bluuebunny/crossref_metadata_2025_split huggingface dataset:
P706 Tofacitinib in Moderate to Severe Ulcerative Colitis patients naïve to biological therapy: A prospective real world analysis of efficacy and safety
Authors: Banerjee R , Dhanush M , Raghunathan N , Pal P , Joshi V , Patel R , Godbole S , Akki Y , Valluri S , Nagasuri P , Haridas A 
Published: January 2024

Abstract

Background
Tofacitinib is an oral non-selective Janus Kinase inhibitor approved for Ulcerative colitis (UC) after the failure of biological therapy. Tofacitinib as first line therapy in biologic naive patients has not been evaluated.

Methods
We conducted a prospective study to assess the safety and efficacy of Tofacitinib as first line therapy in biologic naive moderate to severe UC. Tofacitinib was given at a dose of 10mg BD for 8 weeks followed by de-escalation to 5mg BD maintenance in responders. Dose escalation was done for relapses. Demographics, disease characteristics, concomitant medication, adverse events, severity and time to relapse were recorded. Clinical response and remission (defined as partial Mayo score: PMS decrease ≥2 and PMS ≤1 respectively) were measured at 4 weeks, 8 weeks, 24 weeks and 52 weeks. Endoscopic response (UCEIS score decrease ≥2) and remission (UCEIS 0-1) were assessed at 1 year. Time to event analysis was done to evaluate the cumulative rate of clinical response.

Results
176 patients (136 biologic naive, 58% male; median age 40y [IQR:31-48y]) were included. Median baseline PMS and UCEIS score were 5 (IQR: 5-7 and 4-6 respectively) (Table 1). Of the biologic naïve cohort, clinical response was achieved in 68.4% and 79.4% at 4 and 8 weeks respectively. Clinical remission was achieved in 45.6%(4-weeks) and 55% (8-weeks). Maintenance of remission was seen in 44.1% and 32.4% in 24 and 52 weeks respectively (Fig1A). There was a significant reduction in PMS from baseline to end of 8-weeks (p&lt;0.001) (Fig 1B). Corticosteroid-free clinical remission was achieved in 64.8% at 24-weeks. 106 patients (77.9%) maintained response till last follow-up. 11 relapsed after dose de-escalation (median time of 5m [range 3-22m]. 7/11 responded to dose escalation to 10mg. Endoscopic response was noted in 62.5% and remission in 33.9% with significant reduction in UCEIS from baseline to 52-weeks(p&lt;0.001) (Fig 1B). Severe and minor adverse events were noted in 4 and 3 patients respectively (Table 1). Overall 1/3 of patients discontinued therapy at 24-weeks (14%) and 52 weeks (10%).
No significant difference in proportion of clinical or endoscopic remission was observed between the biologic naïve and those with history of prior biologic usage (n=31, median time from withdrawal of biologics to Tofacitnib initiation=9 months).

Conclusion
Tofacitinib was effective in induction of clinical remission in more than half of biologic naive, moderate to severe UC . Three-fourth of these patients continued to be in remission at one year with few serious adverse events. Tofacitinib can be considered as upfront oral therapy after failure of conventional management.
P714 Immunogenicity and safety of adjuvated recombinant zoster vaccine in IBD patients on different immunosuppressive therapies
Authors: Franco M , De Bona M , Brun P , Bortoluzzi M , Nappo A , Zaetta D , Roncen E , Riguccio G , Boito C , Piselli P , Castagliuolo I , Savarino E V , Buda A 
Published: January 2024

Abstract

Background
Aberrant immune regulation and the use of immunosuppressive therapy make IBD patients more susceptible to complications of primary Varicella Zoster Virus (VZV) infection and significantly increase the risk of Herpes Zoster (HZ). HZ can be prevented by vaccination and RZV is the first HZ vaccine approved for immunocompromised persons. Limited data on immunogenicity and safety of RZV in immunosuppressed IBD patients are available. We investigated humoral and cell-mediated response and safety of RVZ vaccination in IBD patients under different immunosoppressive therapies.

Methods
In this prospective single centre study, adult IBD patients were enrolled and vaccinated with 2 doses of RZV between May and July 2022. Different immunosuppressive regimens (anti-metabolites, anti-TNF mono and combination therapy; ustekinumab and vedolizumab monotherapy; mofetyl mycofenolate/steroid combination therapy) were not discontinued and the administration schedule maintained. Immunogenicity was evaluated by quantitative detection of serum IgG anti-VZV antibodies and anti-VZV glycoprotein E (gE) antibodies before and 1 month after vaccination completion using ELISA. Reactogenicity was evaluated by diary cards reporting adverse events for 7 days after each dose. Events were graded from 1 (mild, not interfering with everyday activities) to 3 (severe, preventing normal everyday activities). Disease activity was assessed by SCCAI and HBI before vaccination, 7 and 30 days after each dose.

Results
Vaccination was completed in 104 (98.1%) out of 106 enrolled patients (median age 49.7 years, 59.4% male; 55.7% UC, 44.3% CD). Humoral response was observed in all patients, with a significant increase of anti-VZV antibodies (median UTI 23.8; IQR: 20.2-26.2 vs median UTI 419; IQR: 20.2-26.2, 376-458, p&lt;0.001, median 17.8 fold increase, figure 1) and anti-gE antibody concentration compared to baseline (median OD 0.24; IQR: 0.21-0.26 vs OD 0.53; IQR:0.4-0.6, median 2.3 fold increase, p&lt;0.001, figure 1). Imunosuppressive agents, either in mono or combination therapy, did not influence anti-VZV titre, anti-gE concentration and CMI response. Local and systemic solicited reactions after any dose were reported in 96.2% (grade 3=24.8%) and 88.6% (grade 3=33.3%) of patients respectively, with higher grade of intensity after the second dose. No severe adverse events related to vaccination were observed; 2 patients (1.9%) reported a disease flare.

Conclusion
RZV vaccine is able to induce a robust gE-specific humoral immune response. The type and intensity of immunosuppressive regimens did not influence humoral immunogenicity. RZV vaccination was safe and well tolerated in terms of both reactogenicity and exacerbation of disease.
P731 Relapse rate following withdrawal of anti-TNF therapy in patients with inflammatory bowel disease: A single-center experience
Authors: Sina Dr. M , Pemaj X , Djegsi A , Telaku S , Prifti S 
Published: January 2024

Abstract

Background
Discontinuation of anti–tumor necrosis factor alpha treatment (anti-TNFα) in patients with inflammatory bowel disease (IBD) poses a significant risk for relapse. The aim of this study is to analyze relapse rates and to possibly identify factors associated with relapse in IBD patients after treatment cessation with anti-TNFα.

Methods
This is a prospective study conducted at University Clinic of Gastroenterology in Albania from 2019-2022. IBD patients who discontinued biologic therapy with infliximab (IFX) or adalimumab (ADA) were included. All the patients discontinued therapy due to reimbursement issues. Demographic, clinical,laboratory and endoscopic data were collected for each patient. Relapse rates and predictors for relapse were studied using survival and Cox regression analysis.

Results
A total of 52 IBD patients, mean age 50.8±14.7 years (46 UC and 6 CD), 25(48%) males, were included in the study. Mean follow-up was 29 months. 47.4% were treated with ADA and 51.5 % with IFX. The mean period of biologic therapy was 33.3 months for all patients. Upon treatment cessation, 55.8% of patients were in complete clinical remission, and 30.8% were in partial clinical remission.
Cumulative relapse rates at 6, 12, 24 and 36 months were 23.9%, 39.1%, 44.2% and 69.7% respectively for all UC patients while 66.7% of CD patients relapsed within 6 months. The mean time to relapse was 13 months for UC and 5 months for CD patients.
Among all IBD patients in complete clinical remission at the time of treatment discontinuation, the cumulative relapse rates at 6, 12, 24 and 36 months, were: 6.9%, 24.8%, 57.7%, and 58% respectively. Significantly higher cumulative relapse rates were found in patients with partial remission, the at the same time points: 37.5%, 50%, 75%, and 81.2% respectively (p=0.01).
Multivariable Cox analysis revealed that the only factor associated with lower risk of relapse was mucosal healing (vs nonmucosal healing: HR, 0.322; 95% CI, 1.26 to 6.677; p=0.012).

Conclusion
The majority of IBD patients relapsed within 3 years after anti TNFα discontinuation, Mucosal healing was the only factor associated with a lower risk of relapse. These results emphasise the crucial role of mucosal healing in guiding treatment decisions for IBD patients.
P744 Evaluation of a lifestyle program based on physical activity on quality of life and fatigue in patients with Inflammatory Bowel Disease: a pilot study
Authors: Van De Pol N , Visser E H , van der Woude C J , de Vries A C , de Jonge V , West R L 
Published: January 2024

Abstract

Background
Patients with inflammatory bowel disease (IBD) tend to be less physical active, whilst maintaining an active lifestyle has been associated with enhanced disease control, diminished fatigue and improved quality of life. The primary objective was to evaluate the potential impact on physical fitness, fatigue, quality of life and disease control of a specially designed exercise program for IBD patients.

Methods
Patients with IBD, treated at two teaching hospitals in the southwest of the Netherlands, participated in a 16-week exercise program (IBD-Fit) between March until June 2023. The program was designed especially for patients with IBD to sport with peers and was adjusted to a patient's fitness level. Improvement of physical fitness (measured with body composition, grip strength, sit-and-reach test, Y-balance test and 6-minute walk test) was analysed. In addition, patients were asked to fill in validated questionnaires at baseline and at the end of the program (IBD-Quality of life, IBD-Fatigue and IBD-control), to assess the effect of the exercise program on quality of life, fatigue and disease control. For statistical analyses, a paired t-test or Wilcoxon matched paired rank test was used.

Results
A total of 27/32 patients completed the entire exercise program, with a mean age of 50.4 years (SD 12.5), 40.7% were male, 48.1% had Crohn’s disease and 51.9% had ulcerative colitis (table 1). After 16 weeks, body composition, such as BMI and muscle mass improved compared to baseline; fat percentage significantly decreased (32.3 to 29.7%; Z=-2.983; P=0.003). Physical fitness improved significantly, based on the sit-and-reach test (23 to 29 cm; Z=-3.03; P=0.002), the absolute reach distance of the Y-balance test (73.7 to 79 cm; Z=-2.77; P=0.006), and the mean distance during a 6-minute walk test (505.2 to 557.5 m; 95%CI 32.6 – 72.2; P&lt;0.001). Grip strength showed no significant improvement. Quality of life improved on average with 8.0 points on the IBDQ. The Systemic Symptoms domain improved significantly (mean difference 2.7; 95%CI 0.1–5.4, P=0.043). The program significantly improved fatigue scores (Z = -2.296, P=0.022). Disease control showed no significant improvement after the program. Overall, patients were very satisfied with the exercise program. Average rating was 8.6 out of 10.

Conclusion
This pilot study in a small number of patients shows that a specially designed exercise program has a positive effect on IBD patients. These results underline the importance to broaden our standard of care and can be used as a steppingstone to implement the program on a larger scale and ultimately become part of the standard of care for patients with IBD.
P745 Assessment of Crohn’s disease patients following risankizumab initiation using intestinal ultrasound: A prospective study
Authors: Rosentreter R , Ingram R , Ma C , Chan M , Shukla T , Devlin S , Kaplan G , Seow C , Panaccione R , Novak K , Lu C 
Published: January 2024

Abstract

Background
Risankizumab (RIS) is a humanized monoclonal antibody that inhibits interleukin-23 by binding to its p19 subunit. The use of RIS in the treatment of moderate to severe Crohn’s Disease (CD) was approved in December 2022. Intestinal ultrasound (IUS) is an accurate and well-tolerated modality for evaluating response to therapy. Here, we assessed the IUS response at 3 and 6 months following RIS therapy.

Methods
CD patients initiating RIS were recruited and evaluated by IUS at baseline (within 14 days of initiation), 3, and 6 months. Data elements collected at baseline included demographics, medication exposures, surgical history, as well as inflammatory biomarkers. IUS response (decrease in bowel wall thickness (BWT) ≥ 25%)) and transmural remission (TR) (normalization of BWT normalization, color doppler signal (CDS, modified Limberg (ML) score 0), wall stratification, inflammatory fat)) for each segment were evaluated. Paired t-tests were used to compare values at 3 and 6 months relative to baseline.

Results
A total of thirty-three (20, 60.6% female) patients were recruited; 30 completed baseline and 3 month IUS, while 18 patients have also completed a 6 month IUS. Median age was 55 years (IQR 39-63), with a 12 year median CD duration (IQR 5-28). Five had inflammatory behaviour, 19 had stricturing, and 6 had fistulizing behaviour. CD distribution was 18 ileal, 1 colonic, and 11 ileocolonic. Baseline mean CRP (4.1 ± 4.9 mg/L) did not differ at 3 months (5.0 ± 6.8 mg/L, p=0.16), nor at 6 months for patients with values available (6.2mg/L ± 8.3, p = 0.38). Of patients with FC concentrations, 3 month mean FC (129.4 ±70 mcg/g) (9 patients) had significantly decreased from baseline (427.6 ± 271 mcg/g) (p=0.008), and similarly at 6 months (9 patients; baseline 396 ± 299 vs. 129 ± 75, p = 0.02). 80.0% (4/5) patients with colonic BWT &gt; 3mm had IUS response (baseline mean BWT 5.6±1.4mm vs 3.5 ± 0.8mm at 3 months (p=0.011). IUS response was achieved in 20% (5/25) with ileal CD at 3 months (BWT 6.3 ± 2.1mm vs 3 month 6.0 ± 2.5mm (p=0.31). 21.4% (3/14) of ileal CD patients had an IUS response at 6 months. There was a non-significant ileal BWT reduction (5.4 ± 1.6mm) from baseline (6.0 ± 1.7mm) at 6 months. Of the 9 with moderate to severe CDS, 55% (5/9) had reduction to mild CDS by 3 months. TR was achieved by one patient with ileal CD at 6 months.

Conclusion
IUS response was achieved in 80.0% of CD patients with colonic disease at 3 months follow RIS initiation. IUS response was detected for 20% of ileal CD patients at 3 months and 21.4% at 6 months A significant FC reduction by 3 and 6 months was attained. Further prospective patient recruitment and IUS at 6 and 12 months to assess preliminary results and longer-term response is needed.
P767 Pharmacokinetics of subcutaneous infliximab induction and maintenance in patients with moderate-to-severely active Crohn’s disease
Authors: Anjie S , Mâthot R A A , Gecse K B , D'Haens G R A M 
Published: January 2024

Abstract

Background
Since 2021, subcutaneous (SC) infliximab (IFX) has been available for maintenance treatment of Crohn’s disease (CD) after an induction phase of 2 intravenous administrations of 5 mg/kg. The DIRECT-CD study is an ongoing randomised multicentre trial in which CD patients receive SC IFX also during induction. The applied SC IFX doses in the DIRECT-CD are based on population pharmacokinetics derived during maintenance treatment with SC IFX. We aimed to validate our induction regimen and correlate serum concentrations with clinical efficacy.

Methods
Patients with moderate-to-severe CD (Crohn’s disease activity index [CDAI]) &gt;220 and endoscopic ulceration) received fixed SC IFX induction doses of 240 mg at week 0 and 2, followed by maintenance treatment (120 mg every other week). IFX serum concentrations and CDAI were evaluated at week 2, 4, 8, 14 and 26. Clinical remission was defined as a CDAI ≤150. For this analysis, body weight is defined as low if &lt;80 kg and high if ≥80 kg.

Results
In total, 48 samples of 12 Crohn’s disease patients were analysed (Table 1). During the induction phase (week 2 and 4), observed IFX serum concentrations were lower than expected by the population pharmacokinetic model for all patients (median 15.0 µg/mL [IQR 9.4-20.0]). Moreover, concentrations were significantly lower in patients with a low versus high body weight (median 20.0 µg/mL [IQR 15.0-21.0] vs median 10.2 µg/mL [IQR 4.4-15.8], resp., P=0.004). During the maintenance phase (week 8, 14 and 26), median IFX serum concentrations were also higher in patients with a low body weight compared to patients with a high body weight (17.5 µg/mL [IQR 14.8-19.5] vs 8.9 µg/mL [IQR 5.8-13.8], P&lt;0.001). No patients in the first quartile of IFX serum concentrations (≤7.0 µg/mL) at week 2 reached clinical remission at Week 8, whereas all patients who had an IFX serum concentration at week 2 of ≥15.0 µg/mL reached clinical remission at week 8. At the end of the study (week 26), clinical remission was reached in 67% of patients with a low body weight whereas only 33% of patients with a high body weight reached clinical remission.

Conclusion
These data implicate the importance of body weight in SC IFX dosing strategies. Based on these findings, SC IFX induction and maintenance treatment is changed to a weight-based dosing scheme in the ongoing DIRECT-CD trial.
P787 Use of upadacitinib to treat IBD in post-liver transplant
Authors: Miyatani Y , Choi D , Choi N K , Aronsohn A I , Pillai A , Cohen R D , Rubin D T 
Published: January 2024

Abstract

Background
Approximately 2% of patients with inflammatory bowel disease (IBD) have concurrent primary sclerosing cholangitis (PSC). Liver transplantation (LT) is sometimes required due to progressive PSC. However, the management of active IBD post-LT is challenged due to concomitant anti-rejection immunotherapies. Janus kinase inhibition has been previously described to have anti-rejection properties in patients who have had renal transplants. Here, we describe our experience with upadacitinib (UPA), a selective Janus kinase-1 inhibitor, for post-LT active IBD combined with anti-rejection immunosuppression therapy.

Methods
This is a retrospective, single-center observational study in a tertiary IBD center. We identified patients with LT treated with UPA for their IBD. Patient related outcomes including transplanted liver status and clinical efficacy and safety of UPA for IBD activity were reviewed.

Results
We identified four patients (3 with Crohn’s disease, 1 with ulcerative colitis) treated with UPA after LT due to PSC, with the UPA indication for the treatment of IBD (n=3) and organ rejection (n=1). Median follow-up was 3 months (interquartile range (IQR) 1.5-7.1), median age at starting UPA was 41.5 years (IQR 40-44), and median interval from the transplant was 3.2 years (IQR 2.3-5.6). Two patients with Crohn’s disease clinically responded to UPA, one weaned off prednisone 30mg/day and remained in clinical remission after reducing UPA from 30 mg/day to 15 mg/day. Two patients developed elevated AST/ALT of up to 107/57 U/L and 83/228 U/L; one required discontinuation of UPA at one month with subsequent AST/ALT normalization; the other remained on UPA with 1.5 month follow-up so far. One UC patient was treated with UPA combined with vedolizumab in an attempt to discontinue prednisone for their immunosuppression for organ rejection, however, they were unable to wean off prednisone due to recurrent ALT and Alk Phos elevations. One patient acquired a mild case of COVID-19 which resolved without change in therapy. No life-threatening adverse events were observed.

Conclusion
We describe 4 patients with IBD who had LT for PSC and who were treated with UPA with successful management of active IBD in 2 cases but lack of efficacy in one case and liver enzyme elevations limiting UPA use in a second. These findings support further exploration of this novel mechanism for treatment of IBD in the post-LT setting.
P799 Deficits in geriatric assessment are dynamic over 18 months and impacted by therapeutic treatment in older patients with Inflammatory Bowel Disease
Authors: Fons A , Asscher V , Stuyt R , Baven-Pronk M , van der Marel S , Jacobs R , van der Meulen-de Jong A , Mooijaart S , Kalisvaart K , Maljaars J 
Published: January 2024

Abstract

Background
Frailty is a dynamic condition, however most previous studies in patients with IBD measured frailty at one point in time. Therefore, we aimed to study the course frailty, reflected by deficits measured in a geriatric assessment, during 18 months follow-up in older patients with Inflammatory Bowel Disease (IBD). In addition, we aimed to identify factors associated with changes in geriatric deficits over time.

Methods
In a prospective, multicenter cohort study, a geriatric assessment was performed at baseline and repeated after 18 months in 154 older patients with IBD. This geriatric assessment evaluated the presence of deficits in five geriatric domains: the somatic domain, mental domain, social domain, activities of daily living and physical capacity. The number and type of impaired domains at baseline were compared to follow-up. An increase in number of domains suggests worsening frailty, whereas a decrease in number of impaired domains suggests improving frailty. Logistic regression was performed to identify factors associated with change in number of domains. All analyses were adjusted for age, sex, type of IBD and educational level.

Results
During follow-up, 32.5% had increased and 26.0% decreased ≥ 1 in number of impaired domains, compared to baseline. At domain level, the proportion of patients with impaired activities of daily living decreased from 49.4% at baseline to 37.7% at follow-up (p-value=0.001). The proportion with impaired physical capacity increased from 14.3% to 26.0% (p-value=0.001). Use of systemic corticosteroid at baseline and/or the year prior to baseline was associated with an increase in impaired domains (aOR 3.00; 95% confidence interval (95% CI) 1.11-8.08; p-value= 0.030), while initiation of biological therapy was associated with a decrease in impaired domains at follow-up compared to baseline (aOR 4.92, 95%CI 1.41-17.15, p-value=0.013).

Conclusion
Geriatric deficits, reflecting levels of frailty, are dynamic over 18 months in older patients with IBD. Therapeutic IBD management appeared an important determinant for the longitudinal course of frailty. This study provides the first longitudinal data on the course of geriatric deficits, measured in a geriatric assessment, in older patients with IBD.