Introduction

Mirikizumab [(miri), a p19-directed IL-23 antibody] has been shown to be effective in patients with moderately to severely active ulcerative colitis (UC) in Phase 3, randomised, double-blind, placebo-controlled trials (LUCENT-1 NCT03518086; LUCENT-2 NCT03524092).¹ Given the importance of understanding treat-to-target strategies, the relationship between improved histologic and endoscopic endpoints and improvement of the inflammatory biomarkers faecal calprotectin (fCal) and C-reactive protein (CRP) was studied within miri-treated patients enrolled in the programme.

Aims & Methods

This analysis focused on miri-treated patients (n=868) from the induction study receiving intravenous (IV) every 4 weeks (Q4W) until week (W)12 and miri induction responders at week W12, who were rerandomised for the maintenance period, receiving subcutaneous miri (n=365) Q4W up to W52. The relationship between achieving histologic-endoscopic mucosal improvement (HEMI), histologic-endoscopic mucosal remission (HEMR) (definitions in Tables) and improvement of fCal (≤250µg/g) and CRP (≤6mg/L) levels at W12 and W52 was explored using Fisher’s exact tests.

Results

At W12, a significantly higher percentage of miri-treated patients achieving HEMI (n=235/868) had normalised fCal and CRP values (76.2% and 88.5%), compared to miri-treated patients who did not achieve HEMI (n=633/868) (21.8% and 72.7%, both p<0.001; Table). Similarly, a higher proportion of patients achieving HEMR (n=193/868) had normalised fCal and CRP values (79.3% and 89.6%), compared to those who did not achieve HEMR (n=675/868) (24.3% and 73.3%, both p<0.001; Table). At W52, a significantly higher percentage of the miri induction responder patients rerandomised to miri achieving HEMI (174/365) had normalised fCal and CRP values (74.1% and 87.9%), compared to patients not achieving HEMI (191/365) (32.5% and 61.3%; both p<0.001). Similarly, at W52, a higher proportion of patients achieving HEMR (n=158/365) had normalised fCal and CRP values (76.6% and 88.0%), versus patients not achieving HEMR (n=207/365) (33.8% and 63.3%; both p<0.001, Table).

Conclusion

At both W12 and W52, patients treated with miri who achieved HEMI or HEMR showed statistically significant improvements in fCal and CRP levels. This suggests that CRP and fCal may be useful markers of histology and endoscopy outcomes after induction and maintenance with miri.

References

1. Magro et al., MP245 Efficacy of mirikizumab in resolving active histologic inflammation in Ulcerative Colitis in Lucent-1 induction and Lucent-2 maintenance trials (2022), UEG Week Moderated Posters. United European Gastroenterol J, 10: 185-472.

Disclosure

R. Panaccione has received speaker fees and/or served as a consultant and/or advisory board member for: Abbott, AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmo Pharmaceuticals, Eisai, Elan Pharma, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Oppilan Pharma, Pandion Therapeutics, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma and UCB Pharma; and has received research and/or educational support from: AbbVie, Ferring Pharmaceuticals, Janssen, Pfizer and Takeda; C. Sapin, F. Chan-Diehl and R. Moses are employees and shareholders of: Eli Lilly and Company;
B. Siegmund has served as a consultant and/or speaker for: AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Boehringer Ingelheim, CED Service GmbH, Celgene, Dr Falk Pharma, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Janssen, Novartis, Pfizer, Prometheus Therapeutics and Takeda;
A. Walsh has received grant and/or research support from: AbbVie and Pfizer; and has received consultancy fees from: AbbVie, Eli Lilly and Company, Novartis and UCB Pharma;
T. Kobayashi has served as a speaker, consultant and advisory board member for: AbbVie, Ajinomoto Bio-Pharma, Alfresa Pharma, Asahi Kasei Pharma, Astellas, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eisai, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Gilead Sciences, Janssen, JIMRO, Kyorin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, Thermo Fisher Scientific and Zeria Pharmaceutical; and has received research funding from: AbbVie, ActivAid, Alfresa Pharma, Asahi Kasei Pharma, EA Pharma, Google, JMDC, Kyorin, Mochida Pharmaceutical, Nippon Kayaku, Otsuka, Sekisui Medical, Thermo Fisher Scientific and Zeria Pharmaceutical;
P. S. Dulai has served as a consultant for: AbbVie, Abivax, Addiso, Bristol Myers Squibb, Eli Lilly and Company, Janssen, Pfizer, Precidiag, Prometheus and Takeda;
S. Travis has received grants from: AbbVie, BUHLMANN Diagnostics, ECCO, Eli Lilly and Company, Ferring Pharmaceuticals, International Organization for the Study of Inflammatory Bowel Disease, Janssen, Merck Sharp & Dohme, Norman Collision Foundation, Pfizer, Procter & Gamble, Schering-Plough, Takeda, UCB Pharma, Vifor Pharma and Warner Chilcott; and reports other disclosures from: Abacus Pharma, AbbVie, Actial Farmaceutica, ai4gi, Alcimed, Allergan, Amgen, Aptel, Arena Pharmaceuticals, Asahi Kasei Pharma, Aspen Pharmacare, Astellas, AstraZeneca, Atlantic Pharmaceuticals, Barco, Biocare Medical, Biogen, BL Pharma, Boehringer Ingelheim, Bristol Myers Squibb, BUHLMANN Diagnostics, Calcico Therapeutics, Celgene, Cellerix, Cerimon Pharmaceuticals, ChemoCentryx, Chiesi, Cisbio, Comcast, Coronado Biosciences, Cosmo Pharmaceuticals, Dr Falk Pharma, Ducentis BioTherapeutics, Dynavax Technologies, Elan, Eli Lilly and Company, Enterome, Equillium, Ferring Pharmaceuticals, Galapagos NV, Genentech/Roche, Genzyme, Gilead Sciences, GlaxoSmithKline, Glenmark Pharmaceuticals, Grünenthal, GW Pharmaceuticals, Immunocore, Indigo Biosciences, Janssen, Lexicon Pharmaceuticals, Medarex, MedTrix, Merck, Merrimack Pharmaceuticals, Mestag Therapeutics, Millennium Pharmaceuticals, Neovacs, Novartis, Novo Nordisk, NPS Pharmaceuticals/Nycomed, Ocera Therapeutics, OPTIMA Pharma, Origin Pharma, Otsuka, Procter & Gamble, Palau Pharma, Pentax Medical, Pfizer, PharmaVentures, Phesi, Phillips Pharma Group, Pronota, Proximagen, Resolute, Robarts Clinical Trials, Sandoz, Santarus, Satisfai Health, Sensyne Health, Shire, Sigmoid Pharma, Sorriso Pharmaceuticals, Souffinez, SynDermix, Synthon, Takeda, Theravance Biopharma, TiGenix, Tillotts Pharma AG, Topivert, Trino Therapeutics with Wellcome Trust, TxCell, UCB Pharma, Vertex Pharma, VHsquared, Vifor Pharma, Warner Chilcott and Zeria Pharmaceutical

Introduction

There is limited research on HealthCare Resource Utilization (HCRU) and costs among patients receiving ustekinumab (UST) treatment. This study aims to evaluate HCRU and costs in patients with Crohn's Disease (CD) and Ulcerative Colitis (UC) who received UST treatment through Janssen’s BIOADVANCE® patient support program (PSP) in Ontario, Canada.

Aims & Methods

The primary objective of this study is to compare annual HCRU and costs (excluding medication expenses) during a period of one year before initiating UST treatment and up to four years post-initiation.
This retrospective observational study analyzed data from a consecutive cohort of Ontario CD and UC patients who initiated UST treatment through Janssen’s BIOADVANCE® PSP.
Patients were indexed based on their first recorded UST prescription fill, spanning from January 1, 2017, to July 31, 2021, for CD patients, and from February 1, 2020, to July 31, 2021, for UC patients.
Quasi-identifiers (date of birth, gender, postal code, indication) were used for probabilistic linkage of patients in BIOADVANCE® PSP to those in Ontario Crohn’s and Colitis Cohort (OCCC) from the Institute for Clinical Evaluative Sciences (ICES). A follow-up period for up to four years post-index date was used to assess all-cause and IBD-specific HCRU and costs. A 12-month lookback period was utilized to establish baseline demographic and clinical profiles and baseline HCRU and costs. A mixed gamma regression model was employed to compare costs before and after UST initiation. IBD-specific HCRU and costs included general practitioner visits, specialist visits, emergency department visits, inpatient hospitalization, and same-day surgeries. IBD-specific HCRU and costs were identified based on the IBD-specific diagnosis code as the most responsible diagnosis.

Results

A probabilistic linkage of 88.1% for CD cases and UC cases was achieved. A total of 2,279 patients with CD and 626 patients with UC were included. UST was the initial biologic therapy for 35.72% and 22.68% of patients with CD and UC, respectively. The average time since diagnosis was 10.72 years for CD and 8.07 years for UC. The mean age was 45.6 ± 17.2 years for UC patients and 45.7 ± 16.2 years for CD patients. UC showed a male-female ratio of 56% to 44%, whereas for CD, it was 46% to 54%.
IBD-specific HCRU and costs significantly decreased post-UST initiation in Years 1, 2, and 3 for both CD patients and UC patients, compared to baseline.
[See Table]

Conclusion

Initiation of UST through the BIOADVANCE® PSP was related to substantial reductions in IBD-specific HCRU and costs among patients with CD and UC in Ontario, Canada. These findings underscore the potential benefits of UST as an advanced therapy in IBD treatment, in managing CD and UC, and support its role in optimizing patient outcomes while reducing the burden on healthcare resources.

References

Data source:

1. Janssen BIOADVANCE® Database (January 1, 2016 – March 31, 2023) and Ontario Crohn’s and Colitis Cohort (OCCC) data in Institute for Clinical Evaluative Sciences (ICES).

Disclosure

Laura Targownik has received grants from AbbVie Canada, Janssen Canada and Pfizer Canada; consulting fees from AbbVie, Takeda, Janssen, Pfizer, Amgen, Viatris, Fresenius Kabi, Bristol Myers Squibb, Sanofi, Lilly; honoraria from AbbVie, Takeda, Janssen, Pfizer, Amgen, Viatris, Fresenius Kabi, Bristol Myers Squibb, Sanofi; has participated on a data safety monitoring board of advisory board for GoodCap Pharmaceuticals, Pfizer, Takeda, Janssen, Bristol Myers Squibb, and is a member of the Crohn’s and Colitis Canada Scientific and Medical Advisory Board; Eneda Pone, Martin G. Latour, and Kasra Boyerahmadi are Janssen employee, and Huijuan Yang, Juejing Ling, Ali Tehrani, and Shane Golden are employee of IQVIA, and John K Marhsall is a consultant for AbbVie, Amgen, Bausch Health, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, Lilly, Organon, Paladin, Pfizer, Pharmascience, Roche, Sandoz, Takeda, Viatris and a speaker for AbbVie, Amgen, Bausch Health, Ferring, Fresenius Kabi, Janssen, Lupin, Organon, Pfizer, Pharmascience, Roche, Takeda.

Introduction

Few population-based studies have investigated the long-term surgery rates of Crohn’s disease (CD). The present study is a continuation of the Veszprem IBD population based cohort with a follow-up since 1977.

Aims & Methods

Our aim was to analyze the long-term disease course and surgery rates over different therapeutic eras in a prospective population-based database from Veszprem Province, including incident CD patients. Patient inclusion was between January 1, 1977 and December 31, 2018; follow-up ended December 31, 2020. Both in-hospital and outpatient records were collected and comprehensively reviewed at diagnosis and during clinical follow-up. Immunomodulators became widespread in Hungary from the mid-1990s, while biological therapies have been covered by the National Health Insurance Fund since 2008. Surgery rates were examined in three different eras based on time of diagnosis: cohort-A, 1977-1995; cohort-B, 1996-2008; and cohort-C, 2009-2018.

Results

Data of 946 incident CD patients were analyzed (male/female: 496/450; median age at diagnosis:28 years(y) [IQR: 22-40]), with a median of 15y(IQR 9-21) follow-up. Overall immunosuppressive therapy use was increasing by time (48.0%/62.4%/65.5%), as well as the probability of biological therapy initiation within 5 years of diagnosis (0.0±0%/7.3±1.2%/22.7±2.2%) in cohorts A/B/C. The probability of disease behavior progression from luminal (B1) disease to stenosing or penetrating phenotype (B2/B3) was significantly decreasing (27.1±SD5.3%/ 21.5±2.5%/11.3±2.2% in cohorts A/B/C after 5 years [pLogRank<0.001]). The probability of first resective surgery between cohorts A/B/C were 33.3±3.8%/26.5±2.1%/28.1±2.4% after 5 years; 46.1±4.1%/32.6±2.2%/33.0±2.7% after 10 years; and 59.1±4.0%/41.4±2.6% (cohorts A/B) after 20 years. There was a significant decrease in surgery risk between cohorts A and B [pLog Rank=0.002]. Surgery risk remained similar between cohorts B and C [pLog Rank=0.665]. The cumulative probability of re-resection in cohorts A/B/C was also decreasing (17.3±4.1%/12.6±2.6%/4.7±2.0% after 5 years [pLog Rank=0.001]). A cox-regression multivariate analysis showed that stenosing or penetrating disease (B2/B3) behavior (HR 4.52; 95%CI 3.60-5.68; p<0.001) and ileal (L1) location at diagnosis (HR 1.30; 95%CI 1.05-1.61; p=0.016) were independent predictors of resective surgery.Table 1.

Table 1. Predictive factors for first resective surgery in incident CD patients diagnosed between 1977 and 2018 – Cox-regression analysis

Conclusion

We report a gradual decline in reoperation rates and disease behavior progression in CD over time with the lowest values in the biological era. In contrast, there was no further decrease in the probability of first major resective surgery after the immunosuppressive era.

Introduction

The LIR!C trial demonstrated that laparoscopic ileocaecal resection (ICR) is a cost-effective alternative to infliximab therapy (IFX) in patients with uncomplicated ileocaecal Crohn’s disease (CD), with comparable quality of life outcomes. The aim of this study was to assess the 10-year follow-up of patients enrolled in the LIR!C trial.

Aims & Methods

This retrospective follow-up study included patients from the original LIR!C trial, a multicentre randomized controlled trial comparing ICR to IFX treatment in patients with ileal CD. Long term follow-up data were collected between February 3 and April 14, 2025. Data extraction was focused on initiation or switch of IBD treatments (corticosteroids, immunomodulators and/or advanced medical therapies) and (re)-resections. The follow-up period ranged from trial enrolment to the last visit with the gastroenterologist or surgeon. Primary outcomes were: (1) proportion of patients in clinical remission without therapy switch (no medical therapy or re-resection in the ICR group, and continuation or the cessation of IFX in case of remission in the IFX group), and (2) therapy-free remission, defined as clinical remission without IBD medication and (re)resections.

Results

Follow-up data were available from 60 ICR patients and 57 IFX patients (87% of 134 patients originally included). The median follow-up time was 12 years (IQR 9-14). The clinical remission rate without therapy switch was 40% in the ICR group compared to 26.3% in the IFX group (p=0.117). Of the 60 ICR patients, 24 (40%) had no additional therapy, 13 (21.7%) received an immunomodulator, 18 (30%) biological therapy and 5 (8.3%) underwent a second resection after biological treatment. In the IFX group, 33 (57.9%) required an ICR of whom 25 (75.8%) had previously received second-line biological treatment. Additionally, 7/57 patients (12.3%) were therapy free, 8 (14%) continued IFX treatment, 6 (10.5%) received other biological treatment, and 3 (5.3%) switched to an immunomodulator. Therapy-free remission was significantly higher in the ICR group when compared to the IFX group (40% vs 12%, p < 0.001).

Conclusion

After 10 years of follow-up, the clinical remission rate without therapy switch was comparable between both groups, highlighting the long-term durability of both treatment approaches. The majority of IFX patients needed ICR within 10 years of follow-up. 40% of the ICR group did not require any additional therapy further supporting ICR as first-line treatment option in ileal CD.

References

Ponsioen, C. Y., de Groof, E. J., Eshuis, E. J., Gardenbroek, T. J., Bossuyt, P. M. M., Hart, A., Warusavitarne, J., Buskens, C. J., van Bodegraven, A. A., Brink, M. A., Consten, E. C. J., van Wagensveld, B. A., Rijk, M. C. M., Crolla, R. M. P. H., Noomen, C. G., Houdijk, A. P. J., Mallant, R. C., Boom, M., Marsman, W. A., Stockmann, H. B., … LIR!C study group (2017). Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial. The lancet. Gastroenterology & hepatology, 2(11), 785–792. https://doi.org/10.1016/S2468-1253(17)30248-0

Disclosure

GD'H served as a consultant for AbbVie, Alimentiv, AstraZeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Exeliom Biosciences, Johnson & Johnson, Pfizer, and Takeda; and has received speakers bureau fees from AbbVie, Eli Lilly, Pfizer, Bristol Myers Squibb, and Takeda.

Introduction

Microscopic colitis (MC) has been associated to various autoimmune diseases. Previous studies on the association between MC and psoriasis have focused on psoriasis as a risk factor for MC. Data from large scale cohort studies investigating the risk of future psoriasis in MC, however, are lacking.

Aims & Methods

We aimed to examine the association between MC and psoriasis by conducting a nationwide, population-based, matched cohort study in Sweden from 2007-2021. In total, we identified 8,404 patients with biopsy-verified MC (diagnosed in 2007-2017), 37,303 matched reference individuals, and 8,381 siblings without MC. Information on MC was obtained through the ESPRESSO cohort (a histopathology database containing data on all gastrointestinal biopsies in Sweden from 1965-2017). Data on incident psoriasis was gathered from the National Patient Register. Using Cox regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

During a median follow-up of 9.2 years (interquartile range=6.7-11.7), 179 MC patients and 440 reference individuals were diagnosed with psoriasis (241 vs 131 events per 100,000 person-years), corresponding to one extra case of psoriasis in 91 patients with MC followed for 10 years. After adjustment for the matching variables (birth year, sex, county of residence and calendar period) and level of education – as a proxy for socioeconomic status - we computed an aHR of 1.82 (95%CI=1.53-2.17). Stratifying by sex, estimates were similar and when examining the aHR across different lengths of follow-up, we found significantly elevated estimates up to 10 years after MC diagnosis. Compared to MC-free siblings, the aHR was 1.85 (95%CI=1.36-2.51).

Conclusion

Patients with MC are at an almost doubled risk of being diagnosed with psoriasis compared to the general population. Our findings suggest clinicians should consider psoriasis in MC patients with skin lesions.

Disclosure

Dr. Ludvigsson coordinates a study on behalf of the Swedish IBD quality register (SWIBREG). That study has received funding from the Janssen corporation. Dr Ludvigsson has also received financial support from MSD to develop a paper reviewing national healthcare registers in China. Dr. Ebrahimi has served as an advisory board member for Boehringer Ingelheim. AS has received consultancy fees from ICON plc, Abbvie, Novarits, and Eli Lilly. AS has received lecture fees from Janssen Cilag and UCB.