Introduction

Bowel urgency (BU) is a common symptom in patients with inflammatory bowel disease (IBD). More than 80% of patients with ulcerative colitis (UC) and more than 60% of patients with Crohn’s disease (CD) experience BU during their life. Although BU negatively impacts the quality of life and psychosocial status, currently it is an overlooked symptom. Furthermore, there is little evidence of the effectiveness of available advanced therapies on BU.

Aims & Methods

We aimed to evaluate the impact of different advanced therapies for IBD in improving BU. This was a retrospective cohort study conducted at two third-level centers (IRCCS San Raffaele hospital and university of Naples Federico II) between April 2023 and April 2024. All consecutive patients with confirmed diagnosis of CD or UC who started an advanced therapy (any biological drug or small molecule) with available data regarding BU at baseline (before starting an advanced therapy) and after induction therapy were eligible. BU was assessed using the numeric rating scale urgency score (NRS-us), a validated tool for quantifying BU in IBD. BU was defined as ≥3 in NRS-us. All available clinical (partial Mayo score for UC and Harvey-Bradshaw Index (HBI) for CD), biochemical (fecal calprotectin (FC) and C-reactive protein (CRP)), endoscopic (Mayo endoscopic score or SES-CD score) and intestinal ultrasound data were collected before and after the induction of an advanced therapy. Patients with history of bowel surgery or radiotherapy were excluded. The primary endpoint was BU improvement, defined as an NRS-us ≤3 or a score reduction of at least 2 points. A logistic regression multivariate analysis was performed to identify any correlation between socio-demographic factors, disease features, and treatment at baseline and changes in NRS-us. Analyses were subjected to correction using the false discovery rate (FDR) method.

Results

In total, 159 patients were included (89 male (56%) with a median age of 36 years and a median BMI of 22,1, 104 (65,4%) UC) (Table 1). Patients were treated with infliximab (24,5%), adalimumab (24,5%), ustekinumab (22,6%), vedolizumab (13,2%), upadacitinib (9,4%), tofacitinib (3,1%), filgotinib (1,3%), golimumab (0,6%) risankizumab (0,6%). A small proportion of patients underwent concomitant steroid (8,8%) or immunosuppressant therapy (12,6%). At baseline the median NRS-us was 7. Approximately half of the patients (81, 50,9%) experienced BU improvement after induction with a mean reduction of NRS-us of 2,3 ± 2,9. In the multivariate analysis, improvement in BU was associated with clinical remission (FDR=0.009 for CD and FDR=0.01 for UC), normalization of fecal calprotectin (FDR=0.001) and CRP (FDR=0.008), and normalization of bowel wall thickness to IUS (FDR=0.0006). No statistically significant difference in obtaining an improvement in BU was identified between the different drugs investigated.

Conclusion

The available advanced therapies improve bowel urgency after the induction phase. Improvement in BU is associated with clinical, biochemical, and ultrasound remission.

Introduction

Bismuth-based quadruple therapy (BQT) is recommended as the first-line therapy for Helicobacter pylori eradication as it is not associated with resistance. Tegoprazan, a new, fast, and strong potassium-competitive acid blocker, has been approved for the treatment of gastric acid-related diseases in México. However, real-world clinical data regarding this drug are scarce. We aimed to compare the Helicobacter pylori eradication rates of tegoprazan- and omeprazole-based quadruple therapy.

Aims & Methods

Aim: To investigate the efficacy and safety profiles of tegoprazan-based BQT (TBMT) versus omeprazole-based BQT (OBMT) for H. pylori eradication.
Methods: We included patients older than 18 with an H. pylori infection without a history of H. pylori eradication who visited two centers between January 2024 and April 2024. H. pylori infection was diagnosed using histology. Patients received tegoprazan 50 mg BID , bismuth subcitrate 300 mg QID, metronidazole 500 mg QID, and doxycycline 100 mg QID for 14 days. An historic control groups was used as comparator. Historic controls were age-sex matched subjects that received omeprazole 40 mg BID , bismuth subcitrate 300 mg QID, metronidazole 500 mg QID, and doxycycline 100 mg QID, in the previous year.

Results

Until now, 80 patients have been included (40 TBMT and 40 OBMT). Most common indication for erradication was dyspeptic symptoms (78%), followed by peptic ulcer disease (10%), folicular gastritis (9%) and familiar hystory of cance (2.5%). Eradication rates of TBMT and OBMT were 90% and 77.4% (=OR 2.61, CI 95% 0.73-9.37, p=0.12), respectively. There was no significant difference in the rate of adverse events between the TBMT and OBMT groups (42.5% vs. 55,5%, p = 0.37). Nausea was the most common adverse effect (37.5% vs 40%, p=0.92) , followed by abdominal pain (12.5% vs 17.5%, p=0.16%)Adherence to the treatments was similar between groups (> 90%, 10% vs 12%, p=0.98)

Conclusion

TBMT showed a noninferior eradication rate and similar adverse events to OBMT as a first-line eradication regimen. Our results suggest that tegoprazan might be substituted for proton pump inhibitors in H. pylori eradication regimens in Mexico. A further randomized controlled trial es required to confirm our findings.

Disclosure

JMRT has served as advisory board for Takeda, Asofarma, Carnot and and Biocodex. Also is a speaker for Takeda, Asofarma, Alfasigma, Carnot, Chinoin, Medtronic, Ferrer, and Sanofi. ECA and LRVD are speakers for Carnot and Asofarmna. ACC and GM do not have any conflict of interest

Introduction

Guselkumab (GUS) intravenous (IV) induction followed by subcutaneous (SC) maintenance with 200mg q4w or 100mg q8w was effective in the GALAXI 2 & 3 phase 3 treat-through studies of participants (pts) with moderately to severely active Crohn’s disease (CD), with similar efficacy between both maintenance doses in the overall study populations. Here, we evaluated the efficacy of maintenance doses in subgroups by baseline disease activity and severity and inflammatory burden at Week (Wk) 12 to determine if some pts may receive additional benefit from the higher maintenance dose.

Aims & Methods

Eligible pts had moderately to severely active CD (CDAI 220–450 and mean daily stool frequency score >3 or abdominal pain score >1), SES-CD ≥6 (≥4 for isolated ileal disease), and inadequate response or intolerance to oral corticosteroids, AZA, 6-MP, MTX, or biologics. Pts were randomly assigned to GUS 200mg IV at Wks 0, 4, and 8, followed by GUS SC 100mg q8w (N=286) or 200mg q4w (N=296). The studies also included placebo and ustekinumab arms, but this analysis focused on differences between GUS maintenance doses. Wk48 endpoints included clinical remission (CDAI <150) and endoscopic response (≥50% improvement in SES-CD or SES-CD ≤2). Analyses of subgroups by baseline disease activity (CDAI >300 or SES-CD >12), and inflammatory burden (CRP >5) or endoscopic response at Wk 12 were prespecified but not multiplicity controlled.

Results

In the pooled GALAXI 2 & 3 dataset, pts with baseline high disease activity (CDAI >300 or SES-CD >12) had numerically greater clinical and endoscopic outcomes at Wk 48 with 200mg q4w compared with 100mg q8w. Pts with baseline CDAI >300 had numerically greater percentages of clinical remission (200mg: 68.0% [83/122] vs 100mg: 55.1% [65/118], respectively) and endoscopic response (52.5% [64/122] vs 44.1% [52/118]) at Wk 48. Pts with baseline SES-CD >12 also had numerically greater percentages of these outcomes (clinical remission: 77.0% [94/122] vs 65.1% [82/126] and endoscopic response 67.2% [82/122] vs 58.7% [74/126]). Pts with baseline CDAI ≤300 or SES-CD ≤12 had similar Wk 48 outcomes for both maintenance doses. Pts with greater inflammatory burden (CRP >5mg/L) at Wk 12 or who were not in endoscopic response at Wk 12 also had numerically greater clinical and endoscopic outcomes at Wk 48 with 200mg compared with 100mg (Table). Pts with CRP ≤5mg/L or who were in endoscopic response at Wk 12 had similar clinical and endoscopic outcomes for both maintenance doses. Results for individual GALAXI 2 & 3 studies generally trended in the same direction for all subgroups.

Conclusion

Pts with high clinical or endoscopic disease severity at baseline, greater inflammatory burden after induction, or who had not achieved endoscopic response after induction showed greater clinical and endoscopic outcomes at Wk 48 with GUS 200mg SC q4w compared with 100mg SC q8w.

Disclosure

AA: AbbVie, Bristol Myers Squibb/Celgene, DiaSorin, Eli Lilly, Gilead, IBD Horizons, Johnson & Johnson, Pfizer, Takeda, and TLL Pharmaceuticals
TH: grants from AbbVie GK, Boston Scientific Corporation, EA Pharma Co. Ltd., JIMRO Co. Ltd., Kissei Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Pfizer Inc., Takeda Pharmaceutical Co. Ltd., and Zeria Pharmaceutical Co. Ltd.; consulting fees from AbbVie GK, Abivax, Bristol Myers Squibb, EA Pharma Co. Ltd., Gilead Sciences, Janssen Pharmaceutical K.K., Lilly, Mitsubishi Tanabe Pharma Corporation, and Pfizer Inc.; lecture fees from AbbVie GK, EA Pharma Co. Ltd., Janssen Pharmaceutical K.K., JIMRO Co., Kissei Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co. Ltd.
DTR: consulting/speaker fees/advisory board for AbbVie, Altrubio, Apex, Avalo, Bristol Myers Squibb, Buhlmann Diagnostics, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Johnson & Johnson, Lilly, Pfizer, Samsung Neurologica, and Takeda; Altrubio, Datos Health, and Iterative Health stock options; grants from Takeda; membership on Board of Directors of Cornerstones Health, Inc and Crohn’s & Colitis Foundation’s Board of Trustees.
NAT, RVR, JY, KYYW, and ZY: employees of and may own Johnson & Johnson stock.
WR: speaker for AbbVie, Celltrion, Ferring, Johnson & Johnson, Galapagos Medice, MSD, Roche, Pfizer, Sobi, Takeda; consultant for AbbVie, Amgen, AOP Orphan, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celltrion, Eli Lilly, Galapagos, Gilead, Index Pharma, Johnson & Johnson, Medahead, Microbiotica, Pfizer, Takeda; advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Galapagos, Johnson & Johnson, Pfizer; funding from AbbVie, Johnson & Johnson, Sandoz, Sanofi, Takeda.
BES: consulting fees from AbbVie, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Celltrion, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Microba, Mirador Therapeutics, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Sorriso Pharmaceuticals, Spyre Therapeutics, Sun Pharma, Surrozen, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences, and Vividion Therapeutics; consulting /speaking fees from Abivax; consulting/speaking fees/other support from Lilly; research grants/consulting/speaking fees/other support from Bristol Myers Squibb, Johnson & Johnson, Pfizer, and Takeda; stock/options from Ventyx Biopharma.
SD: consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB, and Vifor; lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, and Takeda.
RP: consulting fees from Abbivax, Abbott, AbbVie, Alimentiv, Amgen, AnaptsyBio, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Johnson & Johnson, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Spyre Therapeutics, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Union Biopharma, Viatris, Ventyx, and UCB; speaker’s fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Johnson & Johnson, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda Pharmaceuticals; Advisory Boards for AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Johnson & Johnson, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, and Ventyx.

Introduction

Anti-TNF drugs are highly effective for treating Inflammatory Bowel Disease (IBD) but have a high chance of loss of response, particularly due to immunogenicity. Using immunomodulators (IMM) can partly overcome this. The HLA-DQA105 polymorphism was identified as a predictor of anti-infliximab antibodies (AIA). However, the impact of this polymorphism in real-world studies and its association with other factors related to the development of immunogenicity needs to be established.

Aims & Methods

We aim to study the association of the polymorphism HLA-DQA1*05 with the development of AIA in a real-life cohort of patients with IBD. We conducted a retrospective cohort study including adult patients with Crohn's Disease (CD) and Ulcerative Colitis (UC) who were or have been taking infliximab (IFX) with a minimum follow-up of 6 months. DNA amplification and sequencing by Sanger methodology were used to identify the presence of the HLA-DQA1*05 polymorphism. The presence of AIA was evaluated through ELISA, and IFX trough levels (IFX TL) were assessed by a point-of-care methodology. A Cox regression analysis was performed to assess the impact of the polymorphism on the time until the development of AIA and its association with other relevant factors (use of concomitant IMM, body mass index, gender, IFX TL, baseline albumin and type of disease - CD vs UC).

Results

We included 115 patients (76% CD and 24% UC) of whom 60% were male with a median age at diagnosis of 30 years old (IQR 20-42). Almost half of the patients (52%) started combination therapy with IMM. Thirty patients (26%) developed AIA, with no significant difference between patients with CD and UC (23% vs 36%, p=0.2). The median time until the development of AIA was 8 (IQR 5-16) months. During follow-up, 34% had a primary or secondary loss of response; 37% stopped IFX and 21% had adverse effects. The prevalence of the polymorphism was 70.4%. Among patients who developed AIA, there was no difference between HLA-DQA1*05 carriers and non-carriers (21% vs 38%, p=0.06). However, there was a significant difference in the concomitant use of IMM, which was lower in the group of patients who developed AIA (13% vs 40%, p<0.01). Half of the patients needed to optimize IFX dosing and there were no differences among polymorphism carriers and non-carriers (48% vs 53%p=0.6). Patients who developed AIA had significantly lower median IFX TL when compared to patients without AIA (0.4, IQR 0.35-1.4 vs 7.4, IQR 3.4-13.5, p<0.001). There was no difference in the median IFX TL according to the presence of the polymorphism (p=0.8). The risk of developing AIA was similar between HLA-DQA1*05 carriers and non-carriers (HR 0.8, 95%CI 0.4-1.6, p=0.4) even after adjusting for the other risk factors associated with immunogenicity (HR 0.5, 95%CI 0.1-1.9, p=0.3). No differences were found according to the type of disease. Patients with the HLA-DQA1*05 polymorphism and who were using a concomitant IMM had the lowest risk of developing AIA, which was significantly lower when compared to patients who carried the polymorphism and were not taking the IMM (HR 0.2, 95%CI 0.04-0.9, p=0.03).

Conclusion

In this Portuguese cohort of IBD patients, the HLA-DQA105 polymorphism was highly prevalent and did not influence the development of AIA. Further real-world studies with larger sample sizes are needed to determine the utility of this polymorphism as a predictor of AIA.

References

1) Sazonovs A et al. HLA-DQA1*05 Carriage Associated With Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients With Crohn’s Disease. Gastroenterology, 2019;
2) Fuentes-Valenzuela E et al. Influence of HLADQA1*05 Genotype in Adults With Inflammatory Bowel Disease and Anti-TNF Treatment With Proactive Therapeutic Drug Monitoring: A Retrospective Cohort Study. Inflammatory Bowel Diseases, 2023

Introduction

Pfizer's Institute for Translational Equitable Medicine and our Chief Medical Officer, Aida Habtezion, MD, hosted an IBD Health Equity Summit at DDW 2023 in Chicago, Illinois on May 5, 2023 with a group of 22 key opinion leaders in the gastroenterology field. The purpose of the Summit was to uncover health equity research gaps and quality of care gaps that will enable Pfizer and our partners to determine future directions in IBD research and contribute to achieving healthcare equity by providing opportunities to improve patient outcomes, as well as address practice-based disparities.

Aims & Methods

A full day Summit was designed and developed, bringing together thought leaders and experts (representing research, HCPs and patients) to discuss health disparity gaps and possible solutions. The day was split into two parts: a morning session focused on research, with IBD researchers presenting different facets of the research construct with follow-on discussion with the audience. The afternoon was dedicated to clinical care and also included IBD experts addressing Health Equity concerns and opportunities. A follow-on summary report was developed, distributed and serves as the basis for current and future strategies aimed at closing disparity gaps among IBD patients.

Results

Several overarching themes emerged, highlighting IBD as a global affliction, and challenges that transcend geographical borders. Addressing these challenges will require solutions tailored to local and regional contexts that consider factors such as race, ethnicity, socio-economic status, culture, diets, and sexual orientations. It was also recognized that many of the challenges posed by IBD are not unique to this disease, and that valuable insights can be gained by examining other complex disease states to improve the quality of care and address health disparities in patients with IBD.

Conclusion

IBD Research
Key gaps include low clinical trial participation of patients from diverse communities due to lack of healthcare literacy, low historical representation, bias in recruitment, lack of diversity in providers.
Strategies to address these gaps include improving health literacy, workforce development and educating providers, adequate compensation for time, flexibility for participating in trials, and incorporation of digital health tools for follow-ups.
Clinical Care
There are groups of patients in several regions that lack any care, and addressing healthcare disparities in IBD care for these patients cannot be done online but will need to be done on a local and regional level on the ground.
When addressing health inequities, the heterogeneities within underserved populations like Black and Hispanic patients need to be considered.
Gaps in data on the effectiveness of therapies in specific patient populations (ie, response to anti-TNFs in black patients and patients with comorbidities).
Sponsorship is lacking to establish efforts in underserved communities on a global level; There is an opportunity to provide connection for minority physicians to resources.
By identifying gaps and potential strategies to close them, the participants have provided Pfizer and our partners a roadmap to address health disparities among IBD patients worldwide. These data and information have served as the basis for a go-forward plan to support and invest in change initiatives to close gaps. Our desire is to enlist additional partners and collaborators through a Call to Action to identify solutions at the local level that can accelerate improved IBD care and outcomes for some of the most vulnerable populations in the world.

Disclosure

Employee of Pfizer Inc