EFFICACY AND SAFETY OF THE SELECTIVE SPHINGOSINE 1-PHOSPHATE RECEPTOR MODULATOR, ETRASIMOD, IN ADULT PATIENTS WITH EOSINOPHILIC OESOPHAGITIS OVER 52 WEEKS IN THE PHASE 2 VOYAGE STUDY

UEG Poster

Standard Poster

Log in to access this content.

Free for all myUEG account holders. Your access level is set automatically based on your occupation. Medical professionals get full access to all content. If you are a non-medical user, you can only access UEG Week content from congresses you attended.

Log In Create a free account

Not sure what you can access? Learn more about account types.

Introduction

C-reactive protein (CRP) and fecal calprotectin (FeCal) are non-invasive inflammatory biomarkers used to assess disease activity in UC. The Phase 3 QUASAR induction study evaluated the efficacy and safety of guselkumab (GUS), an IL-23 p19 subunit antagonist, in patients (pts) with moderately to severely active UC. Here, we analyze the effect of GUS treatment on CRP and FeCal through Week (Wk) 12 in pts with elevated CRP and/or FeCal.

Aims & Methods

Pts with a modified Mayo score of 5-9 and a Mayo endoscopy subscore ≥2 at baseline (BL) were randomized 3:2 to receive either GUS 200mg IV or placebo (PBO) IV at Wks0, 4, and 8. CRP and FeCal were assessed at BL, Wk4, Wk8 (for CRP only), and Wk12.

Results

A total of 701 pts were evaluated and approximately 50% of randomized pts had a history of inadequate response/intolerance to advanced therapies (ADT) for UC; 47.4% of these pts had inadequate response/intolerance to ≥2 ADT classes. Median BL concentrations of CRP and FeCal were similar between the GUS-treated and PBO-treated pts (4.34 vs 3.83mg/L and 1651 vs 1606mg/kg, respectively). Among pts with elevated CRP and/or FeCal at BL, greater reductions in CRP and FeCal were observed at the earliest timepoint assessed (Wk4) with GUS and continued through Wk12 compared with PBO (Table).
At BL, 248 GUS-treated pts and 160 PBO-treated pts had elevated CRP (>3mg/L); the proportions were similar between treatment groups (58.9% vs 57.1%, respectively). Among these pts, median change from BL in CRP concentration (mg/L) at Wk12 for the GUS and PBO cohorts were -3.99 and -0.51mg/L, respectively (nominal p<0.001); the proportions of pts achieving 50% and 75% reduction in CRP levels (or ≤3mg/L) at Wk12 were higher for GUS-treated pts than those receiving PBO (59.7% vs 28.1% and 47.2% vs 19.4%, respectively; both nominal p<0.001). Similarly, a higher proportion of GUS-treated pts achieved CRP≤3mg/L at Wk12 than PBO-treated pts (40.3% vs 16.3%, nominal p<0.001).
At BL, 333 GUS-treated pts and 225 PBO-treated pts had elevated FeCal (>250mg/kg); the proportions were similar between treatment groups (79.1% vs 80.4%, respectively). Median change from BL in FeCal concentration (mg/kg) for pts with elevated FeCal at BL at Wk12 were -800 and -86mg/kg for the GUS and PBO cohorts, respectively (nominal p<0.001); the proportions of pts achieving 50% and 75% reduction in FeCal levels (or ≤250 mg/kg) at Wk12 were higher for GUS-treated pts than those receiving PBO (51.1% vs 33.8% and 41.4% vs 23.6%, respectively; both nominal p<0.001). A larger percentage of pts treated with GUS achieved FeCal≤250mg/kg at Wk12 than pts treated with PBO (29.4% vs 17.3%, nominal p<0.001).

Table. Change from baseline in CRP and FeCal through Week 12 among patients with elevated CRP (>3mg/L) or FeCal (>250mg/kg) at baseline
	Placebo IV	Guselkumab 200 mg IV
CRP (mg/L) Baseline, N Median [IQR]	160 8.02 [5.40; 16.85]	248 9.26 [5.31; 18.05]
Wk 4, N Median change from baseline [IQR]	158 -2.06 [-5.70; 1.58]	245 -3.35 [-8.60; -0.23]***
Wk 8, N Median change from baseline [IQR]	156 -1.75 [-5.68; 1.46]	239 -3.80 [-10.77; -0.19]***
Wk 12, N Median change from baseline [IQR]	153 -0.51 [-4.64; 2.72]	239 -3.99 [-11.46; -0.85]***
FeCal (mg/kg) Baseline, N Median [IQR]	225 1743 [1120; 3395]	333 1787 [920; 4009]
Wk 4, N Median change from baseline [IQR]	213 -227 [-1041; 658]	308 -603 [-1866; 230]***
Wk 12, N Median change from baseline [IQR]	201 -86 [-1254; 504]	293 -800 [-2532; 0]***
***Nominal P≤0.001. Patients who had a prohibited change in UC medication, an ostomy or colectomy, or discontinued study agent due to lack of efficacy or an AE of worsening of UC or other reasons except for COVID-19 related reasons (excluding COVID-19 infection) or regional crisis in Russia and Ukraine prior to the designated timepoint had their baseline value carried forward from the time of the event onward. The p-values of treatment comparison were based on the mixed-effect model repeated measures with CRP and FeCal values being log-transformed.

Conclusion

In this phase 3 induction study, pts with moderately to severely active UC and elevated inflammatory markers treated with GUS 200mg IV induction showed greater improvement from BL in both CRP and FeCal levels compared with PBO. Differences were observed as early as the first assessments at Wk4 and continued through Wk12.

Disclosure

Tadakazu Hisamatsu received consulting fees from Janssen Research & Development, LLC.
Laurent Peyrin-Biroulet reports personal fees from Janssen.
Axel Dignass reports fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees from Janssen; consultancy fees from Janssen; and payment from lectures including service on speakers bureaus from Janssen.
Kuan-Hsiang G. Huang, Matthew Germinaro, Nicole Houck,Ye Miao, and Hongyan Zhang are employees of Johnson & Johnson and own company stock/stock options.
Marjorie Argollo reports consulting fees from Janssen.
Ken Takeuchi has served as a speaker for Janssen.
Rafal Filip reports lecture fees and research/education support from Janssen.
Jessica R. Allegretti is a consultant and speaker for Janssen.
Brian G. Feagan received consulting fees from Janssen; a member of the speakers bureau for Janssen; support for attending meetings and/or travel from Janssen; and participation on a Data Safety Monitoring Board or Advisory Board from Janssen.
Bruce E. Sandsreports grants, consulting and speaking fees and other support from Janssen.

IMPROVEMENT IN INFLAMMATORY BIOMARKER LEVELS THROUGH WEEK 12 IN MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS PATIENTS TREATED WITH GUSELKUMAB: RESULTS FROM THE PHASE 3 QUASAR INDUCTION STUDY

Tadakazu Hisamatsu 1, Laurent Peyrin-Biroulet 2, Axel Dignass 3, Gary KH Huang 4, Matthew Germinaro 4, Nicole Houck 4, Ye Miao 4, Hongyan Zhang 4, Marjorie Costa Argollo 5, Ken Takeuchi 6, Rafal Filip 7, Jessica Allegretti 8, Brian G. Feagan 9, Bruce E. Sands 10

1 Kyorin University, Tokyo, Japan

2 Nancy University Hospital, Université de Lorraine, Nancy, France

3 Agaplesion Markus Hospital, Goethe University, Frankfurt, Germany

4 Janssen Research & Development, LLC, Spring House, United States

5 Onco Star SP Oncologia Ltda, Sao Paulo, Brazil

6 Tsujinaka Hospital Kashiwanoha, Kashiwa, Japan

7 Clinical Hospital No. 2, Rzeszow, Poland

8 Brigham and Women´s Hospital, Boston, United States

9 Alimentiv Inc, London, Canada

10 Icahn School of Medicine at Mount Sinai, New York, United States

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

PP 05 IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

UEG Poster

Standard Poster

Log in to access this content.

Free for all myUEG account holders. Your access level is set automatically based on your occupation. Medical professionals get full access to all content. If you are a non-medical user, you can only access UEG Week content from congresses you attended.

Log In Create a free account

Not sure what you can access? Learn more about account types.

Introduction

The Phase 3 QUASAR Maintenance Study is a randomized-withdrawal, double-blind, placebo (PBO)-controlled, study that evaluated the efficacy and safety of maintenance treatment with subcutaneous (SC) guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor that binds to CD64, in patients (pts) with moderately to severely active ulcerative colitis (UC) who had prior inadequate response or intolerance to conventional or advanced therapy (ADT) and demonstrated a clinical response to GUS IV induction.

Aims & Methods

At maintenance baseline, clinical responders to 12 weeks of GUS IV induction from QUASAR Phase 2b and Phase 3 induction studies (NCT04033445) were randomized 1:1:1 to SC GUS 200mg q4w, GUS 100mg q8w, or PBO (GUS withdrawal). The primary endpoint was clinical remission at Week (Wk) 44. Major secondary endpoints included corticosteroid-free clinical remission, maintenance of clinical remission, maintenance of clinical response, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization (remission) at Wk44.

Results

The primary analysis population included 568 pts (mean age, 40.7yr; mean UC duration, 7.8yr; mean modified Mayo score, 6.9 [63.9% with severe disease]; Mayo endoscopy subscore of 3, 66.4%; baseline oral corticosteroid use, 40.0%). Approximately 42% had prior inadequate response or intolerance to ADT (TNF antagonists, vedolizumab, or tofacitinib), and 48.3% of these pts failed ≥2 ADT. Disease characteristics were similar across treatment groups at induction and maintenance baseline.
With both GUS SC maintenance regimens, a significantly higher proportion of pts achieved the primary endpoint and all the major secondary endpoints at Wk44 compared with GUS withdrawal (Table 1).
The proportion of pts with ≥1 adverse events (AEs) was similar across treatment groups: GUS 200mg q4w, 70.0%; GUS 100mg q8w, 64.5%, and GUS withdrawal, 68.2%. The most common AEs in the combined GUS group vs withdrawal group were COVID-19 (11.2% vs 14.1%), UC (11.2% vs 29.7%), and arthralgia (6.1% vs 6.8%), respectively.
No cases of death, active tuberculosis, opportunistic infection, anaphylaxis, serum sickness, Hy’s Law, or serious hepatic AEs were reported. Two cases of malignancy (clear cell renal carcinoma, rectal adenocarcinoma) and 1 major adverse cardiovascular event (hemorrhagic stroke) were reported among GUS-treated pts (primary safety population).

Table 1. Primary and major secondary endpoints at Week 44: Primary analysis population

	GUS Withdrawal (Placebo) (N=190)	GUS 100 mg q8w (N=188)	GUS 200 mg q4w (N=190)
Clinical remission (primary endpoint), n (%)^a Adjusted treatment difference (95% CI)	36 (18.9%)	85 (45.2%) 25.2 (16.4, 33.9), P<0.001	95 (50.0%) 29.5 (20.9, 38.1), P<0.001
Corticosteroid-free clinical remission, n (%)^b Adjusted treatment difference (95% CI)	35 (18.4%)	85 (45.2%) 25.7 (17.0, 34.5), P<0.001	93 (48.9%) 29.0 (20.5, 37.6), P<0.001
Maintenance of clinical remission, n/N (%)^c Adjusted treatment difference (95% CI)	20/59 (33.9%)	40/66 (60.6%) 25.9 (9.2, 42.5), P=0.004	50/69 (72.5%) 38.4 (22.7, 54.1), P<0.001
Maintenance of clinical response, n (%)^d Adjusted treatment difference (95% CI)	82 (43.2%)	146 (77.7%) 33.6 (24.5, 42.7), P<0.001	142 (74.7%) 30.7 (21.5, 40.0), P<0.001
Symptomatic remission, n (%)^e Adjusted treatment difference (95% CI)	71 (37.4%)	132 (70.2%) 31.9 (22.5, 41.2), P<0.001	131 (68.9%) 30.5 (21.2, 39.9), P<0.001
Endoscopic improvement, n (%)^f Adjusted treatment difference (95% CI)	36 (18.9%)	93 (49.5%) 29.5 (20.7, 38.3), P<0.001	98 (51.6%) 31.1 (22.5, 39.8), P<0.001
Histo-endoscopic mucosal improvement^g Adjusted treatment difference (95% CI)	32 (16.8%)	82 (43.6%) 25.7 (17.1, 34.3), P<0.001	91 (47.9%) 29.6 (21.1, 38.0), P<0.001
Endoscopic normalization (remission), n (%)^h Adjusted treatment difference (95% CI)	29 (15.3%)	65 (34.6%) 18.5 (10.2, 26.8), P<0.001	64 (33.7%) 16.8 (9.0, 24.7), P<0.001
Primary Analysis Population included randomized patients with a modified Mayo score of 5-9 at induction baseline who received at least 1 maintenance study treatment dose. Adjusted treatment difference (Δ) was based on the Wald statistic with Cochran-Mantel-Haenszel (CMH) weight. P-values were based on the CMH test, stratified by clinical remission status at maintenance baseline and induction treatment, except for the maintenance of clinical remission, which was based on the CMH test stratified by induction treatment. ^aClinical remission: A Mayo stool frequency subscore of 0 or 1 and not increased from induction baseline, a Mayo rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1 with no friability. ^bCorticosteroid-free clinical remission: Not requiring any treatment with corticosteroids for at least 8 weeks prior to Week 44 and also meeting the criteria for clinical remission (98.9% of guselkumab-treated patients who achieved clinical remission at Week 44 were not taking corticosteroids for at least 8 weeks prior to Week 44). ^cMaintenance of clinical remission: Clinical remission at Week 44 among patients in clinical remission at maintenance baseline. ^dClinical response: A decrease from induction baseline in the modified Mayo score by ≥30% and ≥2 points, with either a ≥1-point decrease from induction baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. ^e Symptomatic remission: A stool frequency subscore of 0 or 1 and not increased from induction baseline, and a rectal bleeding subscore of 0. ^fEndoscopic improvement: An endoscopy subscore of 0 or 1 with no friability present on the endoscopy.^gHisto-endoscopic mucosal improvement: Achieving a combination of histologic improvement (neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue per Geboes grading system) and endoscopic improvement. ^hEndoscopic normalization (remission): An endoscopy subscore of 0.

Conclusion

Among pts with moderately to severely active UC who responded to GUS IV induction, maintenance therapy with both GUS SC regimens was safe and efficacious. The primary endpoint of clinical remission and all secondary endpoints across clinical, symptomatic, endoscopic, and histologic measures were met with statistical significance by both GUS SC maintenance regimens. Safety results through maintenance Wk44 were consistent with the known and favorable safety profile of GUS in approved indications.

Disclosure

DTR: AbbVie, Altrubio, Allergan, Inc., Arena Pharmaceuticals, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Ltd., Bristol Myers Squibb, Celgene Corp/Syneos, Connect BioPharma, GalenPharma/Atlantica, Genentech/Roche, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen Pharmaceuticals, Eli Lilly, Materia Prima, Pfizer, Prometheus Biosciences, Reistone, Takeda, Techlab, Inc and is a co-founder of Cornerstones Health, Inc.
JRA: Finch Therapeutics, Artugen, Pfizer, Takeda, Janssen, and Iterative Scopes, Merck and BMS.
JP: 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.
NS, SY, KGH, MG, RW, and HZ: Employees of Johnson & Johnson.
BGF: AbbVie Inc., Amgen Inc., AdMIRx Inc., Akebia Therapeutics, Allergan, AstraZeneca/MedImmune Ltd., Applied Molecular Transport, Aptevo Therapeutics, Asta Pharma, Atlantic Pharmaceuticals Ltd., Avaxia Biologics Inc., Avir Pharma, Biogen Idec, BioMx Isreal, Boehringer -Ingelheim, Boston Pharmaceuticals, Bristol-Myers Sqibb, Calypso Biotech, Celgene Corporation, Celltech, Centocor Inc, Elan/Biogen, Ferring Pharma, Genentech Inc/Hoffmann-La Roche Ltd., Galapagos, Galen/Atlantica, GiCare Pharma, Gilead Sciences Inc., Gossamer Pharma, GlaxoSmithKline (GSK), Inception IBD Inc, Intact Therapeutics, Janssen Research & Development LLC., Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech, merck, Mesoblast Pharma, Millennium, Nestles, Nextbiotix, Novonordisk, ParImmune, Parvus Therapeutics, Pfizer Inc., Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Qu Biologics, Rebiotix, Receptos Inc. / Celgene International, Salix Pharma, Sanofi, Santarus Inc., Shire, Sienna Biologics, Sihmoid Pharma, Sterna Biologics, Synergy Pharma Inc., Takeda Development Center Americas Inc., Teva Pharam, TiGenix, Tillotts Pharma AG, UCB, Vertex Pharma, Vivelix Pharma, VHsquared Ltd., Zyngenia and Senior Scientific Officer – Robarts Clinical Trials Inc.
TH: AbbVie, Daiichi-Sankyo, EA Pharma Co, Ltd. Janssen Research & Development LLC., JIMRO, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmacuetical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co., Ltd.,
GRL: Abbvie, Allergan, American College of Gastroenterology, American Gastroenterological Association, American Regent, Celgene, Chemed, Eli Lilly, Endo Pharmaceuticals, Ferring, Gastroenterology and Hepatology, Gilead, IMEDEX, Ironwood, Janssen/ Janssen Orthobiotech, MedEd Consultants, Merck, Morphic Therapeutics, Pfizer Pharmaceuticals, Professional Communications, Inc., Prometheus Laboratories, Inc, Romark, Sandoz, Salix Pharmaceuticals/Valeant, Shire Pharmaceuticals, SLACK, Inc, Springer Science and Business Media, Takeda, University of Kentucky, UCB, Up-To-Date, Vindico, and Virgo.
BB: Abbvie, Amgen, BI, BMS, Ferring, Janssen, Merck, Novartis, Organon, Pfizer, Sandoz, Takeda, Alimentiv, Allergan, AMT, Bausch Health, Celgene, Celltrion Healthcare, Eupraxia, Fresenius Kabi, Genentech, GSK, Gilead, Iterative Scopes, Jamp Pharma, Merck Amgen, Microbiome Insights, Mylan, Pendopharm, Protagonist, Qu Biologic, and Viatrisgen.
LPB: AbbVie, Allergan, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, CTMA, Enterome, Enthera, Ferring, Fresenius, Genentech, Gilead, Hikma, Index Pharmaceuticals, Janssen, Lilly, MSD, Mylan, Nestlé, Norgine, Oppilan Pharma, OSE Immunotherapeutics, Pfizer, Pharmacosmos, Roche, Samsung Bioepis, Sandoz, Sterna, Sublimity Therapeutics, Takeda, Tillots and Vifor; grants from AbbVie, MSD and Takeda.
BES: Abbvie, Abbivax, Alimentiv, Amgen, Arena Pharmaceuticals, Artugen Therapeutics, Astra Zeneca, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Morphic Therapeutics, MRM Health, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Sun Pharma, Surrozen, Takeda, Target RWE, Teva, Theravance Biopharma, TLL Pharmaceutical, and Ventyx Biosciences.
AD: Abivax, AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, CED Service GmbH, Celltrion, Dr Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Gilead, High5MD, Janssen, Lilly, Materia Prima, MedToday, MSD, Pfizer, Pharmacosmos, Roche/Genetech, Sandoz/Hexal, Takeda, Thieme, Tillotts, UniMed Verlag, and Vifor Pharma.

THE EFFICACY AND SAFETY OF GUSELKUMAB AS MAINTENANCE THERAPY IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM THE PHASE 3 QUASAR MAINTENANCE STUDY

David T. Rubin 1, Jessica Allegretti 2, Julian Panés 3, Nicole Shipitofsky 4, Shadi Yarandi 4, Gary KH Huang 4, Matthew Germinaro 4, Rebbecca Wilson 4, Hongyan Zhang 4, Brian G. Feagan 5, Tadakazu Hisamatsu 6, Gary Lichtenstein 7, Brian Bressler 8, Laurent Peyrin-Biroulet 9, Bruce E. Sands 10, Axel Dignass 11

1 University of Chicago Medicine, Chicago, United States

2 Brigham and Women´s Hospital Crohn's and Colitis Center, Boston, United States

3 Hospital Clínic Barcelona, Barcelona, Spain

4 Janssen Research & Development, LLC, Spring House, United States

5 Alimentiv Inc, London, Canada

6 Kyorin University School of Medicine, Tokyo, Japan

7 University of Pennsylvania School of Medicine, Merion Station, United States

8 University of British Columbia, Vancouver, Canada

9 Nancy University Hospital, Nancy, France

10 Icahn School of Medicine at Mount Sinai, New York, United States

11 Agaplesion Markus Krankenhaus, Frankfurt/ Main, Germany

Conference

UEG Week Vienna 2024

Topics

IBD

Submission format

Abstract

Session

IL-23 inhibitor in UC and Crohn's disease: Part 2 (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

Table. Change from BL (CFB) in oesophageal PEC at Wk 16 (primary endpoint) and additional efficacy endpoints at Wks 24 and 52 in the VOYAGE study
	Time point
Endpoint	BL	Wk 16^a			Wk 24^a			Wk 52^b
Dose; PBO‑controlled period/ extension treatment period	Mean (SD) [median]	Observed value, mean (SD) [median]	Mean CFB (SD or SE)^c [median]	Mean difference from PBO [median]	Observed value, mean (SD) [median]	Mean CFB (SD or SE)^c [median]	Mean difference from PBO [median]	Observed value, mean (SD) [median]
PEC^c,d Etrasimod 2 mg QD (N=41) /Etrasimod 2 mg–2 mg QD (N1=26) Etrasimod 1 mg QD (N=39) /Etrasimod 1 mg–1 mg QD (N1=30) EoE-HSS grade^c,^d,e Etrasimod 2 mg QD (N=41) /Etrasimod 2 mg–2 mg QD (N1=26) Etrasimod 1 mg QD (N=39) /Etrasimod 1 mg–1 mg QD (N1=30) EoE-HSS stage^c,d,e Etrasimod 2 mg QD (N=41) /Etrasimod 2 mg–2 mg QD (N1=26) Etrasimod 1 mg QD (N=39) /Etrasimod 1 mg–1 mg QD (N1=30) EREFS^c,f,g Etrasimod 2 mg QD (N=41) /Etrasimod 2 mg–2 mg QD (N1=26) Etrasimod 1 mg QD (N=39) /Etrasimod 1 mg–1 mg QD (N1=30) PGIS^c,f,h Etrasimod 2 mg QD (N=41) /Etrasimod 2 mg–2 mg QD (N1=28) Etrasimod 1 mg QD (N=39) /Etrasimod 1 mg–1 mg QD (N1=30) DSQ Overall^c,f,i Etrasimod 2 mg QD (N=41) /Etrasimod 2 mg–2 mg QD (N1=29) Etrasimod 1 mg QD (N=39) /Etrasimod 1 mg–1 mg QD (N1=30) DSQ - History of dilation = Yes^c,f,i Etrasimod 2 mg QD (N=41) /Etrasimod 2 mg–2 mg QD (N1=18] Etrasimod 1 mg QD (N=39) /Etrasimod 1 mg–1 mg QD (N1=19) DSQ - History of dilation = No^c,f,i Etrasimod 2 mg QD (N=41) /Etrasimod 2 mg–2 mg QD (N1=11) Etrasimod 1 mg QD (N=39) /Etrasimod 1 mg–1 mg QD (N1=11)	116.5 (82.59) [88.0] 106.3 (83.31) [87.0] 0.4 (0.18) 0.4 (0.19) 0.4 (0.20) 0.4 (0.24) 3.7 (1.74) 3.2 (1.59) 2.4 (0.6) 2.3 (0.5) 33.6 (12.9) 32.0 (10.0) 34.9 (11.5) 31.6 (9.4) 32.2 (14.5) 32.5 (11.2)	66.3 (91.73) [27.0] 101.7 (110.45) [67.0] 0.3 (0.19) [0.2] 0.3 (0.19) [0.3] 0.2 (0.20) [0.2] 0.3 (0.24) [0.3] 2.4 (1.78) [2.0] 2.7 (1.53) [3.0] 1.8 (0.64) [2.0] 2.1 (0.68) [2.0] 15.7 (14.57) [14.7] 18.2 (15.20) [13.3] 18.2 (15.17) [16.8) 19.7 (15.18) [14.0] 12.8 (13.79) [7.6] 16.0 (15.49) [8.4]	-38.3 (77.91) [-58.4] 40.3 (269.93) [-39.4] -0.1 (0.02) -0.1 (0.02) -0.2 (0.03) -0.1 (0.03) -1.3 (0.24) -0.8 (0.24) -0.6 (0.10) -0.3 (0.10) -17.1 (2.2) -14.8 (2.2) -9.8 (4.3) -6.7 (4.1) -17.5 (3.0) -18.0 (3.3)	-46.1 [-36.9] p=0.0103 32.5 [-17.9] p=0.2861 -0.11 p=0.0040 -0.07 p=0.0712 -0.13 p=0.0038 -0.06 p=0.1790 -1.0 p=0.0135 -0.5 p=0.2160 -0.1 p=0.5379 0.21 p=0.1906 2.38 p=0.4894 4.70 p=0.1671 4.39 p=0.3295 7.50 p=0.0922 -3.49 p=0.3508 -3.94 p=0.3065	57.8 (111.23) [16.0] 72.2 (80.81) [32.5] 0.2 (0.18) [0.2] 0.2 (0.20) [0.2] 0.2 (0.20) [0.1] 0.2 (0.24) [0.2] 2.4 (1.78) [2.0] 2.4 (1.75) [2.0] 1.6 (0.61) [2.0] 1.9 (0.65) [2.0] 12.4 (14.71) [7.0] 16.4 (16.44) [9.7] 17.1 (14.93) [17.2] 15.6 (15.33) [11.4] 5.1 (11.41) [0.0] 17.3 (18.33) [9.7]	-52.4 (59.66) [-76.2] -27.4 (78.00) [-50.3] -0.2 (0.03) -0.1 (0.03) -0.2 (0.03) -0.2 (0.03) -1.3 (0.26) -1.0 (0.26) -0.7 (0.12) -0.5 (0.11) -18.6 (2.6) -15.7 (2.5) -10.8 (4.4) -9.3 (4.2) -21.6 (3.8) -16.5 (3.8)	-113.7 [-103.9] p<0.0001 -88.7 [-78.0] p=0.0022 -0.21 p<0.0001 -0.19 p<0.0001 -0.23 p<0.0001 -0.20 p=0.0001 -0.91 p=0.0303 -0.61 p=0.1473 -0.48 p=0.0121 -0.28 p=0.1312 -4.16 p=0.3061 -1.29 p=0.7451 0.62 p=0.8992 2.12 p=0.6572 -11.95 p=0.0311 -6.84 p=0.2014	71.4 (81.20) [40.5] 119.2 (176.04) [56.0] 0.3 (0.17) [0.3] 0.3 (0.17) [0.3] 0.2 (0.17) [0.3] 0.2 (0.18) [0.2] 1.9 (1.77) [1.5] 2.3 (1.71) [2.0] 1.3 (0.48) [1.0] 1.7 (0.72) [2.0] 5.2 (10.0) [0.0] 11.5 (14.8) [3.8] 4.8 (7.40) [0.0] 11.1 (13.96) [5.6] 6.0 (14.40) [0.0] 12.0 (16.75) [3.5]
Proportion with PEC <15 eos/HPF, % Etrasimod 2 mg QD (N=41) /Etrasimod 2 mg–2 mg QD (N1=26) Etrasimod 1 mg QD (N=39) /Etrasimod 1 mg–1 mg QD (N1=30) Proportion with PEC ≤6 eos/HPF, % Etrasimod 2 mg QD (N=41) /Etrasimod 2 mg–2 mg QD (N1=26) Etrasimod 1 mg QD (N=39) /Etrasimod 1 mg–1 mg QD (N1=30)	N/A N/A N/A N/A	22.0 12.8 12.2 7.7			31.7 30.8 24.4 15.4			34.6 23.3 23.1 13.3
^aFull analysis set; includes all randomised pts who received at least one dose of study treatment. ^bEfficacy evaluable set; includes all randomised pts who received at least one dose of study treatment with an extension BL measurement and a Wk 52 measurement in the extension treatment period. The efficacy evaluable set can vary with endpoints since some pts may have the required data for some endpoints but not others. ^c%CFB (mean [SD] [median]) calculated for PEC, and CFB (least squares mean [SE]) calculated for EoE-HSS grade and stage, EREFS, PGIS and DSQ. All PBO-adjusted differences from PBO are expressed as least squares mean, except %CFB in PEC, which is expressed as the mean and median difference. ^dp values are from an analysis of covariance model for rank score of %CFB, including factors for treatment group, BL history of oesophageal dilation (Yes/No), concurrent PPI therapy (Yes/No), and BL eosinophil PEC (eos/HPF) as a covariate. ^eGrade and stage score range from 0–3 for each individual component of the EoE-HSS. Total scores are reported and are the ratio of observed component scores divided by the maximum possible score depending on the number of individual components that are present/evaluable. ^fp values are from a linear mixed effects model for change from BL, including factors for treatment group, visit, interaction of treatment-by-visit, BL history of oesophageal dilation (Yes/No), concurrent PPI therapy (Yes/No), and BL score as a covariate. ^gScore ranges from 0–9. ^hScore ranges from 0–4. ⁱScore ranges from 0–84. %CFB, percentage change from baseline; BL, baseline; DSQ, Dysphagia Symptom Questionnaire; EoE-HSS, Eosinophilic Oesophagitis-Histology Scoring System; eos, eosinophils; EREFS, Eosinophilic Oesophagitis Endoscopic Reference Score; HPF, high power field; N, number of pts in the treatment group; N1, number of pts in the efficacy evaluable set for the extension treatment period; N/A, not available; PBO, placebo; PEC, peak eosinophil count; PGIS, Patient Global Impression of Severity; PPI, proton pump inhibitor; pt, patient; QD, once daily; SD, standard deviation; SE, standard error; Wk, Week.

	No history of ADT-IR			History of ADT-IR
	Placebo IV	GUS 200mg IV	Adjusted Treatment Difference (95% CI)^c	Placebo IV	GUS 200mg IV	Adjusted Treatment Difference (95% CI)^c
Primary analysis population, N	144	213		136	208
Clinical remission at Wk12^a1,b (primary endpoint), N (%)	17 (11.8%)	69 (32.4%)	20.6% (12.4%, 28.8%)***	5 (3.7%)	26 (12.5%)	8.8% (3.4%, 14.3%)**
Symptomatic remission at Wk 12,^a2,b N (%)	39 (27.1%)	130 (61.0%)	33.9% (24.2%,43.7%)***	19 (14.0%)	80 (38.5%)	24.5% (15.7%, 33.3%)***
Clinical response at Wk 12,^{a3, b} N (%)	51 (35.4%)	152 (71.4%)	36.0% (26.1%,45.8%)***	27 (19.9%)	107 (51.4%)	31.6% (22.0%, 41.1%)***
Endoscopic improvement at Wk 12,^a4,bN (%)	24 (16.7%)	82 (38.5%)	21.8% (12.9%,30.8%)***	7 (5.1%)	31 (14.9%)	9.8% (3.7%, 15.8%)**
Histo-endoscopic mucosal improvement at Wk 12,^a5,b N (%)	15 (10.4%)	71 (33.3%)	22.9% (14.9%, 31.0%)***	6 (4.4%)	28 (13.5%)	9.1% (3.3%, 14.8%)**
Endoscopic normalization at Wk 12,^a6,bN (%)	11 (7.6%)	45 (21.1%)	13.5% (6.5%, 20.4%)***	3 (2.2%)	18 (8.7%)	6.4% (1.9%, 11.0%)*
Nominal p-value <0.05. Nominal p-value <0.01. **Nominal p-value <0.001. The p-values were based on the Cochran-Mantel-Haenszel (CMH) chi-square test. ^a1 Clinical remission is defined as stool frequency subscore of 0 or 1 with no increase from induction baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.^a2Symptomatic remission is defined as a stool frequency subscore of 0 or 1 with no increase from induction baseline and a rectal bleeding subscore of 0. ^a3Clinical response is defined as decrease from induction baseline in the modified Mayo score by ≥30% and ≥2 points, with either a ≥1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. Modified Mayo score is a 3-component (stool frequency, rectal bleeding, and endoscopy subscores) Mayo score without the physician’s global assessment. ^a4Endoscopic improvement is defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. ^a5Histo-endoscopic mucosal improvement is defined as achieving a combination of histologic improvement (neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system) and endoscopic improvement. ^a6Endoscopic normalization is defined as an endoscopy subscore of 0. ^b Patients who had a prohibited change in UC medication, an ostomy or colectomy, or discontinued study agent due to lack of efficacy or an adverse event of worsening of UC or other reasons except for COVID-19 related reasons (excluding COVID-19 infection) or regional crisis in Russia and Ukraine prior to the Week 12 visit were considered not to have achieved the endpoint. Patients who were missing one or more components pertaining to a specified endpoint at Week 12 were considered not to have achieved the endpoint.^c The adjusted treatment difference and confidence intervals were based on the Wald statistic with Cochran-Mantel-Haenszel weight.

Table 1. Clinical efficacy and endoscopic outcomes at Week 144
Endpoint	Analysis	Combined Guselkumab^a	Ustekinumab^b
Clinical remission (CDAI<150), % (n/N)	Primary efficacy analysis set (NRI)^c LTE efficacy analysis set (NRI)^d Observed case analysis set^e	54.1 (100/185) 68.2 (103/151) 95.4 (103/108)	46.0 (29/63) 64.6 (31/48) 83.8 (31/37)
PRO-2 remission (AP mean daily score ≤1 and SF mean daily score ≤3, and no worsening of AP or SF from baseline), n/N (%)	Primary efficacy analysis set (NRI)^c LTE efficacy analysis set (NRI)^d Observed case analysis set^e	51.4 (95/185) 64.2 (97/151) 89.8 (97/108)	39.7 (25/63) 58.3 (28/48) 75.7 (28/37)
Endoscopic response (≥50% improvement from baseline in SES-CD or SES-CD≤2), n/N (%)	Primary efficacy analysis set (NRI)^c LTE efficacy analysis set (NRI)^d Observed case analysis set^e	34.7 (61/176) 43.0 (61/142) 73.5 (61/83)	19.4 (12/62) 25.5 (12/47) 41.4 (12/29)
AP, abdominal pain; CDAI, Crohn's Disease Activity Index; LTE, long-term extension; NRI, nonresponder imputation; PRO-2, patient reported outcome components of the CDAI [abdominal pain and stool frequency]; SES-CD, Simple Endoscopic Score for Crohn’s Disease; SF, stool frequency ^aIncludes patients randomized to the following guselkumab induction/maintenance regimens: 200 mg IV →100 mg SC q8w; 600 mg IV →200 mg SC q4w; 1200 mg IV →200 mg SC q4w ^bPatients randomized to ustekinumab ^cPrimary efficacy analysis set consists of randomized patients who received ≥1 dose of study medication, with NRI for patients with treatment failure or missing data, including those who did not enter the LTE ^dLTE efficacy analysis set consists of randomized patients who entered the LTE and received ≥1 dose of study medication in the LTE, with NRI for patients with treatment failure or missing data ^eObserved case analysis set consists of randomized patients who entered the LTE, received ≥1 dose of study medication in the LTE, and had available data at the outcome visit. Patients who received dose adjustment were excluded

UEG's educational platform for gastroenterology education bringing recordings, courses, guidelines, and more together in one place.

Most popular content

Rate for better recommendations!