ABSTRACT
Background: Infections are an important safety concern in patients with IBD and may be due to its therapies, such as corticosteroids. Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 (S1P1,4,5) modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). The biologic effect of etrasimod leads to selective and reversible lymphocyte retention in lymph nodes with a decrease in peripheral lymphocyte count. We report the infection events from the phase 3 ELEVATE programme. Method(s): Infection events were evaluated in the pivotal UC pooled safety analyses set comprising two phase 3 studies: ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369). Subjects (16- 80 years) with moderately to severely active UC were randomised 2:1 to once-daily etrasimod 2 mg or placebo (PBO). We report the n (%) and exposure-adjusted incidence rate (EAIR) of infections including serious infections, severe infections, opportunistic infections (including tuberculosis), and herpes infections. Infections were considered adverse events of special interest (AESI) if they were severe (>= CTCAE Grade 3), were opportunistic infections, or were herpes zoster or herpes simplex infections. Result(s): From the pooled ELEVATE UC 12 and ELEVATE UC 52 trials, 527 subjects received >=1 dose of etrasimod 2 mg (265.6 subject-years of exposure) and 260 subjects were randomised to PBO (103.0 subjectyears of exposure). Infections were similar between treatment groups (etrasimod: 99 [18.8%], EAIR=0.41;PBO: 46 [17.7%], EAIR=0.52). The most frequent infections in both groups were COVID-19, urinary tract infections, and nasopharyngitis (Table 1). Serious infections occurred in 3 (0.6%) subjects in the etrasimod arm (EAIR=0.01) and 5 (1.9%) in PBO arm (EAIR=0.05). Two cases of herpes zoster were reported in each treatment group (etrasimod: 0.4%, EAIR<0.01;PBO: 0.8%, EAIR=0.02);these were localised and nonserious. One opportunistic infection was reported in each arm (etrasimod: Subject withdrew from the study on day 20, the AE of Cytomegalovirus infection [Grade 2] was reported on day 36;PBO: Tuberculosis [Grade 2]). Overall, 3 cases of infection led to discontinuation: 2 in the etrasimod arm (both mild) and 1 in the PBO arm (Table 2). No subject with an absolute lymphocyte count <0.2x109/L subsequently reported a serious/ severe or opportunistic infection. There were no deaths. Downloaded from https://academic.oup.com/ecco-jcc/article/17/Supplement-1/i689/7010119 by guest on 04 February 2023 Sample output to test PDF Combine only i690 Poster presentations In these trials, etrasimod-treated subjects reported no in-crease in infections relative to PBO. Serious infections and herpes zoster were more commonly reported in the PBO-treated group. Longer-term follow-up data from the ongoing 5-year open-label extension will fur-ther characterize the etrasimod safety profile.
ABSTRACT
Background IBD patients on immune-modulatory therapies are considered high-risk for SARS-CoV-2 infection. Direct comparisons of serological responses to SARS-CoV-2 infection in IBD patients across different continents and medications are lacking. We performed SARS-CoV-2 sero-surveillance of IBD patients prior to vaccination at seven large tertiary centres in Asia, Europe, and North America. Methods Clinical data and sera were collected from, 2,213 IBD patients receiving routine care at institutions in Belgium, Canada, Hong Kong, India, Japan, the United Kingdom, and the United States between, 26 May, 2020 and, 24 September, 2021 (Table, 1). Sera were taken prior to vaccination. Clinical data were collected through patient questionnaires and medical records. Antibody reactivity to the SARS-CoV-2 spike protein was assessed using the Roche SARS-CoV-2 anti-spike total antibody and/or Siemens Healthineers COV2T anti-spike total antibody assays, which showed, 99.4% concordance. Univariate analysis was performed to evaluate association between individual variables and sero-status. Results The pre-vaccination seroprevalence of antibodies to SARS-CoV-2 in IBD patient varied widely according to location from, 0% in Hong Kong to, 57.9% in New Delhi, India (p<0.001). Rates in Europe and North America were similar (range, 3.57%-8.94%). Overall, SARS-CoV-2 seroprevalence appears to be equal to or less than local populations (Table, 2). Seroprevalence rates were associated with IBD type (7.8% CD, 12.4% UC, 15% IBD-U, p<0.001), smoking status (p<0.001), and history of COVID diagnosis (p<0.001) or COVID hospitalization (p=0.001), and any IMM (p<0.001). (Table, 3). Whilst there were no significant differences in seroprevalence between patients receiving infliximab (IFX), vedolizumab (VDZ), and ustekinumab (UST), antibody levels were attenuated in patients on IFX monotherapy and combination therapy (both p=0.002) and VDZ (p=0.02), compared with no medications (Figure 1). Conclusion We confirm in diverse poulations that exposure to biologics or immunomodulators, type of disease, and smoking status are associated with seroprevalence and antibody levels. We show for the first time the dominant influence of geographical location on sero-status in these patients. These observations should be considered as we look towards post-vaccination data to help stratify patients for clinical guidelines on SARS-CoV-2 vaccination.
ABSTRACT
Background: IBD patients on immune-modulatory therapies are considered high-risk for SARS-CoV-2 infection. Direct comparisons of serological responses to SARS-CoV-2 infection in IBD patients across different continents and medications are lacking. We performed SARSCoV- 2 sero-surveillance of IBD patients prior to vaccination at seven large tertiary centres in Asia, Europe, and North America. Methods: Clinical data and sera were collected from 2,241 IBD patients receiving routine care at institutions in Belgium, Canada, Hong Kong, India, Japan, United Kingdom, and the United States between May 2020 and September 2021 (Table 1). Sera were taken prior to vaccination. Clinical data were collected from patient questionnaires and medical records. Antibody reactivity to the SARS-CoV-2 spike protein was assessed using the Roche SARS-CoV-2 anti-spike total antibody and/or Siemens Healthineers COV2T anti-spike total antibody assays, which showed 99.4% concordance. We performed univariate analysis to evaluate association between variables and sero-status. Results: The pre-vaccination seroprevalence of antibodies to SARS-CoV-2 in IBD patient varied widely according to location from 0% in Hong Kong, China, to 57.9% in New Delhi, India. Rates in Europe and North America were similar (range 3.6%-8.9%). Overall, SARSCoV- 2 seroprevalence appears to be equal to or less than local populations (Table 1). Seroprevalence rates were associated with IBD type (Crohn's disease 7.8%, ulcerative colitis 12.4%, IBD-unclassified 15.0%, p<0.001), smoking status (p<0.001), and history of COVID diagnosis (p<0.001) or COVID hospitalization (p=0.001), and any immunomodulator (IMM) (p<0.001) (Table 1). Infection as indicated by seropositivity in the absence of known COVID infection occurred in 7.3% of patients. Whilst there were no significant differences in seroprevalence between patients receiving anti-tumor necrosis factor (anti-TNF) medications, vedolizumab (VDZ), and ustekinumab (UST), antibody levels were attenuated in patients on anti-TNF monotherapy (p=0.002), anti-TNF + IMM combination therapy (p=0.002), and VDZ (p=0.02), compared with no medications (Figure 1). Conclusion: We confirm in diverse populations that exposure to anti-TNFs, vedolizumab and immunomodulators, type of disease, and smoking status are associated with seroprevalence and antibody levels. We show for the first time the dominant influence of geographical location on sero-status in these patients. These observations should be considered as we look towards post-vaccination data to help stratify patients for clinical guidelines on SARS-CoV-2 vaccination. (Table Presented) Table 1. Seroprevalence of total anti-SARS-CoV-2 spike antibodies in IBD patients by ICARUS centre with non-IBD controls noted for New Delhi, India, and publicly reported local seroprevalence and by selected patient characteristics.(Figure Presented) Figure 1. Antibody levels by medication group.
ABSTRACT
Background: Cases of Coronavirus disease 2019 (COVID-19) have emerged in discrete waves across different regions in the world. We explored temporal trends in the reporting of COVID-19 in patients with inflammatory bowel disease (IBD), in a large global database. Methods: The Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is an international registry to study the character-istics and outcomes of patients with IBD diagnosed with COVID-19. Joinpoint regression models calculated the average percent change (APC) with 95% confidence intervals (CI) in weekly reported cases of COVID-19 in patients in the registry stratified by geographic regions (Asia, Europe, Latin America, and North America) during two time periods: March 22 to September 12 and September 13 to November 14, 2020. We also determined the APC in US regions (Midwest, Northeast, South and West) during the two time periods. Results: Across 63 countries and dependencies, 3,195 cases of COVID-19 in people with IBD were reported over an 8-month period. Overall, COVID-19 reporting steadily decreased throughout the world by 4.5% per week (95% CI: −5.7, −3.2) from March 22 to September 12, 2020 but then steadily climbed by 12.4% per week (95% CI: 6.8, 18.3) from September 13 to November 14, 2020. After stratification by geographic region, weekly reporting declined before September 13 in North America (APC = −2.0%;95% CI: −3.7, −0.4), Asia (APC =− 4.4%;95% CI: −7.8, −0.9), and Europe (APC = −8.6%;95% CI: −10.6, −6.6), but escalated in Latin America (APC = 3.4%;95% CI: 0.7, 6.1) (Figure 1). After September 12, the rate of weekly cases decreased in Latin America (APC = −19.0%;95% CI: −33.3, −1.7) and Asia (APC = −19.3%;95% CI: −34.6, −0.5), while increased in North America (APC = 10.7%;95% CI: 4.3, 17.4) and Europe (APC = 28.0%;95% CI: 17.3, 39.6) (Figure 1). Within the US, temporal trends differed by region: Midwest (stable APC: −0.8%;95% CI: −3.5, 1.9 then increase APC: 27.3%;95%: 16.1, 39.6), Northeast (decrease APC: −9.1%;95% CI:− 11.8, −6.2 then stable APC: 2.4%;95% CI: −9.9, 16.5), South (increase APC: 5.3%;95%CI: 2.5, 8.3 then decrease APC: −12.0;95% CI: −18.4, −5.0), and West (stable APC: 0.2%;95% CI: −3.0, 3.5 then stable APC: 9.0%;95% CI: −13.8, 37.9) (Figure 2). Conclusion: COVID-19 reporting to SECURE-IBD declined steadily during the first wave of the pandemic throughout the world except Latin America. Starting in September, reports to SECURE-IBD rose in both Europe and North America, consistent with the second wave of the pandemic in these countries.(Figure presented)Figure 1. Global regional temporal trends in reporting of COVID-19 in patients with IBD from the SECURE-IBD registry: A. Asia, B. Europe, C. Latin America, and D. North America: March 22–28 to September 6-12 and September 13-19 to November 8–14, 2020(Figure presented)Figure 2. United States regional temporal trends in reporting of COVID-19 in patients with IBD from the SECURE-IBD registry: A. Midwest, B. Northeast, C. South, and D. West: March 22–28 to September 6-12 and September 13-19 to November 8–14, 2020