P=0.2). In a subgroup of patients with a follow-up of one year, 71% (5/7) and 40% (6/15) were in SFCR at week 52 (P=0.36) (Figure 1B). Of the patients who achieved SFCR at week 12, 85% in both groups maintained SFCR at week 26 (23/27 and 17/20 in ustekinumab-naïve and ustekinumab-experienced cohorts, respectively).

Conclusion

In this large real-world experience with long-term follow-up, we found that patients with CD treated with risankizumab were statistically similarly likely to achieve and sustain SFCR regardless of prior ustekinumab experience. Non-statistical differences noted may reflect the longer disease duration and prior treatment exposure of the ustekinumab-experienced group. These findings support the consideration of risankizumab as a treatment option for patients with CD regardless of their prior exposure to ustekinumab.
P851 Therapeutic drug monitoring of infliximab and adalimumab versus clinical control during maintenance therapy in patients with Inflammatory Bowel Disease
Authors: Muñoz Villafranca M D C , Merino O , Gómez L , Higuera R O , Arreba P , Nagore D , Ruiz-Argüello B , Gorostiza I , López M L , Ortiz de Zárate J
Published: January 2024

Background

Although it is known that the levels of infliximab or adalimumab are correlated with clinical response, there is controversy about the best strategy to follow in patients with Inflammatory Bowel Disease (IBD) in remission and undergoing maintenance treatment.

Methods

We conducted a randomized, prospective, single-blinded, and multicentre trial in patients with Crohn’s Disease (CD) or Ulcerative Colitis (UC) who have remained in clinical remission for at least 12 weeks and are receiving adalimumab (ADA) or infliximab (IFX) as maintenance treatment. Patients were assigned to two groups. In the first group, patient management was done considering therapeutic drug monitoring (TDM). In the second, according to usual clinical practice (CP). The optimal serum range was within 3-7µg/ml and 5-8µg/ml for IFX and ADA respectively, based on the use of Promonitor-IFX, and Promonitor-ADL kits. The primary endpoint was to maintain patients in clinical remission (target >16% between both groups at 12 months) and diminish the frequency of flare-ups.

Results

In total, 209 patients were randomized, 29 UC (27.6%), 76 CD (72.4%) as the clinical practice group, and 24 UC (23.1%), 80 CD (76.9%) as the drug monitoring therapeutic group.

Infliximab was administered in 105 patients and adalimumab in 104. Remission at the end of the study was achieved in 98.1% of the proactive dosing group and 90.5% of the clinical practice group (p=0.02), with a difference between both groups of 7.6%. The number of flare-ups was 1.3/10 patient-years in the TDM group and 2.4/10 patient-years in the CP group. The IRR of flare-up throughout the study was 0.71 (95% CI 0.32 – 1.55). In the group with IFX: IRR = 0.56 (95% CI 0.08 – 3.81) and with ADA: 0.78 (95% CI 0.29-2.16). The changes made in the drug dose are shown in Table 1.

Conclusion

Differences were found in favour of the TDM group, with increasing remission rates (7.6%) and half number of flare-ups. However, the pre-established effectiveness remission target (16%) was not met.

In the subgroup of patients with Infliximab, management through TDM seems to have an advantage over usual clinical control.
P868 Patients with inflammatory bowel disease who are intolerant to thiopurine treatment
Authors: Karling P , Gensmyr-Singer H
Published: January 2024

Background

Approximately 15-40% of patients with inflammatory bowel disease (IBD) treated with thiopurines experience side-effects that leads to drug withdrawal. The aim of this retrospective observational study was to compare patients who stop thiopurine treatment due to side effects with patients who tolerate thiopurine treatment in the use of other IBD treatments, the risk of surgery and in the chance of reaching remission (a median faecal calprotectin level < 200 mg/g).

Methods

We included all patients in our clinic who were born after 1956 and diagnosed with Ulcerative colitis (UC) and with Crohn´s disease (CD) after the year of 2006 (n=698). In the patients who at least once started thiopurine treatment, prescription of IBD drugs, surgery and f-calprotectin values were noted for the first five years after start of thiopurine treatment. Patients who stopped treatment due to intolerance (side effects) was compared to patients who were tolerant to thiopurine treatment (no side-effects reported).

Results

The proportion of patients with IBD who initiated thiopurine treatment at our clinic was 44% (32% UC and 64% CD). For patients who started thiopurine treatment 31% (n=94) had to stop treatment within five years due to side effects. Patients who stopped thiopurine treatment due to intolerance were significantly older (median age 32 vs 25 years, p=0.002), were significantly more often on steroids (89% vs 76%, p=0.009) and used to a lesser extent TNF inhibitors at the start of thiopurine treatment (3% vs 9%, p=0.062). There were no statistically significant differences in the proportion of patients that at least once yearly used steroids, TNF-inhibitors or surgery in the first five years after initiated thiopurine treatment between the group of patients who stopped due to intolerance and the group of patients who were tolerant to thiopurine treatment. Budesonide treatment and non TNF-inhibitor biologic therapy was significantly more common used in the patients that stopped thiopurine treatment due to side-effects. The proportion of patients with a median faecal calprotectin >200 mg/g was significantly higher in the patients with UC who stopped thiopurine treatment due to side effects (Figure).

Conclusion

Patients who stopped thiopurines due to side-effects did not in general differ in the use of other treatment for IBD the first five year after initiated thiopurine treatment, except for the use of budesonides and non-TNF inhibitor biologics which was more commonly used in patients who stopped thiopurines due to side-effects. Patients with UC who stopped treatment due to side-effects had higher faecal calprotectin levels at follow-up than patients who tolerated thiopurines.
P874 Impact of immunogenicity on clinical outcomes in patients with Crohn’s disease receiving maintenance treatment with subcutaneous infliximab: A post hoc analysis of the LIBERTY-CD study
Authors: Colombel J F , Danese S , Schreiber S , Sands B E , Yarur A , Kim D H , Lee Y N , Hanauer S B
Published: January 2024

Background

The Phase 3 LIBERTY-CD study showed that subcutaneous (SC) CT-P13 was more effective than placebo as maintenance therapy and was well tolerated in patients with moderate-to-severe active Crohn’s disease (CD) who responded to intravenous CT-P13 induction. This post hoc analysis aimed to evaluate the impact of anti-drug antibodies (ADAs) on drug levels and efficacy in patients treated with SC CT-P13.

Methods

This post hoc analysis of the randomised, parallel-group, placebo-controlled LIBERTY-CD study (NCT03945019) evaluated the impact of ADAs on clinical outcomes in patients with CD who received SC CT-P13 maintenance treatment. ADAs were measured using a new generation, highly sensitive, drug tolerant assay. The following clinical outcomes were evaluated at Week (W) 54 according to ADA occurrence: proportions of patients achieving the co-primary endpoints of clinical remission and endoscopic response, mean Crohn’s Disease Activity Index (CDAI) score and mean Simple Endoscopic Score for CD (SES-CD). Sensitivity analyses were conducted using multiple imputation methods. Discontinuation rates up to W54 according to ADA occurrence were examined by survival analysis. Trough serum infliximab concentrations at W54 were assessed according to ADA occurrence.

Results

The analysis included the 231 patients (ADA-positive, n=150; ADA-negative, n=81) who received at least one dose of SC CT-P13 as maintenance treatment. There were no statistically significant differences in clinical outcomes at W54 between the ADA-positive and ADA-negative patients in each group across imputation methods (Table). Based on observed data at W54 in the ADA-negative vs. ADA-positive groups, 79.7% vs. 69.5% of patients achieved clinical remission (p=0.1335) and 65.2% vs. 57.5% had an endoscopic response (p=0.3595); mean CDAI score was 83.6 vs. 86.0 (p=0.8342), and mean SES-CD was 3.37 vs. 3.94 (p=0.3796). In a survival analysis, discontinuation rates were comparable between the ADA-positive and ADA-negative groups (log-rank p=0.95; Figure). Mean trough serum infliximab concentrations at W54 were significantly lower in the ADA-positive group than in the ADA-negative group (11.7 vs. 19.3 μg/mL; p<0.00001), but in both groups, they exceeded the historical therapeutic target concentration of 5 μg/mL.

Conclusion

Despite affecting drug levels, ADA status appeared to have no significant impact on W54 clinical outcomes or discontinuation rates. These findings could be explained by the relatively high trough serum infliximab concentrations achieved by ADA-positive patients. Further studies are warranted focusing on long-term effects of immunogenicity and optimal drug concentrations in patients receiving maintenance therapy with SC CT-P13.
P876 Efficacy and safety of microencapsulated butyrate add-on therapy in induction of remission in patients with mild-to-moderate Ulcerative Colitis - results from multi-center, double-blind, randomized, placebo-controlled clinical study
Authors: Karlowicz K , Lewandowski K , Tulewicz-Marti E , Domżał-Magrowska D , Talar-Wojnarowska R , Małecka – Wojciesko E , Rydzewska G
Published: January 2024

Background

Butyrate is the most beneficial among short-chain fatty acids (SCFA’s) that plays a key role in intestinal homeostasis by modifying: gut microbiome, gut barrier integrity, and reducing inflammation. There are some evidence of its usefulness in the treatment of Ulcerative Colitis (UC), however the data are not clear. The aim of our study was to assess the efficacy and safety of oral microencapsulated sodium butyrate (MSB) as add-on treatment in induction of remission in active UC.

Methods

100 patients with mild to moderate UC were enrolled in the study and randomized to MSB group treated with 2x300 mg/d of butyrate or placebo group (C); 96 of those patients completed all study protocol. Total Mayo Score (TMS), endoscopic images and fecal calprotectin were investigated to estimate the effect of MSB administration in induction remission, as well as relation between fecal butyrate concentrations (C4) and effectiveness of treatment.

Results

Clinical and endoscopic improvement (p < 0.001 and p = 0.042) and clinical remission (p < 0.001) was observed in MSB group. Accordingly, an improvement in the endoscopic image(defined as Mayo Score (MS) difference ≥ 1) at 8 weeks of follow up was achieved in 26patients (55.3%) in the study group and 16 (32.7%) in placebo group (p=0.042). Clinical improvement (defined as TMS difference ≥ 3) was observed in 39 (83%) study group patients and 15 (30.6%) in placebo group (p < 0.001). Clinical remission (TMS at visit 2 ≤ 2) was obtained in 30 (63.84%) MSB group patients and 11 (22.4%) in control group (p < 0.001). Significant improvement was also expressed as reduction of calprotectin level. In MSB group significant increase of C4 was observed in the group with clinical improvement, clinical remission and endoscopic improvement, and it was significantly higher than among non-responders. (MD =1.35 CI 95 [0.51;3.56], p < 0.001), clinical remission (MD = 1.69 CI 95 [0.44;3.45], p = 0.001) and endoscopic improvement (MD = 1.99 CI 95 [0.84;2.82], (p < 0.001)). In C group the level of C4 was significantly lower, regardless of clinical response. No side effects was observed during treatment.

Conclusion

MSB supplementation increases the fecal butyrate concentration and results in clinical remission and endoscopic improvement in mild to moderate UC. Our study clearly showed that MSB appears to be a beneficial and safe add-on treatment of those patients.