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

Helicobacter pylori (Hp) infection is highly prevalent in Portugal, affecting over 60% of the population. Antibiotic resistance poses a significant challenge to Hp treatment; however, empirical regimens remain the standard of care over susceptibility-guided approaches. This study aims to evaluate the most recommended therapeutic options for Hp eradication and to identify risk factors associated with treatment failure.

Aims & Methods

Prospective cohort study conducted in a single centre, including all patients treated for Hp infection between 2013 and 2024. We analysed four eradication regimens: triple therapy (Tri), bismuth quadruple therapy (QuadB), concomitant quadruple therapy (QuadC) and sequential quadruple therapy (QuadS). We collected data on patient demographics and clinical characteristics and compared adherence rates, treatment effectiveness and incidence of adverse events.

Results

Included 591 patients, with a median age of 57 years (IQR 47-66) and female sex 57.2%. The main indication for Hp testing was dyspeptic symptoms (61.1%). The prescribed therapeutic regimens were QuadC in 34.0% of patients, QuadB in 32.8%, Tri in 23.2% and QuadS in 10.0%. According to the intention-to-treat analysis, QuadC (92.9%) and QuadB (90.4%) showed significantly higher eradication rates compared with Tri (73.9%, p<0.001), with no difference observed for QuadS (84.2%, p=0.30 vs QuadC; p=0.61 vs QuadB). Adverse events were significantly less frequent with Tri (0.06%) and QuadS (0.02%) compared to QuadC (0.18%, p<0.01) and QuadB (0.17%, p<0.05), but overall adherence to treatment was 97.1%, with no significant difference among regimens (p=0.19). Logistic regression identified predictive factors for treatment failure: prior eradication attempts (OR 2.31; 95% CI 0.3-1.4), poor adherence (OR 14.5; 95% CI 0.7-4.7) and absence of statin use (OR 2.33; 95% CI 0.07-1.6), with an AUC of 0.72.

Conclusion

QuadC and QuadB therapies are more effective for Hp eradication but are associated with increased rates of adverse events, without a negative impact on overall treatment adherence. Therapeutic failure is more likely in non-naive patients, those with poor adherence to treatment and without statin use.

Introduction

Minocycline is considered the most potent semi-synthetic tetracycline, demonstrates promising pharmacokinetic and antimicrobial properties against Helicobacter pylori (H. pylori). While previous studies suggested the efficacy of minocycline-containing bismuth quadruple therapy for H. pylori eradication, real-world evidence remains limited.

Aims & Methods

his study aimed to evaluate the clinical efficacy, safety, and cost-effectiveness of minocycline-containing bismuth quadruple therapy in routine clinical practice.This multicenter, real-world observational study was conducted at 25 hospitals in Fujian China between January and March 2025. Patients diagnosed with H. pylori infection received one of three 14-day bismuth-containing quadruple regimens with b.i.d. esomeprazole 20 mg and bismuth 220 mg, plus amoxicillin 1000 mg b.i.d. and clarithromycin 250 mg b.i.d. (PBAC), or minocycline 100 mg b.i.d. and clarithromycin 250 mg b.i.d. (PBMC), or minocycline 100 mg twice b.i.d. and levofloxacin 500mg q.d. (PBML). The primary outcome was the H. pylori eradication rate, secondary outcomes included the frequency of adverse events, patient compliance, and cost-effectiveness.

Results

A total of 347 patients were enrolled, with 110 patients completing treatment in each group. In the intention-to-treat (ITT) analysis, eradication rates were 77.4% (PBAC), 85.5% (PBMC), and 84.3% (PBML). In the per-protocol (PP) analysis, eradication rates were 80.9%, 90.9%, and 88.2%, respectively. Although the differences among the three regimens were not statistically significant, minocycline-based regimens achieved numerically higher eradication rates. Adverse event incidence was 32.73%, 20.91%, and 23.64% in the three groups, respectively. Compliance rates exceeded 94% across all groups. Cost-effectiveness analysis showed PBML had the lowest cost-effectiveness ratio (5.38 CNY per 1% eradication), followed by PBAC (5.41 CNY) and PBMC (6.06 CNY).

Conclusion

H. pylori eradication, with favorable patient compliance and pharmacoeconomic profiles. These regimens present a viable alternative to traditional amoxicillin-or tetracycline-based therapies. Further large-scale randomized controlled trials are warranted to confirm these findings.