Introduction

The therapeutic goal in inflammatory bowel disease (IBD), which includes Crohn´s disease (CD) and ulcerative colitis (UC), is the control of the inflammatory process frequently through biologic and JAK-inhibitor therapies, which are generally expensive and can cause adverse effects. Unfortunately, only about one-third of patients respond to these treatments, and there are no markers that accurately predict this response.

Aims & Methods

The aim of this study was to identify potential serum and urinary metabolic biomarkers predictive of IBD response to different drugs at baseline (before treatment), which could facilitate the selection of the most appropriate therapy for each patient. For this purpose, a prospective multicenter study was conducted including CD and UC patients who initiated biologic (anti-TNF, ustekinumab or vedolizumab) or JAK-inhibitor (tofacitinib) therapies. Patients were assessed at 14 weeks to determine if they had achieved an endoscopic response, based on the SES-CD and on the endoscopic subscore of the Partial Mayo Score. The analyses of the serum and urine metabolome, along with the deconvolution of the serum lipoprotein profile, were performed using nuclear magnetic resonance for a quantitative differential analysis comparing the baseline serum samples of responders and non-responders.

Results

A total of 150 patients were included (30 CD anti-TNF, 30 UC anti-TNF, 30 CD ustekinumab, 30 UC vedolizumab and 30 UC tofacitinib). Metabolomic analysis identified 55 potential predictive biomarkers of IBD treatment response with significantly altered levels (p<0.05) in the baseline urine and serum samples of subsequent responders compared to non-responders. Among them, 44 were drug-specific and none were shared between serum and urine. Moreover, based on ROC curve analysis, some of these biomarkers showed good sensitivity and specificity for distinguishing between responders and non-responders before treatment (Table 1). Finally, the integrated metabolite set enrichment analysis of urine and serum samples identified distinct biological pathways associated with the response to each treatment for IBD, with common pathways highlighted, including the metabolism of short-chain fatty acids, the citrate cycle and the metabolism of amino acids such as alanine, aspartate, glutamate, and arginine.

Conclusion

The present study represents a step towards personalized medicine in the selection of targeted therapies for IBD patients, addressing an important unmet need. Although further validation is needed, we have identified serum and urinary metabolic biomarkers with the potential to predict response to biologic and JAK-inhibitor therapies.

Table 1. Summary of potential metabolic biomarkers identified as predictive of endoscopic response before each IBD treatment.

*Biomarkers with significantly altered levels (p<0.05) in baseline serum or urine samples of responders vs non-responders. **AUC corresponding to the biomarkers with the best sensitivity and specificity for distinguishing between responder and non-responder patients before treatment. AUC: Area Under the Curve calculated using the Metabolanalyst software in univariate analysis; CD: Crohn's disease; IBD: Inflammatory bowel disease; UC: Ulcerative colitis.

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

Epithelial injury is a hallmark of chronic mucosal damage in Crohn’s disease (CD), which can lead to fibrostenotic strictures. Type VII collagen, a critical component of the epithelial basement membrane, forms U-shaped anchoring fibrils that link the basement membrane to the interstitial matrix by binding fibrillar collagen. Genetic mutations in the COL7A1 gene, which encodes type VII collagen, are known to impair fibril formation and reduce tissue tensile strength, resulting in epithelial dysfunction, as seen in disorders such as dystrophic epidermolysis bullosa. This highlights the essential structural role of type VII collagen in maintaining matrix stability. In CD, the importance of this protein is underscored by the presence of autoantibodies targeting type VII collagen in up to 50% of patients with CD. Loss of tissue integrity, because of loss of the interaction between the basement and interstitial matrix, leads to tissue dysfunction and fibrosis.

Aims & Methods

We investigated C7M, a biomarker of type VII collagen degradation, to assess its specificity for intestinal mucosal damage. We analyzed serum samples from CD patients enrolled in a prospective cohort study. The cohort included 62 CD patients undergoing surgical resection for fibrostenotic strictures and 49 patients with luminal disease receiving treatment adjustments without surgery. Serum was collected at baseline, post-operative day 1 (POD1), and one-month post-resection. C7M levels were quantified using a competitive ELISA.

Results

At baseline, C7M levels were significantly elevated in fibrostenotic CD patients (median: 9.79ng/mL) compared to those with luminal CD patients (median: 6.03ng/mL) (p<0.01, AUC: 0.69). In the resected group, C7M levels rose sharply on POD1 (p<0.0001, AUC: 0.81), suggesting acute release in response to surgical injury. By one-month post-surgery, C7M levels had returned to baseline, closely resembling those observed in luminal CD patients (p<0.0001, AUC: 0.80). C7M also demonstrated mild-moderate correlations to biochemical markers of inflammation, including CRP (rho=0.62, p<0.0001), hemoglobin (rho=-0.28, p=0.0024), thrombocytes (rho=0.24, p=0.0105), albumin (rho=-0.52, p<0.0001), and fecal calprotectin (rho=0.25, p=0.019).

Conclusion

C7M was elevated in fibrostenotic CD patients relative to luminal CD, indicating its potential as a biomarker of more severe or complex mucosal pathology. The pronounced but transient increase following surgery, with normalization within one month, further supports C7M as a dynamic marker of intestinal epithelial damage. These findings suggest C7M may serve as a novel, disease-specific biomarker for assessing mucosal integrity and inflammatory burden in CD.

Disclosure

Full time employee at Nordic Bioscience

Introduction

Early identification of factors that predict disease course in ulcerative colitis (UC) is essential to guide therapeutic decisions and improve patient outcomes. Recognizing patients at higher risk of unfavorable evolution allows for more intensive monitoring and timely escalation of therapy. Clinical severity, disease extent, histological activity, and concomitant infections may all influence prognosis. Among these, Clostridioides difficile infection (CDI) is increasingly recognized in UC patients, but its independent impact on disease evolution remains uncertain. The objective of our study was to assess various baseline severity markers, including histological activity, and concomitant CDI at the time of UC diagnosis as potential predictors of disease-related morbidity during the first year following UC diagnosis.

Aims & Methods

We conducted a retrospective study on a cohort of 125 patients newly diagnosed with UC and followed for at least 12 months. Data collected included demographic characteristics, clinical presentation, biochemical markers, endoscopic findings, histologic disease activity (assessed using the Nancy Histological Index – NHI), and the presence of CDI at diagnosis. Disease-related morbidity was defined as any UC-related hospitalization occurring in the first year after diagnosis, excluding the initial admission for diagnostic purposes. Statistical analysis involved bivariate comparisons and multivariate logistic regression to identify independent predictors of hospitalization.

Results

Independent predictors of UC-related hospitalization were Mayo clinical score (OR = 1.32; p = 0.016), pancolitis (OR = 2.82; p = 0.024), and histological activity (NHI; OR = 1.97; p = 0.014). CDI was identified in 20% of patients and was associated with significantly higher histological activity (median NHI = 3.5 vs. 3.0; p = 0.036), but did not independently predict hospitalization (OR = 1.84; p = 0.265).

Conclusion

Clinical activity, disease extent, and histological severity, at the time of diagnosis are strong, independent predictors of UC-related morbidity within the first year, underscoring their prognostic value beyond the initial presentation. These parameters retain their significance over the medium-term disease course, supporting early risk stratification and individualized treatment planning. Although CDI is associated with greater histologic inflammation at baseline, it does not independently influence outcomes during the first year. Notably, the identification of UC in 20% of patients during a CDI episode suggests that acute infection may unmask previously subclinical disease. These findings highlight the need for comprehensive and careful diagnostic evaluation - including clinical, endoscopic, and histologic assessment, in all patients with newly diagnosed UC.

Introduction

Combination therapy targeting pathogenic pathways may overcome the current therapeutic efficacy ceiling and benefit patients with inflammatory bowel disease (IBD). Emerging preclinical evidence suggests that the costimulatory molecule OX40-ligand (OX40L) represents a promising target in both Crohn’s disease (CD) and ulcerative colitis (UC), particularly when inhibited in combination with anti-TNF agents. Despite these data, a comprehensive understanding of OX40L and its receptor, OX40, in IBD patients is lacking, especially related to potential synergy of OX40L and TNF blockade, particularly in previous anti-TNF non-responders.

Aims & Methods

We investigated OX40L biology in IBD using single-cell transcriptomic data from the terminal ileum of CD patients [n=73] and control subjects [n=106] (Open Targets Consortium) to query cell-specific gene expression profiles for OX40L and OX40 (TNFSF4, TNFRSF4). We also leveraged bulk transcriptomic studies profiling CD terminal ileum [n=99] and both UC [n=272] and control [n=18] colon, as well as available clinical metadata. We assessed enrichment of OX40L biology by gene set variation analysis (GSVA) using OX40L gene signatures. Patterns of gene and signature expression were then associated with endoscopic disease activity and longitudinal response to anti-TNF therapy.

Results

In cross-sectional analyses, increased mucosal OX40 gene expression was associated with higher endoscopic disease activity scores in both CD and UC patients (Simple Endoscopic Score, Mayo endoscopic score; p<0.05). Cellular estimates of lymphocyte subsets associated with resistance and/or residual disease post-anti-TNF therapy were found to correlate with mucosal enrichment of OX40L gene signature in both CD and UC (FDR<0.05; bicor range UC: 0.94-0.21, CD: 0.89-0.67). In longitudinal analyses, UC patients demonstrated elevated expression of OX40L gene signature in colon at baseline which, after anti-TNF therapy initiation, was progressively reduced in responders while persistently elevated in non-responders (p<0.05) throughout induction (week 4-8) and maintenance (week 30) phases. Exploratory single-cell analyses in CD terminal ileum showed cell type-specific increases in OX40L and OX40 gene expression relative to control, with enrichment in T-cell subsets (both), NK cells and dendritic cells (OX40L), myeloid and epithelial cells (OX40). In UC, stronger associations were found between OX40L gene signature enrichment and cellular estimates for multiple lymphocyte subsets (ILC1, PD1⁺CD4⁺ T-cells, plasma cells, mature and germinal center B-cells) as compared to TNF signature (FDR<0.05; bicor range OX40: 0.94-0.67, TNF: 0.69-0.37).

Conclusion

Expression of OX40L and its receptor OX40 is increased in pathogenic cell types from IBD intestinal tissue relative to control and operates in distinct cellular subnetworks compared to TNF. Additionally, increased OX40 gene expression is associated with higher disease activity in both CD and UC. OX40L signatures, which correlate with presence of lymphocyte subsets that may promote TNF resistance, are found to be persistently elevated in UC anti-TNF non-responders. These results provide a novel, data-driven rationale for combining anti-OX40L therapy with anti-TNF therapy in future experiments and clinical trials. This combination may optimize treatment efficacy in IBD by targeting mechanisms that are associated with anti-TNF resistance as well as residual disease following anti-TNF therapy.

Disclosure

CAR, RM, MRD, GF, MT, SK, EdR, CB, IW and HM are employees of Sanofi and may hold stock options or equity in Sanofi; ZH, HHB, RS, AC, ASM, YC are employees of CytoReason and may hold stock options or equity; SSO holds equity and is a consultant of CytoReason and holds an unpaid position with the Human Immunome Project

Introduction

Rescue treatment is administered to patients with acute severe ulcerative colitis (ASUC) who do not respond sufficiently to the initial treatment with intravenous (iv) corticosteroids. Gastrointestinal ultrasound (GIUS) can be used to detect the degree of inflammation in ulcerative colitis and show response in the treatment of ASUC^1,2, but can it be used to detect treatment response of rescue treatment?

Aims & Methods

Can GIUS be used for early prediction of treatment response in patients receiving rescue treatment for ulcerative colitis?
Patients with ulcerative colitis were included from June 2020 to Nov 2024 at two hospitals in Bergen, Norway and treated with iv corticosteroids. At day 3 to 5 patients with insufficient clinical response were treated with infliximab (10mg/kg) as rescue. The patients were examined with GIUS before rescue treatment (baseline), at the day of the 2nd infusion (after 1-2 weeks) and after 3 months. Bowel wall thickness (BWT), bowel wall vessel density with colour Doppler, loss of haustration and fatty tissue reaction was registered for every segment of the colon as well as an activity score (UC-score) based on these parameters³. The two main outcomes of the study based on the partial MAYO score (pMAYO) at 3 months. Clinical response was defined as a change in pMAYO ≥ 3 points and ≥ 30% and with an absolute reduction in the rectal bleeding score ≥ 1 or with the score for rectal bleeding ≤ 1. Clinical remission was defined as pMAYO ≤2.

Results

68 patients with colitis were recruited and of these 37 failed the initial treatment with iv corticosteroids and were given rescue treatment. At baseline 8 had left-sided colitis while 29 had subtotal or total colitis. After 3 months 3 patients had received surgery, 28/34 had treatment response compared to baseline and 24/34 were in remission. There were significantly more patients with left-sided colitis in remission (p=0.034). At the 2^nd infusion there were no significant differences between responders and non-responders for the GIUS parameters, but patients in remission at 3 months had significantly lower BWT in the ascending colon (1.3 ±0.5 vs 2.9 ±2.2 mm, p=0.002) and the transverse colon (1.7 ±0.9 vs 2.8 ±0.9 mm, p<0.001), lower sum of BWT (9.1 ±3.0 vs 13.1 ±5.0 mm, p=0.005) and UC-score (8.0 ±4.7 vs 12.9 ±7.2, p=0.018). At 3 months there was a significant difference in BWT for all segments, the sum of BWT (7.0 ±2.6 vs 14.0 ±4.5, p<0.001) and the UC-score (3.9 ±4.6 vs 16.3 ±5.6, p<0.001) for responders. For patients in remission similar results were found except for the rectum. The sum of BWT (6.8 ±2.6 vs 11.9 ±4.6 mm, p<0.001) as well as the UC-score (3.8 ±4.6 vs 11.7 ±7.8, p<0.001) was significantly lower.

Conclusion

The significant differences in BWT of the ascending and transverse colon at the 2^nd infusion could reflect prognostic differences between left-sided and total colitis. At 3 months the BWT of all colon segments was lower except for the rectum for patients in remission.

References

1) Ilvemark J, Wilkens R, Thielsen P, et al. Early Intestinal Ultrasound Predicts Intravenous Corticosteroid Response in Hospitalised Patients With Severe Ulcerative Colitis. J Crohns Colitis. Nov 23 2022;16(11):1725-1734. doi:10.1093/ecco-jcc/jjac083
2) Nylund, K., et al. ⟪ Sonorescue⟫-treatment response in acute severe Ulcerative Colitis measured with ultrasound. In: J Crohns Colitis. Great Clarendon St, Oxford OX2 6DP, England: Oxford Univ press, 2025. p. i239-i239.
3) Bots S, Nylund K, Lowenberg M, Gecse K, D'Haens G. Intestinal Ultrasound to Assess Disease Activity in Ulcerative Colitis: Development of a novel UC-Ultrasound Index. J Crohns Colitis. Aug 2 2021;15(8):1264-1271. doi:10.1093/ecco-jcc/jjab002

Disclosure

Odd Helge Gilja has received speaker’s honoraria from AbbVie, Bracco, Allmirall, GE healthcare, Takeda AS, Ferring AS, Allergan and Janssen-Cilag and has served as a consultant for Bracco, GE Healthcare, Takeda and Samsung. ​The other authors have nothing to dislose.

Introduction

Mirikizumab (miri), a humanized IgG4-variant monoclonal antibody that specifically binds to subunit p19 of interleukin-23, showed efficacy in phase (Ph)3 induction (LUCENT-1) and maintenance (LUCENT-2) studies involving patients with ulcerative colitis.¹
Here we report the efficacy and safety of the Ph3 LUCENT-2 study, a double-blind, randomized withdrawal maintenance study, in Chinese subpopulation who responded to miri induction therapy from LUCENT-1.

Aims & Methods

Miri clinical responders after 12-week induction therapy (54.3%)were re-randomized in a 2:1 ratio to receive blinded miri 200 mg or placebo (PBO) subcutaneously (SC) every four weeks (Q4W) for 40 weeks (Chinese primary efficacy population N=80). Randomization was stratified by biologic agent/tofacitinib failed status, induction remission status and baseline corticosteroid (CS) use.
The primary objective was to test the hypothesis that Miri was superior to PBO in achieving clinical remission at Week 40. Key secondary endpoints included alternate clinical remission, CS-free remission, endoscopic remission, histologic-endoscopic mucosal remission (HEMR), improvement in bowel urgency, bowel urgency remission, and maintenance of clinical remission. Analyses in Chinese subpopulation were descriptive.

Results

Baseline demographic and disease characteristics were generally balanced across the two treatment groups, including the proportion of baseline CS/ immunomodulator use, biologic agent/tofacitinib failure status and pancolitis.
A greater proportion of patients treated with miri achieved clinical remission at Week 40 (miri 50.0%, PBO 12.5%; Δ=40.4 [95% confidence interval (CI) 22.5, 58.4]). Miri also improved key secondary endpoints at Week 40 including proportion of patients who achieved alternate clinical remission (miri 55.4%, PBO 12.5%; Δ=45.4 [95%CI 27.3, 63.4]), and who achieved CS-free remission, clinical remission, bowel urgency remission and HEMR compared to PBO.
The frequencies of treatment-emergent adverse events were similar between groups in Chinese patients. There were fewer serious adverse events and discontinuations due to adverse events in miri patients compared to PBO. No deaths were reported in Chinese subpopulation during this study.

Conclusion

In Chinese patients who responded to miri induction therapy, miri's maintenance treatment provided positive efficacy and safety profiles consistent with LUCENT-2 overall population, supporting benefits of miri treatment in the Chinese ulcerative colitis patients.

Table 1: Primary and key secondary endpoints of LUCENT-2 at Week 40 in Chinese population (Miri Induction Respondersa)	Placebo SC N=24	Miri 200 mg SC N=56
Clinical Remissionb, n (%) Common risk difference vs placebo	3 (12.5)	28 (50.0) 40.4
Alternate Clinical Remission c, n (%) Common risk difference vs placebo	3 (12.5)	31 (55.4) 45.4
Corticosteroid-free Clinical Remissiond, n (%) Common risk difference vs placebo	2 (8.3)	26 (46.4) 40.2
Endoscopic Remissione, n (%) Common risk difference vs placebo	4 (16.7)	33 (58.9) 45
HEMRf, n (%) Common risk difference vs placebo	2 (8.3)	24 (42.9) 35.6
Bowel Urgency Improvement from BLg, LSM (SE) LSM difference vs placebo (SE)	-2.23 (0.47)	-4.52 (0.33) -2.29 (0.53)
Bowel Urgency Remissionh, n/N (%) Common risk difference vs placebo	1/24 (4.2)	23/52 (44.2) 41.4
Maintenance of Clinical Remissioni, n/N (%) Common risk difference vs placebo	0/8 (0)	11/18 (61.1) 60.6
Modified Intent-to-Treat population. BL = baseline (Week 0 of LUCENT-1 induction study); LSM = least squares mean; miri = mirikizumab; SC = subcutaneous; SE = standard error. aMiri induction responders: Patients who had clinical response to miri at Week 12 of LUCENT-1 (decrease in the modified Mayo score of ≥2 points and ≥30% decrease from baseline (BL); and decrease of ≥1 point in the Rectal Bleeding (RB) subscore from BL or a RB score of 0 or 1) after receiving 300mg IV miri every 4 weeks for 12 weeks. bClinical Remission: Stool Frequency (SF) = 0, or SF = 1 with a ≥1-point decrease from BL; RB = 0; Endoscopic Subscore (ES) = 0 or 1 (excluding friability). cAlternate Clinical Remission: SF subscore = 0, or SF = 1, and RB subscore = 0, and ES = 0 or 1 (excluding friability). dCorticosteroid-free Clinical Remission: Clinical remission at Week 40; Symptomatic remission at Week 28; No corticosteroid use for ≥12 weeks prior to Week 40. eEndoscopic Remission: ES = 0 or 1 (excluding friability). fHEMR (Histologic-endoscopic mucosal remission): Histologic remission with absence of mucosal neutrophils, defined using the Geboes scoring system with subscores of 0 for grades: 2b (lamina propria neutrophils); 3 (neutrophils in epithelium); 4 (crypt destruction); 5 (erosion or ulceration), and Endoscopic Remission. gBowel Urgency Improvement: Change from induction baseline in the Urgency Numeric Rating Scale (NRS). The Urgency NRS is a patient-reported measure of the severity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency). hBowel Urgency Remission: Urgency NRS = 0 or 1 among patients induced into clinical response with miri in LUCENT-1 and had Urgency NRS ≥3 at induction baseline. iMaintenance of Clinical Remission: Clinical remission at Week 40 among patients induced into clinical remission with miri in LUCENT-1.

References

1. Geert D'Haens, Marla Dubinsky, Taku Kobayashi, et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2023 Jun 29;388(26):2444-2455.

Disclosure

Zhihua Ran, Jie Zhong, Chengdang Wang, Xiang Gao, Xiaolan Zhang, Yijuan Ding and Qian Cao have been investigators of Eli Lilly and Company; Dan Tang, Chenxi Qian, Jiao Yu are employees and minor stockholders of Eli Lilly and Company.