Banerjee, Rupa

Abstract Background Patient age can impact the safety and efficacy of ulcerative colitis (UC) treatments. Etrasimod is an oral, once daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active UC. Here, we evaluate the impact of age on etrasimod safety and efficacy in patients with UC in the phase 3 ELEVATE UC clinical program. Methods Data were pooled from ELEVATE UC 52 and ELEVATE UC 12 in patients receiving etrasimod 2 mg QD or placebo. Proportions and incidence rates (IRs) per 100 patient-years of treatment-emergent adverse events (AEs) were stratified by age (<40, 40-59, and ≥60 years). With the same age stratifications, efficacy was evaluated in patients with baseline Modified Mayo scores of 5-9 and 4-9 for the primary efficacy endpoint (clinical remission) and secondary efficacy endpoints. Results Overall, 787 patients were enrolled (<40 years, n = 420 [53.4%]; 40-59 years, n = 276 [35.1%]; and ≥60 years, n = 91 [11.6%]). Arthralgia, fatigue, and hypertension IRs were higher in older patients, irrespective of treatment. Serious AEs and AEs leading to treatment discontinuation were low and consistent across age groups. Significantly more patients receiving etrasimod 2 mg QD vs placebo achieved efficacy endpoints, regardless of age. Conclusions The safety profile of etrasimod 2 mg QD in the ELEVATE UC population was consistent across age groups, with no change in the incidence of AEs. Patients receiving etrasimod vs placebo showed significant clinical benefit, regardless of age. ClinicalTrials.gov NCT03945188; NCT03996369.

Abstract Background Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Previous work has shown age can impact treatment safety and efficacy in patients with inflammatory bowel disease.1 This post hoc analysis investigated the impact of age on the safety and efficacy of etrasimod in patients with UC in the phase 3 ELEVATE UC clinical programme. Methods Data pooled from the ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials were analysed in patients receiving etrasimod 2 mg QD and placebo. ELEVATE UC 52 had a treat-through design comprising a 12-week induction period followed by a 40-week maintenance period. ELEVATE UC 12 was a 12-week induction trial. Proportions and incidence rates (IRs) per 100 patient-years from pooled data of treatment-emergent adverse events (TEAEs) and events of interest were stratified by age (<40 years, 40–59 years, ≥60 years) and analysed in patients who received ≥1 dose of etrasimod or placebo. Efficacy analyses were evaluated in patients with baseline Modified Mayo score (MMS) 5–9 for the primary efficacy endpoint (clinical remission) and select secondary endpoints at Week 12 (both trials) and Week 52 (ELEVATE UC 52) stratified by age. Results There were 787 patients enrolled in the ELEVATE UC programme, of whom 420 (53.4%) were aged <40 years, 276 (35.1%) were aged 40–59 years and 91 (11.6%) were aged ≥60 years. The proportions and IRs of TEAEs and events of interest were mostly similar between age groups and treatment arms (Table). IRs of arthralgia, fatigue, hypertension and pyrexia were higher in older age groups, regardless of treatment arm. Serious AEs and AEs leading to treatment discontinuation were low and consistent across all age subgroups. Serious infections and infection events of interest were balanced across age groups and treatment arms. Regardless of age subgroup, significantly more patients treated with etrasimod 2 mg QD vs placebo achieved the primary and select secondary efficacy endpoints at Week 12 and Week 52 (Figure). Conclusion The safety profile of etrasimod 2 mg QD in the UC population was consistent across age groups, and with no new risks other than the estimated risks associated with increasing age.2 Patients receiving etrasimod in the ELEVATE UC programme showed significant clinical benefit as assessed by clinical remission, symptomatic remission and endoscopic improvement compared with placebo, regardless of age. References 1. Lichtenstein GR et al. Inflamm Bowel Dis 2023; 29: 27–41. 2. Luo J et al. JMIR Med Inform 2016; 4: e30.

Abstract During the 20th century, inflammatory bowel disease (IBD) was considered a disease of early-industrialized regions in North America, Europe, and Oceania. At the turn of the 21st century, incidence of IBD increased in newly-industrialized and emerging regions in Africa, Asia, and Latin America, while prevalence in early-industrialized regions started to grow steadily. Changes in incidence and prevalence denote evolution of IBD across four epidemiologic stages: Stage 1 (Emergence), characterized by low incidence and prevalence; stage 2 (Acceleration in Incidence), characterized by rapidly rising incidence and low prevalence; and stage 3 (Compounding Prevalence), characterized by decelerating, plateauing, or declining incidence and steadily rising prevalence. A fourth stage (Prevalence Equilibrium) has been proposed where the slope of prevalence plateaus due to shifting demographics of an aging IBD population, but it has not yet been evidenced. To date, these stages have been theoretical without specific incidence/prevalence indicators defining transition points. Using real-world data from 490 population-based studies comprising 80 global regions and spanning over a century (1920–2023), we show spatiotemporal transitions across stages 1–3 and model transition towards stage 4. Understanding the evolution of IBD across epidemiologic stages allows healthcare systems to better prepare for the future worldwide burden of IBD.

Abstract Background Current guidelines recommend endoscopic resection of visible and endoscopically resectable colorectal colitis-associated neoplasia (CAN) in patients with inflammatory bowel disease (IBD). However, patients with high risk CAN are often not amenable to conventional resections techniques and a consensus approach for the endoscopic management of these lesions is presently lacking. This Delphi study aims to reach consensus amongst experts on the endoscopic management of these lesions. Methods A three-round modified Delphi process was conducted to reach consensus amongst worldwide IBD and/or endoscopy experts (n=18) from three continents. Experts were chosen based on the extensive clinical experience with IBD and/or EMR/ESD in patients with IBD, and the authorship on multiple peer-reviewed publications on CAN, the endoscopic resection of CAN and/or EMR/ESD. Consensus was considered if ≥ 75% agreed or disagreed. Quality of evidence was assessed by the criteria of the Cochrane Collaboration group. Results Consensus was reached on all statements (n=14). Experts agreed on a definition for CAN and high-risk CAN (HR-CAN). Consensus was reached on the examination of the colon with enhanced endoscopic imaging prior to resection, the endoscopic resectability of a HR-CAN lesion and endoscopic assessment and standard report of CAN lesions. In addition, experts agreed on type of resections of HR-CAN (< 20mm, >20 mm, with or without good lifting), endoscopic success (technical success and outcomes), histologic assessment and follow-up in HR-CAN. Conclusion This is the first step in developing international consensus-based recommendations for endoscopic management of (HR-)CAN. Although the quality of available evidence was considered low, consensus was reached on several aspects of the management of (HR-)CAN. The present work and proposed standardization might benefit future studies.