Introduction

Crohn’s disease (CD) is a chronic relapsing disorder of the gastrointestinal tract characterized by excessive inflammation sustained by the induction and expansion of Th1 and Th17 cells. Ustekinumab (UST), a fully humanized monoclonal antibody approved for the treatment of CD patients, inhibits both IL12 and IL23, two cytokines involved in the Th1 and Th17-mediated immune response, by targeting the common subunit p40. To be effective UST needs, in addition to the expression of target cytokines, the presence of cells responsive to IL12 and IL23, therefore we focused our attention on the expression of IL12 and IL23 receptors in target cells.

Aims & Methods

This study aimed at correlating the expression of IL12 and IL23 and their receptors in the lamina propria Th1, Th17 and innate lymphoid cells (ILCs) from CD patients’ biopsies collected before UST treatment start to the clinical disease activity evaluated after 16 weeks of therapy.
This is a prospective, observational, single-center open-label study. All CD patients with clinical indications to receive UST for active luminal disease were enrolled. Patients had baseline endoscopy to confirm disease activity by SES-CD and to collect biopsies to isolate LPMC. Clinical remission to therapy was assessed at week 16 and defines as Harvey Bradshaw Index (HBI) <5. IL12 (p40 and p35) and IL23 (p40 and p19) cytokines subunits and IL12 (IL12Rb1 and IL12Rb2) and IL23 (IL12Rb1 and IL23R) receptors subunits was evaluated in remitters (R) and not remitters (NR) by real-time PCR. Moreover, IL12Rb2 and IL23R expression was analyzed in Th1 (defined as CXCR3⁺/CCR6^-), Th17 (CXCR3^-/CCR6⁺); Th1/Th17 (CXCR3⁺/CCR6⁺), ILCs (127⁺/161⁺) by flow cytometry. Differences between groups were analyzed by Mann-Whitney test and statistical significance was considered for p<0.05.

Results

From April 2019 to April 2022, 12 CD patients were enrolled in the study. Clinical and demographic characteristics are described in Table 1. At week 16 6/12 (50%) patients were in remission. There was no statistically significant difference in il12rb2, il12rb1, and il23r RNA expression between R and NR. Regarding cytokines subunits, p40 and p35 expression was significantly higher in R than in NR (p=0,001). p19 expression in R was higher as compared to NR although the difference did not reach statistical significance. No difference in Th and ILCs subgroups frequencies between R and NR was observed by flow cytometry. IL12Rb2 and IL23R were equally expressed by Th17, Th1/Th17, ILC1, and ILC2/3 cells in the two groups. In contrast, IL23R expression in Th1 cells was significantly higher in R group (18.0%) as compared to NR (5.8%; p=0.009).

Conclusion

In CD patients treated with UST, high IL12 and Th1-restricetd IL23R expression in the lamina propria cells was associated with remission at week 16.

Disclosure

This study is supported by Janssen.

Introduction

Ulcerative colitis (UC) is associated with debilitating symptoms that impair the quality of life (QoL) of patients; restoration of QoL is an important long-term treatment goal.¹ Upadacitinib (UPA), an oral, reversible Janus kinase inhibitor approved for the treatment of UC, improves health-related QoL (HRQoL) and patient-reported outcomes (PROs) with 1 year (yr) of maintenance therapy.^2-4 This post hoc analysis of the U-ACTIVATE long-term extension (LTE) study evaluated the long-term efficacy of UPA in sustaining PROs and HRQoL outcomes in patients who had received up to a total of 4 years (yrs) of UPA maintenance therapy.

Aims & Methods

This analysis included patients who completed 1 yr (52 weeks [wks]) in the U-ACHIEVE maintenance study and received UPA15 mg once-daily (QD) (UPA15) or UPA 30 mg QD (UPA30) maintenance treatment in the U-ACTIVATE LTE study. Patients receiving UPA15 or UPA30 who achieved clinical remission per Adapted Mayo score at maintenance wk 52 continued their double-blind treatment upon entering the LTE study. Nonremitters receiving UPA15 were escalated to UPA30, those receiving UPA30 continued UPA30, and those assigned to PBO were escalated to UPA15, all in a blinded manner. The UPA UC program was not designed to compare UPA15 and UPA30 doses. Efficacy was assessed at LTE wks 0, 96, and 144 (data cutoff date: 30 June 2024) and included the percentage of patients who achieved absence of abdominal pain, absence of bowel urgency, Inflammatory Bowel Disease Questionnaire (IBDQ) response, IBDQ remission, and a meaningful within-person change (MWPC) in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue; Short-Form Health Survey-36 version 2 Mental Component Score (SF-36v2 MCS), and SF-36v2 Physical Component Score (PCS). Data were reported using as-observed (AO) and modified nonresponder imputation (mNRI) methods (shown in Table). Safety was reported previously.²

Results

This analysis included 369 patients treated with UPA15 or UPA30 at wk 0 of LTE trial. In the AO analysis, patients treated with UPA15 or UPA30 achieved sustained improvements from LTE wk 0 to wk 144 in PROs and HRQoL assessments (Table), including the absence of abdominal pain, absence of bowel urgency, IBDQ response, IBDQ remission; and achieved MWPC in FACIT-Fatigue, SF-36v2 PCS, and SF-36v2 MCS. Similar results were observed for all endpoints with the more conservative mNRI analysis (Table).

Conclusion

Patients with UC who responded to induction therapy and received long-term UPA maintenance therapy showed a sustained absence of symptoms and improvements in HRQoL, suggesting that UPA maintains long-term improvements in patient-reported outcomes.

References

1. Turner D, Ricciuto A, Lewis A, D’Amico F, Dhaliwal J, et al. Gastroenterology. 2021;160:1570–83.
2. Panaccione R, et al. J Crohn’s Colitis. 2025;19(S1):i84-i86 [abstract].
3. AbbVie Inc. RINVOQ (Upadacitinib) [package insert] U.S. Food and Drug Administration website. https://www.rxabbvie.com/pdf/rinvoq_pi.pdf. Revised May 2023. Accessed 25 Feb 2025.
4. AbbVie DG& CoK. RINVOQ. Summary of Product Characteristics. European Medicine Agency website. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf. Revised Feb 2025. Accessed 25 Feb 2025.

Disclosure

Funding: AbbVie funded this study (U-ACTIVATE; NCT03006068) and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, 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.

Acknowledgments: AbbVie and the authors thank the participants, study sites, and investigators who participated in this clinical trial. Paulette A. Krishack, PhD, of AbbVie, provided medical writing support; Angela T. Hadsell, BA, of AbbVie, provided editorial support.

Joana Torres has received grant funding/speaker fees from and/or has participated in advisory boards for AbbVie, Lilly, Takeda, Janssen, and Pfizer.

Corey A Siegel has served as a consultant, advisor, and/or speaker for CME activities and/or received grant funding from AbbVie, BMS, Celltrion, Fresenius, Janssen, Lilly, Napo, Pfizer, Prometheus, Prometheus Labs, Roivant, and Takeda.

Julian Panés received consultancy fees/honorarium from AbbVie, Alimentiv, Athos, Atomwise, Boehringer Ingelheim, Celsius, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Surrozen, Takeda, and Wasserman, and has served on a data safety monitoring board for Alimentiv, Mirum, Sorriso, Sanofi, and Surrozen.

Edward V. Loftus Jr. has served as a consultant for AbbVie, Abivax, Amgen, Astellas, Avalo, Biocon, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Fresenius Kabi, Genentech, Gilead, Iota Biosciences, Iterative Health, Janssen, Morphic Therapeutics, Ono Pharma, Takeda, and TR1X Bio; has received research grants from AbbVie, Genentech, Gilead, Janssen, Merck, and Takeda; and is a share owner of Exact Sciences and Moderna.

Remo Panaccione has received consulting fees, speaker fees, and research support from Abbott, AbbVie, Abbivax, Alimentiv Amgen, AnaptysBio, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen Pharmaceuticals, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Sanofi, Satisfai Health, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx, and UCB.

Si Xuan, Nidhi Shukla, Ari Stromberg, Sina Ogholikhan, Leah Rizzo, and Dolly Sharma, are employees of AbbVie and may own stock options.

Gareth Parkesreports personal payments, honoraria, speaker fees, travel grants and/or fellowships from AbbVie, Allergan, Bristol Myers Squibb, Celltrion, Ferring, Galapagos, Janssen, Napp, Takeda, and Tillotts, and directorship and shareholding with Ampersand Health. TR reports personal grants from AbbVie; personal consulting fees from AbbVie, Arena, Aslan, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, MonteRosa, Mylan, MSD, Novartis, Numab, Pfizer, Roche, Sandoz, Takeda, UCB and XAP; membership of the ECCO Scientific Committee, and membership in the UEG Scientific Committee; director of Endoread.

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

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

Patients with ulcerative colitis (UC) are at an increased risk of cytomegalovirus (CMV) infection. CMV infection in acute severe ulcerative colitis (ASUC) may worsen disease severity and clinical outcomes. Current guidelines recommend colonic biopsies for the exclusion of CMV in all patients with ASUC. One study found that CMV positivity in ASUC was associated with greater need for rescue therapy, longer hospital length of stay (LOS) and higher readmission rates but found no difference in rate of colectomy.¹ We aimed to investigate the impact of positive CMV result on clinical outcomes in patients presenting with ASUC.

Aims & Methods

A retrospective review included all ASUC presentations to a quaternary hospital over a 10-year period based on modified Truelove and Witts’ criteria. ASUC presentations were grouped based on CMV positivity as determined by colonic biopsy. Data on pre-admission medications was collected. Data was collected on rates of rescue therapy, referral to colorectal surgery, colectomy, total parenteral nutrition (TPN). Outcomes assessed included intensive care unit (ICU) admission, 30- and 90-day readmission rates, 30- and 90-day mortality rates and mean LOS.

Results

A total of 172 ASUC presentations were identified. Of these, 133 had available colonic biopsy CMV results. 11 patients (8%) had positive CMV. Positive CMV result was significantly associated with increased need for TPN (36% vs 11%, p=0.02), ICU admission (27% vs 5%, p=0.004) and referral to colorectal surgery (82% vs 43%, p=0.01). Patients with CMV had longer LOS (27.1±14.0 vs 11.0±7.4, p=0.003). There were no significant differences in rates of rescue therapy, inpatient colectomy, readmission or mortality rates. 9 of the patients (82%) were treated with ganciclovir or valganciclovir. Patients on maintenance advanced UC therapies, including biologics and small molecule inhibitors, had significantly higher rate of CMV (22% vs 5%, p=0.01). Biologic therapy alone was associated with higher rate of CMV (24% vs 7%, p=0.02), whereas small molecule inhibitor alone was not (p=0.6). Pre-admission use of 5-aminosalicylates, high dose steroids, thiopurines or combination therapies were not associated with CMV positivity.

Table 1: Comparison data of clinical outcomes in ASUC between patients with and without CMV positivity on colonic biopsy

Conclusion

Patients with CMV positive colonic biopsies tend to require more inpatient interventions, including increased need for TPN, ICU admission, referral to colorectal surgery and longer hospital length of stay. Despite more complex admission course of ASUC patients with concurrent CMV infection, these patients were not observed to have worse outcomes than those without CMV diagnosis. Maintenance biologic and small molecule inhibitor use was associated with higher rates of CMV, reflecting the immunosuppressant effects of advanced UC therapies. CMV detection needs to be considered as a potential exacerbating factor in disease severity.

References

1. Huang D, Rennie M, Krasovec A, Nagubandi S, Liu S, Ge E, Khehra B, Au M, Sivagnanam S, Kwan V, Rogge C, Mitrev N, Kariyawasam V. Impact of cytomegalovirus on outcomes in acute severe ulcerative colitis: a retrospective observational study. Ther Adv Chronic Dis. 2024 Mar 28;15:20406223241233203. doi: 10.1177/20406223241233203. PMID: 38560721; PMCID: PMC10981253.