Long-term safety of 3 years of ozanimod in moderately to severely active ulcerative colitis: an interim analysis of the True North open-label extension

Background: The phase 3, randomised True North (TN) study demonstrated the efficacy and safety of ozanimod for up to 52 weeks in patients (pts) with moderately to severely active ulcerative colitis (UC). The ongoing TN open-label extension (OLE) aims to assess the long-term efficacy and safety of ozanimod in UC. This analysis evaluated the cumulative long-term safety of ozanimod in these studies, which included pts with up to ~3 years of treatment exposure. Method(s): In TN, pts were randomised to once-daily ozanimod 0.92 mg or placebo, or to open-label ozanimod for a 10-week induction period. Ozanimod clinical responders were rerandomised at Week 10 to ozanimod or placebo in the maintenance period through Week 52. TN pts were eligible to enrol in the OLE and receive ozanimod if they did not achieve clinical response at the end of induction (Week 10), lost response during maintenance, or completed maintenance at Week 52. This interim analysis of the TN OLE (data cutoff: 10 January 2022) included all pts who entered the OLE from TN (n=823). Safety was monitored from the first dose of ozanimod in TN and throughout the subsequent OLE. Exposureadjusted incidence rates per 100 patient-years (PY) were calculated. Result(s): The average age of TN OLE study participants was 41.7 years (+/-13.6), 41% were female, 62% had left-sided UC disease, and 35% had prior exposure to tumor necrosis factor inhibitors. Total PY exposure to ozanimod was 2219 years (mean [SD] exposure = 2.7 [1.6]). The most frequent treatment-emergent adverse events (TEAEs) reported through OLE Week 94 (up to 146 weeks of continuous treatment) are listed in the Table. Most TEAEs were nonserious;TEAEs leading to discontinuation were uncommon. Bradycardia was reported in 3 pts (0.4%;EAIR 0.1/100 PY;2 in TN and 1 in OLE;no pts were discontinued from treatment). Macular edema was reported in 2 (0.2%;EAIR 0.1/100 PY) pts. Reductions in ALC were common (470 [57.1%] had ALC < 500 cells/mm3), as previously described, but ALC reductions were not associated with the occurrence of TEAEs. Malignancies were uncommon (n=13 [1.6%];EAIR 0.6/100 PY), and included 6 basal cell carcinomas and 3 colorectal neoplasms. Two deaths were reported: 1 due to COVID-19 and 1 sudden death. Investigators deemed both to be unrelated to treatment. Ozanimod was not associated with an increased risk of ischemic heart disease or thromboembolic events. Conclusion(s): Long-term exposure to ozanimod for up to 3 years was well tolerated in pts with moderately to severely active UC. No new safety signals were observed with long-term ozanimod use in UC (2219 PY exposure). Safety findings are consistent with previous reports from the UC and multiple sclerosis development programs (>16,512 PY exposure). (Table Presented).

Etrasimod for the treatment of ulcerative colitis: analysis of infection rates from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 clinical trials

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.

Trans-continental analysis of over, 2000 Inflammatory Bowel Disease patients implicates geography, disease type, and exposure to immunosuppression as drivers of SARS-CoV-2 seroprevalence: data from the ICARUS-IBD Consortium

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.

TRANS-CONTINENTAL ANALYSIS OF OVER 2,000 INFLAMMATORY BOWEL DISEASE PATIENTS IMPLICATES GEOGRAPHY, DISEASE TYPE, AND EXPOSURE TO IMMUNOSUPPRESSION AS DRIVERS OF SARS-COV-2 SEROPREVALENCE

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.

CONSCIENTIZAÇÃO PARA DOAÇÃO DE SANGUE E CADASTRO PARA DOAÇÃO DE MEDULA ÓSSEA EM PERÍODO DE INTERAÇÕES SOCIAIS LIMITADAS

Considerando a situação da pandemia de COVID-19 que diminuiu significativamente o número de pessoas aptas a doar sangue e que as doenças do sangue, câncer, cirurgias e traumas continuam, o Programa de Extensão “Amizade Compatível - uma doação para a vida” manteve initerruptamente o seu objetivo em conscientizar a comunidade da importância do cadastro e doação de sangue (DS) e de medula óssea (MO). Dessa maneira, o objetivo deste trabalho é apresentar ações extensionistas de conscientização para doação de sangue e de medula óssea realizadas em período de interações sociais limitadas. Materiais e métodos: Foram promovidos por alunos extensionistas, pela plataforma Google Meet, dezenove encontros com a participação de universitários, pacientes e seus familiares, profissionais de saúde, membros de associações, atiradores do Tiro de Guerra (TG) do município de Uberaba e comunidade em geral, durante 15 meses, com os temas: Indicações de hemocomponentes, Tipos Sanguíneos, Quem precisa de sangue, Abordagem de Redes Sociais para incentivo a DS, Campanhas Universitárias para captação de DS com curso de Medicina, Odontologia e Direito, Leucemia Pediátrica e uso de hemocomponentes, Conscientização para DS e para o cadastro de MO, Comemoração do Dia Nacional do Doador de MO, Comemoração do Dia Estadual da Anemia Falciforme, Comemoração do Dia Mundial da Luta contra o Câncer, Comemoração do Dia Nacional e Internacional da Talassemia além de relatos de pacientes com doença falciforme, talassemia, leucemia mieloide aguda, familiares de paciente com leucemia linfóide aguda e com doador de medula óssea. O programa também realizou na Universidade e no Hospital Universitário a Campanha intitulada Junho Vermelho para incentivar o espírito solidário das pessoas para doação de sangue. A divulgação de todas as ações foi realizada pelas redes sociais do Programa de Extensão, da Universidade e de forma particular pelos incentivadores e parceiros do programa de extensão. Resultados: O total de participantes dos dezenove encontros foi de 1636 pessoas. Momentos de relato de pacientes e seus familiares sobre a doença, sobre a dependência de transfusões e sobre a busca do doador de MO foram os que mais sensibilizaram os participantes. As postagens da Campanha do Junho Vermelho contaram com 2951 interações. Discussão: Ações extensionistas realizadas de forma online constituíram uma maneira segura de conscientizar a população da importância da realização da DS e o cadastro para doação de MO, de proporcionar o contato de alunos/comunidade com pacientes e profissionais de saúde, além de trazer à tona a dificuldade de os hemocentros manterem seus estoques de sangue principalmente em período de pandemia. Conclusão: A partir de diferentes plataformas online é possível contactar com facilidade diferentes públicos e realizar ações extensionistas de conscientização para DS e MO, colocando não só o universitário, potencial doador, em contato com os necessitam diretamente da transfusão sanguínea, mas também a comunidade em geral.

Patient Adherence to Fecal Calprotectin Testing Is Low Compared to Other Commonly Ordered Tests in Patients with IBD

INTRODUCTION: Reliable, non-invasive biomarkers are important in the management of inflammatory bowel disease (IBD) to minimize colonoscopies, especially in the era of the COVID-19 pandemic. Many studies have demonstrated that fecal calprotectin (FCP) can be used as a biomarker for active inflammation. Indeed, FCP has been shown to have superior sensitivity compared to serum C-reactive protein (CRP). Although FCP is a useful marker in the management of IBD patients, we observed that patients often do not complete this test when requested. In this study, we assessed completion rates for FCP in our tertiary referral center for IBD as compared to other routine tests. METHODS: We identified all patients with ICD 9/10 codes for IBD. 3,082 IBD patients were found with at least one FCP test ordered. We determined the mean completion rate for FCP. A subset of 1564 patients who also had at least one order for CRP, complete blood count (CBC), and Clostridium difficile (CDIFF) was also identified. R Studio was used to prepare the data for statistical analysis using SPSS. RESULTS: In the 3,082 patients initially identified, the mean completion rate for FCP was 49.7%. When subgroup analysis was performed for the 1564 patients with FCP, CDIFF, CRP and CBC tests, mean completion rates for these tests were noted to be 53.9%, 61.4%, 72.6% and 74.2%, respectively. We found statistically fewer patients adhering to tests involving collection of stool than blood. There was a statistical difference in FCP completion rates between age groups, with older patients having generally higher completion rates than younger patients. There was no statistical difference in completion of FCP tests based on gender or ethnicity. A similar pattern was also found for CDIFF testing. With blood tests, including the serum biomarker of CRP, no statistical difference was noted between completion rates based on age, gender or ethnicity. CONCLUSION: Although FCP is a sensitive marker for intestinal inflammation, patients are less likely to perform the test, especially compared to blood tests. Younger patients are the least likely to complete FCP and other stool tests. These results suggest that patients may have an aversion to stool based tests and/or have a reduced understanding of their value. These results also indicate the continued need to develop better serum biomarkers that reflect intestinal inflammation with greater sensitivity and specificity. Knowledge of these high rates of non-adherence may improve the discussion with patients.

Use of the endoscopic healing index for monitoring of disease activity in patients with Crohn's disease in the COVID era

Management of Crohn's disease (CD) during COVID-19 is challenging when colonoscopy is not feasible. This study describes a blood-based test that has been validated against colonoscopy in patients with CD as an alternative even in patients with high inflammation from infections.