Introduction

The Phase 3 QUASAR induction study (NCT04033445) was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study that evaluated efficacy and safety of guselkumab (GUS), an interleukin-23 p19 antagonist, as induction therapy in patients (pts) with moderately to severely active UC who had an inadequate response or intolerance to conventional (ie, thiopurines or corticosteroids) and/or advanced therapies (ie, TNF alpha antagonists, integrin receptor antagonists, or Janus kinase inhibitors).

Aims & Methods

The primary analysis population included randomized pts with a baseline modified Mayo score of 5 to 9, inclusive, a rectal bleeding subscore ≥1, and an endoscopy subscore ≥2 (centrally read). Pts were randomized 3:2 to receive IV GUS 200mg or placebo (PBO) at Weeks (Wks) 0, 4, and 8. The primary endpoint was clinical remission at Wk12. Symptomatic remission, clinical response, endoscopic improvement, histo-endoscopic mucosal improvement (HEMI), endoscopic normalization, and safety were also assessed.

Results

The primary analysis population included 701 pts (mean age, 40.5yrs; female, 43.1%; mean UC duration, 7.5yrs; mean modified Mayo score, 6.9; Mayo endoscopy subscore=3 (severe disease), 67.9%; median fecal calprotectin, 1641mg/kg; median CRP, 4.2mg/L; baseline oral corticosteroid use, 43.1%). Baseline characteristics were balanced across treatment groups. Approximately 50% had prior inadequate response/intolerance to advanced therapies (ADT-IR) for UC; nearly half of these (47.4%) had ≥2 ADT-IR classes. A significantly greater proportion of GUS- vs PBO-treated pts achieved clinical remission at Wk12 (22.6% vs 7.9%, adjusted ∆=14.9%, p<0.001; Table). Relative to PBO, GUS induction treatment resulted in significantly greater proportions of pts achieving symptomatic remission, clinical response, endoscopic improvement, and HEMI at Wk12 and symptomatic remission at Wk4. Adverse event (AE) frequencies through Wk12 in GUS group were similar to PBO (49.4% vs 49.3%, respectively). Most frequently reported AEs were anemia, COVID-19, worsening of UC, and headache. Infections and serious infections occurred at similar rates for GUS- vs PBO-treated pts (15.7% vs 15.4% and 0.7% vs 0.4%, respectively). GUS- vs PBO treated pts had numerically fewer serious AEs (2.9% vs 7.1%) and AEs leading to discontinuation (1.7% vs 3.9%). Through Wk12, 2 PBO-treated pts and 1 GUS-treated pt died (all cardiovascular in nature). No AEs within 1 hour of infusion were considered serious or resulted in treatment discontinuation. The incidence of anti-drug antibodies through Wk12 was low (1.5%, 6/409), and no neutralizing antibodies were detected.

Table. Primary and key secondary endpoints

	Placebo IV	GUS 200 mg IV	Adjusted treatment difference (95% CI)
Full Analysis set, N	280	421	-
Clinical remission at Wk12, n (%)a	22 (7.9%)	95 (22.6%)	14.9% (9.9%, 19.9%) p<0.001
Symptomatic remission at Wk4, n (%)b	36 (12.9%)	95 (22.6%)	9.9% (4.4%, 15.4%) p<0.001
Symptomatic remission at Wk12, n (%)b	58 (20.7%)	210 (49.9%)	29.4% (22.8%, 36.0%) p<0.001
Clinical response at Wk12, n (%)c	78 (27.9%)	259 (61.5%)	33.8% (26.9%, 40.7%) p<0.001
Endoscopic improvement at Wk12, n (%)d	31 (11.1%)	113 (26.8%)	16.0% (10.5%, 21.4%) p<0.001
Histo-endoscopic mucosal improvement at Wk12, n (%)e	21 (7.5%)	99 (23.5%)	16.2% (11.1%, 21.2%) p<0.001
Endoscopic normalization at Wk12, n (%)f	14 (5.0%)	63 (15.0%)	10.1% (5.9%, 14.3%)***
***Nominal p-value <0.001. a Clinical remission was defined as a Mayo stool frequency subscore of 0 or 1 and not increased from baseline, a Mayo rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1 with no friability present on the endoscopy. b Symptomatic remission was defined as a stool frequency subscore of 0 or 1 and not increased from baseline, and a rectal bleeding subscore of 0. c Clinical response was defined as a decrease from 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. d Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. e Histo-endoscopic mucosal improvement was 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, i.e., Geboes score ≤ 3.1) and endoscopic improvement. f Endoscopic normalization was defined as an endoscopy subscore of 0. Note: Patients who had a prohibited change in UC medication, an ostomy or colectomy, or discontinued study agent due to lack of therapeutic effect or due to an AE of worsening of UC prior to the designated analysis timepoint were considered not to have achieved the endpoint. Data after discontinuation of study agent due to COVID-19 related reasons (excluding COVID-19 infection) were considered to be missing. Patients who were missing one or more components pertaining to a specified endpoint at Week 12 were considered not to have achieved the endpoint. The p-values were based on the Cochran-Mantel-Haenszel (CMH) chi-square test.

Conclusion

In this Phase 3 study, GUS 200mg IV induction was safe and effective in the treatment of pts with moderately to severely active UC compared to PBO, with clinically meaningful improvements demonstrated across symptomatic and histo-endoscopic outcome measures. Overall, safety results through Wk12 were consistent with the known and favorable safety profile of GUS in approved indications.

Disclosure

Laurent Peyrin-Biroulet reports personal fees and Steering Committee member for Janssen.
Jessica R. Allegretti is a consultant and Steering Committee member for Janssen.
Brian G. Feagan received grant/research support from Janssen Research & Development LLC.; a consultant for JnJ/Janssen; a member of the speakers bureau for JnJ/Janssen; a member of the scientific advisory board for JnJ/Janssen.
Brian Bressler is an advisor/speaker/Steering Committee member for and has received research support from Janssen.
Gary R. Lichtenstein discloses relationships with Janssen/ Janssen Orthobiotech (Consultant, Research, Funding to University of PA [IBD Fellow Education]).
Kuan-Hsiang G. Huang is an employee of Johnson & Johnson and owns company stock/stock options.
Matthew Germinaro is an employee of Johnson & Johnson and owns company stock/stock options.
Nicole Shipitofsky is an employee of Johnson & Johnson and owns company stock/stock options
Lingjing Jiang is an employee of Johnson & Johnson and owns company stock/stock options.
Hongyan Zhang is an employee of Johnson & Johnson and owns company stock/stock options.
Tadakazu Hisamatsu is a Steering Committee member and has received consulting fees from Janssen Research & Development, LLC.
Julián Panés reports consulting fees/honorarium from Janssen; payment for lectures including service on speakers bureaus and Steering Committee for Janssen; payment for development of educational presentations 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;Steering committee member for Janssen; consultancy fees from Janssen; payment from lectures including service on speakers bureaus from Janssen.
Bruce E Sands discloses research grants and consulting fees from Janssen and is a Steering Committee Member for Janssen.
David T Rubin has served as a consultant and a Steering Committee member to Janssen Pharmaceuticals.

Introduction

Patients with moderately to severely active ulcerative colitis (UC) have debilitating symptoms that may incur substantial negative effects on health-related quality of life (HRQoL). According to the STRIDE-II consensus, restoration of HRQoL is a desirable long-term treatment goal for patients with active UC.¹ In this post-hoc analysis, we evaluated the extent to which patients treated with upadacitinib (UPA) achieved normalisation of HRQoL after induction and maintenance treatment.

Aims & Methods

Data from the multicentre, double-blind, Phase 3 trials, U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026), were analysed. During induction, patients were randomised 1:2 to oral placebo (PBO) or UPA 45 mg once daily (QD) for 8 weeks. Patients achieving a clinical response to UPA per Adapted Mayo score at Week 8 were re-randomised 1:1:1 to PBO, UPA 15 mg, or UPA 30 mg QD for 52 weeks of maintenance. The proportion of patients achieving normalisation of each individual HRQoL outcome, per literature-base normative value thresholds, was assessed at Weeks 8 and 52: FACIT-Fatigue score; IBDQ score; WPAI-UC (overall work impairment, work time missed, impairment while working, activity impairment); SF-36 PCS; SF-36 MCS; EQ-5D-5L VAS; and EQ-5D-5L index. A stringent composite score including these outcomes was also calculated to determine the proportion of patients who achieved normalisation of all individual HRQoL-related scores. Point estimates were calculated for all outcomes and treatment differences between UPA and PBO were compared using the Cochran-Mantel-Haenszel test.

Results

During induction, 660 patients were randomised to UPA 45 mg and 328 patients to PBO. In patients receiving UPA 45 mg vs PBO, more patients achieved normalisation of each individual HRQoL outcome at Week 8 of induction (p<0.001; Table 1). Improvements were also observed at Week 52 of maintenance in patients receiving UPA 15 mg (n=148) and 30 mg (n=154), with more patients achieving normalisation of each HRQoL outcome with both doses of UPA vs PBO (p<=0.01). More patients achieved normalisation of composite HRQoL scores at Weeks 8 (UPA 45 mg: 18.9%; PBO: 5.5%) and 52 (UPA 30 mg: 24.0%; UPA 15 mg: 22.3%; PBO: 8.7%) with all doses of UPA compared to PBO (p<=0.001).
Table 1. Proportion of patients with UC achieving normalisation of HRQoL outcomes after treatment

HRQoL endpoints at Weeks 8 and 52, n (%)	Induction (Week 8) PBO N=328	Induction (Week 8) UPA 45 mg QD N=660	Between group diff. (UPA 45 mg vs PBO) % [95% CI]	Maintenance (Week 52) PBO N=149	Maintenance (Week 52) UPA 15 mg QD N=148	Maintenance (Week 52) UPA 30 mg QD N=154	Between group diff. (UPA 15 mg vs PBO) % [95% CI]	Between group diff. (UPA 30 mg vs PBO) % [95% CI]
FACIT-F score ≥40.1	109 (33.2)	357 (54.1)	20.8 *** [14.6, 27.1]	53 (35.7)	77 (52.0)	86 (55.7)	15.7 ** [5.1, 26.3]	19.1 *** [8.3, 29.8]
IBDQ score ≥170	85 (25.9)	407 (61.6)	35.6 *** [29.6, 41.5]	42 (28.5)	91 (61.5)	111 (72.3)	32.2 *** [22.1, 42.6]	42.8 *** [32.7, 52.8]
WPAI-UC 0% Overall work imp.a,b Work time misseda,b Imp. while workinga,b Daily activity imp.	24 (11.9) 92 (45.8) 27 (13.4) 37 (11.3)	112 (26.2) 261 (61.0) 126 (29.5) 199 (30.2)	13.7 *** [7.7, 19.7] 14.7 *** [6.5, 22.9] 15.3 *** [9.1, 21.6] 18.8 *** [14.0, 23.6]	14 (13.9) 41 (40.6) 14 (13.9) 28 (18.8)	37 (33.9) 72 (66.1) 39 (35.8) 55 (37.2)	33 (32.7) 62 (61.4) 35 (34.7) 62 (40.3)	21.1 *** [10.6, 31.6] 24.3 *** [11.4, 37.2] 23.1 *** [12.5, 33.7] 18.8 *** [9.2, 28.5]	19.0 *** [7.9, 30.1] 19.7 ** [6.5, 33.0] 21.0 *** [9.8, 32.2] 21.0 *** [11.2, 30.8]
SF-36 PCS ≥50	106 (32.3)	369 (55.9)	23.4 *** [17.2, 29.7]	44 (29.7)	89 (60.1)	102 (66.3)	29.5 ** [19.2, 39.8]	35.4 *** [25.1, 45.6]
SF-36 MCS ≥50	98 (29.9)	316 (48.0)	17.9 *** [11.7, 24.1]	38 (25.2)	70 (47.3)	82 (53.0)	22.1 *** [12.0, 32.2]	27.4 *** [17.2, 37.7]
EQ-5D-5L VAS ≥80	68 (20.7)	298 (45.1)	24.3 *** [18.6, 30.1]	40 (26.9)	65 (43.9)	88 (57.1)	15.6 ** [5.1, 26.0]	29.0 *** [18.5, 39.6]
EQ-5D-5L Index ≥0.825	89 (27.1)	339 (51.4)	24.3 *** [18.2, 30.4]	49 (33.0)	79 (53.4)	90 (58.5)	18.7 *** [8.3, 29.1]	24.1 *** [13.7, 34.6]
Composite HRQoL endpointc	18 (5.5)	125 (18.9)	13.2 *** [9.4, 17.1]	13 (8.7)	33 (22.3)	37 (24.0)	13.8 *** [6.0, 21.6]	14.8 *** [6.9, 22.7]
**p≤0.01. ***p≤0.001. aInduction: PBO, N=201; UPA 45 mg, N=428. bMaintenance: PBO, N=101; UPA 15 mg, N=109; UPA 30 mg, N=101. cProportion of patients achieving FACIT-F score ≥40.1, IBDQ score ≥170, 0% for WPAI-UC Daily Activity Impairment, SF-36 PCS ≥50 and MCS ≥50, EQ-5D-5L VAS ≥80.0 and EQ-5D-5L Index ≥0.825; employment-related scores were excluded. For induction data, the Cochran-Mantel-Haenszel test was used to calculate the 95% CI for differences between treatment groups and was adjusted for strata: baseline corticosteroid use (yes or no), baseline Adapted Mayo score (≤7 or >7) and bio-IR status (bio-IR or non–bio-IR). For maintenance data, the Cochran-Mantel-Haenszel test was used to calculate the 95% CI for differences between treatment groups and was adjusted for strata: bio-IR status (bio-IR or non-bio-IR) at the baseline of the induction study, clinical remission status at Week 0 (yes or no), and corticosteroid use at Week 0 (yes or no). Bio-IR, biologics inadequate response; CI, confidence interval; diff., difference; EQ-5D-5L, European Quality of Life 5 Dimensions 5 Levels; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; HRQoL, health-related quality of life; IBDQ, Inflammatory Bowel Disease Questionnaire; imp., impairment; MCS, Mental Component Summary; PBO, placebo; PCS, Physical Component Summary; QD, once daily; SF-36, Short Form 36; UC, ulcerative colitis; UPA, upadacitinib; VAS, visual analogue scale; WPAI, Work Productivity and Activity Impairment Questionnaire.

Conclusion

UPA is more efficacious than PBO at achieving normalisation of patients’ HRQoL, at induction and through Week 52 of maintenance. These results suggest that UPA may help patients with moderately to severely active UC achieve the long-term treatment goal of normalisation of HRQoL.

References

1. Turner D, et al. Gastroenterology. 2021;160:1570–83.

Disclosure

Joana Torres has received grant funding/speaker fees from and/or has participated in advisory boards for AbbVie, Galapagos, Janssen, and Pfizer.
Gareth Parkes received personal payments/honoraria/speaker fees and/or accepted travel grants or fellowships from AbbVie, Allergan, BMS, Celltrion, Ferring, Galapagos, Janssen, Napp, Takeda, and Tillotts; and is a Director and Shareholder in Ampersand Health.
Corey Siegel has served as a consultant, advisor, speaker for CME activities, and/or received grant funding from AbbVie, BMS, Celltrion, Fresenius, Janssen, Lilly, Napo, Pfizer, Prometheus, Prometheus Labs, Roivant, and Takeda.
Julian Panés received 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.
Edward V. Loftus Jr: served as a consultant for AbbVie, Alvotech, Amgen, Arena, Avalo, Boehringer Ingelheim, Bristol-Myers Squibb, Calibr, Celgene, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iota, Iterative Scopes, Janssen, Morphic Therapeutics, Ono Pharma, Pfizer, Protagonist, Scipher Medicine, Surrozen, Sun Pharma, Takeda, and UCB; and received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Genentech, Gilead, Gossamer Bio, Janssen, Pfizer, Receptos, Robarts Clinical Trials, Takeda, Theravance, and UCB.
Remo Panaccione served as a consultant for Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, 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, Spyre Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Union Biopharma, Viatris, Ventyx, UCB; and received 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, and Takeda Pharmaceuticals; and was an advisory board member 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, SandozShire, Sublimity Therapeutics, Takeda Pharmaceuticals, and Ventyx.
Yuri Sanchez Gonzalez, Si Xuan, Valencia Remple, Justin Klaff, Cecile Holweg, and Dolly Sharmaare full-time employees of AbbVie and may hold AbbVie stock and/or stock options.
Funding statement: Financial support for the study was provided by AbbVie. AbbVie participated in interpretation of data, review, and approval of the abstract. All authors contributed to development of the abstract and maintained control over final content. No honoraria or payments were made for authorship. Medical writing services provided by Kay Hallam, MSc, of Fishawack Facilitate, Ltd, part of Avalere Health and funded by AbbVie.

Introduction

Fatigue is a debilitating, multifactorial symptom experienced by many patients with Crohn’s disease (CD).¹ Mirikizumab (MIRI), an anti-interleukin-23p19 antibody, demonstrated significant improvement in fatigue in patients with moderately to severely active CD in the Phase 2 AMAG² and Phase 3 VIVID-1³ studies.

Aims & Methods

This analysis examines the association of changes in clinical, endoscopic (endo) and selected patient-reported outcomes with changes in fatigue in MIRI-treated patients in the VIVID-1 study. Co primary and gated secondary outcomes, including comparisons with ustekinumab, have been presented elsewhere^4,5Adult patients (N=1065) with moderately to severely active CD were randomized 6:3:2 to MIRI, ustekinumab or placebo. MIRI was given every 4 weeks (W) as 900 mg intravenous at W0, W4, and W8, then 300 mg subcutaneous from W12 to W52. Fatigue was assessed via the validated Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire (scale from 0-52, higher scores indicating less fatigue⁶ andat least 6-point increase identified as a clinically meaningful within-patient change). Achievement of ≥6-point increase in FACIT-F at W52 was reported among those with and without clinical remission by Crohn’s Disease Activity Index (CDAI), endo response, endo remission, and Urgency Numeric Rating Scale (NRS) ≤2 at W52. For stool frequency (SF), abdominal pain (AP), fecal calprotectin (FCP), and C-reactive protein (CRP), the association of the change from baseline (CFB) at W52 vs. the CFB in FACIT-F at W52 was assessed by the Pearson correlation coefficient.

Results

At W52, 50.9% (268/527) of MIRI-treated patients achieved FACIT-F ≥6-point increase from baseline. Greater proportions of patients who achieved clinical and endo outcomes had ≥6-point increase in FACIT-F (p<0.05) vs. those who did not achieve the outcome (Table). There was weak/moderate correlation between CFB at W52 in AP, SF and log-transformed FCP and CRP, and the CFB in FACIT-F at W52 (Table).

Table: W52 FACIT-F, A: ≥6-pt Increase From BL by Outcomes at W52 and B: CFB Correlation With CFB at W52 in Outcomes

A. W52 FACIT-F ≥6-point Increase From BL by Outcome at W52a, NRI	Outcome Achieved n/N (%) (95% CI)b	Outcome NOT Achieved n/N (%) (95% CI)b	Risk Difference (95% CI)b	p-Valuec
Clinical remission by CDAId	185/280 (66.1) (60.5-71.6)	83/247 (33.6) (27.7-39.5)	32.5 (24.4-40.6)	<0.0001
Endo responsee	154/256 (60.2) (54.2-66.2)	114/271 (42.1) (36.2-47.9)	18.1 (9.7-26.5)	<0.0001
Endo remissionf	59/96 (61.5) (51.7-71.2)	209/431 (48.5) (43.8-53.2)	13.0 (2.1-23.8)	0.0216
Urgency NRS ≤2g	127/188 (67.6) (60.9-74.2)	127/311 (40.8) (35.4-46.3)	26.7 (18.1-35.4)	<0.0001
B. CFB in FACIT-F vs. CFB in Outcomes at W52	N	Pearson Correlation Coefficient	95% CIh	p-Value
CFB in AP score	574	-0.379	-0.447 to -0.306	<0.0001
CFB in SF score	572	-0.306	-0.378 to -0.230	<0.0001
CFB in log-transformed FCP	461	-0.112	-0.201 to -0.020	0.0166
CFB in log-transformed CRP	576	-0.208	-0.285 to -0.128	<0.0001

^aMIRI-treated patients with baseline (BL) FACIT-F score ≤46 points; ^bConfidence interval (CI) constructed using asymptotic method without continuity correction; ^cChi Square test; ^dCDAI <150; ^eSimple Endoscopic Score for CD (SES-CD) Total Score ≥50% improvement from BL; ^fSES-CD Total Score ≤4, ≥2-point reduction from BL and no subscore >1; ^gIn those with BL Urgency NRS ≥3; ^hPearson correlation with Fisher’s z-transformation. A negative correlation indicates an improvement in outcome is associated with an improvement in FACIT-F. Correlation strength defined as: >0.5=strong, 0.3 to ≤0.5=moderate, 0.1 to <0.3=weak, <0.1=insubstantial⁷
NRI=nonresponder imputation.

Conclusion

In patients with moderately to severely active CD treated with MIRI, improvements in clinical, endoscopic, and selected patient-reported outcomes were associated with clinically meaningful improvements in fatigue at W52.

References

1. D’Silva A, et al. Clin Gastroenterol Hepatol. 2022;20:995-1009.
2. Regueiro MD, et al. Am J Gastroenterol. 2023;118:S816.
3. Travis S, et al. J Crohn's Colitis.2024;18:i21–i23.
4. Ferrante M, et al. J Crohn's Colitis. 2024;18:S1 i7–i9.
5. Jairath V, et al. J Crohn's Colitis. 2024;18:i62–i64.
6. Tinsley A, et al. Aliment Pharmacol Ther. 2011;34:1328-36.
7. Cohen J. Statistical Power Analysis for the Behavioural Sciences, 1988, Routledge.

Disclosure

P. Bossuyt has received financial support for research from: AbbVie, Amgen, Janssen, Pfizer, and Viatris; lecture fees from: AbbVie, Bristol Myers Squibb, CAG, Celltrion, Eli Lilly and Company, EPGS, Galapagos NV, Globalport, Janssen, Materia Prima, Pentax, Scope, and Takeda; and advisory board fees from: AbbVie, Bristol Myers Squibb, Celltrion, CIRC, Dr. Falk Pharma Benelux, Eli Lilly and Company, Galapagos NV, Janssen, Pentax, PSI-CRO, Roche, Takeda, and Tetrameros; M. Regueiro has served as an advisor and/or consultant for: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Genentech, Gilead Sciences, Janssen, Organon, Pfizer, Prometheus Therapeutics and Diagnostics, Salix Pharmaceuticals, Takeda, and UCB Pharma; M. Fischer has received consulting fees from: AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Ferring Pharmaceuticals, Janssen, Pfizer, Rebiotix, Scioto Biosciences, and Seres Therapeutics; K. Traxler, G. Yu, M. Protic, K. Tsilkos, and A. Vadhariya are employees and shareholders of: Eli Lilly and Company; T. Hisamatsu has received lecture fees from: AbbVie, EA Pharma, Gilead Sciences, Janssen Pharmaceutical K.K., JIMRO, Kyorin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Pfizer, and Takeda; has received honoraria as an advisory board member or consultant for: AbbVie, Brystol Myers Squibb, EA Pharma, Eli Lilly and Company, Gilead Sciences, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma, Pfizer, and Takeda; and has received pharmaceutical/research grants from: AbbVie, Boston Scientific, Daiichi Sankyo, EA Pharma, Kissei Pharmaceutical, JIMRO, Kyorin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nichi-lko Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, and Zeria Pharmaceutical; P. Juillerat has received fees for lectures and consulting/advisory board from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly and Company, Ferring Pharmaceuticals, Gilead Sciences, Janssen, Merck Sharp & Dohme, Pfizer, Pierre Fabre, Sandoz, Takeda, Tillotts Pharma AG, and UCB Pharma

Introduction

Tumor necrosis factor-like cytokine 1A (TL1A), a membrane costimulatory protein that also exists as a serum cytokine, drives multiple pro-inflammatory and fibrotic pathways relevant to the immunopathogenesis of inflammatory bowel disease (IBD). Intestinal inflammation and chronic mucosal injury are associated with submucosal fibrosis in ulcerative colitis (UC). In ARTEMIS-UC, a phase 2 placebo-controlled, multicenter, double-blind study, the anti-TL1A inhibitory monoclonal antibody PRA023 showed efficacy in adults with moderately to severely active UC. A significantly greater proportion of patients who received PRA023 achieved the primary endpoint of clinical remission at week 12. This study analyzed molecular biomarkers from ARTEMIS-UC patient samples obtained before and after treatment with PRA023 compared to placebo control.

Aims & Methods

Serum and RNAseq data from intestinal mucosal biopsies were analyzed for cytokines and gene expression, respectively, to evaluate the effects of TL1A blockade in 68 UC patients treated with PRA023 and 60 patients treated with placebo during the 12-week induction period. Serum cytokine levels were measured at baseline, weeks 2, 6, and 12, using mesoscale discovery (MSD) multiplexing. Intestinal mucosal biopsy RNAseq data were analyzed at baseline and week 12 using differential gene expression, pathway analysis (gene set variation analysis), and single-cell deconvolution approaches. Pathway signatures were curated from public datasets or derived from in vitro studies. Pharmacodynamic (PD) changes were correlated with modified Mayo score clinical remission, the primary clinical endpoint of the study, defined as an endoscopic score of 0 or 1, rectal bleeding of 0, and stool frequency of 0 or 1 and not greater than baseline.

Results

PRA023 reduced serum levels of T cell-derived cytokines (e.g., IL-5, IL-13, IL-17A, IL-22) and the monocyte/macrophage inflammatory cytokine IL-6 compared to placebo controls (p<0.05). In colonic tissue, 12 weeks of PRA023 treatment significantly reduced the expression of pro-inflammatory cytokine genes and pathways including Th1, Th17, Th2, and inflammatory monocyte gene sets, as well as TL1A-induced CD4+ T cell gene signatures (p<0.05); these changes were not observed in the placebo controls. These PD effects of PRA023 were only statistically significant in patients who achieved clinical remission. PRA023 also reduced the expression of fibrosis-associated genes and signatures in patients who achieved clinical remission (p<0.05). Cell-type deconvolution of bulk RNAseq using IBD single-cell reference datasets showed a reduction in the frequency of proliferating T cells and activated fibroblasts in PRA023-treated patients compared to placebo controls (p<0.01). The percent reduction in these cell types was greater in PRA023-treated patients who achieved clinical remission compared to non-remitters (p<0.0001).

Conclusion

Consistent with a role of TL1A in the immunopathogenesis of UC, biomarker analysis of PRA023-treated UC patients showed a reduction in Th1, Th17, Th2, and activated fibroblast gene signatures and peripheral inflammatory cytokines, providing insights into the mechanism of action of PRA023.

Disclosure

SD has received consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Dr. Falk Pharma, Eli Lilly and Company, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, and Vifor and lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, and Takeda.
MA has consulted and/or served on an advisory board for AbbVie Inc, Amgen, Arena Pharmaceuticals, Bristol Myers Squibb, Celsius Therapeutics, Eli Lilly and Company, Gilead Sciences, Janssen Pharmaceuticals, Microba Life Sciences, Pfizer Pharmaceutical, Prometheus Biosciences, UCB Biopharma SRL, and WebMD Global LLC; has taught, lectured and spoken for Alimentiv, Amgen, Janssen Pharmaceuticals, and Takeda Pharmaceuticals.
YW, HL, ED, FT, DDN, and EM are employees and shareholders of Prometheus Biosciences.
BGF has served as a consultant for AbbVie, AbolerIS Pharma, AgomAb, AllianThera, Amgen, AnaptysBio, Applied Molecular Transport, Arena, Avoro Capital Advisors, Atomwise, BIOJAMP, Biora Therapeutics, Boehringer Ingelheim, Boxer, Celsius Therapeutics, Bristol Myers Squibb/Celgene, Connect Biopharma, Cytoki, Disc Medicine, Duality, EcoR1 Capital, Eli Lilly and Company, Equillium, Ermium, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer Bio, GSK, Hinge Bio, HotSpot Therapeutics, Index Pharma, Imhotex, Immunic Therapeutics, JAK Academy, Janssen, Japan Tobacco, Kaleido, Landos Biopharma, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic Therapeutics, Mylan, OM Pharma, Origo Biopharma, Orphagen, Pandion Pharma, Pendopharm, Pfizer, Prometheus Therapeutics, PlayToKnow AG, Progenity, Protagonist Therapeutics, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen, Takeda, Teva, Thelium, TiGenix, Tillotts Pharma, Ventyx Biosciences, VHsquared, Viatris, Ysios, Ysopia, Zealand Pharma; on the speaker’s bureau for AbbVie, Janssen, and Takeda; and on advisory boards for AbbVie, Amgen, AMT, AnaptysBio, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Eli Lilly and Company, Genentech/Roche, Janssen, MiroBio, Origo BioPharma, Pfizer, Prometheus, REDX, Sanofi, Takeda, Tillotts Pharma, Teva, Progenity, Index, EcoR1 Capital, Morphic, GSK, and Axio Research.
BES has served as a consultant for or received speaker’s fees from AbbVie, Abivax, Adiso Therapeutics, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion Healthcare, ClostraBio, Connect Biopharma, Cytoki Pharma, Eli Lilly and Company, Entera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead, Genentech, GSK, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kallyope, Merck, MiroBio, Morphic Therapeutic, MRM Health, OSE Immunotherapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, RedHill Biopharma, Sun Pharma Global, Surrozen, Synlogic, Takeda, Target RWE, Theravance Biopharma R&D, TLL Pharmaceutical, USWM Enterprises, Ventyx Biosciences, and Viela Bio and has received stock options from Ventyx Biosciences.
FR is consultant to or on advisory board of Adiso, Adnovate, Agomab, Allergan, AbbVie, Arena, Astra Zeneca, Boehringer-Ingelheim, Celgene/BMS, CDISC, Celsius, Cowen, Ferring, Galapagos, Galmed, Genentech, Gilead, Gossamer, Granite, Guidepoint, Helmsley, Horizon Therapeutics, Image Analysis Limited, Index Pharma, Landos, Jannsen, Koutif, Mestag, Metacrine, Mopac, Morphic, Organovo, Origo, Palisade, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Sanofi, Surmodics, Surrozen, Takeda, Techlab, Teva, Theravance, Thetis, UCB, Ysios, and 89Bio.
ST has received consulting fees from Robarts Clinical Trials and Prometheus Biosciences and owns stock in Prometheus Biosciences; is a member of steering committees of Janssen, AbbVie, Boehringer Ingelheim, Gilead, Celgene, and Bristol Meyers Squibb; has received speaker honoraria from AbbVie, Takeda, Janssen, Ferring, Pfizer, and Celltrion; and has served on advisory committees of Janssen, Takeda, AbbVie, Eli Lilly, Pfizer, Gilead, Galapagos, and Roche.

Introduction

Interleukin (IL)-23 is a key driver in the pathogenesis of Crohn’s disease (CD). IL-23 is a heterodimer, consisting of p19 and p40 subunits encoded by IL-23A and -23R, respectively. Signaling through the IL-23 receptor complex leads to the transcription of effector cytokine genes, including IL-17A, -17F and -22. Risankizumab (RZB), a monoclonal antibody with specificity for IL-23p19 has demonstrated safety and efficacy for the treatment of CD.^1,2 Here we investigate if baseline (BL) IL-23 pathway gene expression (IL-17A, -17F, -22, -23R, and -23A) in CD patients (pts) is associated with clinical remission and endoscopic response at week (wk) 12 of induction in patients treated with RZB (see Table footnote for endpoint definitions).

Aims & Methods

RNA-sequencing was performed to examine IL-23 pathway gene expression at BL in intestinal biopsy samples (n=280) obtained from pts (n=160) in the 600 mg intravenous (IV) RZB arms of the ADVANCE and MOTIVATE induction studies.¹ Biopsies were taken from the site of active disease (colon [n=146] and/or ileum [n=134]). A linear model based differential expression was conducted between response and non-response using the co-primary endpoints of SF/APS clinical remission and endoscopic response at induction wk 12. Data were normalized using trimmed mean of M-values and log2 counts per million. P-values were adjusted using Benjamini-Hochberg method of multiple testing correction. Comparisons were performed between endoscopic responders or clinical remitters (R) and endoscopic non-responders or clinical non-remitters (NR) in all pts. Analyses were stratified by disease location and/or prior biologic response status.

Results

In the total cohort, IL-23A gene expression was higher at BL in clinical R versus (vs) NR (p=0.03) (see Table for results). However, this difference was only significant in patients with prior bio-failure (p=0.03). Additionally, no difference was observed in IL-23 pathway gene expression between endoscopic R vs NR. When stratifying by disease location, higher BL expression of IL-17A, -17F, -22 and -23A were observed in patients with colonic disease in clinical R vs NR with (p<0.05). This difference was observed in both bio-failure and non-bio-failure patients (p<0.05). No difference was observed between endoscopic R vs NR. In pts with ileal disease, no differences in IL-23 pathway gene expression were observed between clinical R versus NR. Higher BL expression of IL-17A and -17F, and lower BL expression of IL-23R, were demonstrated in endoscopic R vs NR at wk 12 (p<0.05). However this difference was only significant in bio-failure patients.

Conclusion

Endpoint	Patient Subgr​oups​​​​​	Baseline Gene Expression NR vs R Adjusted P-value (p<0.05 denoted in bold)
		IL-17A	IL-17F	IL-22	IL-23R	IL-23A
Clinical Remission at Week 12a	All Patients N=160 (62 R, 98 NR) Colonic Disease N=146 (56 R, 90 NR) Ileal Disease N=134 (47 R, 87 NR) Prior Bio-Failure N=113 (37 R, 76 NR) Without Prior Bio-Failure N=47 (25 R, 22 NR) Colonic Disease + Prior Bio-Failure N=101 (33 R, 68 NR) Colonic Disease + Without Prior Bio-Failure N=45 (23 R, 22 NR) Ileal Disease + Prior Bio-Failure N=94 (26 R, 68 NR) Ileal Disease + Without Prior Bio-Failure N=40 (21 R, 19 NR)	0.40 0.04 0.21 0.11 0.79 0.048 0.51 0.99 0.26	0.5 0.04 0.94 0.10 0.82 0.06 0.50 0.70 0.73	0.17 0.03 0.78 0.26 0.30 0.04 0.41 0.68 0.52	0.95 0.84 0.65 0.23 0.30 0.25 0.45 0.77 0.44	0.03 0.002 0.92 0.03 0.73 0.005 0.44 0.71 0.65
Endoscopic Response At Week 12b	All Patients N=160 (69 R, 91 NR) Colonic Disease N=146 (37 R, 109 NR) Ileal Disease N=134 (35 R, 99 NR) Prior Bio-Failure N=113 (23 R, 90 NR) Without Prior Bio-Failure N=47 (19 R, 28 NR) Colonic Disease + Prior Bio-Failure N=101 (20 R, 81 NR) Colonic Disease + Without Prior Bio-Failure N=45 (17 R, 28 NR) Ileal Disease + Prior Bio-Failure N=94 (18 R, 76 NR) Ileal Disease + Without Prior Bio-Failure, N=40 (17 R, 23 NR)	0.83 0.08 0.01 0.77 0.65 0.10 0.57 0.049 0.19	0.45 0.44 0.049 0.35 0.98 0.49 0.85 0.02 0.9	0.44 0.06 0.42 0.48 0.53 0.09 0.43 0.49 0.90	0.44 0.06 0.42 0.48 0.53 0.09 0.43 0.49 0.90	0.79 0.07 0.10 0.84 1.00 0.09 0.71 0.14 0.63
aAverage daily SF ≤ 2.8 and not worse than BL AND average daily AP score ≤ 1 and not worse than BL; bDecrease in SES-CD > 50% from BL (or for subjects with isolated ileal disease and a BL SES-CD of 4, at least a 2 point reduction from BL), as scored by central reviewer

Minimal differences in BL expression of IL-23 pathway genes were detected in the total cohort between clinical R vs NR and endoscopic R vs NR. Significant differences in BL expression of several IL-23 pathway genes were identified between clinical R and NR in pts with colonic disease. Shared and unique IL-23 pathway genes were significantly altered in pts with ileal disease between endoscopic R vs NR. However, these differences are unlikely to be clinically meaningful or predictive of response to RZB.

References

1. D’Haens G, Panaccione R, Baert F, Bossuyt P, Colombel JF, Danese S, et al. Risankizumab as induction therapy for Crohn’s disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. The Lancet. 2022 May;399(10340):2015–30.
2. Ferrante M, Panaccione R, Baert F, Bossuyt P, Colombel JF, Danese S, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. The Lancet. 2022 May;399(10340):2031–46.

Disclosure

James Lindsay: Consultant and an advisory board participant for AbbVie, Atlantic Healthcare, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Gilead, GSK, Janssen, MSD, Napp, Pfizer, Shire, Takeda, and Vifor Pharma; has received speaker fees and sponsorship for academic meetings from AbbVie, Ferring Pharmaceuticals, Janssen, MSD, Napp, Norgine, Pfizer, Shire, Tillotts Pharma, and Takeda; and has received investigator-led research grants from AbbVie, Gilead, Pfizer, Shire and Takeda.
Bram Verstockt: Research support from AbbVie, Biora Therapeutics, Landos, Pfizer, Sossei Heptares and Takeda. -Speaker’s fees from Abbvie, Biogen, Bristol Myers Squibb, Celltrion, Chiesi, Falk, Ferring, Galapagos, Janssen, MSD, Pfizer, R-Biopharm, Takeda, Truvion and Viatris. Consultancy fees from Abbvie, Alimentiv, Applied Strategic, Atheneum, Biora Therapeutics, Bristol Myers Squibb, Galapagos, Guidepont, Mylan, Inotrem, Ipsos, Janssen, Pfizer, Progenity, Sandoz, Sosei Heptares, Takeda, Tillots Pharma and Viatris.
Jean Frederic Colombel: Research grants from AbbVie, Janssen Pharmaceuticals and Takeda; receiving payment for lectures from AbbVie, Amgen, Allergan, Inc. Ferring Pharmaceuticals, Shire, and Takeda; consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, BMS, Celgene Corporation, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Genentech, Glaxo Smith Kline, Janssen Pharmaceuticals, Kaleido Biosciences, Imedex, Immunic, Iterative Scopes, Merck, Microbia, Novartis, PBM Capital, Pfizer, Protagonist Therapeutics, Sanofi,Takeda, TiGenix, Vifor; and hold stock options in Intestinal Biotech Development
Valerie Pivorunas, Naim Al Mahi, Nizar Smaoui, F. Stephen Laroux, Kristina Kligys Kori Wallace, and Heath Guay are AbbVie employees and may own AbbVie stock and/or options.

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.