Introduction

Mirikizumab (MIRI) has shown promising results in ulcerative colitis (UC) based on the data from the pivotal clinical trials (LUCENT). However, these results still need to be validated in clinical practice.

Aims & Methods

This study aims to assess the short-term real-world effectiveness and safety of MIRI in patients with UC.
All patients with UC who received MIRI and without previous colectomy included in the prospectively-maintained ENEIDA registry were included. Clinical disease activity was assessed by partial Mayo score (pMS). The primary outcome was clinical remission (defined as pMS ≤2 with no subscore >1 and no rectal bleeding) at week 8 and 12, alongside its safety profile.

Results

A total of 171 patients from 43 Spanish hospitals were included (mean age of 49.5 years [SD 18], 54% male, median disease duration of 128 months [SD 97], 55% non-smokers, 62% extensive colitis. Concomitant therapy at baseline included 44% with steroids and 7.6% with immunosuppressants. Prior advanced therapies exposure was: 89% Anti-TNF, 69% vedolizumab, 54% ustekinumab, and 40% JAK inhibitors, with 54% exposed to > 2 mechanisms of action (MoA). At baseline patients had a median pMS 5 (IQR, 4-7) and faecal calprotectin of 557 ug/g (IQR, 120-1000). All but one patient started MIRI 300 mg iv every 4 weeks. Mean follow-up was 5.3 (SD 4.4) months. Clinical response and clinical remission at week 8 were 44% and 26%, respectively, and this increased up to 45% and 30% at week 12. Clinical remission rate at week 12 was higher among those with prior exposure to 1 MoA vs 2 or more than 2 (65%, 25%, 27% respectively, p=0.04, p=0.02). Previous exposure to ustekinumab was associated with a numerically lower, not statistically significant, rate of clinical remission at week 12 (28% vs. 38%, p=0.4). Faecal calprotectin significantly decreased at week 12 (160 ug/g [IQR, 54-852], p=0.001). The overall hospitalization and colectomy rates were 5.8% and 1.7% respectively. MIRI was generally well tolerated, with 10% of patients reporting at least one adverse event, but only one of them categorized as severe.

Conclusion

MIRI demonstrated its real-life effectiveness in the short-term, even in a highly-refractory cohort. Prior advanced therapy exposure to more than one MoA significantly impacts the effectiveness of MIRI during the induction. Safety was consistent with the known profile of this drug.

Introduction

Tulisokibart is a monoclonal antibody that targets tumor necrosis factor-like cytokine 1A (TL1A), a regulator of inflammation and fibrosis in inflammatory bowel disorders. In the Phase 2 ARTEMIS-UC study, a significantly higher proportion of participants on tulisokibart compared to placebo achieved clinical remission after 12 weeks of induction treatment in patients with moderate to severe active ulcerative colitis (UC) and conventional or advanced treatment failure.¹ In a post hoc analysis from ARTEMIS-UC, re-induction and delayed induction treatment with tulisokibart were effective in participants who did not respond during the initial induction period.² We explored the efficacy and safety of tulisokibart maintenance therapy up to 1 year during the open-label extension of ARTEMIS-UC among patients who responded to induction, re-induction, and delayed induction.

Aims & Methods

Participants (≥18 years) were randomized to intravenous (IV) tulisokibart 1000 mg on day 1 and 500 mg at weeks 2, 6, and 10 or placebo. The study population consisted of 2 cohorts based on a genetic diagnostic test (Dx) assessing likelihood for responding to anti-TL1A treatment. Cohort 1 included participants stratified by Dx results while Cohort 2 included only Dx positive participants. Cohort 1 is the population used in this analysis. Participants were classified as induction responders (defined as reduction of ≥2 points and ≥30% in modified Mayo score from baseline, accompanied by a reduction ≥1 in rectal bleeding subscore or absolute rectal bleeding subscore ≤1 at week 12) or induction nonresponders. Induction non-responders in the tulisokibart and placebo groups were assigned to an open label 12-week re-induction with the aforementioned tulikosibart induction dosing regimen. Cohort 1 induction, re-induction, and delayed induction responders were randomized (stratified by Dx status) to open-label IV tulisokibart 100 mg or 250 mg every 4 weeks.

Results

In Cohort 1, 47 tulisokibart induction responders, 13 re-induction responders, and 29 delayed induction responders were randomized to open-label maintenance treatment with tulisokibart 100 mg or 250 mg every 4 weeks. Maintenance of treatment effect was generally similar with a trend for higher efficacy with tulisokibart 250 mg vs 100 mg maintenance treatment observed across the 3 groups. The safety profile of tulisokibart maintenance treatment was similar across the 3 groups, with no new safety signals being observed.

Conclusion

Tulisokibart was effective as a maintenance treatment in patients with moderate to severe UC. The effect was generally similar across Cohort 1 tulisokibart induction responders, re-induction responders, and delayed induction responders. Tulisokibart maintenance treatment was well tolerated across the 3 groups, with no identified safety signals. Altogether, this suggests that a second induction regimen in tulisokibart non-responders may result in a long-term efficacy benefit without increased safety risk. Larger trials are needed to confirm these findings.

Table: Efficacy and fecal calprotectin

References

1. Sands et al. N Engl J Med 2024; 26;391:1119-1129
2. Hoque et al. J Crohns Colitis 2025; 19(suppl 1):i1158-i1159

Disclosure

Sami Hoque: ​Received Lecture fees and research grants from Tillotts, Ferring and Eli Lilly.
Bruce E. Sands: Travel fees from Eli Lilly and Company, Janssen Research & Development, LLC, Takeda Development Center Americas, Inc.; Received food & beverage from AnX Robotica Corp.; Grant from Janssen Research & Development, LLC; Owns stock options in Ventyx Biosciences; Consulting fees from AbbVie, Abivax, Aclaris Therapeutics, Adiso Therapeutics, Agomab Therapeutics, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb Company, Celltrion Healthcare, Celltrion Healthcare, Connect Biopharm, Cytoki Pharma, Eli Lilly and Company, Entera, Enveda Biosciences, Equilium, Evommune, F. Homann-La Roche AG, Ferring, Fresenius Kabi USA, LLC, Galapagos, Genentech USA, Inc., Gilead Sciences , GlaxoSmithKline, GossamerBio, HMP Acquisition, Imhotex, Immunic, Immunyx Pharma Ltd., Index Pharmaceuticals, Innovation Pharmaceuticals, Janssen Biotech, Inc., Janssen Scientific Affairs, LLC, Johnson & Johnson Health Care Systems Inc., Kaleido, Kallyope, Kyowa Kirin Co., Ltd, Merck & Co., Inc., Microba, Microbiotica Limited, MiroBio, Mobius Care, Morphic Therapeutic, MRM Health, Nexus Therapeutics, Nimbus Therapeutics, Odyssey Therapeutics, Pfizer, Progenity Inc., Prometheus Biosciences, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Recludix Pharma, SANOFI US SERVICES INC., Spyre Therapeutics, Surrozen, Synlogic Operating Company, Takeda Pharmaceuticals International, Inc., Target RWE, Teva Branded Pharmaceutical Products R&D, Theravance Biopharma Inc., TLL Pharmaceutical, VectivBio AG, Ventyx Biosciences
Brian G. Feagan: Consulting fees from Abbvie, Adiso Therapeutics, Agomab, Alimentiv Inc, Allianthera, Amgen Canada, AnaptysBio, Applied Molecular Transport, Arena Pharma, Biora Therapeutics, Blackbird Laboratories, Boehringer Ingelheim AB, Bristol-Myers Squibb, Celgene, Celsius Therapeutics, Connect BioPharma, Duality, Eli Lilly and Company, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen Global Services, LLC, JapanTobacco, Klick Health, Mage Biologics, Mestag Therapeutics, Mobius Therapeutics, LLC, Monte Rosa Therapeutics, Nexys Therapeutics, Nimbus Discovery Inc, Orphagen Inc., PFIZER CANADA INC, Prometheus, SANOFI US SERVICES INC., Seres Therapeutics, Sobi, Inc, Spyre Therapeutics, Surrozen, Synedgen, Takeda Canada, Takeda Development Center Americas, Inc., Televant, Tillotts, Triastek Inc.
Mark Yen: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Bin Dong: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Wen Zhou: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Silvio Danese: Consulting fees from AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion Healthcare, Ferring, Gilead Sciences, Hospira, Inc., Janssen Biotech, Johnson & Johnson Health Care Systems Inc., Pfizer, Sandoz, UCB Inc., Vifor (International) Ltd.

Introduction

​​​​​PSC is chronic infammatory disease of bile ducts leading to strictures of bile duct and eventually to liver cirrhosis. Chronic inflammation is associated with markedly increased risk of cholangiocancer (CCA). In addition, gall bladder abnormalities are common in patients with PSC¹ such as cholecystitis, gallstones, polys and gallbladder carcinoma (GBCA). Increased fasting gallbladder volume has been reported with normal gallbladder emptying². Due to the increased risk of GBCA³ cholecystectomy is recommended in PSC with gallbladder polyps ≥8 mm and smaller polyps growing⁴. However, cholecystectomy has been associated with impaired PSC outcome. A study consisting of 11 PSC patients with cholecystectomy suggested protective role of gallbladder based on MRCP changes and elevated AST levels in patients with cholecystectomy. No significant difference in serum bile acids was observed in patients with or w/o cholecystectomy⁵. Another small study including five PSC patients with cholecystectomy showed that cholecystectomy was associated with worse Mayo scores and an elevated FIB4⁶. More than 50% of PSC have enlarged gallbladder which is suspected to be caused by hyperpressure in the biliary tract⁵. Cholecystectomy may thus eliminate this reserve function and lead to progression of bile duct strictures.

Aims & Methods

To evaluate the impact of cholecystectomy on liver enzyme levels, biliary bile acid composition, bile duct disease progression, and overall outcomes in a large PSC patient cohort, we analyzed data from 1,009 individuals enrolled in the prospective Helsinki PSC registry. Of these, 114 patients (11.3%) had undergone cholecystectomy—34 prior to and 80 following the PSC diagnosis. Patients with gallbladder cancer were excluded. Clinical and laboratory parameters were collected, along with data on disease progression based on sequential ERC examinations scored by the Helsinki ERC score⁷. Additionally, bile composition was analyzed in a subgroup of 157 patients receiving UDCA therapy, 32 of whom had undergone cholecystectomy.

Results

Demographics, liver function tests, and outcomes stratified by cholecystectomy, are presented in the table. We found no differences between the three groups (no cholecystectomy, cholecystectomy done prior or after PSC dg) regarding the progression of bile duct disease or its severity, liver function tests, development of biliary dysplasia or need for dilatation, Mayo- and MELD-scores. The cumulative incidence of the composite end point (= transplantation, liver related death, HCC or CCA) did not differ between groups. The molar-% of phospholipids were lower and cholic acid and deoxycholic acid (mg) elevated in bile in patients with cholecystectomy, whereas no differences were found in UDCA content.

Conclusion

In this large study investigating the impact of cholecystectomy on PSC outcomes, we found no effect on liver enzyme levels, prognostic indices, bile duct disease progression, or overall prognosis, regardless of whether the procedure was performed before or after the PSC diagnosis.

References

1. Said K, eta al. Journal of Hepatology 2008; 48:598–605
2. Said K, et al. World J Gastroenterol 2009; 15: 3498-3503
3. van Erp LW, et al. Liver Int 2020; 40:382–92.
4. Chazouilleres O et al. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol 2022; 77:761–806
5. Cazzagon N, et al. JHEP Reports 2023. https://doi.org/10.1016/j.jhepr.2022.100649
6. Miyake N, et al. Cureus 17(3): e80184. DOI 10.7759/cureus.80184
7. Boyd S, et al. Endoscopy. 2016;48:432-9.

Introduction

Risankizumab (RZB) is a high-affinity humanised immunoglobulin (Ig) G1 monoclonal antibody that selectively binds to the p19 subunit of the interleukin-23 (IL-23) cytokine and inhibits its interaction with the IL-23 receptor.^1,2 Long-term RZB therapy for 3 years of maintenance showed durable efficacy and a well-tolerated safety profile in patients with ulcerative colitis (UC) in the COMMAND open-label extension (OLE) study.^1,3 This post hoc analysis evaluated the long-term efficacy of RZB in improving patient-reported outcomes through week (wk) 96 of the ongoing COMMAND OLE study.

Aims & Methods

COMMAND OLE is a 220-wk study enrolling patients who completed 52-wks maintenance dosing or enrolled directly as responders to induction.^1,3 This analysis included patients who completed 52 wks maintenance and an additional 96 wks of RZB treatment in the OLE. All patients received subcutaneous (SC) RZB180 Q8w starting at OLE wk 0, except patients who had prior rescue therapy (single RZB 1200 mg intravenous dose, then SC RZB360 Q8w) who continued RZB360 in the OLE. The OLE study was not designed to compare RZB180 and RZB360 groups. The data cut-off date for this interim analysis was 30 June 2024. Efficacy outcomes included the percentage of patients who achieved the absence of abdominal pain, bowel urgency, faecal incontinence, nocturnal bowel movements, tenesmus, sleep disruption due to UC symptoms; Inflammatory Bowel Disease Questionnaire (IBDQ) response; 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). Results were reported using as-observed (AO; Table) and nonresponder imputation (NRI) methods (Table). Safety was reported previously.³

Results

Of the 1003 patients (RZB180 = 701; RZB360 = 302) who entered the OLE, 398 (39.7%) patients (RZB180 = 262; RZB360 = 136) completed wk 96 at data cut-off date. In the AO analysis, RZB180- or RZB360-treated patients showed sustained improvements from OLE wks 0 to 96 in the absence of abdominal pain, bowel urgency, nocturnal bowel movements, tenesmus, faecal incontinence, sleep disruption due to UC symptoms, IBDQ response, MWPC in FACIT-Fatigue, SF-36 PCSv2, and SF-36v2 MCS (Table). Using the more conservative NRI analysis, similar results were observed for most endpoints through OLE wk 96 (Table). Despite RZB360-treated patients were more likely to have numerically higher clinical and endoscopic activity at OLE wk 0 compared with RZB180-treated patients (Adapted Mayo Score [AMS], mean [standard deviation], RZB180, 2.0 [1.4]; RZB360, 3.5 [2.0]; endoscopic subscore: RZB180, 1.1 [1.0]; RZB360, 1.9 [1.0]; clinical remission per AMS, RZB180, 54.8%; RZB360, 24.8%), at OLE wk 96, both RZB dosing regimens exhibited consistent and similar sustained improvements throughout all investigated patient-reported outcomes.

Conclusion

RZB-treated patients who completed OLE wk 96 (3 years of total maintenance therapy) experienced sustained improvement in quality of life and patient-reported outcomes.

References

1. Louis E, et al. JAMA. 2024; 332:881-97.
2. Singh S, et al. mAbs. 2015;7:778-91.
3. Atreya R, et al. J Crohn’s Colitis. 2025;19(S1):i108-i110 [Abstract].

Disclosure

Funding: AbbVie funded this study (COMMAND; NCT03398135) 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; S. Michael Austin, of AbbVie, provided editorial support.
Disclosures: Luc Biedermann has received lecture and consulting fees from Takeda, Sanofi, AbbVie, Falk, Bristol Myer Squibb, and Pfizer and is on advisory boards for AbbVie, Amgen, Bristol Myers Squibb, Falk, Janssen, Pfizer, Takeda, and Sanofi.
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.
Silvio Danese has received consultancy fees from AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Enthera, Ferring, Gilead, Hospira, Janssen, Johnson & Johnson, Lilly, Merck Sharp and Dohme, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB and Vifor.
Satoshi Tanida received speaker fees from JIMRO, Mitsubishi Tanabe Pharma, AbbVie, Janssen, Kissei, writing fees from Pfizer, and research funding from AbbVie.
Parambir S. Dulai received research support and/or consulting for AbbVie, Abivax, Adiso, Alimentiv, Bristol Meyer Squibb, Celltrion, Genentech/Roche, Geneoscopy, Janssen, Pfizer, Takeda.
Nidhi Shukla, Jasmina Kalabic, Pierre Morisset, Cecile Holweg, and Dolly Sharma, are employees of AbbVie and may own stock options.
Joana Torres has received grant funding/speaker fees from and/or has participated in advisory boards for AbbVie, Galapagos, Janssen, and Pfizer.