bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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&lt;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 &lt; 0.05] and [4%, 8%, 15% and 27% vs. 10%, 16%, 25% and 40%, p &lt; 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

Abstract

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

Abstract

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 &gt;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

Abstract

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 &lt; 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 &gt;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

Abstract

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&lt;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

Abstract

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 &lt; 0.001 and p = 0.042) and clinical remission (p &lt; 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 &lt; 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 &lt; 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 &lt; 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 &lt; 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.