A0381 - Biomarkers for the Evaluation of Pouch Inflammation: A Systematic Review

Sunday, October 23, 2022

5:00 PM – 7:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Katherine Falloon, MD

Cleveland Clinic
Cleveland, OH

Katherine Falloon, MD¹, Benjamin Cohen, MD¹, Ronald Ottichilo, PhD¹, David Grove, PhD¹, Florian Rieder, MD², Taha Qazi, MD¹
¹Cleveland Clinic, Cleveland, OH; ²Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH

Introduction: Pouch inflammation is a common problem following ileal pouch anal anastomosis (IPAA). Despite its high prevalence, diagnosis remains multimodal and requires endoscopic assessment. The use of biomarkers in this setting has not been well characterized. We performed a systematic review to summarize the evidence for use of biomarkers in the evaluation of pouch inflammation.

Methods: A search of Ovid, MEDLINE, Cochrane Library, EMBASE, and Web of Science was conducted. Inclusion criteria included studies in the English language that evaluated biomarkers for the evaluation and prediction of inflammation in patients with IPAA utilizing pouchoscopy as the gold standard for diagnosis. Exclusion criteria included studies on the role of the microbiome and/or genetic markers as well as studies in non-human subjects.

Results: 28 studies, five case control and 23 observational cohort studies, were identified (Figure 1). Fecal biomarkers were assessed in 23 studies. Fecal calprotectin was the most commonly studied stool biomarker with sensitivities ranging from 57 to 100% and specificities from 69 to 92% (Table 1). Six studies examined serum biomarkers. None of the serum biomarkers demonstrated high sensitivity or specificity in association with pouch inflammation. Six studies described the longitudinal assessment of biomarkers. Of these studies, only three reported a predictive role of biomarkers in diagnosing endoscopic inflammation.

Discussion: Biomarkers have emerged as a potential option to help improve the management of pouchitis given the relative ease of sampling compared to endoscopy. Unfortunately, the evaluated biomarkers have not consistently demonstrated accuracy in predicting inflammation. Moreover, these biomarkers have not been reliably shown to be sensitive or specific in association with endoscopic pouch inflammation to merit their widespread use in clinical practice. Hence, identification of novel, validated biomarkers for pouchitis is a research priority.

Figure: Figure 1: PRISMA Diagram of Included Studies

Author	Year	Study Design	Patient Number	Median Age (range)	Pre-Operative Diagnosis	Pouchitis Definition	Biomarker	Cut-Off (μg/g)	Association Between Biomarker and PDAI	Sensitivity (%)	Specificity (%)
Thomas	2000	Prospective Cohort	24	NP	UC (16) FAP (8)	Macroscopic inflammation and histologic inflammation	Fcalpro	NP	All patients with inflammation had elevated fcalpro	NP	NP
Pronio	2016	Prospective Cohort	40	52 (33-71)	UC	PDAI ≥7	Fcalpro	66.2 37.6	Endoscopy subscore: NP Total PDAI: r=0.55 p=0.002 AUC: 0.832	85 92	38 19
Johnson	2009	Prospective Cohort	54	47	UC (46) FAP (8)	PDAI ≥7	Fcalpro	92.5	Endoscopy subscore: r=0.605 p< 0.0001 Total PDAI: r=0.71 p<0.001	90	76.5
Farkas	2015	Prospective Cohort	33	NP (30-40)	UC (46) FAP (8)	PDAI ≥7	Fcalpro	262	Endoscopy Subscore: Significant association with p=0.0001 Total PDAI: AUC=0.78	67	89
Pakarinen	2010	Prospective Cohort	32	24 (17-31)	UC	Histologic neutrophil count and episodes of pouchitis	Fcalpro	300	Histologic neutrophil count: r=0.715 p< 0.001 Episodes of pouchitis: r=0.457 p< 0.01	57	92
Ollech	2021	Prospective Cohort	156	43 (35-58)	UC	Endoscopic PDAI ≥5	Fcalpro	462	Severity of pouchitis: r=0.526 p=0.0017	66.7	82.4

Table: Table 1: Association of Fecal Calprotectin with Pouch Inflammation
Legend: NP=not provided, UC = ulcerative colitis, FAP=familial adenomatous polyposis, fcalpro = fecal calprotectin, PDAI=pouchitis disease activitiy, index

Disclosures:

Katherine Falloon: Crohn's and Colitis Foundation – Grant/Research Support.

Benjamin Cohen: Abbvie – Speakers Bureau. Abbvie, Celgene- Bristol Myers Squibb, Pfizer, Sublimity Therapeutics, Takeda, TARGET RWE – Advisory Committee/Board Member, Consultant. Cornerstones, Vindico – CMECompanies. Pfizer – Grant/Research Support.

Ronald Ottichilo indicated no relevant financial relationships.

David Grove indicated no relevant financial relationships.

Florian Rieder: 89Bio – Advisory Committee/Board Member, Consultant. AbbVie – Advisory Committee/Board Member, Consultant. Adnovate – Advisory Committee/Board Member, Consultant. Agomab – Advisory Committee/Board Member, Consultant. Allergan – Advisory Committee/Board Member, Consultant. Arena – Advisory Committee/Board Member, Consultant. Boehringer-Ingelheim – Advisory Committee/Board Member, Consultant. CDISC – Advisory Committee/Board Member, Consultant. Celgene/BMS – Advisory Committee/Board Member, Consultant. Cowen – Advisory Committee/Board Member, Consultant. Ferring – Advisory Committee/Board Member, Consultant. Galapagos – Advisory Committee/Board Member, Consultant. Galmed – Advisory Committee/Board Member, Consultant. Genentech – Advisory Committee/Board Member, Consultant. Gilead – Advisory Committee/Board Member, Consultant. Gossamer – Advisory Committee/Board Member, Consultant. Guidepoint – Advisory Committee/Board Member, Consultant. Helmsley – Advisory Committee/Board Member, Consultant. Horizon Therapeutics – Advisory Committee/Board Member, Consultant. Image Analysis Limited – Advisory Committee/Board Member, Consultant. Index Pharma – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant. Koutif – Advisory Committee/Board Member, Consultant. Mestag – Advisory Committee/Board Member, Consultant. Metacrine – Advisory Committee/Board Member, Consultant. Morphic – Advisory Committee/Board Member, Consultant. Organovo – Advisory Committee/Board Member, Consultant. Origo – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Pliant – Advisory Committee/Board Member, Consultant. Prometheus Biosciences – Advisory Committee/Board Member, Consultant. Receptos – Advisory Committee/Board Member, Consultant. RedX – Advisory Committee/Board Member, Consultant. Roche – Advisory Committee/Board Member, Consultant. Samsung – Advisory Committee/Board Member, Consultant. Surmodics – Advisory Committee/Board Member, Consultant. Surrozen – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant. Techlab – Advisory Committee/Board Member, Consultant. Theravance – Advisory Committee/Board Member, Consultant. Thetis – Advisory Committee/Board Member, Consultant. UCB – Advisory Committee/Board Member, Consultant. Ysios – Advisory Committee/Board Member, Consultant.

Taha Qazi: Abbvie – Advisory Committee/Board Member, Consultant, Speakers Bureau. Bristol Meyers – Advisory Committee/Board Member, Speakers Bureau. Iterative Scopes – Advisor or Review Panel Member. Janssen – Speakers Bureau.

Katherine Falloon, MD¹, Benjamin Cohen, MD¹, Ronald Ottichilo, PhD¹, David Grove, PhD¹, Florian Rieder, MD², Taha Qazi, MD¹. A0381 - Biomarkers for the Evaluation of Pouch Inflammation: A Systematic Review, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.