Introduction

Histologic activity has emerged as an aspirational therapeutic goal in IBD management. It is not yet a formal treatment-target in either CD or UC. However, it could be used as an adjunct to mucosal healing to represent a deeper level of healing. Recent studies show that histologic healing is associated with decreased risk of clinical relapse, medication escalation and corticosteroid use, both in ulcerative colitis and Crohn's disease [1,2]. We investigated histologic remission (HR) rates and potential predictors of achieving histologic remission in an IBD cohort.

Aims & Methods

We conducted a retrospective subgroup analysis of data collected from IBD patients enrolled in an ongoing prospective cohort study. Clinical, biological, endoscopic data (including the Mayo endoscopic subscore and SES-CD score) and histopathology results were available at multiple time-points for the enrolled patients (annual visits). Mucosal healing was defined as SES-CD <3 or Mayo endoscopic score=0[3]. Histologic healing was defined as microscopic normalization of mucosal biopsies.

Results

219 patients (88 CD, 131 UC) were enrolled in our study and were prospectively followed for a median length of 2 years (range 0-5 years), totaling 452 study visits. Mucosal healing was recorded for 51 (27 UC, 24 CD, 23,2%) patients at 76(16%) different study visits. Overall, only 35(15%) patients achieved histologic healing. In the mucosal healing subgroup, histologic remission was achieved in 30(58%) patients. After logistic regression analysis, none of the investigated factors was associated with histologic remission.

Conclusion

Mucosal healing and endoscopic remission rates are low in real-life settings. Frequently used patient and disease related factors, including mucosal healing are not reliable predictors for histologic remission.

References

[1] Christensen B, Erlich J, Gibson PR, Turner JR, Hart J, Rubin DT. Histologic Healing Is More Strongly Associated with Clinical Outcomes in Ileal Crohn's Disease than Endoscopic Healing. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2518-2525.e1. doi: 10.1016/j.cgh.2019.11.056. Epub 2019 Dec 5.
[2]Battat R, Duijvestein M, Guizzetti L, Choudhary D, Boland BS, Dulai PS, Parker CE, Nguyen TM, Singh S, Vande Casteele N, Pai RK, Feagan BG, Sandborn WJ, Jairath V. Histologic Healing Rates of Medical Therapies for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Am J Gastroenterol. 2019 May;114(5):733-745. doi: 10.14309/ajg.0000000000000111.
[3] Turner D, Ricciuto A, Lewis A, D'Amico F, Dhaliwal J, Griffiths AM, Bettenworth D, Sandborn WJ, Sands BE, Reinisch W, Schölmerich J, Bemelman W, Danese S, Mary JY, Rubin D, Colombel JF, Peyrin-Biroulet L, Dotan I, Abreu MT, Dignass A; International Organization for the Study of IBD. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021 Apr;160(5):1570-1583. doi: 10.1053/j.gastro.2020.12.031. Epub 2021 Feb 19. PMID: 33359090.

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

Inflammatory Bowel Diseases (IBD) can lead to various complications, with Acute Severe Colitis (ASC) being among the most critical. ASC is a medical and surgical emergency that poses a significant risk to life, necessitating prompt and effective diagnosis and management. The first-line treatment typically involves intravenous corticosteroids. However, some cases are resistant to corticosteroids and require second-line medical therapy or immediate surgical intervention.

Aims & Methods

The objective was to identify factors associated with the failure of first-line medical treatment in patients with ASC. A retrospective descriptive and analytical study was conducted over ten years (January 2014 to March 2024) in the gastroenterology department of Charles Nicolle Hospital. The study included patients with IBD complicated by ASC, defined by the Truelove and Witts criteria and a Lichtiger score greater than 10.Patients with bacterial superinfection were not included.

Results

Forty-five patients over 18 years old were included, with a mean age of 37.87 years (range: 18–74 years). There was a slight female predominance (53%), with a male-to-female ratio of 0.87. In 31% of cases, ASC was the initial presentation of the disease. Endoscopic signs of severity at admission were observed in 49% of patients. All patients received intravenous corticosteroid therapy with hydrocortisone hemisuccinate as the first-line treatment. The response rate to first-line treatment was 64.5%. Second-line medical therapy was administered to 24.4% of patients, consisting of cyclosporine in 11.1% and infliximab in 13.3%. Five patients (11.1%) underwent subtotal colectomy due to corticosteroid failure.
In univariate analysis, factors associated with corticosteroid failure included male gender (p=0.011), absence of extraintestinal manifestations (p=0.017), higher average number of stools on the first day (p=0.013), Lichtiger score >10 on the third (p=0.011) and fifth day (p<0.001), hemoglobin levels >11 g/dL on the first day (p<0.001), >10 g/dL on the third day (p=0.009), >9 g/dL on the seventh day (p=0.013), white blood cell count >10,000/mm³ on the first day (p=0.008), >12,000/mm³ on the third (p=0.001) and seventh day (p=0.004), C-reactive protein (CRP) level >30 mg/L on the seventh day (p=0.005), and persistent endoscopic signs of severity after three to five days of corticosteroid therapy (p=0.001).
Multivariate Analysis showed that only the presence of severe endoscopic signs on follow-up endoscopy after three to five days of corticosteroid therapy was predictive of corticosteroid failure (Odds Ratio = 42.2; p=0.028).

Conclusion

Acute Severe Colitis is a potentially life-threatening complication. The presence of severe endoscopic signs after five days of corticosteroid therapy should prompt the initiation of second-line therapy. Understanding the predictive factors for corticosteroid failure is essential for individualized management to improve both immediate and long-term outcomes.

Disclosure

The authors declare no conflicts of interest.

Introduction

Biologic therapies such as anti-TNF-alpha agents (infliximab, adalimumab), interleukin modulators, and gut-selective integrin antagonists like vedolizumab have significantly improved outcomes in inflammatory bowel disease (IBD), leading to enduring remission, better quality of life, and reduced surgical intervention and hospitalizations. However, many patients may eventually lose response, often due to factors like the formation of anti-drug antibodies, altered drug metabolism, or individual patient characteristics. Dose escalation—by increasing dosage or reducing intervals—is commonly used to counteract this loss, especially for anti-TNF therapies guided by therapeutic drug monitoring. Vedolizumab poses a greater challenge in this regard due to the lack of standardized monitoring protocols. We aimed to investigate the effectiveness of dose-escalated infliximab, adalimumab, and vedolizumab in IBD patients who worsened after initial response, evaluating outcomes such as treatment persistence and clinical remission, to guide more personalized, cost-effective treatment strategies.

Aims & Methods

We conducted a retrospective analysis of IBD patients who underwent Infliximab (IFX), vedolizumab, or adalimumab (ADA) therapy dose escalation between 2020-2024 at a tertiary IBD centre. Primary outcomes included clinical remission using disease activity scores (Simple Clinical Colitis Activity/SCCAI Index for UC, Harvey-Bradshaw Index/HBI for CD), biochemical markers (CRP, faecal calprotectin) and treatment persistence, evaluated at 3-12 months, 12 months, and annually up to 36 months post-escalation.

Results

A total of 155 patients (median age 31 years, 46% female) were included, of which 89 patients (57%) were prescribed dose-escalated IFX, 48 patients (31%) were prescribed dose-escalated ADA and 18 patients (12%) were prescribed dose-escalated Vedolizumab. Of those included, 118 patients (76%) had Crohn’s disease, 36 patients (23%) had ulcerative colitis (UC) and 1 patient (1%) had indeterminate disease. Indications for dose escalation included secondary loss of response (SLOR) (105/155; 68%) and/or low drug levels (65/155; 42%). Dose-escalated IFX led to significant improvements in disease activity scores at 3 months (HBI: p=0.002; SCCAI: p=0.0003). Improvement in SCCAI was maintained at 12 months (p=0.00007), 2 years (p=0.0008) and 3 years (p=0.025). Improvement in HBI was maintained at 2 years (p=0.01) and 3 years (p=0.049). Significant improvement in CRP following dose-escalated IFX was reported at 3 months (p=0.011), 12 months (p=0.004), 2 years (p=0.006) and 3 years (p=0.03). Dose-escalated ADA led to a significant improvement in HBI at 3 months (p=0.023). This improvement was maintained at 12 months (p=0.005) and 2 years (p=0.008). Early improvement in faecal calprotectin was reported at 3 months (p=0.046). Significant initial improvement in SCCAI following dose-escalated Vedolizumab was reported at 3 months (p=0.043). This improvement was not maintained at any further follow-up points (p>0.05). Minor adverse events were reported in 3 patients receiving dose escalated ADA and in 6 patients receiving dose escalated IFX.

Conclusion

Our study demonstrates that biologic dose escalation is an effective and safe mechanism to recapture clinical remission, with high rates of treatment persistence.

Introduction

Upadacitinib has shown to be more effective than placebo for treating extraintestinal manifestations (EIM) in post-hoc analyses. However, real-world data on the effectiveness of upadacitinib in patients with inflammatory bowel disease (IBD) and EIMs are lacking.

Aims & Methods

A multicenter, retrospective and observational study was conducted at 19 Spanish hospitals. Patients with IBD and active EIMs when initiating upadacitinib were eligible. The primary outcome was EIM improvement at weeks 8-12. The EIM assessment was based on the physician's subjective evaluation and categorized into clinical remission, partial response, nonresponse and worsening. EIM improvement was defined as either clinical remission or partial response. Axial arthropathy, peripheral arthropathy, pyoderma gangrenosum, erythema nodosum, sweet syndrome, aphthous stomatitis, uveitis, episcleritis, primary sclerosing cholangitis and bronchiectasis were considered. In patient experiencing >1 EIM, all had to be resolved or improved to be considered. If not, the worst outcome was recorded. Patients’ visits were scheduled at weeks 0, 8-12, and 6 months. Multivariate analysis was performed to find factors associated with EIM improvement at w8-12.

Results

A total of 160 patients were included, 120 patients with Crohn’s Disease (75.6%), 90 females (56.3%) with a median age of 46.6 years (IQR 37.9-56.7). Upadacitinib was initiated in one hundred twenty-six (78.8%) patients due to EIMs and luminal activity and 35 patients (21.3%) exclusively due to EIMs. All patients were bio-experienced with 84 patients previously treated with ≥3 biologics (52.5%). Baseline EIMs assessment was for at least 1 EIM in 107 patients (66.9%), 42 patients presented 2 EIMs (26.3%) while 11 patients (6.9%) experienced ≥ 3 EIMs.
At w8-12, 99 patients (61.9%) achieved EIM improvement, 40 patients (25 %) clinical remission, 58 patients (36.9%) partial response, 58 patients (36.5 %) nonresponse and worsening in 3 patients. Patients initiating Upadacitinib due to exclusively active EIMs was associated with EIM improvement at weeks 8-12 (OR 2.99 95% CI 1.06-8.42; p=0.04). IBD clinical remission at w8-12 was achieved in 75 patients (61%).
Evaluation at 6 months was available for 103 patients, 73 patients (70.9%) presented EIM improvement, 41 patients (39.8%) clinical remission, 32 patients (31.1%) partial response, 20 patients (19.4%) nonresponse and 10 patients (9.7%) worsening. IBD clinical remission at 6 months was achieved in 51 patients (62.2%).
During the follow-up, Upadacitinib was ceased in 27 patients (16.9%). Adverse events were detected in 39 patients (24.3%) and 7 patients (4.4%) experienced worsening of previous inactive EIMs.

Conclusion

Upadacitinib was highly effective in the short term for treating bio-experienced patients with active EIMs, particularly for patients without luminal activity

Disclosure

No conflict

Introduction

Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking drug indicated for ulcerative colitis (UC), is administered intravenously at Weeks 0, 2, and 6, then every 8 weeks (Q8W). Dose escalation to every 4 weeks (Q4W) may recapture response to treatment in ~50% of patients with inadequate response. Real-world outcomes and factors associated with VDZ dose escalation from Q8W to Q4W remain underexplored.

Aims & Methods

Adults with moderate to severe UC initiating VDZ Q8W maintenance were prospectively followed in a Canadian patient support program (2015-2023). Two cohorts were included: 1) patients escalated to Q4W during maintenance after week 14 infusion (Q8W>Q4W maintenance) and 2) patients maintained on Q8W treatment for ≥2 years without escalating (Q8W maintenance). Rates of clinical remission (partial Mayo Score [PMS]<3) were described by prior biologic experience. Associations between baseline characteristics and clinical remission 3 months after Q4W dose escalation were assessed using Wilcoxon rank sum test and Fisher’s exact test. Treatment persistence at 12 and 24 months after initiation and dose escalation were evaluated in Q8W>Q4W maintenance using Kaplan-Meier survival analysis.

Results

373 patients (68% bio-naïve) and 300 patients (72% bio-naïve) were included in the Q8W>Q4W maintenance and Q8W maintenance cohorts, respectively. Median age at treatment initiation was 47 years in Q8W>Q4W maintenance and 48 years in Q8W maintenance. Both cohorts had a median baseline PMS score of 6. In Q8W>Q4W maintenance, median disease duration before treatment initiation was 4 years and median follow-up was 19 months. In Q8W maintenance, median disease and follow-up duration were 5 years and 35 months, respectively. 14 weeks post-treatment initiation, rates of remission in Q8W>Q4W maintenance were 49% (bio-naïve) and 42% (bio-experienced), and in Q8W maintenance were 72% (bio-naïve) and 70% (bio-experienced) (Table 1). Among patients in Q8W>Q4W maintenance not in remission when dose escalating, 40% achieved clinical remission 3 months after dose escalation. These patients were older at treatment initiation (49 vs. 41 years, p=0.043) and had longer disease duration (6 vs. 3 years, p=0.029) than those who did not achieve remission. In Q8W>Q4W maintenance, 12- and 24-month treatment persistence after initiation was 83% and 48% (bio-naïve) and 79% and 51% (bio-experienced), respectively. After dose escalation, 12- and 24-month treatment persistence was 48% and 39% (bio-naïve) and 53% and 45% (bio-experienced).

Conclusion

Patients with UC who underwent VDZ Q8W>Q4W dose escalation achieved lower rates of remission than those remaining on Q8W, regardless of prior bio-experience. Age at treatment initiation and disease duration were significantly associated with remission among those who escalated to Q4W.

Disclosure

JFL: AbbVie, BMS, Janssen, Frenesius-Kabi, Pfizer, Sandoz, Takeda.
EJB: Participation in advisory boards or speaker services: Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, Eli Lilly, BMS, Grant/Research: Janssen, Abbvie, Any other investment or relationship that could be judged by a reasonable and knowledgeable participant to have the potential to influence the content of the training activity, Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, BMS.
AHS: Advisory Board Membership/Consultant: Abbvie, Amgen, BioJAMP, BMS, Celltrion, Fresenius Kabi, Janssen, McKesson, Mylan Pharmaceuticals, Organon, Pendopharm, Roche, Pfizer, Sandoz, Takeda, Viatris, Speakers’ Bureau: Abbvie, Amgen, Ferring, Fresenius Kabi, Janssen, Organon, Pfizer, Sandoz, Takeda, Research Grants: Abbvie, Arena, Celgene/BMS, Genentech, Janssen, Roche, Takeda.
PW: Personal fees from AbbVie, Ferring, Biogen, and Janssen
MJA, AW, RW: were employees of Takeda Canada Inc. at the time of the study.
RM, JW, CP: were employees of Pentavere Research Group Inc. at the time of the study.
LPB: Consulting from 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, HACPharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, and Vectivbio; grants from Takeda, Fresenius Kabi, and Celltrion; and lecture fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, and Medac.
BB: Advisor/Speaker: Ferring, Janssen, Abbvie, Takeda, Pfizer, BMS, Merck, Sandoz, Organon, Lifelabs, Celltrion. Advisor: Alimentiv, Gilead, Iterative Health, AMT, Celgene, Merck, Amgen, Pendopharm, Eli Lilly, BMS, Fresenius Kabi, Mylan, Viatris, Bausch Health, Celltrion Healthcare, BioJamp Pharma, Eupraxia. Research support: Janssen, Abbvie, GSK, BMS, Amgen, Genentech, Merck. Stock Options: Qu Biologic.