Multicenter real-world study: Etrasimod provides rapid symptom relief and high early remission rates in ulcerative colitis

Multicenter real-world study: Etrasimod provides rapid symptom relief and high early remission rates in ulcerative colitis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Multicenter real-world study: Etrasimod provides rapid symptom relief and high early remission rates in ulcerative colitis Joëlle St‑Pierre, David Choi, Cheng-Yu Chen, Russell Yanofsky, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9273653/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Purpose Etrasimod, an oral sphingosine-1-phosphate receptor modulator, demonstrated efficacy and safety in pivotal phase 3 trials for moderate-to-severe ulcerative colitis (UC). This study aimed to evaluate the real-world effectiveness, safety, and treatment persistence of etrasimod in patients with UC treated. Methods We conducted a prospective, observational study across two tertiary centers. Adult UC patients initiating etrasimod were followed for up to 52 weeks. Primary outcome was treatment persistence. Secondary outcomes included clinical response (≥ 3-point SCCAI reduction), clinical remission (SCCAI ≤ 2) and safety. Results Forty-four patients were included; median age was 38.5 years, and 29.5% had prior advanced therapy. Persistence on etrasimod was 61.4% at week 12, 40.9% at week 26, and 35.1% at week 52. Median SCCAI decreased from 3.0 (IQR 1.0-6.8) at baseline to 0.0 at weeks 8 and 12 (p < 0.05). Among patients with active disease (n = 26), median SCCAI fell from 5.0 to 0.5 by week 12 (p ≤ 0.0003). Clinical remission was achieved in 70% at week 2 and 76% at week 12, with 75% remission among those with baseline SCCAI ≥ 3. By week 12, 86% of patients were corticosteroid-free, and the majority remained off systemic steroids during follow-up. No serious adverse events (SAEs) occurred; discontinuation was primarily due to disease exacerbation. Conclusions In this first multicenter real-world cohort, etrasimod provided rapid and sustained symptom improvement in UC. High early remission rates support its effectiveness in routine practice, though persistence declined over time, highlighting the need for early response assessment and proactive treatment optimization. ulcerative colitis etrasimod sphingosine‑1‑phosphate modulator real‑world evidence observational study Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease characterized by continuous mucosal inflammation of the colon and rectum. It is associated with substantial morbidity, impaired quality of life, and increased healthcare costs[ 1 ]. Globally, the burden of UC has grown dramatically over the past century and now affects millions of individuals worldwide as its incidence accelerates in newly industrialized and emerging regions[ 1 ]. Projections suggest that prevalence may approach or exceed 1% in many countries by 2040[ 1 ]. This global trend underscores the pressing need for effective and sustainable treatment strategies. Therapeutic advances over the past two decades, including biologics and small molecules, have transformed UC management; however, a substantial proportion of patients fail to achieve sustained remission or discontinue therapy due to lack of efficacy or safety concerns[ 2 ]. Sphingosine-1-phosphate receptor (S1PR) modulators represent a novel class of oral therapies that reduce lymphocyte trafficking to the gut by internalizing S1P receptors and sequestering lymphocytes in lymph nodes[ 2 – 4 ]. Among these, etrasimod, a selective S1PR 1,4,5 modulator, offers advantages such as no need for dose titration, and a favorable cardiovascular safety profile[ 2 ]. The efficacy and safety of etrasimod have been demonstrated in the pivotal phase 3 ELEVATE UC 12 and ELEVATE UC 52 trials, where etrasimod significantly improved clinical remission, endoscopic and histologic outcomes compared with placebo during both induction and maintenance[ 5 ]. At week 12, clinical remission rates were approximately 25–27% with etrasimod versus 7–15% with placebo, and benefits were sustained through week 52[ 5 ]. These findings, combined with an acceptable safety profile and oral route of administration, have positioned S1PR modulators as a recommended induction and maintenance option for patients with moderate-to-severe UC[ 6 – 8 ]. Indirect comparisons from network meta-analyses suggest that etrasimod ranks among the most effective agents for maintenance remission in UC, particularly in treat-through designs[ 9 – 11 ], but validation in routine clinical practice remains essential. Although randomized controlled trials provide high internal validity and are the basis for drug approval, their strict eligibility criteria and standardized monitoring may not reflect real-world clinical practice and efficacy, where patients often present with comorbidities, laboratory abnormalities, and variable disease activity. Real-world evidence is therefore essential to assess treatment effectiveness, corticosteroid-sparing potential, persistence, and safety under routine care conditions. We describe the first real-world effectiveness and safety analysis of etrasimod in patients with UC across two tertiary care centers in the United States and Australia. Specifically, we examined clinical response, remission, corticosteroid use, treatment persistence, and adverse events for up to 52 weeks. METHODS Study design and patient selection We conducted a prospective, observational, multicenter cohort study at two tertiary care centers: the University of Chicago IBD Center (Chicago, IL, USA) and the Mater Hospital Brisbane (Brisbane, QLD, Australia). Consecutive adult patients (≥ 18 years) with an established diagnosis of UC who were initiated on etrasimod were included. Patients were recruited beginning in December 2023, with clinical data collected through June 2025. Patients were eligible if etrasimod was started for active disease, defined by clinical, biochemical, endoscopic, or imaging evidence of inflammation, or for a non-medical switch from a prior advanced therapy. Active disease was defined by at least one of the following: SCCAI ≥ 3, elevated biomarkers (CRP > 5 mg/L or fecal calprotectin > 150 µg/g), endoscopic evidence of inflammation (Mayo endoscopic subscore [MES] ≥ 2), or imaging evidence of colitis (bowel wall thickening, hyperenhancement, and/or pericolonic inflammatory changes on cross-sectional imaging). Patients with previous colectomy or an indication other than UC were excluded as disease activity parameters are not comparable in post-surgical populations. Etrasimod was prescribed according to local regulatory approvals and clinical judgment. All patients received the standard oral dose of etrasimod (2 mg once daily). There was no mandated washout period for prior therapy. Patients were followed from treatment initiation (Week 0) through subsequent clinical visits as part of routine care. Data Collection & Variables Demographic and clinical characteristics were extracted from electronic health records. Baseline data included age, sex, age at UC diagnosis, disease duration, Montreal classification extent, smoking status, prior UC medication exposure, and concomitant therapy at etrasimod initiation. Corticosteroid use at initiation and during follow-up was recorded. Follow-up data were reviewed at prespecified time points according to our real-world prospective data collection protocol. Disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI) at baseline and weeks 2, 4, 8, 12, 26, and 52[ 12 ]. Laboratory markers included C-reactive protein (CRP), fecal calprotectin (FCP), and albumin. CRP was collected at baseline, week 4, and week 12; FCP at baseline, week 8, and week 12; and absolute lymphocyte count (ALC) at baseline, week 4, and week 12. Albumin was included as a marker of systemic inflammation and nutritional status, which has been shown to correlate with disease severity and predict therapeutic responses in patients with UC[ 13 , 14 ]. Endoscopic and cross-sectional imaging data were recorded when available but were not systematically obtained. Additional investigations were obtained at the discretion of the treating physician. The number of patients with available data at each prespecified time point is indicated in figures and tables. Analyses were based on observed data without imputation for missing values. Outcomes The primary outcome of interest was treatment persistence on etrasimod, defined as the time from initiation to permanent discontinuation for any reason, and analyzed using time-to-event methods across the observation period. Persistence was chosen as the primary endpoint as it reflects both effectiveness and tolerability in routine care, integrating clinical response, safety, and patient/physician decision-making. Secondary outcomes included clinical effectiveness and safety measures. Clinical response was defined as a reduction of at least three points in the SCCAI from baseline among patients with an initial SCCAI score of 3 or higher, and clinical remission was defined as an SCCAI score of 2 or less, consistent with established definitions[ 12 , 15 ]. These secondary outcomes were assessed at Weeks 12, 26, and 52 when available. Additional secondary outcomes included changes in inflammatory biomarkers, specifically CRP and FCP. Absolute lymphocyte count (ALC) was recorded at baseline and during follow-up when available. Lymphopenia was categorized as mild/moderate (< 1.0 × 10⁹/L) and severe (< 0.5 × 10⁹/L) for descriptive analysis, consistent with thresholds applied in the ELEVATE UC program and aligned with CTCAE criteria[ 5 , 16 ]. As in prior S1PR modulator trials, lymphopenia was considered an expected pharmacodynamic effect rather than an adverse event unless it resulted in clinical consequences (e.g., infection or drug discontinuation)[ 5 , 17 ]. Safety outcomes included the occurrence of adverse events (AEs) and serious adverse events (SAEs). AEs were defined as any untoward medical occurrence in a patient receiving etrasimod, whether considered related to the study drug or not. SAEs were defined as events resulting in death, life-threatening complications, hospitalization, persistent or significant disability, congenital anomaly, or any other medically important event, including events leading to permanent discontinuation of etrasimod. Statistical analysis Continuous variables were summarized as medians with interquartile ranges (IQR), and categorical variables as frequencies and percentages. For the primary endpoint of treatment persistence, Kaplan-Meier analyses were performed using an intention-to-treat framework in which permanent discontinuation of etrasimod or loss to follow-up was counted as an event at the time of last contact. This approach yields conservative estimates of persistence, as patients with missing follow-up were not censored but considered to have discontinued therapy. We defined “eligible” patients at each landmark time point (weeks 12, 26, and 52) as those who had initiated etrasimod at least that many weeks before database lock. The flow diagram summarizes, among eligible patients, the number remaining on therapy, those who discontinued, and those with missing clinical data (Supplementary Fig. 1). In contrast, analyses of clinical and biochemical outcomes were based on available data without imputation and therefore reflect only patients with documented assessments at each time point. Pairwise comparisons of disease activity scores (i.e., SCCAI) between baseline (week 0) and each follow-up time point (weeks 2, 4, 8, and 12) were performed using the Wilcoxon signed-rank test, given the non-parametric distribution and ordinal nature of SCCAI. Analyses were restricted to these intervals due to sufficient paired data availability; sample sizes at later time points (weeks 26 and 52) were too limited to permit meaningful statistical testing. Because this was an exploratory real-world study with prespecified follow-up intervals, repeated pairwise comparisons were conducted without formal adjustment for multiplicity given the small sample size which substantially reduce statistical power. Therefore, p-values are interpreted descriptively and in conjunction with effect magnitude. A two-sided p-value < 0.05 was considered statistically significant. Analyses were performed using GraphPad Prism (version 10.4.2). Analyses were based on available data, and missing values were not imputed. Ethical considerations The study was approved by the Institutional Review Boards of the University of Chicago and the Mater Misericordiae Ltd Human Research Ethics Committee. RESULTS Baseline Characteristics Forty-four patients were included across two tertiary care centers (University of Chicago, Chicago, IL, USA and Mater Hospital Brisbane, Brisbane, QLD, Australia). Population characteristics are reported in Table I. The median age at etrasimod initiation was 38.5 years (IQR 30.5–48.0), and 16 patients (36.4%) were female. The median age at UC diagnosis was 28 years (IQR 21-38.3), with a median disease duration of 6.0 years (IQR 3.0-11.3). Most patients were never smokers (n = 37, 84.1%), and none reported active smoking at treatment initiation. With respect to disease extent, 8 patients (18.2%) had proctitis (E1), 19 patients (43.2%) had left-sided colitis (E2), and 16 patients (36.3%) had extensive colitis (E3), while 1 patient (2.3%) had unknown extent of disease. Prior exposure to 5-ASA was common (n = 38, 86.4%), and 10 patients (22.7%) had been treated with thiopurines. Thirteen patients (29.5%) had previously received advanced therapy, including anti-TNF agents (n = 7), vedolizumab (n = 8), ustekinumab (n = 1), Janus kinase (JAK) inhibitors (n = 3), and ozanimod (n = 2). Four patients (9%) were previously exposed to more than two advanced therapies. At etrasimod initiation, 12 patients (27.3%) were receiving systemic corticosteroids, and 3 patients (6.8%) were on rectal steroids. Within 12 weeks of treatment initiation, 3 patients (6.8%) required new systemic corticosteroids, and 2 patients (4.5%) required new rectal steroids. The most common reason for starting etrasimod was active disease (n = 36, 82%), defined by clinical, biochemical, endoscopic, or imaging evidence of inflammation, while 8 patients (18%) were switched for non-medical reasons. Of these, two patients were switched due to side effects from their previous advanced therapy and three for preference in mode of delivery (oral as compared to IV). Among patients with available SCCAI data at baseline (n = 44), 18 patients (40.9%) were in clinical remission (SCCAI 0–2), while 26 patients (59.1%) had active disease (SCCAI ≥ 3). Baseline laboratory data, where available, showed that 10 of 32 patients (31.3%) had an elevated CRP (> 5 mg/L), and 19 of 24 patients (79.2%) had fecal calprotectin > 150 µg/g, with a median FCP of 669.5 µg/g (IQR 195.5–1604). The median serum albumin at baseline was 4.4 g/dL (IQR 4.2–4.6). Treatment persistence Treatment persistence on etrasimod over the 52-week observation period is shown in Fig. 1 . Using an intention-to-treat approach, where loss to follow-up was considered a treatment discontinuation event, the estimated probability of remaining on etrasimod was 88.6% at Week 8, 61.4% at Week 12, 40.9% at Week 26, and 35.1% at Week 52. The number of patients at risk decreased from 44 at baseline to 39 at Week 12, 24 at Week 26, and 7 at Week 52. The median time to treatment discontinuation was not reached within the study period. Clinical disease activity For the overall cohort (n = 44), the median SCCAI at baseline was 3.0 (IQR 1.0-6.8). Median SCCAI decreased to 2.0 at week 2 (IQR 0–3.0), 1.0 at week 4 (IQR 0–3.0), and 0.0 at weeks 8 and 12 (IQR 0–3.0 and 0–2.0, respectively) (Fig. 2 A). Significant reductions compared to baseline were observed at all follow-up points (week 2: p = 0.0076; week 4: p = 0.0022; week 8: p = 0.0199; week 12: p = 0.0188, Wilcoxon signed-rank test). The number of patients with available SCCAI data at each time point ranged from 29 to 44 and is shown in Fig. 2 . Among patients with clinically active disease at baseline (SCCAI ≥ 3, n = 26), the median SCCAI was 5.0 (IQR 4.0–9.0) at initiation. This decreased to 2.0 (IQR 1.0–4.0) at week 2, 2.0 (IQR 0-3.3) at week 4, 1.5 (IQR 0-4.5) at Week 8, and 0.5 (IQR 0–2.0) at week 12 (Fig. 2 B). Reductions from baseline were significant at all time points (week 2: p = 0.0004; week 4: p = 0.0001; week 8: p = 0.0056; week 12: p = 0.0003). The number of patients with available SCCAI data for this subgroup ranged from 16 to 26, as shown in Fig. 2 . Categorical outcomes are summarized in Table II. At baseline (week 0), 18 of 44 patients (41%) were already in clinical remission (SCCAI 0–2). By week 2, remission was observed in 70% of patients and remained relatively stable thereafter (71% at week 4, 72% at week 8, 76% at week 12, 71% at week 26, and 83% at week 52). The majority of patients with clinical response, defined as a decrease in SCCAI ≥ 2 from baseline, achieved this by week 3 (30%). Only one patient achieved clinical response beyond week 12. In the subgroup with active disease at baseline (SCCAI ≥ 3), 50% achieved clinical response by week 2 and an additional 35% at week 12. Clinical remission occurred in 56% at week 2, increasing to 75% at week 12 and 80% at week 52, albeit only 6 patients (out of 21 included patients at that timeline) were still on etrasimod at that time point. These findings indicate that many patients achieved remission early, with sustained benefit in those remaining on therapy. Corticosteroid use At baseline, nine patients were receiving systemic prednisone at a dose of 20 mg or higher. Three patients (6.8%) were also using rectal corticosteroids at the start of etrasimod. Three patients of the patients on systematic steroids at baseline were successfully weaned off steroids and continued etrasimod while the other 9 patients eventually discontinued etrasimod. During follow-up, three patients who were not on corticosteroids at baseline required initiation of systemic steroids prior to Week 12, including two patients who were in clinical remission at baseline and one with active disease at baseline (SCCAI ≥ 3). By 24 weeks, one additional patient required rectal corticosteroid therapy. Rates of corticosteroid-free remission could not be meaningfully assessed due to the small number of patients on systemic corticosteroids at baseline and during follow-up; therefore, this outcome was not analyzed further. Biochemical markers CRP data were available for 32 patients at baseline, 15 at Week 4, and 16 at Week 12. At baseline, the median CRP was 3.0 mg/L (IQR 1.6-5.0). At Week 4, the median CRP remained 3.0 mg/L (IQR 3.0-3.6), and at Week 12, it was also 3.0 mg/L (IQR 1.8–7.3). Among patients with paired CRP measurements (n = 10), individual trends were variable, and no formal statistical testing was performed due to limited paired data. FCP was available for 24 patients at baseline, 8 at Week 8, and 13 at Week 12. At baseline, the median FCP was 669.5 µg/g (IQR 190.5-1,648). At Week 8, the median FCP decreased to 171.3 µg/g (IQR 10.3-2,866), and at Week 12, it was 234 µg/g (IQR 51.0–1,320). Among patients with paired measurements (n = 8), trends were heterogeneous, and no formal statistical testing was performed due to limited sample size. ALC declined significantly following etrasimod initiation (Fig. 3 ). The median ALC at baseline was 1.83 ×10⁹/L (IQR 1.35–2.14), compared to 0.68 ×10⁹/L (IQR 0.48–1.04) at week 4 and 0.70 ×10⁹/L (IQR 0.46–1.16) at week 12. Among patients with paired measurements, ALC was significantly lower at week 4 compared to baseline (p = 0.0039) and at week 12 compared to baseline (p = 0.0015) using the Wilcoxon signed-rank test. The proportion of patients with lymphopenia (< 1.0 × 10⁹/L) increased from 10.5% (n = 4/38) at baseline to 68.8% (n = 11/16) at week 4 and 78.6% (n = 11/14) at week 12. Severe lymphopenia (< 0.5 × 10⁹/L) was observed in 5.3% (n = 2/38), 25.0% (n = 4/16), and 28.6% (n = 4/14) of patients at these respective timepoints. No patients discontinued etrasimod due to lymphopenia. Safety No SAEs were reported during the study period. Two patients experienced mild AEs of lightheadedness, occurring at Week 2 and Week 8, respectively; both episodes resolved without intervention and did not lead to etrasimod discontinuation. There were no instances of symptomatic bradycardia. The most frequent safety-related event leading to treatment discontinuation was disease exacerbation, which accounted for all discontinuations observed in the cohort. No other treatment-related adverse events were documented. DISCUSSION This multicentre analysis is the first real-world report of etrasimod in UC and provides complementary evidence to the pivotal ELEVATE UC trials[ 5 ]. Etrasimod induced a rapid fall in median SCCAI from 5.0 to 0.5 among patients with clinically active disease at baseline (SCCAI ≥ 3), with significant improvement apparent by week 2 and maintained through week 12. Comparable onset and depth of response were documented in ELEVATE UC[ 5 ]. Recent network meta-analyses extend these observations: Barberio et al. (2025) ranking etrasimod first for clinical and corticosteroid-free remission in treat-through designs, while Dai et al. (2025) placed it among the most effective agents for maintenance remission, and Solitano et al. (2023) similarly demonstrating high efficacy of etrasimod compared with other advanced therapies in the maintenance setting[ 9 – 11 ]. Together, these data and our findings suggest that the clinical benefits of etrasimod observed in clinical trials may extend to real-world practice, although confirmation in larger cohorts with standardized follow-up is needed. These findings align with contemporary positioning frameworks that recommend S1PR modulators as effective induction and maintenance options for moderate-to-severe UC, particularly in biologic-naïve patients or those seeking oral therapy[ 7 ]. Real-world experience with other S1PR modulators, such as ozanimod, supports the translation of pivotal trial efficacy into routine clinical practice, but also highlights the challenge of maintaining long-term persistence. In a prospective cohort of 45 patients with UC treated at a tertiary center, Cohen et al. reported week 10 clinical remission in 53% and response in 58%, but only 25% maintained either outcome at 52 weeks, despite a favorable safety profile and absence of new safety signals[ 18 ]. The observed decline in persistence in our etrasimod cohort parallels these findings and may reflect similar real-world factors, including treatment-refractory populations, heterogeneous monitoring, and broader eligibility compared with clinical trials. Steroid exposure was low at baseline in our cohort (14% receiving systemic corticosteroids), and most patients remained off steroids during follow-up. While this may point toward a steroid-sparing profile, the small sample size and limited corticosteroid use at initiation restrict firm conclusions. Treatment persistence fell from 61% at week 12 to 29% at week 52, lower than the 52-week continuation observed in the treat-through trial programme. Attrition in routine care likely reflects broader inclusion criteria, heterogeneous treatment goals, and less intensive follow-up than in clinical trials. Early assessment (weeks 8–12) therefore remains essential to distinguish responders from those requiring an alternative strategy. Biochemical markers demonstrated heterogeneous changes; however, the average change in inflammatory biomarkers trended in a favorable direction. ALC declined significantly after treatment initiation, consistent with the expected pharmacodynamic effect of S1PR modulation described in the ELEVATE UC safety analyses[ 17 ] and in real-world data from multiple sclerosis populations showing variable degrees of lymphopenia across S1P receptor modulators, although etrasimod was not included in this study[ 19 ]. Lymphopenia (< 1.0 × 10⁹/L) was common by weeks 4 and 12 (68.8% and 78.6%, respectively), with severe lymphopenia (< 0.5 × 10⁹/L) observed in up to 28.6% of patients, yet no cases required discontinuation or resulted in infection. These findings have several practical ramifications for routine care. First, we demonstrate real-world applicability of this novel therapy for patients with UC. Second, the rapid symptom improvement observed in everyday practice confirms that etrasimod can provide early relief; however, discontinuation in 39% of patients by week 12 and 71% by week 52 underscores the need for early response assessment and ongoing management to monitor the sustained benefit. Further, our low baseline use, subsequent reduction of corticosteroids point to a steroid‑sparing profile, and post‑hoc ELEVATE analyses demonstrating no additional benefit from concomitant corticosteroids or 5‑aminosalicylates support an initial monotherapy or rapid steroid weaning strategy when appropriate[ 20 ]. Importantly, the predictable, reversible lymphopenia seen with etrasimod was not accompanied by excess serious, severe or opportunistic infections, consistent with pooled ELEVATE safety data that showed comparable or lower serious‑infection rates versus placebo[ 17 ]. Taken together, this evidence demonstrates that etrasimod is a convenient, oral, first‑line advanced therapy that delivers rapid symptom control while maintaining a favourable infection profile; nonetheless, treat‑to‑target monitoring between weeks 8 and 12 remains essential to confirm durable benefit and to expedite therapeutic escalation when needed. This analysis has several important limitations. First, although multicentre, the cohort comprised only 44 patients and follow‑up visits were not protocol‑driven, limiting statistical power. Repeated pairwise comparisons were exploratory and not adjusted for multiplicity, increasing the risk of type I error. Second, while treatment persistence was selected as our primary outcome given its pragmatic importance in real-world studies, we acknowledge that it may be influenced by factors beyond drug effectiveness, including access, insurance coverage, and patient preference. We therefore reported detailed clinical outcomes in parallel to better capture real-world effectiveness. Third, objective indicators of deep remission were incompletely captured, including biochemical, sonographic, endoscopic and histologic assessments were available in less than one‑third of participants, precluding robust evaluation of mucosal or transmural healing. Fourth, safety analyses were under‑powered to detect uncommon adverse events and ALC monitoring was not standardised across centres. Fifth, persistence estimates may be confounded by non‑medical switching and formulary changes that affected 18% of the cohort. Next, baseline corticosteroid exposure was low, restricting our ability to explore the drug’s steroid‑sparing potential. In addition, the proportion of women in our cohort was relatively low (36%), which may reflect clinician caution given the limited safety data for S1P receptor modulators during pregnancy. This underlines the need for further research on etrasimod use in women of childbearing potential, particularly regarding pregnancy outcomes and lactation safety. Finally, participants were drawn from early adopters of etrasimod in the USA and Australia, which may limit generalizability to regions with different prescribing patterns or health‑care systems. Prospective registries incorporating standardised biomarker and endoscopic assessments are required to validate durability of remission and to identify predictors of long-term persistence. Comparative-effectiveness studies against other top-ranked agents and evaluations of sequencing strategies will be important to optimise care. Finally, interventional trials testing biomarker-guided treat-to-target algorithms may help translate early clinical gains into sustained corticosteroid-free remission for a larger proportion of patients. CONCLUSION In this first real-world, multicenter analysis of etrasimod for UC, rapid symptom improvement, high early remission rates, and a favorable safety profile were observed. However, declining persistence underscores the importance of early response assessment and timely treatment optimization, including consideration of therapy change when appropriate. Larger, prospective studies with standardized biomarker and endoscopic endpoints are needed to validate durability, identify predictors of long-term success and optimize sequencing strategies. Abbreviations UC, ulcerative colitis; IBD, inflammatory bowel disease; S1P, sphingosine-1-phosphate; S1PR, sphingosine-1-phosphate receptor; ALC, absolute lymphocyte count; SCCAI, Simple Clinical Colitis Activity Index; CRP, C-reactive protein; FCP, fecal calprotectin; IQR, interquartile range; TNF, tumor necrosis factor; JAK, Janus kinase Declarations Funding: No funding was received for conducting this study. Competing interests: ZF, EF, RY, NKC, CC and RG have no conflicts or disclosures. JSP has served as a consultant for Abbvie, Eli Lilly, Pendopharm, Pfizer, as well as speaker fees from Abbvie, Eli Lilly, Merck, Pfizer, Takeda. DC has served on the speaker bureau for Janssen Pharmaceuticals, Abbvie, Eli Lilly and has served as a consultant to Bristol Myers Squibb (09/18/2024), and Boehringer Ingelheim (08/19/2022), Abbvie, Eli Lilly, Janssen Pharmaceuticals, Pfizer. YKA: YKA has received grants from Janssen, during the conduct of the study; has received speaking and consulting fees from Abbvie, Bristol Myers Squibb, Celltrion, Chiesi, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Shire and Takeda; served on advisory boards member for Abbvie, Bristol Myers Squibb, Chiesi, Janssen, NPS Medicine wise; received research and educational funding from Abbvie, Celltrion, Dr Falk, Janssen, Pfizer, Sandoz and Takeda. JB: JB has received speaking and consulting fees from Abbvie, Bristol Myers Squibb, Celltrion, Chiesi, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Shire, and Takeda; served on advisory boards member for Abbvie, Takeda, Ferring, Celltrion, Bristol Myers Squibb, Chiesi, Janssen, NPS Medicine wise, Anatara, Microba; received research and educational funding from Abbvie, Janssen, Pfizer, Ferring and Takeda. DTR: DTR has received grant support from Takeda; and has served as a consultant for Abbvie, Altrubio, Amgen, Avalo Therapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Chronicles Health, ClostraBio, Connect BioPharma, Cytoki Pharma, Douglas Pharmaceuticals, EcoR1, Ferring Pharma, Image Analysis Group, Index Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Lilly, Odyssey Therapeutics, Pfizer, Prometheus Biosciences, Reistone Biopharma, Samsung Neurologica, Sangamo Therapeutics, Shanghai Pharma Biotherapeutics USA, Takeda, Tissium S.A., and Trellus Health. Author Contributions Conceptualization: JSP, DC, DTR Data curation: CYC, RY, YKA, JB, RG, ZF, EF, NKC Formal analysis: JSP Methodology: JSP, DC, CYC, YKA, JB, RG, NKC, DTR Project administration: NKC, DTR Supervision: DTR Visualization: JSP Writing - original draft: JSP, DTR Writing - review & editing: All authors All authors approved the final manuscript. Consent to Participate: Informed consent was obtained from all individual participants included in the study. Ethics approval statement: This study was performed in line with the principles of the Declaration of Helsinki. The study was approved by the Institutional Review Boards of the University of Chicago and the Mater Misericordiae Ltd Human Research Ethics Committee. Data Availability: The data that support the findings of this study are available from the corresponding author upon reasonable request. Artificial intelligence use: No generative artificial intelligence tools were used in the drafting, analysis, or interpretation of the data presented in this manuscript. References Hracs L, Windsor JW, Gorospe J, Cummings M, Coward S, Buie MJ, et al. Global evolution of inflammatory bowel disease across epidemiologic stages. Nature. 2025;642(8067):458–66. Choi D, Becker M, Ivanov M, Bhat S. Etrasimod: A Sphingosine-1-Phosphate Receptor Modulator for the Treatment of Ulcerative Colitis. Annals of Pharmacotherapy. 2024;(February). DOI: 10.1177/10600280231225770 Fantini MC, Centonze D, Giacobazzi G, Benemei S, Romeo E. Sphingosine-1-Phosphate Receptor Modulators for the Treatment of Ulcerative Colitis: A Narrative Review Focusing on Safety. United European Gastroenterol J. 2025;1–15. Choden T, Cohen NA, Rubin DT. Sphingosine-1 Phosphate Receptor Modulators: The Next Wave of Oral Therapies in Inflammatory Bowel Disease. Gastroenterol Hepatol (N Y). 2022;18(5):265–71. Sandborn WJ, Vermeire S, Peyrin-Biroulet L, Dubinsky MC, Panes J, Yarur A, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies. The Lancet. 2023;401(10383):1159–71. Rubin DT, Ananthakrishnan AN, Siegel CA, Barnes EL, Long MD. ACG Clinical Guideline Update: Ulcerative Colitis in Adults. 2025. DOI: 10.14309/ajg.0000000000003463 Fudman DI, McConnell RA, Ha C, Singh S. Modern Advanced Therapies for Inflammatory Bowel Diseases: Practical Considerations and Positioning. Clinical Gastroenterology and Hepatology. 2025;23(3):454–68. Singh S, Loftus E V., Limketkai BN, Haydek JP, Agrawal M, Scott FI, et al. AGA Living Clinical Practice Guideline on Pharmacological Management of Moderate-to-Severe Ulcerative Colitis. Gastroenterology. 2024;167(7):1307–43. Barberio B, Gracie DJ, Black CJ, Ford AC. Network Meta-Analysis: Efficacy of Biological Therapies and Small Molecules as Maintenance Therapy in Ulcerative Colitis. Aliment Pharmacol Ther. 2025;62(1):4–21. Dai Y, Yang W, Xu L, Pan P, Liu S, Sun Y, et al. Comparative Efficacy of Different Targeted Therapies in Patients With Moderate-to-Severe Ulcerative Colitis: Systematic Review/Network Meta-Analysis and Mechanistic Overview. Pharmacol Res Perspect. 2025;13(3). DOI: 10.1002/prp2.70108 Solitano V, Vuyyuru SK, MacDonald JK, Zayadi A, Parker CE, Narula N, et al. Efficacy and safety of advanced oral small molecules for inflammatory bowel disease: Systematic review and meta-analysis. J Crohns Colitis. 2023;(June):1–17. Walmsley RS, Ayres RC, Pounder RE, Allan RN. A simple clinical colitis activity index. Gut. 1998;43(1):29–32. Zheng J, Zhang X, Zhang L, Li L, Chen M, Chen R, et al. Serum Albumin and Its Trajectory Are Associated With Therapeutic Outcomes in Ulcerative Colitis. Clin Gastroenterol Hepatol. 2025;23(10):1808–16. Massironi S, Viganò C, Palermo A, Pirola L, Mulinacci G, Allocca M, et al. Inflammation and malnutrition in inflammatory bowel disease. Lancet Gastroenterol Hepatol. 2023;8(6):579–90. Higgins PDR, Schwartz M, Mapili J, Krokos I, Leung J, Zimmermann EM. Patient defined dichotomous end points for remission and clinical improvement in ulcerative colitis. Gut. 2005;54(6):782–8. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 [Internet]. Common Terminology Criteria for Adverse Events (CTCAE) Version 50. 2017 [cited 2025 Sep 27]. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf Regueiro M, Siegmund B, Yarur AJ, Steinwurz F, Gecse KB, Goetsch M, et al. Etrasimod for the Treatment of Ulcerative Colitis: Analysis of Infection Events from the ELEVATE UC Clinical Programme. J Crohns Colitis. 2024;18(10):1596–605. Cohen NA, Choi D, Choden T, Cleveland NK, Cohen RD, Rubin DT. Ozanimod in the Treatment of Ulcerative Colitis: Initial Real-World Data from a Large Tertiary Center. Clinical Gastroenterology and Hepatology. 2022;21(9):2407–2409.e2. Maniscalco GT, Sparaco M, Di Gregorio M, Cafasso G, Signoriello E, Romano F, et al. Real-world comparison of lymphopenia profiles in S1P receptor modulators for multiple sclerosis: a multicenter retrospective study. J Neurol. 2025;272(9):559. Yarur AJ, Chiorean M V, Allegretti JR, Cross RK, Ha C, Goetsch M, et al. Etrasimod as a Monotherapy or With Concomitant Use of Corticosteroids and/or Aminosalicylates: Results From the ELEVATE UC Clinical Program. Inflamm Bowel Dis. 2024 Dec DOI: 10.1093/ibd/izae288 Tables Table I. Population characteristics Characteristics Total population ( n = 44) Female Sex ( n, % ) 16 (36.4%) Age, in years (Median [Q1, Q3]) 38.5 [30.5-48.0] Smoking ( n ) Never 37 (84.1%) Ex-smoker 7 (15.9%) Active 0 (0%) Age at diagnosis, in years (Median [Q1, Q3]) 28 [21-38.3] Disease duration, in years (Median [Q1, Q3]) 6.0 [3.0-11.3] Disease extent E1 8 (18.2%) E2 19 (43.2%) E3 16 (36.3%) Unknown 1 (2.3%) Prior therapies 5-ASA 38 (86.4%) Thiopurine 10 (22.7%) Number of advanced therapies 13 (29.5%) 1 prior advanced therapy 9 >2 prior advanced therapies 4 Prior advanced therapy exposure to Anti-TNF 7 Ustekinumab 1 Vedolizumab 8 JAK inhibitor 3 Ozanimod 2 Steroids Systemic steroids at initiation 9 (20.5%) Rectal steroids at initiation 3 (6.8%) Reason for etrasimod start Active disease* 36 (82%) Medication change without inflammation** 8 (18%) SCCAI at time of etrasimod start ( n =44) Clinical remission (0-2) 18 (40.9%) Clinically active disease (3 or more) 26 (59.1%) Laboratory investigations at baseline Elevated CRP, in mg/L 10/32 (31.3%) FCP >150 19/24 (79.2%) Median FCP, in μg/g (Median [Q1, Q3]) ( n = 16) 669.5 [195.5, 1604] Albumin ( n = 38) 4.4 [4.2-4.6] * Active disease by either clinical symptoms, elevated biomarkers, endoscopically active disease or inflammation seen on imaging ** Non-medical switch reasons included side effects from prior therapies and mode of delivery Table II. Proportion of patients achieving clinical response, remission, or worsening at each follow-up visit Week 0 N = 44 # Week 2 N = 44 Week 4 N = 44 Week 8 N = 44 Week 12 N = 44 Week 26 N = 35 Week 52 N = 21 All patients Clinical response* N/A 9 /30 (30%) 2/31 (7%) 3/29 (10%) 7/37 (19%) 3/21 (14%) 0/6 (0%) Clinical remission** 18/44 (41%) 21/30 (70%) 22/31 (71%) 21/29 (72%) 28/37 (76%) 15/21 (71%) 5/6 (83%) Patients with active disease at baseline (SCCAI ≥ 3) Clinical response* N/A 9/18 (50%) 2/18 (11%) 2/16 (13%) 7/20 (35%) 1/13 (8%) 0/5 (0%) Clinical remission** 0/26 (0%) 10/18 (56%) 10/18 (56%) 10/16 (63%) 15/20 (75%) 9/13 (69%) 4/5 (80%) *Clinical response is defined as a decreased in SCCAI ≥ 2 **Clinical remission is defined as SCCAI 0-2 # Number of eligible patients at each time point. Additional Declarations Competing interest reported. JSP has served as a consultant for Abbvie, Eli Lilly, Pendopharm, Pfizer, as well as speaker fees from Abbvie, Eli Lilly, Merck, Pfizer, Takeda. DC has served on the speaker bureau for Janssen Pharmaceuticals, Abbvie, Eli Lilly and has served as a consultant to Bristol Myers Squibb (09/18/2024), and Boehringer Ingelheim (08/19/2022), Abbvie, Eli Lilly, Janssen Pharmaceuticals, Pfizer. YKA: YKA has received grants from Janssen, during the conduct of the study; has received speaking and consulting fees from Abbvie, Bristol Myers Squibb, Celltrion, Chiesi, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Shire and Takeda; served on advisory boards member for Abbvie, Bristol Myers Squibb, Chiesi, Janssen, NPS Medicine wise; received research and educational funding from Abbvie, Celltrion, Dr Falk, Janssen, Pfizer, Sandoz and Takeda. JB: JB has received speaking and consulting fees from Abbvie, Bristol Myers Squibb, Celltrion, Chiesi, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Shire, and Takeda; served on advisory boards member for Abbvie, Takeda, Ferring, Celltrion, Bristol Myers Squibb, Chiesi, Janssen, NPS Medicine wise, Anatara, Microba; received research and educational funding from Abbvie, Janssen, Pfizer, Ferring and Takeda. DTR: DTR has received grant support from Takeda; and has served as a consultant for Abbvie, Altrubio, Amgen, Avalo Therapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Chronicles Health, ClostraBio, Connect BioPharma, Cytoki Pharma, Douglas Pharmaceuticals, EcoR1, Ferring Pharma, Image Analysis Group, Index Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Lilly, Odyssey Therapeutics, Pfizer, Prometheus Biosciences, Reistone Biopharma, Samsung Neurologica, Sangamo Therapeutics, Shanghai Pharma Biotherapeutics USA, Takeda, Tissium S.A., and Trellus Health. Supplementary Files SuppFig1Flowdiagramcompressed.tiff Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 08 Apr, 2026 Editor assigned by journal 01 Apr, 2026 Submission checks completed at journal 31 Mar, 2026 First submitted to journal 30 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9273653","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":621207547,"identity":"54453202-58c6-4534-8478-d1be4e58c784","order_by":0,"name":"Joëlle St‑Pierre","email":"","orcid":"","institution":"University of Calgary","correspondingAuthor":false,"prefix":"","firstName":"Joëlle","middleName":"","lastName":"St‑Pierre","suffix":""},{"id":621207548,"identity":"c0fc26e1-7d8c-4470-b493-f7a4ddc64f74","order_by":1,"name":"David Choi","email":"","orcid":"","institution":"University of Chicago Medical Center","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Choi","suffix":""},{"id":621207549,"identity":"b970dd7a-4758-4f1d-9249-714027dd599d","order_by":2,"name":"Cheng-Yu Chen","email":"","orcid":"","institution":"Mater Hospital","correspondingAuthor":false,"prefix":"","firstName":"Cheng-Yu","middleName":"","lastName":"Chen","suffix":""},{"id":621207554,"identity":"184afd32-54c4-4fc6-bc28-ef471714b161","order_by":3,"name":"Russell Yanofsky","email":"","orcid":"","institution":"University of Chicago Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Russell","middleName":"","lastName":"Yanofsky","suffix":""},{"id":621207556,"identity":"1b6a84e3-0f86-49e9-9ffe-f5c0c4af3c1f","order_by":4,"name":"Yoon-Kyo An","email":"","orcid":"","institution":"Mater Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yoon-Kyo","middleName":"","lastName":"An","suffix":""},{"id":621207559,"identity":"5e1be2a1-cfa4-4637-a301-b9b39666b68b","order_by":5,"name":"Jakob Begun","email":"","orcid":"","institution":"Mater Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jakob","middleName":"","lastName":"Begun","suffix":""},{"id":621207569,"identity":"1ec76673-07d9-4f23-9545-89b848880a6a","order_by":6,"name":"Robert Gilmore","email":"","orcid":"","institution":"Mater Hospital","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"","lastName":"Gilmore","suffix":""},{"id":621207573,"identity":"e6fed777-2015-459e-9b5c-435343e8851e","order_by":7,"name":"Zachary Fine","email":"","orcid":"","institution":"University of Chicago Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Zachary","middleName":"","lastName":"Fine","suffix":""},{"id":621207575,"identity":"18c1b2c2-a3d4-43a9-8a66-c8e83d5bfdc1","order_by":8,"name":"Evan Fear","email":"","orcid":"","institution":"University of Chicago Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Evan","middleName":"","lastName":"Fear","suffix":""},{"id":621207578,"identity":"423ba38e-7bf3-46cd-85ed-53849f6ce1b9","order_by":9,"name":"Natalie K. Choi","email":"","orcid":"","institution":"University of Chicago Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Natalie","middleName":"K.","lastName":"Choi","suffix":""},{"id":621207580,"identity":"0e6e183f-539f-4ded-96b2-b6fdb7dd90c8","order_by":10,"name":"David T. Rubin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYDCCAwxsDAkMNgkMQJKBsUECKsxGUEsaqVoYGA7DtMCE8Wjhu33G7MHDHefz5NsT2CR+7rCQ5+9ffIDhQ9lhnFokz+WYGySeuV1scOYBm2TvGQnDGTeeJTDOOIdbi8EZHjOJxLbbiRskEtikGdskEhhunDFg5m0jqOVc4vwZUC3yIC1/CWs5kNhwA6rF4HyPATMjHi2SZ9jKDRLbkoF+edhs2dsmYbjxBlvCwZ5z6Ti18J1h3vbwZ5sdMMSSD9742VYnL3f+8MEHP8qscWpBArBIAYbAAWLUIwF+UjWMglEwCkbBcAcAV7tbRRjhiLYAAAAASUVORK5CYII=","orcid":"","institution":"University of Chicago Medical Center","correspondingAuthor":true,"prefix":"","firstName":"David","middleName":"T.","lastName":"Rubin","suffix":""}],"badges":[],"createdAt":"2026-03-31 03:10:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9273653/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9273653/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107246858,"identity":"106d21b1-32c4-473c-8a4d-9c112e03e9c0","added_by":"auto","created_at":"2026-04-19 08:10:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1667241,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTreatment persistence on etrasimod through week 52.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKaplan-Meier survival curve illustrating the proportion of patients who remained on etrasimod therapy during the 52-week observation period. All 44 enrolled patients contributed to the baseline risk set (time 0). Permanent discontinuation of etrasimod for any reason (loss of response, adverse event, withdrawal of consent, or investigator decision) was treated as an event, while patients still receiving therapy at their last recorded visit were censored (tick marks on the curve). Numbers at risk in the table denote the size of the evaluable cohort at prespecified time points.\u003c/p\u003e","description":"","filename":"FIGURE1Treatmentpersistencecompressed.png","url":"https://assets-eu.researchsquare.com/files/rs-9273653/v1/fc73a87052810e4193086c15.png"},{"id":107246895,"identity":"a6cdb1d7-9fba-4206-b604-0cf8bffc0e1a","added_by":"auto","created_at":"2026-04-19 08:10:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":460237,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChange in SCCAI scores through Week 12 in the overall cohort and in patients with baseline SCCAI ≥3. \u003c/strong\u003eA. Median SCCAI values with IQR are shown at baseline (week 0) and at weeks 2, 4, 8, and 12 following etrasimod initiation for the overall cohort. Significant reductions in SCCAI compared to baseline were observed at week 2 (p = 0.0076), week 4 (p = 0.0022), week 8 (p = 0.0199), and week 12 (p = 0.0188) using the Wilcoxon signed-rank test.\u003cstrong\u003e \u003c/strong\u003eB. Median SCCAI values with IQR for patients with baseline SCCAI ≥3 (active disease) at the same time points. Significant reductions from baseline were observed at week 2 (p = 0.0004), week 4 (p = 0.0001), week 8 (p = 0.0056), and week 12 (p = 0.0003).\u003cstrong\u003e \u003c/strong\u003eTables below each panel display the number of patients with available SCCAI data at each time point.\u003c/p\u003e","description":"","filename":"Figure2SCCAIhirescompressed.png","url":"https://assets-eu.researchsquare.com/files/rs-9273653/v1/deb8c2009805efdf2939ae43.png"},{"id":107246707,"identity":"d620d629-d54a-4a60-8a27-eed557f15b83","added_by":"auto","created_at":"2026-04-19 08:10:31","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1391649,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChange in ALC following etrasimod initiation.\u003c/strong\u003eMedian ALC values with interquartile ranges (IQR) are shown at baseline (week 0), week 4, and week 12. A significant reduction in ALC was observed from baseline to week 4 (p = 0.0039) and from baseline to week 12 (p = 0.0015) using the Wilcoxon signed-rank test (n = 14 and n = 12 paired samples, respectively.\u003c/p\u003e","description":"","filename":"FIGURE3.Abslymphgraphcompressed.png","url":"https://assets-eu.researchsquare.com/files/rs-9273653/v1/4089ca2c216c166cc1e242b4.png"},{"id":107246953,"identity":"da6a8671-b5b3-4bc6-b326-1c6a623d4fb2","added_by":"auto","created_at":"2026-04-19 08:11:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4320308,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9273653/v1/6f1d4d91-4171-4fc6-9afb-b190a2766677.pdf"},{"id":107246706,"identity":"ec702baa-5e8c-4417-ae3b-28934bcede23","added_by":"auto","created_at":"2026-04-19 08:10:30","extension":"tiff","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":151555,"visible":true,"origin":"","legend":"","description":"","filename":"SuppFig1Flowdiagramcompressed.tiff","url":"https://assets-eu.researchsquare.com/files/rs-9273653/v1/a5cb709dc53eb37292d6edfa.tiff"}],"financialInterests":"Competing interest reported. JSP has served as a consultant for Abbvie, Eli Lilly, Pendopharm, Pfizer, as well as speaker fees from Abbvie, Eli Lilly, Merck, Pfizer, Takeda. DC has served on the speaker bureau for Janssen Pharmaceuticals, Abbvie, Eli Lilly and has served as a consultant to Bristol Myers Squibb (09/18/2024), and Boehringer Ingelheim (08/19/2022), Abbvie, Eli Lilly, Janssen Pharmaceuticals, Pfizer. YKA: YKA has received grants from Janssen, during the conduct of the study; has received speaking and consulting fees from Abbvie, Bristol Myers Squibb, Celltrion, Chiesi, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Shire and Takeda; served on advisory boards member for Abbvie, Bristol Myers Squibb, Chiesi, Janssen, NPS Medicine wise; received research and educational funding from Abbvie, Celltrion, Dr Falk, Janssen, Pfizer, Sandoz and Takeda. JB: JB has received speaking and consulting fees from Abbvie, Bristol Myers Squibb, Celltrion, Chiesi, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Shire, and Takeda; served on advisory boards member for Abbvie, Takeda, Ferring, Celltrion, Bristol Myers Squibb, Chiesi, Janssen, NPS Medicine wise, Anatara, Microba; received research and educational funding from Abbvie, Janssen, Pfizer, Ferring and Takeda. DTR: DTR has received grant support from Takeda; and has served as a consultant for Abbvie, Altrubio, Amgen, Avalo Therapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Chronicles Health, ClostraBio, Connect BioPharma, Cytoki Pharma, Douglas Pharmaceuticals, EcoR1, Ferring Pharma, Image Analysis Group, Index Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Lilly, Odyssey Therapeutics, Pfizer, Prometheus Biosciences, Reistone Biopharma, Samsung Neurologica, Sangamo Therapeutics, Shanghai Pharma Biotherapeutics USA, Takeda, Tissium S.A., and Trellus Health.","formattedTitle":"Multicenter real-world study: Etrasimod provides rapid symptom relief and high early remission rates in ulcerative colitis","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eUlcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease characterized by continuous mucosal inflammation of the colon and rectum. It is associated with substantial morbidity, impaired quality of life, and increased healthcare costs[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Globally, the burden of UC has grown dramatically over the past century and now affects millions of individuals worldwide as its incidence accelerates in newly industrialized and emerging regions[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Projections suggest that prevalence may approach or exceed 1% in many countries by 2040[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This global trend underscores the pressing need for effective and sustainable treatment strategies.\u003c/p\u003e \u003cp\u003eTherapeutic advances over the past two decades, including biologics and small molecules, have transformed UC management; however, a substantial proportion of patients fail to achieve sustained remission or discontinue therapy due to lack of efficacy or safety concerns[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Sphingosine-1-phosphate receptor (S1PR) modulators represent a novel class of oral therapies that reduce lymphocyte trafficking to the gut by internalizing S1P receptors and sequestering lymphocytes in lymph nodes[\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Among these, etrasimod, a selective S1PR\u003csub\u003e1,4,5\u003c/sub\u003e modulator, offers advantages such as no need for dose titration, and a favorable cardiovascular safety profile[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe efficacy and safety of etrasimod have been demonstrated in the pivotal phase 3 ELEVATE UC 12 and ELEVATE UC 52 trials, where etrasimod significantly improved clinical remission, endoscopic and histologic outcomes compared with placebo during both induction and maintenance[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. At week 12, clinical remission rates were approximately 25\u0026ndash;27% with etrasimod versus 7\u0026ndash;15% with placebo, and benefits were sustained through week 52[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These findings, combined with an acceptable safety profile and oral route of administration, have positioned S1PR modulators as a recommended induction and maintenance option for patients with moderate-to-severe UC[\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Indirect comparisons from network meta-analyses suggest that etrasimod ranks among the most effective agents for maintenance remission in UC, particularly in treat-through designs[\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], but validation in routine clinical practice remains essential.\u003c/p\u003e \u003cp\u003eAlthough randomized controlled trials provide high internal validity and are the basis for drug approval, their strict eligibility criteria and standardized monitoring may not reflect real-world clinical practice and efficacy, where patients often present with comorbidities, laboratory abnormalities, and variable disease activity. Real-world evidence is therefore essential to assess treatment effectiveness, corticosteroid-sparing potential, persistence, and safety under routine care conditions.\u003c/p\u003e \u003cp\u003eWe describe the first real-world effectiveness and safety analysis of etrasimod in patients with UC across two tertiary care centers in the United States and Australia. Specifically, we examined clinical response, remission, corticosteroid use, treatment persistence, and adverse events for up to 52 weeks.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and patient selection\u003c/h2\u003e \u003cp\u003e We conducted a prospective, observational, multicenter cohort study at two tertiary care centers: the University of Chicago IBD Center (Chicago, IL, USA) and the Mater Hospital Brisbane (Brisbane, QLD, Australia). Consecutive adult patients (\u0026ge;\u0026thinsp;18 years) with an established diagnosis of UC who were initiated on etrasimod were included. Patients were recruited beginning in December 2023, with clinical data collected through June 2025. Patients were eligible if etrasimod was started for active disease, defined by clinical, biochemical, endoscopic, or imaging evidence of inflammation, or for a non-medical switch from a prior advanced therapy. Active disease was defined by at least one of the following: SCCAI\u0026thinsp;\u0026ge;\u0026thinsp;3, elevated biomarkers (CRP\u0026thinsp;\u0026gt;\u0026thinsp;5 mg/L or fecal calprotectin\u0026thinsp;\u0026gt;\u0026thinsp;150 \u0026micro;g/g), endoscopic evidence of inflammation (Mayo endoscopic subscore [MES]\u0026thinsp;\u0026ge;\u0026thinsp;2), or imaging evidence of colitis (bowel wall thickening, hyperenhancement, and/or pericolonic inflammatory changes on cross-sectional imaging). Patients with previous colectomy or an indication other than UC were excluded as disease activity parameters are not comparable in post-surgical populations.\u003c/p\u003e \u003cp\u003eEtrasimod was prescribed according to local regulatory approvals and clinical judgment. All patients received the standard oral dose of etrasimod (2 mg once daily). There was no mandated washout period for prior therapy. Patients were followed from treatment initiation (Week 0) through subsequent clinical visits as part of routine care.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData Collection \u0026 Variables\u003c/h3\u003e\n\u003cp\u003eDemographic and clinical characteristics were extracted from electronic health records. Baseline data included age, sex, age at UC diagnosis, disease duration, Montreal classification extent, smoking status, prior UC medication exposure, and concomitant therapy at etrasimod initiation. Corticosteroid use at initiation and during follow-up was recorded. Follow-up data were reviewed at prespecified time points according to our real-world prospective data collection protocol. Disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI) at baseline and weeks 2, 4, 8, 12, 26, and 52[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Laboratory markers included C-reactive protein (CRP), fecal calprotectin (FCP), and albumin. CRP was collected at baseline, week 4, and week 12; FCP at baseline, week 8, and week 12; and absolute lymphocyte count (ALC) at baseline, week 4, and week 12. Albumin was included as a marker of systemic inflammation and nutritional status, which has been shown to correlate with disease severity and predict therapeutic responses in patients with UC[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Endoscopic and cross-sectional imaging data were recorded when available but were not systematically obtained. Additional investigations were obtained at the discretion of the treating physician. The number of patients with available data at each prespecified time point is indicated in figures and tables. Analyses were based on observed data without imputation for missing values.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome of interest was treatment persistence on etrasimod, defined as the time from initiation to permanent discontinuation for any reason, and analyzed using time-to-event methods across the observation period. Persistence was chosen as the primary endpoint as it reflects both effectiveness and tolerability in routine care, integrating clinical response, safety, and patient/physician decision-making. Secondary outcomes included clinical effectiveness and safety measures. Clinical response was defined as a reduction of at least three points in the SCCAI from baseline among patients with an initial SCCAI score of 3 or higher, and clinical remission was defined as an SCCAI score of 2 or less, consistent with established definitions[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. These secondary outcomes were assessed at Weeks 12, 26, and 52 when available. Additional secondary outcomes included changes in inflammatory biomarkers, specifically CRP and FCP. Absolute lymphocyte count (ALC) was recorded at baseline and during follow-up when available. Lymphopenia was categorized as mild/moderate (\u0026lt;\u0026thinsp;1.0 \u0026times; 10⁹/L) and severe (\u0026lt;\u0026thinsp;0.5 \u0026times; 10⁹/L) for descriptive analysis, consistent with thresholds applied in the ELEVATE UC program and aligned with CTCAE criteria[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. As in prior S1PR modulator trials, lymphopenia was considered an expected pharmacodynamic effect rather than an adverse event unless it resulted in clinical consequences (e.g., infection or drug discontinuation)[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Safety outcomes included the occurrence of adverse events (AEs) and serious adverse events (SAEs). AEs were defined as any untoward medical occurrence in a patient receiving etrasimod, whether considered related to the study drug or not. SAEs were defined as events resulting in death, life-threatening complications, hospitalization, persistent or significant disability, congenital anomaly, or any other medically important event, including events leading to permanent discontinuation of etrasimod.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were summarized as medians with interquartile ranges (IQR), and categorical variables as frequencies and percentages. For the primary endpoint of treatment persistence, Kaplan-Meier analyses were performed using an intention-to-treat framework in which permanent discontinuation of etrasimod or loss to follow-up was counted as an event at the time of last contact. This approach yields conservative estimates of persistence, as patients with missing follow-up were not censored but considered to have discontinued therapy. We defined \u0026ldquo;eligible\u0026rdquo; patients at each landmark time point (weeks 12, 26, and 52) as those who had initiated etrasimod at least that many weeks before database lock. The flow diagram summarizes, among eligible patients, the number remaining on therapy, those who discontinued, and those with missing clinical data (Supplementary Fig.\u0026nbsp;1). In contrast, analyses of clinical and biochemical outcomes were based on available data without imputation and therefore reflect only patients with documented assessments at each time point. Pairwise comparisons of disease activity scores (i.e., SCCAI) between baseline (week 0) and each follow-up time point (weeks 2, 4, 8, and 12) were performed using the Wilcoxon signed-rank test, given the non-parametric distribution and ordinal nature of SCCAI. Analyses were restricted to these intervals due to sufficient paired data availability; sample sizes at later time points (weeks 26 and 52) were too limited to permit meaningful statistical testing. Because this was an exploratory real-world study with prespecified follow-up intervals, repeated pairwise comparisons were conducted without formal adjustment for multiplicity given the small sample size which substantially reduce statistical power. Therefore, p-values are interpreted descriptively and in conjunction with effect magnitude. A two-sided p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Analyses were performed using GraphPad Prism (version 10.4.2). Analyses were based on available data, and missing values were not imputed.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEthical considerations\u003c/h3\u003e\n\u003cp\u003e The study was approved by the Institutional Review Boards of the University of Chicago and the Mater Misericordiae Ltd Human Research Ethics Committee.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eBaseline Characteristics\u003c/h2\u003e \u003cp\u003eForty-four patients were included across two tertiary care centers (University of Chicago, Chicago, IL, USA and Mater Hospital Brisbane, Brisbane, QLD, Australia). Population characteristics are reported in Table I. The median age at etrasimod initiation was 38.5 years (IQR 30.5\u0026ndash;48.0), and 16 patients (36.4%) were female. The median age at UC diagnosis was 28 years (IQR 21-38.3), with a median disease duration of 6.0 years (IQR 3.0-11.3). Most patients were never smokers (n\u0026thinsp;=\u0026thinsp;37, 84.1%), and none reported active smoking at treatment initiation. With respect to disease extent, 8 patients (18.2%) had proctitis (E1), 19 patients (43.2%) had left-sided colitis (E2), and 16 patients (36.3%) had extensive colitis (E3), while 1 patient (2.3%) had unknown extent of disease.\u003c/p\u003e \u003cp\u003ePrior exposure to 5-ASA was common (n\u0026thinsp;=\u0026thinsp;38, 86.4%), and 10 patients (22.7%) had been treated with thiopurines. Thirteen patients (29.5%) had previously received advanced therapy, including anti-TNF agents (n\u0026thinsp;=\u0026thinsp;7), vedolizumab (n\u0026thinsp;=\u0026thinsp;8), ustekinumab (n\u0026thinsp;=\u0026thinsp;1), Janus kinase (JAK) inhibitors (n\u0026thinsp;=\u0026thinsp;3), and ozanimod (n\u0026thinsp;=\u0026thinsp;2). Four patients (9%) were previously exposed to more than two advanced therapies. At etrasimod initiation, 12 patients (27.3%) were receiving systemic corticosteroids, and 3 patients (6.8%) were on rectal steroids. Within 12 weeks of treatment initiation, 3 patients (6.8%) required new systemic corticosteroids, and 2 patients (4.5%) required new rectal steroids.\u003c/p\u003e \u003cp\u003eThe most common reason for starting etrasimod was active disease (n\u0026thinsp;=\u0026thinsp;36, 82%), defined by clinical, biochemical, endoscopic, or imaging evidence of inflammation, while 8 patients (18%) were switched for non-medical reasons. Of these, two patients were switched due to side effects from their previous advanced therapy and three for preference in mode of delivery (oral as compared to IV). Among patients with available SCCAI data at baseline (n\u0026thinsp;=\u0026thinsp;44), 18 patients (40.9%) were in clinical remission (SCCAI 0\u0026ndash;2), while 26 patients (59.1%) had active disease (SCCAI\u0026thinsp;\u0026ge;\u0026thinsp;3).\u003c/p\u003e \u003cp\u003eBaseline laboratory data, where available, showed that 10 of 32 patients (31.3%) had an elevated CRP (\u0026gt;\u0026thinsp;5 mg/L), and 19 of 24 patients (79.2%) had fecal calprotectin\u0026thinsp;\u0026gt;\u0026thinsp;150 \u0026micro;g/g, with a median FCP of 669.5 \u0026micro;g/g (IQR 195.5\u0026ndash;1604). The median serum albumin at baseline was 4.4 g/dL (IQR 4.2\u0026ndash;4.6).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTreatment persistence\u003c/h3\u003e\n\u003cp\u003eTreatment persistence on etrasimod over the 52-week observation period is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Using an intention-to-treat approach, where loss to follow-up was considered a treatment discontinuation event, the estimated probability of remaining on etrasimod was 88.6% at Week 8, 61.4% at Week 12, 40.9% at Week 26, and 35.1% at Week 52. The number of patients at risk decreased from 44 at baseline to 39 at Week 12, 24 at Week 26, and 7 at Week 52. The median time to treatment discontinuation was not reached within the study period.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eClinical disease activity\u003c/h2\u003e \u003cp\u003eFor the overall cohort (n\u0026thinsp;=\u0026thinsp;44), the median SCCAI at baseline was 3.0 (IQR 1.0-6.8). Median SCCAI decreased to 2.0 at week 2 (IQR 0\u0026ndash;3.0), 1.0 at week 4 (IQR 0\u0026ndash;3.0), and 0.0 at weeks 8 and 12 (IQR 0\u0026ndash;3.0 and 0\u0026ndash;2.0, respectively) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). Significant reductions compared to baseline were observed at all follow-up points (week 2: p\u0026thinsp;=\u0026thinsp;0.0076; week 4: p\u0026thinsp;=\u0026thinsp;0.0022; week 8: p\u0026thinsp;=\u0026thinsp;0.0199; week 12: p\u0026thinsp;=\u0026thinsp;0.0188, Wilcoxon signed-rank test). The number of patients with available SCCAI data at each time point ranged from 29 to 44 and is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Among patients with clinically active disease at baseline (SCCAI\u0026thinsp;\u0026ge;\u0026thinsp;3, n\u0026thinsp;=\u0026thinsp;26), the median SCCAI was 5.0 (IQR 4.0\u0026ndash;9.0) at initiation. This decreased to 2.0 (IQR 1.0\u0026ndash;4.0) at week 2, 2.0 (IQR 0-3.3) at week 4, 1.5 (IQR 0-4.5) at Week 8, and 0.5 (IQR 0\u0026ndash;2.0) at week 12 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Reductions from baseline were significant at all time points (week 2: p\u0026thinsp;=\u0026thinsp;0.0004; week 4: p\u0026thinsp;=\u0026thinsp;0.0001; week 8: p\u0026thinsp;=\u0026thinsp;0.0056; week 12: p\u0026thinsp;=\u0026thinsp;0.0003). The number of patients with available SCCAI data for this subgroup ranged from 16 to 26, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eCategorical outcomes are summarized in Table II. At baseline (week 0), 18 of 44 patients (41%) were already in clinical remission (SCCAI 0\u0026ndash;2). By week 2, remission was observed in 70% of patients and remained relatively stable thereafter (71% at week 4, 72% at week 8, 76% at week 12, 71% at week 26, and 83% at week 52). The majority of patients with clinical response, defined as a decrease in SCCAI\u0026thinsp;\u0026ge;\u0026thinsp;2 from baseline, achieved this by week 3 (30%). Only one patient achieved clinical response beyond week 12. In the subgroup with active disease at baseline (SCCAI\u0026thinsp;\u0026ge;\u0026thinsp;3), 50% achieved clinical response by week 2 and an additional 35% at week 12. Clinical remission occurred in 56% at week 2, increasing to 75% at week 12 and 80% at week 52, albeit only 6 patients (out of 21 included patients at that timeline) were still on etrasimod at that time point. These findings indicate that many patients achieved remission early, with sustained benefit in those remaining on therapy.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eCorticosteroid use\u003c/h2\u003e \u003cp\u003eAt baseline, nine patients were receiving systemic prednisone at a dose of 20 mg or higher. Three patients (6.8%) were also using rectal corticosteroids at the start of etrasimod. Three patients of the patients on systematic steroids at baseline were successfully weaned off steroids and continued etrasimod while the other 9 patients eventually discontinued etrasimod. During follow-up, three patients who were not on corticosteroids at baseline required initiation of systemic steroids prior to Week 12, including two patients who were in clinical remission at baseline and one with active disease at baseline (SCCAI\u0026thinsp;\u0026ge;\u0026thinsp;3). By 24 weeks, one additional patient required rectal corticosteroid therapy. Rates of corticosteroid-free remission could not be meaningfully assessed due to the small number of patients on systemic corticosteroids at baseline and during follow-up; therefore, this outcome was not analyzed further.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eBiochemical markers\u003c/h2\u003e \u003cp\u003eCRP data were available for 32 patients at baseline, 15 at Week 4, and 16 at Week 12. At baseline, the median CRP was 3.0 mg/L (IQR 1.6-5.0). At Week 4, the median CRP remained 3.0 mg/L (IQR 3.0-3.6), and at Week 12, it was also 3.0 mg/L (IQR 1.8\u0026ndash;7.3). Among patients with paired CRP measurements (n\u0026thinsp;=\u0026thinsp;10), individual trends were variable, and no formal statistical testing was performed due to limited paired data. FCP was available for 24 patients at baseline, 8 at Week 8, and 13 at Week 12. At baseline, the median FCP was 669.5 \u0026micro;g/g (IQR 190.5-1,648). At Week 8, the median FCP decreased to 171.3 \u0026micro;g/g (IQR 10.3-2,866), and at Week 12, it was 234 \u0026micro;g/g (IQR 51.0\u0026ndash;1,320). Among patients with paired measurements (n\u0026thinsp;=\u0026thinsp;8), trends were heterogeneous, and no formal statistical testing was performed due to limited sample size.\u003c/p\u003e \u003cp\u003eALC declined significantly following etrasimod initiation (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The median ALC at baseline was 1.83 \u0026times;10⁹/L (IQR 1.35\u0026ndash;2.14), compared to 0.68 \u0026times;10⁹/L (IQR 0.48\u0026ndash;1.04) at week 4 and 0.70 \u0026times;10⁹/L (IQR 0.46\u0026ndash;1.16) at week 12. Among patients with paired measurements, ALC was significantly lower at week 4 compared to baseline (p\u0026thinsp;=\u0026thinsp;0.0039) and at week 12 compared to baseline (p\u0026thinsp;=\u0026thinsp;0.0015) using the Wilcoxon signed-rank test. The proportion of patients with lymphopenia (\u0026lt;\u0026thinsp;1.0 \u0026times; 10⁹/L) increased from 10.5% (n\u0026thinsp;=\u0026thinsp;4/38) at baseline to 68.8% (n\u0026thinsp;=\u0026thinsp;11/16) at week 4 and 78.6% (n\u0026thinsp;=\u0026thinsp;11/14) at week 12. Severe lymphopenia (\u0026lt;\u0026thinsp;0.5 \u0026times; 10⁹/L) was observed in 5.3% (n\u0026thinsp;=\u0026thinsp;2/38), 25.0% (n\u0026thinsp;=\u0026thinsp;4/16), and 28.6% (n\u0026thinsp;=\u0026thinsp;4/14) of patients at these respective timepoints. No patients discontinued etrasimod due to lymphopenia.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eSafety\u003c/h2\u003e \u003cp\u003eNo SAEs were reported during the study period. Two patients experienced mild AEs of lightheadedness, occurring at Week 2 and Week 8, respectively; both episodes resolved without intervention and did not lead to etrasimod discontinuation. There were no instances of symptomatic bradycardia. The most frequent safety-related event leading to treatment discontinuation was disease exacerbation, which accounted for all discontinuations observed in the cohort. No other treatment-related adverse events were documented.\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis multicentre analysis is the first real-world report of etrasimod in UC and provides complementary evidence to the pivotal ELEVATE UC trials[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Etrasimod induced a rapid fall in median SCCAI from 5.0 to 0.5 among patients with clinically active disease at baseline (SCCAI\u0026thinsp;\u0026ge;\u0026thinsp;3), with significant improvement apparent by week 2 and maintained through week 12. Comparable onset and depth of response were documented in ELEVATE UC[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Recent network meta-analyses extend these observations: Barberio et al. (2025) ranking etrasimod first for clinical and corticosteroid-free remission in treat-through designs, while Dai et al. (2025) placed it among the most effective agents for maintenance remission, and Solitano et al. (2023) similarly demonstrating high efficacy of etrasimod compared with other advanced therapies in the maintenance setting[\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Together, these data and our findings suggest that the clinical benefits of etrasimod observed in clinical trials may extend to real-world practice, although confirmation in larger cohorts with standardized follow-up is needed. These findings align with contemporary positioning frameworks that recommend S1PR modulators as effective induction and maintenance options for moderate-to-severe UC, particularly in biologic-na\u0026iuml;ve patients or those seeking oral therapy[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Real-world experience with other S1PR modulators, such as ozanimod, supports the translation of pivotal trial efficacy into routine clinical practice, but also highlights the challenge of maintaining long-term persistence. In a prospective cohort of 45 patients with UC treated at a tertiary center, Cohen et al. reported week 10 clinical remission in 53% and response in 58%, but only 25% maintained either outcome at 52 weeks, despite a favorable safety profile and absence of new safety signals[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The observed decline in persistence in our etrasimod cohort parallels these findings and may reflect similar real-world factors, including treatment-refractory populations, heterogeneous monitoring, and broader eligibility compared with clinical trials.\u003c/p\u003e \u003cp\u003eSteroid exposure was low at baseline in our cohort (14% receiving systemic corticosteroids), and most patients remained off steroids during follow-up. While this may point toward a steroid-sparing profile, the small sample size and limited corticosteroid use at initiation restrict firm conclusions. Treatment persistence fell from 61% at week 12 to 29% at week 52, lower than the 52-week continuation observed in the treat-through trial programme. Attrition in routine care likely reflects broader inclusion criteria, heterogeneous treatment goals, and less intensive follow-up than in clinical trials. Early assessment (weeks 8\u0026ndash;12) therefore remains essential to distinguish responders from those requiring an alternative strategy.\u003c/p\u003e \u003cp\u003eBiochemical markers demonstrated heterogeneous changes; however, the average change in inflammatory biomarkers trended in a favorable direction. ALC declined significantly after treatment initiation, consistent with the expected pharmacodynamic effect of S1PR modulation described in the ELEVATE UC safety analyses[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and in real-world data from multiple sclerosis populations showing variable degrees of lymphopenia across S1P receptor modulators, although etrasimod was not included in this study[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Lymphopenia (\u0026lt;\u0026thinsp;1.0 \u0026times; 10⁹/L) was common by weeks 4 and 12 (68.8% and 78.6%, respectively), with severe lymphopenia (\u0026lt;\u0026thinsp;0.5 \u0026times; 10⁹/L) observed in up to 28.6% of patients, yet no cases required discontinuation or resulted in infection.\u003c/p\u003e \u003cp\u003eThese findings have several practical ramifications for routine care. First, we demonstrate real-world applicability of this novel therapy for patients with UC. Second, the rapid symptom improvement observed in everyday practice confirms that etrasimod can provide early relief; however, discontinuation in 39% of patients by week 12 and 71% by week 52 underscores the need for early response assessment and ongoing management to monitor the sustained benefit. Further, our low baseline use, subsequent reduction of corticosteroids point to a steroid‑sparing profile, and post‑hoc ELEVATE analyses demonstrating no additional benefit from concomitant corticosteroids or 5‑aminosalicylates support an initial monotherapy or rapid steroid weaning strategy when appropriate[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Importantly, the predictable, reversible lymphopenia seen with etrasimod was not accompanied by excess serious, severe or opportunistic infections, consistent with pooled ELEVATE safety data that showed comparable or lower serious‑infection rates versus placebo[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Taken together, this evidence demonstrates that etrasimod is a convenient, oral, first‑line advanced therapy that delivers rapid symptom control while maintaining a favourable infection profile; nonetheless, treat‑to‑target monitoring between weeks 8 and 12 remains essential to confirm durable benefit and to expedite therapeutic escalation when needed.\u003c/p\u003e \u003cp\u003eThis analysis has several important limitations. First, although multicentre, the cohort comprised only 44 patients and follow‑up visits were not protocol‑driven, limiting statistical power. Repeated pairwise comparisons were exploratory and not adjusted for multiplicity, increasing the risk of type I error. Second, while treatment persistence was selected as our primary outcome given its pragmatic importance in real-world studies, we acknowledge that it may be influenced by factors beyond drug effectiveness, including access, insurance coverage, and patient preference. We therefore reported detailed clinical outcomes in parallel to better capture real-world effectiveness. Third, objective indicators of deep remission were incompletely captured, including biochemical, sonographic, endoscopic and histologic assessments were available in less than one‑third of participants, precluding robust evaluation of mucosal or transmural healing. Fourth, safety analyses were under‑powered to detect uncommon adverse events and ALC monitoring was not standardised across centres. Fifth, persistence estimates may be confounded by non‑medical switching and formulary changes that affected 18% of the cohort. Next, baseline corticosteroid exposure was low, restricting our ability to explore the drug\u0026rsquo;s steroid‑sparing potential. In addition, the proportion of women in our cohort was relatively low (36%), which may reflect clinician caution given the limited safety data for S1P receptor modulators during pregnancy. This underlines the need for further research on etrasimod use in women of childbearing potential, particularly regarding pregnancy outcomes and lactation safety. Finally, participants were drawn from early adopters of etrasimod in the USA and Australia, which may limit generalizability to regions with different prescribing patterns or health‑care systems.\u003c/p\u003e \u003cp\u003eProspective registries incorporating standardised biomarker and endoscopic assessments are required to validate durability of remission and to identify predictors of long-term persistence. Comparative-effectiveness studies against other top-ranked agents and evaluations of sequencing strategies will be important to optimise care. Finally, interventional trials testing biomarker-guided treat-to-target algorithms may help translate early clinical gains into sustained corticosteroid-free remission for a larger proportion of patients.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn this first real-world, multicenter analysis of etrasimod for UC, rapid symptom improvement, high early remission rates, and a favorable safety profile were observed. However, declining persistence underscores the importance of early response assessment and timely treatment optimization, including consideration of therapy change when appropriate. Larger, prospective studies with standardized biomarker and endoscopic endpoints are needed to validate durability, identify predictors of long-term success and optimize sequencing strategies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eUC, ulcerative colitis; IBD, inflammatory bowel disease; S1P, sphingosine-1-phosphate; S1PR, sphingosine-1-phosphate receptor; ALC, absolute lymphocyte count; SCCAI, Simple Clinical Colitis Activity Index; CRP, C-reactive protein; FCP, fecal calprotectin; IQR, interquartile range; TNF, tumor necrosis factor; JAK, Janus kinase\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e No funding was received for conducting this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e ZF, EF, RY, NKC, CC and RG have no conflicts or disclosures. JSP has served as a consultant for Abbvie, Eli Lilly, Pendopharm, Pfizer, as well as speaker fees from Abbvie, Eli Lilly, Merck, Pfizer, Takeda. DC has served on the speaker bureau for Janssen Pharmaceuticals, Abbvie, Eli Lilly and has served as a consultant to Bristol Myers Squibb (09/18/2024), and Boehringer Ingelheim (08/19/2022), Abbvie, Eli Lilly, Janssen Pharmaceuticals, Pfizer. YKA: YKA has received grants from Janssen, during the conduct of the study; has received speaking and consulting fees from Abbvie, Bristol Myers Squibb, Celltrion, Chiesi, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Shire and Takeda; served on advisory boards member for Abbvie, Bristol Myers Squibb, Chiesi, Janssen, NPS Medicine wise; received research and educational funding from Abbvie, Celltrion, Dr Falk, Janssen, Pfizer, Sandoz and Takeda. JB: JB has received speaking and consulting fees from Abbvie, Bristol Myers Squibb, Celltrion, Chiesi, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Shire, and Takeda; served on advisory boards member for Abbvie, Takeda, Ferring, Celltrion, Bristol Myers Squibb, Chiesi, Janssen, NPS Medicine wise, Anatara, Microba; received research and educational funding from Abbvie, Janssen, Pfizer, Ferring and Takeda. DTR: DTR has received grant support from Takeda; and has served as a consultant for Abbvie, Altrubio, Amgen, Avalo Therapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Chronicles Health, ClostraBio, Connect BioPharma, Cytoki Pharma, Douglas Pharmaceuticals, EcoR1, Ferring Pharma, Image Analysis Group, Index Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Lilly, Odyssey Therapeutics, Pfizer, Prometheus Biosciences, Reistone Biopharma, Samsung Neurologica, Sangamo Therapeutics, Shanghai Pharma Biotherapeutics USA, Takeda, Tissium S.A., and Trellus Health. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: JSP, DC, DTR\u003c/p\u003e\n\u003cp\u003eData curation: CYC, RY, YKA, JB, RG, ZF, EF, NKC\u003c/p\u003e\n\u003cp\u003eFormal analysis: JSP\u003c/p\u003e\n\u003cp\u003eMethodology: JSP, DC, CYC, YKA, JB, RG, NKC, DTR\u003c/p\u003e\n\u003cp\u003eProject administration: NKC, DTR\u003c/p\u003e\n\u003cp\u003eSupervision: DTR\u003c/p\u003e\n\u003cp\u003eVisualization: JSP\u003c/p\u003e\n\u003cp\u003eWriting - original draft: JSP, DTR\u003c/p\u003e\n\u003cp\u003eWriting - review \u0026amp; editing: All authors\u003c/p\u003e\n\u003cp\u003eAll authors approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate: \u003c/strong\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval statement:\u003c/strong\u003e This study was performed in line with the principles of the Declaration of Helsinki. The study was approved by the Institutional Review Boards of the University of Chicago and the Mater Misericordiae Ltd Human Research Ethics Committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability:\u003c/strong\u003e The data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eArtificial intelligence use:\u003c/strong\u003e No generative artificial intelligence tools were used in the drafting, analysis, or interpretation of the data presented in this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHracs L, Windsor JW, Gorospe J, Cummings M, Coward S, Buie MJ, et al. Global evolution of inflammatory bowel disease across epidemiologic stages. Nature. 2025;642(8067):458\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoi D, Becker M, Ivanov M, Bhat S. 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Common Terminology Criteria for Adverse Events (CTCAE) Version 50. 2017 [cited 2025 Sep 27]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf\u003c/span\u003e\u003cspan address=\"https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRegueiro M, Siegmund B, Yarur AJ, Steinwurz F, Gecse KB, Goetsch M, et al. Etrasimod for the Treatment of Ulcerative Colitis: Analysis of Infection Events from the ELEVATE UC Clinical Programme. J Crohns Colitis. 2024;18(10):1596\u0026ndash;605.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCohen NA, Choi D, Choden T, Cleveland NK, Cohen RD, Rubin DT. Ozanimod in the Treatment of Ulcerative Colitis: Initial Real-World Data from a Large Tertiary Center. Clinical Gastroenterology and Hepatology. 2022;21(9):2407\u0026ndash;2409.e2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eManiscalco GT, Sparaco M, Di Gregorio M, Cafasso G, Signoriello E, Romano F, et al. Real-world comparison of lymphopenia profiles in S1P receptor modulators for multiple sclerosis: a multicenter retrospective study. J Neurol. 2025;272(9):559.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYarur AJ, Chiorean M V, Allegretti JR, Cross RK, Ha C, Goetsch M, et al. Etrasimod as a Monotherapy or With Concomitant Use of Corticosteroids and/or Aminosalicylates: Results From the ELEVATE UC Clinical Program. Inflamm Bowel Dis. 2024 Dec DOI: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/ibd/izae288\u003c/span\u003e\u003cspan address=\"10.1093/ibd/izae288\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable I. Population characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTotal population (\u003cem\u003en\u003c/em\u003e = 44)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFemale Sex (\u003cem\u003en, %\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16 (36.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAge, in years (Median [Q1, Q3])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e38.5 [30.5-48.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003eSmoking (\u003cem\u003en\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Never\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e37 (84.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Ex-smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7 (15.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Active\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAge at diagnosis, in years (Median [Q1, Q3])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e28 [21-38.3]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDisease duration, in years (Median [Q1, Q3])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6.0 [3.0-11.3]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003eDisease extent\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; E1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; E2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e19 (43.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; E3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16 (36.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1 (2.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePrior therapies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 5-ASA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e38 (86.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Thiopurine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Number of advanced therapies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13 (29.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 1 prior advanced therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026gt;2 prior advanced therapies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Prior advanced therapy exposure to\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Anti-TNF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Ustekinumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Vedolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; JAK inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Ozanimod\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003eSteroids\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Systemic steroids at initiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9 (20.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Rectal steroids at initiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3 (6.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003eReason for etrasimod start\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Active disease*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e36 (82%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Medication change without inflammation**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8 (18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003eSCCAI at time of etrasimod start (\u003cem\u003en\u003c/em\u003e=44)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Clinical remission (0-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e18 (40.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Clinically active disease (3 or more)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e26 (59.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003eLaboratory investigations at baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Elevated CRP, in mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10/32 (31.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; FCP \u0026gt;150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e19/24 (79.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Median FCP, in \u0026mu;g/g (Median [Q1, Q3]) (\u003cem\u003en\u003c/em\u003e = 16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e669.5 [195.5, 1604]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Albumin (\u003cem\u003en\u003c/em\u003e = 38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.4 [4.2-4.6]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*\u003cem\u003eActive disease by either clinical symptoms, elevated biomarkers, endoscopically active disease or inflammation seen on imaging\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e**\u003cem\u003eNon-medical switch reasons included side effects from prior therapies and mode of delivery\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable II. Proportion of patients achieving clinical response, remission, or worsening at each follow-up visit\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"651\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek\u0026nbsp;0\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN = 44\u003csup\u003e#\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek\u0026nbsp;2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN = 44\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek\u0026nbsp;4\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN = 44\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek\u0026nbsp;8\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN = 44\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek\u0026nbsp;12\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN = 44\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek\u0026nbsp;26\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN = 35\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek\u0026nbsp;52\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN = 21\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"8\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll patients\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical response*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e9 /30\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e2/31\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e3/29\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e7/37\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e3/21\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e0/6\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical remission**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e18/44\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(41%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e21/30\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e22/31\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e21/29\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e28/37\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e15/21\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e5/6\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"8\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients with active disease at baseline (SCCAI\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u0026ge; 3)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical response*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\"\u003e\n \u003cp\u003e9/18\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\"\u003e\n \u003cp\u003e2/18\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\"\u003e\n \u003cp\u003e2/16\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\"\u003e\n \u003cp\u003e7/20\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\"\u003e\n \u003cp\u003e1/13\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\"\u003e\n \u003cp\u003e0/5\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical remission**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0/26\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\"\u003e\n \u003cp\u003e10/18\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\"\u003e\n \u003cp\u003e10/18\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\"\u003e\n \u003cp\u003e10/16\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(63%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\"\u003e\n \u003cp\u003e15/20\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\"\u003e\n \u003cp\u003e9/13\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(69%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\"\u003e\n \u003cp\u003e4/5\u003c/p\u003e\n \u003cp\u003e(80%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Clinical response is defined as a decreased in SCCAI \u0026ge; 2\u003c/p\u003e\n\u003cp\u003e**Clinical remission is defined as SCCAI 0-2\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e#\u003c/sup\u003eNumber of eligible patients at each time point.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"digestive-diseases-and-sciences","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ddsj","sideBox":"Learn more about [Digestive Diseases and Sciences](http://link.springer.com/journal/10620)","snPcode":"10620","submissionUrl":"https://submission.nature.com/new-submission/10620/3","title":"Digestive Diseases and Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"ulcerative colitis, etrasimod, sphingosine‑1‑phosphate modulator, real‑world evidence, observational study","lastPublishedDoi":"10.21203/rs.3.rs-9273653/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9273653/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003e Etrasimod, an oral sphingosine-1-phosphate receptor modulator, demonstrated efficacy and safety in pivotal phase 3 trials for moderate-to-severe ulcerative colitis (UC). This study aimed to evaluate the real-world effectiveness, safety, and treatment persistence of etrasimod in patients with UC treated.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a prospective, observational study across two tertiary centers. Adult UC patients initiating etrasimod were followed for up to 52 weeks. Primary outcome was treatment persistence. Secondary outcomes included clinical response (\u0026ge;\u0026thinsp;3-point SCCAI reduction), clinical remission (SCCAI\u0026thinsp;\u0026le;\u0026thinsp;2) and safety.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eForty-four patients were included; median age was 38.5 years, and 29.5% had prior advanced therapy. Persistence on etrasimod was 61.4% at week 12, 40.9% at week 26, and 35.1% at week 52. Median SCCAI decreased from 3.0 (IQR 1.0-6.8) at baseline to 0.0 at weeks 8 and 12 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Among patients with active disease (n\u0026thinsp;=\u0026thinsp;26), median SCCAI fell from 5.0 to 0.5 by week 12 (p\u0026thinsp;\u0026le;\u0026thinsp;0.0003). Clinical remission was achieved in 70% at week 2 and 76% at week 12, with 75% remission among those with baseline SCCAI\u0026thinsp;\u0026ge;\u0026thinsp;3. By week 12, 86% of patients were corticosteroid-free, and the majority remained off systemic steroids during follow-up. No serious adverse events (SAEs) occurred; discontinuation was primarily due to disease exacerbation.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn this first multicenter real-world cohort, etrasimod provided rapid and sustained symptom improvement in UC. High early remission rates support its effectiveness in routine practice, though persistence declined over time, highlighting the need for early response assessment and proactive treatment optimization.\u003c/p\u003e","manuscriptTitle":"Multicenter real-world study: Etrasimod provides rapid symptom relief and high early remission rates in ulcerative colitis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-19 08:10:02","doi":"10.21203/rs.3.rs-9273653/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-04-08T22:48:10+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-01T21:02:07+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-31T07:57:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"Digestive Diseases and Sciences","date":"2026-03-31T03:01:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"digestive-diseases-and-sciences","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ddsj","sideBox":"Learn more about [Digestive Diseases and Sciences](http://link.springer.com/journal/10620)","snPcode":"10620","submissionUrl":"https://submission.nature.com/new-submission/10620/3","title":"Digestive Diseases and Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"922efae9-ea62-4d10-beb4-49ce12b010d7","owner":[],"postedDate":"April 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-19T08:10:03+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-19 08:10:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9273653","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9273653","identity":"rs-9273653","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}