Introduction

Identifying patient populations and factors associated with long-term treatment response can enable personalised management strategies in ulcerative colitis (UC). Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active UC.

Aims & Methods

Our aim was to identify patient subgroups with distinct response trajectories based on changes in combined rectal bleeding subscore (RBS) and stool frequency subscore (SFS) over time. In this post hoc analysis of etrasimod-treated patients from the ELEVATE UC 52 trial, PRO2 (SFS+RBS) was assessed to identify unique disease response trajectories, with further evaluation of the Week 52 achievement of primary and secondary endpoints. Additionally, a composite of objective and subjective disease activity measures, previously used in trajectory modelling, was assessed as comprehensive disease control (CDC). CDC was defined as meeting all the following criteria by Week 52: complete treatment (up to Week 50), clinical remission, RBS and SFS =0, endoscopic subscore =0/1, complete Mayo score ≤2, histological remission (Geboes score <2 or Robarts Histopathology Index <3), and C-reactive protein and/or faecal calprotectin within normal range. Longitudinal k-means was used to analyse PRO2 disease activity data as individual time-series connected datasets. Response-trajectory groups (TGs) were related to maintenance outcomes and baseline clinical characteristics. We evaluated the clinical relevance of grouping patients this way by assessing the proportions achieving key endpoints and their association with baseline demographics.

Results

Among the cohort of 283 etrasimod-treated UC patients, five TGs were identified (Table). 57% of the super-responders who achieved CDC were clustered in TGs C and E, characterised by rapid response and sustained clinical remission (TG C: 34/51 patients, TG E: 25/44 patients). Baseline characteristics of these patients included lower baseline disease activity, as measured by histology and Mayo score components. In TGs B and D, clinical remission was achieved by 31.7% and 34%, respectively, with clinical response achievement of 48.3% (29/60) and 53.2% (25/47). In TG E, symptomatic improvement according to PRO2 continued beyond Week 12.

Conclusion

Trajectory modelling allows the identification of distinct phenotypic subgroups among UC patients responding to a targeted therapy, highlighting heterogeneity often masked when analysed as a single population or clinical trial. Notably, a subset of etrasimod patients demonstrated super-fast and fast response dynamics, associated with higher rates of clinical remission and CDC. This may provide an important utility for therapeutic choice and patient management under therapy. Further studies across different modes of action are ongoing to validate these results and identify similarities and differences across patient populations and treatment effects.

Disclosure

VS is an employee of Pfizer Inc.
JCW is an employee and shareholder of Pfizer Inc.
CWL has served as a speaker for AbbVie, Dr Falk, Ferring, Hospira, Janssen, MSD, Pfizer Inc, Shire, Takeda, and Warner-Chilcott; has served as a consultant for AbbVie, Dr Falk, Gilead, GSK, Hospira, Iterative Scopes, Janssen, MSD, Oshi Health, Pfizer Inc, Pharmacosmos, Takeda, Topivert, Trellus Health, and Vifor Pharma; and has received research funding from AbbVie and Gilead.
SJ is an employee of Pfizer Inc.
WN is an employee and shareholder of Pfizer Inc.
SS has received lecture/speaker fees from AbbVie, Arena, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Falk, Fresenius, Janssen, MSD, Pfizer Inc, Takeda. Consultancy/advisory fees: AbbVie, Arena, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Falk, Fresenius, Gilead Sciences, IMAB, Janssen, MSD, Mylan, Pfizer Inc, Protagonist, Provention Bio, Takeda, Theravance and Ventyx Biopharma.

Introduction

Etrasimod (2 mg/day, oral) is a novel alternative for moderate-to-severe active ulcerative colitis (UC), which has proved to be effective in ELEVATE UC12 and UC52 trials^1,2.

Aims & Methods

This cost-effectiveness analysis compared etrasimod vs. most frequently used biologics in Spain³, for patients with moderate-to-severe active UC experienced to advanced therapies (AT), from the perspective of the Spanish national health system.
A hybrid model simulated the induction (decision tree) and maintenance (Markov model, 8-week cycles during lifetime) phases treatment to estimate costs (€, 2025) and quality-adjusted life years (QALYs), both yearly discounted (3%). All model inputs derived from scientific literature and were validated by national experts. The patients’ characteristics proceeded from etrasimod trials^1,2. Rates of efficacy, safety, and loss of response of etrasimod, adalimumab, ustekinumab, intravenous (IV) vedolizumab and subcutaneous (SC) vedolizumab were obtained from a Bayesian network meta-analysis^4,5.
After loss of response, a loop of subsequent AT in perpetuity was applied. Total costs included drugs acquisition (authorized posology and dose intensifications when required, both based on the European Public Assessment Reports [EPARs])^6,7, IV administration (€77.16)⁸, adverse events (€5,964.49 per serious infection)⁸ and management of UC (cost): active UC (€4,471)^9,10, response without remission (€1,801)^9,10, remission (€762)^9,10, surgery (€4,448)⁹, post-surgery without complications (€1,101)^9,10 and with complications (€6,428)^9,10. The annual surgery rate in UC was 0.34%¹⁰ (urgent: 38.2%; elective: 61.8%)¹¹, early and late complications occurred in 18.4%¹² and 46% (for 6.5 years)¹³. Utility values were 0.78 for active UC^1,2, 0.82 for response without remission^1,2, 0.89 for remission^1,2, 0.74 for surgery¹⁴, 0.90 for post-surgery without complications¹⁴ and 0.71 with complications¹⁴. Concomitant treatment with azathioprine (35% patients, biologics only), mercaptopurine (15% patients, biologics only), mesalazine (40% patients), prednisone (20% patients) and beclomethasone (10% patients) were considered^7,15. In addition to age and sex-specific mortality in Spain¹⁶, the excess mortality associated with colectomy was considered (relative risk: 1.3)¹⁷. A probabilistic sensitivity analysis (PSA) tested the results’ robustness.

Results

Etrasimod yielded more QALYs compared to each biologic and produced cost-savings in all pairwise comparisons except for IV vedolizumab (Table 1). Thus, etrasimod was cost-effective compared to IV vedolizumab (€16,212/QALY), and dominant compared with all remaining biologics. PSA revealed that etrasimod was dominant compared to each biologic (average of Monte Carlo simulations). Under a willingness to pay threshold of €27,000/QALY¹⁸, etrasimod was cost-effective in a minimum of 58.5% simulations (vs. IV vedolizumab) and a maximum of 99.9% (vs. adalimumab), varying between pairwise comparisons of etrasimod vs. biologic.

Conclusion

Etrasimod represents a cost-effective alternative for AT-experienced patients with moderate-to-severe active UC compared with biologics available in Spain.

References

¹ https://clinicaltrials.gov/study/NCT03945188; ² Sandborn WJ. Lancet. 2023;401:1159–71; ³ Gómez-Labrador C. Pharmaceutics. 2024;16:629; ⁴ Jaraith V. J Comp Eff Res. 2025:e240225; ⁵ https://scientificpubs.congressposter.com/p/k0b1nw0im7astcj2; ⁶ https://cima.aemps.es/cima/publico/home.html; ⁷ https://botplusweb.farmaceuticos.com/; ⁸ https://esalud.oblikue.com/; ⁹ Trigo-Vicente C. Expert Rev Pharmacoecon Outcomes Res. 2018;18:321–9; ¹⁰ Guasch M. Dig Liver Dis. 2021;53:54–60; ¹¹ Núñez L. Gastroenterol Hepatol. 2023;46:369–75; ¹² García MJ. J Clin Med. 2021;10:4402; ¹³ Ferrante M. Inflamm Bowel Dis. 2008;14:20–8; ¹⁴ Kosmas C. Value Health. 2015;18:A630; ¹⁵ https://www.nice.org.uk/guidance/ta828; ¹⁶ https://ine.es/dyngs/INEbase/es/operacion.htm?c=Estadistica_C&cid=1254736177004&menu=ultiDatos&idp=1254735573002; ¹⁷ Jess T. Am J Gastroenterol. 2007;102:609–17; ¹⁸ Vallejo-Torres L. PharmacoEconomics. 2025;43:109-22.

Disclosure

This work was sponsored by Pfizer®.
IRL, FMN, AJLV and EMB have received fees for their scientific advice and contribution to the publication.
AC and ALJ are employees of Pfizer SLU.
ACG and IO are employees of Pharmacoeconomics & Outcomes Research Iberia (PORIB), a consultant company specializing in health economics and outcomes research, which has received fees from Pfizer SLU for conducting the present study.
IRL has received financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Alfasigma, Biogen, Chiesi, Faes Farma, Ferring, Fresenius Kabi, Galapagos, Johnson & Johnson, Eli Lilly, Mirum Pharmaceuticals, Merck, Pfizer, Roche, Takeda, and Tillotts Pharma.

Introduction

Lower gastrointestinal bleeding (LGIB) is a frequent clinical challenge, particularly in elderly patients and those on anticoagulants. While anticoagulants are known to increase bleeding risk, their impact on LGIB outcomes remains uncertain.

Aims & Methods

To assess whether anticoagulant use is independently associated with adverse outcomes in patients hospitalized with acute LGIB, using robust propensity score-based methods to adjust for confounding.
Methods: This study was a post-hoc analysis of prospectively collected data from a multicenter, international cohort of 1911 patients hospitalized for LGIB. Propensity score matching (PSM) was performed using a logistic regression model, incorporating key covariates including demographics, comorbidities, comedications (antiplatelets, nonsteroidal anti-inflammatory drugs), prior history of LGIB, bleeding presentation (melena or hematochezia, hemodynamic instability) and care setting (inpatient vs. outpatient). Patients on anticoagulants were matched 1:1 with controls using nearest-neighbor matching (caliper=0.2). Covariate balance after adjustment was assessed using standardised mean differences (SMDs), with all variables achieving an SMD<0.2. Primary outcomes were in-hospital death and rebleeding. Secondary outcomes included red blood cell (RBC) transfusion and surgery. McNemar’s test was used for outcome comparisons between anticoagulant users and matched controls. Subgroups analysis to compare DOACs vs. VKAs was conducted using chi-squared and Mann–Whitney U tests, as appropriate.

Results

Among the original cohort of 1911 patients (mean age 77 years, IQR 66-84; 54.2% male), 610 (31.9%) were on anticoagulants (310 direct oral anticoagulant [DOACs], 188 vitamin K antagonists [VKAs], 89 low-molecular-weight or unfractionated heparin, and 23 unspecified). Overall, in-hospital death occurred in 72 (3.8%), rebleeding in 166 (8.7%), surgery in 104 (5.4%), and RBC transfusion in 836 (43.7%) patients. The matched cohort included 980 patients (490 per group). Anticoagulant use was not significantly associated with higher in-hospital mortality (OR 1.16, 95% CI 0.63-2.14), rebleeding (OR 1.42, 95% CI 0.90-2.25), or surgery (OR 0.75, 95% CI 0.43-1.32). However, it was related with higher RBC transfusion rates (OR 1.66, 95% CI 1.28-2.14). In the subgroup analysis, outcomes were comparable between DOACs and VKAs.

Conclusion

In patients hospitalized with LGIB, anticoagulant use is not associated with increased mortality, rebleeding, or surgical intervention but is linked to a higher need for RBC transfusion.

References

Oakland K., et al., Re-bleeding and Mortality After Lower Gastrointestinal Bleeding in Patients Taking Anti-platelets or Anti-coagulants, Clin Gastroenterol Hepatol, 2019
Radaelli F., et al., Clinical management and patient outcomes of acute lower gastrointestinal bleeding. A multicenter, prospective, cohort study, Dig Liver Dis, 2021
Dajti E., et al., In-hospital Mortality in Patients with Lower Gastrointestinal Bleeding: Development and Validation of a Prediction Score, Endoscopy, 2025

Disclosure

Emanuele Rondonotti and Franco Radaelli have received speaker honoraria from Fujifilm Co. The other authors have no disclosures.

Introduction

Previous studies reported a positive correlation between serum and tissue drug levels in IBD receiving intravenous (IV) infliximab (IFX) therapy, except in those with severely inflamed tissue (1). Tissue drug levels in patients with IBD receiving SC IFX have not yet been investigated. We aimed to compare both the serum and tissue drug levels between SC and IV IFX maintenance therapy in IBD patients.

Aims & Methods

Any IBD patients under maintenance therapy with SC or IV stable doses IFX who underwent a colonoscopy for routine follow-up were eligible. Patient and disease characteristics, as well as clinical and endoscopic activity were recorded. Clinical activity was defined by high activity score (CDAI or pMAYO score) with at least one elevated biomarker (fecal calprotectin >250 mg/g, serum CRP >5 mg/L). Endoscopic disease activity was categorized as absent (normal), low (mild inflammation), moderate (friability, aphthoid lesions), or severe (ulcerations), as reported by the endoscopist blinded to the results of serum and tissue drug levels. Two biopsies were taken from the same location (either the most active area or randomly if no endoscopic lesion), and tissue and serum IFX levels were measured simultaneously in a centralized manner blinded to clinical and endoscopic disease activity. Frozen biopsy specimens were treated with the Bio-Plex® Cell Lysis Kit after tissue cutting and homogenates were sonicated at 4°C (Omni Ruptor 205). Tissue extracts were then frozen at -80°C prior drug measurements (iTrack10; Theradiag).

Results

Thirty-five patients were enrolled (CD in 65%, Sex ratio 1.4, 14 % with clinically and 57 % with endoscopically active disease, and 23 under SC IFX therapy). The characteristics of both IV and SC IFX groups were comparable, except for drug dose intensification in 90% of those treated with IV IFX group and 5% in the SC IFX cohort (p < 0.001). In patient in endoscopic remission, tissue levels were undetectable or very low for both IV and SC IFX therapy. Serum and tissue drug levels were significantly higher in the SC IFX cohort compared with the IV IFX group (22 mg/mL vs 9 mg/mL for serum; p < 0.001 and 25 mg/g vs 10 mg/g for tissue; p = 0.002, respectively). A moderate correlation was found between serum and tissue drug levels for both IV and SC IFX therapy (Spearman r = 0.42; p = 0.014 and r = 0.43; p = 0.001, respectively). Tissue drug levels increased gradually in patients with minimal or moderate endoscopic activity and were lower in those with severe endoscopic activity for both IV and SC IFX groups (p < 0.001). Tissue drug levels remained significantly higher in minimal or moderate endoscopically active disease in SC compared with IV route of IFX administration. The two independent factors associated with drug tissue levels > 14 mg/g (median levels) were the SC IFX route (OR: 2.25, 95% CI = [1.19–2.23]; p = 0.001) and the serum IFX levels (OR: 1.63, 95% CI = [1.19–2.23]; p = 0.002). A serum IFX level greater than 16.1 mg/mL was highly predictive of a tissue drug level > 14 mg/g tissue (Se: 0.94, Spe: 0.94, PPV: 0.94, NPV: 0.94, and Accuracy = 94.3%).

Conclusion

Serum and tissue drug levels are positively correlated in IBD patients under IV and SC maintenance IFX therapy. Interestingly, drug levels were higher both in serum and tissue in patients under SC IFX compared with IV IFX and tissue drug levels gradually increased in minimally to moderately inflamed intestine but were lower or undetectable in more severe inflamed areas.

References

1. Yarur AJ, et al. The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: the ATLAS study. Gut 2016; 65: 249-255.

Introduction

Total abdominal proctolectomy with ileal-pouch anastomosis (IPAA) for ulcerative colitis (UC) is associated with substantial complications, including the inflammation of the pouch, namely pouchitis. Its estimated cumulative probability is 80% in 30-year1. The antibiotic therapy is highly effective2; however, up to 15-20% of patients develop chronic pouchitis (CP)3. The aim of our study is to provide new evidence about effectiveness of biologic agents to treat CP.

Aims & Methods

We performed an observational retrospective multicentre study at six Italian IBD referral units including adult patients with IPAA for UC surgery treated with biologic/small molecule therapy due to CP. Primary aim was to evaluate clinical response at 6 and 12 months (defined as a reduction of clinical Pouchitis Disease Activity Index - PDAI - sub-score by 2 points or more). Secondary aims were clinical and endoscopic response (defined as a reduction of the modified PDAI - mPDAI - by 2 points or more) at 6 and 12 months, clinical remission (defined as clinical PDAI sub-score <3) at 6 and 12 months, endoscopic remission (defined as endoscopic PDAI sub-score <2) at 12 months and rate of treatment failure, defined as need for re-intervention or change of therapy. Rate of adverse events were calculated too.

Results

77 patients (pts), male 66.2%, mean age 47.7 ± 14.6, 47 (64.4%) treated with advanced therapy before surgery, were included. Some of them has been treated with more than one advanced therapy after IPAA surgery and we used a total of 88 therapeutic lines for analyses (our population was distributed as following: 11.4% infliximab, 14.8% adalimumab, 1.1% golimumab, 54.6% vedolizumab, 14.8% ustekinumab, 2.3% tofacitinib, 1.1% upadacitinib and none with filgotinib). Amongst them, 45 pts (51.1%) reached clinical response at 6 months, whereas 50 (56.8%) at 12 months. No statistical differences were found between each drug neither at 6 (p 0.597) nor at 12 months (p0.610). However, infliximab had higher rate of response compared to the others (Table 1). Considering the mPDAI, 11 pts (44%) reached clinical and endoscopic response at 6 months, whereas 16 (47.1%) at 12 months. Moreover, 51 (58%) pts achieved clinical remission at 6 months and 54 (61.4%) at 12 months. Analyzing data about anti-TNFs, out of 19 pts with clinical and endoscopic response at 12 months, 8 failed at anti-TNFs before surgery. Therefore, 8 pts over 19 (42.1%) had a good answer to anti-TNFs even though they resulted failure before surgery. Endoscopic remission was achieved by 11/34 pts (32.4%) at 12 months. IPAA failure, with consequent ileostomy surgery was performed in just 3 pts, 2 at six months and 1 at 12 months. Adverse events occurred only in 1 pt (hitching).

Conclusion

In our multicentre experience, clinical remission was achieved in 61.4% of patients with CP under advanced therapy. Infliximab in one-year therapy seems to have higher efficacy rate compared to the others.

References

1. Results up to 30 Years after ileal pouch-anal anastomosis for chronic ulcerative colitis - Lightner AI, Mathis KI, Dozonis EJ, et al. Inflamm Bowel Dis 2017;23(5);781-90
2. Systematic review with meta-analysis: the management o chrronic refractory pouchitis with an evidence-based treatment algorithm - Segal JP, Ding NS, Worley G, et al. Aliment Pharmacol Ther 2017;45:581-92
3. Pouchitis following ileal pouch-anal anastomosis: definition, pathogenesis, and treatment. Sandborn WJ. Gastroenterology 1994;107:1856-60.