Introduction

Microscopic colitis (MC) has been associated to various autoimmune diseases. Previous studies on the association between MC and psoriasis have focused on psoriasis as a risk factor for MC. Data from large scale cohort studies investigating the risk of future psoriasis in MC, however, are lacking.

Aims & Methods

We aimed to examine the association between MC and psoriasis by conducting a nationwide, population-based, matched cohort study in Sweden from 2007-2021. In total, we identified 8,404 patients with biopsy-verified MC (diagnosed in 2007-2017), 37,303 matched reference individuals, and 8,381 siblings without MC. Information on MC was obtained through the ESPRESSO cohort (a histopathology database containing data on all gastrointestinal biopsies in Sweden from 1965-2017). Data on incident psoriasis was gathered from the National Patient Register. Using Cox regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

During a median follow-up of 9.2 years (interquartile range=6.7-11.7), 179 MC patients and 440 reference individuals were diagnosed with psoriasis (241 vs 131 events per 100,000 person-years), corresponding to one extra case of psoriasis in 91 patients with MC followed for 10 years. After adjustment for the matching variables (birth year, sex, county of residence and calendar period) and level of education – as a proxy for socioeconomic status - we computed an aHR of 1.82 (95%CI=1.53-2.17). Stratifying by sex, estimates were similar and when examining the aHR across different lengths of follow-up, we found significantly elevated estimates up to 10 years after MC diagnosis. Compared to MC-free siblings, the aHR was 1.85 (95%CI=1.36-2.51).

Conclusion

Patients with MC are at an almost doubled risk of being diagnosed with psoriasis compared to the general population. Our findings suggest clinicians should consider psoriasis in MC patients with skin lesions.

Disclosure

Dr. Ludvigsson coordinates a study on behalf of the Swedish IBD quality register (SWIBREG). That study has received funding from the Janssen corporation. Dr Ludvigsson has also received financial support from MSD to develop a paper reviewing national healthcare registers in China. Dr. Ebrahimi has served as an advisory board member for Boehringer Ingelheim. AS has received consultancy fees from ICON plc, Abbvie, Novarits, and Eli Lilly. AS has received lecture fees from Janssen Cilag and UCB.

Clinical Case Summary

Crohn’s disease (CD) is a multi-factorial immune-mediated inflammatory condition of the gastrointestinal tract (GIT). While CD-related granulomas typically occur within the GIT, they can appear in other areas such as lymph nodes, mesentery, peritoneum, liver, and lungs. This case highlights a rare instance of renal granuloma secondary to CD and discusses an effective treatment approach. An 18-year-old male presented to a GP with a one-year history of abdominal pain. There was no significant medical or family history. Physical examination was unremarkable. Laboratory findings showed raised white cell count, elevated erythrocyte sediment rate, and renal dysfunction. He was referred to a nephrologist who noted additional symptoms of diarrhoea and occasional per-rectal bleeding with no significant improvement in symptoms or renal function after complete cessation of non-steroidal anti-inflammatory drugs. Renal biopsy confirmed acute interstitial nephritis and granuloma, therefore he was referred to a gastroenterologist to rule out CD or sarcoid. Colonoscopy showed pancolitis with rectal sparing and segmental biopsies revealed chronic colitis with granulomas confirming CD. Fecal calprotectin was raised. Further investigations ruled out autoimmune disease, tuberculosis and sarcoidosis as causes for renal impairment. Treatment involved steroid tapering followed by intravenous infliximab induction and maintenance therapy with subcutaneous injections fortnightly. Renal function and GIT symptoms improved with infliximab monotherapy, though dose escalation to weekly infliximab injections was required at seven months due to loss of response from subcutaneous infliximab. At one year, colonoscopy showed endoscopic remission, with ongoing improvement in renal function (creatinine 194 to 111 umol/L) and resolution of pyuria. In conclusion, we present a rare case of CD-associated interstitial nephritis, showing a positive clinical response to infliximab monotherapy.

References

1. Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68:s1-s106.
2. Eade MN, Cooke WT, Williams JA. Liver disease in Crohn's disease. Scand J Gastroenterol. 1971;6:199-204.
3. Whitehead R. Pathology of Crohn's disease. In: Kirsner JB, Shorter RG, eds. Inflammatory bowel disease. 2nd ed. Philadelphia: Lean and Febiger; 1980:296-310.

Disclosure

Nil

Introduction

Inflammatory bowel disease (IBD) is characterized by chronic inflammation due to an uncontrolled immune response orchestrated through, i.e. neutrophils. The basement membrane acts as a front-line defense promoting tissue integrity, where the α-3 chain of type IV collagen is solely expressed on the outermost layer of the mucosa. Detection of subclinical ulceration is crucial since early-stage IBD presents a unique window of opportunity for intervention, as the disease might become a self-sustaining process once deep inflammation becomes established. We therefore, wanted to develop a biomarker reflecting early tissue injury, aiding in the implementation of prompt treatment.

Aims & Methods

A competitive enzyme-linked immunosorbent assay quantifying a human neutrophil elastase (HNE) degraded fragment of type IV collagen α-3 chain was developed (C4A3-HNE). Dilution- and spiking recovery, inter- and intra-variability, and interference were evaluated. Acceptance criteria for technical validation were a recovery of 100% ±25 and an inter-intra variability of <15%. Commercial serum samples were purchased from ProteoGenex. Biological relevance was validated in an observational study from Odense University Hospital (OUH) and healthy controls. Groups were compared using Kruskal Wallis (Dunn‘s corrected).

Results

The technical validation of the C4A3-HNE assay demonstrated acceptable results for recovery, variation, and interference. Biological relevance was assessed in commercial IBD samples and healthy donors. C4A3-HNE was elevated in both CD and UC compared to healthy (p=0.001 and <0.0001)(AUC [95% CI]: 0.820 [0.669-0.971]; 0.875 [0.775-1.000]). The results were validated in an independent cohort of IBD patients (both p<0.0001). For UC, analysis showed that compared to patients in endoscopic remission, C4A3-HNE is elevated in patients with mild endoscopic activity, decreasing dose-dependently for moderate and severe disease (T1). Fecal calprotectin and CRP levels were also lower in IBD patients with high levels of C4A3-HNE (T1). With a cut-off value of 54.1 ng/ml, C4A3-HNE could significantly discriminate between mild and severe endoscopic disease (T1).

	Median conc. (ng/ml)	[IQR]	Patients (n)
Remission Mild Moderate Severe	61.16 71.77 56.07 40.52	49.74, 65.52 53.96, 79.17 39.21, 68.71 25.65, 69.01	10 18 19 10
	Low C4A3-HNE	High C4A3-HNE	Δ %
CD: Fecal Calprotectin (µg/g) UC: Fecal Calprotectin (µg/g) CD: CRP (mg/L) UC: CRP (mg/L)	721.8 840.0 8.4 7.4	365.7 491.6 6.5 5.0	67.7 52.3 26.5 38.5
	AUC [95% CI]	Cut-off value	Sens./Spec. (%)	OR
Remission vs. mild Mild vs. moderate Mild vs. severe	0.68 [0.48–0.85] 0.68 [0.51–0.83] 0.74 (*) [0.54–0.89]	68.8 59.9 54.1	61.1/90.0 72.2/73.3 77.8/70.0	14.1 (*) [1.7–166.6] 6.9 (*) [1.8–31.1] 6.4 (*) [1.2–33.5]

Conclusion

Our study demonstrates the biological and possible clinical relevance of the novel C4A3-HNE biomarker. The biomarker is elevated in patients with IBD compared with healthy, and high levels may reflect early mucosal damage in patients with UC. Furthermore, inflammatory markers were lower in IBD patients with high levels of C4A3-HNE, pointing towards high levels being indicative of early disease. C4A3-HNE may provide early detection of mucosal damage or prediction of relapse; however, further studies are required to assess the clinical validity of this biomarker.

Disclosure

MA, MP, MK, and JM are employees of Nordic Bioscience A/S. MK owns stocks in Nordic Bioscience A/S.

Introduction

Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Histological outcomes and the immune landscape were assessed in an UC patient cohort at baseline and after 8 weeks tofacitinib.

Aims & Methods

In this prospective study, 40 patients with moderate to severely active UC received tofacitinib 10 mg twice daily for 8 weeks. Clinical, endoscopic and histological outcomes were assessed at baseline and week 8 and colon biopsies were stained for JAK1-3, Tyrosine kinase 2 (TYK2) and Signal transducer and activator of transcription (STAT) 1-6 total protein expression using immunohistochemistry (IHC). Histological remission was defined as a Robarts Histopathology Index (RHI) ≤3 points without mucosal neutrophils and histological response as 50% decrease in RHI compared to baseline. Response was defined as histological remission and endoscopic Mayo score (EMS) ≤1 (histo-endoscopic mucosal improvement). Biopsies were scored by a blinded pathologist. Whole slide images with multiple biopsies per patients were stained using IHC, analyzed using automated cell detection (QuPath) and quantified in percentages by dividing the number of positive stained cells by the total number of cells on the slide. Outcomes were compared between responders and non-responders (NR).

Results

Out of 40 patients, 26 (65%) had severe endoscopic disease (EMS 3) with a median RHI of 14. Thirty-one patients (78%) had failed prior anti-Tumor Necrosis Factor (anti-TNF) agents and 18 (55%) failed vedolizumab. At week 8, 23 patients (58%) achieved histological remission, 34 (85%) histological response and 15 (38%) histo-endoscopic mucosal improvement. A significant decline in RHI compared to baseline was observed after 8 weeks both in responders (14 vs 0, p<0.001) and NR (15 vs 6, p=0.002). In the entire cohort, total STAT1 (p<0.001), STAT3 (p=0.002) and STAT5 (p=0.026) expression significantly decreased after 8 weeks treatment compared to baseline, which was not different between responders and NR (Table). However, responders to tofacitinib expressed significantly lower total STAT1 levels compared to NR at 8 weeks (p<0.001). Likewise, JAK2 (p=0.008) and total STAT2 expression (p=0.004) were significantly lower in responders compared to NR at 8 weeks, although no significant decrease compared to baseline was observed. A trend towards lower baseline JAK1, JAK2 and total STAT4 expression and higher total STAT6 expression was seen in responders compared to NR.

	Responders Baseline	NR Baseline	p-value Baseline Responders vs NR	Responders Week 8	NR Week 8	p-value Week 8 Responders vs NR
JAK1, median % [IQR]	6.2 [1.1-12.1]	13.7 [6.9-17.6]	0.113	8.4 [5.2-13.1]	9.7 [5.6-13.6]	0.811
JAK2, median % [IQR]	0.4 [0.1-2.1]	2.7 [0.1-7.7]	0.125	0.2 [0.1-1.7]	1.8 [0.6-8.6]	0.008
TYK2, median % [IQR]	13.3 [1.3-27.6]	10.0 [5.5-25.4]	0.761	11.9 [7.4-15.4]	17.5 [10.3-26.6]	0.156
STAT1, median % [IQR]	13.0 [5.2-24.9]	13.5 [7.5-22.0]	0.709	0.2 [0.1-1.8]*	4.3 [1.2-11.9**	<0.001
STAT2, median % [IQR]	0.3 [0.1-1.7]	0.7 [0.2-1.8]	0.393	0.3 [0.1-0.6]	0.8 [0.4-2.6]	0.004
STAT3, median % [IQR]	0.3 [0.0-6.7]	0.8 [0.1-6.6]	0.361	0.0 [0.0-0.2]	0.1 [0.0-1.0]**	0.106
STAT4, median % [IQR]	0.9 [0.3-2.4]	1.9 [0.4-3.3]	0.315	1.2 [0.5-3.2]	2.1 [1.4-3.9]	0.175
STAT5, median % [IQR]	0.1 [0.0-1.1]	0.2 [0.2-1.3]	0.235	0.0 [0.0-0.3]	0.2 [0.0-0.9	0.159
STAT6, median % [IQR]	23.6 [4.2-28.8]	17.4 [7.6-32.1]	0.455	14.1 [5.3-45.7]	22.1 [10.9-32.5]	0.472

Table legend: IQR, interquartile range; * statistically significant decrease after 8 weeks compared to baseline in responders; ** statistically significant decrease after 8 weeks compared to baseline in NR.

Conclusion

Tofacitinib resulted in histological response in the majority of UC patients and led to a substantial decline of total STAT1, STAT3 and STAT5 expression both in responders and NR. Yet, after 8 weeks significantly lower total STAT1 levels were observed in responders compared to NR. Responders tended to express lower JAK1, JAK2 and total STAT4 and higher total STAT6 levels at baseline.

Disclosure

This study was funded and supported by Pfizer.

Introduction

The LIR!C trial demonstrated that laparoscopic ileocaecal resection (ICR) is a cost-effective alternative to infliximab therapy (IFX) in patients with uncomplicated ileocaecal Crohn’s disease (CD), with comparable quality of life outcomes. The aim of this study was to assess the 10-year follow-up of patients enrolled in the LIR!C trial.

Aims & Methods

This retrospective follow-up study included patients from the original LIR!C trial, a multicentre randomized controlled trial comparing ICR to IFX treatment in patients with ileal CD. Long term follow-up data were collected between February 3 and April 14, 2025. Data extraction was focused on initiation or switch of IBD treatments (corticosteroids, immunomodulators and/or advanced medical therapies) and (re)-resections. The follow-up period ranged from trial enrolment to the last visit with the gastroenterologist or surgeon. Primary outcomes were: (1) proportion of patients in clinical remission without therapy switch (no medical therapy or re-resection in the ICR group, and continuation or the cessation of IFX in case of remission in the IFX group), and (2) therapy-free remission, defined as clinical remission without IBD medication and (re)resections.

Results

Follow-up data were available from 60 ICR patients and 57 IFX patients (87% of 134 patients originally included). The median follow-up time was 12 years (IQR 9-14). The clinical remission rate without therapy switch was 40% in the ICR group compared to 26.3% in the IFX group (p=0.117). Of the 60 ICR patients, 24 (40%) had no additional therapy, 13 (21.7%) received an immunomodulator, 18 (30%) biological therapy and 5 (8.3%) underwent a second resection after biological treatment. In the IFX group, 33 (57.9%) required an ICR of whom 25 (75.8%) had previously received second-line biological treatment. Additionally, 7/57 patients (12.3%) were therapy free, 8 (14%) continued IFX treatment, 6 (10.5%) received other biological treatment, and 3 (5.3%) switched to an immunomodulator. Therapy-free remission was significantly higher in the ICR group when compared to the IFX group (40% vs 12%, p < 0.001).

	ICR group (N=60)	IFX group (N=57)
Total follow-up time (y), median (ICR)	11 (9-14)	13 (9-15)
Prophylactic immunomodulator usage, n (%)	26 (43.3)	35 (61.4)
			P-values
Clinical remission, n (%)	24 (40)	15 (26.3)	0.117
Therapy-free remission, n (%)	24 (40)	7 (12.3)	<0.001
(Re-)resection, n (%)	5 (8.3)	33 (57.9)	<0.001

Conclusion

After 10 years of follow-up, the clinical remission rate without therapy switch was comparable between both groups, highlighting the long-term durability of both treatment approaches. The majority of IFX patients needed ICR within 10 years of follow-up. 40% of the ICR group did not require any additional therapy further supporting ICR as first-line treatment option in ileal CD.

References

Ponsioen, C. Y., de Groof, E. J., Eshuis, E. J., Gardenbroek, T. J., Bossuyt, P. M. M., Hart, A., Warusavitarne, J., Buskens, C. J., van Bodegraven, A. A., Brink, M. A., Consten, E. C. J., van Wagensveld, B. A., Rijk, M. C. M., Crolla, R. M. P. H., Noomen, C. G., Houdijk, A. P. J., Mallant, R. C., Boom, M., Marsman, W. A., Stockmann, H. B., … LIR!C study group (2017). Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial. The lancet. Gastroenterology & hepatology, 2(11), 785–792. https://doi.org/10.1016/S2468-1253(17)30248-0

Disclosure

GD'H served as a consultant for AbbVie, Alimentiv, AstraZeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Exeliom Biosciences, Johnson & Johnson, Pfizer, and Takeda; and has received speakers bureau fees from AbbVie, Eli Lilly, Pfizer, Bristol Myers Squibb, and Takeda.

Introduction

Acute severe colitis (ASC) is an important cause of morbidity and mortality in Ulcerative Colitis (UC), requiring hospitalisation and, frequently, colectomy. Intravenous corticosteroids (CS) remain the first-line medical treatment. Approximately 40% of episodes of ASC do not respond to this treatment and require rescue therapy with ciclosporin (CIC) or infliximab (IFX)¹. In the past decades, these treatments and protocol-driven management algorithms led to reduced mortality and colectomy rates. A simple clinical scoring system (the Admission Model for the Intensification of Therapy in Acute Severe Colitis (ADMIT-ASC))³, based on CRP, albumin, and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score, was recently developed to predict the steroid response on admission.

Aims & Methods

We aimed to retrospectively assess the steroid non-response during admission with ASC and the usefulness of the new prognostic clinical index ADMIT-ASC at admission to predict steroid response in a Belgian tertiary center. All patients admitted with ASC between 1^st January 2015 and 1^st April 2023 were identified from our inflammatory bowel disease database at Erasme University Hospital. Inclusion criteria were ASC patients admitted at the hospital, standard treatment with at least 3 days of intravenous CS and endoscopy evaluation upon admission. ASC was defined according to modified Truelove and Witts’ criteria as ≥6 bloody stools/day with one or more markers of systemic disturbance (tachycardia >90 beats/min, temperature >37.8°C, haemoglobin <105 g/L or CRP >30 mg/L). Steroid non-response was defined as the need for medical rescue therapy (CIC of IFX) or colectomy during the admission. ADMIT-ASC index consists of four points: CRP ≥100 mg/L (1 point), albumin ≤25 g/L (1 point) and UCEIS score ≥4 (1 point) or ≥7 (2 points).

Results

Table I Admission Demographics data (n= 84)	Steroid response (n=49)	Steroid non-response (n=35)	P value
Median disease duration (years) (IQR)	3.6 (0.3-0.9)	2.1 (0.8-5.5)	0.5
Montreal Classification	E1 : 5/49 (10%) E2 : 20/49 (41%) E3 : 24/49 (49%)	E1 : 0/35 E2 : 12/35 (34%) E3 : 23/35 (66%)	0.084
5-ASA, n (%)	22 (45%)	10 (29%)	0.13
Methotrexate or thiopurine, n (%)	6 (12%)	9 (26%)	0.11
Infliximab, n (%)	4 (8.2%)	8 (23%)	0.058
Vedolizumab, n (%)	7 (14%)	5 (14%)	>0.9
Tofacitinib, n (%)	2 (4.1%)	2 (5.7%)	>0.9
Readmission, n (%)	12 (24%)	10 (29%)	0.7
5-ASA, 5-aminosalicylate P values from Wilcoxon rank-sum test or Fisher’s exact test.

Out of 127 patients admitted with UC and treated with intravenous CS during three days, 84 (45% male, median age of 31 years old) were included in the study. Admission demographics and clinical characteristics are described in Table 1.
For 17 patients (20%), the admission was their index presentation of UC. Response to CS was seen in 49 patients (58%). Thirty-three patients (39%) received medical rescue therapy (17/33 IFX and 16/33 CIC). Colectomy rate during admission was 13% after a median duration of 18 days (IQR: 16-54). Admission C reactive protein (CRP) (p=0.036), albumin (p=0.026) and UCEIS scores (p=0.022) were significantly associated with steroid non-response. Patients scoring 0, 1, 2, 3 and 4 had steroid response rates of 90%,75%, 55%, 19% and 0%, respectively. Scoring of ≥3 was 75% (95% CI, 0.43 to 0.95) predictive of steroid failure (OR 5.08, 95%, CI 1.38 to 24.5).

Conclusion

In this tertiary referral cohort study, we confirmed that the ADMIT-ASC index is a simple clinical tool that can be used on the day of admission to predict steroid non-response in ASC with a threshold of ≥3 to identify patients who are unlikely to respond to intravenous CS and enabling timely treatment escalation or surgery.

References

1. Travis S, Satsangi J, Lémann M. Predicting the need for colectomy in severe ulcerativecolitis: a critical appraisal of clinical parameters and currently available biomarkers. Gut 2011;60:3–9.
2. Travis SP, Farrant JM, Ricketts C, et al. Predicting outcome in severe ulcerative colitis.Gut 1996;38:905–10.
3. Adams A, Gupta V, Mohsen W, et al. Gut 2023;72:433–442.

Disclosure

VB has not disclosure.
CDT has not disclosure.
CM has not disclosure.
AC has received lecture fees from Galapagos, Abbvie, Janssen, celltrion, Pfizer, Takeda.
DF has received lecture fees from Abbvie, Astrazeneca, Dr.Falk Pharma, Ferring, Janssen, Mundipharma, MSD, Pfizer, Takeda, Amgen, and advisory board fees from Abbvie, Janssen,Takeda, Celltrion, Amgen.
CL has received consultancy fees from Janssen, Abbvie, Takeda and Galapago and speaker fees from Sandoz, Janssen, Abbvie