Introduction

Due to lack of published data on ustekinumab (UST) use in Greece, REASSURE study aimed to generate real-world evidence (RWE) on treatment persistence, and patient-reported outcomes (PROs) in patients with Crohn’s Disease (CD).

Aims & Methods

REASSURE was a non-interventional, 24-month prospective study of adult (18-80 years old) CD patients newly initiated on UST as 1st, 2^nd, or 3rd biologic therapy per the approved label in Greece. Data were collected by routine assessments, including Harvey-Bradshaw Index (HBI), and PROs at baseline (start of UST) and at 4 follow-up visits at 6-month intervals, with a final visit at Month 24 (±2 months) or at treatment discontinuation (whichever occurred first). PROs included the validated Greek version of the Inflammatory Bowel Disease Questionnaire (IBDQ), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale and the Work Productivity and Activity Impairment Questionnaire in Crohn's Disease (WPAI:CD). PROs at 24 months are presented herein.

Results

Between Apr/2019 and Feb/2021, 169 eligible patients were enrolled in 19 Gastroenterology Clinics in Greece. The median (IQR) age at baseline was 45.0 (35.0-54.0) years; of the evaluable patients, 17.5% were overweight, 49.0% had tertiary level of education, and 68.5% were ever-smokers. In terms of employment, 43.4% (72/166) of patients were employed, 29.5% (49/166) unemployed (due to CD in 21.6%; 8/37), 16.3% (27/166) retired (due to CD in 24.0%; 6/25), and 10.8% (18/166) reported other status. Among UST treated patients, 35.5% were bio-naïve (BN) and 64.5% were bio-experienced (BE).
Median (IQR) duration of study participation was 23.9 (18.3-24.7) months (median treatment duration: 24.0 months). At 24 months, 72.8% (123/169) [BN: 76.7% (46/60); BE: 70.6% (77/109)] remained on treatment with UST, while 21.9% (37/169) had discontinued UST after a mean (SD) of 10.2 (6.4) months mainly due to lack/loss of response (15/37), safety issues (10/37), or loss to follow-up (6/37). The proportion of evaluable patients in remission (HBI score 0-4) at 24 months was 87.7% (100/114) [BN: 90.7% (39/43); BE: 85.9% (61/71)].
Baseline median IBDQ (170.0), FACIT-F (34.0), WPAI:CD work productivity loss (WPL) (30.0) and activity impairment scores (30.0) significantly improved (P<0.01) at 24 months, with median changes of 24.0, 6.0, -20.0, and -20.0, respectively, among paired observations. Significant improvements were also noted based on imputed data and in both bio-naive and bio-experienced patients. At 24 months, among patients with paired observations, 56.8% achieved an IBDQ response (≥16-point increase), 59.3% a significant FACIT-F improvement (≥4-point increase) and 68.4% a clinically meaningful improvement in WPL (≥7-point decrease) from baseline. Further details on baseline characteristics and 24-month PROs are shown in Table 1.

Conclusion

These data provide RWE on the beneficial effect of UST on health-related quality of life, fatigue, and work productivity in both bio-naïve and bio-experienced CD patients in Greece.

Disclosure

This study was sponsored by Janssen - Cilag, Greece.
Giorgos Bamias Advisor/lecturer for Janssen, Pfizer, Takeda, Abbvie, MSD, Mylan, Genesis Pharma, Adacyte Therapeutics, Amgen, Ferring, Cooper, BMS; Funding (Grants/Honoraria): Pfizer, Takeda, Abbvie, Aenorasis; Research/Clinical Trials: Abbvie, Takeda, Janssen.
Gerassimos J. Mantzaris has received consultant and/or speaker fees from AbbVie, MSD, Celtrion,Ferring, Aenorasis, Janssen, Pfizer, Takeda, Falk Pharma, and Vianex and research support from AbbVie, Ferring, MSD, and Vianex
Maria Tzouvala has received clinical research funding from Janssen-Cilag Pharmaceuticals SACI, Takeda HELLAS SA, AbbVie Pharmaceuticals S.A. Consulting and/or speaking fees MSD Sharp& Dohme, Janssen-Cilag Pharmaceuticals SACI, Takeda, AbbVie Pharmaceuticals S.A, Pfizer, Amgen. Advisory boards: Janssen-Cilag Pharmaceuticals SACI, Takeda, AbbVie Pharmaceuticals S.A, Pfizer, Amgen
Dimitrios Christodoulou has received consulting and speaking fees for Janssen, MSD, Galenica. Advisory Board for Galenica
Ioannis Koutroubakis has received clinical research funding: Abbvie, Faran, Ferring, Pfizer, Viatris, Vianex, Vifor, Unipharma. Consulting and/or speaking fees Abbvie, Genesis, Janssen, MSD, Takeda, Vianex. Advisory boards: Abbvie, Janssen, MSD, Pfizer, Takeda, Vianex
Christos Liatsos has received clinical research funding from: Janssen, and consulting and/or speaking fees from: MSD, Pfizer, Boston SCI, Amgen, Galenica.
Georgios Papatheodoridis Clinical research funding: Abbvie, Gilead, Takeda, Vianex. Consulting and/or speaking fees: Abbvie, Astra-Zeneca, BioARS Therapeutics, Elpen, Genesis, Gilead, GlaxoSmithKline, Ipsen, Novo Nordisk, Roche, Sobi. Advisory boards: Abbvie, Astra-Zeneca, Albireo, Amgen, Galenica, Genesis, Gilead, GlaxoSmithKline, Ipsen, Janssen, Novo Nordisk, Roche, Takeda
Dr Katsanos Konstantinos received honoraria for consulting services (educational services, scientific articles, participation in Advisory Boards, clinical trials, lecture fees, other) from the companies as follows:AbbVie, AMGEN, ENORASIS, Epsilon Health, Ferring, Genesis, Grifols S.A., JANSSEN, MSD, Mylan, Shire and Takeda.
Evanthia Zampeli has received clinical research funding: Janssen, TAKEDA, ABBVIE. Consulting and/or speaking fees: Janssen, TAKEDA, BMS, AMGEN, MYLAN. Advisory boards: BMS, GALENICA
Georgios Germanidis has received clinical research funding from Janssen.
Konstantinos Soufleris Consulting and/or speaking fees: AbbVie, Janssen, MSD, Pfizer, Takeda. Clinical research funding:Pfizer. Advisory board: BMS, Galenica.
Matina-Lydia Chatzinikolaou has received consulting fees from Abbvie, Takeda, Amgen, Ferring, Janssen
George Kokkonis has received clinical Research funding from Janssen and speaking fees from Janssen and Amgen
Alexandros Boubonaris has served as advisory board member for Amgen, Takeda
Marios Giakoumis has received clinical research funding from Janssen
Artemis Trikola has received clinical research funding from Janssen
George Michalopoulos has received speaker fees: Takeda, MSD, , Abbvie, Jannsen, Pfizer, Amgen
Vasileios Delis, Konstantina Paraskeva, Theodosios Sdonas, Athanasia Tasovasili, Evgenia Papathanasiou, Maria Palatianou, Andreas Nakos, Nikoletta Mathou, George Kalopitas, Panagiotis Giannelis, Kalliopi Foteinogiannopoulou, Konstantina Chalakatevaki, Eleni Beka, Evmorfia Karamintziou, Eleftheria Giannakoulopoulou have no conflicts to disclose.
Konstantinos Thomopoulos, Stergios Vradelis, Andreas Protopapas, Ioannis Pachiadakis, Ioannis Goulis, Pantelis Karatzas, George Theocharis, George Tribonias, Angeliki Machaira, Nikolaos Kyriakos, Adonis Protopapas, Konstantinos Fasoulas, Evdoxia Stergiou and Charilaos Taloumtzis have not disclosed any conflicts
Spyridon Michopoulos has received clinical research funding from Janssen, Takeda, BMS, consulting and/or speaking fees from Takeda, and has served as advisory board member for Takeda.
Christos Gkamaloutsos, Ioannis Kanistras and Aikaterini Mpartsea are employees of Janssen - Cilag, Greece

Introduction

Ileocolonoscopy and Rutgeerts endoscopic score (RS) remains the gold standard to evaluate post-operative recurrence (POR) in Crohn's disease (CD). Intestinal ultrasound (IUS) is proposed as a non-invasive alternative for the diagnosis of POR, with a sensitivity of 89%, specificity of 86% and area under curve (AUC) of 0.93 (1). Bowel wall thickness (BWT) alone has a high accuracy in the diagnosis of POR and it is proposed that the association of other parameters such as hyperemia, loss of bowel wall stratification, involvement of mesenteric fat (i-fat) or ultrasound scores, increases sensitivity and specificity in the diagnosis of POR (2).

Aims & Methods

The aim of this study is to assess whether IUS parameters and ultrasound scores correlate with endoscopy in the diagnosis of POR. A unicentric retrospective study was performed. There were included patients with CD with both an ileocolonoscopy and intestinal ultrasound performed for the detection of POR, the time between tests was less than 6 months or there was no therapeutic change between tests.
Endoscopic POR was evaluated with Rutgeers score (RS), RS i0 and i1 was considered no POR and RS ≥i2a was POR. The IUS parameters were: BWT, Limberg Score, bowel wall stratification, inflammation of mesenteric fat, Simple US Score, SUS-CD and IBUS-SAS score.

Results

129 patients were included, baseline characteristics are in Table 1. In 108 patients (83.7%) the time between test was <6 months and in 21 (16.3%) >6 months without therapeutic changes. 38 (29.7%) were classified as endoscopic POR (RS i0 – i1) and 90 (69.8%) as POR: 28 (21.2%) i2a, 17 (13.3%) i2b and 45 (35.1%) severe (RS i3 – i4). With IUS, 42 patients (32.6%) were classified as no POR and 87 (67.4%) as POR. The mean BWT by IUS in patients without endoscopic POR was 2.6 mm (SD +/- 1.2) versus 4.8 (SD +/- 1.6) in patients with RS ≥i2a (p 0.001). BWT ≥3 had a sensitivity of 86.6%, specificity 78.9% and AUC of 0.83 in the diagnosis of POR. Hyperemia (Limberg ≥1) was present in 75 patients (84.3%) with RS ≥i2a versus in 8 patients (21.1%) without endoscopic POR (p 0.001). 21 patients (23.9%) of patients with RS ≥i2a presented loss of bowel wall stratification versus 0 (0%) with i0-i1 (p 0.001). I-fat was present in 16 patients (12.4%), all of them RS ≥i2a (p 0.02).
The mean results of IUS scores were: Simple Us score 5.6 (SD +/- 2.9), SUS-CD 2.1 (SD +/- 1.8) and IBUS-SAS 31.6 (SD +/- 23.3). In patients without endoscopic POR the mean result of Simple US Score was 3.0 (SD +/- 2.0) versus 6.7 (SD +/- 2.4) in RS ≥i2a (p>0.05). The mean result of SUS-CD without POR was 0.5 (SD +/ 1.0) versus 2.8 (SD +/- 1.5) in POR (p>0.05). In IBUS-SAS the mean result in RS i0-i1 was 13.4 (SD +/- 10.8) versus 39.2 (SD +/- 22.9) in RS ≥i2a (p>0.05). Simple US Score showed an AUC of 0.85 in the diagnosis of POR (95% CI 0.78 – 0.92), SUS-CD of 0.87 (95% CI 0.81 – 0.93) and IBUS-SAS of 0.85 (95% CI 0.77 – 0.92).

Conclusion

In our experience, IUS parameters such as BWT, Limberg score, loss of wall stratification, i-fat and IUS scores (IBUS-SAS, SUS-CD and Simple US Score), have a high accuracy in the diagnosis of POR.

References

1. Barchi, Alberto et al. “Recent advances in the use of ultrasound in Crohn's disease.” Expert review of medical devices vol. 20,12 (2023): 1119-1129. doi:10.1080/17434440.2023.2283166
2. Yung, Diana E et al. “Capsule Endoscopy, Magnetic Resonance Enterography, and Small Bowel Ultrasound for Evaluation of Postoperative Recurrence in Crohn's Disease: Systematic Review and Meta-Analysis.” Inflammatory bowel diseases vol. 24,1 (2017): 93-100. doi:10.1093/ibd/izx027

Introduction

Autoimmune atrophic gastritis (AAG) leads to significant changes in the gastric mucosa, including hypo-achlorhydria and increased gastrin (G) levels, providing proliferative stimuli on the gastric mucosa (1-5).

Aims & Methods

The aim of our study is to evaluate the occurrence and characteristics of gastric polyps in AAG patients across six tertiary centers in Italy. We conducted a multicentric, cross-sectional study from January to June 2023, prospectively enrolling consecutive patients diagnosed with AAG, from January 2000 to June 2023, who underwent at least one endoscopy. Data on demographics, clinical history, biochemical profiles, serological data, and endoscopic and histopathological findings were collected.

Results

Among 612 AAG patients (73.9% female, median age 66) followed up for a median of 4 (IQR 2-7.5) years, 222 (36.3%) had at least one gastric polyp. Non-endocrine polyps (214) were found in 162 patients, including 151 (70.5%) inflammatory, 29 (13.6%) adenomatous, 18 (8.4%) fundic gland polyps, 13 (6.1%) adenocarcinomas, and one MALT lymphoma. Additionally, 108 patients (48.6% of the population with polyps and 17.6% of the overall AAG patients) presented with gastric neuroendocrine neoplasms (gNENs), 48 of whom also had non-endocrine polyps. The median polyp size was 4 (IQR 2-7) mm. Older age, smoking prevalence, and higher levels of G and chromogranin A (CgA) were associated with polyp presence. No significant differences in OLGA/OLGIM stages or H. pylori status were noted between patients with and without polyps.

Conclusion

This study represents the largest multicentric cohort of AAG patients, highlighting the significant presence of gastric polyps, including gNENs and various non-endocrine types including a not negligible proportion of patients who showed gastric adenocarcinoma. These results emphasize the importance of proactive endoscopic monitoring and comprehensive histopathological evaluation in patients with AAG, to effectively identify and manage these different gastric lesions.

References

1. Zhang H, Jin Z, Cui R, Ding S, Huang Y, Zhou L. Autoimmune metaplastic atrophic gastritis in chinese: a study of 320 patients at a large tertiary medical center. Scand J Gastroenterol. 2017;52(2):150-6.
2. Krasinskas AM, Abraham SC, Metz DC, Furth EE. Oxyntic mucosa pseudopolyps: a presentation of atrophic autoimmune gastritis. Am J Surg Pathol. 2003;27(2):236-41.
3. Kishino M, Nonaka K. Endoscopic Features of Autoimmune Gastritis: Focus on Typical Images and Early Images. J Clin Med. 2022;11(12).
4. Park JY, Cornish TC, Lam-Himlin D, Shi C, Montgomery E. Gastric lesions in patients with autoimmune metaplastic atrophic gastritis (AMAG) in a tertiary care setting. Am J Surg Pathol. 2010;34(11):1591-8.
5. Massironi S, Elvevi A, Gallo C, Laffusa A, Tortorella A, Invernizzi P. Exploring the spectrum of incidental gastric polyps in autoimmune gastritis. Dig Liver Dis. 2023.

Introduction

Crohn’s disease (CD) is characterized by discontinuous inflammation. Failure to identify skipping lesions of the terminal ileum (TI) or transmural changes can lead to incorrect management.

Aims & Methods

Eligible adult patients with CD undergoing ileo-colonoscopy and computed tomography enterography (CTE) or magnetic resonance enterography (MRE) within six months. We determined the prevalence of endoscopic skipping (normal ileum on colonoscopy but proximal small bowel inflammation on cross-sectional imaging), skip lesions (discontinuous inflammation along the gastrointestinal tract identified on cross-sectional imaging), and penetrating complications.

Results

Among 202 patients, 45 (22.3%) had endoscopic skipping proximal to TI intubation. Fifty patients (24.5%) had small bowel skip lesions, primarily in the ileum. Strictures were identified in 34 patients (16.8%) through both imaging and ileo-colonoscopy, in 21 patients (10.4%) solely through cross-sectional imaging, and in 3 patients (1.5%) solely through ileo-colonoscopy. Approximately 63.8% of stricturing cases would be missed without cross-sectional imaging. Penetrating complications, including abscesses (2.5%) and various fistula types (4.9%), were detected in 15 (7.4%) patients.

Table. Comparison between patients who had active Crohn’s disease with and without abnormal TI on colonoscopy

Conclusion

Ileo-colonoscopy missed detection of active CD in approximately one-fifth of cases due to more proximal disease location. Stricturing disease would be missed in more than half of cases if cross-sectional imaging was not performed.

Disclosure

Virginia Solitano no conflict of interests.
Sudheer Kumar Vuyyuru has received consultancy fees from Alimentiv Inc.
Achuthan Aruljothy no conflict of interests.
Maan Alkhattabi has received consulting fees from Janssen. Speaker’s fees from Janssen, Takeda & Pfizer.
Melanie Beaton has received advisory board fees from AbbVie, Astra Zeneca, Gilead,
Janssen, Novo Nordisk, Lupin, Pfizer and Takeda.
Jamie Gregor has no conflict of interests.
Zahra Kassam has received Bayer Pharmaceuticals speaker honorarium and research grant, Fusion MD speaker fees, Alimentiv Inc consulting fees.
Rocio Sedano has received consultancy fees from Alimentiv Inc.
Harry Marshall has no conflict of interests,
Darryl Ramsewak has no conflict of interests.
Michael Sey has received consultant fees from Medtronic; Research grants and speaker fees from Pendopharm; Educational grant from Cook Medical.
Vipul Jairath has received consultancy/advisory board fees from AbbVie, Alimentiv Inc., Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert, Ventyx, and Vividion; and speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, and Fresenius Kabi.

Introduction

Few population-based studies have investigated the long-term surgery rates of Crohn’s disease (CD). The present study is a continuation of the Veszprem IBD population based cohort with a follow-up since 1977.

Aims & Methods

Our aim was to analyze the long-term disease course and surgery rates over different therapeutic eras in a prospective population-based database from Veszprem Province, including incident CD patients. Patient inclusion was between January 1, 1977 and December 31, 2018; follow-up ended December 31, 2020. Both in-hospital and outpatient records were collected and comprehensively reviewed at diagnosis and during clinical follow-up. Immunomodulators became widespread in Hungary from the mid-1990s, while biological therapies have been covered by the National Health Insurance Fund since 2008. Surgery rates were examined in three different eras based on time of diagnosis: cohort-A, 1977-1995; cohort-B, 1996-2008; and cohort-C, 2009-2018.

Results

Data of 946 incident CD patients were analyzed (male/female: 496/450; median age at diagnosis:28 years(y) [IQR: 22-40]), with a median of 15y(IQR 9-21) follow-up. Overall immunosuppressive therapy use was increasing by time (48.0%/62.4%/65.5%), as well as the probability of biological therapy initiation within 5 years of diagnosis (0.0±0%/7.3±1.2%/22.7±2.2%) in cohorts A/B/C. The probability of disease behavior progression from luminal (B1) disease to stenosing or penetrating phenotype (B2/B3) was significantly decreasing (27.1±SD5.3%/ 21.5±2.5%/11.3±2.2% in cohorts A/B/C after 5 years [pLogRank<0.001]). The probability of first resective surgery between cohorts A/B/C were 33.3±3.8%/26.5±2.1%/28.1±2.4% after 5 years; 46.1±4.1%/32.6±2.2%/33.0±2.7% after 10 years; and 59.1±4.0%/41.4±2.6% (cohorts A/B) after 20 years. There was a significant decrease in surgery risk between cohorts A and B [pLog Rank=0.002]. Surgery risk remained similar between cohorts B and C [pLog Rank=0.665]. The cumulative probability of re-resection in cohorts A/B/C was also decreasing (17.3±4.1%/12.6±2.6%/4.7±2.0% after 5 years [pLog Rank=0.001]). A cox-regression multivariate analysis showed that stenosing or penetrating disease (B2/B3) behavior (HR 4.52; 95%CI 3.60-5.68; p<0.001) and ileal (L1) location at diagnosis (HR 1.30; 95%CI 1.05-1.61; p=0.016) were independent predictors of resective surgery.Table 1.

Table 1. Predictive factors for first resective surgery in incident CD patients diagnosed between 1977 and 2018 – Cox-regression analysis

Conclusion

We report a gradual decline in reoperation rates and disease behavior progression in CD over time with the lowest values in the biological era. In contrast, there was no further decrease in the probability of first major resective surgery after the immunosuppressive era.

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.