Introduction

The concept of disease clearance (DC), which includes symptomatic, endoscopic and histologic remission, has been proposed as the ultimate goal in ulcerative colitis (UC) treatment. However, the prognostic value of this endpoint remains uncertain.¹ Etrasimod is an investigational, oral, once-daily, selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator in development for the treatment of moderately to severely active UC.

Aims & Methods

We report a post hoc analysis from the ELEVATE UC trials to assess relationships between histological/composite endpoints, biomarkers and efficacy outcomes in etrasimod-treated patients (pts). In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), pts with moderately to severely active UC were randomised 2:1 to once‑daily etrasimod 2 mg or placebo (PBO). DC was defined as Nancy Histological Index=0, Mayo endoscopic subscore [ES]=0, rectal bleeding subscore=0, stool frequency subscore=0 or 1 (if 1, must have ≥ 1 point decrease from baseline). Other endpoints are defined in the Table. Kappa correlation coefficients² were estimated between histological endpoints at Wk 12 and efficacy outcomes at Wk 52, and between histological endpoints and biomarkers at Wks 12 and 52.

Results

At Wk 12 in both trials, DC was achieved by more etrasimod- than PBO-treated pts (8.4% [23/274] vs 1.5% [2/135] and 9.9% [22/222] vs 4.5% [5/112], p<0.001 and p=0.042, respectively). The proportion of pts with clinical remission at Wk 52 was higher among pts who achieved DC at Wk 12 (17/23; 74%) vs pts who did not (71/251; 28%). Histologic-endoscopic mucosal improvement at Wk 12 had the highest correlation with efficacy outcomes at Wk 52 (κ 0.357–0.438; Table). Faecal calprotectin and C‑reactive protein normalisation showed slight/fair to substantial agreement with histologic endpoints (κ 0.223–0.630; 0.075–0.6, respectively; Table). Absolute lymphocyte count < 0.5x10⁹/L showed no agreement (κ -0.100–0.216; Table).

Conclusion

Early achievement of DC showed only fair correlation with Wk 52 efficacy outcomes. Correlation of faecal calprotectin < 150 mg/kg with histological endpoints was most often moderate and improved from Wks 12 to 52. A different approach is needed for development of robust predictive models.

References

1. D’Amico F et al. United Eur Gastroenterol J 2022;10:777–784
2. Cohen JA et al. Educ Psychol Meas 1960;20:37–46

Disclosure

FM: grant support: GEDII and National Science Foundation; personal fees: AbbVie, Amgen, Biogen, Celgene, Celltrion, Dr. Falk Pharma, Ferring Pharmaceuticals, Hospira, Janssen, Laboratórios Vitória, MSD, Pfizer, Sandoz, Takeda, UCB, Vifor.
LPB: grant/research support: Takeda, Fresenius Kabi and Celltrion; consultancy fees: AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Biogen, Bristol-Myers Squibb, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Eli Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par'Immune, Pfizer Inc, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, TiGenix, Tillotts, Viatris, Vifor, Ysopia and Abivax; lecture/speaker fees: Galapagos, AbbVie, Janssen, Genentech, Ferring Pharmaceuticals, Tillotts, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena Pharmaceuticals, Eli Lilly, Gilead Sciences, Viatris, Medac, Sanofi; holds stock in CTMA.
BES: research grants: Arena, Janssen. Lecture fees/Speakers Bureau: Bristol-Myers Squibb, Janssen, Lilly, Pfizer, Takeda. Consultancy, Advisory Committee/Board Member: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Genentech, Glaxo SmithKline, Janssen, Lilly, Merck, Pfizer, Prometheus Biosciences, Sun Pharma Global, Takeda Pharmaceuticals International, Teva Branded Pharmaceutical Products R&D. Shareholder/Stock Options: Ventyx Biosciences. Other non-financial support: Janssen, Lilly, Pfizer, Takeda.
SD: consultancy/advisory fees: AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring Pharmaceuticals, Gilead Sciences, Hospira, Janssen, Johnson & Johnson, MSD, Mundipharma, Pfizer Inc, Roche, Sandoz, Takeda, TiGenix, UCB and Vifor; lecture/speaker fees: AbbVie, Amgen, Ferring Pharmaceuticals, Gilead Sciences, Janssen, Mylan, Pfizer Inc, Takeda; has directorship/ownership interests in Gastroenterology and Endoscopy.
VJ: financial support: Celgene/Bristol-Myers Squibb, Pfizer, AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Takeda, Gilead and TiGenix; consultancy: AbbVie, Alimentiv, Amgen, Anokion, Applied Strategic, Arena, Asahi Kasei, Asieris, AstraZeneca, BIOJAMP, Celgene/Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, F Hoffmann La Roche, Flagship Pioneering, Fresenius Kabi, Fusion MD, Galapagos, Genentech, Gilead, GSK, Janssen, Knightslab, Organon, Landos, McKesson, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Prometheus, Protagonist, Reistone, Roche, Sandoz, Second Genome, Sorriso, Takeda, Teva, Topivert, Ventyx, Viatris, Vividion; lecture: AbbVie, Ferring, Galapagos, Janssen, Pfizer, Takeda, Bristol-Myers Squibb.
MG: employee & shareholder of Pfizer AG.
AB: employee of Pfizer Healthcare India & shareholder of Pfizer.
JW, DB & IM: employees & shareholders of Pfizer.
BGF: consultant/on advisory board: AbbVie, AbolerIS, AgomAB, AllianThera, Amgen, AnaptysBio, Applied Molecular Transport, Arena, Avoro Capital, Atomwise, BIOJAMP, Biora, Boehringer Ingelheim, Boxer, Celsius, Celgene/Bristol-Myers Squibb, Connect, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, FirstWord, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer, GSK, Hinge, HotSpot, InDex, Imhotex, Immunic, JAK, Janssen, Japan Tobacco, Kaleido, Landos, Leadiant, L.E.K., Lenczner Slaght, LifeSci, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic, Mylan, OM, Origo, Orphagen, Pandion, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist, PTM, Q32, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres, Silverback, Surrozen, Takeda, Teva, Thelium, TiGenix, Tillotts, Ventyx, VHSquared Ltd., Viatris, Ysios, YSOPIA, Zealand; speaker: AbbVie, Janssen, Takeda; Alimentiv Senior Scientific Director, provides central reading services; not a company employee, no equity stake; shareholder: Gossamer.

Introduction

Mirikizumab (miri), an anti-IL-23p19 antibody, has shown efficacy in patients with moderately-to-severely active Crohn’s disease (CD) to Week (W)52. We explored the potential relationship between early histologic and endoscopic responses on long term clinical outcomes after 2 years of miri treatment in a double-blind, placebo (PBO)-controlled Phase 2 trial (NCT02891226) in patients with CD.

Aims & Methods

Patients were randomized 2:1:1:2 to 4 treatment arms: miri 1000mg, 600mg, 200mg, and PBO administered intravenously (IV) at W0, W4, and W8. Patients who received miri and achieved ≥1 point improvement at W12 in Simple Endoscopic Score for Crohn’s disease score were re-randomized to either continue their induction IV dose or receive miri 300mg subcutaneously (SC) every 4 weeks up to W52. Subjects reported to experience clinical benefit received 300mg SC from W52 to W104. Biopsies were obtained during endoscopy at W0, W12 and W52 from the edges of any ulcers or from the most inflamed mucosa in the terminal ileum and 4 colonic segments and were scored by blinded central readers. Endpoints were defined post-hoc and prior to analyses (see Table 1). Among patients receiving miri with active histological disease at baseline, we determined the relationship between histologic and/or endoscopic response or remission at W12 and W52 and with clinical remission based on the Crohn’s Disease Activity Index (CDAI), patient-reported outcomes (PRO), and hospitalization rates at W104. Non-responder imputation for CDAI or PRO at W104 was used for patients who have observed histologic and endoscopic outcome value at W52 or W12. Hospitalizations were summarized by observed value. P-values for categorical values were determined with Fisher’s exact test.

Results

At W104, 56.9% patients (N=137) achieved CDAI remission compared to 41.5% of 176 patients at W52. We observed no association between early (W12) histologic, endoscopic, or combined (histo-endo) response and clinical remission (CDAI & PRO) at 2 years. After 2 years, the percentage of patients achieving remission based on CDAI varied according to their response at W52 by histology (60%), endoscopy (25.9%), both histo-endo (56.3%), or neither (10.5%, p=0.006; Table 1). Similarly, the proportion of patients who achieved 2-year clinical remission (by CDAI) varied according to W52 remission by histology (72.7%), endoscopy (40%), both histo-endo (40%) or neither (19.5%, p=0.007). Hospitalization rates during this period were low and varied according to W52 response by histology (16.7%), endoscopy (0%), both (0%) or neither (3.9%, p=0.021).

Table 1. Week 104 clinical remission and hospitalization rates by histologic and endoscopic response at Week 12 and Week 52, and by histologic and endoscopic remission at Week 52

Conclusion

In CD patients treated with miri for 2 years, long term clinical remission (CDAI, PRO) was significantly correlated with histologic response alone as well as combined histologic-endoscopic response at Week 52, but not at Week 12. The small sample size was likely a limitation. This data will be further studied in Phase 3 trials.

Disclosure

VJ reports consulting/advisory board fees from AbbVie, Alimentiv Inc (formerly Robarts Clinical Trials), Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert, Vividion; speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen, Pfizer, Shire, Takeda, Fresenius Kabi. 
WR reports lecture fees from AbbVie, Actelion, Alpha Wasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson & Johnson, Millennium, Merck, NovoNordisk, Nycomed, Pfizer, Pharmacosmos, Schering-Plough, Salix, Takeda, UCB Pharma, and Vifor; consultant fees from AbbVie, Actelion, Alpha Wasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson & Johnson, Millennium, Merck, NovoNordisk, Nycomed, Pfizer, Pharmacosmos, Schering-Plough, Salix, Takeda, UCB Pharma, and Vifor; and serves as an advisory board member for AbbVie, Actelion, Alpha Wasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson & Johnson, Millennium, Merck, NovoNordisk, Nycomed, Pfizer, Pharmacosmos, Schering-Plough, Salix, Takeda, UCB Pharma, and Vifor.
GDH reports that his institution has received fees for his clinical trial activities with Centocor J&J.
NH has served as an advisory board member or consultant for Eli Lilly and Company, Abbvie Inc., Bristol Meyer Squibb, Inc., and PathAI, Inc.
RP reports consulting fees from Seres Therapeutics, Eli Lilly, Protagonist, Genentech, and Robarts Clinical Trials.
MP, ZL, RH, HC are employees and minor shareholders of Eli Lilly and company. 
FM served as speaker for Abbvie, Arena, Biogen, Bristol-Myers Squibb, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Pfizer, Lilly, Merck Sharp & Dohme, Sandoz, Takeda, UCB, Vifor.

Introduction

Tumor necrosis factor–like cytokine 1A (TL1A) promotes inflammation and fibrosis. PRA023 is an anti-TL1A monoclonal antibody in development for multiple inflammatory/fibrotic diseases. ARTEMIS-UC was a phase 2 multicenter, double-blind, placebo-controlled trial of PRA023 in adults with moderately to severely active ulcerative colitis (UC). The primary endpoint of clinical remission was statistically significantly higher in the PRA023 arm compared with the placebo arm. Here, we report the impact of PRA023 on endoscopic and histologic outcomes.

Aims & Methods

Adults with a modified Mayo score of 4 to 9, centrally read endoscopy subscore of ≥2, rectal bleeding subscore of ≥1, and history of insufficient response, loss of response, and/or intolerance to conventional and/or advanced therapies (≤4 advanced agents from ≤3 classes allowed) were randomized 1:1 to receive placebo or intravenous PRA023 (1000 mg on day 1, and 500 mg at weeks 2, 6, and 10). Endoscopic improvement (defined as a Mayo endoscopic subscore ≤1 with no friability), endoscopic remission (defined as a Mayo endoscopic subscore of 0), histologic improvement (defined as Geboes score ≤3.1), and mucosal healing (defined as Geboes score ≤2B.1 and endoscopy subscore ≤1) were measured after 12 weeks of induction therapy. Improvements in other histologic parameters were assessed by changes in Geboes scores.

Results

Of 135 randomized patients, 60/67 (89.6%) in the placebo arm and 68/68 (100%) in the PRA023 arm completed the 12-week induction period. Baseline characteristics were similar between treatment groups. Among alpha-controlled secondary endpoints, endoscopic improvement was observed in 36.8% of PRA023-treated vs 6.0% of placebo-treated patients (Δ30.8%, p<0.0001) at week 12. Histologic improvement occurred in 46.2% of patients receiving PRA023 vs 17.5% receiving placebo (Δ28.6%, p=0.0009) and mucosal healing in 30.8% vs 3.5% (Δ27.3%, p<0.0001), respectively. The mean change (SD) from baseline in the Mayo endoscopic subscore was −0.8 (0.93) for PRA023 vs −0.2 (0.54) for placebo. Furthermore, in a post hoc analysis, a significantly greater proportion of patients who received PRA023 achieved endoscopic remission (11.8% PRA023 vs 0% placebo, Δ11.8%, p=0.004). Of the patients with eosinophils in the lamina propria (LP) at baseline, 21.8% receiving PRA023 and 5.8% receiving placebo experienced complete resolution. Similarly, the resolution rates in those with neutrophils in the LP at baseline were 41.2% and 15.4% in PRA023-treated and placebo-treated patients, respectively; and of those with neutrophils in the epithelium at baseline, values were 40.4% vs 11.3%, respectively.

Conclusion

In patients with moderately to severely active UC, PRA023 resulted in a significantly greater proportion of patients achieving endoscopic remission, endoscopic improvement, histologic improvement, and mucosal healing, endpoints associated with an improved prognosis. Resolution of eosinophil and neutrophil infiltration suggests a reduction in the inflammation associated with UC.

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.
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.
LPB has served as a consultant for or has received fees from AbbVie, Allergan, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Eli Lilly and Company, Enterome, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, Hikma, Index Pharmaceuticals, Inotrem, Janssen, MSD, Mylan, Oppilan Pharma, OSE Immunotherapeutics, Nestlé, Norgine, Roche, Pandion Therapeutics, Pfizer, Pharmacosmos, Samsung Bioepis, Sandoz, sterna biologicals, Sublimity Therapeutics, Takeda, Theravance Biopharma, Tillotts Pharma, and Vifor; has received grants from AbbVie, Fresenius Kabi, MSD, and Takeda; and has stock options from CTMA.
DTR has served as a consultant for AbbVie, AltruBio, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Chronicles, Corp/Syneos, ClostraBio, Connect Biopharma, Eco R1, Eli Lilly and Company, Genentech/Roche, Gilead Sciences, Iterative Health, Janssen Pharmaceuticals, Kaleido, Pfizer, Prometheus Biosciences, Reistone Biopharma, Seres Therapeutics, Takeda, Target RWE, and Trellus Health and has received grant support from Takeda, Helmsley Charitable Trust, and the Gastro-Intestinal Research Foundation.
DDN, QD, AM, JL and BD are employees and shareholders of Prometheus Biosciences.
RK has received grants from Janssen and Takeda.
TER has been a speaker for Takeda Pharmaceuticals, Janssen, Pfizer, Bristol Myers Squibb, and Abbvie; has served on advisory boards for AbbVie, Ardelyx, Arena, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Eli Lilly and Company, Ferring, Genentech/Roche, Gilead, Intercept, Iterative Scopes, Janssen, Pfizer, Prometheus Biosciences, Sanofi, and Takeda; and has been a shareholder for Iterative Scopes.
RP has been a consultant for Abbott, AbbVie, Abivax, Alimentiv (formerly Robarts), Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly and Company, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma, Trellus, Viatris, Ventyx, and UCB; has received speakers fees from AbbVie, Amgen, Arena, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda; and has served on advisory boards for AbbVie, Alimentiv (formerly Robarts), Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda, and Ventyx.

Introduction

Histologic inflammation persists in up to 1/4 of patients (pts) with Crohn’s Disease (CD) despite endoscopic mucosal healing. Responsiveness of histologic inflammation and of combined endoscopic-histologic endpoints to treatment are evolving measures of disease activity in CD. Mirikizumab (MIRI) increased histologic response (H-Res) and remission (H-Rem) relative to placebo (PBO) in the Phase 2 SERENITY trial.¹

Aims & Methods

To evaluate the impact of MIRI and ustekinumab (UST) on H-Res and H-Rem and combined endoscopic-histologic response (EH-Res) and remission (EH-Rem) in all pts, pts with prior biologic failure (BF), pts without prior BF in moderately to severely active CD, in the randomized, double-blind, double-dummy, treat-through Phase 3 VIVID-1 trial (NCT03926130). Two biopsy specimens from each of 5 intestinal segments (1 ileal and 4 colonic) were obtained from the edge of the ulcers, or the most inflamed mucosa from randomized pts at screening, and weeks (W)12, and 52. Criteria for H-Res were the absence of epithelial neutrophils and epithelial damage, erosions and ulceration or ≥50% decrease in either the active Robarts Histopathology Index or the active Global Histologic Disease Activity Score. H-Rem was defined as complete absence of mucosal neutrophils (in epithelium and lamina propria), and no epithelial damage, erosions and ulcers; these criteria had to be met in all biopsy specimens. Endoscopic response was defined as ≥50% improvement from baseline in Simple Endoscopic Score for CD (SES-CD). Endoscopic remission was defined as SES-CD total score ≤4 and ≥2-point reduction from baseline and no subscore >1 in any individual variable.

Results

At W52, nominally significant differences between MIRI and UST were observed in achieving H-Res in all pts (58.2% vs 48.8%; p=.007 and in BF pts (56.5% vs 41.3%; p=.006). For EH-Res, differences of MIRI vs UST were numerically greater but not statistically significant in all pts (41.1% vs 34.4%; p=.063) but were nominally significant among BF pts (39.6% vs 27.8%; p=.023). While numerical differences between MIRI and UST were observed in H-Rem and EH-Rem in all pts (H-Rem: 30.2% vs 28.9%; p=.685; EH-Rem: 17.2% vs 14.8%; p=.363) and in BF pts (H-Rem: 24.3% vs 19.8%; p=.365; EH-Rem: 13.3% vs 8.7%; p=.237), no significant differences were observed in these endpoints(Table).

Conclusion

Using strict definitions, all histology-based endpoints were achieved by MIRI versus PBO. For comparison versus UST, MIRI also showed nominal statistical difference for H-Res, which was prespecified and is considered the most sensitive to change, particularly driven by BF pts. The implication of these results on clinical endpoints and long-term outcomes, including hospitalization rates and surgeries, requires further evaluation.

References

1. Magro F, et al. Clin Gastroenterol Hepatol. 2023:S1542-3565(23)00948-5.

Disclosure

• V. Jairath received consulting/advisory board fees: AbbVie, Alimentiv, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris Pharmaceuticals, AstraZeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Endpoint Health, Enthera, Ferring Pharmaceuticals, Flagship Pioneering, Fresenius Kabi, Galapagos NV, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead Sciences, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Reistone Biopharma, Roche, Roivant Sciences, Sandoz, SCOPE, Second Genome, Sorriso Pharmaceuticals, Takeda, TD Securities, Teva, Topivert, Ventyx Biosciences, and Vividion Therapeutics; and speaker’s fees: AbbVie, Bristol Myers Squibb, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos NV, Janssen, Pfizer, Shire, and Takeda
• F. Magro speaker: AbbVie, Arena, Biogen, Bristol Myers Squibb, Eli Lilly and Company, Falk, Ferring Pharmaceuticals, Hospira, Janssen, Laboratórios Vitoria, Merck Sharp & Dohme, Pfizer, Sandoz, Takeda, UCB, and Vifor
• G. De Hertogh received fees for clinical trial activities with Centocor Inc; and received consultancy fees: Eli Lilly and Company and MRM Health
• B. Feagan was a consultant: AbbVie, AbolerIS Pharma, Agomab Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport, Arena Pharmaceuticals, Avoro Capital Advisors, Atomwise, BioJamp, Biora Therapeutics, Boehringer Ingelheim, Boxer, Celgene/BMS, Celsius Therapeutics, Connect BioPharma, Cytoki Pharma, Disc Medicine, Duality, EcoR1, Eli Lilly and Company, Equillium, Ermium Therapeutics, First Wave BioPharma, First Word Group, Galapagos NV, Galen Atlantica, Genentech/Roche, Gilead Sciences, Gossamer Pharma, GlaxoSmithKline, Hinge Bio, Hot Spot Therapeutics, InDex Pharma, Imhotex, Immunic Therapeutics, JAKAcademy, Janssen, Japan Tobacco, Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lument AB, Millennium Pharmaceuticals, MiroBio, Morgan Lewis, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist Therapeutics, PTM Therapeutics, Q32 Bio, Rebiotix, Redx Pharma, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc., Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx Biosciences, VHsquared, Viatris, Ysios, YSOPIA Bioscience, and Zealand Pharma; was on the speaker’s bureau: AbbVie, Janssen, and Takeda; member of the Scientific Advisory Board, DSMB for: AbbVie, Amgen, AMT, AnaptysBio, Axio Research, Boehringer Ingelheim, Celgene/BMS, Ecor1Capital, Eli Lilly and Company, Genentech/Roche, GlaxoSmithKline, InDex Pharma, Janssen, MiroBio, Morphic, Origo BioPharma, Pfizer, Progenity, Prometheus, Redx Pharma, Sanofi, Takeda, Tillotts Pharma, and Teva; stock shareholder of: Gossamer Pharma; and employee as Senior Scientific Director of: Western University and Alimentiv
• N. Harpaz advisory board member and/or consultant: AbbVie, Bristol Meyers Squibb, Eli Lilly and Company, and PathAI Inc
• T. Hisamatsu received lecture fees: AbbVie, EA Pharma, Gilead Sciences, Janssen Pharmaceutical K.K., JIMRO, Kyorin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Pfizer, and Takeda; received honoraria as an advisory board member or consultant: AbbVie, EA Pharma, Eli Lilly and Company, Gilead Sciences, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma, Pfizer, and Takeda; and received pharmaceutical/research grants from: AbbVie, Alfresa Pharma, Daiichi Sankyo, EA Pharma, JIMRO, Kyorin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nichi-lko Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, and Zeria Pharmaceutical
• G. D’Haens advisor: AbbVie, Agomab Therapeutics, Alimentiv, AstraZeneca, Biora, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Exeliom Biosciences, Galapagos NV, Genentech/Hoffmann-La Roche, GlaxoSmithKline, Immunic Therapeutics, Johnson & Johnson, Merck Sharp & Dohme, Pfizer, Protagonist Therapeutics, Samsung Bioepis, Sandoz, Seres Therapeutics/Nestec/Nestlé, Takeda, Tillotts Pharma AG, Ventyx; received speaker fees: AbbVie, Johnson & Johnson, Takeda, Pfizer, Tillotts Pharma AG
• R. Pai received consulting fees: Alimentiv Inc, Allergan, and BRACCO
• Z. Lin, N. Morris, M. Protic, E. Hon, C. Owen, R. Escobar are employees and shareholders: Eli Lilly and Company
• W. Reinisch received lecture and consulting fees from and/or served as an advisory board member: AbbVie, Actelion, Alpha Wasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Genentech, Grunenthal, Johnson & Johnson, Millennium, Merck, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, Schering-Plough, Salix Pharmaceuticals, Takeda, UCB Pharma, and Vifor Pharma