Introduction

Long-term treatment of chronic inflammation after ileal pouch-anal anastomosis (IPAA) remains difficult. While biologics are widely used, real-world data on their persistence and the factors that prompt discontinuation are scarce.

Aims & Methods

We aim to describe long‑term use of bioloics as first- and advanced-line therapies, and identify predictors of discontinuation. Patients post-IPAA were prospectively followed in a comprehensive pouch clinic at a tertiary referral center. Inclusion: patients initiating biologics for chronic pouch phenotypes, specifically chronic pouchitis and Crohn's like disease of the pouch. Exclusion: biologics initiated with an existing ileostomy or for extra-intestinal manifestations. Primary outcome: drug persistence. Treatment courses were further divided into first-line and advanced-line therapies. Clinical and endoscopic remission was assessed at 26 weeks in available patients, using the corresponding PDAI subscores. Kaplan-Meier curves, log-rank tests, and Cox models were used to analyze discontinuation-free survival. A recurrent-event Cox model assessed persistence across multiple lines of therapy.

Results

Of 186 patients post-IPAA, 38 patients (21 [55%] females, median 16.8 y post‑IPAA) initiated biologics with overall 63 treatment courses: adalimumab (33.3%), infliximab (26.9%), ustekinumab (25.4%), vedolizumab (6.3%), upadacitinib (4.8%), risankizumab and golimumab (1.6% each). Median biologics overall persistence was 686 days (IQR 210‑1,702). Most treatment courses (34/63, 54%) were discontinued, mainly for primary non‑response (41%), immunogenicity (15%), or adverse events (15%).
In first‑line biologics, 16/38 (42%) patients had persistent therapy at last follow‑up. Week‑26 clinical remission was achieved by 19/21 patients (90%) and endoscopic remission by 5/10 (50%).
Predictors of earlier discontinuation of first-line biologic were: biologics initiation ≤ 5 years post-IPAA (HR 2.46, 95 % CI: 1.13‑5.97), reuse of a biologic administered pre‑IPAA (7/7 failures; HR 3.41, 1.33‑8.76) and female sex (male sex protective; HR 0.30, 0.10‑0.92). All patients of Arab‑ethnicity (5/5, 100%) discontinued therapy (p=0.05). Concomitant antibiotics (17/38, 45%) or immunomodulators (6/38, 16%) did not affect persistence. Anti-glycan antibodies developed in 4 patients (10.8%), and all discontinued biologics. All patients with NOD2 or IRGM homozygous variants discontinued biologics as well.
After first‑line failure, 15/38 (39.5%) patients underwent 25 advanced‑line courses; each additional treatment line doubled the discontinuation hazard (HR 2.48, 95% CI: 1.26‑4.90), while prior therapy duration did not predict future persistence (p=0.5). Ustekinumab accounted for 12/25 courses (48%) and showed the highest persistence rate (63.6%), whereas vedolizumab (n=3), upadacitinib (n=2) and risankizumab (n=1) were universally discontinued.

Conclusion

In patients post-IPAA with phenotypes of chronic pouch inflammation, biologics achieved high short‑term efficacy, including clinical and endoscopic remission. Clinical and surgical factors independently predicted earlier treatment discontinuation. In advanced-line therapies, treatment success declined with each subsequent treatment line. Ustekinumab demonstrated the highest persistence regardless of treatment line. This raises the possibility of a valuable rescue option even after prior biologic failure. These findings call for improved approach to biologics selection in pouch-related inflammatory conditions.

Disclosure

Jacob E Ollech: Has received grant support from Pfizer, consulting fees from Takeda, and
speaker fees from Abbvie, Janssen, Pfizer, Takeda, Novartis, and Bristol Myers Squibb.
Iris Dotan: consultation fee or honorarium from: Abbott, Abbvie, Athos, Arena, Altman
Research, Cambridge Healthcare, Celltrion, Celgene/BMS, Eli-Lilly, Ferring, Falk Pharma, Food
Industries Organization, Gilead, Galapagos, Iterative Scopes, Integra Holdings, Janssen,
Neopharm, Pfizer, Rafa laboratories, Roche/Genentech, Sangamo, Sublimity, Sandoz, Takeda,
Wildbio. Grants: Altman Research, BMS, Pfizer

Introduction

Microscopic colitis is a chronic inflammatory condition defined by a clinical triad: chronic diarrhea, endoscopy without significant abnormalities, and distinct histopathological features characterized by a largely normal appearance of the mucosa but increased numbers of lymphocytes in the epithelium and lamina propria on microscopy.

Aims & Methods

This study aims to explore the relationship between clinical presentation and histopathological features in microscopic colitis, with a focus on identifying prognostic factors linked to therapeutic response and symptom resolution.
This is a retrospective, descriptive study conducted over a 10-year period (September 2015 to May 2025), involving 54 patients diagnosed with microscopic colitis based on histological examination of colonic biopsies. Among them, 19 cases were identified as collagenous colitis and 35 as lymphocytic colitis. Data collected included epidemiological, clinical, endoscopic, histopathological, therapeutic, and follow-up information.
The histological parameters assessed were: characteristics of the lamina propria, intraepithelial lymphocytosis, presence and thickness of the subepithelial collagen band, and surface epithelial damage.

Results

A total of 54 cases of microscopic colitis were included in the study, among which 51 patients (94.4%) presented with chronic diarrhea, with a median of 7 diarrheic stools [IQR: 4.5–10.5]. One patient with lymphocytic colitis had concomitant celiac disease. Concerning medication use, 2 patients (3.7%) were taking proton pump inhibitors, and 3 (5.6%) were on venotonic agents.
Our analysis revealed several statistically significant correlations:

• A very strong positive correlation between the number of intraepithelial lymphocytes (IELs) and the frequency of diarrheal stools (r = 0.873; p < 0.001).

• A strong positive correlation between the number of diarrheal stools and the rate of clinical improvement (r = 0.633; p < 0.001).

• A strong association between subepithelial collagen band thickness and clinical improvement (r = 0.509; p < 0.001).

In addition, patients with an IEL count <30% experienced a significantly faster clinical response compared to those with ≥30%, with a median time to symptom resolution of 2 weeks versus 4 weeks, respectively (p < 0.001). Similarly, patients with subepithelial collagen band thickness <20 µm showed more rapid improvement than those with ≥20 µm (median time to improvement: 2 weeks vs. 6 weeks; p < 0.002).
Regarding treatment, 49 patients (90.7%) received budesonide, while 5 (9.3%) were managed with loperamide. A follow-up histological assessment performed 12 months after treatment initiation showed complete normalization of the colonic mucosa in all patients.

Conclusion

Microscopic colitis is a common cause of chronic diarrhea and represents a treatable condition. Accurate diagnosis relies on the recognition of characteristic histopathological features, highlighting the importance of a thorough histological assessment. The integration of clinical context with microscopic findings enables the pathologist to establish a confident diagnosis in most cases and to provide the gastroenterologist with precise and clinically relevant information.

Introduction

Despite debilitating symptoms, no standardized disease severity index exists for microscopic colitis (MC). This gap hinders alignment with US Food and Drug Administration (FDA) and European Medicines Agency (EMA) standards, which emphasize the importance of patient-reported outcome measures (PROMs) in new therapy approval.

Aims & Methods

This study aimed to validate the Microscopic Colitis Symptom Questionnaire (MCSQ) and develop the Microscopic Colitis Score (MCS), a novel disease severity index.
This prospective, multicenter study included 131 patients with biopsy-confirmed MC (67 remission, 64 active disease). Patients completed MCSQ and HRQoL assessments (IBDQ-32, SHS) at baseline and follow-up. Clustering analysis systematically identified distinct disease severity groups. MCS was developed as a composite score derived from MCSQ.

Results

Factor analysis revealed a three-factor MCSQ model with good internal consistency (Cronbach’s alpha = 0.88). Test-retest reliability (ICC=0.88) and responsiveness to treatment (p<0.01) of all MCSQ items were high. MCS, ranging from 0 (asymptomatic) to 15 (maximum symptoms), correlated strongly with HRQoL measures such as IBDQ-32 total score (r_p=-0.78), IBDQ-32 bowel symptoms (r_p=-0.80) and SHS bowel symptoms (r_s=0.69). Receiver-operating characteristic curves indicated that MCS could accurately identify patients in remission (as per Hjortswang criteria; AUC=0.85), as well as mild (AUC=0.97), moderate (AUC=0.93), or severe disease (AUC=0.96).

Conclusion

MCSQ and MCS are valid, reliable, and responsive tools that meet FDA and EMA standards. Both accurately reflect the diverse symptoms of MC. Compared to the binary Hjortswang criteria, MCS provides a nuanced evaluation of disease activity and holds promise for assessing therapeutic efficacy in future trials.

Disclosure

This work was supported with research grants from Mag-tarmfonden (grant 1–23 and 5-24) and Region Östergötland.
KPL has received speaker fees from Eli Lilly and Takeda; research support from Takeda and Ferring. YZ has received support for conference attendance, speaker fees, research support and consulting fees from: AbbVie, Adacyte, Alfa-Sigma, Almirall, Amgen, Boehringer Ingelheim, Dr Falk Pharma, FAES Pharma, Fresenius Kabi, Ferring, Galapagos, Janssen, J&J, Kern, Eli Lilly, MSD, Otsuka, Pfizer, Sanofi, Shire, Takeda, Tillots. AMü has received speaker fees from Tillotts, Ferring, Eli Lilly, Falk Foundation, Jansson, Vifor; research support from Ferring.