Introduction

The comparable efficacy and safety of both IV and SC induction with guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, in pts with moderately to severely active CD has been established in the phase 3 GALAXI and GRAVITI studies.^1,2,3 To determine whether pts with higher baseline disease severity respond differently to IV or SC induction, we compared the efficacy of GUS IV and SC induction in subgroups based on baseline disease characteristics.

Aims & Methods

Pts had moderately to severely active CD (CDAI 220-450 and SES-CD≥6 or if ileal disease only, SES-CD≥4), and a history of inadequate response/intolerance to oral corticosteroids, AZA/6-MP/MTX, or biologics. GUS induction regimen was 200mg IV q4w in GALAXI 2 & 3 (N=582) and 400mg SC q4w in GRAVITI (N=230), while matching IV/SC PBO q4w (N=148 and N=117, respectively) was the comparator regimen. Clinical remission (CDAI<150) and endoscopic response (≥50% improvement from baseline SES-CD) were evaluated at Wk12 for predefined subgroups based on baseline involved disease location, CDAI, SES-CD, C-reactive protein (CRP), and fecal calprotectin (FeCal). Abnormal CRP was defined as >3 mg/L and >5 mg/L for GALAXI and GRAVITI, respectively.

Results

GALAXI and GRAVITI had similar entry criteria, and baseline disease characteristics of the randomized study populations were also similar. Pts treated with IV or SC GUS induction achieved clinical remission at Wk12 in greater proportions than those who received PBO across subgroups of disease location (ileal only [IV: GUS=44%, PBO=13%; SC: GUS=56%, PBO=27%], colon only [IV: GUS=44% vs PBO=18%; SC: GUS=56% vs PBO=18%], and both ileum and colon [IV: GUS=52% vs PBO=24%; SC: GUS=57% vs PBO=22%]), baseline CDAI (≤300 [IV: GUS=52%, PBO=25%; SC: GUS=66%, PBO=26%] and >300 [IV: GUS=40% vs PBO=10%; SC: GUS=41% vs PBO=14%]), baseline SES-CD (≤12 [IV: GUS=43%, PBO=21%; SC: GUS=52%, PBO=24%] and >12 [IV: GUS=53% vs PBO=16%; SC: GUS=62% vs PBO=18%]), baseline CRP (≤3mg/L or ≤5mg/L in GALAXI and GRAVITI, respectively, [IV: GUS=45%, PBO=17%; SC: GUS=53%, PBO=28%] and >3mg/L or >5mg/L [IV: GUS=48% vs PBO=20%; SC: GUS=59% vs PBO=17%]), and baseline FeCal (≤250μg/g [IV: GUS=49%, PBO=25%; SC: GUS=60%, PBO=26%] and >250μg/g [IV: GUS=46% vs PBO=16%; SC: GUS=54% vs PBO=20%]). Endoscopic response at Wk12 was also achieved by greater proportions of GUS- than PBO-induced pts across all subgroups with either IV or SC induction (Table).

Table. Endoscopic Response at Week 12 by Baseline Disease Characteristics

Conclusion

Both IV and SC induction with GUS were similarly effective in pts with moderately to severely active CD across predefined subgroups of disease location and baseline clinical, endoscopic, and inflammatory biomarker disease activity. The treatment effects were consistent in the subgroups following IV and SC induction, particularly in those that represent high disease severity.

References

1. Sachen K, Hammaker D, Sarabia I, et al. Frontiers in Immunology. 2025: doi:10.3389/fimmu.2025.1532852.
2. Panaccione R, Danese S, Feagan BG, et al. Gastroenterology. 2024; 166(5): S1057b.
3. Hart A, Panaccione R, Steinwurz F, et al. Gastroenterology. 2025: doi:10.1053/j.gastro.2025.02.033.

Disclosure

BES reports consulting fees from Abbvie, Adiso Therapeutics, Agomab, Alimentiv , Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, Astra Zeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Fresenius Kabi, Fzatat, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Microba, 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, Spyre Therapeutics, Sun Pharma, Surrozen, Target RWE,Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences; consulting and speaking fees from Abivax; consulting and speaking fees and other support from Lilly; research grants, consulting and speaking fees and other support from Bristol Myers Squibb, Janssen, Pfizer, Takeda; research grants and consulting fees from Theravance Biopharma; and stock/stock options from Ventyx Biopharma.
TH received grant support from Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co. Ltd., Boston Scientific Corporation, Kissei Pharmaceutical Co. Ltd., consulting fees from Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, Janssen Pharmaceutical K.K., Pfizer Inc., Nichi-Iko Pharmaceutical Co. Ltd., Eli Lilly, Gilead Sciences, Bristol Myers Squibb, and lecture fee from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA pharma Co. Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc. Kissei Pharmaceutical Co. Ltd.
AA reports potential conflicts of interest with AbbVie, Bristol Myers Squibb/Celgene, DiaSorin, Eli Lilly, Gilead, IBD Horizons, Janssen, Pfizer, Takeda, and TLL Pharmaceuticals.
NAT, MO, RVR, JY, and WvD are employees of Johnson & Johnson and own company stock/stock options.
AH served as a clinical investigator and consultant for Janssen.
SD reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB and Vifor; and reports lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer and Takeda.
RP reports having received consulting fees from Abbivax, Abbott, AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring,Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx, UCB; Speaker’s Fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, Takeda Pharmaceuticals and served on Advisory Boards for: AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, and Ventyx.

Introduction

Differences in endoscopic response and biological features across ileal, ileocolonic, and colonic Crohn’s disease (CD) suggest distinct mechanisms for healing. We developed an endoscopic clustering method using segmental intestinal endoscopic scores in patients with moderately to severely active CD to investigate the potential influence of regional mucosal heterogeneity on treatment effect. We then evaluated endoscopic outcomes across subtypes between placebo (PBO), guselkumab (GUS), and ustekinumab (UST) in the Phase 3 GALAXI 2 and 3 studies.

Aims & Methods

Endoscopic clustering was established using baseline segment Simple Endoscopic Score for CD (SES-CD) values from terminal ileum, right colon, transverse colon, left/sigmoid colon, and rectum from cohort 1 (1233 patients, GALAXI 1, GALAXI 2, GRAVITI trials) and cohort 2 (525 patients, GALAXI 3). Patient clusters were identified using consensus hierarchical clustering, and a machine learning classification model was developed for patient cluster assignment of cohort 2. GALAXI 2 and GALAXI 3 patients were combined to evaluate Week (WK) 12 and WK48 endoscopic outcomes between PBO, GUS, and UST.

Results

We identified 7 CD endoscopic subtypes (ileum only, ileum dominant, right colon dominant, mid-colon, colonic, ileocolonic, rectum dominant), highlighting heterogeneity within Montreal classification. In total, GUS showed higher endoscopic remission rates than UST at WK12 and at WK48. Patient clusters were used with baseline stricturing data (SES-CD narrowing > 0) to consolidate groups with differential treatment effects: Group 1 (62% of patients, mixed ileocolonic/colonic) showed similar endoscopic remission rates at WK12 between GUS (26%) and UST (27%) with higher rates for GUS at WK48 (39-44% GUS, 30% UST); Group 2 (ileum only) and Group 3 (characterized by strictured right colon), totaling 38% of patients, showed higher endoscopic remission rates with GUS at WK12 (19%, 20%), where UST showed placebo-like efficacy (7%, 2%), with higher rates with GUS at WK48 (Group 2: 20-26% GUS, 18% UST; Group 3: 28-30% GUS, 12% UST). Endoscopic responders to GUS, and not UST, at WK12 in Group 2 and 3 patients with baseline stricturing showed greater reduction in narrowing than non-responders, contributing to 21% vs 5% reduction in total SES-CD.

Conclusion

Endoscopic patient clustering provides higher resolution of CD subtypes to delineate differential treatment effects. GUS demonstrated endoscopic efficacy across all patients at WK12, where UST showed placebo-like efficacy in 38% of patients, supporting superior endoscopic efficacy over UST across all patients by WK48. Reductions in narrowing with GUS proposes a role of GUS in affecting stricture biology in addition to broader segment-specific molecular treatment effects that will be explored in future research.

Disclosure

Dylan Richards, Loqmane Seridi, Klebea Sohn, Brad Mcrae, Natalie A. Terry, Marion Vetter, Daniel Cua, Patrick Branigan are employees of Janssen and may hold stock in Johnson & Johnson.
Walter Reinisch reports serving as a speaker for AbbVie, Celltrion, Ferring, Janssen, Galapagos Medice, MSD, Roche, Pfizer, Sobi, Takeda; serving as a consultant for AbbVie, Amgen, AOP Orphan, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celltrion, Eli Lilly, Galapagos, Gilead, Index Pharma, Janssen, Medahead, Microbiotica, Pfizer, and Takeda; serving as an advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Galapagos, Janssen, and Pfizer; and receiving research funding from AbbVie, Janssen, Sandoz, Sanofi, and Takeda.
Raja Atreya has served as a speaker or consultant, or received research grants from AbbVie, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, DrFalk Pharma, Galapagos, Gilead, InDex Pharmaceuticals, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Novartis, Pandion Therapeutics, Pfizer, Roche, Samsung Bioepis, Takeda, and Viatris.

Introduction

Accurate and timely identification and treatment of celiac disease (CeD) by clinicians is increasingly recognized to be an important issue. This study aimed to identify educational needs of healthcare providers (HCPs) in diagnosing and managing CeD by surveying HCPs across Europe (EU) and the United States (US).

Aims & Methods

A survey focused on practices, knowledge, experience, and attitudes towards CeD was conducted among gastroenterology (GI) physicians (EU and US), nurse practitioners (NPs), and physician associates (PAs); primary care physicians (PCPs), NPs, and PAs; and dietitians (US only) who see patients with CeD. The survey used a simulated patient case for decision-making context and was distributed from August to September 2023.

Results

Respondents included 378 HCPs (75 EU, 303 US); most were physicians in group practices, with significant representation from community settings. After reviewing the case, most GIs (76%-88%) included CeD in their top 3 differential diagnosis versus 65% of PCPs. 83% of PCPs recommended starting a gluten-free diet (GFD) before endoscopy vs 36%-37% for GIs. Most dietitians were comfortable providing dietary guidance for CeD but the majority would also recommend initiation of a GFD prior to endoscopy. 87%-93% of GIs would order an endoscopy to confirm diagnosis, but many are not obtaining a guideline-recommended number of biopsies, particularly from the distal duodenum.

Conclusion

This study highlights a significant need for targeted interventions to enhance the identification and evidence-based diagnosis of CeD across various healthcare specialties. In particular, the practice of initiating a GFD prior to diagnosis should be addressed.

Disclosure

NC, SC, AS, MA and DL are employees and shareholders of Takeda.