Introduction

Per the STRIDE II consensus, mucosal healing and normalization of quality of life are considered long-term treatment goals in ulcerative colitis (UC). Results from Phase 2/3 induction and maintenance trials (U‑ACHIEVE and U‑ACCOMPLISH) showed that patients with moderately to severely active UC treated with upadacitinib (UPA) had significant improvements in these outcomes individually. However, there is a need to understand better the extent to which patients treated with UPA can achieve both treatment goals jointly within one year of maintenance therapy.

Aims & Methods

In the U-ACHIEVE and U-ACCOMPLISH trials, patients with a clinical response after 8-week induction treatment with UPA 45 mg QD were re-randomized 1:1:1 to UPA 15 mg QD, UPA 30 mg QD or placebo (PBO) QD. Long-term treatment goals were determined based on the percentage of patients who achieved the composite endpoint of endoscopic remission (ER), complete symptom resolution (CSR), and Inflammatory Bowel Disease Questionnaire (IBDQ) remission at the end of induction week 8 and maintenance week 52. ER was defined as an endoscopic score of 0; CSR as stool frequency subscore ≤1, rectal bleeding subscore of 0, no bowel urgency, no abdominal pain; and IBDQ remission as IBDQ total score ≥170. The response rate between PBO and UPA was calculated using the Cochran-Mantel-Haenszel test, adjusting for baseline characteristics. The percentage of patients who maintained vs achieved ER+CSR+IBDQ remission during maintenance week 52 was also calculated.

Results

At induction week 8, a significantly greater percentage of patients treated with UPA 45 mg achieved ER+CSR+IBDQ remission vs PBO (6.4% vs 0.9%, respectively, p<0.001, Table). At maintenance week 52, the percentage of induction responders who achieved ER+CSR+IBDQ remission reached 18.3% with UPA 30 mg and 13.1% with UPA 15 mg vs 4.5% with PBO (p<0.001). Of the patients who achieved ER+CSR+IBDQ remission by week 0 of maintenance, 42.1% (8/19), 23.5% (4/17), and 22.2% (4/18) in the UPA 30 mg, UPA 15 mg, and PBO groups, respectively, sustained the composite endpoint at week 52. Among patients who did not achieve this composite endpoint by week 0 of maintenance, 16.2% (35/214), 12.3% (26/208), and 2.9% (6/205) in the UPA 30 mg, UPA 15 mg, and PBO groups, respectively, achieved it at week 52.

Conclusion

Results of this post hoc analysis indicate that the rigorous, long-term treatment goals of ER+CSR+IBDQ remission can be achieved with UPA in some patients with moderately to severely active UC by week 8 of induction. By maintenance week 52, nearly one in five patients treated with UPA 30 mg and approximately one in eight patients treated with UPA 15 mg achieved the stringent target. Sustained maintenance treatment with UPA results in an increasing proportion of patients achieving or maintaining these long-term goals of treatment after only one year.

Disclosure

J Panes received financial support for research from AbbVie and Pfizer; consultancy fees/honorarium from AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celsius, Celltrion, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Morphic, Nestlé, Origo, Pandion, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Robarts, Sanofi, Takeda, Theravance and Wasserman; reports payment for lectures including service on speaker bureau from Abbott, Ferring, Janssen, Pfizer and Takeda; and reports payment for development of educational presentations from Abbott, Janssen, Pfizer Roche and Takeda.
R Panaccione has received consulting fees, speaker fees, research/educational support from, and/or advisory board member for AbbVie, Abbott, Alimentiv (formerly Robarts), Amgen, Arena, AZ, BI, BMS, Celgene, Celltrion, Cosmos, Eisai, Elan, Ferring, Galapagos, Genentech, Gilead, GSK, Janssen, Lilly, Merck, Mylan, Oppilan, Pandion, Pfizer, Progenity, Protagonist, Roche, Satisfai, Sandoz, Schering-Plough, Shire, Sublimity, Theravance, Takeda, and UCB.
MC Dubinsky has received consultancy fees from AbbVie, Allergan, Amgen, BI, Celgene, Gilead, Janssen, Lilly, Pfizer, Prometheus, Roche, Takeda, and UCB; and is a shareholder of Trellus Health.
Y Ishiguro has received a research grant from Mitsubishi Tanabe Pharmaceutical; speaker/consultation fees from AbbVie, Janssen, Daiichi-Sankyo, Kissei Pharmaceutical and EA Pharma.
J Tran is currently a contractor at AbbVie and a funded PhD candidate at the University of Washington.
D Ilo, J Eccleston, Y Sanchez Gonzalez are full-time employees of AbbVie and may hold AbbVie stock and/or stock options.
B Feagan is a consultant, member of the speakers bureau, and/or member of the scientific advisory board for AbbVie, AbolerIS, AgomAB, Allianthera, Amgen, AMT, AnaptysBio, Arena, Atomwise, Avoro Capital Advisors, Axio, BI, BioJamp, Biora, Boxer, Celgene/BMS, Celsius, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Equillium, Ermium, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer, GSK, Hinge Bio, Hot Spot, Imhotex, Immunic, Index, JAKAcademy, Janssen, Japan Tobacco, Kaleido, Landos, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lilly, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion, Pendopharm, Pfizer, Prometheus, Play to Know AG, Progenity, Protagonist, PTM, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres, Silverback, Surrozen, Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx, VHSquared, Viatris, Ysios, Ysopia, and Zealand; is a stock shareholder for Gossamer; is an employee of Western University; and is Senior Scientific Director of Alimentiv Inc.

Introduction

Inflammatory Bowel Disease (IBD), encompassing Crohn's Disease (CD) and Ulcerative Colitis (UC), shares chronic and inflammatory characteristics with Non-Alcoholic Fatty Liver Disease (NAFLD). While their precise pathogenesis remains unclear, emerging evidence implicates dysbiosis and metabolic changes. This study aims to investigate the association between IBD and NAFLD, focusing on metabolic syndrome and its nutritional implications

Aims & Methods

Objective: To evaluate the nutritional status and body composition in IBD patients, comparing groups with and without NAFLD, and identifying the associated factors.
Methods: A cross-sectional study was conducted, assessing clinical data, metabolic syndrome presence, nutritional status, and biochemical markers. Patients were categorized into IBD+NAFLD and IBD-only groups based on hepatic ultrasound findings. Statistical analysis included descriptive statistics and logistic regression.

Results

127 patients were included, comprising 58 CD and 69 UC, with a mean age of 45.56 years. Most patients were female and did not engage in physical activity. Patients were mostly in clinical remission and endoscopic activity. 58 patients (45.67%) had hepatic steatosis on ultrasound, forming the IBD+NAFLD group. The IBD+NAFLD group had higher BMI, fat mass, and all circumference values, Table 1, as well as a higher prevalence of hypertension (p=0.0446) and dyslipidemia (p=0.0377). It is noteworthy that, although most of these patients were classified as overweight by BMI, considering anthropometric data, most IBD+NAFLD patients were classified as eutrophic. 86.21% of patients in the IBD+NAFLD group met the criteria for MAFLD. No difference was observed regarding medication in use. Regarding biochemical tests, the IBD+NAFLD group had higher values of hematocrit (p=0.0023), liver enzymes (AST, p=0.0141 and ALT, p<0.0001), fasting glucose (p=0.0107), glycated hemoglobin (p=0.0146), basal insulin (p=0.0003), and triglycerides (p=0.0001), with lower HDL cholesterol (p=0.0101)

Conclusion

The study highlights a significant association between nutritional status and NAFLD in IBD patients. Those categorized as eutrophic had a higher prevalence of hepatic steatosis, potentially linked to dietary factors.

References

Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and
natural history of non‐alcoholic fatty liver disease and non‐alcoholic
steatohepatitis in adults. Alimentary pharmacology & therapeutics.
2011;34(3):274-285./ Silva A.F; Schieferdecker M.H; Amarante M. B. Ingestão alimentar em pacientes
com doença inflamatória intestinal ABCD, arq. bras. cir. dig. 24 (3) • Set 2011/ Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA.
2015;313(22):2263-73

Introduction

Inflammatory bowel disease (IBD) represents a group of chronic inflammatory disorders of the gastrointestinal tract. While the hallmark features of IBD involve inflammation and damage to the digestive system, the impact of the disease often extends beyond the gut, manifesting as a spectrum of extraintestinal manifestations (EIM), affecting various organs and contributing to the complexity and heterogeneity of IBD.

Aims & Methods

The aim of this study was to assess the impact of EIM in IBD on disease course. We conducted a retrospective, descriptive and comparative study including patients hospitalized for IBD over a 9-year period [January 2011-January 2020]. Patients with less than 2 years of follow-up were excluded. Clinico-biological data, disease severity, and long-term outcomes (surgery and disease course) were collected. Data were entered and analyzed via SPSS 26 software.

Results

We included 225 men and 227 women. We enrolled 341 patients diagnosed with Crohn's disease (CD) and 111 patients with ulcerative colitis (UC). The mean age at diagnosis was 36.15 ± 12.74 years. One-hundred and sixty-five patients (36.4%) had EIM with respectively: rheumatological manifestations (n=144), dermatological manifestations (n=26), ocular manifestations (n=17) and hepatic manifestations (n=8). We noticed a significant association of EIM with male gender (56.3% vs 45.9%; p=0.03). Rheumatological EIM were associated with a significant older age at disease onset (36.7 years vs 32.8 years; p=0.003). No significant association was noted between EIM with neither family history of IBD nor the type of IBD (p=0.33 and p=0.3 respectively). In case of CD, we noted a higher frequency of ileal involvement in patients with EIM, without a significant difference (61.4% vs 51.4%; p=0.07). No association was noted between EIM with neither fistulising behaviour nor with extended ileal disease nor with upper gastrointestinal tract involvement (p=0.1; p=0.5 and p=0.5 respectively). In case of UC, no association was noted between EIM and an extensive disease (p=0.7). As for treatment, EIM had no impact on corticosteroids’ use or immunosuppressive treatment (p=0.36 and p= 0.08), but was associated with a significant higher use of anti-TNF therapy (83.4% vs 27.2%; p=0.01). Response to corticosteroids and anti-TNF therapy was similar whether with or without EIM (p= 0.36 and p=0.24 respectively). In the sub-group of ocular EIM, we noted a higher failure of immunosuppressive treatment (70% vs 36.6%; p=0.04). We noted that EIM was associated with a rarer urge to surgical treatment (35.7% vs 44.9%;p=0.05) with a significant longer timeframe to surgery (47.7 months vs 27,2 months; p=0.03). The mean number of years of active disease was significantly higher in patients with EIM (3.3 vs 2.5; p=0.002) with a higher number of flare-ups (p=0.009) and hospitalizations (p<0.001), reflecting a better disease course in patients without EIM.

Conclusion

In our study, EIM were associated with an overall more severe disease course in IBD, thus, emphasizing the importance of comprehensive assessment and management strategies tailored to address both intestinal and extra-intestinal manifestations in the holistic care of IBD patients.

Introduction

The efficacy and safety of upadacitinib (UPA), an oral reversible Janus kinase inhibitor, were demonstrated for patients with Crohn’s disease (CD) in three phase 3 randomized, controlled, double-blind clinical trials: U-EXCEL (NCT03345849), U-EXCEED (NCT03345836), and U-ENDURE (NCT03345823).^1–3 UPA is approved for the treatment of moderately to severely active CD.^4,5 The STRIDE-II CD treat-to-target guidelines recommend using composite clinical and endoscopic treatment targets to improve patient outcomes.⁶ We assess the efficacy of UPA in patients with moderately to severely active CD using stringent, composite efficacy endpoints.

Aims & Methods

In two phase 3 induction studies, U‑EXCEL and U-EXCEED, patients were randomized 2:1 to receive once-daily UPA 45 mg or placebo (PBO) for 12 weeks. Those who achieved a clinical response (≥30% decrease in average daily very soft or liquid stool frequency [SF] and/or ≥30% decrease in average daily abdominal pain score [APS] and both not worse than baseline) to UPA were re-randomized 1:1:1 to receive UPA 15 mg, UPA 30 mg, or PBO in the 52-week U-ENDURE maintenance study. Five composite clinical and endoscopic endpoints were assessed at weeks 12 of induction and 52 of maintenance therapy: (1) enhanced clinical response (per very soft/liquid SF and APS) and endoscopic response; (2) clinical response (CR-100) and endoscopic response; (3) clinical remission per CD Activity Index (CDAI) and endoscopic response; (4) SF/APS clinical remission and endoscopic remission; and (5) CDAI clinical remission and endoscopic remission. Treatment group differences were compared using the Cochran-Mantel-Haenszel test, adjusted for stratification factors. Analyses used nonresponder imputation while incorporating multiple imputation to handle missing data due to COVID-19.

Results

A greater proportion of patients receiving UPA 45 mg vs PBO achieved stringent clinical and endoscopic endpoints at week 12: enhanced clinical response and endoscopic response (33.7 vs 6.1%); CR-100 and endoscopic response (27.8 vs 5.2%); CDAI clinical remission and endoscopic response (24.7 vs 5.2%); SF/APS clinical remission and endoscopic remission (15.7 vs 3.5%); and CDAI clinical remission and endoscopic remission (15.0 vs 3.7%; for all comparisons, nominal P values ≤ .001; Table). At week 52, a greater proportion of patients who received UPA 15 mg or UPA 30 mg achieved stringent clinical and endoscopic endpoints vs patients in the PBO group (Table). Composite endpoint achievement rates were numerically greater with UPA 30 mg than with UPA 15 mg (Table). The safety of UPA in CD was previously reported.^1–3
​

Conclusion

In both induction and maintenance studies, patients receiving UPA had greater achievement of stringent efficacy endpoints vs patients who received PBO. UPA 30 mg demonstrated numerically greater clinical and endoscopic efficacy vs UPA 15 mg. The largest differences between UPA and PBO treatment groups occurred for the enhanced clinical response and endoscopic response endpoint.

References

1. Colombel JF, et al. Gastroenterology. 2022;162(Suppl):1394.
2. Loftus EV Jr. United European Gastroenterol J. 2022;10(Suppl 8):103–104.
3. Panés J, et al. Am J Gastroenterol. 2022;117(Suppl):10.
4. RINVOQ. Summary of Product Characteristics. AbbVie Deutschland GmbH & Co. KG; 2023. Accessed 24 April 2023. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
5. RINVOQ. Summary of Product Characteristics. AbbVie Inc.; 2023. Accessed March 27, 2023. https://www.medicines.org.uk/emc/product/12830/smpc.
6. Turner D, et al. Gastroenterology. 2021;160(5):1570–1583.

Disclosure

SD has served as a speaker, consultant, and advisory board member for AbbVie, Actelion, Alfa Wasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson & Johnson, Millennium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, Schering-Plough, UCB Pharma, and Vifor.
BGF has consulted for AbbVie, AbolerIS, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport Inc, Arena Pharma, Avoro Capital Advisors, Atomwise,, BioJamp, Biora Therapeutics, Boehringer-Ingelheim, Boxer, Celsius Therapeutics,Celgene/BMS, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium,, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer Pharma, GSK, Hinge Bio, Hot Spot Therapeutics, Index Pharma, Imhotex, Immunic Therapeutics, JAKAcademy, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc., Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx Biosciences, VHSquared Ltd., Viatris, Ysios, Ysopia, and Zealand Pharma; a speaker for AbbVie, Janssen, and Takeda; an advisor for AbbVie, Amgen, AMT, AnaptysBio, Axio Research, Boehringer-Ingelheim, Celgene/BMS, Ecor1Capital, Eli Lilly, Genentech/Roche, GSK, Index, Janssen, MiroBio, Morphic, Origo BioPharma, Pfizer, Progenity, Prometheus, REDX Pharma, Sanofi, Takeda, Teva, and Tillotts Pharma; a senior scientific director for Alimentiv Inc.; an employee of Western University; and holds stocks in Gossamer Pharma.
FM has served as a speaker and received honoraria from AbbVie, Biogen, Falk Pharma, Ferring, Hospira, Laboratorios Vitoria, Merck Sharp & Dohme, and Vifor.
PLL has been a speaker and/or advisory board member for AbbVie, Arena, Falk Pharma, Ferring, Genentech, Janssen, Kyowa Hakko Kirin Pharma, Mitsubishi Tanabe Pharma, MSD, Pfizer, Roche, Shire, Takeda, and Tillots; and has received unrestricted research grants from AbbVie, MSD, and Pfizer.
JOL has received grants for investigator led research from Takeda, Hospira / Pfizer, Abbvie, Gilead and has been a speaker and / or advisory board member for Allergan, Abbvie, Bristol Myers Squib, Celgene, Celltrion, Cornerstones US, Galapagos, Gilead, GSK, Lily, MSD UK, Shire, Ferring, Takeda, Pfizer, Janssen, Bristol Myers Squib,
TH has received research grants from AbbVie, Alfresa Pharma, Daiichi Sankyo, EA Pharma, JIMRO, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Pfizer, and Takeda. He has received lecture fees from AbbVie, EA Pharma, Janssen, Mitsubishi Tanabe Pharma, Pfizer, and Takeda.
BS has served as consultant for AbbVie, Boehringer, BMS, Celgene, Falk Pharma, Galapagos, Gilead, Janssen, Landos, Lilly, Pfizer, Prometheus, and Takeda, and received speaker’s fees from AbbVie, CED Service GmbH, BMS, Falk Pharma, Ferring, Galapagos, Janssen, Novartis, Pfizer, and Takeda.
ED, APL, AG, and CD, are employees of AbbVie, and may own AbbVie stock and/or stock options.
JDL has received personal fees, grants, and/or other support from AbbVie, Amgen, Arena Pharmaceuticals, Bridge Biotherapeutics, Bristol-Myers Squibb, Celgene, Galapagos, Gilead, Janssen Pharmaceuticals, Johnson & Johnson Consumer Inc., Lilly, Merck, Nestle Health Science, Pfizer, Protagonist Therapeutics, Samsung Bioepis, Sanofi, Takeda, and UCB.
Funding: AbbVie Inc. funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. AbbVie and authors thank all the trial investigators and the patients who participated in this clinical trial. Medical writing support was provided by Morgan A Gingerich, PhD, of JB Ashtin, and funded by AbbVie.

Introduction

There is conflicting data on the risk factors linked to Gastroesophageal Reflux Disease (GERD) and Functional Dyspepsia (FD). Studies that explore the association between anxiety/depression and GERD phenotypes (Esophagitis/EE and Non-Erosive Reflux Disease/NERD), FD, and Rome-IV syndromes are scarce.

Aims & Methods

The aim was to evaluate the association between epidemiological factors and comorbidities with GERD phenotypes, FD, and Rome-IV syndromes, as well as the relationship of these processes with anxiety/depression.
338 participants were selected from 357 patients referred to three tertiary centers in Granada (Spain) for endoscopic assessment. A gastroenterologist individually interviewed each participant prior to the procedure and administered three validated questionnaires (GERD-Q, Rome-IV, and HADS) to detect the presence of GERD, FD, and anxiety/depression, respectively.

Results

45/338 patients were controls, 198/58.6% were classified as GERD, 81/24.0% EE (49/14.5% symptomatic, and 32/9.5% asymptomatic), 117/34.6% NERD, 176/52.1% FD (43/12.7% epigastric pain syndrome, 36/10.7% postprandial distress syndrome, and 97/28.7% overlapping syndrome). 81 patients were mixed GERD-FD. Multivariate analysis found significant independent associations: age in NERD and FD; sex in EE, asymptomatic EE and FD; body mass index in NERD and FD; alcohol in EE; anxiety/depression in FD; use of calcium channel antagonists in EE; and inhalers in FD. We compared controls vs different groups/subgroups finding significantly more anxiety in NERD, FD, all Rome-IV syndromes, and mixed GERD-FD; more depression in FD, overlapping syndrome, and mixed GERD-FD; and higher levels of anxiety+depression in NERD, FD, overlapping syndrome, and mixed GERD-FD.

Table: Multivariate analysis (logistic regression) of factors associated with different groups and subgroups of GERD and FD

Conclusion

The existence of shared demographic and psychopathological risk factors in Non-Erosive Reflux Disease (NERD) and Functional Dyspepsia (FD) implies that they could be part of the same pathophysiological spectrum. The prevalence of anxiety was higher in NERD, while anxiety and depression were more frequent in FD. These results suggest that psychological therapy could be a supportive strategy for both conditions.