bluuebunny/crossref_metadata_2025 huggingface dataset:
P600 Efficacy of different modalities of faecal microbiota transplantation to induce clinical remission in patients with ulcerative colitis: a systematic review and network meta-analysis
Authors: Chapon J , Scanzi J , Pereira B , Sokol H , Buisson A
Published: January 2024

Background

We aimed to compare the efficacy of different modalities of faecal microbiota transplantation (FMT) to induce clinical remission in patients with ulcerative colitis (UC).

Methods

We performed a systematic review and network analysis (random effects model) of randomized controlled trials including at least one arm of FMT in adult patients with active UC. Primary endpoint, i.e. clinical remission (total Mayo score≤ 2 with Mayo endoscopic score≤ 1), was assessed between week 6 and 12. Results are expressed as relative risk with 95% confidence intervals, adjusted for bowel cleansing and pre-FMT antibiotics therapy. Ranking of FMT modalities for clinical remission was calculated as their surface under the cumulative ranking (SUCRA), which represents the percentage of efficacy achieved by an agent compared with an imaginary agent that is always the best without uncertainty. Heterogeneity among studies was evaluated by τ² (global statistical heterogeneity across all comparisons).

Results

Among the 12 selected studies, patients were exclusively bio-naïve in 4 studies (4/12), while between 9 and 32% had prior biologics exposure in the other trials. Risk of bias was low across all domains in 7 studies. Global heterogeneity was negligible (τ² = 0). After adjustment on bowel cleansing and pre-FMT antibiotics, oral capsule (RR=7.1[1.8-33.3]), lower GI FMT (RR=4.5[1.7-12.5] and combination of both (RR=12.5[2.1-100]) were more effective than placebo to induce clinical remission contrary to upper GI FMT (RR=1.1[0.2-7.7]) and autologous FMT (RR = 0.8[0.2-3.8](Table 1).

The combination of lower GI FMT and oral capsule was significantly more effective than upper GI FMT to induce clinical remission (RR=10.7[1.1-104.2]). Combination of lower GI FMT and oral capsule ranked highest for the induction of clinical remission (SUCRA=0.93), followed by oral capsule (SUCRA=0.82) and lower GI FMT (SUCRA=0.72). Autologous FMT ranked lower than placebo (SUCRA=0.12vs0.22). We performed a sensitivity analysis distinguishing single donor FMT and multi-donor FMT (pooled samples from different donors). Combination of lower GI FMT and oral capsule ranked highest for the induction of clinical remission (SUCRA=0.89), followed by single donor lower GI FMT (SUCRA=0.70), multi-donor (pooled samples) lower GI FMT (SUCRA=0.65), multi-donor (pooled samples) oral capsule (SUCRA=0.61), single donor oral capsule (SUCRA=0.60).

Conclusion

In this network meta-analysis, we confirmed the efficacy of FMT to induce clinical remission in patients with UC. The combination of lower GI and oral capsule FMT seems to be the best modality of FMT for patients with UC while upper GI FMT is not suitable. In clinical trials, autologous FMT should be avoided due to a potential detrimental effect.
P603 Comparison of the safety and efficacy of ustekinumab and vedolizumab in patients with Crohn’s disease. - A systematic review and meta-analysis of propensity score matched cohort studies
Authors: Bodini G , Calabrese F , Pasta A , Marabotto E , Furnari M , Demarzo M G , Giannini E G
Published: January 2024

Background

Ustekinumab and vedolizumab represent both valid therapeutic options in patients with Crohn’s Disease following anti-TNF failure. Comparison data regarding safety and efficacy between these drugs are indirect, and reports conflicting results. The aim of the study was to assess the safety and efficacy profile of ustekinumab and vedolizumab in patients with Crohn’s Disease who failed prior anti-TNF treatment, including studies that applied propensity score matching to reduce confounding bias.

Methods

We identified 52 reports that compared ustekinumab and vedolizumab after a propensity score match analysis, of which 14 were assessed for eligibility, and finally 8 retrospective studies were included. The main outcomes considered were clinical steroid-free remission at 14±4, 24±4, and 52±weeks, drug discontinuation rate, adverse events, serious infections, and hospitalisation during the first year of treatment.

Results

A total of 3,185 patients were treated with ustekinumab (n=1,906, 59.8%) or vedolizumab (n=1,279, 40.2%). Steroid-free clinical remission was not significantly different between ustekinumab and vedolizumab at 12±4 weeks (OR 1.14, 95CI 0.76-1.72), at 24±4 weeks (OR 0.92, 95CI 0.56-1.51, p=0.73), and at 52±4 weeks (1.07, 95CI 0.73-1.56, p=0.75). Risk of adverse events was not different between the two drugs (OR 0.65, CI95 0.30-1.41, p=0.28). In patients receiving ustekinumab, the rate of infection (OR:0.52, CI95 0.30-0.91, p=0.02) and the need of hospitalisation at 1-year (OR:0.68, CI95 0.57-0.81, p<0.0001) appeared to be lower.

Conclusion

Ustekinumab and vedolizumab do not significantly differ in inducing and maintaining clinical steroid-free remission, while ustekinumab was associated with a lower risk of serious infections and hospitalisation during the first year of treatment.
P617 Persistent active inflammation may predict non-improvement in bone mass density in patients with Crohn's disease
Authors: Koifman E , Krasnopolsky M , Weisshof R , Waterman M
Published: January 2024

Background

Osteopenia and osteoporosis are associated with Crohn’s disease (CD). Diagnosis is made by dual-energy X-ray absorptiometry scan (DEXA). Pathophysiology of osteoporosis may reflect an interplay between persistent inflammation, steroid usage, as well as risk factors similar to general population. We aimed to identify factors associated with low or deteriorating bone mineral density (BMD) among patients.

Methods

A retrospective case-control study, included patients with CD followed at our IBD clinic from January 2000 to February 2023, with ≥ 2 DEXA scans. The observation started one year before the initial DEXA scan and extended until one year after the second scan. Demographic, clinical and laboratory data as well as medication exposure were collected before and during F/U. Patients were classified into three groups based on change in DEXA results: improved, worsened and no change. Multivariable proportional odds regression model was built to assess independent predictors of change in BMD.

Results

121 patients [60 (49.6%) females, median age 33 years (IQR 23-43), median disease duration 5 years (IQR 0-35), median baseline BMI 22.4 kg/m2 (IQR 12.9-39.3), baseline CRP 1.4 ULN (IQR 0.5-4.5), baseline vitamin D 54.2 nmol/L (IQR 40.9-67.5)], were enrolled and followed for a median of 48 (IQR 29-71) months. At baseline, patients with osteoporosis had a lower BMI (18.5 kg/m2) than patients with normal BMD (26 kg/m2) and osteopenia (22.4 kg/m2), p<0.001. During F/U 63%, 59% and 66% of patients were exposed to high dose CS, anti-TNF and thiopurines respectively.

At the end of F/U,19 (15.7%) patients had deterioration in BMD status while 78 (64.5%) remained unchanged, and in 24 (19.8%) BMD improved. Baseline vitamin D levels (in nmol/L) were higher in patients with improvement in BMD status at the end of the F/U compared to those with maintained or deterioration in BMD (66, 54.2, 41.2; p=0.001, Figure 1). Active smoking was associated with decline in BMD status (p=0.03). No correlation was found between different types of medication exposure and changes in BMD status. In multivariable analysis, elevated CRP was the only independent variable associated with lower odds of improvement in BMD (OR=0.45 (CI 0.2-1.0), p=0.05,Table 1).

Conclusion

Low BMI, low baseline vitamin D levels, and active smoking were found to be risk factors for low BMD status. Elevated CRP was associated with lack of improvement in BMD during the F/U. No correlation was found between different medications and changes in BMD status.
P618 Comparison of vedolizumab and ustekinumab treatment persistence in anti-TNF experienced Crohn's Disease patients
Authors: Eroglu Z , Yilmaz V , Er R E , Soykan I , Toruner M
Published: January 2024

Background

After the approval of vedolizumab and ustekinumab for the treatment of IBD, discussions continue regarding the prioritization of which drug will be used as the first-line treatment. Despite numerous studies in various indications on this matter, there is still no definitive information. It is known that the success of treatments decreases after the use of Anti-TNF in the first step. In this study, we aimed to compare the drug persistence rates of vedolizumab and ustekinumab used as second-line treatments in Crohn's patients with prior experience with Anti-TNF.

Methods

A total of 171 Anti-TNF experienced Crohn's disease patients were included in this study. Age, gender and other demographical info were recorded from patients electronic medial charts. Drug persistence rates were calculated and compared by using Kaplan-Meier Analysis.

Results

Seventy eight patients who received vedolizumab and 93 patients who received ustekinumab were analyzed. In vedolizumab group, 60% of the patients were male where as in ustekinumab group, 57% of the patients were male. Mean age was 39.4 years in vedolizumab group and 41.2 years in ustekinumab group. All patients were anti-TNF experienced. In addition, 70% of the patients in ustekinumab group was vedolizumab experienced. Concomitant azathioprine use was 56% in vedolizumab group where as 34% in ustekinumab group. Drug persistence was significantly higher in ustekinumab group when compared to vedolizumab group (Figure 1). Interestingly, concomitant azathioprine use did not change drug persistence in ustekinumab group however it increased drug persistence in vedolizumab group.

Conclusion

In anti-TNF experienced Crohn's disease patients, ustekinumab treatment persists more longer than vedolizumab treatment. Ustekinumab persistence was independent from concomitant azathiprine use where as concomitant azathioprine use increases vedolizumab persistence.
P639 Tofacitinib induces clinical remission in patients with chronic pouchitis
Authors: de Jong D C , Goetgebuer R , Müskens B , Neefjes-Borst A , Gecse K , Löwenberg M , de Jonge W , Bemelman W , Ponsioen C , D'Haens G , Duijvestein M
Published: January 2024

Background

Up to 10% of ulcerative colitis patients and an ileal-pouch anal anastomosis will develop chronic or antibiotic refractory pouchitis. Several case reports and -series investigated the effect of tofacitinib for refractory pouchitis, but reported conflicting results(1-5). In this study, we aimed to prospectively evaluate the efficacy of tofacitinib in chronic or antibiotic refractory pouchitis using clinical and objective outcome measures.

Methods

We conducted a prospective single centre pilot study in which thirteen patients with chronic or antibiotic refractory pouchitis (Pouchitis Disease Activity Index (PDAI) ≥ 7, ≥2 episodes in the preceding year for which antibiotic therapy was started, or ≥4 weeks symptoms requiring maintenance therapy) were treated with tofacitinib 10mg BID for eight weeks. Clinical, biochemical, endoscopic and histologic disease activity was assessed at baseline and week 8. The primary endpoint was the proportion of patients reaching clinical remission, defined as a PDAI < 7 and a reduction of ≥ 3 points from baseline at week 8. Pouch endoscopy videos were scored by two gastroenterologists and pouch biopsies were assessed by an IBD pathologist, who were blinded to the time points and clinical outcomes. Medians and interquartile ranges were calculated, and Wilcoxon signed rank test was used to analyse changes from baseline.

Results

Thirteen patients (61% male, median age 34 years) were included(table 1). Three patients did not complete eight weeks of treatment due to adverse events (pyelonephritis, primo EBV infection, worsening of pouchitis), two of whom underwent an early termination endoscopy. In total, 31% achieved clinical remission (4/13) and 62% showed clinical response (8/13). Both the total PDAI score (11 (IQR 9 – 12.75) vs 8 (4.5 – 9.75), p = 0.033), and the clinical PDAI subscore (4 (3 – 4) vs 2 (0.25 – 3.75), p = 0.014) decreased significantly from baseline compared to week 8 or early withdrawal, respectively (figure 1). We did not observe a significant change in endoscopic PDAI subscore (4.5 (2 – 5.75) vs 3 (1 – 4.75), p = 0.120) or histologic subscore (3 (2 – 4) vs 2 (1 – 4), p = 0.214). Biochemical parameters did not decrease significantly compared to baseline (faecal calprotectin: 389 mg/kg (38 – 1222) vs 116 mg/kg (31 – 466), p = 0.530 (figure 2) and CRP: 1,2 mg/L (0.75 – 15.2) vs 0.95 mg/L (0.58 – 17.7), p = 0.307, (figure 3)).

Conclusion

In this pilot study, a clinical remission rate of 31% was achieved in patients with chronic pouchitis after eight weeks of treatment with tofacitinib. However, treatment duration of eight weeks is presumably too short to achieve biochemical, endoscopic or histologic response in these refractory patients.
P643 Magnifying Endoscopy with Narrow Band Imaging for Graft Failure and Disease Recurrence in Patients with Crohn’s Disease after Intestinal Transplantation
Authors: Chung C S , Lee T H , Tsai C C , Yu C H , Chen Y
Published: January 2024

Background

Crohn’s disease (CD) is one of the common causes of short bowel syndrome (SBS) and intestinal failure (IF). Intestinal transplantation (IT) is sometimes needed for patients with CD who develop IF after multiple intestinal resections due to CD-related complications, such as uncontrollable bleeding and penetrating diseases. However, there have been limited case reports concerning the endoscopic surveillance of CD patients after IT.

Methods

We retrospectively investigated two patients with CD who underwent IT because of SBS-IF after multiple intestinal resection. We administered post-transplantation immunosuppressants and conducted regular magnifying endoscopy with narrow-band imaging (ME-NBI) via ileostomy chimney for surveillance of grafte rejection. Endoscopic prediction of rejection were based on our previously published "VENCH" score which is composed of five parameters: "V" (villi appearance), "E" (erythema), "N" (capillary network), "C" (crypt widening), and "H" (heterogeneity). Endoscopic biopsy were taken for histologic confirmation of graft rejection severity.

Results

Case 1 was a 60-year-old male patient with CD who received three times of intestinal resection for small bowel stricture and perforation, followed by IT due to SBS-IF. He lived uneventful until seven years thereafter with bloody diarrhea presented. Endoscopic surveillance revealed normal VENCH score of background mucosa but deep longitudinal ulcers which was indicative of recurrence of CD rather than graft rejection. Anti-tumor necrosis factor alpha with adalimumab was prescribed and his diarrhea and graft ulcers improved. Case 2 was a 39-year-old male patient with CD who received extensive intestinal resection due to multiple perforations, followed by IT because of SBS-IF. Endoscopic surveillance revealed normal VENCH score without histologic graft rejection two years thereafter. Both enrolled cases demonstrated favorable outcomes after endoscopic surveillance of intestinal graft with ME-NBI and management accordingly.

Conclusion

The post IT follow-up of CD patients remains challenging. We highlight the usefulness of the ME-NBI using VENCH score for early detection of graft rejection and its value in monitoring CD patients after IT. Additionally, ulcerations without changes in morphology of surrounding villi should take into consideration the disease recurrence of underlying CD. Further research is needed in endoscopic follow-up and molecular genetics to better understand CD after IT.
P652 Transitioning Inflammatory Bowel Disease patients from an intravenous to a subcutaneous infliximab protocol: a single centre experience and patient satisfaction survey
Authors: Mohamed I , Naughton T , Okuwobi K , Walker G , Hanna M
Published: January 2024

Background

Infliximab is used for the treatment of Ulcerative colitis (UC) and Crohn's disease (CD). Subcutenanous (SC) infliximab (CT-P13) received regulatory approval from the European Medicines Agency for Inflammatory Bowel Disease (IBD) in July 2020. Our study aim was to assess the efficacy and safety of SC infliximab in our patient cohort at University Hospital Lewisham as well as gain patient feedback on their experience of subcutaneous infliximab compared to intravenous infliximab.

Methods

We retrospectively analysed the records of all patients receiving infliximab treatment from May 2022 to May 2023 for age, gender, diagnosis, clinical response, faecal calprotectin levels and side-effects. We designed a patient questionnaire for patients who were switched from IV to SC infliximab to assess patient preferences with regards to route of administration, satisfaction with treatment as well as reported side effects.

Results

60 patients (M:F ratio 1:1; average age 36.2y) were receiving infliximab during this time frame. 23 patients were switched to SC infliximab whilst 37 patients remained on IV infliximab. 37/60 (61.7%) had CD, 20/60 (33.3%) UC, and 3/60 (5.0%) IBD unclassified (IBD-U).

Mean faecal calprotectin (FC) levels during treatment were comparable in both groups (Mean FC 117 in IV group; Mean FC 94 in SC group). No patient in either group required hospital admission or gastrointestinal surgery. 1/23 (4.3%) patients switched to an alternate biologic in SC group due to loss of response, whist 3/37 (8.1%) patients in IV group required a switch of biologic therapy over the same time frame.

There were no major side effects reported in either the SC group or IV group. There were 5 minor side-effects recorded in the IV group - 4/37 (10.8%) rash; 1/37 (2.7%) mildly deranged liver function tests. There was 1 minor side effect reported in the SC infliximab group of mild injection site skin reaction 1/23 (4.3%)

18/23 (78.2%) SC infliximab patients completed the patient satisfaction questionnaire. All respondents (18/18, 100%) found the drug more convenient to self-administer than attending the infusion unit for IV infliximab. 1 patient (4.3%) reported mild pain and skin reaction at the injection site. 22/23 (95.7%) of the SC group were satisfied with their treatment and preferred to continue on the SC regimen rather than receive IV infliximab. The one patient who preferred IV infusions reported fear of needles and self-injections as the reason for the IV preference.

Conclusion

Our study showed that SC infliximab was a safe, well tolerated and efficacious treatment compared to IV infliximab. Our patient satisfaction survey showed that a large majority of patients preferred the SC method of administration and were satisfied with their treatment.
P657 Persistence of subcutaneous infliximab after two years of the switch from intravenous infliximab to subcutaneous infliximab in Inflammatory Bowel Disease patients
Authors: Huguet J M , Iborra M , Marti L , Bosca-Watts M M , Ramirez J J , Ruiz L , Sanchis L , Garrido A , Alemany G , Suria C , Paredes J M
Published: January 2024

Background

Biosimilar infliximab (CT-P13) has been available for subcutaneous (SC IFX) administration since march 2021. It has shown to be equivalent to its every-8-week-intravenous formula (IV IFX), however, we do not have long term efficacy and safety data. Our aim was to evaluate medication persistence, efficacy and safety two years after switching from IFX IV to IFX SC

Methods

Multicentre, descriptive, and observational study, with prospective data collection, of Crohn’s Disease (CD) or Ulcerative Colitis (UC) patients who were going to be changed from IV IFX to SC IFX. All patients were on clinical and biological remission for at least 6 months. Clinical activity, analytical data, trough level determinations and adverse events were gathered. Baseline results were compared with those from week 108 after starting CT-P13 SC. Maintenance of the drug after two years and the reason for removal, if so, or of loss of follow-up, were evaluated.

Results

41 patients were included. 24 of whom had intensified doses while 17 were on standard doses (5 mg/kg every 8 weeks). 51% were male; mean age 40.8. 63,4 % (n = 26) had CD. No PCR differences were observed at baseline (IV IFX) [median 0,17 mg/dL] and week 108 [median0,3 mg/dL]. Fecal calprotectin stayed under 200 ug/mg from baseline to 24 months. No changes in clinical indexes were observed. A considerable increase in drug levels was observed after switching to SC IFX at week 108 (6,8 vs 12.3; p < 0,001). 46% of the patients were also on immunosupressor when they switched to IFX SC, and 52% of these had removed it after 2 years of IFX SC. 85% of the patients were still on IFX SC after two years (only one was removed due to loss of response). There were only 3 adverse events, all of which were mild.

Conclusion

Persistence of IFX SC after two years was observed in 85% of the patients. Switching from IV IFX to SC IFX maintains remission in Inflammatory Bowel Disease (IBD) after a 2-year follow-up. Higher drug levels are obtained with the subcutaneous formulation, despite removing the immunosupressor in over 50% of the patients. Switching from IV IFX to SC IFX is safe in IBD.
P662 Discontinuation of biologic therapy in Inflammatory Bowel Disease: longer term outcomes
Authors: Al-Talib I , Iqbal M , Slater J , Bates B , Jones J , Rattehalli D , King D , De Silva S
Published: January 2024

Background

The National Institute of Health and Care Excellence (NICE) in the UK recommends evaluation of all patients receiving biological therapy for IBD at 12 months, with a view to discontinuation of therapy for those with stable disease in remission. We recently evaluated the outcomes of discontinuation of biologics at our centre and the disease relapse rate at 12 months was 14.5%. Following this, longer-term outcomes were evaluated for patients who did not relapse at 12 months.

Methods

All patients on Biologics therapy who underwent biologics discontinuation were identified via our IBD registry. Retrospective data was collected between January 2015 and January 2022 and these included baseline demographics, disease type, type and duration of biological therapy, when therapy was discontinued and disease relapse initially at 12 months, and beyond. All patients had disease re-assessment prior to discontinuation. Disease relapse was defined as evidence of disease activity requiring steroid, biologic or surgical therapies. Patients with perianal Crohn’s disease were excluded.

Results

A total of 62 patients were included and divided in two groups. 37 (60%) patients had Crohn’s disease (CD) and 25 (40%) had Ulcerative Colitis (UC). Disease extent in the CD group included Ileal (32%), Colonic (53%) and Ileocolonic (15%). In the UC group disease extent included Proctitis (28%), Left sided (56%) and Extensive disease (32%).

At 12 months, 14.5% (9) patients had disease reactivation, 13.5% with CD and 16% with UC. The duration of treatment prior to discontinuation ranged between 9 to 74 months (Median 47.5).

Beyond 12 months of discontinuation, a total of 48 patients (CD 29 and 19 UC) had their data analysed, with 5 patients excluded due to being lost to follow up. 29% of these patients eventually had a relapse (CD 7, UC 7). The median follow up period was 53 months (range 21-84 months) in the CD group and 42 months (range 24-76 months) in the UC group. The rate of relapse post 12 months of de-escalation was 24% in the CD group and 36% in the UC group.

Conclusion

In this study, the rate of disease recurrence beyond 12 months of discontinuation of biological therapy was 29 % (median follow up in CD 53 months and UC 42 months) compared to 14.5% at 12 months. Despite careful selection of patients with up-to-date disease activity assessment prior to discontinuation, our data suggests that the overall disease recurrence rate was high at 40% (35% in CD and 48% in UC) and recurrence rates increase over time. We would therefore suggest that discontinuing treatment should only be considered after clear discussions with patients about the high risk of disease relapse and based on an individual basis.
P663 Efficacy of jak inhibitors in inflammatory bowel disease patients with extraintestinal manifestations– Retrospective study
Authors: Livne Margolin M , González Lama2 Y , Koutroubakis I , Drygiannakis I , Shitrit A , Goldenberg R , Farkas K , Molnar T , Ivány E , Amiot A , Carbonnel F , Girod P , Doherty G , Mateescu B , Ben-Horin1 S , Kopylov U
Published: January 2024

Background

JAK inhibitors have demonstrated efficacy in ulcerative colitis (UC), Crohn’s disease (CD), and inflammatory arthritis. However, limited data exist on their effectiveness in treating extraintestinal manifestations (EIM) in patients with inflammatory bowel disease (IBD) in real-world scenarios. This multicenter, retrospective study aims to assess the efficacy of JAK inhibitors (JAKI), specifically tofacitinib or upadacitinib, in IBD patients with EIM.

Methods

This was a retrospective multicenter cohort study. Inclusion criteria included IBD patients with active EIM documented before JAKI treatment initiation, with a follow-up up to 52 weeks. EIM Clinical response was defined as either improvement or remission of EIM complaints, as subjectively described by the patient or taken from the treating physician’s assessment.

Results

Eighty-six patients from eight centers were included, with 64% having UC (n=55). Women constituted 60% of the patients (n=51). Tofacitinib and upadacitinib were administered to 63% (n=54/86) and 36% (n=32/86) of patients, respectively. Eleven patients (13%) were biologically naïve, all treated with tofacitinib. Arthralgia was the predominant complaint, affecting 55% (n=30/54) of tofacitinib-treated and 44% (n=14/32) of upadacitinib-treated patients. Patient characteristics, including EIM distribution, are detailed in Table 1.

At 3 months, 86% (n=72/83) achieved EIM clinical response, with tofacitinib responders at 94% (n=49/52) compared to 74% (n=23/31) for upadacitinib (p=0.01). Seven percent (n=6) discontinued treatment due to lack of response. Peripheral arthralgia improved or achieved remission in 86% (n=32/38) of patients, while 68% (n=13/19) with axial arthropathy experienced clinical response.

At 6 months, EIM clinical response was achieved by 76% (n=44/75), with tofacitinib at 86% (n=44/51) and upadacitinib at 54% (n=13/24) (p=0.004). Twelve percent(n=10) discontinued treatment due to loss of response. Peripheral arthralgia responded in 86% (n=31/36), and axial arthropathy responded in 42% (n=8/19).

At 12 months, 65% (n=44/68) of patients improved or had remission, with tofacitinib responders at 73% (n=35/48) and upadacitinib responders at 45% (n=9/20) (p<0.05). Eighty-eight percent (n=23/26) with peripheral arthralgia and 50% (n=5/10) with axial arthropathy achieved clinical response.

Conclusion

This study demonstrates the effectiveness of JAK inhibitors in treating EIM, with a high percentage of responders. Tofacitinib appears more effective than upadacitinib, possibly influenced by a higher proportion of biologically experienced patients and differences in IBD subtype distribution between the two groups, with upadacitinib mainly used in CD patients and tofacitinib in UC patients.
P668 Dashboard-guided anti-TNF induction as an effective proactive strategy in Inflammatory Bowel Disease's treatment
Authors: Céspedes Martínez E , Robles-Alonso V , Herrera-De Guise C , Mayorga L , Serra X , Pérez Z , Oller E , Larrosa M , García-García S , Casellas F , Borruel N
Published: January 2024

Background

Infliximab (IFX) and Adalimumab (ADA) are effective treatments for managing Inflammatory Bowel Disease (IBD) but treatment failure is common. Therapeutic drug monitoring (TDM) of trough serum drug concentrations (C Trough) has been used to optimize treatment induction, mitigate immunogenicity, and ensure appropriate drug exposure. HLA DQA1*05 genotype variants have been identified as predictors of immunogenicity. This study aimed to investigate the impact of dashboard-guided optimized induction dosing strategy on clinical and pharmacokinetics outcomes of anti-TNF, with the goal of analysing the HLA DQA1*05 effect.

Methods

We conducted a retrospective single-centre cohort analysis of IBD patients, Crohn’s disease (CD) and Ulcerative Colitis (UC), who initiated treatment with IFX or ADA between January 2020 and March 2023, using a pharmacokinetic dashboard-guided induction, protocolized with the Pharmacy Department. C Trough measurements were taken at week 2, 6 and 14, first drug intervention based on the model was in week 4. Targeted C Trough levels during induction were set at 10-15 mcg/mL for ADA and > 17 mcg/mL for IFX. Primary objective was to assess clinical remission (CR). Secondary outcomes included treatment failure (TF) and endoscopic remission (ER). We performed a descriptive analysis and generated Kaplan Meier curves to assess drug survival

Results

We enrolled 147 patients, 92 having CD (74 treated with ADA and 18 with IFX) and 55 having UC (36 treated with ADA and 19 CU with IFX). HLA DQA1*05 genotype variant was present in 44,14% of patients. Combined treatment with thiopurine was used in 45,58% and 11,54% had been previously received biologic treatment. After 24 weeks, 91,83% (135/147) of patients achieved CR and 65,81% (77/117) at week 56. ER was observed in 59,84% (76/127) after a year. Anti-TNF drug survival probability was 85% after a year, meanwhile ADA drug survival in UC patients was 75%. A 77,7% of patients were prescribed an accelerated dose in the first year, which was associated with improved drug durability. Only a patient out of 147 developed antibodies to ADA. The HLA DQA1*05 variant was not a statistically significant predictor of adverse treatment or pharmacokinetic outcomes.

Conclusion

Optimizing anti-TNF induction with a Dashboard-guide dosing strategy proves to be a valuable approach to enhance clinical remission and durability rates in IBD patients. The role of HLADQA1*05 variant in immunogenicity appears to be mitigated by the model.
P669 Efficacy of Ustekinumab-based integrated medicine therapy in patients with symptomatic stricturing Crohn's disease: a multicentre, prospective, observational cohort study
Authors: Liu J , Hu W , Li S , Xu D , Wu Q , Chen Y
Published: January 2024

Background

Strictures are the most common structural complication of Crohn's disease (CD). Surgery and endoscopic balloon dilation are the main treatments; however, there is no data about the efficacy of ustekinumab (UST) in patients with symptomatic stricturing CD.

Methods

In this multicentric study, we prospectively included adult CD patients treated with their first UST therapy for symptomatic strictures (confirmed on endoscopy or imaging). The primary endpoint was success at week 52, defined as UST continuation without prohibited treatment (corticosteroids, other biologics), endoscopic dilation, or bowel resection. The long-term endpoint was discontinuation of treatment for failure, bowel damage progression and time to surgery in the whole cohort. The effectiveness was determined by the relief of stenosis while the baseline factors independently associated with success were identified using a logistic regression model.

Results

Overall, 28 patients were included and analyzed for baseline [median age-34 (range 24-46) years; males-64.3%; median disease duration-10 (range 2–216) months; active smokers-10.7%]. The ileum was the most common site of stricture (67.9%), 21.4% of patients had colonic strictures, and 17.9% had multiple strictures. 35.7% of patients were steroid-dependent. Before enrollment, 10.7% of patients had got bowel surgery, 25.0% got perianal surgery, and 3.6% got endoscopic dilation treatment. 14.3% had received treatment of other biologics.

The rate of success at 52 weeks was 71.4% while 8 patients quit due to stricture surgery, changed to anti-TNFs, or resumed exclusive enteral nutrition. In terms of stenosis remission, the SES-CD of strictures and DBE-CD decreased from 6.71±0.18 and 3.85±0.15 to 3.14±0.14 and 3.04±0.24, respectively. The Crohn’s disease obstructive score (CDOS) significantly decreased from 4.85±0.61 to 1.14±0.39 (p=0.025).

In the assessment of disease activity, UST down-regulated the IBUS-SAS of ultrasound from 71.71±5.23 to 54.73±5.41 (p=0.036). HBI (p=0.14) had a downtrend during the follow-up period, and the concentrations of CRP (p=0.04) and FCP (p=0.025) also decreased respectively.

The predictive factors of remission in patients who received ustekinumab were bowel wall thickness < 5 mm (p=0.031). No significant risk of surgery or failure has been observed yet (p=0.25).

Conclusion

Ustekinumab seems to be effective in controlling the progress of intestinal strictures in CD patients. Nevertheless, further cohort size expansion and data analysis are indispensable.
P694 Age is a strong of predictive risk factor for anti-TNF therapy related adverse events in IBD patients
Authors: Majumder S , Bhaduri A , Sharma N , Mohammed Nabil Quraishi N Q , Cooney R , Ghosh S , Iacucci M , Shivaji U N
Published: January 2024

Background

Anti-TNFα is the first class of biologics approved for treatment of moderate-to-severely active Inflammatory Bowel Disease (IBD). More than two decades on, anti-TNFs remain one of the most commonly used biologics for both Ulcerative Colitis (UC) and Crohn’s Disease (CD), and often as first-line therapy. Although effective, they cause several adverse events (AEs), sometimes requiring withdrawal of therapy. We aimed to record AEs and understand factors that could predict risk of AEs.

Methods

All IBD patients exposed to anti-TNF therapy were identified from EMR at two centres of a large tertiary hospital between January 2009 and June 2022. All relevant demographic and clinical data were collected for those patients with well recorded AEs and follow-up. Data on cumulative AEs directly attributed to anti-TNFs that ranged from mild reactions to serious AEs (defined as those requiring review/withdrawal of anti-TNF), were collected. Adverse events (AEs) were recorded as per relevant systems involved e.g.- haematological, cardiac etc., including infections and malignancies as separate categories. All analysis (normalization, hypothesis testing, and visual reports were performed using R software package Version: R 4.2.1.

Results

A total of 844 IBD patients (Male =408) were included with an age range of 18-75yrs. Majority were Caucasian in ethnicity (514) and more patients with CD [605(71%)] were exposed to anti-TNF than UC. The age profiling analysis was performed across ethnic groups (Asian, Caucasian and Others). Age associated AE was reported across all the groups (data not shown). It must be mentioned that though not significant, Caucasian patients were more susceptible towards AE as compared to Asian.

Conclusion

· Patient age above 50yrs has a strong predictive risk factor for AEs related to anti-TNF therapy for IBD.

· In our cohort, more than half of patients >50yrs reported at least one AE in UC, and the age was lower in CD.

· Although Caucasians were more vulnerable to AEs, this was not statistically significant.

· Clinicians should consider and discuss this risk before selecting patients for anti-TNF therapy.

· With multiple biologic choices currently available, another class could be considered where possible, for the >50yr patient cohort.
P702 Long term outcomes following de-escalation of dose-intensified ustekinumab in patients with Crohn’s disease
Authors: Demase K , Smith R L , Luber R , Taylor K M , Ward M G , Sparrow M P , Little R D
Published: January 2024

Background

Data on outcomes following de-escalation of dose-intensified ustekinumab (UST) in Crohn’s disease (CD) have not been reported. This retrospective cohort study aimed to evaluate the failure rates 6, 12, and 24 months after de-escalation from dose-intensified UST to standard dose UST and identify predictors of failure.

Methods

Single centre, retrospective study of consecutive CD patients undergoing de-escalation of dose-intensified UST (90mg 4-weekly) to standard dosing (90mg 8-weekly). De-escalation and post de-escalation decisions were informed by protocolised 6-monthly assessment using Harvey-Bradshaw Index, C-reactive protein (CRP), faecal calprotectin (FCP), drug level and intestinal ultrasound. Failure was defined by re-escalation of UST, corticosteroids, switch out of class, or IBD-related hospitalisation or surgery. Success was defined by continued standard UST dosing. Categorical variables were compared using Fisher-exact and continuous variables using Mann-Whitney U tests between groups.

Results

14 patients underwent de-escalation from April 2020 to March 2023. The median age was 41 years, disease duration 15 years, and duration on dose-intensified UST 34 months. 43% received IV reinduction at time of escalation, 86% had previous exposure to advanced therapies, of which 43% were dose-intensified. 36% were on an immunomodulator (IMM) at de-escalation. In the 6 months prior to de-escalation, the median CRP was 3.5mg/L, FCP 96mg/g, and 91% were in sonographic remission. 5/14 (36%) failed de-escalation at 6 months and 9/14 (64%) failed by 12 months. Of those with 24 months follow up, 9/12 (75%) failed de-escalation. Median time to failure was 8 months (IQR 4.5-13). All patients who failed underwent re-escalation and 2 required surgery. UST drug levels reduced from 3.6 to 1.9mg/mL 6 months post de-escalation. Re-escalation successfully recaptured response in 7/9 (78%). A greater proportion of patients with successful de-escalation at 12 months received concomitant IMM compared to those that failed (80% vs. 11%, respectively; p = 0.02). There were no other significant differences in clinical or disease characteristics between those with failure vs. success at 6, 12, or 24 months, although numbers were small (Table 1).

Conclusion

One-third of patients failed de-escalation of dose-intensified UST at 6 months, two-thirds failed at 12 months and three-quarters by 24 months. Patients considered for a trial of de-escalation need close, objective monitoring as most failure occurs early, and re-escalation is successful in the majority. Concomitant IMM may reduce failure rates and should be considered. Further studies are required to confirm these findings and identify additional predictors of de-escalation failure.
P705 Assessment of age on the efficacy and safety among patients in the etrasimod ELEVATE ulcerative colitis clinical programme
Authors: Lichtenstein G R , Allegretti J R , Loftus Jr E V , Irving P M , Banerjee R , Charabaty A , Kuehbacher T , Bananis E , Woolcott J C , Dalam A B , Lazin K , Keating M , McDonnell A , Danese S
Published: January 2024

Background

Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Previous work has shown age can impact treatment safety and efficacy in patients with inflammatory bowel disease.1 This post hoc analysis investigated the impact of age on the safety and efficacy of etrasimod in patients with UC in the phase 3 ELEVATE UC clinical programme.

Methods

Data pooled from the ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials were analysed in patients receiving etrasimod 2 mg QD and placebo. ELEVATE UC 52 had a treat-through design comprising a 12-week induction period followed by a 40-week maintenance period. ELEVATE UC 12 was a 12-week induction trial. Proportions and incidence rates (IRs) per 100 patient-years from pooled data of treatment-emergent adverse events (TEAEs) and events of interest were stratified by age (<40 years, 40–59 years, ≥60 years) and analysed in patients who received ≥1 dose of etrasimod or placebo. Efficacy analyses were evaluated in patients with baseline Modified Mayo score (MMS) 5–9 for the primary efficacy endpoint (clinical remission) and select secondary endpoints at Week 12 (both trials) and Week 52 (ELEVATE UC 52) stratified by age.

Results

There were 787 patients enrolled in the ELEVATE UC programme, of whom 420 (53.4%) were aged <40 years, 276 (35.1%) were aged 40–59 years and 91 (11.6%) were aged ≥60 years. The proportions and IRs of TEAEs and events of interest were mostly similar between age groups and treatment arms (Table). IRs of arthralgia, fatigue, hypertension and pyrexia were higher in older age groups, regardless of treatment arm. Serious AEs and AEs leading to treatment discontinuation were low and consistent across all age subgroups. Serious infections and infection events of interest were balanced across age groups and treatment arms. Regardless of age subgroup, significantly more patients treated with etrasimod 2 mg QD vs placebo achieved the primary and select secondary efficacy endpoints at Week 12 and Week 52 (Figure).

Conclusion

The safety profile of etrasimod 2 mg QD in the UC population was consistent across age groups, and with no new risks other than the estimated risks associated with increasing age.2 Patients receiving etrasimod in the ELEVATE UC programme showed significant clinical benefit as assessed by clinical remission, symptomatic remission and endoscopic improvement compared with placebo, regardless of age.

References

1. Lichtenstein GR et al. Inflamm Bowel Dis 2023; 29: 27–41.

2. Luo J et al. JMIR Med Inform 2016; 4: e30.
P713 The introduction of an intestinal ultrasound service significantly reduces diagnostic endoscopy usage in an Inflammatory Bowel Disease service – The SCOPELESS Study
Authors: Feng G , Little R , Ardalan Z , Friedman A , Smith R , Taylor K , Sparrow M
Published: January 2024

Background

Endoscopic assessment is the gold standard for monitoring of inflammatory bowel disease (IBD) activity. Intestinal ultrasound (IUS) is increasingly utilised as a non-invasive, alternative disease monitoring strategy. Our study aim was to quantify and compare endoscopy usage for evaluation of IBD disease activity before and after the introduction of an IUS service.

Methods

A retrospective single-centre study was performed. Total numbers of lower GI endoscopies (ileocolonoscopy or flexible sigmoidoscopy) performed for luminal Crohn’s disease (CD) or ulcerative colitis (UC) disease evaluation were collected across two 5-year time periods: the pre-IUS era (2010-2014) and the IUS era (2015-2019). Endoscopies for dysplasia surveillance were excluded. The primary endpoint was a comparison of the cumulative number of endoscopies for IBD disease activity evaluation annually relative to the annual number of patients seen in clinic in the pre-IUS and IUS eras. Secondary endpoints included evaluating the number of endoscopies by individual year within each time period, endoscopies according to diagnosis (CD vs. UC), and the number of IUS performed within the IUS era. Categorical variables were compared using a Chi-squared test. A p value <0.05 was considered statistically significant.

Results

The number of endoscopies performed for IBD disease evaluation decreased from 576 in the pre-IUS era to 474 in the IUS era despite an increase in cumulative annual patient reviews (1985 vs. 3337 patient reviews, respectively). The annual number of endoscopies for disease evaluation per patient in the pre-IUS and IUS eras is illustrated in Figure 1. The proportion of cumulative annual endoscopies relative to patients reviewed across the 5-years reduced from 29 per 100 patients in the pre-IUS era to 14 per 100 patients in the IUS era (OR 2.47, 95% CI 2.15-2.84; p < 0.001). There was a reduction in total endoscopies for CD evaluation from 325 to 264 and UC evaluation from 251 to 210. The proportion of endoscopies performed for CD vs. UC was unchanged between the two eras (56.4% vs. 55.7%; p = 0.81). In the IUS era, a total of 3319 IUS were performed (2673 CD, 646 UC). This included 1467 IUS for assessment of suspected activity (44 per 100 patients/year) and 1852 IUS for objective confirmation of clinical remission (55 per 100 patients/year).

Conclusion

In the 5 years following introduction of an IUS service, the number of endoscopies performed for evaluation of IBD activity per patient was halved. IUS was performed for both assessment of disease activity and objective confirmation of clinical remission. The potential workflow and cost savings of reduced endoscopies for IBD disease activity evaluation are significant.
P716 Efficacy and safety of upadacitinib during induction in Crohn’s disease: Real-world experience
Authors: Jairath R , Zoughlami A , Pilote N , Afif W , Bitton A , Wild G , Narula N , Lakatos P L , Bessissow T
Published: January 2024

Background

Upadacitinib is a selective JAK1 inhibitor that has recently been approved for treatment of moderate-severe Crohn’s disease, with Phase III clinical trials showing positive efficacy and safety profiles. Our aim was to evaluate the real-world experience of upadacitinib in a refractory cohort of Canadian patients with Crohn’s disease.

Methods

This was a two-centre retrospective study looking at 12-week induction data for patients with active Crohn’s disease from McGill University Health Centre and Hamilton Health Sciences. The primary outcome was clinical remission at 12 weeks, with secondary outcomes including clinical response, biochemical remission, and biochemical response. Clinical remission was defined as a Harvey-Bradshaw index (HBI) < 5. Clinical response was defined as an HBI reduction of ≥ 3. Biochemical remission was defined as a c-reactive protein (CRP) < 5 mg/L and/or fecal calprotectin (FCP) < 250 μg/g. Biochemical response was defined as a reduction of CRP or fecal calprotectin by 50% from baseline. These parameters were all evaluated at 8 and 12 weeks. Adverse events were summarized for patients who had follow up data available and included in the efficacy analysis.

Results

There were 28 patients who were treated in total, all of which had multiple biologic treatment failures. Baseline median age was 37, median HBI was 9, median CRP was 9.41 mg/L, and median FCP was 580 μg/g. The median disease duration was 13.5 years. Four patients discontinued upadacitinib due to no response or side effects. For all available data including patients who discontinued upadacitinib, clinical remission was achieved at 12 weeks in eight patients (8/11, 72.7%). Clinical response was achieved in eight patients (8/11, 72.7%), biochemical remission was achieved in four patients (4/11, 36.4%), and biochemical response was achieved in six patients (6/11, 54.6%). Of those that were initially on steroids (n=5), four patients (4/5, 80.0%) were able to wean off steroids and achieved a steroid-free clinical or biochemical response at 12 weeks. Of those who had previously been on off-label tofacitinib (n=5), clinical follow-up data was available for three patients at the end of the 12-week induction period. Two patients achieved clinical remission (2/3, 66.7%) and three patients had a clinical response (3/3, 100%). Among 13 patients with follow-up data, adverse events were observed in three patients (3/13, 23.1%), with two having non-serious infections (2/13, 15.4%) and one having fevers of unknown origin (1/13, 7.69%).

Conclusion

This real-world multicentre Canadian induction study shows favourable efficacy and tolerability of upadacitinib in refractory active Crohn’s disease.