Introduction

Restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) is one of the surgical options for patients with medically refractory ulcerative colitis (UC). It does, however, have long term complications, such as chronic idiopathic pouchitis, which develops in 10%–15% of patients with acute pouchitis.
Chronic inflammatory pouch conditions often require biologic treatment. Anti-tumour necrosis factor (anti-TNF) medications are commonly prescribed as first line biologic treatment for chronic inflammatory pouch conditions. However, their use in these conditions is based on studies of relatively small numbers of patients that lack long term follow up.

Aims & Methods

We aimed to describe the long term outcomes of first line anti-TNF therapy in a large, multi-centre multi-national cohort of patients with chronic inflammatory pouch conditions.
This was an observational retrospective study.
We included patients with chronic inflammatory pouch conditions initially treated with anti-TNF drugs infliximab (IFX) or Adalimumab (ADA), who had a follow up of at least 1 year.
The primary outcome was anti-TNF treatment persistence, defined as continuation of anti-TNF throughout the study period. Secondary outcome was pouch failure, defined by the need for a defunctioning ileostomy or pouch excision.

Results

We recruited 87 patients initially treated with anti-TNFs.
Average follow up length was 101 months.
The most common indication for biologic treatment was chronic pouchitis with concomitant pre-pouch ileitis (62/87 patients, 71.3%). Chronic pouchitis without pre-pouch ileitis was the treatment indication in 19 patients (21.8%). Pre-pouch ileitis, without concomitant pouchitis, was seen in 7 patients (6.9%).
IFX was the most common first line anti-TNF treatment (55/87 patients, 63.2%), while 32 patients (36.8%) were treated with first line ADA.
Anti-TNF was administered as monotherapy in 46 patients, while 27 patients received it in combination with an immunomodulator.
Second line treatments included IFX (6 patients), ADA (15 patients), Vedolizumab (16 patients), Ustekinumab (12 patients) and Upadacitinib (one patient).
At the end of the study period only 13/87 patients (14.9%) were still on first line anti-TNF treatment.
The median time to anti-TNF discontinuation was 12.2 months.
The most common cause for anti-TNF discontinuation was lack of efficacy despite adequate serum drug levels and absence of anti-drug antibody formation (28 patients, 32.2%). Loss of response due to anti-drug antibody formation was the cause in 18 patients (20.7%), while 12 patients (13.8%) stopped treatment because of side effects/safety concerns.
Compared to patients receiving ADA, patients receiving IFX had an HR of 2.0 for treatment discontinuation (p=0.016).
Compared to patients receiving combination therapy of anti TNFs with immunomodulators, patients receiving anti-TNF monotherapy had similar rates of treatment discontinuation (p=0.155).
Out of the 74 patients who discontinued first line anti-TNF treatment, 42 (48.3%) are currently treated with a different medical therapy, and 32 (36.8%) developed pouch failure.
The median time to pouch failure was 38.6 months.
Patients receiving IFX were not at increased risk of pouch failure compared to those receiving ADA (p=0.2).

Conclusion

First line anti-TNF therapy for chronic pouch inflammatory conditions is associated with low long term persistence rates.
A significant proportion of patients initially treated with anti-TNF therapy develop pouch failure.

These patients should be counselled about the high risk of pouch failure.

Introduction

Chronic inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis, are associated with an increased risk of various cancers, particularly colorectal cancer, but also other types, such as small intestine, biliary tract, or liver cancers. Additionally, certain extra-digestive cancers may also occur in patients with these conditions. These risks vary depending on the duration and severity of inflammation, as well as other factors such as family history or exposure to certain treatments. This work explores the diversity of cancers associated with IBD, their prevalence, and their clinical characteristics, highlighting the importance of considering these risks in the medical management of patients.

Aims & Methods

This is a retrospective and descriptive single-center study conducted within a hepatogastroenterology department, focusing on patients followed for inflammatory bowel diseases (IBD) who developed cancer. The study covers the period from 1990 to 2025.

Results

Out of a total of 1,795 patients followed for IBD (1,200 for Crohn's disease and 595 for ulcerative colitis), 2% (36 patients) developed cancer. The male-to-female sex ratio was 0.38, with a clear female predominance. Among the patients, 69.4% (25) had Crohn's disease, and 30.55% (11) had ulcerative colitis.
The most common location of Crohn's disease was colonic involvement (44%, 11 cases),the predominant phenotype was inflammatory (52%, 13 cases) ,for ulcerative colitis the most frequent location was left-sided colitis (54%, 6 cases) ,the median disease duration before the onset of cancer was 60 months.
Digestive cancers were the most commonly associated with IBD (38.8%, 14 cases), followed by breast cancer in women (30.5%, 11 cases), gynecological cancers (11.1%, 4 cases), prostate adenocarcinoma (5%, 2 cases), skin cancers (5%, 2 cases), and other cancers (5%, 2 cases).
Only 30.5% (11 patients) had risk factors (chronic smoking, family history of cancer, etc.).
Regarding treatment, 33% (12 patients) were on biologic therapy , 30.5% (11) were on azathioprin , 16.6% (6) were on therapeutic abstention , 8.3% (3) were on aminosalicylates, and 5.5% (2) were on corticosteroids.
Treatment was discontinued in 63.8% (23) of patients after the discovery of cancer, and 22% (8) experienced a flare-up which was successfully managed with corticosteroid therapy.
Eighty-three point three percent (83.3%, 30 patients) underwent surgical treatment alone or in combination with radiochemotherapy. Sixteen point six percent (16.6%, 6 patients) were at an advanced stage and had metastases, so they received palliative treatment.
Thirty-six percent (36%, 13 patients) had a good outcome, 30.5% (11) were lost to follow-up, and 2.7% (1) died.

Conclusion

The study shows a 2% cancer incidence in IBD patients, slightly higher than the general population's risk (0.3–0.5% annually), likely due to prolonged inflammation and disease duration. These findings highlight the need for enhanced cancer surveillance and preventive strategies, especially for patients with colonic involvement.

Introduction

Risankizumab is an interleukin-23 inhibitor approved for the treatment of Crohn’s disease (CD). Its efficacy and safety have recently been demonstrated in trial-setting but there is yet limited evidence of its real-world effectiveness, especially on the middle- and long-term.

Aims & Methods

Using prospective data from the Dutch Initiative on Crohn and Colitis (ICC) Registry, we aimed to evaluate the effectiveness and adverse events of risankizumab in patients with difficult-to-treat CD, defined as the failure of advanced therapies with at least two different mechanisms of action¹. The primary endpoint was corticosteroid-free (CSF) clinical remission at week (W) 24. CSF clinical remission was defined as Harvey Bradshaw Index (HBI) ≤ 4 and no use of systemic corticosteroids at the time of the visit. As secondary outcomes, we examined clinical remission, biochemical remission (faecal calprotectin (FC) level ≤ 250μg/g) and combined clinical and biochemical remission at W24. Furthermore, remission rates between patients without history of bowel resection (i.e. surgery-naïve) and with bowel resection (i.e. surgery-experienced) at W24, drug survival and adverse events were assessed. Patients were included in the analysis if they received at least one intravenous dose of risankizumab before the 28^th of February 2025. Patients without available remission data at W24 and who remained on treatment were excluded from the W24 analysis population. Patients who discontinued treatment before W24 due to non-response, adverse events or loss to follow-up were considered non-responders.

Results

Eighty-five patients were included in the current analysis; 56 (65.9%) were female. Patients had a median disease duration of 16.0 years (IQR 14.0). Surgery history was available for 83 patients; 33 (39.8%) patients did not undergo surgery, while 50 (60.2%) were considered as surgery-experienced. At baseline, HBI was available for 72 patients; the median HBI was 6 (IQR 5); 24 (33.3%) patients had an HBI ≤ 4. Biochemical data were available for 19 (79.2%) patients in clinical remission: only one (5.3%) was in biochemical remission. At W24, HBI was available for 62 patients; 34 (54.8%) patients were in CSF clinical remission. Independent of CSF status, 62.9% (39/62) of the patients were in clinical remission. FC levels at W24 were available for 55 patients; 17 (30.9%) patients were in biochemical remission. Remission rates were not influenced by surgery history (Table 1). Over time, 16.5% (14/85) patients stopped risankizumab, after a median treatment duration of 182 days (IQR 188). Three (21.4%) patients discontinued risankizumab before W12, three (21.4%) between W12 and W24, and eight (57.2%) between W24 and W52. Reasons for discontinuation were non-response (42.9%), loss of response (42.9%) and adverse events (14.2%). A total of 83 adverse events were reported in 51 patients. Most common adverse events included respiratory infections (13.2%), skin problems (10.8%) and herpes zoster infections (8.4%). No hospitalisation or death were reported.

Conclusion

This prospective real-world study demonstrates the clinical effectiveness and the favourable safety profile of risankizumab at W24 in a difficult-to-treat Crohn’s disease population, including a high proportion of patients with bowel resection.

References

1. Parigi TL, D'Amico F, Abreu MT, Dignass A, Dotan I, Magro F, Griffiths AM, Jairath V, Iacucci M, Mantzaris GJ, O'Morain C, Reinisch W, Sachar DB, Turner D, Yamamoto T, Rubin DT, Peyrin-Biroulet L, Ghosh S, Danese S. Difficult-to-treat inflammatory bowel disease: results from an international consensus meeting. Lancet Gastroenterol Hepatol. 2023 Sep;8(9):853-859. doi: 10.1016/S2468-1253(23)00154-1. Epub 2023 Jul 6. PMID: 37423233.

Disclosure

LMMV - none FDMvS - adviser and/or speaker for Takeda, Galapagos, Dr. Falk, Lilly, and Janssen-Cilag; received an unrestricted grant from Takeda MRN - none ACdV - advisory boards for Takeda, Janssen, Bristol Myers Squibb, Abbvie, Pfizer, and Galapagos; research grants from Takeda, Janssen, and Pfizer AEvdMDJ - speaker fee from AbbVie, Alfasigma, Ferring, Janssen Pharmaceuticals, Takeda, Tramedico, and Vedanta; grants from Norgine, Cablon, Alfasigma, and ZonMW MCV - speaker fees from Janssen-Cilag, Galapagos, and Ferring B.V. WAvD - none WSN - none TER - none RLW - speaker fee from Abbvie, Ferring, and Pfizer BJ - none AGLB - none PV - speaker fee from Takeda, Abbvie, Janssen, Alfa Sigma, Lilly, and BMS BO - advisory boards of Takeda, BMS, Galapagos, Janssen, AbbVie, BMS, and Ferring; grants from Takeda, Pfizer, Galapagos, Ferring, Celltrion, BMS, and AbbVie ML - consultancy/lecture fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen-Cilag, Johnson & Johnson, Medtronic, Pfizer, Takeda, and Tillotts Pharma; grants from Alfasigma, the Netherlands Federation of University Medical Centres, TKI, and ZonMW JELS - none LAAPD - served on advisory boards as a speaker for Abbvie, Alfasigma, Janssen, and Pfizer; independent research funding from Pfizer HHF - none MJP - speaker fee from BMS, Janssen Cilag, and Takeda; non-restricted research grants from Horizon 2020, ZONMW (Dutch national research fund), MLDS, Takeda, Johnson and Johnson, Abbvie, and Galapagos MD - speaking fee from Bristol Meyers Squibb, Takeda, Galapagos, Janssen, and Dr. Falk; advisory board fees from Abbvie, Bristol Meyers Squibb, Celltrion, Galapagos/Alfasigma, Janssen, Takeda; grant/research support from Pfizer, Bristol Meyers Squibb, Galapagos Alfasigma, and Janssen ZM - speaker fee from Friso – Friesland Campina, Galapagos, Eli Lilly, and Takeda (paid to host institution); ; advisory board fees from Johnson & Johnson, Eli Lilly, Pfizer (paid to host institution); grants from ZonMw, Niels Stensen Fellowship, MLDS, Top consortium for Knowledge and Innovation (TKI), and Galapagos