Introduction

Emerging evidence points towards a plausible link between psoriasis, a common chronic inflammatory skin disease, and inflammatory bowel disease (IBD), as both diseases share similar inflammatory pathways(1).

Aims & Methods

Our aim was to identify patterns and potential predictors for the development of IBD in a psoriasis patients cohort.
This retrospective electronic health records-based study utilized data from the Meuhedet Health Maintenance Organization (MHMO) which contains 20 years of continuous follow-up. Patents’ data were evaluated for demographic parameters, comorbidities, auto-antibodies, and medications used.
Prevalence and incidence of IBD were measured. The association between psoriasis and IBD was evaluated using both univariate and multivariate logistic regression models, with adjustments made for possible confounding factors. The prediction model was developed to identify predictors of IBD development in psoriasis

Results

Data between psoriasis patients (n=61,003) and age and gender-matched controls (n=244,012) was compared.
Among psoriasis patients, 2.5% were diagnosed with IBD, compared to 1.6% of controls (OR 1.57, 95%CI 1.48-1.67). The adjusted OR was 1.47 (95% CI 1.37-1.56), p<0.001. IBD was diagnosed before the onset of psoriasis in 51.9% and within 1 year of psoriasis onset in 7.2%. Predictors of IBD development in psoriasis patients were: older age (OR 1.01, 95%CI 1.01-1.02), male gender (OR 1.22, 95%CI 1.03-1.45), axial spondyloarthropathies (OR 1.78, 95%CI 1.29-2.45), severe psoriasis (OR 16.03, 95%CI 11.02-23.34), uveitis (OR 3.13, 95%CI 2.08-4.71), ASCA positivity (OR 10.71, 95%CI 7.38-15.55), and P-ANCA positivity (OR 7.71, 95%CI 2.04-29.04). The specific risk for IBD among psoriasis patients according to disease severity is shown in Table 1.
Decreased risk for IBD in psoriasis patients was observed in patients with obesity (OR 0.76, 95%CI 0.62-0.94), psoriatic arthritis (OR 0.49, 95%CI 0.34-0.72), phototherapy (OR 0.09, 95%CI 0.06-0.15), and methotrexate use (OR 0.13, 95%CI 0.08-0.21). The presence of ANA antibodies was not significantly associated with the risk of IBD within the psoriasis cohort.

Conclusion

Our study provides evidence for a significant association between psoriasis and IBD and identifies several predictors for the development of IBD in psoriasis patients. These findings may improve clinical decision-making and patients’ outcomes.

References

Li, Y., Guo, J., Cao, Z., & Wu, J. (2022). Causal Association Between Inflammatory Bowel Disease and Psoriasis: A Two-Sample Bidirectional Mendelian Randomization Study. Frontiers in immunology, 13, 916645. https://doi.org/10.3389/fimmu.2022.916645

Disclosure

None

Introduction

Ulcerative colitis (UC) treatment requires a patient-centric efficacy endpoint to assess treatment benefits, enabling a shift towards a personalized approach. Comprehensive disease control (CDC) is an individual multi-component endpoint based on findings from a patient and expert Delphi consensus on remission assessment in UC. CDC was defined as IBDQ remission, partial Mayo Clinic Score (pMCS) remission, biomarker (faecal calprotectin [FCP]) remission and endoscopic improvement.

Aims & Methods

We evaluated different definitions of CDC, and the contribution of different CDC components to the net treatment benefit (NTB) of filgotinib 200 mg (FIL200), an oral, once-daily, Janus kinase 1 inhibitor approved for UC treatment following the SELECTION trial (NCT02914522). CDC was assessed at week 58 (W58) of SELECTION in adult patients with active UC treated with FIL200 or placebo (PBO). The CDC definitions evaluated were: 4-component CDC (CDC4) with FCP <150 µg/g, CDC4-150; CDC4 with FCP <250 µg/g, CDC4-250; 5-component CDC (with histological remission [CDC5]) with FCP <150 µg/g, CDC5-150; and CDC5 with FCP<250 µg/g, CDC5-250. The proportion of patients achieving each combination of components was evaluated. NTB of FIL200 was assessed for each endpoint using generalized pairwise comparisons and is reported here for CDC4-150 (and excluding different components).

Results

At W58, 21.6%, 26.6%, 19.1% and 22.6% of FIL200-treated patients achieved CDC4-150, CDC4-250, CDC5-150 and CDC5-250, respectively. Among patients who did not achieve CDC4-150, 0.5% of patients did not achieve this composite endpoint because they did not achieve pMCS remission; whereas 5.0%, 10.1% and 6.0% did not do so because they did not achieve IBDQ remission, biomarker remission or endoscopic improvement, respectively. Positive overall NTB of FIL200 versus PBO was demonstrated with all CDC definitions, including those with histological remission (CDC5). For CDC4-150 at W58, excluding pMCS remission did not substantially change the NTB (Δ −0.33; Table) versus excluding IBDQ or biomarker remission, or endoscopic improvement (Δ 3.87, 6.93 and 3.20, respectively). Similar NTB results were seen for all CDC definitions, with or without histological remission.

Conclusion

CDC is a stringent, patient-level, multi-component endpoint achieved by ~1/5 of FIL200-treated patients at W58. While CDC4-150 could be the optimal operational definition, the addition of histological remission resulted in similar stringency, potentially allowing for the use of different CDC definitions based on context or resources. Additional NTB of FIL200 was identified in patients when IBDQ or biomarker remission or endoscopic improvement were excluded. Overall, CDC appears to be a suitable endpoint to assess individual comprehensive benefit in patients with UC. Prospective validation is needed.

Table. NTB with exclusion of different components of the CDC4-150 endpoint.

Disclosure

We thank Katrien Van Beneden for her contribution to conceptualization, investigation and data interpretation.
The SELECTION trial was sponsored by Gilead Sciences, Inc. (Foster City, CA, USA). Galapagos NV (Mechelen, Belgium) was a collaborator for the SELECTION trial and funded this analysis.
Medical writing support for the development of this abstract was provided by Hannah Stephens, PhD, of PharmaGenesis London, London, UK, and was funded by Alfasigma S.p.A.
VV and AO are employees of Alfasigma S.p.A at the time of abstract submission
SS has received personal fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos/Gilead Sciences, I-Mab, Janssen Pharmaceuticals, MSD, Mylan, Pfizer, Protagonist, Provention Bio, Sandoz/Hexal, Takeda, Theravance Biopharma and UCB.
BGF has received grants and personal fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Janssen Biotech/Centocor, Johnson & Johnson/Janssen, Pfizer, Receptos and Takeda; and personal fees from Ablynx, ActoGeniX, Akebia Therapeutics, Inc., Allergan, Atlantic Pharmaceuticals, Avaxia Biologics, Inc., Avir Pharma, Baxter Healthcare Corporation, Biogen Idec, BiomX Israel, Boehringer Ingelheim, Boston Pharmaceuticals, Calypso Biotech, Celgene, Elan/Biogen, Eli Lilly, enGene, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, gIcare Pharma, Gilead Sciences, Given Imaging, Gossamer Bio, GSK, Inception IBD, Inc., Ironwood Pharmaceuticals, Japan Tobacco Company, Kyowa Hakko Kirin Co. Ltd, Lexicon Pharmaceuticals, Lycera, Mesoblast, Millennium Pharmaceuticals, MSD, Nestlé, Nextbiotix, Novartis, Novo Nordisk, Par’Immune, Progenity, Prometheus, Protagonist, Qu Biologics, Q32 Bio (formerly AdMIRx, Inc.), Salix Pharmaceuticals, Shire, Sienna Biopharmaceuticals, Sigmoid Pharma, Synergy Pharma, Teva Pharmaceuticals, TiGenix, Tillotts Pharma, UCB, Vertex Pharmaceuticals, VHsquared, Vivelix Pharmaceuticals, Wyeth, Zealand Pharma and Zyngenia.
SV receives financial support for research from AbbVie, Galapagos, Johnson & Johnson, Pfizer and Takeda; speaker and/or consultancy fees from AbbVie, Abivax, AbolerIS Pharma, AgomAb Therapeutics, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Bior Therapeutics (formerly Progenity), Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cytoki Pharma, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Genentech-Roche, Gilead Sciences, GSK, Hospira, IMIDomics, Janssen Pharmaceuticals, Johnson & Johnson, Materia Prima, Mestag Therapeutics, MiroBio, Morphic, MRM Health, MSD, Mundipharma, Pfizer, ProDigest, Prometheus, Robarts Clinical Trials, Surrozen, Takeda, Theravance Biopharma, Tillotts Pharma AG, VectivBio, Ventyx Biosciences and Zealand Pharma.
SD reports personal fees from AbbVie, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead Sciences, Hospira, Inotrem, Janssen Pharmaceuticals, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB and Vifor Pharma.
MF is an employee and shareholder of Galapagos NV.
VV and AO are former employees and shareholders of Galapagos NV, and employees of Alfasigma. S.p.A.
LP-B has received consulting fees from Abivax, AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celltrion, CONNECT Biopharma, Cytoki Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, Gossamer Bio, GSK, HAC Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen Pharmaceuticals, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Roivant, Samsung, Sandoz, Sanofi, Takeda, Theravance Biopharma, Thermo Fisher Scientific, TiGenix, Tillotts Pharma, VectivBio, Ventyx, Viatris, Vifor Pharma and Ysopia; grants from Celltrion, Fresenius Kabi and Takeda; and speaking fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Celltrion, Eli Lilly, Ferring Pharmaceutics, Galapagos, Genentech, Gilead Sciences, Janssen Pharmaceuticals, Medac, MSD, Pfizer, Sandoz, Takeda, Tillotts Pharma, Viatris and Vifor Pharma.

Clinical Case Summary

A 62 y/o male complaining from epigastric pain, constipation, vomiting and eructation for two months and CT abd revealed irresectable pancreatic head mass 4.5x4.5 cm encasing PV and SMV with duodenal invasion. Ryle decompression was done before EGD, duodenal obstruction was noted and biopsy showed duodenitis (stasis induced). EUS-FNB confirmed well differentiated AC. Duodenal stenting was successfully performed with improving symptoms.
After one week patient complained from weakness and abnormal gait, examination showed normal vital signs, bilateral lower limb edema and patient was lethargic. Three days after, the patient became confused (GCS 12), so he was admitted to ICU.
CT brain was unremarkable. Lab investigations showed the following:
Na 130, K 4.1, Ca 7.8, Phos 2.8, Mg 2.6, Alb 2.9
Refeeding injury was suspected and TPN was started by the ICU team. No improvement of the consciousness was achieved and patient caught chest infection, developed sepsis and died.
Discussion: Refeeding syndrome is a serious complication that can be easily missed [1] in upper GI malignant obstructions with prolonged decreased oral intake along with the malignancy cachexia status. These obstructions may need surgery or stenting to regain patency and without cautious monitoring of the nutrients repletion rate either enteral or parenteral this will lead to fluid and electrolyte disturbance (Fluid balance abnormalities, Abnormal glucose metabolism, Vitamin deficiency, e.g., vitamin B1 (thiamine), Hypophosphatemia, Hypomagnesaemia and/or Hypokalemia) [2] with symptoms ranging from vague up to life threatening conditions like disturbed conscious level and heart failure. Our patient had high risk of developing refeeding syndrome due to caloric deprivation secondary to duodenal obstruction with development of the symptoms after stenting and restarting oral intake.
Conclusion: Nutritionist counseling after GI stenting of upper GI malignant obstructions is needed to avoid refeeding syndrome.

References

[1] Reber, E., Friedli, N., Vasiloglou, M.F., Schuetz, P. and Stanga, Z., 2019. Management of refeeding syndrome in medical inpatients. Journal of clinical medicine, 8(12), p.2202.
[2] Crook, M.A., Hally, V. and Panteli, J.V., 2001. The importance of the refeeding syndrome. Nutrition, 17(7-8), pp.632-637.

Introduction

The Mediterranean diet identified as a priority because it contributes to the normalization of key metabolic parameters in patients with non-alcoholic fatty liver disease (NAFLD). However, it is necessary to take into account the possibilities of following such a diet and the nutrigenetic characteristics of patients in different regions of the world. Purpose: to study the effect of nutrigenetic parameters in patients with NAFLD on the effectiveness of non-drug treatment.

Aims & Methods

Purpose: to study the effect of nutrigenetic parameters in patients with NAFLD on the effectiveness of non-drug treatment. 105 patients (55 men and 50 women) with NAFLD were examined. In patients, the features of eating disorders (ED) were studied (DEBQ questionnaire), nutrigenetic parameters - 5 polymorphisms: Pro12Ala of the PPARG2 gene (rs1801282), 101027 of the ADRB2 gene (rs1042714) and Arg16Gly of the ADRB2 gene (1010282); (rs4994) and Thr54Ala of the FABP2 gene (rs1799883) associated with the risk of metabolic disorders.

Results

Two polymorphisms associated with disorders of the ED gene (Pro12Ala PPARG2 and Trp64Arg ADRB3) were identified. Sex differences in the frequency of genotypes of the Pro12Ala polymorphism of the PPARG2 gene were not found (pχ2 = 0.90). 83.6% of men and 82.0% of women were carriers of the PPARG2 gene polymorphism (OR=1.10, CI=0.24-4.99) of the Pro12Pro genotype (AB=1.10, men and 16.7% of women of the genotype Pro12Ala (OR = 0.91, OR) = 0.20 - 4.13). The distribution of genotypes and allelic variants of the ADRB3 gene polymorphism had significant differences (px2 = 0.05). The Trp64Trp genotype of the ADRB3 gene polymorphism were found in 80.0% of men and 55.0% of women, the Trp64Arg genotype in 20.0% of men and 32.5% of women, the Arg64Arg genotype was found only in women. An analysis of the distribution of 64Trp and 64Arg alleles by sex using a multiplicative model showed that the significance of the association of the minor female 64Arg allele was confirmed by an odds ratio of 3.13 (CI = 1.01–9.70) versus 0.32 (CI = 0.01–9 .70). 10 - 0.99) for the minor allele. A significant association (px2 = 0.02) of the protective minor allele 12Ala with emotionally restrictive types of ED (OR = 0.11, CI = 0.10 - 0.97) was established, while the external type of oblique ED was associated with the carriage of the main allele polymorphism 12Pro of the Pro12Ala PPARG2 gene (OR = 8.71, CI = 1.03-7.66). Analysis of the distribution of 64Trp and 64Arg alleles depending on the type of EP disorder showed a significant association (px2 = 0.006) of the metabolically unfavorable minor 64Arg allele with the external type of ED disorders (OR = 5.53, CI = 1.48-20.68), while emotional and restrictive types were associated with the carrier of the main 64Trp allele (OR = 0.18, CI = 0.05-0.68). In patients with NAFLD, the external type of ED disorder prevails (p<0.05).

Conclusion

To increase the effectiveness of non-drug treatment, one should take into account nutrigenetic features - the presence of ProARA2 polymorphisms of the PPARG2 gene and Trp64Arg of the ADRB3 gene, which are associated with the peculiarities of nutrient metabolism and malnutrition in patients with NAFLD.

Disclosure

Nothing to disclose

Introduction

​Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract(1,2). Small (less than 20mm ) endoscopic ultrasonography (EUS) suspected GISTs are increasingly incidentally found on endoscopy or cross sectional imaging. The natural history and appropriate management of small (<20mm) GISTs is not well understood. There is lack of data on safety of duration and interval of surveillance for small GISTs.

Aims & Methods

​​​​Our study aims to examine the progression of small GISTs under our EUS surveillance which might aid future guidance for subsequent surveillance.A Retrospective analysis of patients who underwent EUS for GIST between 2012 to 2022 at our institution was performed. A small GIST was defined as a submucosal lesion with characteristic hypoechoic EUS appearances and <20mm in size. GIST between 20-30 mm were also included in our analysis. Data collected included patient demographics; GIST location; EUS features including maximal diameter; frequency, duration and outcomes of surveillance.

Results

A total of 65 patients were identified with GIST on EUS, 21 patients were excluded due to lack of follow up data, or size of lesion more than surveillance guidelines. Patient demographics: 44 patients, 23 males and 21 females, mean age 64.5 years (range 23 - 89). Location of GISTs: 28 gastric, 9 duodenal, 6 GOJ and 1 oesophageal. Frequency of surveillance ranged from 1-4 years. 7 lesions with size more than 20 mm were also included in surveillance. During the mean follow up of 4.4 years, 4 lesions increased in size, 3 lesions with size >20 mm at the time of diagnosis progressed and were referred for surgery. Only 1 lesion less than 20 mm in size increased from 8mm to 13mm. No GIST <20 mm required surgical referral.

Conclusion

The rate of progression of small GISTs (less than 20 mm in size) is very low. In our practice of over one decade not a single patient with a small GIST progressed beyond 20 mm to require surgical referral. We advocate extended follow up intervals for surveillance in GIST less than 20mm in size.

References

1. Miettinen M, Sarlomo-Rikala M, Lasota J. Gastrointestinal stromal tumors: recent advances in understanding of their biology. Hum Pathol. 1999 Oct;30(10):1213-20. doi: 10.1016/s0046-8177(99)90040-0. PMID: 10534170.

Introduction

Advances in medical management of Crohn’s disease (CD) have improved disease outcomes; however, significant gaps remain. Approximately 30% of patients experience primary non-response to induction therapy with biologics, and over 40% will experience loss of response. There is an urgent need to identify new adjunct therapies, including diet, that can alter the disease course. Dietary patterns characterized by increased intakes of fibre, fruit, vegetables and decreased intakes of processed foods, sugar and omega-6 fatty acids are linked to a reduced prevalence of CD and decreased biomarkers of intestinal and systemic inflammation; however, the effects upon mucosal inflammation are unknown in patients who have lost response to usual medical treatments. We developed the CD Therapeutic Dietary Intervention (CD-TDI), a novel dietary approach incorporating best practices and current evidence to determine its therapeutic potential in reducing inflammation in patients with active CD who have lost response to their usual therapies.

Aims & Methods

This 13-week RCT aimed to explore the efficacy of the CD-TDI compared with conventional management (CM) to reduce clinical disease activity (Harvey-Bradshaw Index (HBI) <5) and reduce mucosal inflammation, as measured by fecal calprotectin (FCP) in mild-to-moderately active luminal CD. Patients with mild to moderately active disease, determined by endoscopic, cross-sectional imaging or FCP >100 ug/g, on stable medical therapy 8 weeks prior to recruitment were eligible to participate (n=28). Upon randomization, the CD-TDI group (n=16) met virtually with a registered dietitian trained in the CD-TDI protocol weekly for 13 weeks. Participants assigned to CM (n=12) followed their habitual diet and met with the same registered dietitian as participants in the CD-TDI group at week 0 (W0) and week 13 (W13) to capture their dietary recall. FCP, HBI, and C-reactive protein (CRP) were assessed at W0 and W13.

Results

Twenty-eight participants (53% females, age 40 years (IQR:31-55); BMI 27 kg/m² (IQR:24-31)) were enrolled. Medical therapy did not differ between groups, with 54% (15/28) of participants receiving no drug therapy, 29% (8/28) 5-ASA monotherapy, 21% (6/28) biologic therapy, 11% (3/28) corticosteroids or 14% (4/28) immunomodulators. At W0, the FCP, HBI and CRP did not differ significantly between groups. In the CD-TDI group, FCP decreased significantly from 130 ug/g (IQR: 38-411) at W0 to 72 ug/g (IQR:3-153) at W13 (p= 0.01) and significantly differed between the CM group at W13 (p=0.04). In a sub-group analysis (n=11) of participants with FCP >250 ug/g at W0, at W13 the FCP decreased significantly from 632 ug/g (IQR: 356-1013) to 166 ug/g, (IQR:52-701) (p=0.06) within the CD-TDI group, however, this same trend was not observed in the CM (W0:337 ug/g IQR:324-1013 vs. W13:431 ug/g, IQR:46-1770, p=0.69). At W13, between-group differences in the CRP were found between the CD-TDI group (1.0 mg/L, IQR:0.6-2.4) and the CM group (4.5 mg/L, IQR:2.6-13.0) (p=0.002). The CD-TDI group experienced a significant decrease in HBI from W0 to W13 (W0: 3.0, IQR:1.0-5.3; W13: 2.0, IQR:0-3.0; p=0.05), however, this was not observed in the CM group.

Conclusion

At W13, the CD-TDI significantly decreased clinical and biochemical markers of inflammation in patients with mild-to-moderately active CD. This preliminary analysis suggests that CD-TDI could be a potential adjunct management strategy for reducing inflammation in CD. We hope to confirm these promising results with an adequately powered sample.

Introduction

96-98% of patients survive acute pancreatitis (AP), but in the post-AP phase, patients are at high risk of morbidity and mortality. It has been shown that pancreatic exocrine insufficiency can occur after AP.

Aims & Methods

We aimed to investigate the rate, risk factors, and the effect of pancreatic enzyme replacement therapy (PERT) for PEI in patients with AP. The study protocol was registered on PROSPERO (CRD42024516403). We conducted a systematic search on 5 February 2024 in three databases (PubMed, EMBASE, and CENTRAL). We included in the analysis studies reporting on risk factors and PERT efficacy in PEI associated with AP. Pooled proportion and odds ratios (OR) with a 95% confidence interval (CI) were calculated using a random effect model.

Results

Fifty-six articles were included in our meta-analysis. Among 17896 patients with AP, the pooled proportion of PEI was 20 % ([CI]: 15–26). The odds of PEI development were two-fold higher in severe acute pancreatitis (OR=2.44, [CI]: 0.98–6.11) compared with mild or moderate AP and three times higher after necrosectomy compared to patients without necrosectomy (OR=3.26, [CI]: 1.6–6.64). There was no significant difference between the odds of PEI among AP patients with necrosis (OR=1.43, [CI]: 0.32–6.45) and those without necrosis. However, the odds of PEI were twice as high in patients with infected necrosis (OR=2.13, [CI]: 0.93–4.87) than in patients with sterile necrosis. Pancreatic enzyme replacement therapy was prescribed for 22% ([CI]: 16–30) of patients after AP.

Conclusion

One in five patients with AP develops PEI. The rate is higher in patients with severe AP, infected necrosis, or who need necrosectomy. Patients with AP should be screened for PEI to allow timely PERT administration.