Introduction

Mirikizumab is a monoclonal antibody directed against the p19 subunit of interleukin (IL)-23 approved for the management of patients with moderate-to-severe ulcerative colitis (UC). Currently, there is no large study supporting the effectiveness of mirikizumab in UC in a real-life setting.

Aims & Methods

This study aims to evaluate the effectiveness and safety of mirikizumab in real-life setting. This was a retrospective multicenter cohort study of a prospectively collected database including adult patients with confirmed diagnosis of UC treated with mirikizumab according to clinical practice. Patients were enrolled in three third-level italian centers (San Raffaele Hospital, Humanitas Research Hospital, and Federico II Hospital) from June 2024 to February 2025. All patients with at least 3 months of follow-up after therapy initiation were eligible. The primary outcome was the clinical remission rate (defined as partial Mayo Score (pMS) < 2 with a rectal bleeding subscore of 0) at week 12. Secondary outcomes included changes in bowel urgency (measured by the Numeric Rating Scale (NRS) urgency score), changes in serum C-reactive protein (CRP) and fecal calprotectin (FC) levels from week 0 to 12, safety profile of mirikizumab during induction therapy.

Results

In total 100 patients (60% male, with median age 48.53 ± 15.36) with UC were included. Most patients had a left-sided colitis (55, 55%) or a pancolitis (41, 41%). Most patients (81, 81%) were already treated with at least one advanced therapy before starting mirikizumab (including 28 patients treated with ustekinumab, 28%). A fifth of patients (19, 19%) were exposed to ≥ 4 advanced therapies. A significant reduction in pMS was observed from baseline to week 12 (median [IQR]: 4.0 [1.75–6.0] vs. 2.0 [0.0–4.0]; Wilcoxon signed-rank test: W = 312, Z = -5.35, p < 0.00001, n = 69) with 48 (48%) patients reaching clinical remission at week 12. Moreover, a significant improvement in bowel urgency was observed from baseline to week 12 (t(98) = 6.58, p = 2.28×10⁻⁹), with a moderate-to-large effect size (g = 0.66). From baseline to week 12, both FC and CRP levels showed significant reductions following treatment (FC: V = 1153.00, p = 2.4×10⁻⁵, r = 0.67; CRP: V = 680.00, p = 0.03, r = 0.37). Effect sizes were large for FC and moderate for CRP with paired data from 53 and 47 patients being analyzed, respectively. In total, 39 patients (39%) underwent extended induction while 3 patients (3%) discontinued the drug at week 12. There were no adverse events leading to discontinuation or death. Two mild adverse events were reported (upper respiratory tract infection in 1 patient and pyrexia in 1 patients). No significant changes were observed in liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels over time (AST: χ²(2) = 0.21, p = 0.90, W = 0.005; ALT: χ²(2) = 3.73, p = 0.16, W = 0.08).

Conclusion

This is the largest study demonstrating the effectiveness and safety of mirikizumab in inducing clinical remission in patients with UC in a real-life setting. Patients treated with mirikizumab achieved a significant reduction in bowel urgency, FC and CRP levels. No statistically significant increase in liver toxicity was detected during the induction treatment.

Disclosure

F. D'Amico. OM Nardone, A. Zilli, M. Allocca, S. Danese, L. Peyrin-Biroulet and A. Armuzzi have served as speaker and advisory board member for Lilly

Introduction

Gastric cancer remains one of the leading causes of death internationally and a major health concern in the United States (US). To develop better prevention strategies, this study quantifies trends in gastric cancer related mortality, stratified by age, sex, region, urbanity, and race over two decades.

Aims & Methods

Our study used the CDC WONDER database to analyze death certificates from 1999 to 2022 across the U.S. ICD codes C16.0-C16.9 were used to identify the relevant cases. Demographic variables such as sex, race, age, urban-rural classification, and census regions were analyzed. Trends in AAMR were assessed using the Joint Point Regression Program to determine annual percentage changes (APC).

Results

Overall mortality related to malignant stomach neoplasms in the US declined significantly (Table 1) from 79.26 (1999) to 44.81 (2022), with notable periods of steep decrease between 1999–2006 (APC -3.51, 95% CI: -5.16 to -2.78) and 2006–2018 (APC -2.27, 95% CI: -3.55 to -1.83). Men consistently exhibited higher mortality rates than women (overall men: 81.14 vs women: 42.10). Men experienced an initial significant drop from 113.45 to 78.68 (1999–2009, APC -3.55), followed by a slower decrease till 2022 (APC -2.22). Women's mortality showed an initial sharp decline (1999–2008, APC -3.11), then a modest reduction from 2008–2018 (APC -1.96), plateauing thereafter.

Racially, Non-Hispanic (NH) Black individuals exhibited the highest mortality (109.37), followed by NH Asians/Pacific Islanders (102.47), Hispanic/Latino (91.93), NH American Indian/Alaskan Natives (78.21), and NH White (44.85). NH Blacks demonstrated a marked initial decrease (159.46 to 119.13 by 2017) then plateaued. NH Whites showed a continuous decline (1999–2018), slowing post-2018. Hispanics had two significant declining periods (1999–2011, APC -2.82; 2011–2022, APC -1.56), whereas NH Asians and NH American Indians steadily declined throughout.

Mortality by age was highest among older adults (202.46), followed by middle-aged (60.58) and young adults (40.55). Older adults had two notable decreasing phases (1999–2009, APC -3.56; 2009–2018, APC -2.89), with slower decline afterward. Middle-aged adults showed an initial steep decline (1999–2005, APC -3.65), followed by gradual reduction (2005–2022, APC -0.79). Young adults exhibited minimal, non-significant declines throughout.

Regionally, the Northeast showed highest mortality (64.78), followed by West, South, and Midwest. Both metropolitan and non-metropolitan areas saw significant mortality reductions, with non-metropolitan areas consistently having higher rates overall.

Table 1. Annual Percent Change (APC) in mortality rates by selected demographics, 1999–2022.
APC values are presented with 95% confidence intervals (CI). Asterisk (*) indicates statistically significant APC values (p < 0.05).

Conclusion

Gastric carcinoma has poor prognosis, and although the general trend is decreasing across all socio-demographic areas, further research is required for targeted interventions and health policies for populations at high risk of dying.

References

1. Stahl KA, Olecki EJ, Dixon ME, et al. Gastric cancer treatments and survival trends in the United States. Current Oncology. 2020;28(1):138-151. doi:10.3390/curroncol28010017
2. Kumar RK, Raj SS, Shankar EM, Ganapathy E, Ebrahim AS, Farooq SM. Gastric carcinoma: a review on epidemiology, current surgical and chemotherapeutic options. Gastric Carcinoma-New Insights into Current Management. 2013/1/13 2013;12doi:10.5772/52138
3. Li C, Chen D, Yang H. Trends in incidence, survival and mortality of gastric cancer in the United States: a population-based study, 2001-2015. Asian Pacific Journal of Cancer Prevention: APJCP. 2023;24(6):2011-2020. doi:10.31557/APJCP.2023.24.6.2011
4. Hudler P, Komel R. Clinical Implications of Molecular Heterogeneity of Gastric Cancer. Gastric Cancer. 2017/9/20 2017;doi:10.5772/intechopen.69775
5. Ali H, Ishtiaq R, Tedder B, et al. Trends in mortality from gastrointestinal, hepatic, and pancreatic cancers in the United States: A comprehensive analysis (1999–2020). JGH Open. 2024;8(4):e13064. doi: 10.1002/jgh3.13064

Disclosure

No conflicts of interest to disclose.

Introduction

We conducted a retrospective cohort study comparing the safety of Janus kinase (JAK) inhibitors vs. tumor necrosis factor-a (TNF) antagonists in patients with inflammatory bowel diseases (IBD).

Aims & Methods

Using an administrative claims databasein the U.S, Optum Labs®, we identified patients with IBD who were new users of either JAK inhibitors or TNF antagonists between 2016-2023 and had insurance coverage for at least 1y before and after treatment initiation. We compared the risk of infections (overall, and serious infections requiring hospitalization), venous thromboembolism (VTE) and major adverse cardiovascular events (MACE) between patients treated with JAK inhibitors vs. TNF antagonists through stabilized inverse probability of treatment weighted (IPW) Cox proportional hazards model accounting for baseline disease characteristics, healthcare utilization, comorbidities, and medication exposure.

Results

We included 856 patients treated with JAK inhibitors (age, 47±17y; 82% with ulcerative colitis [UC]; 23% on upadacitinib) and 9422 patients treated with TNF antagonists (age, 45±18y, 44% with UC). JAK inhibitors were associated with higher risk of overall infections (incidence rate [IR], 62.4 per 100-py vs. 37.4 per 100-py; HR, 1.67 [95% CI, 1.44-1.93]), but not serious infections (IR, 4.9 vs. 5.4 per 100-py; HR, 1.02 [0.72-1.44]) compared with TNF antagonists. There was no difference in the risk of VTE (IR, 1.3 vs. 1.2 per 100-py; HR, 0.67 [0.35-1.29]). JAK inhibitors (vs. TNF antagonists) were associated with lower risk of MACE (IR, 0.4 vs. 0.7 per 100-py; HR, 0.37 [0.15-0.96]). Findings were largely stable on subgroup analyses based on type of IBD, type of JAK inhibitors, age and baseline risk of adverse events.

Table 1. Incidence rates and hazard ratios with JAK inhibitors and TNF antagonists in patients with Inflammatory bowel disease

Conclusion

Compared to TNF antagonists, JAK inhibitors were associated with a higher risk of overall infection, no signifcant difference for serioys infection and a lower risk of MACE.

References

1. The Lancet Gastroenterology H. New restrictions on JAK inhibitors in the EU. Lancet Gastroenterol Hepatol 2023;8:1.

2. Ananthakrishnan AN, Murad MH, Scott FI, et al. Comparative Efficacy of Advanced Therapies for Management of Moderate-to-Severe Ulcerative Colitis: 2024 American Gastroenterological Association Evidence Synthesis.

3. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. N Engl J Med 2022;386:316-326.

4. Panes J, D&#39;Haens GR, Sands BE, et al. Analysis of tofacitinib safety in ulcerative colitis from the completed global clinical developmental program up to 9.2 years of drug exposure. United European Gastroenterol J 2024;12:793-801.

Disclosure

DA: No relevant disclosures
KHY: No relevant disclosures
SBP: No relevant disclosures
SWG: No relevant disclosures
CM: Consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol
Myers Squibb, Celltrion, Eli Lilly, Ferring, Forte Biosciences, Fresenius Kabi,
Gilead, Janssen, McKesson, Mirador Therapeutics, Mylan, Pendopharm, Pfizer,
Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's
fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli
Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Organon, Pendopharm, Pfizer,
Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research
support from AbbVie, Eli Lilly, Ferring, Pfizer.
ANA: No relevant disclosures
NS: No relevant disclosures
VJ: Consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena
pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers
Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi,
Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan,
Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma,
Roche, Sandoz, Second Genome,Takeda, Teva, Topivert, Ventyx, Vividion;
speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda,
Fresenius Kabi
RX: No relevant disclosures
SS: Research grants from Pfizer

Introduction

Guselkumab (GUS), interleukin-23p19 subunit inhibitor, has been approved for moderately to severely active Crohn’s disease (CD) in Japan. CNTO1959CRD3003 is a Phase 3, open-label, multicenter study designed to evaluate the safety and efficacy of GUS in Japanese patients with moderately to severely active CD. We report the efficacy of GUS on small bowel lesions.

Aims & Methods

The primary objective was to evaluate safety, and the secondary objective was to evaluate the efficacy of GUS at week 48 (W48). An exploratory objective was to assess the efficacy of GUS for small bowel lesions, evaluated using retrograde balloon-assisted enteroscopy (BAE). Eligible patients in this study were patients with active ileocolonic CD or small bowel CD, as clarified by endoscopic evaluation. GUS 200 mg was administered intravenously on Weeks 0, 4, and 8 and subcutaneously every 4 weeks from week12 until W44. As optional, small bowel lesions were assessed using modified simple Endoscopic Score for Crohn’s Disease [mSES-CD], excluding stricture evaluation. The sum of the proximal ileum (10-300 cm from ileocecal valve) and terminal ileum sub-scores was defined as a partial modified SES-CD (pmSES-CD). Within patients with pmSES-CD score of 4 or more at baseline, those with a score reduction of 50% at W48 from the baseline were defined as endoscopic responder; a pmSES-CD score of less than 4 points was defined as ulcer-free, and a pmSES-CD score of 0 was defined as complete mucosal healing.

Results

A total of 38 patients were enrolled and received GUS treatment. Most participants were male (24/38; 63.2%), and the median age was 40.5 (range: 20-69) years. This group included 8 with ileal type, 9 with colonic type, and 21 with ileocolonic type. The median duration of CD was 7.97 (0.4–33.0) years. Overall, 33/38 patients (86.8%) experienced an adverse event (AE) and 3/38 (7.9%) experienced a serious AE. There were no CD-related hospitalizations or surgeries, and no new safety concerns were identified regarding GUS treatment through W48.
Among the 38 patients, 15 patients were evaluated for small bowel lesion using retrograde BAE, defined as the small bowel (SB) group. Among these, the median age was 41.0 (24-69) years, and the median duration of CD was 2.92 (0.4-16.9) years. The median pmSES-CD was 8.0 (0-14) at baseline and 5.0 (0-13) at W48. 7/15 patients (46.7%) were endoscopic responders, 4/15 patients achieved ulcer-free (26.7%), and 2/15 patients (13.3%) achieved complete mucosal healing at W48 (Table.1). Three participants (20.0%) showed improvement of 5 points or more in the lesions of the proximal ileum as measured by pmSES-CD. Two of three ileal type patients achieved ulcer-free at W48. No AE of strictures were reported through W48.

Table 1. Result of efficacy of guselkumab treatment on small bowel lesions.

Conclusion

Overall, this study showed that GUS is well-tolerated and effective for treating patients with moderately to severely active CD, and the results also suggested the effectiveness of GUS in small bowel lesions.

Disclosure

TH: Grant: EA pharma Co. Ltd., AbbVie GK, Pfizer Inc., Mitsubishi Tanabe Pharma Corporation, Kyorin Pharmaceutical Co. Ltd., JIMRO Co.Ltd, Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Ltd., Zeria Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Kissei Pharmaceutical, Boston Scientific
Consulting fees: EA pharma Co. Ltd.,AbbVie GK,Pfizer Inc.,Mitsubishi Tanabe Pharma Corporation,Takeda Pharmaceutical Co. Ltd.,Gilead Sciences, Inc.,Eli Lilly and Co.,Janssen Pharmaceutical K.K.,Bristol Myers Squibb,Abivax
Payment or honoraria for lectures, presentations, speakers;
EA pharma Co. Ltd.,AbbVie GK,Pfizer Inc.,Mitsubishi Tanabe Pharma Corporation,Kyorin Pharmaceutical Co. Ltd.,JIMRO Co.Ltd,Mochida Pharmaceutical Co., Ltd.,Takeda Pharmaceutical Co. Ltd.,Zeria Pharmaceutical Co. Ltd.,Nippon Kayaku Co. Ltd.,Janssen Pharmaceutical K.K.
TK: Grant: Abbie GK, Alfresa Pharma Corporation, EA Pharma, Gilead Sciences, Inc. Nippon Kayaku Co., Ltd., Eli Lilly Japan K.K., Mochida Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Pfizer Japan Inc., Sekisui Medical, Takeda Pharmaceutical Co., Ltd., Bristol-Myers Squibb, Mitsubishi Tanabe Pharma Corporation, Zeria Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Consulting fees :Takeda Pharmaceutical Co., Ltd., Alfresa Pharma Corporation, Zeria Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Abbie GK, Pfizer Japan Inc., Janssen Pharmaceutical K.K., JIMRO Co., Ltd., Galapagos, Takeda Pharmaceutical Co., Ltd., Expert testimony : EA Pharma Co., Ltd., KISSEI Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd., Pfizer Japan Inc., Nippon Kayaku Co., Ltd., Alfresa Pharma Corporation, Abbie GK, Mochida Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K.
KW: Consulting fees: EA Pharma Co., Ltd., Payment or honoraria for lectures, presentations, speakers: Takeda Pharmaceutical Co., Ltd., AbbVie Japan Co., Ltd., EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., JIMRO Co., Ltd.
Participation on a Data Safety Monitoring Board or Advisory Board: Takeda Pharmaceutical Co., Ltd., Leadership or fiduciary role in other board, society, committee : Japanese Society of Gastroenterology, Japanese Society of Gastrointestinal Endoscopy, Japanese Gastroenterological Association, Japan Society of Coloproctology, Japanese Society of Mucosal Immunology, Japan Society for Inflammatory Bowel Disease, Japanese Society of Small Intestinal Disease, Japanese Association for Capsule Endoscopy, Research group of intractable IBD, the Ministry of Health, Labor and Welfare in Japan
KO All support for the present manuscript : J&J Innovative Medicine, Payment or honoraria for lectures, presentations, speakers: AbbVie Inc, EA Pharma Co.,Ltd, Janssen Pharmaceutical, KYORIN Pharmaceutical, Mitsubishi Tanabe Pharma, MOCHIDA PHARMACEUTICAL, Nippon Kayaku Co.,Ltd, OLYMPUS CORPORATION, Takeda Pharmaceuticals, Zeria Pharmaceutical Co., Ltd.
ME: Grant: Kyorin Pharmaceutical Co. Ltd, Payment or honoraria for lectures, presentations, speakers: AbbVie GK, Mitsubishi Tanabe Pharma, EA Pharma Co., Ltd, Janssen Pharmaceutical, Takeda Pharmaceuticals, Pfizer Japan Inc., Gilead Sciences Inc., Mochida Pharmaceutical Co. Ltd
TO: Payment or honoraria for lectures, presentations, speakers: AbbVie GK., Takeda Pharmaceutical Co. Ltd., and KISSEI Co. Ltd
NH: Expert testimony : J&J Innovative Medicine
TM: None
TS, KM, MC, HH and SY are employees of Johnson & Johnson.