Introduction

The Phase 3 QUASAR induction study (NCT04033445) was a randomized, double-blind, placebo-controlled study that evaluated guselkumab (GUS), an interleukin-23 p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) who had an inadequate response, loss of response, or intolerance to corticosteroids, immunosuppressants and/or advanced therapy (ADT, i.e., tumor necrosis factor antagonists [anti-TNFs], integrin receptor antagonists [vedolizumab], and/or Janus kinase [JAK] inhibitors [tofacitinib]). Here we report induction efficacy results for GUS compared with placebo by history of inadequate response, loss of response, or intolerance to ADT (ADT-IR).

Aims & Methods

Patients were randomized in a 3:2 ratio to receive IV GUS 200 mg or placebo at Weeks (Wks) 0, 4, and 8. The primary analysis population included patients with a baseline modified Mayo score of 5 to 9, inclusive, and a centrally reviewed endoscopy subscore ≥ 2. The primary endpoint was clinical remission at Wk 12. Symptomatic remission, clinical response, endoscopic improvement, histo-endoscopic mucosal improvement (HEMI), and endoscopic normalization were assessed at Wk 12.

Results

Of the 701 patients in the primary analysis population, 357 (50.9%) had no history of ADT-IR (of which 95.0% were ADT-naïve) ; 344 (49.1%) had a history of ADT-IR. Among the ADT-IR patients, the proportions with a history of inadequate response/loss of response/intolerance to TNF antagonists , vedolizumab, tofacitinib, and multiple ADT classes were 87.5%, 54.1%, 18.0% and 47.4%, respectively. At baseline, patients with a history of ADT-IR had longer disease duration (mean 8.9 vs 6.2 yrs), more severe endoscopic disease (endoscopy subscore of 3, 78.5% vs 57.7%), higher CRP (median 5.3 mg/L vs 3.4 mg/L and proportion of patients >3mg/L 64.1% vs 53.7%) and higher fecal calprotectin (median 1647 mg/kg vs 1589 mg/kg and proportion of patients >250 mg/kg 92.3% vs 86.9%) compared with patients without a history of ADT-IR. Greater proportions of patients treated with GUS vs placebo achieved primary and key secondary endpoints at Wk 12 in both subgroups of patients with and without a history of ADT-IR, including clinical remission, symptomatic remission, clinical response, endoscopic improvement, HEMI, and endoscopic normalization (Table 1). The treatment differences for GUS vs placebo were generally greater among patients without a history of ADT-IR compared with those with such a history.

Table 1. Primary and key secondary endpoints by history of inadequate response/loss of response/intolerance to advanced therapy (ADT-IR)

	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 Wk12a1,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,b N (%)	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,b N (%)	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. a3 Clinical 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. a4 Endoscopic improvement is defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. a5 Histo-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. a6 Endoscopic 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.

Conclusion

Induction treatment with GUS 200 mg IV resulted in greater improvements compared with placebo across key clinical, symptomatic, and endoscopic/histologic outcomes at Wk 12 among moderately to severely active UC patients with and without a history of ADT-IR.

Disclosure

Brian Bressler is an advisor/speaker and has received research support from Janssen. Steering Committee member for Janssen.
Laurent Peyrin-Biroulet reports personal fees and serves as a Steering Committee member for Janssen.
Jessica R. Allegretti is a consultant and Steering Committee member for Janssen.
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.
Ye Miao 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.
Martin Bortlik is a clinical investigator and consultant for Janssen.
Tibor Hlavaty is a clinical investigator and consultant for Janssen.
Toshimitsu Fujii has received research grants and speaker’s fees from 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. Steering Committee member for Janssen.
Bruce E. Sands reports grants, consulting and speaking fees and other support from Janssen, and is a Steering Committee member for 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; payment from lectures including service on speakers bureaus from Janssen. Steering Committee member for Janssen.

Introduction

Neoplasia detection in inflammatory bowel disease (IBD) poses a clinical challenge. We have previously reported the efficacy of a novel computer aided detection (CADe) algorithm for use in IBD (CADe-IBD) in images and videos. CADe-IBD is designed for use in high-definition white light endoscopy which may reduce operator variability which comes with chromoendoscopy. The added value of CADe-IBD is yet to be explored which this study aims to address.

Aims & Methods

Based on pilot data this study was powered as a superiority test, with 90% power for increased sensitivity of non-expert endoscopists with CADe-IBD compared to without CADe-IBD. 10 experienced and 11 less experienced endoscopists were asked to review short video clips of high definition white-light IBD endoscopy on a bespoke computer software designed by NEC Japan. The videos were watched once without CADe-IBD and then again with CADe-IBD when the videos were randomly redistributed to reduce recall bias. After each video the endoscopist was asked to select ‘polyp’, ‘no polyp’ or ‘uncertain’. If the endoscopist selected ‘polyp’ for a video they were asked to annotate the suspected abnormality.

Results

The study included 285 videos from IBD colon. 131 videos had lesions which showed a diverse range of size, morphology, histology and background mucosal inflammation. Videos were from all 3 major endoscopy processors (Pentax, Olympus and Fuji).
The standalone CADe-IBD sensitivity and specificity were 94.7% and 70.8% respectively. In comparison, experienced endoscopist sensitivity and specificity were 90.5% and 80.2% and less experienced endoscopists sensitivity and specificity of 73.7% and 82.1%. CADe-IBD sensitivity was significantly better than both experts and non-exerts (p<0.05).
With the addition of CADe-IBD, less experienced endoscopists sensitivity increased significantly to 89.2% (p <0.01) and specificity remained similar at 81.0%. Experienced endoscopist sensitivity also improved with CADe-IBD to 93.4% which was again statistically significant (p<0.05).
Sub-analysis was performed based on neoplastic or non-neoplastic histology, polypoid (Paris Is, Isp, Ip) and non-polypoid (Paris IIa/IIb/IIc) morphology and Mayo endoscopic sub-score for mucosal inflammation (Table 1).

Table 1.	CADe-IBD sensitivity	Less experienced endoscopist sensitivity	Less experienced + CADe-IBD sensitivity	Experienced endoscopist sensitivity	Experienced + CADe-IBD sensitivity
Overall (n=131)	94.7%	73.7%%	89.2%	90.5%	93.4%
Histology Neoplastic (n=62) Non-neoplastic (n=69)	96.8% 92.8%	72.6% 74.7%	90.2% 88.4%	92.1% 89.0%	95.0% 92.0%
Morphology Polypoid (n=29) Non-polypoid (n=102)	100% 93.1%	93.7% 68.0%	98.1% 86.7%	99.3% 87.9%	99.7% 91.7%
Mayo score 0 (n=105) 1 (n=21) 2 (n=5)	95.2% 90.5% 100%	74.1% 68.4% 87.3%	90.9% 80.1% 92.7%	90.7% 89.5% 90.0%	93.7% 92.9% 90.0%

Conclusion

CADe-IBD has a standalone performance which is superior to both less experienced and experienced endoscopists. The addition of CADe-IBD significantly improved lesion detection regardless of experience. This superior performance was observed in neoplastic lesions, non-polypoid lesions and in the presence of mild background mucosal inflammation which is of high clinical importance. This calls for a head to head comparison of CADe-IBD with conventional surveillance techniques.

References

Abdelrahim M, Siggens K, Iwadate Y, et al New AI model for neoplasia detection and characterisation in inflammatory bowel disease Gut 2024;73:725-728.

Disclosure

Professor Bhandari has received research grants or is the advisory board for Fujifilm, Boston, Olympus, Pentax, 3-D matrix, NEC (Japan) and Medtronic

Introduction

Microscopic colitis (MC) refers to two pathologies – Collagenous colitis (CC) and Lymphocytic colitis (LC) that cause chronic watery diarrhoea, urgency, incontinence leading to significantly decreased quality of life¹. It is thought that MC develops due to a pathological immune response to intestinal luminal antigens in genetically predisposed individuals, with microbiota playing an important role^{2, 3}. However, the pathogenesis of MC is still unclear.

Aims & Methods

The aim of this study was to identify and characterize changes in bacterial composition of MC patients in terminal ileum and different colonic segments and determine its relation to the clinical course of disease. Biopsies from terminal ileum and six segments of the colon were collected during diagnostic colonoscopies. DNA extraction was performed using AllPrep DNA/RNA Micro Kit (Qiagen) following the manufacturer’s instructions. To determine bacterial composition, sequencing of the 16S rRNA variable region V3-V4 was conducted using the 27F and 338R polymerase chain reaction primers and sequenced on a MiSeq (2×250 bp; Illumina, Hayward, CA). Bioinformatic analysis was performed using DADA2, and taxonomic classification was carried out with the RDP classifier.

Results

Biopsy samples from 20 active CC patients, 20 active LC patients, and 50 controls demonstrated distinct microbial profiles across different intestinal segments, as revealed by beta-diversity and differential compositional analyses. Compared with controls, CC patients had consistent alterations in three bacterial families throughout the entire colon, with Erysipelatoclostridiaceae and Coriobacteriaceae decreased and Pasteurellaceae increased. Additionally, 35 families had segment-specific changes, and 25 families displayed altered abundance in the terminal ileum.
LC patients exhibited a consistent increase in Erisypelotrichaceae across the entire colon, with 38 other families showing segmental changes, and 12 families displaying altered abundance in the terminal ileum. Comparing LC and CC revealed a significantly different bacterial profile. LC showed lower abundance across many families, particularly in the right colon and terminal ileum. After sample collection, 15 CC patients and 12 LC patients received budesonide, with 3 CC and 2 LC patients having incomplete response. Beta diversity analysis revealed significant differences in the ascending colon and left side of the colon of CC patients based on response to budesonide. Patients with incomplete response to budesonide had an increased abundance of the genus Paucibacter. Similar tendencies were not observed in LC.
1 CC patient exhibited a quiescent disease course, 6 reached a sustained remission after treatment, 7 had a relapsing and 6 had a chronic active disease. Significant differences in beta diversity were observed in transverse, descending colon and rectum. Beta diversity of the descending colon had a medium correlation with disease behaviour. In the LC group 6 patients had a quiescent disease, 8 had a sustained remission after treatment, 3 exhibited a relapsing and 4 had a chronic active disease. No significant correlation between microbiota and disease behaviour was observed in LC.

Conclusion

This study showed significant differences in bacterial composition between CC, LC and controls in the terminal ileum and colon. In both CC and LC, bacterial alterations were not consistent throughout the entire colon but varied between different colonic segments. Microbiome differences based on response to budesonide and disease behaviour were observed in CC, but not LC.

References

1. Verhaegh BPM, Münch A, Guagnozzi D, et al. Course of Disease in Patients with Microscopic Colitis: A European Prospective Incident Cohort Study. J Crohns Colitis. 2021;15(7):1174-1183.
2. Miehlke S, Guagnozzi D, Zabana Y, et al. European guidelines on microscopic colitis: United European Gastroenterology (UEG) and European Microscopic Colitis Group (EMCG) statements and recommendations. United European Gastroenterol J. Published online 2020.
3. Burke KE, D’Amato M, Ng SC, Pardi DS, Ludvigsson JF, Khalili H. Microscopic colitis. Nat Rev Dis Primers. 2021;7(1).

Introduction

Inhibition of interleukin (IL)-23 has been demonstrated as a safe and effective mechanism of action for treating various chronic inflammatory diseases, including Crohn's disease (CD). The phase 3b SEQUENCE study directly compared the efficacy and safety of risankizumab (RZB), a selective IL-23 p19 subunit inhibitor, and ustekinumab (UST), an IL-12/IL-23 p40 subunit inhibitor, in patients (pts) with moderate to severe CD.

Aims & Methods

SEQUENCE, an open-label, multicenter, randomized, efficacy assessment-blinded study, enrolled pts who previously failed ≥1 anti-TNF therapies and had a CD Activity Index score of 220-450, Simple Endoscopic Score for CD ≥6 for ileocolonic or colonic disease (≥4 for isolated ileal disease) excluding the presence of narrowing component, plus an average (avg) daily stool frequency ≥4 and/or avg daily abdominal pain score ≥2. In Part 1 of the trial, described herein, pts were randomized 1:1 to receive RZB (600 mg IV induction dosing at baseline [BL], weeks [wks] 4 and 8, followed by 360 mg SC maintenance dosing every 8 wks [Q8w] starting at wk12) or UST (a single weight-based IV induction dose, followed by 90 mg SC maintenance dosing Q8w starting at wk8) over a period of 48 wks.¹ Randomization was stratified by number of anti-TNF therapies failed (1, >1) and steroid use at BL (Y, N). A mandatory steroid taper started at wk2. Two primary endpoints were clinical remission at wk24 (non-inferiority of RZB vs UST in 50% of planned subjects) and endoscopic remission at wk48 (superiority of RZB vs UST). Ranked secondary endpoints included clinical remission at wk48, endoscopic response at wks 48 and 24, steroid-free (SF) endoscopic remission at wk48, and SF clinical remission at wk48 (all tested for superiority of RZB vs UST). Safety was assessed throughout the trial.

Results

Variable	RZB N=255 n/N (%)	UST N=265 n/N (%)	Treatment Difference RZB – UST % [95% CI]
Primarya 1. Clinical remission at wk 24 (ITT-1Hb) 2. Endoscopic remission at wk 48 (ITT-1d) Ranked Secondarya,d 1. Clinical remission at wk 48 2. Endoscopic response at wk 48 3. Endoscopic response at wk 24 4. Steroid-free endoscopic remission at wk 48 5. Steroid-free clinical remission at wk 48	75/128 (58.6%) 81/255 (31.8%) 155/255 (60.8%) 115/255 (45.1%) 115/255 (45.2%) 80/255 (31.4%) 155/255 (60.8%)	54/137 (39.5%) 43/265 (16.2%) 108/265 (40.8%) 58/265 (21.9%) 70/265 (26.4%) 41/265 (15.5%) 107/265 (40.4%)	Non-inferiorityc met; 18.4 [6.6, 30.3] 15.6 [8.4, 22.9], P<0.0001 19.7 [11.3, 28.1], P<0.0001 23.3 [15.4, 31.2], P<0.0001 18.9 [10.9, 26.9], P<0.0001 15.9 [8.8, 23.1], P<0.0001 20.1 [11.7, 28.4], P<0.0001
Treatment Emergent Adverse Events (AEs)e	RZB N=262 PYs = 257.6 Events (E/100PYs)f	UST N=265 PYs = 269.9 Events (E/100PYs)f	Treatment Difference RZB – UST % [95% CI]
All TEAEs Investigator-defined drug-related AEg,h Severe AE Serious AE AEs leading to study drug discontinuation Death Adverse Events of Special Interest Adjudicated MACE/Extended MACEi Serious infections Active tuberculosis Opportunistic infections excluding tuberculosis and herpes zosterj Herpes zoster Malignant tumoursk Non-melanoma skin cancer (NMSC) Malignancies excluding NMSC Hypersensitivity Serious hypersensitivity Adjudicated anaphylactic reaction Hepatic events Injection site reactions	879 (341.2) 167 (64.8) 60 (23.3) 36 (14.0) 10 (3.9) 0 0 10 (3.9) 0 1 (0.4) 1 (0.4) 1 (0.4) 1 (0.4) 0 37 (14.4) 0 0 26 (10.1) 5 (1.9)	763 (282.7) 111 (41.1) 82 (30.4) 64 (23.7) 14 (5.2) 0 1 (0.4) 14 (5.2) 0 0 1 (0.4) 1 (0.4) 0 1 (0.4) 32 (11.9) 0 0 23 (8.5)i 8 (3.0)	58.5 (28.3, 88.7) 23.7 (11.2, 36.2) -7.1 (-15.9, 1.7) -9.7 (-17.1, -2.4) -1.3 (-4.9, 2.3) 0 -0.4 (-1.1, 0.4) -1.3 (-4.9, 2.3) 0 0.4 (-0.4, 1.1) 0.0 (-1.0, 1.1) 0.0 (-1.0, 1.1) 0.4 (-0.4, 1.1) -0.4 (-1.1, 0.4) 2.5 (-3.7, 8.7) 0 0 1.6 (-3.6, 6.8) -1.0 (-3.7, 1.6)
AE – adverse event; BL - baseline; CD – Crohn’s disease; CDAI – CD activity index; ITT – intention to treat; RZB - risankizumab; PY, patient years; SES-CD, simple endoscopic score for CD; TEAE – treatment emergent AE; UST – ustekinumab; wk, week Clinical remission – CDAI < 150 Endoscopic remission - SES-CD ≤ 4 and at least a 2-point reduction versus BL and no sub score greater than 1 in any individual variable, as scored by a central reviewer blinded to treatment allocation Endoscopic response - decrease in SES-CD > 50% from BL (or for pts with isolated ileal disease and a BL SES-CD of 4, at least a 2-point reduction from BL), as scored by central reviewer Steroid-free endoscopic remission - endoscopic remission and not receiving steroids at the corresponding visit Steroid-free clinical remission - clinical remission and not receiving steroids at the corresponding visit *SEQUENCE Part 1 compared the efficacy and safety of RZB versus UST over 48 wks, while Part 2 is an ongoing open-label long-term extension to evaluate the long-term safety of RZB in pts who received RZB in Part 1 and completed wk48 visit. aCategorical variables were analyzed using Cochran-Mantel-Haenszel (CMH) test. For both the primary and secondary endpoints, the non-responder imputation while incorporating multiple imputation to handle missing data (due to COVID-19 or geopolitical conflict) was used. Primary and secondary endpoints were tested sequentially in the order specified using the CMH risk difference estimate test stratified by the number of failed anti-TNF therapies (1, > 1) and steroid use at baseline (yes, no). bITT1H population is a subset of ITT-1 population and includes approximately 50% of ITT1 subjects who have opportunity to reach wk24 by the time of the primary analysis of CDAI clinical remission at wk24; non-inferiority of RZB vs. UST cNon-inferiority test: If the lower limit of 95% confidence interval based on the CMH estimation for the risk difference between RZB and UST groups (RZB – UST) was greater than the negative of 10% noninferiority margin, then noninferiority was demonstrated for clinical remission at wk24. If non-inferiority was demonstrated for clinical remission (CDAI) at Week 24, the superiority for the endoscopic remission at Week 48 was subsequentially tested at two-sided significance level of 0.05 using the CMH test. dIntent-to-treat-1 (ITT-1) population included all randomized subjects who were randomized to RZB with the selected RZB dose (RZB 600 mg IV followed by RZB 360 mg SC) or UST and who received at least 1 dose of study drug during Part 1 of the study; superiority of RZB vs. UST eTEAEs are events that begin either on or after the first dose of UST or RZB in Part 1 and until the first dose of study drug (RZB) in Part 2 if the pt is enrolled into the Part 2 or within 140 days after the last dose administration of the study drugs (UST or RZB) in Part 1 if the pt does not participate in Part 2. Only safety data obtained before 12JUL2023 or Week 52 dosing date (the first dose date of Part 2), whichever occurred earlier, are reported here. fSA1 population includes all pts who received at least 1 dose of study drug during Part 1 of the study. gAs assessed by investigator hRZB related: 3 patients with SAEs related to RZB (anal fistula, anal abscess, campylobacter, cystitis, localized infection, genital fistula); 8 patients with SAEs related to UST (abdominal pain, anal fistula, CD, ileal stenosis, vomiting) iMACE: Major Adverse Cardiovascular Events, defined as cardiovascular death or death due to stroke, non-fatal myocardial infarction, and non-fatal stroke; extended MACE defined as MACE with hospitalization for unstable angina and coronary revascularization procedures jOpportunistic infection: RZB, oesophageal candidiasis kMalignant tumor: RZB, squamous cell carcinoma of skin; UST, anal squamous cell carcinoma iOne case of potential Hy’s Law in the UST treatment group

In total, 520 pts were randomized and assessed for efficacy: RZB (N=255) and UST (N=265). The proportion of pts who completed the study was numerically higher with RZB (89.4%) vs UST (74.0%). The two primary endpoints of the study were met. At wk24, in half of the patients enrolled, clinical remission rates were 58.6% (75/128) for RZB and 39.5% (54/137) for UST (Δ18.4 [6.6-30.3], non-inferiority met with the pre-defined margin of 10%) (Table). At wk48, endoscopic remission rates were 31.8% (81/255) for RZB and 16.2% (43/265) for UST (Δ15.6% [8.4-22.9], P<0.0001 for superiority). RZB was superior to UST for all secondary endpoints (all P<0.0001). Exposure adjusted adverse event (AE) rates (Events [E/100PYs]) were comparable between RZB (879 [341.2]) and UST (763 [282.7]). Rates of serious AEs and AEs leading to study drug discontinuation were numerically higher with UST than RZB (Table). Rates of serious infections and hepatic events were similar between treatment groups, with no serious hepatic events with RZB. Two cases of malignancy were reported (one in each treatment arm). There was one event of adjudicated MACE with UST. There were no deaths.

Conclusion

In pts with moderate to severe CD who failed anti-TNF therapy, RZB demonstrated non-inferiority to UST in achieving wk24 clinical remission, superiority in achieving wk48 endoscopic remission, and superiority for achieving all secondary endpoints. The safety profiles of RZB and UST were consistent with previously published results.

References

1. Stelara Label [Internet]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125261s161lbl.pdf

Disclosure

Laurent Peyrin-Biroulet: Fees: Galapagos, AbbVie, Janssen, Genentech, Alimentiv, Ferring, Tillots, Celltrion, Takeda, Pfizer, Index, Sandoz, Celgene, Biogen, SamsungBioepis, Inotrem, Allergan, MSD, Roche, Arena, Gilead, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, OSEImmunotherapeutics, Enthera, Theravance, Pandion, Gossamer, Viatris, ThermoFisher, ONOPharma, Mopac, Cytoki, Morphic, Prometheus, Applied MolecularTransport; J. Casey Chapman: Consultant: AbbVie, Medtronic; Advisory Board: AbbVie, Pfizer, Takeda; Speaker: AbbVie, BMS, Janssen, Pfizer, Takeda; Jean-Frederic Colombel: Grants: AbbVie, Janssen, Takeda, BMS; Speaking fees: AbbVie, Takeda; Consultant: AbbVie, Amgen, AnaptysBio, Allergan, Arena, BI, BMS, Celgene, Celltrion, Lilly, Ferring, Galmed, GSK, Genentech (Roche), Janssen, Kaleido, Immunic, IterativeScopes, Merck, Landos, Microba Life Science, Novartis, Otsuka, Pfizer, ProtagonistTherapeutics, Sanofi, Takeda, TiGenix, Vifor; Stock options: IntestinalBiotechDevelopment; Flavio Caprioli: Consultant: AbbVie, MSD, Takeda, Janssen, Roche, Celgene, BMS, Galapagos, Gllead, Pfizer, Mundipharma, Galapagos, Biogen; Speaker: AbbVie, Ferring, Takeda, AllergyTherapeutics, Janssen, Pfizer, Biogen; Research grants: Giuliani, Sofar, MSD, Takeda, AbbVie; Geert D’Haens: Advisor: AbbVie, Ablynx, ActiveBiotechAB, AgomabTherapeutics, Alimentiv, Allergan, Alphabiomics, Amakem, Amgen, AMPharma, AppliedMolecularTherapeutics, Arena, AstraZeneca, Biogen, BMS, BI, Celltrion, DSMPharma; Echo, Engene, Exeliom, Ferring, Dr Falk, Galapagos, Genentech/Roche, Gilead, GSK, Gossamerbio, Immunic, J&J, Kintai, Lilly, Lument, Lycera, Medtronic, MSD, MitsubishiTanabe, NovoNordisk, Otsuka, Pfizer, Photopill, ProciseDx, Prodigest, Progenity, Prometheus/Nestlé, Protagonist, RedHill, SamsungBioepis, Sandoz, Seres, Setpoint, Shire, Takeda, Teva, Tillotts, Topivert, Versant, Vifor. Marc Ferrante: Grants: AbbVie, Amgen, Biogen, EG, Janssen, Pfizer, Takeda, Viatris; Consultant: AbbVie, Agomab, BI, Celgene, Celltrion, Lilly, Janssen-Cilag, Medtronic, MSD, Pfizer, Regeneron, SamsungBioepis, Sandoz, Takeda, ThermoFisher; Speaker: AbbVie, Amgen, Biogen, BI, Falk, Ferring, Janssen-Cilag, Lamepro, MSD, Pfizer, Sandoz, Takeda, Truvion, Viatris; Stefan Schreiber: Consultant: AbbVie, Amgen, Arena, BMS, BI, Celltrion, Dr Falk, Ferring, Fresenius, Galapagos, Genentech, Gilead, GSK, IMAB-Biopharma, Janssen, Lilly, Merck, Novartis/Sandoz, Pfizer, Protagonist, Takeda, Theravance. Raja Atreya: Speaker, consultant, or grants: AbbVie, Amgen, Arena, Biogen, BI, BMS, Cellgene, Celltrion, DrFalk, Galapagos, Gilead, InDex, Janssen-Cilag, Lilly, MSD, Novartis, Pandion, Pfizer, Roche, SamsungBioepis, Takeda, Viatris; Silvio Danese: Consultant: AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, AthosTherapeutics, Biogen, BI, Celgene, Celltrion, Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, J&J, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB, and Vifor; Lecture fees: Abbvie, Amgen, Dr Falk, Ferring, Gilead, Janssen, Mylan, Pfizer, Takeda. James O. Lindsay: Consultant/advisory board: AbbVie, AtlanticHealthcare, BMS, Celgene, Celltrion, Lilly, Ferring, Galapagos, Gilead, GSK, Janssen, MSD, Napp, Pfizer, Shire, Takeda, Vifor; Speaker fees/sponsorship: AbbVie, Ferring, Janssen, MSD, Napp, Norgine, Pfizer, Shire, Tillotts, Takeda; Grants: AbbVie, Gilead, Pfizer, Shire, Takeda; Peter Bossuyt: Grants: AbbVie, Amgen, Janssen, Mundipharma, Mylan, Pfizer; Speaker: AbbVie, Celltrion, Janssen, Pfizer, Takeda; Advisory Board: AbbVie, Arena, BMS, Hospira, Janssen, Lilly, Merck, Mundipharma, PentaxMedical, Pfizer, PSI CRO, Roche, Sandoz, Takeda; Britta Siegmund: Consultant: AbbVie, Arena, BI, BMS, Celgene, Falk, Galapagos, Janssen, Lilly, Pfizer, Prometheus, Takeda; Speaker’s fees: AbbVie, CEDServiceGmbH, Falk, Ferring, Janssen, Novartis, Pfizer, Takeda; Peter Irving: Grants/ Fees: Janssen, MSD,Takeda; Personal fees: AbbVie, Arena, Dr. Falk, Lilly, Ferring, Genentech, Hospira, Pfizer, Pharmacosmos, SamsungBioepis, Sandoz, Shire, Tillotts, TopiVert, VHsquared, Vifor, WarnerChilcott. Remo Panaccione: Consultant: AbbVie, Abbott, Alimentiv, Amgen, Arena, AstraZeneca, BMS, BI, Celgene, Celltrion, Cosmos, Eisai, Elan, Ferring, Galapagos, Genentech, Gilead, GSK, Janssen, Lilly, Merck, Mylan, Oppilan, Pandion, Pfizer, Progenity, Protagonist, Roche, Sandoz, Satisfai, Schering-Plough, Shire, Sublimity, Theravance, UCB, Takeda; Speaker: AbbVie, Arena, Celgene, Ferring, Gilead, Janssen, Lilly, Merck, Pfizer, Roche, Sandoz, Shire, and Takeda; Grants: AbbVie, Ferring, Janssen, Pfizer, Takeda; Advisory board: AbbVie, Amgen, Arena, BMS, Celgene, Celltrion, Ferring, Galapagos, Genentech, Gilead, GSK, Janssen, Lilly, Merck, Mylan, Oppilan, Pandion, Pfizer, Sandoz, Shire, Sublimity, Takeda, Theravance. Marla Dubinsky: Consultant: AbbVie, Arena, BMS, Celgene, Lilly, Genentech, Gilead, Janssen, Pfizer, Prometheus, Takeda; Founder/shareholder Trellus Health.
Ezequiel Neimark, Kori Wallace, Toni Anschutz, Kristina Kligys, W Rachel Duan, Valerie Pivorunas, Xiu Huang, Sofie Berg, Lei Shu: AbbVie full-time employees; may own AbbVie stock or options.