scholarly journals P502 Tumour necrosis factor antagonists are superior to anti-integrin and anti-IL-12/23 therapies for preventing postoperative recurrence in adult Crohn’s disease patients requiring postoperative therapy

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S436-S437
Author(s):  
T Nakamura ◽  
R Shah ◽  
M Sachs ◽  
S Chang ◽  
D Hudesman ◽  
...  

Abstract Background Crohn’s disease (CD) recurrence is common after surgical resection. Prior data have demonstrated that postoperative tumour necrosis factor antagonists (anti-TNF) may reduce recurrence, although little is known about the efficacy of other biologic therapies. The aim of this study was to compare biologic type and timing for preventing postoperative objective recurrence in adult CD patients. Methods We performed a retrospective chart review of CD patients who underwent intestinal resection from 2009 to 2019 at two academic medical centres. We tabulated baseline variables against treatment groups based on the type of postoperative biologic (anti-TNF, anti-integrin, anti-IL-12/23) and timing of postoperative biologic initiation (before or after 6 months post-op). Propensity score matching was utilised for treatment groups using baseline variables as predictors. Recurrence was defined by endoscopy (>i2 Rutgeerts’ score) or radiography (active inflammation in neoterminal ileum). Survival analysis was performed to assess risk of recurrence by treatment group and timing of biologic initiation. Results One hundred and forty-four patients were included (51% male, 13.2% active smokers, 97.9% stricturing and/or penetrating CD, 41.7% prior resection). The majority of patients received anti-TNF therapy. Adjusting for the propensity scores, fewer patients relapsed under anti-TNF compared with anti-integrin (HR 2.87, 1.04–7.99; p = 0.042) and anti-IL-12/23 (HR 3.51, 1.51–8.14; p = 0.03). There was no significant difference in objective relapse between patients on postoperative anti-TNF and no therapy (HR 0.71, 0.31–1.66; p = 0.44) (Figure 1). More patients relapsed when biologics were started after 6 months postoperatively compared with within 6 months (HR = 0.20, 0.08–0.53; p = 0.001) and never started (HR = 0.26, 0.11–0.59; p = 0.001) (Figure 2). Conclusion Among propensity score-adjusted CD patients, initiation of biologics within 6 months and anti-TNF agents were superior in preventing postoperative recurrence among patients receiving postoperative biologic therapy.

2021 ◽  
Author(s):  
Gerassimos J Mantzaris ◽  
Christos Zeglinas ◽  
Angeliki Theodoropoulou ◽  
Ioannis Koutroubakis ◽  
Eleni Orfanoudaki ◽  
...  

Abstract Background Data on the effectiveness of anti–tumour necrosis factor medications in patients with Crohn’s disease with poor prognostic factors are scarce. This study aimed to generate real-world evidence on the effect of early (≤24 months after diagnosis) versus delayed (>24 months) initiation of adalimumab on the 26-week remission rate (Harvey-Bradshaw Index ≤4) in these patients. Methods This multicentre, retrospective, chart-review study performed in 10 Greek hospitals enrolled adult patients with moderate to severe Crohn’s disease (Harvey-Bradshaw Index ≥8) with ≥3 poor prognosis factors who were initiated on adalimumab ≥12 months before enrolment. A sample size of 164 patients (early:delayed cohort allocation ratio, 30:70) was required to address the primary endpoint. Results Eligible patients (n=171) were consecutively enrolled. In the early versus delayed cohorts, the 26-week remission rates (off steroids) using the last-observation-carried-forward imputation method were 60.7% (37/61) versus 47.2% (50/106), respectively (Δ=13.5%, p=0.044). The respective remission rates were 61.2% versus 42.4% among anti–tumour necrosis factor–naive patients (p=0.023) and 58.3% versus 53.2% among anti–tumour necrosis factor–experienced patients (p=0.374). The 52-week remission rates using as-observed data were 78.8% and 60.3%, and the intestinal resection rates were 6.5% and 11.9% in the early versus delayed ADL cohorts, respectively. Conclusions Patients with Crohn’s disease with poor prognostic factors who received early versus delayed treatment with adalimumab achieved higher clinical response and remission rates. This effect was more pronounced in those patients who were bio-naive and steroid-dependent/refractory with concurrent extraintestinal manifestations than those who were not.


2019 ◽  
Vol 13 (7) ◽  
pp. 905-915 ◽  
Author(s):  
Shrinivas Bishu ◽  
Mohammed El Zaatari ◽  
Atsushi Hayashi ◽  
Guoqing Hou ◽  
Nicole Bowers ◽  
...  

Abstract Background and Aims Tumour necrosis factor [TNF]α- and IL-17A-producing T cells are implicated in Crohn’s disease [CD]. Tissue-resident memory T [TRM] cells are tissue-restricted T cells that are regulated by PR zinc finger domain 1 [PRDM1], which has been implicated in pathogenic Th17 cell responses. TRM cells provide host defence but their role in CD is unknown. We thus examined CD4+ TRM cells in CD. Methods Colon samples were prospectively collected at endoscopy or surgery in CD and control subjects. Flow cytometry and ex vivo assays were performed to characterise CD4+ TRM cells. Results CD4+ TRM cells are the most abundant memory T cell population and are the major T cell source of mucosal TNFα in CD. CD4+ TRM cells are expanded in CD and more avidly produce IL-17A and TNFα relative to control cells. There was a unique population of TNFα+IL-17A+ CD4+ TRM cells in CD which are largely absent in controls. PRDM1 was highly expressed by CD4+ TRM cells but not by other effector T cells. Suppression of PRDM1 was associated with impaired induction of IL17A and TNFA by CD4+ TRM cells Conclusions CD4+ TRM cells are expanded in CD and are a major source of TNFα, suggesting that they are important in CD. PRDM1 is expressed by TRM cells and may regulate their function. Collectively, this argues for prospective studies tracking CD4+ TRM cells over the disease course.


2020 ◽  
Author(s):  
Judith Pichler ◽  
Nima Memaran ◽  
Wolf Dietrich Huber ◽  
Christoph Aufricht ◽  
Bettina Bidmon‐Fliegenschnee

2019 ◽  
Vol 50 (11-12) ◽  
pp. 1195-1203
Author(s):  
Joyce Wing Yan Mak ◽  
Whitney Tang ◽  
Terry Cheuk Fung Yip ◽  
Zhi Hua Ran ◽  
Shu Chen Wei ◽  
...  

2010 ◽  
Vol 192 (7) ◽  
pp. 375-377 ◽  
Author(s):  
Daniel C Burger ◽  
Ian C Lawrance ◽  
Peter A Bampton ◽  
Ruth Prosser ◽  
Anthony Croft ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document