Dataset Information

TL1A (TNFSF15) genotype affects the long?term therapeutic outcomes of anti?TNF? antibodies for Crohn's disease patients

ABSTRACT: Abstract

Background and Aim

TL1A (TNFSF15) is a major Crohn's disease (CD) susceptibility gene, especially in the East Asian population, and is also known to be associated with some clinical phenotypes, such as stricturing and penetrating behavior. This study aims to investigate the association between TL1A genotype and the long?term therapeutic outcomes of infliximab and adalimumab in Japanese CD patients.

Methods

We investigated 119 biologic?naïve CD patients treated with infliximab or adalimumab. TL1A ?358C/T (rs6478109) was genotyped as a tag single nucleotide polymorphism (SNP) for CD risk or nonrisk haplotype of TL1A (the ?358C allele is a risk allele for CD development). We compared the long?term therapeutic outcomes of anti?tumor necrosis factor (TNF) antibodies between the TL1A ?358C/C group and the C/T+T/T group.

Results

Sixty?nine cases (58.0%) were homozygous for the risk allele (TL1A ?358C/C group), and 50 cases (42.0%) were heterozygous for the risk allele or homozygous for the protective allele (TL1A ?358C/T+T/T group). No significant differences were found in the cumulative retention rates and the relapse?free survival between the TL1A genotypes. However, the surgery?free survival was significantly lower in the TL1A ?358C/C group than in the C/T+T/T group (log?rank test, P?Conclusion An association was found between the TL1A genotype and the therapeutic outcomes of anti?TNF therapy. Our data indicate that the design of customized therapy with anti?TNF antibodies using TL1A genomic information could be effective in the future. In this study, we investigated the association between TL1A genotype and the long?term therapeutic outcomes of infliximab and adalimumab in Crohn's disease (CD) patients. We investigated 119 biologic?naïve CD patients treated with infliximab or adalimumab and found an association between the TL1A genotype and surgery?free survival during anti?tumor necrosis factor (TNF) therapy. The patients whose genotypes are homozygous for the TL1A ?358C (risk allele of CD development) show lower surgery?free survival with anti?TNF treatment.

SUBMITTER: Endo K

PROVIDER: S-EPMC7731806 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundThe impact of the body composition on the pathophysiology and clinical course of Crohn's disease (CD) has not been fully elucidated.AimsTo reveal the correlations among body composition and long-term outcomes in CD after anti-TNF therapy.MethodsNinety-one patients who received anti-TNF therapy as their first biologic treatment were enrolled. The skeletal muscle index (SMI), visceral and subcutaneous fat area (VFA, SFA), and the ratio of the VFA to SFA (mesenteric fat index; MFI) at the 3rd lumbar level were measured using computed tomography (CT) imaging before the induction. The correlation among the body composition and outcomes were retrospectively analyzed.ResultsThe 5-year cumulative secondary failure- and resection-free rates in patients with a low SMI (39.1% and 64.8%) were significantly lower than those with a high SMI (67.5% and 92.7%; p = 0.0071 and 0.0022, respectively). The 5-year cumulative secondary failure-free rate in the patients with low VF (45.0%) was significantly lower than that in those with high VF (77.6%; p = 0.016), and the 5-year cumulative resection-free rate in patients with a high MFI (68.9%) was significantly lower than that in those with a low MFI (83.0%; p = 0.031). Additionally, patients with low age and BMI had significantly lower cumulative secondary failure- and resection-free rates than those with high age and BMI (low age: 37.4% and 71.2%; high age: 70.7% and 88.9%; p = 0.0083 and 0.027, respectively) (low BMI: 27.2% and 64.8%; high BMI: 68.3% and 87.9%; p = 0.014 and 0.030, respectively), respectively. In the multivariate analyses, a low SMI was the only independent risk factor for secondary failure (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.04-4.44), while low age (HR 4.06, 95% CI 1.07-15.4), a low SMI (HR 4.19, 95% CI 1.01-17.3) and high MFI were risk factors for bowel resection (HR 4.31, 95% CI 1.36-13.7).ConclusionThe skeletal muscle mass and ratio of visceral to subcutaneous fat were suggested to reflect the long-term clinical outcome and may be helpful as prognostic markers after anti-TNF therapy in CD.

Project description:BackgroundUstekinumab and vedolizumab are both effective for treating Crohn's disease (CD). However, no head-to-head trials have been conducted thus far. We aimed to compare the effectiveness of ustekinumab and vedolizumab in CD patients either naïve or exposed to tumor necrosis factor-alpha inhibitors (TNFi).MethodsPatients treated with vedolizumab or ustekinumab for luminal CD were included from six centers in China from May 2020 to July 2023. Steroid-free remission, clinical remission, objective response, and remission at Weeks 26 and 52 were evaluated in a retrospective multicenter propensity score-weighted cohort.FindingsA total of 536 patients were included (386 ustekinumab, and 150 vedolizumab). After adjustment, ustekinumab showed higher rates of clinical remission (56.4% vs. 47.8%, P = 0.005), steroid-free remission (55.4% vs. 46.1%, P = 0.003), and objective response (67.8% vs. 42.7%, P < 0.001) than vedolizumab at Week 26. At Week 52, ustekinumab exhibited significantly higher rates of clinical remission (65.8% vs. 37.5%, P < 0.001), steroid-free remission (65.8% vs. 37.5%, P < 0.001), objective response (66.7% vs. 23.8%, P < 0.001), and objective remission (31.4% vs. 12.7%, P < 0.001). Subgroup analyses revealed that ustekinumab had higher rates of clinical remission, steroid-free remission, and objective response at Weeks 26 and 52, and objective remission at Week 52 in TNFi-exposed patients, while ustekinumab showed higher rates of objective response at Weeks 26 and 52 and clinical remission, steroid-free remission and objective remission at Week 52 in TNFi-naïve patients. Adverse event rates were similar between the groups (4.9% ustekinumab vs. 6.7% vedolizumab, P = 0.423).InterpretationUstekinumab showed superior clinical and objective outcomes compared to vedolizumab, with comparable safety outcomes. The therapeutic superiority was observed in both short-term and long-term phases in TNFi-exposed patients, and the long-term phase in TNFi-naïve patients.FundingNational Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Key Research Projects of the Sixth Affiliated Hospital, Sun Yat-sen University, the program of Guangdong Provincial Clinical Research Center for Digestive Diseases, and National Key Clinical Discipline.