Refractory Ulcerative Colitis Research Articles

Inpatient Infliximab Biosimilar Cost-Savings - Cost analysis of inpatient treatment with originator Infliximab (Remicade™) vs biosimilar Infliximab (Renflexis™) for acute severe ulcerative colitis. .

Infliximab (IFX) is a standard, salvage therapy for refractory acute severe ulcerative colitis (ASUC). Remicade™ is the originator IFX. Its biosimilar Renflexis™ offers a reduced cost structure. We performed a cost-minimization analysis to compare costs with Remicade and Renflexis for inpatient treatment of ASUC. Methods: Retrospective clinical and financial data was obtained from 34 patients with refractory ASUC who received Renflexis (n=17) or Remicade (n=17) between 2019-2021. Clinical data included admission and discharge lab values. Financial data included a decision support drug cost (DSDC), constituting the total cost associated with inpatient infliximab administration, and total inpatient cost of care. No differences were found in baseline or discharge clinical parameters. Median unadjusted ratio of DSDC to total inpatient cost of care was 0.387 vs. 0.241 in the Remicade vs. Renflexis groups (p=0.0025), respectively, representing an absolute difference of ~14%. Median adjusted rDSDC was 0.04 vs. 0.024 in the Remicade vs. Renflexis groups, respectively, representing a relative cost reduction of ~40% (p = 0.0001) Discussion: The unadjusted absolute cost reduction and adjusted relative cost reduction were respectively 14% and 40% in the Renflexis group as compared to Remicade. Our calculation included median decision support drug cost as a percentage of the total inpatient cost of care, controlling for infliximab dose and length of stay. This reduced cost structure promotes use of Renflexis for ASUC inpatients and may reduce costs for patients and hospitals.

Effectiveness and Safety of Ustekinumab in Pediatric Ulcerative Colitis: A Multi-center Retrospective Study from the Pediatric IBD Porto Group of ESPGHAN.

Current data on ustekinumab therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBDU) are limited. We aimed to evaluate the effectiveness and safety of ustekinumab in pediatric UC and IBDU. This multicenter retrospective study included 16 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. Children with UC or IBDU treated with ustekinumab were enrolled. Demographic, clinical, laboratory, endoscopic, and imaging data as well as adverse events were recorded. Analyses were all based on the intention-to-treat principle. Fifty-eight children (39 UC and 19 IBDU, median age 14.5 [IQR 11.5-16.5] years) were included. All had failed biologic therapies, and 38 (66%) had failed two or more biologics. Corticosteroid-free clinical remission (CFR) was observed in 27 (47%), 33 (57%), and 37 (64%) children at 16, 26, and 52 weeks, respectively. Normalization of C-reactive protein and calprotectin <150μg/g were achieved in 60% and 52%, respectively, by 52 weeks. Endoscopic and radiologic remissions were reached in 8% and 23%, respectively. The main predictors of CFR were diagnosis of UC compared with IBDU (hazard ratio [HR] 2.2, 95% CI 1.03-4.85; p=0.041) and no prior vedolizumab therapy (HR 2.1, 95% CI 1.11-4.27; p=0.023). Ustekinumab serum levels were not associated with disease activity. Adverse events were recorded in six (10%) children, leading to discontinuation of the drug in three. Based on these findings, ustekinumab appears as an effective therapy for pediatric refractory UC and IBDU. The potential efficacy should be weighed against the risks of serious adverse events.

Combination of granulocyte–monocyte apheresis and ustekinumab: Multicentre and retrospective study

ObjectiveGranulocyte–monocyte apheresis (GMA) has shown to be safe and effective in ulcerative colitis (UC), also in combination with biologics, mainly with anti-TNF. The aim of this study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. Patients and methodsA retrospective study was performed in 12 IBD Units, including all patients with refractory UC or unclassified IBD (IBD-U) who received combined GMA plus UST. The number and frequency of GMA sessions, filtered blood volume and time of each session were registered. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. ResultsSeventeen patients were included (15 UC, 2 IBD-U; median age 47 years [IQR, 35–61]; 59% male; 53% E3). Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab; 65% were also receiving steroids at baseline. Median partial Mayo score at baseline was 6 (IQR, 5–7) and it significantly decreased after 1 and 6 months (p=0.042 and 0.007, respectively). Baseline FC significantly decreased after 6 months (p=0.028) while no differences were found in CRP. During follow-up, 18% patients started a new biologic therapy and 12% required surgery; 64% of patients under steroids were able to discontinue them. Adverse events were reported in one patient. ConclusionGMA can recapture the response to UST in selected cases of UC after PNR or LOR to this drug.

Transanal ileal pouch-anal anastomosis for inflammatory bowel disease: a systematic review and meta-analysis of short-term outcomes.

Restorative proctocolectomy with transabdominal ileal pouch-anal anastomosis (abd-IPAA) has become the standard surgical treatment for medically refractory ulcerative colitis (UC). However, it requires a technically difficult distal anorectal dissection and anastomosis due to the bony confines of the deep pelvis. To address these challenges, the transanal IPAA approach (ta-IPAA) was developed. This novel approach may offer increased visibility and range of motion compared with abd-IPAA, although its postoperative benefits remain unclear. The aim of this work was to perform a systematic review and meta-analysis to compare and inform the frequency of postoperative outcomes between ta-IPAA and abd-IPAA for patients with UC. Several databases were searched from inception until May 2022 for studies reporting postoperative outcomes of patients undergoing ta-IPAA. Reviewers, working independently and in duplicate, evaluated studies for inclusion and graded the risk of bias. Odds ratios (OR), mean differences (MD) and prevalence ratio (PR) and their corresponding 95% confidence intervals (CIs) were calculated using random-effects models. Sensitivity analysis was performed. Ten retrospective studies comprising 284 patients with ta-IPAA were included. Total mesorectal excision was performed in 61.8% of cases and close rectal dissection in 27.9%. There was no difference in the odds of Clavien-Dindo (CD) I-II complications, CD III-IV and anastomotic leak (OR 0.96, 95% CI 0.27-3.40; OR 1.18, 95% CI 0.65-2.16; OR 1.37, 95% CI 0.58-3.23; respectively) between ta-IPAA and abd-IPAA. The ta-IPAA pooled CD I-II complication rate was 18% (95% CI 5%-35%) and for CD III-IV 10% (95% CI 5%-17%), and the anastomotic leak rate was 6% (95% CI 2%-10%). There were no deaths reported. This meta-analysis compared the novel ta-IPAA procedure with abd-IPAA and found no difference in postoperative outcomes. While the need for randomized controlled trails and comparison of functional outcomes between both approaches remains, this evidence should assist colorectal surgeons to decide if ta-IPAA is a viable alternative.

Real-World Effectiveness of Ustekinumab in Ulcerative Colitis in a United States Multicenter Cohort Consortium.

Pivotal trials have shown that ustekinumab is effective in ulcerative colitis (UC). However, the population included in these trials do not represent the cohort of patients treated in the real world. In this study, we aimed to describe the effectiveness and safety of ustekinumab in a clinical cohort of patients with UC. We performed a multicenter retrospective cohort study and included patients with active UC starting ustekinumab. Variables collected included demographics, clinical data, and disease activity (measured using partial Mayo score [PMS] and endoscopic Mayo score) at follow-up. The primary outcomes were cumulative rates of steroid-free clinical and biochemical remission (SFCBR), defined as a PMS <2 while off steroids and a normal C-reactive protein and/or fecal calprotectin. A total of 245 patients met inclusion criteria. The median time of follow-up was 33 (interquartile range, 17-53) weeks, and 214 (87.3%) had previous exposure to a biologic and/or tofacitinib. Rates of SFCBR, clinical remission, and endoscopic remission at 6 and 12 months were 12.0% (n = 16 of 139), 29.0% (n = 71 of 175), and 18.0% (n = 7 of 39), and 23.8% (n = 15 of 63), 54.3% (n = 57 of 105), and 31.0% (n = 9 of 29), respectively. Non-Hispanic White race, higher baseline PMS, and the use of concomitant corticosteroids were independently associated with failure to achieve SFCBR. Of the 73 that were dose escalated, 28.4% did not respond, 49.3% experienced a benefit, and 21.6% achieved remission. In a population enriched with refractory UC, ustekinumab was well tolerated and induced remission in a significant number of patients. Larger studies with a longer follow-up are warranted.

Effect of Tofacitinib on One-Year Colectomy Risk in Anti-TNF Refractory Ulcerative Colitis: A Prospective Multicenter Italian Study.

Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC). Considering the number of anti-TNF non-responders, this study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52weeks. From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events. We included 58 patients with UC with an age of 42 ± 14.4years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10mg bid at W8 (p = 0.023) and W24 (p = 0.004), and with a higher partial Mayo score at W8 (p = 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation. In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52weeks with a good safety profile.

Real-world effectiveness of ustekinumab and vedolizumab in TNF-exposed pediatric patients with ulcerative colitis.

Vedolizumab (VDZ) and ustekinumab (UST) are second-line treatments in pediatric patients with ulcerative colitis (UC) refractory to antitumor necrosis factor (anti-TNF) therapy. Pediatric studies comparing the effectiveness of these medications are lacking. Using a registry from ImproveCareNow (ICN), a global research network in pediatric inflammatory bowel disease, we compared the effectiveness of UST and VDZ in anti-TNF refractory UC. We performed a propensity-score weighted regression analysis to compare corticosteroid-free clinical remission (CFCR) at 6 months from starting second-line therapy. Sensitivity analyses tested the robustness of our findings to different ways of handling missing outcome data. Secondary analyses evaluated alternative proxies of response and infection risk. Our cohort included 262 patients on VDZ and 74 patients on UST. At baseline, the two groups differed on their mean pediatric UC activity index (PUCAI) (p = 0.03) but were otherwise similar. At Month 6, 28.3% of patients on VDZ and 25.8% of those on UST achieved CFCR (p = 0.76). Our primary model showed no difference in CFCR (odds ratio: 0.81; 95% confidence interval [CI]: 0.41-1.59) (p = 0.54). The time to biologic discontinuation was similar in both groups (hazard ratio: 1.26; 95% CI: 0.76-2.08) (p = 0.36), with the reference group being VDZ, and we found no differences in clinical response, growth parameters, hospitalizations, surgeries, infections, or malignancy risk. Sensitivity analyses supported these findings of similar effectiveness. UST and VDZ are similarly effective for inducing clinical remission in anti-TNF refractory UC in pediatric patients. Providers should consider safety, tolerability, cost, and comorbidities when deciding between these therapies.

Dietary Interventions and Supplementation in Patients With an Ileal Pouch-Anal Anastomosis: A Systematic Review.

Lay Summary The restorative proctocolectomy with ileal pouch–anal anastomosis is the preferred surgery for patients with medically refractory ulcerative colitis. Although the ileal pouch–anal anastomosis provides gastrointestinal continuity and is an excellent alternative to a permanent end ileostomy, it is not without its complications including acute pouchitis, which occurs in up to 80% of patients. Diet may have a significant impact on pouch function and the development of pouchitis by virtue of its impact on motility and the microbiome. Multiple studies have evaluated the ability of different diets and supplements to improve pouch function and manage pouchitis, yet results are conflicting; thus, evidence-based dietary recommendations are lacking. Patients with an ileoanal pouch routinely ask about dietary interventions to maintain pouch health, and it is crucial that concrete evidence-based recommendations are identified to provide guidance. The goal of this systematic review is to summarize the available data on dietary patterns in patients with an ileoanal pouch, dietary interventions in this cohort, and the impact of supplements on pouch function and pouchitis.

Comparison between tofacitinib and ustekinumab as a third-line therapy in refractory ulcerative colitis: A multicenter international study.

Ustekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third-line therapies in UC patients in whom anti-TNF and vedolizumab had failed. This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC-related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C-reactive protein, endoscopic remission, treatment withdrawal, and adverse events. One-hundred seventeen UC patients were included in the study and followed for a median time of 11.6months (q1 -q3, 5.5-18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow-up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 [95% CI: 1.06-3.50] p=0.030). Twenty-eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow-up period (log-rank test, p<0.054). No significant differences were observed for the secondary outcomes. Six and 22 adverse events occurred in the ustekinumab and tofacitinib groups, respectively (15% vs. 31%, p=0.11). Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head-to-head clinical trials are needed as to confirm these data.

Effectiveness of Tofacitinib in Ulcerative Proctitis Compared to Left Sided Colitis and Pancolitis.

Ulcerative proctitis (UP), though associated with high symptom burden and poor quality of life, is excluded from most of the randomized controlled trials in UC, including the OCTAVE trials. We aimed to analyse the effectiveness of tofacitinib in UP, and compare it to that in left sided colitis (LSC) and pancolitis (PC). This was a prospective cohort study. Patients with either steroid-dependent or refractory ulcerative colitis, who received tofacitinib, were divided into three groups based on the disease extent [UP, LSC and PC]. The primary outcome was comparison of proportion of patients in clinical remission in the three groups, at weeks 8, 16 and 48. Safety outcomes were reported using incidence rate per patient year of exposure. Clinical remission was achieved in 47%(15/32), 24%(23/94), and 43%(23/54) of patients at week 8, 56%(18/32), 37%(35/94), and 56%(30/54) of patients at week 16, and 59%(19/32), 38%(36/94), and 24%(13/54) of patients at week 48 in groups UP, LSC and PC, respectively. Corticosteroid-free clinical remission rates were significantly higher in patients in groups UP at week 48. Five (15%) patients with UP were primary non-responders to tofacitinib at week 16, while three (9%) patients had secondary loss of response at week 48. The probability of sustained clinical response was highest in patients with UP. Patients with UP had the lowest incidence of adverse effects. The effectiveness of tofacitinib in inducing and maintaining clinical remission is greater in patients with UP compared to LSC and PC.

A76 COMBINING TOFACITINIB AND USTEKINUMAB FOR REFRACTORY ULCERATIVE COLITIS: A CASE REPORT

Abstract Background The paradigm for Inflammatory Bowel Disease (IBD) management has shifted towards prioritizing remission of inflammation over symptom control, emphasizing sustained, corticosteroid-free remission at the clinical, endoscopic, and histologic levels. The shift is due to the recognition that uncontrolled inflammation often causes morbidity; after one year of biological therapy, 40% of patients still experience persistent disease activity. Several approaches have been proposed to address this challenge, including drug level monitoring, dosage titration, antibody screening, and, as a last resort, surgical intervention. Emerging limited studies suggest the potential efficacy of combining two biological agents or a biological agent with small molecules in IBD, contrasting the efficacy and safety concerns encountered with their use in rheumatological diseases. Aims To describe a case of successful combination therapy with Tofacitinib and Ustekinumab in refractory Ulcerative Colitis with a review of the current literature. Methods This case describes a 35-year-old male patient with severe Ulcerative Colitis refractory to 5-ASA, Azathioprine, Infliximab with Methotrexate, Vedolizumab, Ustekinumab and Tofacitinib. His disease persisted with primary treatment failures requiring hospital admissions and rescuing with parenteral steroids. He was switched back to Ustekinumab with minimal symptom improvement but required repeated steroid courses to achieve control. After deliberations, Tofacitinib was added. This combination achieved remission of his symptoms and inflammatory markers, mainly guided by fecal calprotectin (from 3728 µg/g to 46 µg/g), as well as endoscopic and histologic remission. He is being weaned off the oral budesonide he had been on to augment his response. Results After 4 years of combination therapy, he remains in remission with no adverse events or infections. Reassuringly, Janus Kinase inhibitors (i.e., Tofacitinib) have a short half-life, allowing prompt discontinuation if indicated, especially in the event of infection. Furthermore, biologics such as Vedolizumab, Ustekinumab, and Risankizumab offer minimal systemic immunosuppression and do not appear to raise the risk of infection. Apart from safety concerns and limited data on the use of combination therapy, significant economic implications exist. However, the attainability of cheaper generic forms of small molecules (e.g., Tofacitinib roughly costs a quarter of the brand price in Ontario, Canada) adds another advantage to their combination use. Conclusions Combination therapy with biologics and small molecules is a potential consideration for treating severe or refractory Ulcerative Colitis or IBD. To bridge the knowledge gap regarding combination therapies in IBD, further studies are needed on efficacy, safety, long-term effects, and economic impact. Funding Agencies None

Ustekinumab for anti-tumor necrosis factor refractory pediatric ulcerative colitis: a promising approach towards endoscopic healing.

To describe the role of ustekinumab in inducing remission and endoscopic healing in anti-tumor necrosis factor α nonresponsive pediatric ulcerative colitis patients at a tertiary care inflammatory bowel disease center. A retrospective chart review was performed on patients with ulcerative colitis receiving ustekinumab. Primary outcome was steroidfree clinical remission at follow-up. Secondary outcomes were biochemical remission and endoscopic healing. Ten children were analyzed; 7 (70%) had ulcerative colitis, and 3 (30%) had inflammatory bowel disease unspecified with colitis. Median follow-up period was 56 weeks. Nine patients (90%) achieved steroid-free clinical remission and biochemical remission. Seven patients had follow-up colonoscopies, out of which 6 (86%) achieved endoscopic remission, while 1 (14%) underwent colectomy. Out of the 3 patients without a follow-up colonoscopy, fecal calprotectin levels downtrended to < 150 mg/kg in 2 patients and < 400 mg/kg in 1 patient from baseline level of > 2,000 mg/kg. Ustekinumab appears efficacious in achieving not only clinical and biochemical remission but also has promising role in inducing endoscopic healing end point in patients who fail other biologics.

Evaluation of the Factors Associated with Post-Operative Outcome in Patients of Ulcerative Colitis Undergoing Ileal Pouchanal Anastomosis with Comparison of Functional Outcome between Stapler and Hand-Sewn Anastomosis

ntroduction Ulcerative colitis defined as a non-granulomatous idiopathic inflammatory disease which mainly affects the colon and rectum. The disease may arise at any age but most commonly affects the adults between the age group of 30–40 years.1,2. The etiology of the disease is multifactorial, involving genetic predisposition, dysregulated immune responses, epithelial barrier defects and environmental factors. No sex predilection is seen in ulcerative colitis.3,5 The peak age of onset of disease is between 30 to 40 years.4,6 The environmental factors has also been found to play an important role in the etiopathogenesis of ulcerative colitis. Cigarette smoking is one of the major factor associated with ulcerative colitis, non-smokers have a milder disease course and active smokers are less likely to develop ulcerative colitis7 Appendectomy also confers a protective effect against ulcerative colitis, especially in young patients operated for acute appendicitis.8. Classic findings in endoscopy in patients with ulcerative colitis include loss of normal vascular pattern, erythema, erosions, granularity, friability, ulcerations and bleeding9 . The primary aim of medical management is to induce and maintain remission with the long-term goals of improving quality of life and prevent disability. Absolute indications for surgery include uncontrolled hemorrhage, perforation, and colorectal carcinoma or dysplastic lesions not amenable to endoscopic removal.10 Surgery is also indicated in refractory acute severe ulcerative colitis or medically refractory disease. The most commonly performed surgery for ulcerative colitis is restorative proctocolectomy with ileal pouchanal anastomosis (IPAA). An important aspect of the surgery is the use of either sutures or staplers for anastomosis. Two types of ileal pouch-anal anastomosis (IPAA) have been described: a mucosectomy of the rectal stump followed by a hand-sewn ileal pouch-anal anastomosis.11 The alternative technique is to retain the mucosa of the rectal stump and perform a stapled pouch-anal anastomosis.

EPITHELIAL MITOCHONDRIAL DYSFUNCTION IN CHRONIC POUCHITIS

Abstract BACKGROUND Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for patients with refractory ulcerative colitis (UC). However, patients with IPAA are at risk of pouch-related disorders like “pouchitis” with an incidence rate range from 20-50%. The underlying etiopathogenesis of pouchitis has been unclear, which makes management and treatment of active pouchitis difficult. Mitochondrial (Mito) dysfunction is commonly associated with pathogenesis of inflammatory bowel diseases (IBD). We posit the reduced Mito function contributes to chronic pouchitis in IPAA patients. In this study we performed comparative analysis of Mito complex levels in pouchitis patients compared to normal controls. METHODS Biopsies collected from ileal pouches +/- inflammation (n=6), and normal (n=3) and inflamed ileum (CD Ileitis; n=3 mean SES=5.2) were preserved in Allprotect® or formalin. Total RNA was extracted, cDNA synthesized and analyzed by RT-qPCR for genes specific for Mito biogenesis and complexes, cytokines and cellular antioxidant machinery. Formalin-fixed tissues were processed for IHC staining of Mito complex-I (NDUFB6) and complex-IV (MTCO1). RESULTS Transcriptomic analysis of active pouchitis tissue showed significant (**p&amp;lt;0.01) reduction of Mito biogenesis genes (PGC1α: 69.5±13.9%, TFAM: 48.7±14.5%, NRF1:48.9±17.7%) compared to normal pouch. Similar mRNA analysis in CD-ileitis showed 90.6±15.2% reduction in PGC1α gene (**p&amp;lt;0.01) and more than 62% reduction in TFAM and NRF1 genes compared normal ileum. We also observed 21.6±9.8% reduction in Mito complex I (Ndufa1, Ndufa4, Ndufb2, Ndufb6), 33.6±8.7% reduction in complex-IV (Cox5a Cox6a1, Cox5e) and 38.8±11.8% reduction in complex-V (ATP5a, ATP5b, ATP5e) in chronic pouchitis compared to normal controls. In contrast, CD-ileitis showed 59.5±10.2% reduction in Mito complexes at mRNA level compared to normal ileum. Altogether, CD-ileitis showed 26.3% and 23.8% reduction in Mito complexes and biogenesis genes, respectively, compared to pouchitis. At protein level, tissues from chronic pouchitis showed significantly reduced expression of NDUFB6 and MTCO1 compared to normal controls. However, the decreased expression of NDUFB6 and MTCO1 was more pronounced in active CD-ileitis patients. Concertedly, suppression of Mito biogenesis and complex genes correlated with upregulation of pro-inflammatory cytokines (IL1β and IL-6) and concomitant reduction of anti-oxidant genes (Sod1, Sod2, Gpx, Prdx-2,3,4,6). CONCLUSION These data indicate decreased levels of Mito complexes in pouchitis, although reductions are less prominent in active CD. We postulate that Mito dysfunction plays a role in the pathogenesis of chronic pouchitis after IPAA surgery in IBD patients. Furthermore, we posit mitochondria-targeted therapy may deliver therapeutic benefits in refractory pouchitis.

P636 Comparison of the real-world efficacy of filgotinib with tofacitinib in patients with refractory ulcerative colitis: A single-center retrospective study

Abstract Background Several Janus kinase inhibitors have recently been launched for the treatment of ulcerative colitis (UC). However, there are few reports comparing the efficacy and safety of each drug in patients with refractory UC, especially with filgotinib (FIL), which was recently launched and can be concomitantly used with thiopurines. We herein aimed to compare the real-world efficacy and safety of tofacitinib (TOF) and FIL in induction therapy for patients with refractory UC. Methods Patients with refractory UC, who received either TOF 20mg/day or FIL 200mg/day from May 2018 to October 2023 in Hyogo Medical University Hospital were included in this study. Primary outcomes were clinical response rates at 2, 4, and 8 weeks after administration of TOF or FIL. Clinical response was defined as a decrease of partial Mayo Score (pMS) of ≥2 from baseline and rectal bleeding subscore is ≤1 or a decrease of ≥1 from baseline. Secondary outcomes were cumulative incidences of adverse events during the observation period. Results Of the 230 refractory patients with UC, 197 received TOF and 33 received FIL treatment. The median age was 37 [IQR 27–49] and 49 [33–54] years, and the median disease duration was 3 [1–10] and 5 [2–10] years, respectively. Median durations of observation were 118 [52–188] weeks in the TOF group and 41 [29–60] weeks in the FIL group, median baseline pMS were 6 [5–7] and 5 [5–6], and serum CRP levels were 3.8 [1.3–12.3] and 1.8 [0.3–3.3] mg/L, respectively. Thirty-eight (19.3%) patients in the TOF group and 3 (9.0%) patients in the FIL group received systemic steroids, and 8 (24.2%) in the FIL group received thiopurine at baseline. The clinical response rates at 2, 4 and 8 weeks were 58.4%, 59.4% and 62.9% in the TOF group, and 42.4%, 57.6% and 48.9% in the FIL group, respectively, and the rate tended to be higher in the TOF group than in the FIL group at 2 weeks (p = 0.092). Of the patients who did not respond at 4 weeks, the TOF group had a significantly higher clinical response rate (31.3%) than the FIL group (0%) at 8 weeks (p = 0.032). Among 124 patients with prior anti-TNF-α antibody failure, 59.6% (65/109) of patients in the TOF group and 46.7% (7/15) in the FIL group achieved comparable clinical responses at 8 weeks (p = 0.407). Fifteen of 197 (7.6%) patients in the TOF group and 2 of 33 (6.1%) in the FIL group did not continue treatment until 8 weeks due to adverse events, but there were no significant differences between the groups. Conclusion Even in patients without a response for up to 4 weeks, TOF treatment may provide a higher clinical response than FIL treatment at 8 weeks.

P904 Appendectomy for refractory ulcerative colitis: results of prospective observational study

Abstract Background Appendectomy is suggested to improve the course of the disease in many patients with refractory ulcerative colitis (UC). The present prospective observational study demonstrates middle-term outcomes after an appendectomy in 26 patients with refractory UC. Methods Between 5/2022 and 2/2023, 26 selected patients underwent appendectomy for refractory UC. Refractory UC was defined as a failure of at least one biologic therapy. Patients with Dysplasia or Cancer were excluded. The appendectomy was performed without the removal of the cecal base. Primary Endpoint of the study was the Mayo clinical score (MCS) at 6 months after the appendectomy. Secondary Endpoint was the “Treatment failure” which was defined as occurrence of one of the following events during the first 6 months after appendectomy: 1) high-dosed steroid treatment, 2) change of biologic treatment, 3) colectomy. Results Mean age was 35 years (18 to 59 years) and there were 11 female patients. 15 had a pancolitis (58%). Twelve were taking steroids (46%). Median number of biologic therapies taken by patients prior to surgery was 3 (range, 1-5). One patient underwent surgery for sever acute UC. The appendix appeared to be inflamed histologically in 16 patients (62%). Hospital stay was median 2 days, there was one wound infection at the port site and one postoperative hematoma. A significant improvement of disease symptoms was reported by 21 patients during the first 4 weeks (81%). At 6 months, MCS improved from mean 6.4 to 4.5 (p=0.057). Therapy failure was observed in 15 patients (58%) – two underwent colectomy, 11 needed at least one high-dose steroid treatment and biologic therapy was changed due to refractory symptoms in 9 patients. Intake of JAK-inhibitors at the time of appendectomy was the only factor to be associated with lower probability of treatment failure (30% vs. 75%, p=0.043). The only patient undergoing appendectomy for severe acute UC was free of symptoms 14 months after surgery. Conclusion The majority of patients with refractory UC demonstrated rapid clinical response to the appendectomy. After 6 months, more than 40% of patients did not experience disease flares necessitating intensification of treatment.

P1218 Non-invasive point-of-care stool sample for detection of Cytomegalovirus infection in patients with Active or Refractory Ulcerative Colitis using multiplex polymerase chain reaction (mPCR): a pilot feasibility study

Abstract Background Cytomegalovirus (CMV) infection is associated with more flare-ups and deteriorates the prognosis of active inflammatory bowel disease (IBD). Patients with refractory IBD should be tested for CMV colitis, especially if they are not responding to immunosuppressive therapy. The prevalence of CMV co-infection ranges from 10% to 30% in steroid-refractory acute colitis. Concurrent CMV-colitis is associated with an increased risk of worse therapeutic outcomes, resistance to corticosteroids, and need for salvage therapy. One of the two gold standards of diagnosis of CMV colitis in IBD patients with active disease requires the analysis of tissue biopsies using PCR. The aim of our pilot study was to evaluate the diagnostic accuracy of non-invasive point-of-care faecal samples using mPCR for detecting CMV in patients with ulcerative colitis compared to standard practice biopsies PCR. Methods We performed a prospective, observational, feasibility study including 62 consecutive patients with active ulcerative colitis (UC) requiring intravenous steroids or steroid-refractory UC in the Department of Gastroenterology of University Hospital „Tsaritsa Yoanna – ISUL", from April 2022 to October 2023. In all UC patients, colonic tissue biopsies were performed and analyzed by qualitative CMV PCR. Faecal sample mPCR CMV was performed on the positive patient cohort to compare the feasibility of (ME) Panel IVD using FilmArray mPCR (Biofire, bioMerieux, France). All the tested patients had undergone immunosuppressive therapy and initial stool specimen cultures were obtained to exclude infection with C. difficile and other pathogen flora. Results Out of 62 active UC patients with colonic tissue samples qualitative CMV PCR, n=5 (8%) were positive. Of these n=5 UC patients, n=4 (80%) were positive from the Fecal sample mPCR CMV, resulting in a compatibility of 80% for diagnosing CMV in these patients by the two DNA extraction methods. Calculated Sensitivity and diagnostic accuracy was 80% (95% CI) for the mPCR CMV. The patient cohort predominantly comprised males (75%) with a median age of 45 years (range: 30–72 years). Three patients (75%) out of this cohort group were treated with peroral antiviral agent Valganciclovir, one (25%) of them went into clinical and endoscopic remission after the treatment and two patients (50%) received colectomy. The median time performing the Faecal sample mPCR CMV was approx. 1 hour. Conclusion This novel faecal mPCR point-of-care test is a promising, fast and easy non-invasive tool for detection CMV in active or refractory UC patients, comparable with the colonic tissue CMV-DNA PCR.

P944 Ustekinumab in refractory Ulcerative Colitis: single-center, real-world experience

Abstract Background Ustekinumab, an anti-interleukin 12/23 agent, was approved by the European Medicines Agency in 2019 as a treatment for moderate-to-severe ulcerative colitis (UC). Limited real-world data is available regarding the utilization of ustekinumab in UC, particularly medication persistence and escalation, which are indicators of medication performance in real-world settings. Our aim was to describe our experience with ustekinumab in refractory UC patients. Methods This was an observational single-center study on UC patients who received at least one intravenous dose of ustekinumab 16 weeks before data analysis due to active UC (Simple clinical colitis activity index (SCCAI)&amp;gt;5). Data regarding disease activity prior to and post-induction were analyzed. Patients were followed up until the last ustekinumab administration. Clinical response to therapy was assessed at 16, 24,52 weeks, and the end of follow-up. Response was defined as SCCAI&amp;lt;4, and remission as SCCAI≤2. Dose adjustment or IV maintenance was considered part of the treatment regimen. Patients who discontinued ustekinumab due to lack of therapeutic effect or worsening of UC were considered failures. When available, colonoscopy data was analyzed. Results Forty-seven patients who received ustekinumab for refractory UC were included. Thirty-eight percent were female, and 34% were former smokers. Median age was 46 [37.5-61.5]; 62% had extensive disease, and 15% had perianal disease. Ninety-three percent received at least one biologic before ustekinumab, and 24% had received a JAK inhibitor. Thirty-eight patients required dose escalation, and 11 were on maintenance IV. Clinical response at week 16 was achieved in 74% and remission in 46%. At 24 and 52 weeks, 65% and 61% were in remission, respectively. At the end of follow-up, 59% of patients had endoscopic remission (Endoscopic Mayo score ≤ 1). Sixty percent continued treatment during a mean follow-up of 12 months [6-21]. No variable was associated with risk of discontinuation. No serious adverse events were reported. Discontinuation of treatment was due to treatment failure in all cases. Conclusion Ustekinumab was effective for induction and maintenance in our cohort of UC patients, although a significant proportion required dose escalation. Drug persistence was higher than 50% during the follow-up. The safety profile of ustekinumab was similar to that in controlled studies and other real-world studies.

P727 Clinical efficacy of apheresis in Ulcerative Colitis. The experience of four tertiary centers

Abstract Background Selective depletion of myeloid lineage leucocytes by adsorptive granulocyte and monocyte apheresis (GMA) with Adacolumn ® was introduced as a nonpharmacologic treatment for ulcerative colitis (UC) in 2000. It has been reported that GMA may be effective in combination with immunosuppressive treatment in a subset of patients. Τhe purpose of our study is the evaluation of the effectiveness and safety of GMA as a complementary treatment in patients with refractory ulcerative colitis. Methods Prospective data collection of a patient cohort with refractory UC receiving Adacolumn ® as an adjunct to their medical treatment. The therapeutic protocol has 2 phases: The induction phase entails two sessions per week for at least 3 weeks. The maintenance includes one weekly session for one month, one session every 15 days for one the next month, and monthly sessions thereafter. The patients’ medical treatment was maintained during the sessions. As a failure to GMA was considered the need for colectomy, the switch to a different treatment and inability to discontinue steroids. Response was evaluated after completion of at least 6 sessions of GMA. Results Ten patients with refractory UC were offered Adacolumn® between February 2021 and September 2023. Mean age was 39.6 years (22-61years). All patients had failed at least one biologic treatment and two-thirds two biologics. Their treatment which was maintained during GMA was: tofacitinib 10mg bid for 4 patients, ustekinumab 90mg sc every 8 weeks for 3, vedolizumab 300 mg every 8 weeks for 2, and corticosteroids 16mg for one. The median duration of treatment was 5.1 months (2-13 months), while the median number of sessions was 16 (6-45). Clinical and endoscopic remission was achieved in two cases (20%), after 13 sessions for both (in brackets in the Table) whereas two patients (20%) responded clinically according to partial Mayo score. Treatment failure was documented for 6 patients (60%) after 6-45 sessions. Patient number 4 performed 45 sessions in different hospitals because he was reluctant to be operated. Three underwent colectomy and three discontinued due to non-response. No adverse effects were observed. The initial median of partial Mayo score was 6 (5-9) while at the end of the evaluation was 4.5 (0-9). Table 1 summarizes the results of our study. Conclusion 1) GMA may be beneficial as an adjunct to biologics in refractory to medical treatment UC patients. 2) Interestingly, all patients on tofacitinib showed a favorable response after the addition of GMA. This observation may help define a subset of UC patients who may benefit the most.

P847 Effectiveness of tofacitinib in ulcerative proctitis compared to left sided colitis and pancolitis

Abstract Background Ulcerative proctitis (UP), though associated with high symptom burden and poor quality of life, is excluded from most of the randomized controlled trials in UC. We aimed to analyse the effectiveness of tofacitinib in UP, and compare it to that in left sided colitis (LSC) and pancolitis (PC). Methods This was a prospective observational cohort study. Patients with either steroid-dependent or refractory ulcerative colitis, who received tofacitinib, were divided into three groups based on the disease extent [UP, LSC and PC]. The primary outcome was comparison of proportion of patients in clinical remission in the three groups, at weeks 8, 16 and 48. Safety outcomes were reported using incidence rate per patient year of exposure. Results Clinical remission was achieved in 47%(15/32), 24%(23/94), and 43%(23/54) of patients at week 8, 56%(18/32), 37%(35/94), and 55%(30/54) of patients at week 16, and 59%(19/32), 38%(36/94), and 24%(13/54) of patients at week 48 in groups UP, LSC and PC, respectively. (Figure 1) Corticosteroid-free clinical remission rates were significantly higher in patients in groups UP at week 48. Five (15%) patients with UP were primary non-responders to tofacitinib at week 16, while three (9%) patients had secondary non-response at week 48. The median fecal calprotectin values at week 8 were 119.5 (53.75-611.25), 134 (63-456) and 208 (48.25-876) in patients with UP, LSC and PC, respectively. Similarly at week 48, the median fecal calprotectin values were the lowest in patients with UP (57[36-99]) as compared to patients with LSC (113[41-572]) and PC (150[89-1562]). The endoscopic remission rates at week 48 were similar in all the three groups (31%, 21% and 18% in groups UP, LSC and PC, respectively (UP vs LSC, p=0.25; UP vs PC, p=0.18; LSC vs PC, p=0.68). The probability of sustained clinical response was highest in patients with UP (cumulative probability of maintaining response 0.88) followed by groups LSC (cumulative probability of maintaining response 0.74) and PC (cumulative probability of maintaining response 0.60). The between group difference, was significant (Log Rank, p=0.03). (Figure 2) Patients with UP had the lowest incidence of adverse effects. Conclusion The effectiveness of tofacitinib in inducing and maintaining remission is greater in patients with UP compared to LSC and PC.