Introduction

Mirikizumab (MIRI), a p19-directed antibody against interleukin-23, demonstrated improvements in fatigue, abdominal pain (AP) and stool frequency (SF) at Week (W) 12 and W52 in the VIVID-1 clinical trial.¹

Aims & Methods

The aim of this analysis is to show the effect of MIRI on fatigue, AP, SF and achievement of clinical remission by Patient-Reported Outcome (PRO; SF ≤3 and AP ≤1 and neither worse than baseline) in the VIVID-2 open-label extension study through W104. This analysis includes data from primary analysis set in patients with Crohn’s disease (CD) randomised to the MIRI treatment arm in VIVID-1 who achieved endoscopic response (≥50% reduction from baseline in Simple endoscopic score for CD) at W52 and continued the MIRI subcutaneous dosing (300 mg) in VIVID-2. Change from VIVID-1 baseline was measured for continuous endpoints. Endpoints included fatigue measured using FACIT-Fatigue (measured as change from baseline, and clinically-meaningful improvement of ≥6-points among patients with baseline ≤46), AP improvement (measured as change from baseline, and achievement of ≤1 among patients with baseline >1), SF improvement (measured as change from baseline, and achievement of ≤3 among patients with baseline >3) and clinical remission by PRO, assessed at W64 and 104. Missing data were handled using observed case (OC) and modified non-responder imputation (mNRI) for response rates, while using modified baseline observation carried forward (mBOCF) for change from baseline. Response rates were presented as unadjusted proportions with 2-sided 95% confidence intervals using the Rubin's Rules (mNRI). ANCOVA models were used for continuous variables, adjusting for baseline values and intervention group.

Results

Fatigue mean (standard error [SE]) change from baseline was 10.7 (0.56) at W64; 9.4 (0.59) at W104, (observed response, n [%]: 152 [67.6%] at W64; 136 [64.8%] at W104; Table). AP improved (mean [SE] change: −1.5 [0.04] at W64; −1.6 [0.05] at W104), with response rates increasing from 174 (77.3%) to 161 (84.7%). SF showed sustained improvement (mean [SE] change: −4.3 [0.14] at W64; −4.3 [0.16] at W104), with response rates reaching 155 (89.6%) at W104 (Table). Similar rates of achievement of clinical remission by PRO were observed (178 [73.6%] at W64; 165 [80.1%] at W104) (Table).

Table: Improvement in fatigue, abdominal pain, stool frequency and achievement of clinical remission by PRO up to Week 104

Conclusion

MIRI sustained improvement in fatigue, AP, SF and clinical remission by PRO through 104 weeks of continuous treatment. These consistent findings support the long-term treatment with MIRI to address key symptoms of CD.

References

1. Ferrante, MarcTron, Emiliano, et al. The Lancet. 404 (10470):2423-2436.

Disclosure

PB: Received financial support for research from AbbVie, EG; lecture fees from AbbVie, AMC ICP, Amgen, Bristol Myers Squibb, Celltrion, Dr Falk Benelux, EG, Galapagos, Globalport, Lilly, Medtalks, Materia Prima, Pentax, Springer Media; served on an advisory board for AbbVie, Bristol Meyers Squibb, CIRC, Galapagos, Janssen, Lilly, Pentax, PSI-CRO, Roche, Takeda, Tetrameros. AA: Consultant for Geneoscopy; received research support from Takeda. AV, GY and JW: Employee and shareholder of Eli Lilly and Company. NL: Consultant for Eli Lilly and Company. JRA: Consultant for Janssen, Pfizer, Abbvie, Vedanta, Geneteche, Seres Therapeutics, Ferring, GSK, Merck, Bristol Myer Squibb, Roivant, Celltrion, and TRXBio, Xencor, Shattuck Labs; Speaker for Abbvie, Janssen. MC: Provided educational activities for AbbVie, China Medical System, IPSEN, Janssen, and Takeda; served on an advisory board for Boehringer Ingelheim and Janssen; and has support for clinical research from Janssen and Takeda.

Introduction

Vedolizumab (VDZ), a monoclonal antibody therapy approved for moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD) in China in 2020¹ has a unique, gut-selective, anti-lymphocyte trafficking (GSALT) mechanism of action.² However, there is limited data on VDZ's real-world effectiveness and safety in Chinese IBD patients.³ Interim results from the VALUE study that enrolled patients with UC have been published ^3,4 and final results are reported here.

Aims & Methods

VALUE (NCT04872491), a multicenter, single-arm, prospective, observational study evaluated the safety and effectiveness of VDZ in adult Chinese patients with IBD (N = 500) over 72 weeks. Clinical response, clinical remission, and endoscopic remission were assessed at Weeks 14, 30, and 54. Partial Mayo and Mayo endoscopic subscores at baseline and Weeks 14, 30, and 54 were calculated. Clinical response was defined as ≥2-point reduction in Partial Mayo Clinic score and ≥25% decrease from baseline score accompanied with ≥1-point decrease in the rectal bleeding or absolute rectal bleeding subscore ≤1. Clinical remission was defined as Partial Mayo Clinic score ≤2 with no subscore >1, endoscopic remission as Mayo endoscopic subscore ≤1, and complete endoscopic remission as Mayo endoscopic subscore 0. Safety results and CD patients’ data are presented in separate VALUE abstracts (IDs: AS-UEG-2025-01329 and AS-UEG-2025-01324).

Results

Among 409 UC patients enrolled in the final analysis, 91.9% (376/409) were included in the effectiveness analysis set. Mean age (±standard deviation [SD]) of patients was 46.3 (±15.1) years, and 59.4% (n=243) were male. At baseline, 30.8% (126/409) of patients had moderate UC, and 29.8% (122/409) had severe UC. The median duration of UC was 2.5 years, concomitant steroids were prescribed in 18.9% (71/376). Mean (±SD) partial Mayo score was 5.1 (2.1) at baseline, which declined to 1.7 (1.7), 1.5 (1.7) and 1.3 (1.5) by Weeks 14, 30 and 54, respectively, post-VDZ treatment. Patients achieving clinical response, clinical remission, endoscopic remission, and complete endoscopic remission were 76.9% (220/286), 71.1% (207/291), 63.6% (35/55), and 21.8% (12/55) at Week 14; 78.1% (193/247), 76.3% (190/249), 63.6% (28/44), and 27.3% (12/44) at Week 30; and 80.3% (155/193), 83.3% (165/198), 71.4% (20/28), and 50.0% (14/28) at Week 54, respectively. Patients with moderate and severe UC; biologic naïve patients and patients with prior exposure to biologics at baseline also achieved clinical response, clinical remission, and endoscopic remission (Table). Compared with baseline, mean (±SD) reduction of C-reactive protein (mg/L) at Weeks 14, 30, and 54 were 7.8 (20.2), 6.5 (22.2), and 3.4 (24.8), respectively; mean (±SD) reduction of fecal calprotectin (mu g/g) was 42.7 (150.7) at Week 14 and 212.6 (480.1) at Week 30. The proportion of patients achieving clinical remission without steroid use by Week 14 was 37.7% (23/61), which increased to 60.6% (20/33) by Week 54.

Conclusion

This study indicated that VDZ demonstrated a good effectiveness profile in Chinese UC patients in the real-world setting.

References

1. Yan J et al., Medicine (Baltimore). 2024; 103: e38759.
2. Soler D et al. J Pharmacol Exp Ther. 2009; 330: 864-875.
3. Baili C et al. Am J Gastroenterol. 2023; 118: S213-S214.
4. Yan C et al. Am J Gastroenterol. 2023; 119: S894-S895.

Disclosure

This study was funded by Takeda (China) International Trading Co. Ltd. Xiuli Zuo, Ye Chen, and Yingchao Li have no conflicts of interest. Lifei Gu and Fang Zhou are Takeda employees and hold Takeda stock options. Minhu Chen received speaker honorariums from Takeda China, AstraZeneca China, Xian Janssen, and Eisai China.
Medical writing support for the development of this abstract under the direction of the authors was provided by Vibhuti Singh, Ph.D., of Cactus Life Sciences (part of Cactus Communications), funded by Takeda (China) International Trading Co., Ltd.

Introduction

Postoperative recurrence (POR) after ileocecal resection for Crohn's disease (CD) represents a significant clinical challenge

Aims & Methods

This study aimed to identify clinical risk factors for surgical recurrence in patients undergoing ileocecal resection for CD. This multicenter retrospective cohort study included 1,066 patients with CD who underwent ileocecal resection across 13 Italian centers. Univariate and multivariate logistic regression analyses were performed to identify clinical risk factors associated with surgical recurrence.

Results

The cohort comprised 59.0% males with a median age at diagnosis of 29 years [IQR: 22-40]. Most patients presented with stricturing disease (55.2%) or penetrating disease (40.9%), with ileal (49.6%) and ileocolonic (47.6%) locations predominating. Over a median follow-up of 70 months [IQR: 31-131], 101 patients (9.5%) required recurrent surgery. The median time to recurrent surgery was 78.5 months [IQR: 19.0-138.0]. Most patients (72.3%) had at least one clinical risk factor for POR, with penetrating phenotype (40.4%), previous intestinal resections (27.2%), and perianal disease (21.4%) being most common.
Univariate analysis identified significant risk factors for surgical recurrence including prior intestinal resection (OR 5.56, 95% CI 3.62-8.56, p<0.001), perianal disease (OR 3.50, 95% CI 2.28-5.35, p<0.001), large intestinal resection ≥50 cm (OR 4.80, 95% CI 3.04-7.58, p<0.001), and continued smoking after surgery (OR 1.84, 95% CI 1.16-2.94, p=0.010). Disease duration >10 years (OR 2.20, 95% CI 1.44-3.36, p<0.001) and colonic involvement (L2: OR 3.00, 95% CI 1.18-7.65, p=0.021) increased risk, while ileal localization (L1) was protective (OR 0.35, 95% CI 0.22-0.54, p<0.001). Bowel perforation as surgical indication significantly increased recurrence risk (OR 2.58, 95% CI 1.29-5.16, p=0.007). Multivariate analysis confirmed perianal disease (aOR 2.58, 95% CI 1.56-4.26, p<0.001), previous intestinal resection (aOR 5.70, 95% CI 3.52-9.23, p<0.001), and large resection (aOR 4.04, 95% CI 2.43-6.72, p<0.001) as independent predictors of recurrence. Unlike previous studies, penetrating behavior was not associated with increased risk, while disease duration >10 years and colonic involvement emerged as significant factors. Additionally, this study uniquely identified bowel perforation as a surgical indication distinct from other penetrating complications in predicting recurrence.

Table 1: Independent Risk Factors for Surgical Recurrence After Ileocecal Resection in Crohn's Disease

Conclusion

This large cohort study identified several robust predictors of surgical recurrence after ileocecal resection for CD, with some notable differences from prior research. Previous intestinal resection, perianal disease, large intestinal resection, colonic involvement, and continued smoking emerged as particularly strong risk factors, while penetrating disease behavior was not confirmed as a predictor. These findings challenge some aspects of current risk stratification guidelines and can help inform personalized postoperative management strategies.

Introduction

Despite the benefits of available therapies for Crohn’s disease (CD), many patients (pts) lose treatment response over time, highlighting the need for options with sustained effectiveness.^1-3 Part 2 of the SEQUENCE trial is an open-label extension (OLE) study that evaluates the long-term efficacy and safety of the interleukin-23 p19 inhibitor risankizumab (RZB) in pts with moderate to severe CD and prior anti-TNF failure. Here, we evaluated the durability of clinical remission, quality of life (QoL), and inflammatory biomarker outcomes in RZB-treated pts through week (wk) 100 of SEQUENCE.

Aims & Methods

In SEQUENCE (NCT04524611), pts randomised to the RZB arm during Part 1 who completed the wk48 visit continued to receive open-label 360mg subcutaneous RZB maintenance dose every 8 wks starting at wk52 (baseline of Part 2).⁴ We assessed the proportion of pts achieving clinical remission (per CD activity index [CDAI] and stool frequency/abdominal pain score [SF/APS]) and Inflammatory Bowel Disease Questionnaire (IBDQ) remission at wks 8, 24, 52, 76, and 100. Additionally, pts with elevated high-sensitivity C-reactive protein (hs-CRP; > 5 mg/L) or faecal calprotectin (FCP; > 250 µg/g) at baseline were assessed for normalization of hs-CRP or FCP at wks 8, 24, 52, 76, and 100. We also assessed the proportion of pts who achieved these endpoints at wk100 among pts who also achieved that endpoint previously at either wk8 or at wk52. Data were assessed for all intent-to-treat pts using As Observed (AO) and per Non Responder imputation (NRI). Safety was not assessed in this post hoc analysis, although previously reported.⁵

Results

Of the 224 pts who entered SEQUENCE Part 2, the proportion of pts who achieved clinical remission (per AO data) increased from wk8 to wk52, and remained stable up to wk100 (CDAI: 48.0% [n/N=96/200] at wk8, 75.3% [168/223] at wk52, and 84.4% [141/167] at wk100; SF/APS: 44.0% [88/200] at wk8, 71.2% [158/222] at wk52, and 74.7% [124/166] at wk100) (Table). Similar trends were observed (per AO data) for IBDQ remission (41.5% [88/212] at wk8, 62.1% [139/224] at wk52, and 65.3% [126/193] at wk100), normalisation of hs-CRP (38.8% [54/139] at wk8, 53.1% [76/143] at wk52, and 62.0% [80/129] at wk100), and normalisation of FCP (34.6% [46/133] at wk8, 56.9% [87/153] at wk52, and 60.0% [75/125] at wk100). Most pts who achieved clinical remission at wk8 remained in remission at wk100, and the same was observed for patients in remission at both wk52 and wk100 (AO data; respectively, CDAI: 96.1% [73/76] and 91.1% [123/135]; SF/APS: 90.1% [64/71] and 86.8% [112/129]). A durable effect was also observed from wk8 to wk100 and from wk52 to wk100 in the majority of RZB-treated pts across all other endpoints (AO data; respectively, IBDQ remission: 91.5% [65/71] and 85.7% [102/119]); normalisation of hs-CRP: 80.0% [40/50] and 81.2% [56/69]; normalisation of FCP: 81.1% [30/37] and 85.1% [57/67]). Similar results to AO data were observed per NRI data (Table).

Conclusion

Pts with moderately to severely active CD receiving RZB demonstrated durable clinical remission, IBDQ remission, and inflammatory biomarker reductions through wk100 in the SEQUENCE OLE. Notably, most pts who achieved efficacy endpoints early maintained effectiveness during continued RZB treatment.

References

1. Colombel JF, et al. Gastroenterology. 2007;132:52–65.
2. Hanauer SB, et al. Lancet. 2002;359:1541–9.
3. Turner D, et al. Gastroenterology. 2021;160:1570–83.
4. Peyrin-Biroulet L, et al. N Engl J Med. 2024;391:213–23.

Disclosure

Raja Atreya has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AlfaSigma, AstraZeneca, Bristol Myers Squibb, CED Service, Celltrion Healthcare, Dr Falk, Galapagos, Johnson & Johnson, Eli Lilly, MSD Sharp & Dohme, Pfizer, Takeda Pharma.
James O. Lindsay has served as a consultant and an advisory board participant for AbbVie, Astra Zeneca, Bristol Myers Squibb, , Celltrion, Eli Lilly, Engytix, Ferring Pharmaceuticals, Galapagos, Gilead, GSK, Janssen, MSD, Pfizer, Takeda, and Vifor Pharma; has received speaker fees and sponsorship for academic meetings from AbbVie, Ferring Pharmaceuticals, Janssen, MSD, Pfizer, Tillotts Pharma, and Takeda; and has received investigator-led research grants from AbbVie, Gilead, Pfizer, and Takeda.
Marc Ferrante has received research grants from AbbVie, EG Pharma, Janssen, Pfizer, Takeda, and Viatris; consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, Merck Sharp and Dohme, MRM Health, Pfizer, Takeda, and ThermoFisher; and speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare, and Viatris.
Britta Siegmund has received consulting fees from AbbVie, Abivax, Boehringer Ingelheim, BMS, Dr Falk, Endpoint Health, Galapagos, Gilead, Janssen, Landos, Lilly, Pfizer, and Takeda, and speaker’s fees from AbbVie, AlfaSigma, BMS, CED Service, Dr Falk, Ferring, Galapagos, Janssen, Lilly, MSD, Pfizer, and Takeda.
Qian Cao has served as a steering committee adviser for Bristol Myers Squibb Company, and Janssen Research Development, LLC; and has received research grants from Takeda and Johnson & Johnson.
Stijn van Haaren, Jameson Crowley, Toni Anschutz, and Andrew Garrison are full-time employees of AbbVie and may own AbbVie stock or stock options.
Marla Dubinsky has received consulting and advisory fees from AbbVie, Abivax, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, GSK, Janssen, Johnson and Johnson, Merck, Pfizer, Prometheus Labs, Prometheus Biosciences, Sanofi, Spyre and Takeda
Funding: AbbVie funded this trial and participated in the trial design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. Medical writing support was provided by Mahesh Chemudupati, PhD of AbbVie. Editorial support was provided by Amy Kuang, PhD of AbbVie.