Colectomy Rates did not Decrease in Paediatric- and Adult-Onset Ulcerative Colitis During the Biologics Era: A Nationwide Study From the epi-IIRN

Abstract

Background It is still of debate whether the advent of biologics has been associated with a change in the natural history of ulcerative colitis [UC]. In this nationwide study we evaluated trends of long-term outcomes in all patients diagnosed with UC in Israel during the biologic era. Methods Data in the epi-IIRN cohort were retrieved from the four Israeli Health Maintenance Organizations covering 98% of the population, and linked to the Ministry of Health prospective registry on surgeries and hospitalizations. Joinpoint Regression and Kaplan–Meier survival analyses were used, reporting annual average percentage change [AAPC] for each outcome. Results A total of 13 231 patients were diagnosed with UC since 2005 (1426 [11%] paediatric-onset, 10 310 [78%] adults, 1495 [11%] elderly) with 93 675 person-years of follow-up. The probabilities of surgery after 1, 3 and 5 years from diagnosis were 1.1, 2.3 and 4.1%, respectively, and the corresponding rates of hospitalizations were 22, 33 and 41%. The overall utilization of biologics in UC increased from 0.1% in 2005 to 9.6% in 2019 [AAPC 22.1%] and they were prescribed earlier during the disease course (median of 5.6 years [interquartile range 2.8–9.1] in 2005–2008 vs 0.8 years [0.4–1.5] in 2015–2018; p < 0.001]. Annual rates of surgeries [AAPC −1.3; p = 0.6] and steroid-dependency [AAPC −1.2; p = 0.3] remained unchanged, while rates of hospitalizations slightly decreased [AAPC −1.2; p < 0.001]. Outcomes were consistently worse in paediatric-onset disease than in adults, despite higher utilization of biologics [28% vs 12%, respectively; p < 0.001]. Conclusion During the biologic era rates of surgeries and steroid-dependency have remained unchanged in patients with UC, while rates of hospitalizations have slightly decreased.

Children included in randomised controlled trials of biologics in inflammatory bowel diseases do not represent the real‐world patient mix

“…1 However, real-world studies have shown conflicting results regarding the effectiveness of biologics in terms of changing the natural history of disease. [2][3][4][5] This seeming disparity between the more optimistic results of RCTs as compared with real-world data may be explained by the tight disease monitoring in RCTs, but also by the fact that enrolled patients may differ from those seen in daily clinical practice. Eligibility criteria for clinical trials typically aim to maximise internal validity of the study by enrolling a homogenous cohort while excluding more severe and complicated patients who are potentially less likely to respond to the study drug.…”

“…Regulatory randomised control trials (RCTs) conducted in children and adults with inflammatory bowel disease (IBD) have shown that anti‐tumour necrosis factor (TNF) drugs, most notably infliximab and adalimumab, are effective for inducing and maintaining remission in moderate–severe disease, while reducing the rate of hospitalizations and IBD‐related surgeries 1 . However, real‐world studies have shown conflicting results regarding the effectiveness of biologics in terms of changing the natural history of disease 2–5 . This seeming disparity between the more optimistic results of RCTs as compared with real‐world data may be explained by the tight disease monitoring in RCTs, but also by the fact that enrolled patients may differ from those seen in daily clinical practice.…”

Honokiol Ameliorates DSS-Induced Mouse Colitis by Inhibiting Inflammation and Oxidative Stress and Improving the Intestinal Barrier

“…However, none is effective in most patients, let alone the biologic-experienced patients [ 5 ]. In a nationwide study in Israel, colectomy and steroid dependency rates have remained unchanged in patients with UC during the biological era [ 6 ]. The large proportion of primary nonresponders to each molecularly targeted agent may be due to different dominant cytokine levels depending on disease stage and patient characteristics [ 7 ].…”

Nestin+ Peyer's patch resident MSCs enhance healing of inflammatory bowel disease through IL‐22‐mediated intestinal epithelial repair

“…Nowadays, corticosteroids still are the mainstay of conventional therapy of IBD patients 5 . However, when this strategy fails, patients are often subjected to intestinal resection to remove the affected gut 6,7 . In turn, surgery can be associated with inevitable complications, which lead to loss of function within the digestive system 8,9 .…”

“… 5 However, when this strategy fails, patients are often subjected to intestinal resection to remove the affected gut. 6 , 7 In turn, surgery can be associated with inevitable complications, which lead to loss of function within the digestive system. 8 , 9 Therefore, developing new approaches for IBD is urgently needed.…”