Introduction

SOR102 is a novel, orally delivered, bispecific construct with two humanized single domain antibodies (SDA) targeting TNFα and IL-23p19 bound by a trypsin-labile linker, enabling monomer separation in the small intestine and inhibition of TNFα and IL-23 activity in GI tissue, with minimal systemic exposure. SOR102 SDAs were engineered for stability to intestinal and inflammatory proteases, enabling oral dosing.¹ The Phase 1, first-in-human study (NCT06080048) had 3 parts. Parts 1 and 2 enrolled healthy subjects. Part 3 was a Phase 1b randomized, double-blind, placebo-controlled study in patients (pts) with mild to severe ulcerative colitis (UC). Results for Parts 1 and 2, and clinical results (safety, efficacy, immunogenicity) for Part 3 were previously presented.^2,3 Here, we present Part 3 biodistribution and tissue pharmacodynamic (PD) results, and their correlation with clinical results.

Aims & Methods

Pts with Mayo endoscopy score ≥2, rectal bleeding score ≥1 and stool frequency score ≥1 were randomized 1:1:1 to receive SOR102 810mg BID, SOR102 810mg QD, or placebo for 6 weeks. Pts underwent a baseline and end of treatment sigmoidoscopy and biopsies. The primary objective was safety and tolerability. Secondary objectives were concentrations of SOR102 and monomers in serum, urine and feces, and anti-drug antibodies. Exploratory efficacy endpoints included change from baseline in Mayo Score (MS), modified Mayo Score (mMS), and UC-100 score, and MS and mMS clinical response and symptomatic remission (SR). Exploratory colonic tissue biodistribution and PD endpoints included measurements of SOR102, cytokine protein levels and gene expression changes. Serum cytokine protein levels were also assessed. Outcomes are reported in pts who completed the study.

Results

22 pts were randomized; 17 pts completed the study (SOR102 BID=5; SOR102 QD=6; placebo=6). Mean age was 50 yrs; 45% were male; median MS was 8 (range 6-11). Most pts were advanced therapy-naïve. One patient (QD arm) had detectable SOR102-IL-23 monomer levels in serum (<135.2 ng/ml). High and consistent micromolar levels of active monomers and low levels of intact SOR102 in feces confirm SOR102 is efficiently cleaved and activity is maintained after oral dosing in UC patients, as demonstrated through TNF/IL-23 binding analysis. Median colonic tissue concentrations of SOR102 monomers were 20-35x higher in the SOR102 BID arm compared to QD. Higher rates of MS and mMS clinical response, and SR, and greater decreases in MS, mMS, and UC-100 score were observed in the SOR102 BID arm compared to placebo. In the SOR102 BID arm there was strong correlation between clinical activity, tissue drug concentrations, and PD outcomes, which included reduced colonic tissue IL-1b, IL-6, TNFα, IFNγ, IL-17A, and IL-10 protein levels and changes in gene expression corresponding to reduced myeloid inflammation and T & B cell responses, with upregulation of cellular repair mechanisms. No notable changes were observed in serum cytokine protein levels. In the QD arm, there was a tendency towards favorable tissue PD responses, suggesting a higher dose or longer duration of treatment are needed for higher clinical responses.

Conclusion

High and sustained levels of active monomers in feces confirmed SOR102 is efficiently cleaved, and activity is maintained after oral dosing in UC patients. Levels of SOR102 monomers in sigmoid colonic tissue increased with oral dose, with minimal systemic exposure. In the BID arm, SOR102 demonstrated strong and consistent activity across multiple clinical and tissue PD endpoints in patients with UC.

References

1. Roberts KJ et al. Preclinical development of a bispecific TNFα/IL-23 neutralising domain antibody as a novel oral treatment for inflammatory bowel disease. Sci Rep 2021;11:19422.
2. Jairath V et al. First in human study of SOR102, a novel, orally delivered bispecific anti-TNF/anti-IL-23 domain antibody in clinical development for the treatment of inflammatory bowel disease. UEG Journal 2024;12(S8):72-73.
3. Jairath V et al. Phase 1b study of SOR102, a novel, orally delivered bispecific anti-TNF/anti-IL-23 domain antibody in patients with mild to severe ulcerative colitis. J Crohns Colitis 2025;19(S1):i62-i63.

Disclosure

VJ reports potential conflicts of interest with AbbVie, Alimentiv, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Gilead, Innomar, JAMP Pharma Group, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, F. Hoffmann La Roche Ltd/Genentech, Roivant, Sandoz, Second Genome, Shire, Sorriso, Synedgen, Takeda, Toronto Dominion Securities, Teva, Topivert, Ventyx, Vividion.
SD reports potential conflicts of interest with 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, Vifor.
GDH reports potential conflicts of interest with AbbVie, Agomab, Alimentiv, Arena, AstraZeneca, AMT, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Galapagos, Gilead, GlaxoSmithKline, Immunic, Johnson & Johnson, Pfizer, Polpharma, Procise Diagnostics, Prometheus Biosciences, Prometheus Laboratories, Progenity, Protagonist Therapeutics Inc., Seres Health, Spyre, Takeda.
BGF reports potential conflicts of interest with AbbVie, Abivax, Adiso, AgomAB Therapeutics, Akros, Alira Health, Ally Bridge Group, AnaptysBio, Apini Therapeutics, Argenx, Attovia Tx, Avoro Capital Advisors, Belmore Law, BioFactura, BioJamp, Biora Therapeutics, Blackbird Laboratories, Boehringer-Ingelheim, Boxer Capital, Celsius Therapeutics, Celgene/BMS, Celltrion, Clarivate, Connect BioPharma, Disc Medicine, Duality, EcoR1 Capital, Eli Lilly, EnGene, Ensho Therapeutics, Equillium, Evida, Enveda, Faes Farma, First Wave, Forbion, Galapagos, Galen Atlantica, Genentech/Roche, General Atlantic, Genesis Therapeutics, Gilead, Gossamer Pharma, GSK, Imhotex, ImmiDomics, Immunic Therapeutics, Intercept, Janssen, Japan Tobacco Inc., Klick Health, LifeMine Therapeutics, Mage Biologics, Merck, Mestag, Mirador Therapeutics, MiroBio, Mobius Care, Monte Rosa Tx, Morphic Therapeutics, Nexys Therapeutics, Nighthawk Therapeutics, Nimbus Therapeutics, Novartis, OncoC4, OrbiMed, Origo BioPharma, Orphagen, Palisade Bio, Pendopharm, Pfizer, Protagonist,32 Bio, REDX, Roivant/Televant, Sanofi, Sobi, Sorriso, Spyre Therapeutics, SRT Therapeutics, Sun Pharma, Surrozen Inc., Synedgen, Takeda, Teva, Triastek, Trex Bio, TR1X Inc. TVM Lifesciences, Ventyx Biosciences, Versant Ventures, Vida Ventures, Zagbio.
LP-B reports potential conflicts of interest with Abbvie, Abivax, Adacyte, Alimentiv, Alfasigma, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, BMS, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Kern Pharma, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par' Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx, Ysopia.
BES reports potential conflicts of interest with Abbvie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, Astra Zeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb Calibr, Celgene, Celltrion, ClostraBio, Eli Lilly & Company, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Fresenius Kabi, Fzata, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Merck & Co., Inc., Microbiotica, Mitsubishi Tanabe, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, OSE Immunotherapeutics, Palisade Bio, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Sorriso Therapeutics, Spyre Therapeutics, Surrozen, Takeda, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences.
MW is an employee of Inotiv.
ICG is an employee of Tytgat Institute for Liver & Intestinal Research.
BS is an employee of Alimentiv Inc.
KR, AT, SB, PW, CS and JB are employees of Sorriso Pharmaceuticals.

Introduction

Steroid-refractory acute severe ulcerative colitis (SR-ASUC) is a life-threatening emergency that results in colectomy in approximately 40% of cases.¹ Several medical therapies have emerged as rescue treatments aimed at reducing the need for colectomy.^2-3However, direct comparative studies evaluating the relative efficacy of these therapies remain limited.⁴ This network meta-analysis aims to systematically review and compare the efficacy and safety of available rescue therapies for SR-ASUC, including biologics and small molecule treatments.

Aims & Methods

A systematic literature search was conducted using the MEDLINE, SCOPUS, and CENTRAL databases. Colectomy-free survival probabilities were extracted from Kaplan-Meier curves. A one-stage network meta-analysis using parametric Weibull regression was performed to estimate and compare the relative treatment effects of biologics and small molecule therapies. The primary outcome was colectomy-free survival at 4 and 12 weeks. This study was registered in PROSPERO (CRD420251030353).

Results

A total of 18 studies (5 randomized controlled trials and 13 cohort studies), including 1,706 patients with SR-ASUC, were included. Compared to placebo, standard-dose infliximab [hazard ratio (HR) 0.34, 95% CI: 0.20–0.60, p < 0.001], accelerated-dose infliximab [HR 0.38, 95% CI: 0.21–0.68, p = 0.001], and tofacitinib [HR 0.36, 95% CI: 0.19–0.69, p = 0.002] significantly improved colectomy-free survival. Cyclosporine also showed a trend toward reduced colectomy risk, though it did not reach statistical significance [HR 0.57, 95% CI: 0.31–1.01, p = 0.056]. There were no significant differences in overall adverse events or infection rates among the therapies. Based on SUCRA rankings, colectomy-free survival at both 4 and 12 weeks was highest for tofacitinib (SUCRA: 0.90 and 0.87), followed by accelerated-dose infliximab (0.95 and 0.85), standard-dose infliximab (0.87 and 0.83), and cyclosporine (0.81 and 0.74). (Figure 1 Colectomy free survival probability ; Kaplan-Meier curves)
Table 1. Pairwise table showing comparative efficacy in reducing colectomy risk of biologics and small molecule for SR-ASUC

Placebo	0.36 (0.19,0.69)	0.38 (0.21,0.68)	0.57 (0.31,1.01)	0.34 (0.20,0.60)
	Tofacitinib	1.04 (0.46,2.39)	1.57 (0.69,3.57)	0.96 (0.43,2.11)
		Accelerated Infliximab	1.51 (1.04,2.18)	0.92 (0.69,1.21)
			Cyclosporin	0.61 (0.48,0.78)
				Infliximab

Conclusion

Tofacitinib and accelerated-dose infliximab appear to be the most effective rescue therapies for improving colectomy-free survival in patients with SR-ASUC.

References

1. Dong C, Metzger M, Holsbø E, et al. Aliment Pharmacol Ther. 2020 Jan;51(1):8-33.
2. Honap S, Jairath V, Sands BE, et al. Gut. 2024 Sep 9;73(10):1763-1773.
3. Calméjane L, Laharie D, Kirchgesner J, et al. United European Gastroenterol J. 2023 Oct;11(8):722-732.
4. Choy MC, Seah D, Faleck DM, et al. Inflamm Bowel Dis. 2019 Jun 18;25(7):1169-1186.

Introduction

Crohn's disease (CD) is a chronic inflammatory bowel disease of unknown etiology with no cure. Reliable tools for the early identification of patients at risk, especially for long-term prediction, remain to be defined.

Aims & Methods

This study aimed to employ machine learning to develop proteomics-based models to predict future CD onset. We utilized data from 39,634 participants without baseline CD from the UK Biobank (UKB) as the training cohort. Feature selection involved Cox regression to identify proteins associated with incident CD, followed by automated machine learning-based importance ranking using five-fold cross-validation (10 repeats). Four machine learning algorithms were applied to construct predictive models. Independent validation was conducted in a geographically distinct UKB cohort (n = 13,262) and an external Southern China cohort (n =74).

Results

Among 2,736 proteins, Cox regression identified 44 proteins significantly associated with incident CD. CD274, CHI3L1, REG1B, ITGAV, PRSS8, ITGA11, GDF15, DEFA1_DEFA1B, and IL6 were ranked the top 9 in protein importance ordering. Machine learning models using four algorithms were constructed based on these proteins, with XGBoost demonstrating the best performance. In the geographically distinct UKB cohort, the protein model (area under the curve [AUC] 0.76) outperformed clinical risk models (highest AUC 0.67, P < 0.05) and was externally validated in the Southern China cohort (AUC 0.79). Combining these proteins with clinical data enabled desirable predictions up to 16 years pre-diagnosis (AUC 0.78). Our model performed better than existing PREDICTS model (AUC 0.68, P < 0.05) when applied to the UK Biobank population. Individuals in the high-risk group stratified by the protein model were 4.23 times more likely to develop CD.

Conclusion

Our findings suggest that proteomics-based models could be used to predict individuals who will develop CD up to 16 years in advance. The novel approach has important implications in identifying individuals at high-risk for evaluation of early intervention.

Introduction

The CACTUS-CD study (NCT06125678) prospectively evaluated 407 patients with small bowel Crohn’s disease (CD) and demonstrated that intestinal ultrasound (IUS), particularly smal intestinal contrsat ultrasound (SICUS), could approach the diagnostic accuracy of computed tomography enterography (CTE) and magnetic resonance enterography (MRE)[1]. The value of IUS/SICUS in monitoring of known CD in reference to device assisted enteroscopy (DAE) is not known [2].

Aims & Methods

This post hoc analysis aimed to compare these imaging modalities (IUS, SICUS, CTE/MRE) against DAE for lesion localization and stricture detection in a subset of patients.
Forty-eight patients with established small bowel CD underwent IUS, CTE or MRE, and DAE within one week. Segmental localization (proximal, mid, distal) was assessed across all modalities. Strictures on IUS were defined using wall thickness >3 mm, luminal narrowing <1 cm, and pre-stenotic dilatation[3]. Simplified Magnetic Resonance Index of Activity (MARIA) for MRE, International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) for IUS, and modified Simple Endoscopic Score for Crohn’s Disease (SES-CD) score (0-12, based on ileal subscore) for DAE were compared [2,4,5].

Results

The median age was 42 years (range 18–73), with 43.8% female and a median BMI of 21 kg/m². Among MRE patients (n=22), the median simplified MARIA (Magnetic Resonance Index of Activity) score was 4.5 (range 1-5). IUS revealed a median bowel wall thickness of 5.55 mm (range 2.2-8.6), an median International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) of 63.3 (8.8-87). For DAE, modified Simple Endoscopic Score for Crohn’s Disease (SES-CD) median score was 9 (0-11). Technical success of DAE was 46/48 (95.8%, technical failure: both post operative). The approach of DAE was antegrade (n=16), retrograde (n=26) and bidirectional (n=6). Median depth of maximal insertion was 120 cm (30-600 cm) with median time ​30 minutes (10-240).
All modalities had 100% agreement in distal bowel.In mid-bowel, CTE/MRE and DAE were fully concordant; IUS achieved 72.7%. Proximal agreement was 71.4% for CTE/MRE and 57.1% for IUS. For strictures, CTE/MRE yielded the highest sensitivity (81%), specificity (88%), and agreement (kappa 0.65). IUS had lower sensitivity (47%) but excellent specificity (94%). SICUS performed better than IUS with sensitivity of 75% (p=0.039) and kappa 0.62. Spearman’s correlation showed stronger association of MARIA with SES-CD (r = 0.659, p = 0.001) than IBUS-SAS (r = 0.486, p < 0.001).

Parameter	CTE/MRE	IUS	SICUS
Number of patients	48	48	48
Distal SB Localization Accuracy (%)	100	100	100
Mid SB Localization Accuracy (%)	100	72.7	72.7
Proximal SB Localization Accuracy (%)	71.4	57.1	57.1
Sensitivity for Stricture (%)	81	47	75 *
Specificity for Stricture (%)	88	94	94
Accuracy for Stricture (%)	83	62	81#
Kappa	0.65	0.32	0.62
SB: Small bowel, *statistically significant difference between IUS and SICUS (p=0.039), # Not statistically significant (p=0.

Conclusion

Intestinal ultrasound showed excellent concordance with enteroscopy for disease localization in the distal small bowel, supporting its use as a cost-effective, radiation-free, point-of-care modality. The addition of small intestinal contrast ultrasound (SICUS) significantly improved stricture detection. These findings support ultrasound-based strategies as first-line options for monitoring known Crohn’s disease, particularly in settings requiring repeated assessment or where access to cross-sectional imaging and device-assisted enteroscopy is limited.

References

1. Pal P, Mateen MA, Pooja K, et al. S1044 Correlation and Assessment of Small Bowel Lesions Using Cross-Sectional Imaging Techniques vs Small Intestinal Contrast UltraSonography in Known Crohn’s Disease (CACTUS-CD Trial): A Paired, Validating Study (NCT06125678). Official journal of the American College of Gastroenterology | ACG. 2024;119(10S):S731-S732. [10.14309/01.ajg.0001033544.90391.8a]
2. Na JE, Kim HS, Hong SN, et al. Comparison of an Endoscopic Scoring System and the Simplified Magnetic Resonance Index of Activity in Patients with Small Bowel Crohn’s Disease. Gut and Liver. 2024;18(1):97-105.
3. Lu C, Rosentreter R, Parker CE, et al. International expert guidance for defining and monitoring small bowel strictures in Crohn's disease on intestinal ultrasound: a consensus statement. Lancet Gastroenterol Hepatol. 2024;9(12):1101-1110.
4. Novak KL, Nylund K, Maaser C, et al. Expert Consensus on Optimal Acquisition and Development of the International Bowel Ultrasound Segmental Activity Score [IBUS-SAS]: A Reliability and Inter-rater Variability Study on Intestinal Ultrasonography in Crohn's Disease. J Crohns Colitis. 2021;15(4):609-616.
5. Roseira J, Ventosa AR, de Sousa HT, Brito J. The new simplified MARIA score applies beyond clinical trials: A suitable clinical practice tool for Crohn's disease that parallels a simple endoscopic index and fecal calprotectin. United European Gastroenterol J. 2020;8(10):1208-1216.

Introduction

Mirikizumab (MIRI) is an anti-IL-23p19 antibody with demonstrated efficacy compared to placebo (PBO) in the treatment of moderately-to-severely active ulcerative colitis (UC) (LUCENT-1: NCT03518086; LUCENT-2: NCT03524092).¹ Prevention of IBD-related surgery and hospitalizations is a goal in disease-modification trials for preventing disease progression.² We described the rates of these events in the LUCENT-1 and -2 trials.

Aims & Methods

Patients were randomized to intravenous MIRI 300 mg or PBO every 4 weeks (Q4W) for induction in LUCENT-1. Patients randomized to MIRI induction and achieving clinical response at Week (W)12 were re-randomized 2:1 in LUCENT-2 to subcutaneous MIRI 200 mg Q4W or PBO (MIRI withdrawal) for maintenance (W12-52). Descriptive statistics were used for proportion of patients in LUCENT-1 and -2 who had hospitalization and/or surgery by treatment group and the exposure-adjusted incident rate (IR). For LUCENT-1, hospitalizations in the induction period and surgeries during the induction and 16-week follow-up period were included. For LUCENT-2, all events were from the on-treatment period. Only hospitalizations associated with an adverse event with ≥24-hour stay (for any causes) were recorded.

Results

MIRI-treated patients had significantly lower IR of overall hospitalization, UC-related hospitalization, and overall surgery vs PBO-treated patients in LUCENT-1 (IR ratio MIRI vs PBO: 0.4, 0.1, 0.4, respectively). IR of UC-related surgery was 1.3 per 100 patient-years in MIRI-treated patients vs 2.6 per 100 patient-years in PBO group (Table). Mean time to first surgery or hospitalization from randomization was 30.5 days for PBO and 58.7 days for MIRI. Additional analyses revealed that patients on MIRI who had surgery/hospitalization in LUCENT-1 or -2 tended to have prior biologic failure and longer duration of disease. Similarly, in LUCENT-2, MIRI-treated patients had significantly lower IR of all-cause hospitalization and similar all-cause surgery vs PBO. No UC-related hospitalization and surgery were reported in the MIRI group while 2 UC-related hospitalizations (1.8 per 100 person-years) were reported from PBO.

Hospitalization and Surgery Rates in LUCENT-1 and LUCENT-2
Note: * represent p<0.05. IR = incidence rate; IRR = incidence rate ratio; MIRI = mirikizumab; N = number of patients in the analysis population; n = number of patients within each specific category; N/A= not applicable; PBO = placebo; PYE = patient years of exposure; PYR = patient years at risk; UC = ulcerative colitis. a The IR and IRR confidence intervals and the p-values are based on a Poisson distribution b UC-related surgeries are total colectomy, partial colectomy, and proctocolectomy.
LUCENT-1								LUCENT-2
	MIRI 300mg (N=868, PYE=201.0)			PBO (N=294, PYE=65.8)			MIRI vs. PBO	MIRI 200mg (N=365, PYE=267.9)			PBO (N=179, PYE=111.0)			MIRI vs. PBO
	Events, n(%)	PYR	Incidence rate, per-100 py (95%CI)a	Events, n(%)	PYR	Incidence rate, per-100 py (95%CI)a	IRR (95% CI)	Events, n(%)	PYR	Incidence rate, per-100 py (95%CI)a	Events, n(%)	PYR	Incidence rate, per-100 py (95%CI)a	IRR (95% CI)
Overall hospitalization	21 (2.4)	199.7	10.5 (6.5, 16.1)	16 (5.4)	64.6	24.8 (14.1, 40.2)	0.4 (0.2, 0.8)*	10 (2.7)	264.9	3.8 (1.8, 6.9)	11 (6.1)	109.0	10.0 (5.0, 17.9)	0.4 (0.2, 0.9)*
UC-related hospitalization	3 (0.3)	200.9	1.5 (0.3, 4.4)	10 (3.4)	65.2	15.3 (7.4, 28.2)	0.1 (0.0,0.4)*	0	267.9	0 (0.0, 1.4)	2 (1.1)	110.7	1.8 (0.2, 6.5)	0
Overall surgery	11 (1.3)	227.9	4.8 (2.4, 8.6)	9 (3.1)	75.8	11.9 (5.4, 22.5)	0.4 (0.2,1.0)*	13 (3.6)	263.2	4.9 (2.6, 8.4)	5 (2.8)	109.5	4.6 (1.5, 10.7)	1.1 (0.4, 3.0)
UC-related surgeryb	3 (0.3)	228.6	1.3 (0.3, 3.8)	2 (0.7)	76.8	2.6 (0.3, 9.4)	0.5 (0.1, 3.0)	0	267.9	0 (0.0, 1.4)	0	111.0	0 (0.0, 3.3)	N/A

Conclusion

Lower rates of UC-related hospitalizations and UC-related surgery were observed in patients treated with MIRI compared to those treated with PBO during the 12W induction LUCENT-1, and that impact continued through the 40W of maintenance LUCENT-2 with no UC-related hospitalizations or UC-related surgery reported in MIRI-treated patients.

References

1. D’Haens G, et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. New England Journal of Medicine 2023;388(26):2444-2455.
2. Le Berre C, Peyrin-Biroulet L. Selecting End Points for Disease-Modification Trials in Inflammatory Bowel Disease: the SPIRIT Consensus From the IOIBD. Gastroenterology 2021;160(5):1452-1460.e21.

Disclosure

MR serves as a consultant and on advisory boards for AbbVie, Janssen, Bristol-Myers Squibb, UCB, Takeda, Pfizer, Prometheus Laboratories, Lilly, Celgene, and Amgen.
LPB has served as a consultant for AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax; he received grants from Takeda, Fresenius Kabi, Celltrion; he served as a speaker for Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, Medac; he also declares support travel by Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Gossamer Bio, Sandoz, MSD, Amgen, Lilly, Gilead, Thermo Fisher, Medac, CONNECT Biopharm; he declares stock options of Clinical trials Mobile Application.
JW, BZ, IR, KT, CO are employees and minor shareholders of Eli Lilly and Company.
SN has served on advisory board and speaker for Eli Lilly and Company, Pfizer and advisory board for madrigal and speaker for Janssen
TK has served as a paid consultant for Abbvie, Amgen, Biogen, Mundipharma, Hospira, Gilead, Janssen, Pfizer, MSD Sharp & Dome GmbH, and Novartis. He has received reimbursement of meeting participation fees and of travel and accommodation expenses from Abbvie, Janssen, MSD, and Takeda. He has received honoraria for preparing continuing medical education events from Abbvie, Falk, Janssen, MSD, Takeda, and Ferring Arzneimittel GmbH.
LM reports educational grants from Abbvie, Janssen, Pfizer and Takeda; advisory boards: AbbVie, Bristol Myers Squibb, Janssen, and Celltrion; consultant for Abbvie, Pfizer and Pharmacosmos.
FM has served as a speaker and received honoraria from Merck Sharp & Dohme, Abbvie, Vifor, Falk, Laboratorios Vitoria, Ferring, Hospira, and Biogen.

Introduction

Bowel urgency (BU) is a bothersome symptom experienced by patients with ulcerative colitis (UC) and is associated with high clinical and quality-of-life burdens. Mirikizumab (MIRI), an anti-IL-23 antibody approved for the treatment of moderately-to-severely active UC, significantly reduced BU severity compared with placebo (PBO), and these improvements were associated with better clinical outcomes.¹ We evaluated the association between incremental improvement in BU severity at Week (W)12 and W52 with other patient-reported outcomes for MIRI-treated patients.

Aims & Methods

In LUCENT-1 (induction), patients were randomized 3:1 to intravenous MIRI 300 mg or PBO every 4 weeks (Q4W) for 12W. MIRI responders during induction were re-randomized 2:1 to subcutaneous MIRI 200 mg or PBO Q4W for 40W in LUCENT-2 (52W of continuous treatment). BU severity was measured using the Urgency Numeric Rating Scale ([UNRS] 0–10). Incremental improvement of BU severity was assessed as reduction of each single point of UNRS score from baseline (BL). The reduction of >7 points was pooled into one category due to sample size. The accumulative benefit of reducing 1 additional point of UNRS score was evaluated at W12 and W52 and was assessed for its association with mean percent improvement in inflammatory bowel disease questionnaire (IBDQ) total score, fatigue NRS, short-form (SF)-36 mental component score (MCS) and physical component score (PCS), and work productivity activity impairment (WPAI) productivity loss.

Results

Significantly greater proportions of patients receiving MIRI achieved UNRS score reduction at certain points versus PBO at W12 and W52. The reduction of each single point of UNRS score was associated with improvement in patient’s physical and mental health, fatigue, work productivity, and quality of life. At W12, fatigue and IBDQ showed greater percent improvements among all the PRO outcomes studied for each 1-point reduction of UNRS. Similar results were observed at W52 (Table 1).

Week 12 (N=868)	UNRS reduction	Fatigue NRS	IBDQ Total Score	MCS	PCS	WPAIa	Week 52 (N=365)	UNRS reduction	Fatigue NRS	IBDQ Total Score	MCS	PCS	WPAIb
	≤0	-11.9	16.0	6.6	9.4	4.9		≤0	8.9	35.9	18.5	21.2	23.9
	1	15.4	25.9	14.6	11.3	16.9		1	5.8	30.6	13.4	12.7	11.2
	2	28.7	31.1	13.7	14.0	20.1		2	32.4	37.5	18.8	18.6	30.1
	3	43.5	35.8	17.9	16.9	24.1		3	59.5	33.9	10.8	20.4	27.5
	4	49.8	49.1	19.7	23.5	24.2		4	62.4	55.6	17.9	33.7	42.1
	5	54.5	43.3	13.1	22.9	28.8		5	52.2	54.0	21.7	27.7	38.2
	6	59.3	55.2	22.1	24.0	36.4		6	68.9	63.0	26.0	26.5	41.9
	7	81.2	64.6	25.9	30.1	29.8		7	83.8	67.3	30.1	30.1	50.6
	>7	73.6	75.4	29.7	39.1	38.5		>7	88.1	87.6	35.0	45.4	54.8

^a Note: N=532, population was restricted to patients with baseline employment status = Yes.
^b Note: N=224, population was restricted to patients with baseline employment status = Yes.
Abbreviations: IBDQ = inflammatory bowel disease questionnaire; MCS = short-form-36 mental component score; N = number of patients in the analysis population; n = number of patients in the specified category; NRS= numeric rating scale; PBO = placebo; PCS = short-form-36 physical component score; UNRS = urgency numeric rating scale; WPAI= work productivity activity impairment productivity loss.
UNRS score was averaged from daily diary entries for a 7-day period. Data were considered as missing for that week if less than 4 days were available.

Conclusion

Incremental improvement in bowel urgency corresponded to improvements in outcomes important to patients, underscoring the importance of managing BU symptoms in improving the quality of life for patients with UC.

References

1. Dubinsky MC, et al. Crohns Colitis 360 2023;5(1):otac044.

Disclosure

MD reports consultancy fees from AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Gilead Sciences, Janssen, Pfizer, Takeda, and UCB.
ST reports grants and/or research support from AbbVie, Buhlmann Diagnostics, Celgene, Eli Lilly and Company, the International Organization for the Study of Inflammatory Bowel Disease, Janssen, the Norman Collisson Foundation, Takeda, UCB, and Vifor Pharma; consulting fees from Abacus Pharmaceuticals, AbbVie, Actial, ai4gi, Alcimed, Allergan, Amgen, Arena Pharmaceuticals, Asahi Kasei Pharma, Astellas Pharma, AstraZeneca, Atlantic Pharmaceuticals, Barco, Biocare Pharma, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Buhlmann Diagnostics, Calcico, Celgene, Cellerix, Celsius Healthcare, Cerimon Pharmaceuticals, ChemoCentryx, Cisbio, Coronado Biosciences, Cosmo Pharmaceuticals, Ducentis BioTherapeutics, Dynavax, Elan Corporation, Eli Lilly and Company, Enterome, Falk Foundation, Ferring Pharmaceuticals, FPRT Bio, Giuliani, Genentech, Genzyme, GlaxoSmithKline, Glenmark Pharmaceuticals, Grünenthal, GW Pharmaceuticals, Immunocore, Immunometabolism, Indigo Biosciences, Janssen, Lexicon Pharmaceuticals, Medarex, Merck, MSD, Neovacs, Netbiotix, Novartis, Novo Nordisk, NPS Pharma, Ocera Therapeutics, Otsuka, Palau Pharma, Pentax Medical, Pfizer, Philips, Procter & Gamble, Pronota, Proximagen, Ptima Pharma, Receptos, Resolute, Robarts Pharmaceutical, Roche, Sandoz, Santarus, Sensyne Health, Shire, Sigmoid Pharma, SynDermix, Synthon, Takeda, Theravance Biopharma, TiGenix, Tillotts Pharma, TopiVert, TxCell, UCB, Vertex, VHsquared, Vifor Pharma, Warner Chilcott, and Zeria Pharmaceutical; and speaker fees from AbbVie, Amgen, Biogen, Falk Foundation, Ferring Pharmaceuticals, GlaxoSmithKline, Janssen, Shire, Takeda, and Zeria Pharmaceutical.
TK has served as a speaker, a consultant or an advisory board member for AbbVie, Ajinomoto Pharma, Asahi Kasei Medical, Astellas, Alfresa Pharma, Celltrion, Covidien, EA Pharma, Eisai, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen, JIMRO, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Thermo Scientific, Zeria Pharmaceutical, and received research funding from AbbVie, Alfresa Pharma, Asahi Kasei Medical, EA Pharma, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Sekisui Medical, Thermo Fisher Scientific, Zeria Pharmaceutical.
BA-B has served on advisory board for Bristol Myers Squibb, Pfizer; and reports speaker fees from AbbVie, Takeda, Bristol Myers Squibb, Janssen Pharmaceuticals.
JW, BZ, HQ, CM, SF are employees and minor shareholders of Eli Lilly and Company.
DR reports grant support from Takeda and has served as a consultant for AbbVie, AltruBio, Arena Pharmaceuticals, Bristol Myers Squibb, Eli Lilly and Company, Genentech, Gilead Sciences, Iterative Scopes, Janssen, Pfizer, Prometheus Biosciences, Roche, Takeda, and Techlab.