Introduction

Eosinophilic Esophagitis (EoE) is a chronic, inflammatory, immune-mediated disease, characterised by eosinophilic infiltration. EoE requires a lifelong pharmacological treatment, aimed at achieving clinical (ie. symptoms of esophageal dysfunction), endoscopic and histological remission, and slowing down the possible process of esophageal fibrosis. Recently, a novel formulation of budesonide orodispersible tablet (BOT) has become available, showing a high efficacy in randomised placebo-controlled trials. Nowadays, only few real-life data are available in literature.

Aims & Methods

This is a multicentre, prospective, observational study, aimed to evaluate in real-life setting the long-term safety profile and the clinical, endoscopic and histological effectiveness of BOT in EoE patients. Patients diagnosed with EoE, aged ≥ 18 years, treated with BOT 1 mg bid, as induction treatment for 12 weeks (T1), and with 1 mg qd as maintenance for 52 weeks (T2), were enrolled. Clinical, demographic and medication data were collected at baseline. BOT treatment outcomes were evaluated after T1 and after T2, considering EoE Endoscopic Reference Score (EREFS) for endoscopic appearance, and 3-segments eosinophilic peak infiltration for histological assessment. Moreover, the Dysphagia Symptom Questionnaire (DSQ) and Health-Related Quality of Life (HRQoL) were also collected in order to evaluate clinical response.

Results

Two-hundreds ninety-two patients (232 males, 79%; mean age 37±14) treated with BOT were enrolled, in 8 Italian Centres and 1 Israelian Centre. The most frequent symptoms at diagnosis were dysphagia (82%) and food bolus impaction (68%). At least 1 allergic comorbidity was present in 67% of patients. 259 patients were evaluated at T1: endoscopic remission was achieved in 53% of patients, with a reduction of the mean EREFS score from 3±2 to 2±1 (p<0.0001). Histological remission was obtained in 93% of patients, with 19/259 treatment non-responders. The DSQ showed a significant reduction from 30±23 vs 6±12 (p<0.001). HRQoL questionnaire score passed from 112±37 to 153±30 (p<0.0001). 136 patients completed 1 year of treatment, and 76% of them resulted in endoscopic remission. In particular, the presence of stenosis passed from 31/292 at baseline (T0) to 1/136 at T2 (p<0.0001). Histological remission was maintained in 92%, while 11/136 lost histological response after BOT tapering. As well as for T1, both DSQ (4±10) and HRQoL score (153±28) resulted improved (p<0.0001). Side effects occurred in 36 out of 292 patients (12%), and the main one was candidiasis (25/36, 70%). Only 15 of patients needed to stop the treatment. All data are resumed in Table 1.

	n T0	n T1	n T2	T0 vs T1	p	T0 vs T2	p	T1 vs T2	p
EREFS ± SD	292	259	136	3±2 vs 2±1	<0.0001	3±2 vs 1±1	<0.0001	2±1 vs 1±1	0.1
Stenosis, n	31	6	1	31/292 vs 6/259	<0.0001	31/292 vs 1/136	<0.0001	6/259 vs 1/136	0.5
Distal Esophagus Eosinophilic peak ± SD	292	259	136	40±38 vs 5±12	<0.0001	40±38 vs 5±13	<0.0001	5±12 vs 5±13	1
Mid Esophagus Eosinophilic peak ± SD	292	259	136	31±38 vs 3±12	<0.0001	31±38 vs 3±13	<0.0001	3±12 vs 3±13	1
Proximal Esophagus Eosinophilic peak ± SD	292	259	136	28±30 vs 3±11	<0.0001	28±30 vs 1±5	<0.0001	3±11 vs 1±5	0.04
DSQ ± SD	195	172	137	30±23 vs 6±12	<0.0001	30±23 vs 4±10	<0.0001	6±12 vs 4±10	0.1
HRQoL ± SD	191	162	135	112±37 vs 153±30	<0.0001	112±37 vs 153±28	<0.0001	153±30 vs 153±28	1

Table 1: Clinical, endoscopic and histologic data at baseline, after induction period and after maintenance period.

Conclusion

This study confirms the effectiveness of the treatment with BOT in both inducting and maintaining remission of EoE in a real-life setting, either considering clinical, endoscopic and histologic outcomes. Our data also showed a good safety profile, with a few patients requiring drug interruption.

References

Geow R, Arena G, Siah C, Picardo S. A retrospective real-world study on the safety and efficacy of budesonide orodispersible tablets for the induction therapy of eosinophilic oesophagitis. Therap Adv Gastroenterol. 2024 Oct 16;17:17562848241290346. doi: 10.1177/17562848241290346. PMID: 39421000; PMCID: PMC11483688.
Lucendo AJ, Miehlke S, Schlag C, Vieth M, von Arnim U, Molina-Infante J, Hartmann D, Bredenoord AJ, Ciriza de Los Rios C, Schubert S, Brückner S, Madisch A, Hayat J, Tack J, Attwood S, Mueller R, Greinwald R, Schoepfer A, Straumann A; International EOS-1 Study Group. Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial. Gastroenterology. 2019 Jul;157(1):74-86.e15. doi: 10.1053/j.gastro.2019.03.025. Epub 2019 Mar 26. PMID: 30922997.
Straumann A, Lucendo AJ, Miehlke S, Vieth M, Schlag C, Biedermann L, Vaquero CS, Ciriza de Los Rios C, Schmoecker C, Madisch A, Hruz P, Hayat J, von Arnim U, Bredenoord AJ, Schubert S, Mueller R, Greinwald R, Schoepfer A, Attwood S; International EOS-2 Study Group. Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis. Gastroenterology. 2020 Nov;159(5):1672-1685.e5. doi: 10.1053/j.gastro.2020.07.039. Epub 2020 Jul 25. PMID: 32721437.

Introduction

Local excision (LE) is increasingly used to treat early rectal cancer (cT1-2N0M0), but its role in pT2 cancer remains controversial due to a reported 20–30% risk of lymph node metastasis (LNM). Since this risk is largely linked to adverse histological features, patients without these risk factors may safely avoid completion total mesorectal excision (cTME). We aimed to refine LNM risk in pT2 rectal cancer following LE to better guide decisions on rectal-preserving treatment strategies.

Aims & Methods

Patients with pT2 rectal cancer who underwent en bloc LE for cT1-2N0M0 lesions were retrospectivelly enrolled from seven international centres (2015-2025). Eligible patients received either cTME or active surveillance with MRI follow-up for at least two years. Exclusion criteria were positive resection margins (<0.1mm), synchronous or recurrent colorectal cancer and (neo)adjuvant therapy. LNM were confirmed through TME histology or considered absent when no suspicious lymph nodes appeared on follow-up MRI. A detailed histological review of LE specimens was conducted by specialised pathologists at each participating centre using a standardised protocol. Assessed risk factors included high-grade differentiation and/or mucinous subtype, lymphovascular invasion (small and/or large vessels), tumour budding grade 2-3 and/or poorly differentiated clusters grade 2-3, and perineural invasion. Primary endpoint was LNM rate in patients without histological risk factors. Secondary endpoints included the association between individual risk factors and LNM, as well as locoregional recurrences during active surveillance.

Results

A total of 103 patients (mean age 66 (SD 10), 56% male) with a median lesion size of 25mm (IQR 15) were included. Endoscopic LE was performed in 31 patients (30%) and surgical LE in 72 (70%). After LE, 76 patients (74%) underwent cTME while 27 (26%) opted for active surveillance. The overall LNM rate was 17.5% (18/103). Among the 36 patients (35%) without histological risk factors, the LNM rate was 5.6% (2/36; OR 0.19, 95% CI 0.04-0.87, p=0.032). Both LNM cases were detected in the cTME group. LNM rates per individual risk factor are presented in Table 1.
In the active surveillance group, no locoregional recurrences occurred in the ten patients without risk factors during a median follow-up of 53 months (IQR 26). Among patients with risk factors, two of 14 patients with one risk factor developed a locoregional recurrence and one of two patients with two risk factors. All recurrences occurred intramurally following prior surgical LE. The only patient with three risk factors had no locoregional recurrence but died from unrelated cause at 24 months.

Table 1. Univariate analyses of histological risk factors for lymph node metastasis

Risk factor	n/N (%)	Lymph node metastasis rate (%)	Odds ratio (95% CI)	P-value
No histological risk factors	36/103 (35.0)	2/36 (5.6)	0.19 (0.04-0.87)	0.032
Lymphovascular invasion Small vessel invasion Large vessel invasion	47/103 (45.6) 32/103 (31.1) 28/103 (27.2)	12/47 (25.5) 11/32 (34.4) 4/28 (14.3)	7.0 (2.2-21.8) 4.3 (1.5-12.5) 7.5 (2.4-23.3)	0.055 0.004 0.604
Tumour budding and/or poorly differentiated clusters grade 2-3 Tumour budding grade 2-3 Poorly differentiated clusters grade 2-3	36/103 (35.0) 29/103 (28.2) 19/103 (18.4)	13/36 (36.1) 10/29 (34.5) 9/19 (47.4)	7.0 (2.2-21.8) 4.3 (1.5-12.5) 7.5 (2.4-23.3)	<0.001 0.007 <0.001
Adverse histology Poor tumour differentiation Mucinous subtype	13/103 (12.6) 7/103 (6.8) 6/103 (5.8)	6/13 (46.2) 3/7 (42.9) 3/6 (50.0)	5.6 (1.6-19.4) 4.1 (0.8-20.0) 5.5 (1.0-29.7)	0.007 0.086 0.049
Perineural invasion	11/103 (10.7)	5/11 (45.5)	5.1 (1.3-19.0)	0.016

Conclusion

In this group of pT2 rectal cancer patients treated with LE, detailed histological analysis suggests a low LNM risk (5.6%) in patients without histological risk factors. No locoregional recurrences occurred in this low-risk group during active surveillance. As 35% of pT2 rectal cancers lacked histological risk factors, a risk-stratified approach could potentially allow a substantial proportion of patients to avoid cTME. Prospective validation in larger cohorts is needed before clinical implementation.

Introduction

The TOGAS consortium (TOwards GAstric cancer Screening) was established to explore effective gastric cancer screening strategies within Europe. One key method involves the detection and eradication of Helicobacter pylori (H. pylori), the leading causative agent of gastric cancer. In Western Europe, infection rates are higher among males, smokers, and individuals of lower socioeconomic status—groups that tend to engage less with preventive health services.

Aims & Methods

This pilot study aimed to determine whether targeted screening in high-risk occupational settings improves participation and outcomes compared to population-based screening via general practice.
Key outcome measures included;

1. Response rate
2. Prevalence of the infection
3. Treatment effectiveness

This prospective pilot study recruited individuals aged 30–34 years from January 2024 to March 2025. Participants were invited either through general practices (general population group, GP) or through two occupational screening programs (targeted group, TG) representing higher-risk, male-dominated workforces: the Irish Defence Forces and Construction Workers Health Trust. Exclusion criteria included prior H. pylori treatment or gastrectomy. All participants underwent serologic screening (BIOHIT H. pylori IgG antibody). The TG was offered initial on-site screening at their workplace; the GP group attended a local hospital. All seropositive individuals were offered confirmatory 13-C urea breath testing (Richen IR Force 200) in a local hospital. Confirmed cases were offered a 10-day regimen of PYLERA (Metronidazole/Tetracycline/Bismuth subcitrate) with Esomeprazole 40 mg BD. Eradication was assessed ≥6 weeks post-treatment. Response rates, demographics, infection prevalence, and treatment outcomes were analyzed using Mann-Whitney U and Chi² tests (significance p < 0.05).

Results

3030 individuals were invited for screening: 2824 in the GP group(GPG), 206 in the TG. Key demographics and risk factors of each group are shown in Table 1. The invitation response and participation rates were significantly higher in the TG versus the GPG (31% v’s 14%; p < 0.001, 30% v’s 14% p <0.00, respectively). H. pylori seroprevalence rates were similar between groups: 18% (11/60) in the TG, 19% (64/333) in the GPG (p<0.70). Confirmatory 13-C UBT was completed in 91% (10/11) of those who tested positive in the TG and 98% (63/64) of the GPG. Overall, ‘true’ prevalence rates based on serology & confirmatory 13-C UBT results were 10%(6/59) in the TG v’s 14% (44/325) in the GPG(p = 0.47). Treatment adherence exceeded 90% in both groups, with 100% adherence in the TG and 90% in the GPG. Among those who completed post-treatment testing (n=37), eradication was achieved in 100% of the TG (2/2) and 89% of the GPG (31/35).

Table 1 Basic Demographics by Group

	Targeted group	General population
Gender, male	97%	33%
Median age, years	31	32
Smoking status Current/previous Non-smoker	41% (24) 59% (34)	34% (137) 66% (266)
Socioeconomic status(self-rated) Higher Middle Lower Prefer not to answer	69% (40/58) 22% (13/58) 0 9% (5/58)	85% (337/397) 11% (42/397) 0% (2/397) 4% (16/397)
Family history of H.pylori infection	3% (2)	9% (36)

Conclusion

Targeted occupational screening in high-risk populations demonstrated superior response and engagement rates compared to general practice-based screening. These early results suggest this approach may be a more effective and resource-conscious strategy in low-to-intermediate risk countries and merit further evaluation in broader implementation efforts.

References

1. Teo CH, Ng CJ, Booth A, White A. Barriers and facilitators to health screening in men: A systematic review. Soc Sci Med. 2016 Sep;165:168-176. doi: 10.1016/j.socscimed.2016.07.023. Epub 2016 Aug 1. PMID: 27511617. 5.
2. Lou L, Wang L, Zhang Y, et al. Sex difference in incidence of gastric cancer: an international comparative study based on the Global Burden of Disease Study 2017.BMJ Open 2020;10:e033323. doi: 10.1136/bmjopen-2019-033323
3. Salmani H, Ahmadi M, Shahrokhi N. The Impact of Mobile Health on Cancer Screening: A Systematic Review. Cancer Informatics. 2020;19. doi:10.1177/1176935120954191
4. CSO. (2023, May 30). Employment, Occupation, Industry and Commuting - CSO -Central Statistics Office. https://www.cso.ie/en/releasesandpublications/ep/pcpsr/censusofpopulation2022- summaryresults/employmentoccupationindustryandcommuting/

Disclosure

Dr. Deane reports receipt of research funding support from EU4 Health grant GA number: 101101252. Receipt of ​13-C Urea Breath Test bags for this study was provided for by Richen - Dr Deane was the winner of the Richen Global ​Research Competition 2023

Introduction

The phase 2b GALAXI 1 and phase 3 GALAXI 2&3 studies evaluated guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, in participants (pts) with moderately to severely active CD.¹ Pts treated with ustekinumab (UST) who met inadequate response criteria during the long-term extension (LTE) could cross over to GUS 200 mg SC q4w. Here, we present efficacy and safety results in pts who received GUS after experiencing an inadequate response to UST in the pooled GALAXI LTE.

Aims & Methods

Individuals with prior inadequate response or intolerance to UST were excluded from GALAXI; however, during the LTE, pts treated with UST 90 mg SC q8w who met inadequate treatment response criteria (not in clinical response [≥100-point reduction in CDAI score from baseline or CDAI<150] and CDAI ≥220) between Wks 52-80 of LTE were eligible for a treatment switch to GUS 200 mg SC q4w, without IV induction. Clinical response and clinical remission (CDAI<150) were both assessed 16 weeks after treatment switch. Endoscopic response (≥50% improvement from baseline SES-CD or SES-CD≤2) and endoscopic remission (SES-CD≤4 and ≥2-point reduction from baseline and no subscore >1 in any individual component) were assessed at Wk 96. Safety was assessed through Wk 96.

Results

In total, 80 pts treated with UST underwent treatment switch to GUS 200 mg SC q4w maintenance therapy due to meeting inadequate treatment response criteria between Wks 52-80 of the LTE. Of these 80 pts, 75 were included in the efficacy analyses (baseline mean age, 35.2yrs; male, 64.0%; mean CD disease duration, 8.21yrs; mean CDAI, 291.5; mean SES-CD, 12.8; history of inadequate response/intolerance to biologics [BIO-IR], 60.0%).
The proportions of pts achieving clinical response and clinical remission 16 weeks after treatment switch from UST to GUS 200 mg SC q4w were 61.3% and 52.0%, respectively. These results were comparable to the proportions of pts treated with GUS 200 mg IV q4w induction in the BIO-IR subgroup of the total LTE population who achieved clinical response and clinical remission at Wk 12 (61.7% and 46.7%, respectively).
The proportions of pts achieving endoscopic response and endoscopic remission at Wk 96 (ie, ~1 year after treatment switch from UST to GUS 200 mg SC q4w) were 49.3% and 30.7%, respectively. These results were similar to the proportions of pts in the BIO-IR subgroup receiving GUS 200 mg SC q4w maintenance who achieved endoscopic response and endoscopic remission at Wk 48 (57.2% and 35.5%, respectively).
Safety results are summarized in the Table.

Table. Safety Summary From Treatment Switch Through Week 96

	Ustekinumab 90 mg SC q8w → Guselkumab 200 mg SC q4wa
N	80
Average duration of follow-up, weeks	34.8
Average exposure, number of administrations	8.4
Participants with 1 or more: AEs, n (%) SAEs, n (%) AEs leading to DC of study agent, n (%) Serious infections,b n (%) Malignancies, n (%) Injection site reaction, n (%)	50 (62.5%) 6 (7.5%) 2 (2.5%) 0 1 (1.3%) 5 (6.3%)
AE= adverse event; DC= discontinuation; SAE= serious adverse event; SC= subcutaneous. a Participants who were randomized to ustekinumab at Week 0 or who switched from placebo to ustekinumab at Week 12 and continued SC maintenance dosing of ustekinumab in the maintenance period and switched to guselkumab 200 mg SC q4w dosing during the long-term extension. b Infections are based on MedDRA system organ class “Infections and Infestations”. Note: Participants are counted only once for any given event, regardless of the number of times they actually experienced the event.

Conclusion

Among pts who experienced inadequate response to UST in the LTE, more than half achieved clinical remission 16 weeks after treatment switch to GUS 200 mg SC q4w, and approximately 50% were in endoscopic response ~1 year after treatment switch. These data suggest pts with an inadequate treatment response to UST may benefit from GUS treatment. Results should be interpreted considering that pts received GUS SC maintenance therapy directly without IV induction. Key safety event rates were consistent with the known safety profile of GUS in approved indications.

References

1) Sachen K, Hammaker D, Sarabia I, et al. Frontiers in Immunology. 2025; doi:10.3389/fimmu.2025.1532852.

Disclosure

AA reports potential conflicts of interest with AbbVie, Bristol Myers Squibb/Celgene, DiaSorin, Eli Lilly, Gilead, IBD Horizons, Janssen, Pfizer, Takeda, and TLL Pharmaceuticals
DW reports consulting fees from AbbVie, Bristol Myers Squibb, Janssen, Lilly, Pfizer, Takeda
RL reports having received advisory board fees from AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, and Takeda; received research grants from Celltrion, Shire, Janssen, Takeda, Joanna Tiddy grant from University of Sydney, McCusker Charitable Trust, Gastroenterological Society of Australia, NHMRC, Gutsy Group, and Pfizer
RVR, WvD, and CB are employees of Johnson & Johnson and own company stock/stock options.
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.
JP reports consultancy fees/honorarium from AbbVie, Alimentiv, Athos, Atomwise, Boehringer Ingelheim, Celsius, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Surrozen, Takeda, and Wasserman, and has served on a data safety monitoring board for Alimentiv, Mirum, Sorriso, Sanofi, and Surrozen.

Introduction

Guselkumab (GUS), a dual-acting interleukin-23p19 subunit inhibitor, demonstrated efficacy in participants (pts) with ulcerative colitis (UC) treated with intravenous (IV) or subcutaneous (SC) induction. Here, we report the efficacy and safety of SC induction followed by SC maintenance through Week (W) 48 in ASTRO, a phase 3, randomized, double-blind, placebo (PBO)-controlled, treat-through study in pts with moderately to severely active UC.

Aims & Methods

Eligible pts had modified Mayo scores of 5 to 9, rectal bleeding subscore of ≥1, and Mayo endoscopic subscore (MES) ≥2. Pts also had documented inadequate response/intolerance to biologics, Janus kinase (JAK) inhibitors, and/or sphingosine-1-phosphate (S1P) inhibitors (BIO/JAKi/S1Pi-IR) or to corticosteroids, 6-mercaptopurine, or azathioprine. Randomization was stratified by baseline BIO/JAKi/S1Pi-IR status and MES with 418 pts allocated 1:1:1 to GUS 400 mg SC every 4 weeks (q4w) (×3)→GUS 200 mg SC q4w (N=140), GUS 400 mg SC q4w (×3)→GUS 100 mg SC every 8 weeks (q8w) (N=139), or PBO SC (N=139). PBO pts who met rescue criteria were switched to GUS at W16; GUS pts who met rescue criteria stayed on their assigned GUS dose regimen (sham rescue).

Results

At W48, greater proportions of pts in the GUS groups achieved clinical remission compared with PBO (36.7% for GUS 100 mg q8w [Δ 29.5%], 42.9% for GUS 200 mg q4w [Δ 35.6%], 7.2% for PBO) (Table). Endoscopic remission proportions were 25.9% for GUS 100 mg q8w (Δ 20.9%), 26.4% for GUS 200 mg q4w (Δ 21.4%), and 5.0% for PBO. Clinical response, symptomatic remission, endoscopic improvement, histologic improvement, and histologic remission proportions were also greater for GUS vs PBO. Consistent with the results of the overall population, efficacy was also observed for subpopulations of BIO/JAKi/S1Pi-naïve and BIO/JAKi/S1Pi-IR pts. Safety events per 100 pts-years were not greater in the GUS groups compared with the PBO group: adverse events (AE) (GUS 100 mg q8w and 200 mg q4w vs PBO: 308.3 and 310.7 vs 357.1), serious AEs (6.5 and 8.2 vs 38.4), serious infections (0.8 and 2.5 vs 3.7), and AEs leading to treatment discontinuation (4.9 and 4.1 vs 19.8).
Table. Efficacy endpoints at Week 48 in the overall population and by biologic, JAK inhibitor, and/or S1P inhibitor history

	Overall			BIO/JAKi/S1Pi-naïve			BIO/JAKi/S1Pi-IR
Outcomes at Week 48	Placebo SC (N=139)	GUS 400 mg SC→ GUS 100 mg SC q8w (N=139)	GUS 400 mg SC→ GUS 200 mg SC q4w (N=140)	Placebo SC (N=79)	GUS 400 mg SC→ GUS 100 mg SC q8w (N=81)	GUS 400mg SC→ GUS 200mg SC q4w (N=83)	Placebo SC (N=56)	GUS 400 mg SC→ GUS 100 mg SC q8w (N=57)	GUS 400 mg SC→ GUS 200 mg SC q4w (N=55)
Clinical remission	10 (7.2)	51 (36.7) Δ 29.5 P<0.001	60 (42.9) Δ 35.6 P<0.001	6 (7.6)	39 (48.1) Δ 40.3 P<0.001	42 (50.6) Δ 43.0 P<0.001	4 (7.1)	12 (21.1) Δ 13.7 P=0.034	18 (32.7) Δ 25.2 P<0.001
Clinical response	26 (18.7)	78 (56.1) Δ 37.4 P<0.001	83 (59.3) Δ 40.6 P<0.001	19 (24.1)	52 (64.2) Δ 39.5 P<0.001	54 (65.1) Δ 40.8 P<0.001	7 (12.5)	25 (43.9) Δ 30.9 P<0.001	29 (52.7) Δ 39.3 P<0.001
Endoscopic improvement	16 (11.5)	62 (44.6) Δ 33.1 P<0.001	66 (47.1) Δ 35.6 P<0.001	10 (12.7)	46 (56.8) Δ 44.0 P<0.001	45 (54.2) Δ 41.7 P<0.001	6 (10.7)	16 (28.1) Δ 16.0 P=0.024	21 (38.2) Δ 26.8 P<0.001
Endoscopic remission	7 (5.0)	36 (25.9) Δ 20.9 P<0.001	37 (26.4) Δ 21.4 P<0.001	5 (6.3)	27 (33.3) Δ 26.9 P<0.001	28 (33.7) Δ 27.5 P<0.001	2 (3.6)	9 (15.8) Δ 11.5 P=0.033	9 (16.4) Δ 12.6 P=0.025
Symptomatic remission	20 (14.4)	66 (47.5) Δ 33.1 P<0.001	75 (53.6) Δ 39.2 P<0.001	15 (19.0)	47 (58.0) Δ 38.6 P<0.001	51 (61.4) Δ 42.3 P<0.001	5 (8.9)	19 (33.3) Δ 24.3 P=0.001	24 (43.6) Δ 34.0 P<0.001
Histologic improvement	18 (12.9)	65 (46.8) Δ 33.8 P<0.001	73 (52.1) Δ 39.2 P<0.001	13 (16.5)	45 (55.6) Δ 38.6 P<0.001	50 (60.2) Δ 43.8 P<0.001	4 (7.1)	20 (35.1) Δ 26.8 P<0.001	23 (41.8) Δ 34.1 P<0.001
Histologic remission	15 (10.8)	52 (37.4) Δ 26.6 P<0.001	63 (45.0) Δ 34.2 P<0.001	11 (13.9)	35 (43.2) Δ 29.1 P<0.001	41 (49.4) Δ 35.5 P<0.001	4 (7.1)	17 (29.8) Δ 21.5 P=0.002	22 (40.0) Δ 32.4 P<0.001
Data are presented as n (%); ∆% (adjusted treatment difference) versus placebo; nominal p-value versus placebo. The adjusted treatment difference was based on the common risk difference by use of the Mantel-Haenszel stratum weights and the Sato variance estimator. In the overall population, the p-values were based on the Mantel-Haenszel test, stratified by BIO/JAKi/S1Pi-IR status (Yes/No) and Mayo endoscopic subscore at baseline (Moderate [2]/Severe [3]). For the BIO/JAKi/S1Pi-naive/-IR subgroups, the p-values were stratified only by the Mayo endoscopic subscore at baseline. Participants who, prior to Week 48, had an ostomy or colectomy, a prohibited change in UC medications, discontinued study agent due to lack of efficacy or an AE of worsening of UC, or met rescue criteria per IWRS were considered not to have achieved any of the key efficacy endpoints shown at Week 48. For participants who discontinued study agent due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis, their observed values were used, if available. Participants who discontinued study agent prior to Week 48 due to other reasons were considered not to have achieved any of the efficacy endpoints shown at Week 48. Participants who were missing one or more of the components pertaining to an endpoint at Week 48 were considered not to have achieved the endpoint. Endpoint definitions: clinical remission, Mayo SFS 0/1 and not increased from BL, Mayo RBS=0, and MES 0/1 with no friability; clinical response, ≥30% and ≥2-point decrease from BL in Modified Mayo score with ≥1-point decrease from BL in RBS or RBS 0/1; endoscopic improvement, MES 0/1 with no friability; endoscopic remission, MES of 0; symptomatic remission, SFS 0/1 and not increased from BL and RBS=0; histologic improvement, neutrophil infiltration in <5% of crypts; no crypt destruction; and no erosions, ulcerations, or granulation tissue per Geboes grading system; histologic remission, absence of neutrophils from the mucosa (both lamina propria and epithelium); no crypt destruction; and no erosions, ulcerations, or granulation tissue per Geboes grading system. AE=adverse event; BIO=biologic; BL=baseline; COVID-19=coronavirus disease 2019; GUS=guselkumab; IR=inadequate response; IWRS=Interactive Web Response System; JAK=Janus kinase; JAKi=JAK inhibitor; MES=Mayo endoscopic subscore; N=population size; n=sample size; [HZ1] q4w=every 4 weeks; q8w=every 8 weeks; RBS=rectal bleeding subscore; S1P=sphingosine-1-phosphate; S1Pi=S1P inhibitor; SC=subcutaneous; SFS=stool frequency subscore; UC=ulcerative colitis

Conclusion

GUS SC induction followed by SC maintenance was efficacious through 1 year in pts with moderately to severely active UC, and the safety profile is consistent with GUS in its approved indications including UC.

Disclosure

ML reports research support from Lilly, Pfizer, and Takeda; consulting for AbbVie, Bristol Myers Squibb, Intercept, Janssen (Johnson & Johnson), Lilly, Pfizer, Prometheus, Roivant, Takeda, and Target RWE.
JRA reports grant support from Janssen, Merck, and Pfizer; consultancy fees from AbbVie, Adiso, Bristol Myers Squibb, Ferring, Genentech, GlaxoSmithKline, Janssen, Merck, Pfizer, Roivant, Celltrion, TrexBio, Shattuck Labs and Seres Therapeutics; payments for speaking from AbbVie, Bristol Myers Squibb, and Janssen; and is a steering committee member and investigator 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.
MG, TB, YA, KH, SJ, LJ, and HZ are employees of and may own stock in Johnson & Johnson.
TH reports research 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.; and 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 reports consulting and/or speaker fees and/or advisory board participation for AbbVie, Altrubio, Apex, Avalo, Bristol Myers Squibb, Buhlmann Diagnostics, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Janssen (Johnson & Johnson), Lilly, Pfizer, Samsung Neurologica, and Takeda; Altrubio, Datos Health, and Iterative Health stock options; grants from Takeda; and membership on the Board of Directors of Cornerstones Health, Inc. and on the Crohn’s & Colitis Foundation’s Board of Trustees.
LPB reports grants or contracts from Celltrion, Fresenius Kabi, Medac, MSD, and Takeda; consulting and/or payment or honoraria and/or data safety monitoring board or advisory board participation for AbbVie, Abivax, Adacyte, Alfasigma, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, Bristol Myers Squibb, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GlaxoSmithKline, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Kern Pharma, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par' Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx, and Ysopia; and meeting attendance/travel support from AbbVie, Alfasigma, Amgen, Celltrion, Connect Biopharm, Ferring, Galapagos, Genentech, Gilead, Gossamer Bio, Janssen, Lilly, Medac, Morphic, MSD, Pfizer, Sandoz, Takeda, Thermo Fischer, and Tillots.