Introduction

The impact of achieving endoscopic remission in ulcerative proctitis (UP) is unclear. The preferred long-term treatment goal in ulcerative colitis (UC) is achieving both the symptomatic resolution and endoscopic remission (ER),¹ which has been associated with reduced risk of complications, including colectomy.^2,3 UP is an anatomically limited form of UC, involving only the rectum. Unlike in extensive or left-sided UC, UP has not been associated with elevated colorectal cancer risk. Therefore, the achievement of endoscopic healing as compared to clinical remission in UP represents an uncertain therapeutic target.⁴

Aims & Methods

This study assessed the impact of achieving EH on subsequent outcomes in UP patients. This was a single-center retrospective cohort study including patients aged ≥ 18 with a confirmed diagnosis of UP based on clinical and endoscopic criteria. Included patients had at least two endoscopies and active endoscopic disease (Mayo endoscopy score [(MES) of 1, 2, or 3]) at the first (baseline) endoscopy. EH was defined as an MES of 0 or 1 at the second (follow-up) procedure. A minimum time of 1 month between scopes was required for inclusion. Descriptive statistics were used for baseline characteristics. The relationship of EH to IBD-related outcomes was assessed using univariate analysis (Pearson's Chi-squared test; Fisher's exact test; Welch Two Sample t-test) and we identified those independently associated with EH using multivariable logistic regression analysis (odds ratio with 95% confidence interval).

Results

Among 200 UP patients with baseline endoscopic activity, 109 patients (54.5%) achieved EH at follow-up. The median time from baseline to follow-up was 15 months (IQR: 6, 31). EH at follow-up was significantly associated with fewer IBD-related ED visits (healing: 8.3%, no healing: 21%) or hospitalizations (5.5% vs 18%) and fewer GI visits (mean: 8 [SD: 9], vs 17 [22]) after the second scope. Patients with EH were less likely to have iron deficiency anemia (IDA; 23% vs 41%), iron infusion (10% vs 25%), C. difficile infection (0.9% vs 6.6%), or to initiate a new biologic after relapse (15% vs 33%). Patients with EH also had a greater time to clinical relapse (650 days [730] vs 270 days [416]). In multivariable analysis, patients with mucosal healing had 68% lower odds of an IBD-related ED visit (OR: 0.32, 95% CI: 0.13, 0.73), 74% lower odds of IBD-related hospitalization (0.26 [0.09, 0.67]), and 64% lower odds of biologic initiation after relapse (0.36 [0.13, 0.95]) compared to patients with no mucosal healing, adjusting for the index MES score.

Conclusion

UP patients with endoscopic healing had less IBD-related healthcare utilization (ED visits, hospitalizations, GI visits), fewer IBD-related complications (IDA, iron infusion, C. difficile infection), and were less likely to escalate to biologics after relapse. Our findings suggest that using a treatment target of endoscopic healing is desirable in UP and shed light on its potential utility in preventing disease-related complications and improving long-term outcomes.

References

1. Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target. Off J Am Coll Gastroenterol ACG. 2015;110(9):1324-1338. doi:10.1038/ajg.2015.233
2. Colombel JF, Rutgeerts P, Reinisch W, et al. Early Mucosal Healing With Infliximab Is Associated With Improved Long-term Clinical Outcomes in Ulcerative Colitis. Gastroenterology. 2011;141(4):1194-1201. doi:10.1053/j.gastro.2011.06.054
3. Impact of mucosal healing on long‐term outcomes in ulcerative colitis treated with infliximab: a multicenter experience - Laharie - 2013 - Alimentary Pharmacology & Therapeutics - Wiley Online Library. Accessed September 24, 2022. https://onlinelibrary.wiley.com/doi/full/10.1111/apt.12289
4. Zhou Q, Shen ZF, Wu B sheng, et al. Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract. 2019;2019:1-11. doi:10.1155/2019/5363261

Disclosure

E.L., A.A.: no conflicts of interest to disclose
R.B.: Consulting/Speaker: Janssen, Abbvie, Bristol Myers Squibb, Prometheus Laboratories, Pfizer, Takeda
R.L.: Consulting/Speaking Fees: Pfizer, Enzymetrics, Ancilia Biosciences. Grant Support: National Institute of Health (NIH)
E.S.: Consulting/Speaking Fees: AbbVie, Crohn’s and Colitis Foundation of America (CCFA), Entera Health, Evidera, GI Health Foundation, Janssen, Protagonist Therapeutics, Seres Health, Takeda Pharmaceuticals, Bristol Myers Squibb. Grant Support: Abbott (AbbVie), AstraZeneca, CCFA, Janssen Research & Development, Johns Hopkins University, National Institute of Diabetes and Digestive and Kidney (NIDDK), National Institute of Health (NIH), New York Crohn’s Foundation, Pfizer, UCB, UCSF–CCFA Clinical Research Alliance, Genentech, Seres Therapeutics, Celgen. R.B.: Consulting: Prometheus
D.L.: Consulting/Speaking Fees: Abbvie, Boehringer Ingelheim, Eli Lilly, Fresenius Kabi, Janssen, Palatin, Pfizer, Prometheus Biosciences, Takeda; Grants: Abbvie, Janssen, Takeda

Introduction

Ulcerative proctitis (also called isolated proctitis) affects approximately 30% of patients with ulcerative colitis , yet achieving disease control remains challenging. Controlling the disease is essential to preventing disability and disease progression. Backbone therapy includes topical and oral 5-aminosalicylic acid (5-ASA) and steroids. One third of patients with ulcerative proctitis are refractory to conventional therapy with 5-ASA and steroids.

Aims & Methods

The aim of this study was to investigate current practice on isolated proctitis management across the globe.
Physicians with experience in treating inflammatory bowel diseases (IBD) were invited to participate in an anonymous, multiple-choice survey between January and February 2025. The survey addressed various aspects of patient care including clinical practice and attitudes towards isolated proctitis identification, disease activity measurement attitudes, and current treatment of isolated proctitis, including the use of advanced therapies.

Results

The survey included 460 physicians from 66 countries. Gastroenterologists were the most represented specialists (89.0%), followed by surgeons (6.3%), and internal medicine doctors (3.5%). Three quarters of participants (74.6%) had > 10 years of experience in IBD.
The majority of participants (87.9%) assessed clinical activity of isolated proctitis within 3 months of treatment initiation, 75.9% used fecal calprotectin, and 67.1% used C-reactive protein (CRP) to measure disease activity. Endoscopic assessment was performed 3 to 6 months (34.2%) or 6 to 12 months (48.4%) after treatment induction. For patients in clinical remission, the participants assessed clinical and biological disease activity every 6 months (54% and 59% respectively), and endoscopic evaluation every 5+ years (rectosigmoidoscopy: 27% and colonoscopy: 31%).
In this survey, 49% of participants were more reluctant to begin an advanced therapy in patients with isolated proctitis compared to pancolitis or left sided colitis. Infliximab (mean 6.55/10; SD: 2.64), vedolizumab (mean 5.64/10; SD: 2.98), upadacitinib (mean 4.88/10; SD: 2.91), and ustekinumab (mean 4.81/10; SD: 2.90) were preferred in refractory proctitis. Two thirds of participants (61.0%) were less likely to use biologics in combination with immunosuppressants in isolated proctitis compared to left sided or pancolitis. Anti-TNF (tumor necrosis factor) (48.4%) was the preferred choice in first line advanced therapy after failing conventional treatment.

Conclusion

This study highlighted differences in management of isolated proctitis compared to left sided colitis or pancolitis. This is likely explained by the fact that isolated proctitis patients were historically excluded from clinical trials, therefore management relied on extrapolation of data from studies on more extensive disease. To date, a single advanced therapy (etrasimod) has demonstrated efficacy in isolated proctitis patients through a double blinded, randomized clinical trial . Future clinical trials on advanced therapies for this frequent and disabling condition are eagerly awaited.

References

1. Fumery M, Singh S, Dulai PS, Gower-Rousseau C, Peyrin-Biroulet L, Sandborn WJ.. Natural history of adult ulcerative colitis in population-based cohorts: a systematic review. Clin Gastroenterol Hepatol 2018;16:343–356.e3.
2. Dubois E, Moens A, Geelen R, Sabino J, Ferrante M, Vermeire S.. Long-term outcomes of patients with ulcerative proctitis: analysis from a large referral centre cohort. United European Gastroenterol J 2020;8:933–41.
3. Peyrin-Biroulet, L., Dubinsky, M. C., Sands, B. E., Panés, J., Schreiber, S., Reinisch, W., Feagan, B. G., Danese, S., Yarur, A. J., D'Haens, G. R., Goetsch, M., Wosik, K., Keating, M., Lazin, K., Wu, J., Modesto, I., McDonnell, A., Bartolome, L., & Vermeire, S. (2024). Efficacy and Safety of Etrasimod in Patients with Moderately to Severely Active Isolated Proctitis: Results From the Phase 3 ELEVATE UC Clinical Programme. Journal of Crohn's & colitis, 18(8), 1270–1282. https://doi.org/10.1093/ecco-jcc/jjae038

Disclosure

This study was conducted as a collaboration between Materia Prima and Pfizer. Materia Prima is the study sponsor.

Introduction

Ulcerative proctitis (UP) is associated with disabling symptoms such as diarrhea, hematochezia and bowel urgency¹. Adequate therapy is crucial for symptom control and may reduce the risk of proximal disease extension. Although prior studies have explored risk factors for disease progression, they are limited by small sample sizes and have conflicting results^2,3.

Aims & Methods

We aimed to (1) assess the incidence and (2) identify risk factors for disease progression in newly diagnosed UP patients. We included all patients diagnosed with UP (inflammation ≤15 cm beyond the anal verge) between January 2000 and January 2024 in a large, non-academic hospital in the Netherlands. Data were collected from diagnosis until the end of follow-up. Disease progression was defined as endoscopic extension of UP (Montreal E1) to either left-sided (E2) or pancolitis (E3). To avoid overestimating the risk of disease progression, we used a Fine & Gray (F&G) regression model to account for patients in long-term remission who had no in-hospital follow-up. Patients who were referred back to primary care and/or had no in-hospital follow-up for ≥2 years were considered in long-term remission, which was used as a competing event in the F&G model. The cumulative incidence of disease progression was calculated at 1-, 5- and 10-years follow-up and compared to the progression rates of traditional Kaplan-Meier survival estimates.

Results

In total, 486 UP patients were included; 283 (58%) were female and median age at diagnosis was 39 years (IQR 29-53). 371 (76%) patients were in clinical remission at last follow-up. Of those, 291 (78%) were treated with topical and/or oral 5-aminosalicylates (5-ASA) and/or topical steroids; 202 (54%) required only topical and/or oral 5-ASA. 50 (10%) patients had refractory UP and required treatment with immunosuppressants or advanced therapies. During a median follow-up of 6.2 years (IQR 2.1-12.2), disease progression occurred in 112 patients (23%), of whom 80 (16%) progressed to E2 and 32 (6.6%) to E3. Median time to progression was 57 months (IQR 22-103). The cumulative incidence of disease progression was 2.8% (95% CI 1.4-4.4%) at 1 year, 13.2% (95% CI 9.9-16.4%) at 5 years and 23.9% (95% CI 19.4-28.4%) at 10 years after diagnosis and would have been overestimated with traditional Kaplan-Meier analysis (5.1% [95% CI 1.9-8.1%] at 1 year, 24.6% [95% CI 14.9-33.3%] at 5 years and 46.3% [95% CI 30.3-58.6%] at 10 years). F&G analyses demonstrated that age <18 years at diagnosis (HR 2.61, p=0.009) and the absence of steroid-free remission at 3 months (HR 1.97, p=0.005) were significant predictors for disease progression (Table 1).

Conclusion

In this large cohort of newly diagnosed UP patients, the 10-year cumulative incidence of disease progression was 23.9%. Most patients responded well to conventional treatment, as 60% reached clinical remission with only topical and/or oral 5-ASA and/or topical steroids. Absence of steroid-free remission at 3 months and age <18 at diagnosis were significant predictors for disease progression. Better prediction of disease progression could help identify high-risk patients who may benefit from tailored monitoring strategies, as well as low-risk patients that may be suitable for referral back to primary care.

References

1. Meucci G, Vecchi M, Astegiano M, et al. The natural history of ulcerative proctitis: a multicenter, retrospective study. Gruppo di Studio per le Malattie Infiammatorie Intestinali (GSMII). Am J Gastroenterol. 2000;95(2):469-473
2. Huguet JM, Ferrer-Barceló L, Suárez P, et al. Endoscopic progression of ulcerative proctitis to proximal disease. Can we identify predictors of progression?. Scand J Gastroenterol. 2018;53(10-11):1286-1290.
3. Walsh E, Chah YW, Chin SM, et al. Clinical Predictors and Natural History of Disease Extension in Patients with Ulcerative Proctitis. Inflamm Bowel Dis. 2017;23(11):2035-2041.
4. Andersen PK, Geskus RB, de Witte T, Putter H. Competing risks in epidemiology: possibilities and pitfalls. Int J Epidemiol. 2012;41(3):861-870.

Disclosure

RJBP, JH, RAJP, REAvD and AGLB have nothing to disclose. LAAPD has served on advisory boards for Abbvie, Janssen, Galapagos, and Pfizer, and has received independent research funding from Pfizer. ACdV has has served on advisory boards for Takeda, Janssen, Bristol Myers Squibb, Abbvie, Pfizer, and Galapagos and has received unrestricted research grants from Takeda, Janssen, and Pfizer.

Introduction

Acute severe ulcerative colitis (ASUC) is a medical emergency requiring hospitalisation. Overtime, there has been an increasing number of biologic and non-biologic treatment options available to induce and maintain disease remission. A previous study found no significant difference in length of stay or colectomy rates for those on biologic or small molecule therapy prior to admission compared to those who were not on advanced ulcerative colitis (UC) therapies, but found they had higher rates of surgical consultation and 90-day readmission rates.¹ We aimed to evaluate the preadmission medications patients were receiving at time of ASUC presentation, and to determine whether maintenance biologic and small molecule therapy had an effect on patient outcomes, including need for rescue therapy, colectomy, total parental nutrition (TPN), length of stay (LOS), readmission rates and mortality.

Aims & Methods

A retrospective review was conducted on all ASUC presentations to a quaternary Sydney hospital over a 10-year period. A modified Truelove and Witts’ criteria was used to define ASUC.Data was collected on preadmission UC medications, including aminosalicylates, thiopurines, steroids and advanced UC therapies, including biologics and small molecule inhibitors. Outcomes assessed included need for biologic rescue therapy, colectomy, TPN, length of stay, 30- and 90-day readmission rates, and 30- and 90-day mortality rate.

Results

A total of 172 ASUC presentations were identified. Of these, 143 presentations (83%) were patients with existing diagnosis of UC. Pre-admission medications in these patients included aminosalicylates (62%, n=89), thiopurines (25%, n=36), steroids (61%, n=87), biologics (17%, n=25), and small molecule inhibitors (2%, n=3). Patients taking aminosalicylates as maintenance therapy had significantly lower rates of need for rescue therapy (32% vs 51%, p=0.015). Patients on aminosalicylates-only had lower rates of 90-day readmission compared to those on both aminosalicylates and additional advanced UC therapies (0% vs 31%, p=0.007). There was no significant difference in need for rescue therapy for those on other maintenance therapies. Patients who presented on prednisolone <20 mg/d had a significantly higher rate of 90-day readmission compared to those on a dose ≥20mg (47% vs 13%, p=0.004). Those on biologic maintenance therapy had significantly higher rates of TPN use, colectomy, 90-day readmission, 30-and 90-day mortality and mean length of stay (Table 1). Patients on small molecule inhibitors had a shorter length of stay (7±1 vs 11±9.2 days, p=0.001), but no difference in other treatment outcomes.

Conclusion

Patients with pre-existing diagnosis of UC on maintenance biologic therapy who presented with ASUC were more likely to require TPN, colectomy, 90-day readmission, 30-and 90-day mortality and longer length of stay. Patients on aminosalicylates-only had lower rates of 90-day readmission. Our study findings may reflect that patients on advanced outpatient UC therapies have a more severe phenotype translating to a more severe ASUC admission course. More research is needed to predict such markers of severity.

References

1. Sabrie, N., Jogendran, M., Jogendran, R. & Targownik, L.E. Outcomes of patients admitted with acute, severe ulcerative colitis on biologic therapy: a retrospective analysis from a tertiary referral hospital. Journal of the Canadian Association of Gastroenterology 7, 306-311 (2024).

Introduction

This report presents the results of a multicenter, randomized, double-blind, placebo-controlled phase 3 study (VP-VLY-686-3301) assessing the efficacy of tradipitant in relieving symptoms of gastroparesis. Tradipitant, a novel NK-1 receptor antagonist, previously demonstrated efficacy in diabetic and idiopathic gastroparesis in reducing gastroparesis symptoms in a phase 2 study (VP-VLY-686-2301).

Aims & Methods

N=201 idiopathic and diabetic gastroparesis patients with delayed gastric emptying, moderate to severe nausea, and at least 1 vomiting episode were included in the ITT (Intent-to-Treat) population. Subjects were randomized to receive 85 mg tradipitant twice a day (n=102) or placebo (n=99) for 12 weeks. Nausea was assessed daily using the 5-point Gastroparesis Core Symptom Daily Diary (GCSDD). Overall gastroparesis symptom improvement was evaluated using the Patient Global Impression of Change (PGI-C) and the Overall Patient Benefit (OPB) scales. Sensitivity analyses were also performed to control for confounders that may have masked the true treatment effect size.

Results

At the primary endpoint of change in nausea from baseline as measured by the GCSDD at week 12, both tradipitant and placebo showed significant and similar reductions from baseline at 1.55 and 1.49 respectively. Comparison between treatment arms did not reach statistical significance in this measure. However, in the PGI-C scale, more tradipitant treated patients demonstrated response as compared to placebo both at week 2 (74% v. 58%, p=0.019) and at week 12 (78% v. 66%, p=0.065). Similarly, in the OPB scale, more tradipitant treated patients demonstrated response as compared to placebo both at week 2 (81% v. 62%, p=0.0003) and week 12 (86% v. 71%, p=0.011).
Sensitivity analysis adjusting for rescue medication use further confirmed the ITT findings in both the PGI-C and OPB analysis at both week 2 and week 12.

Conclusion

Significant but similar improvements from baseline for tradipitant and placebo may have masked the true treatment effect size at the primary endpoint of the study of change in nausea severity as measured by daily diary at week 12 leading to no statistically significant difference between treatments. Despite this large placebo effect, tradipitant was shown to be significantly better than placebo in global measures of patient improvement including the Patient Global Impression of Change (PGI-C) and the Overall Patient Benefit (OPB) scales.

Disclosure

Study was sponsored by Vanda Pharmaceuticals, Inc. Authors are employees of Vanda Pharmaceuticals, Inc.

Introduction

Pain, discomfort, and bloating can occur during and after colonoscopy, secondary to bowel distention. Insufflation is the major reason for bowel distention after a colonoscopy. Room air (RA) has slower re-absorption through the intestinal mucosa than carbon dioxide (CO2). Theoretically, with a faster resorption speed, abdominal pain, discomfort, and bloating are expected to be less with CO2 use. Nevertheless, in some clinical studies, CO2 was not found to be superior to RA in terms of post-procedure pain sensation.

Aims & Methods

The aim of this study was to compare abdominal pain sensation and bloating after colonoscopy using RA versus CO2 insufflation. A prospective randomized controlled study conducted on patients performing diagnostic colonoscopy. Enrolled patients were randomized to RA (group 1) versus CO2 insufflation (group 2). All patients were sedated with midazolam (2.5-5 mg) and all colonoscopies were performed by a single endoscopist. Abdominal pain sensation and bloating after the procedure as the primary outcome measure was assessed by a 10-point visual analogue scale (VAS), numerical rating scales from 0 (no pain) to 10 points (maximal pain). The participants were asked about abdominal pain and bloating at 15, 60, and 180 minutes and 24 hours post-procedural.

Results

From July 2021 to August 2022, a total of 64 patients were enrolled. There was 31 males and 33 females. Their mean age was 48.27±16 years. There was a statistically significant increase in abdominal bloating in group 1 (59.4%) compared to group 2 (18.7%), (P=0.018). Also, there was a statistically significant increase in abdominal pain sensation in group 1 compared to group 2 at 60 min (43.8% vs 21.9%) (P=0.011), 180 min (28.1% vs 9.4%) (P=0.017), respectively. None of the studied patients developed pain after 24 hours and there was no statistically significant difference between the studied groups regarding cecal intubation time and total examination time. No adverse events were noted in both groups.

Conclusion

CO2 insufflation is associated with significantly less bloating and less abdominal pain after diagnostic colonoscopy compared to RA insufflation.