Efficacy of risankizumab by baseline clinical, biochemical, and endoscopic disease severity in moderately to severely active Crohn's disease

Background: Risankizumab (RZB), a p19-anti-interleukin-23 monoclonal antibody, has demonstrated efficacy as induction and maintenance therapy in patients with moderately to severely active Crohn's disease (CD). This post hoc analysis evaluates the efficacy of induction and maintenance RZB therapy by baseline clinical, biochemical, and endoscopic disease severity. Method(s): In the ADVANCE (NCT03105128) and MOTIVATE (NCT03104413) studies, patients with moderately to severely active CD and intolerance/inadequate response to >= 1 biologic (both studies) and/or conventional therapy (ADVANCE) were randomized to receive intravenous (IV) RZB induction therapy or placebo (PBO) for 12 weeks. Patients achieving stool frequency and/or abdominal pain score clinical response to 12 weeks of induction therapy were rerandomized in the FORTIFY (NCT03105102) study to receive subcutaneous (SC) maintenance RZB (180 mg or 360 mg) or PBO (withdrawal). Clinical and endoscopic endpoints were evaluated by baseline disease characteristics (Crohn's Disease Activity Index [CDAI: <= 300, > 300], highsensitivity C-reactive protein [hs-CRP: < 10 mg/L, >= 10 mg/L], and Simple Endoscopic Score for Crohn's Disease [SES-CD: 6-15, > 15]). Induction analyses included patients who received RZB 600 mg or PBO;data from the ADVANCE and MOTIVATE studies were pooled. Nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used. Result(s): The induction analysis included 527 patients who received RZB 600 mg IV and 362 patients who received PBO. Patients treated with RZB 600 mg IV achieved significantly higher response rates vs PBO at week 12, regardless of subgroup (P < .05 for all;Figure 1). In the maintenance study, patients treated with SC RZB continued to achieve higher response rates vs the PBO (withdrawal) group at week 52 regardless of subgroup (P was not < .05 for all;Figure 2). Improvements in clinical and endoscopic outcomes were generally observed from weeks 12 to 52 with RZB treatment across all subgroups. Response rates were generally similar across subgroups in both induction and maintenance studies;endoscopic remission and ulcer-free endoscopy (resolution of ulcer) rates were numerically lower for patients with increased inflammation (hs-CRP > 10 mg/mL) and higher endoscopic activity (SES-CD > 15). Conclusion(s): RZB induction therapy resulted in higher response rates for clinical and endoscopic outcomes compared with PBO at week 12, regardless of baseline clinical, biochemical, and endoscopic disease severity. RZB also showed durable efficacy with continued RZB maintenance therapy, supporting the long-term use of RZB for patients across a range of baseline disease severity and activity.

Clinical response over 24 weeks for initial and delayed responders to induction therapy with risankizumab in Crohn's disease: Data from the ADVANCE and MOTIVATE studies

Background: The efficacy and safety of risankizumab (RZB) in patients with Crohn's disease (CD) has been demonstrated.1,2 We reported that an additional 12 weeks (ie, induction period 2) of RZB therapy could induce clinical response in patients with CD who did not achieve clinical response after an initial 12-week induction period.3 In this post hoc analysis, we report the proportion of patients who achieved clinical response over 24 weeks (initial and delayed responders to RZB induction therapy). Method(s): Data were pooled from the ADVANCE and MOTIVATE phase 3 RZB studies. Patients who had not achieved stool frequency (SF)/abdominal pain score (APS) clinical response (>= 30% decrease in average daily SF and/or >= 30% decrease in average daily APS and both not worse than baseline) after an initial 12-week induction with intravenous (IV) RZB (600 mg or 1200 mg) at weeks 0, 4, and 8 were rerandomized 1:1:1 in induction period 2 to receive IV RZB 1200 mg (at weeks 12, 16, and 20) or subcutaneous (SC) RZB (180 mg or 360 mg at weeks 12 and 20) in a double-dummy-blinded fashion. In this post hoc analysis, efficacy was analysed in patients treated with either 600 mg RZB IV or placebo (PBO) for 12 weeks in the PBO-controlled induction period and patients who did not achieve clinical response with 600 mg RZB IV for 12 weeks and were rerandomized to 360 mg RZB SC every 8 weeks during induction period 2 (currently marketed RZB doses). SF/ APS clinical response was assessed at week 12 for initial responders and at week 24 for delayed responders in induction period 2. Nonresponder imputation with no special data handling for data missing due to COVID-19 was used. No multiplicity adjustment was performed. Result(s): Of the 889 patients randomised to 600 mg IV RZB or PBO in the induction studies, 70.0% (369/527) in the RZB group compared with 45.6% (165/362) in the PBO group achieved SF/APS clinical response at week 12. Of the 47 patients who did not achieve initial clinical response to 600 mg IV RZB and received 360 mg SC in induction period 2, 32 (68.1%) achieved delayed SF/APS clinical response at week 24. The proportion of patients achieving SF/APS clinical response over 24 weeks (either initial or delayed responders) was 89.1% (401/450). The safety profile of RZB in patients with CD has been reported.1,2 Conclusion(s): In patients with moderate-to-severe CD, RZB treatment leads to approximately 9 of 10 patients achieving either initial (600 mg IV) or delayed (600 mg IV followed by 360 mg SC) clinical response over 24 weeks.

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).

ADVERSE EVENTS & SEROLOGICAL RESPONSES FOLLOWING SARS-COV-2 VACCINATION IN INDIVIDUALS WITH INFLAMMATORY BOWEL DISEASE

Background The rapid development and distribution of SARS-CoV-2 vaccines has raised concerns surrounding vaccine safety in immunocompromised populations, such as those with inflammatory bowel disease (IBD). Purpose We described adverse events (AEs) following SARS-CoV-2 vaccination in those with IBD and determined relationships between AEs to post-vaccination antibody titres. Method Individuals with IBD from a prospective cohort in Calgary, Canada (n=670) who received a 1st, 2nd, 3rd, and/or 4th dose of a SARS-CoV-2 vaccine (Pfizer-BioNTech, Moderna, and/or AstraZeneca) were interviewed via telephone for AEs using the Adverse Events Following Immunization form. Subsequently, we assessed injection site reaction as a specific AE outcome. Multivariable logistic regression models were used to assess the association between anti-SARS-CoV-2 spike protein antibody (anti-S) levels within 1–12 weeks of vaccination and injection site reaction following 1st, 2nd, and 3rd dose vaccination. Models were adjusted for age, sex, IBD type, IBD medications, vaccine type, and prior COVID-19 infection. Additionally, we evaluated the risk of flare of IBD within 30 days of vaccination via chart review. Result(s) Table 1 describes AEs in individuals with IBD following 1st dose (n=331), 2nd dose (n=331), 3rd dose (n=195), and 4th dose (n=100) of a SARS-CoV-2 vaccine. AEs were reported in 83.3% of participants after 1st dose, 79.1% after 2nd dose, 77.4% after 3rd dose, and 67.0% after 4th dose. Injection site reaction (pain, redness, etc.) was the most common AE (50.8% of AEs), with fatigue and malaise (18.1%), headache and migraine (8.6%), musculoskeletal discomfort (8.2%), and fever and chills (6.5%) also commonly reported. Multivariable logistic regression determined no associations between anti-S concentration and injection site reaction for all doses. Age above 65 years was associated with decreased injection site reaction following 1st and 3rd doses, while female sex and mRNA vaccine type were associated with increased injection site reaction following 1st and 2nd doses. Prior COVID-19 infection, IBD type, and medication class were not associated with injection site reaction with any dose. Only one participant was diagnosed with a severe AE requiring hospitalization: Immune thrombocytopenic purpura (ITP) following 2nd dose of a Pfizer vaccination. No cases of IBD flare occurred within 30 days of vaccination. Image Conclusion(s) AEs following SARS-CoV-2 vaccination are generally mild and become less common with each consecutive dose. Antibody levels following each dose of the vaccine were not associated with injection site reactions. Females, those under 65 years of age, and those administered mRNA vaccines were more likely to experience an injection site reaction. Prior COVID-19 infection, IBD type, and IBD medication class did not predict injection site reactions. Vaccination was not associated with IBD flare within 30 days of vaccination. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding;Helmsley Disclosure of Interest A. Markovinovic: None Declared, M. Herauf: None Declared, J. Quan: None Declared, L. Hracs: None Declared, J. Windsor: None Declared, N. Sharifi: None Declared, S. Coward: None Declared, L. Caplan: None Declared, J. Gorospe: None Declared, C. Ma Grant / Research support from: Ferring, Pfizer, , Consultant of: AbbVie, Alimentiv, Amgen, Ferring, Pfizer, Takeda, , Speakers bureau of: AbbVie, Alimentiv, Amgen, Ferring, Pfizer, Takeda, R. Panaccione Grant / Research support from: AbbVie, Ferring, Janssen, Pfizer, Takeda, Consultant of: Abbott, AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Oppilan Pharma, Pandion Therapeutics, Pandion Pharma, Pfizer, Progenity, Pro agonist, Roche, Sandoz, Satisfai Health, Schering-Plough, Shire, Sublimity Therapeutics, Takeda, Theravance, UCB, Speakers bureau of: AbbVie, Arena, Celgene, Eli Lilly, Ferring, Gilead Sciences, Janssen, Merck, Pfizer, Roche, Sandoz, Shire, Takeda, R. Ingram: None Declared, J. Kanji: None Declared, G. Tipples: None Declared, J. Holodinsky: None Declared, C. Berstein Grant / Research support from: AbbVie, Amgen, Janssen, Pfizer, Takeda, Speakers bureau of: AbbVie, Janssen, Pfizer, Takeda, D. Mahoney: None Declared, S. Bernatsky: None Declared, E. Benchimol: None Declared, G. Kaplan Grant / Research support from: Ferring, Speakers bureau of: AbbVie, Janssen, Pfizer

DEMOGRAPHIC, SOCIAL AND OCCUPATIONAL FACTORS THAT PREVENTED EXPOSURE TO SARS-COV-2 IN INFLAMMATORY BOWEL DISEASE PATIENTS DURING THE COVID-19 PANDEMIC: A PROSPECTIVE COHORT STUDY

Background The COVID-19 pandemic caused by the SARS-CoV-2 virus is a rapidly evolving public health emergency in which mundane behaviors such as grocery shopping or restaurant dining are considered high-risk for some, such as persons with inflammatory bowel disease (IBD) who are often immunodeficient due to medications. Research on the behavioral exposures experienced by populations with IBD during the COVID-19 pandemic are lacking. Purpose We aim to better understand how the behaviors of persons with IBD are associated with COVID-19 diagnoses. Method We conducted a prospective serosurveillance cohort study in Calgary to assess exposure to SARS-CoV-2 from Nov. 1, 2020 to Aug. 8, 2022 in 485 individuals with IBD. A diagnosis of SARS-CoV-2 was defined as a molecular-confirmed PCR test, a self-report home antigen test, or a positive nucleocapsid antibody level. Participants completed a self-report electronic questionnaire on social and occupational risk activities stratified across two time periods: Jan. 2020 to Mar. 2020 (before lockdown) and post-Jun. 2020 (post lockdown). Univariate analyses (χ2 and Fischer's exact if n≤5) were performed on social activities that occurred following the lockdown among those with IBD who were and were not diagnosed with COVID-19. Occupational exposures were compared across essential workers (EW) (i.e., frontline workers at high risk of COVID) and non-EWs. Result(s) Overall, 37.5% (n=182) of our cohort was diagnosed with COVID-19. Seniors were less likely to be infected with COVID-19 (22.7%) compared to those under the age of 65 (40.8%) (p=0.002). A greater proportion of females (42.6 %) compared to males (32.5%) were COVID positive (p=0.02). Those with Crohn's disease (38.3%) were as likely to test positive for COVID-19 as those with ulcerative colitis (36%) (p=0.65). COVID positive patients were less likely to have 4 vaccine doses (28.5%) compared to those who tested negative (71.5%) (p=0.4). Statistically significant decreases (p<0.001) in engagement post-Jun. 2020 were observed for: bar use (11.6% to 2.1%), visiting a friend (44.5% to 15.2%), having visitors over (38.7% to 12.1%), restaurant dining (38% to 9%), indoor fitness (31.9% to 8.4%), and transit use (11% to 1.3%). There was an increase in regular use of outdoor fitness (31.9% to 67.1%, p<0.003). Persons with IBD who tested positive for COVID-19 were more likely to regularly dine in a restaurant (16.8% vs. 4.7% for COVID negative, p<0.001), engage in indoor fitness activities (14% vs. 5.1%, p<0.001), and travel outside Calgary (21% vs. 11.2%, p=0.004) post-lockdown. Post-lockdown, a greater proportion of EW were COVID positive (50.4%) compared to non-EW (38.6%) (p=0.04). Image Conclusion(s) Over a two-year period, two-thirds of our cohort did not test positive for COVID-19. Those with IBD who avoided COVID tended to be older, male, have 4 doses of vaccine, and reduce their risk of exposure through social and occupational modifications, perhaps in response to public health guidance. Disclosure of Interest None Declared

DURABILITY OF SEROLOGICAL RESPONSES AFTER SECOND, THIRD AND FOURTH DOSE OF SARS-COV-2 VACCINATION IN INFLAMMATORY BOWEL DISEASE: A PROSPECTIVE COHORT STUDY

Background Adequate serological responses following two-dose regimens and additional doses of SARS-CoV-2 vaccination have been demonstrated for the vast majority of those with IBD. However, antibody levels following 2nd, 3rd, and 4th dose SARS-CoV-2 vaccination may decrease over time in the IBD population. Purpose We assessed the durability of serological responses to 2nd, 3rd, and 4th dose SARS-CoV-2 vaccination over time in a cohort of IBD patients. Method Adults with IBD who received at least one dose of a SARS-CoV-2 vaccine (n=559) were evaluated for serological response to the spike protein of SARS-CoV-2 using the Abbott IgG II Quant assay with a seroconversion threshold of ≥ 50 AU/mL. The geometric mean titer (GMT) with 95% confidence intervals (CI) were calculated and stratified by weeks (1–8, 8–16, 16–24, 24+ weeks) after each vaccine dose. We compared stratified GMTs with Mann–Whitney U tests using a significance level of 0.05. Result(s) Our cohort (n=559) comprised the following patient characteristics: 82.8% were 18–65 years-old (n = 463), 53.1% were female (n =297), and 71.6% had Crohn's disease (n =400). IBD medications were classified in the following mutually exclusive groups: No immunosuppressives 10.5% (n = 59), anti-TNF monotherapy 35.8% (n = 200), immunomodulatory monotherapy 2.1% (n =12 ), vedolizumab 11.8% (n =66 ), ustekinumab 20.4% (n =114 ), tofacitinib 1.2% (n =7 ), combination therapy 15.9% (n = 89), and prednisone 2.1% (n =12). For vaccine type, 85.6% and 82.3% had Pfizer for 3rd and 4th dose, respectively, while the remainder had Moderna. Seroconversion rates 1–8 weeks after 3rd and 4th dose were both 99.9%. Figure 1 compares GMTs with 95% CI by weeks after each vaccine dose. GMTs are highest 1–8 weeks after 2nd dose (4053 AU/mL;95% CI: 3468, 4737 AU/mL;n=337), 3rd dose (12116 AU/mL;10413, 14098 AU/mL;n=256), and 4th dose (14337 AU/mL;10429, 19710 AU/mL;n=67). Subsequently, antibody levels decay from 1–8 weeks to 8–16 weeks (p<0.001) for 2nd dose (mean difference: –2224 AU/mL), 3rd dose (mean difference: –7526 AU/mL), and 4th dose (mean difference: –9715 AU/mL). Compared to 16–24 weeks after 2nd dose, antibody levels 24+ weeks after were similar (GMTs: 795 AU/mL vs. 1043 AU/mL, p=0.52). For third dose, antibody levels 8–16 weeks and 16–24 weeks after vaccination were similar (4590 AU/mL vs. 4073 AU/mL, p=0.73) along with 16–24 weeks compared to 24+ weeks after vaccination (4073 AU/mL vs. 5876 AU/mL, p=0.18). Image Conclusion(s) Within 1–8 weeks after each dose of vaccine, serological responses spikes with each subsequent dose yielding a higher GMT. While antibody levels decay 8–16 weeks after each dose, similar GMT levels beyond 16 weeks may indicate durability of antibody levels over a longer duration of time. Disclosure of Interest None Declared

Efficacy of risankizumab induction and maintenance therapy by baseline Crohn's disease location: Post hoc analysis of the Phase 3 ADVANCE, MOTIVATE, and FORTIFY studies

Background and Aim: In patients with Crohn's disease (CD), disease location affects treatment outcomes.1 This post hoc analysis assessed the efficacy of risankizumab (RZB), an interleukin-23 p19 inhibitor, by disease location. Method(s): In the ADVANCE (NCT03105128) and MOTIVATE (NCT03104413) studies, patients with moderately to severely active CD and intolerance or inadequate response to conventional and/or biologic therapy (ADVANCE) or to biologic therapy (MOTIVATE) received intravenous (IV) RZB induction therapy or placebo (PBO) for 12 weeks. Patients achieving clinical response to IV RZB induction were re-randomized in a maintenance study (FORTIFY, NCT03105102) to receive subcutaneous (SC) RZB or SC PBO (i.e. withdrawal) for 52 weeks. This post hoc analysis included patients who received RZB 600 mg IV in either ADVANCE or MOTIVATE and patients who received RZB 360 mg SC in FORTIFY. Clinical and endoscopic outcomes were evaluated in patient subgroups stratified by CD location at baseline (ileal only, colonic only, ileal-colonic) using nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19. Result(s): At Week 12, significantly greater proportions of patients receiving RZB 600 mg IV achieved the co-primary endpoints of CD Activity Index (CDAI)-based clinical remission and endoscopic response compared with PBO in the colonic only (n = 190) and ileal-colonic (n = 252) subgroups (P < 0.001). At Week 12, statistically higher proportions of RZB-treated patients achieved the composite endpoint of CDAI clinical remission and endoscopic response, as well as endoscopic remission, in the colonic only and ileal-colonic subgroups compared with PBO (P < 0.001). At Week 52, significantly greater proportions of patients receiving RZB 360 mg SC achieved the co-primary endpoints of CDAI clinical remission and endoscopic response, composite CDAI clinical remission and endoscopic response, and endoscopic remission, compared with withdrawal (PBO SC) in the colonic only (n = 59) and ileal-colonic (n = 67) subgroups (P <= 0.05;Fig. 1a-1d). In patients with endoscopic remission after 12 weeks of IV RZB (Week 0 of maintenance), significantly more RZB-treated patients achieved sustained endoscopic remission at Week 52 compared with withdrawal (PBO SC) in the colonic only and ileal-colonic subgroups (P <= 0.01;Fig. 1e). At Weeks 12 and 52, efficacy rates were numerically lower in ileal-only CD relative to colonic-only and ileal-colonic CD. Results for ileal-only CD are limited by the small number of patients in this subgroup (induction, 85;maintenance, 15). Conclusion(s): RZB induction and maintenance therapy was effective in patients with moderately to severely active CD, with greater benefits observed in patients with any colonic involvement.

COMPARING CORTIMENT® AND PREDNISONE IN ULCERTATIVE COLITIS: A POPULATION-BASED STUDY OF OUTCOMES

Background: In August 2016 Cortiment® was approved for use in ulcerative colitis (UC) patients in Canada, but not approved for reimbursement;the Canadian Agency for Drugs and Technology in Health cited no comparable benefit for its use over other approved UC medications. Real-world data comparing Cortiment® to other UC medications is limited, especially during the COVID-19 pandemic where the use of steroids is counter-indicated for COVID-19-related outcomes. Aims: To examine the comparative risk of hospitalization, surgery, and infection after initiation of Cortiment® or oral corticosteroids among UC patients using real-world data Methods: Using population-based data from Alberta Canada, two cohorts were compared: 1. Patients dispensed Cortiment® and an ICD diagnostic code for UC [9: 556.X;10: K51.X] (August 1, 2016 to October 31, 2019);and, 2. Validated (algorithm) UC patients dispensed a >30 day supply or >500mg in 24 hours of prednisone/prednisolone (April 1, 2016 to October 31, 2019). All hospitalizations, IBD-surgery, or infections (i.e., pneumonia, c.diff, sepsis, tuberculosis) that occurred 6 or 12 months from initial medication dispensing were identified. Cox-proportional hazard models, with Hazard Ratios (HR), assessed comparative outcomes. Kaplan-Meier survival curves were created, and Poisson regression (or negative binomial) used to assess the Average Monthly Percentage Change (AMPC) with associated 95% confidence intervals (CI). Results: We identified 917 Cortiment® and 2,404 Prednisone patients. Over the study period, prednisone dispensing significantly decreased (AMPC:-2.53% [CI:-2.85,-2.21]) while Cortiment® remained stable. Dispensing of Cortiment® significantly decreased the hazard of hospitalization (all types, except surgery) at 12 months as compared to prednisone, and significantly decreased the hazard of an infection at both 6 and 12 months (Table 1, Fig 1). Conclusions: The use of Cortiment® in a real-world setting is associated with fewer deleterious outcomes, and its use during a pandemic should be preferred, especially when it's counterpart can exacerbate negative COVID-19-related outcomes. (Table Presented).

HEALTHCARE PROVIDER SATISFACTION WITH VIRTUAL CARE DELIVERY IN ALBERTA DURING THE COVID-19 PANDEMIC

Background: In light of the COVID-19 pandemic, gastroenterologists in Alberta moved to virtual care for many clinic visits. As the public health situation evolves, it is important to evaluate provider satisfaction with virtual care during these unprecedented times. Aims: To assess healthcare provider (HCP) satisfaction with virtual care during the COVID-19 pandemic. Methods: We administered a 20-item satisfaction survey that assessed the usefulness, ease of use, interface qualities, reliability, and overall satisfaction with virtual care tools for the delivery of care to patients with gastrointestinal diseases. One hundred and twenty-five gastroenterologists in Alberta were invited to participate via email. We used a modified Telehealth Usability Questionnaire (TUQ) which was open for response from June 19-August 30, 2020. Results: The overall response rate was 19% (24/125) with 46% female respondents. Most respondents worked in an academic facility (63%) and had been in practice for a mean duration of 12.3 years. Respondents were from seven facilities within the South, Calgary, Central and Edmonton health zones. Virtual care reported was a hybrid model consisting of telephone and in-person (54%) or telephone and video consults (42%). Although 90% indicated that virtual care tools improved access to healthcare, provided location flexibility and were appropriate to meet healthcare needs, only 42% agreed that it saved time. Inconclusive virtual consultations due to the absence of physical examination and missing lab values was reported by 75% and 33% of HCPs, respectively. Ninety-five percent of HCPs who used video conferencing found it simple, easy to learn and were able to become productive quickly with it. Over 60% of HCPs reported that virtual care (irrespective of the platform used) was not the same as in-person visits. The mean overall satisfaction for HCPs who rarely or never had virtual care prior to the pandemic, was 0.57 points higher than those who often provided virtual care (4.36 vs 3.79;95% CI: 0.26-0.88, p=0.001). Overall, 88% of providers were satisfied with virtual care and all respondents were willing to use it again (Figure 1). Identified areas of concern included patient safety, patient education on best practices, adequate remuneration, additional administrative duties, and challenges with providing care for new patients on virtual platforms. Conclusions: This survey of GI providers in Alberta showed high satisfaction and acceptance with virtual care. However, the majority reported it to be less reliable than in-person visits. Access to Alberta Netcare to view investigations was deemed valuable. Areas of concern that needs to be addressed include patient education on virtual care best practices and provider resources to assist with new consultations on virtual platforms.

IMPACT OF THE COVID-19 PANDEMIC IN IBD PATIENT CARE

Background: The COVID-19 pandemic is affecting patients and healthcare providers worldwide. During the first wave of the pandemic, healthcare delivery shifted from in-person to virtual clinics. Non-urgent and some emergent procedures, including endoscopies, surgeries, and imaging, were delayed to limit the spread and divert resources to COVID-19. Aims: To assess the impact of the COVID-19 pandemic in care to IBD patients Methods: A survey study was conducted to assess the impact of the COVID-19 pandemic on IBD care. All patients had a virtual clinic appointment between March to July 2020 at either: University of Alberta Hospital or the University of Calgary Clinic. A section of the survey assessed patient experience of virtual clinics and delays in access to IBD care during the COVID-19 pandemic. Results: A total of 1581 patients were contacted to complete the survey. 628 patients agreed to participate in the survey, however not all patients completed each component. The mean age of patients who participated in the survey was 48 years (SD = 15.19). 408 patients responded to satisfaction/future use questions: 84.3% (344) patients agree/strongly agree they were comfortable communicating to the physician using the remote system, 77.5% (316) of patients agree/strongly agree that virtual clinic is an acceptable way to receive healthcare services, 84.8% (346) of patients agree/strongly agree they would use virtual care services again, and 82.6% (337) agree/strongly agree they were satisfied with the telehealth system. Additional challenges were reported by 228 patients. Fear and stress (infection risk/mental health concerns/unemployment) was reported by 57.4% (131) patients. Access to healthcare services, PPE, and community resources was a challenge experienced by 26.3% (60) patients. Additionally, 16.2% (37) patients experienced uncertainty around IBD-specific care, including procedures, treatments, labs, and medications. Overall, 17.3% of patients reported some type of delay in care by July 2020. Table 1 shows the proportion of patients with a delay by type of care and the median delay: 5.7% of patients with IBD had surgery delayed by a median of 10 weeks (8-16 weeks). Conclusions: While some delays in healthcare delivery occurred during the first wave of the pandemic, overall 82.7% of patients with IBD maintained their care without disruption. Sustaining healthcare delivery to the IBD community required adaptation to virtual care;however, patient satisfaction was overwhelming positive among patients with IBD.

SHORTER DISEASE DURATION IS ASSOCIATED WITH BETTER OUTCOMES IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE CROHN'S DISEASE TREATED WITH RISANKIZUMAB: RESULTS FROM THE PHASE 3 ADVANCE, MOTIVATE, AND FORTIFY STUDIES

Background: An association between shorter disease duration and improved clinical efficacy has been shown in post hoc analyses of clinical trial data with biological therapies in Crohn’s disease (CD). The efficacy and safety of risankizumab (RZB) as induction and maintenance therapy have been recently reported.1,2 Here, the efficacy of RZB stratified by baseline CD duration is reported. Methods: In ADVANCE (NCT03105128) and MOTIVATE (NCT03104413), patients with moderately to severely active CD received intravenous (IV) RZB induction therapy or placebo (PBO) for 12 weeks. Patients with clinical response to RZB IV induction were re-randomised in a 52-week maintenance study (FORTIFY NCT03105102) to receive subcutaneous (SC) RZB or PBO (ie, withdrawal). For this posthoc analysis, patient subgroups were stratified by years of CD duration at baseline (< 2, 2– 5, > 5–10, and > 10 years). Induction analyses focused on patients who received RZB 600 mg IV or PBO for 12 weeks. As all patients who entered maintenance responded to RZB IV induction, maintenance analyses were limited to those patients who responded to induction and then received RZB 360 mg SC for 52 weeks. Clinical and endoscopic outcomes were evaluated using nonresponder imputation incorporating multiple imputation to handle missing data due to impact of the COVID-19 pandemic. Safety was assessed throughout the studies. Results: The induction and maintenance analyses included 527 patients who received RZB 600 mg IV and 141 patients who received RZB 360 mg SC, respectively. At the end of induction (week 12), patients with CD duration of < 2 years achieved higher rates of endoscopic outcomes with IV RZB induction vs patients with longer durations of disease (Figure 1), and regardless of baseline CD duration, greater proportions of RZB-treated patients achieved clinical remission (defined by stool frequency and abdominal pain), endoscopic response, endoscopic remission, and ulcer-free endoscopy vs PBO (P ≤ .05). Clinical remission rates at week 12 were numerically higher in patients with CD duration of < 5 years vs > 5 years (Figure 1). Similar results for improved clinical and endoscopic outcomes associated with shorter disease duration were observed at week 52 with RZB 360 mg SC maintenance treatment (Figure 2). RZB was well tolerated with lower rates of serious adverse events and serious infections vs PBO in induction, across CD duration subgroups. Conclusions: RZB induction and maintenance therapy was effective and well tolerated with a safety profile generally similar across CD duration subgroups. Achievement of clinical and endoscopic endpoints were higher in patients with shorter duration of CD, suggesting that earlier introduction of RZB therapy may lead to improved outcomes.

SEROLOGICAL RESPONSES TO SARS-COV-2 VACCINATION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A PROSPECTIVE COHORT STUDY

Background: The immune response of SARS-CoV-2 vaccines is uncertain in those with Inflammatory Bowel Disease (IBD) due to a diverse array of immune-modifying therapies that vary in the mechanism of immunosuppression. Aim: We aimed to quantify the serological response to SARS-CoV-2 vaccines in those with IBD and determine antibody levels across varying therapeutic options. Methods: Individuals with IBD who received a first and/or second dose of a COVID-19 vaccine (Pfizer-BioNTech, Moderna, and/or AstraZeneca) were assessed for serological response (1–8 weeks after first dose;1–8 weeks after second dose, 8–18 weeks after second dose, 18+ weeks after second dose) using the SARS-CoV-2 IgG II Quant assay to the receptor-binding domain of the SARS-CoV-2 spike protein. The cohort was stratified based on age, sex, vaccine received, IBD type, IBD therapeutic, and prior confirmed diagnosis of COVID-19. The primary outcome was seroconversion defined as IgG levels of ³50 AU/mL. Secondarily, we evaluated the geometric mean titer (GMT) with 95% confidence intervals (CI). Results: Table 1 describes the characteristics of individuals with IBD (n=466) with serological data following the first dose (n=247) and/or second dose (n=413) of a COVID-19 vaccine. After 1–8 weeks following first dose of the vaccine, 81.4% seroconverted, with the lowest first-dose conversion rates in patients taking anti- TNF monotherapy (80.3%), anti-TNF combination therapy (51.5%), and corticosteroids (50.0%) (Table 1). Overall, 98.4% of the cohort seroconverted within 1–8 weeks of the second dose. Over time, seropositive rates decreased with 95.8% seroconversion within 8– 18 weeks of the second dose and 90.5% after 18 weeks. Seroconversion after second dose was consistently high across all medication classes (range: 94.6%–100.0%), except for oral corticosteroids (62.5%). GMT levels significantly increased (p<0.0001) from first dose (1825 AU/mL [95% CI: 981, 2668 AU/mL]) to second dose at 1–8 week (9059 AU/mL [7698, 10420 AU/mL]) but fell significantly (p<0.0001) to 3649 AU/mL (95% CI: 2562, 4736 AU/ mL) 8–18 weeks from second dose and 2527 AU/mL (95% CI: 883, 4172 AU/mL) 18+ weeks after second dose (Table 1, Figure 1). GMT levels 1–8 weeks after second dose were higher in those with prior COVID-19 (16,770 AU/mL), but lower in those receiving anti- TNF combination therapy (4231 AU/mL) and oral corticosteroids (5996 AU/mL) (Table 1). Conclusion: Seroconversion rates following full-regimen vaccination are high in patients with inflammatory bowel disease across all medication classes except for anti-TNF combination therapy and oral corticosteroids. Antibody titres and seroconversion rates tend to decrease after eight weeks post-full vaccination, which is consistent across medication classes. (Table Presented) Table 1. Patient and vaccine characteristics, seroconversion rates, and geometric mean titres by prior PCR-confirmed COVID-19 status for each medication class. (Figure Presented) Figure 1. Log-transformed anti-SARS-CoV-2 spike antibody concentration per vaccine category. Black points represent GMTs while narrow black bars represent bounds of 95% CI associated with each GMT. Solid blue line represents threshold for positive seroconversion [ln (50 AU/mL)].

A THIRD DOSE OF SARS-COV-2 VACCINE YIELDS HIGH ANTIBODY LEVELS COMPARED TO TWO DOSE VACCINATION SCHEDULE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Background: The immune response to a two-dose regimen of SARS-CoV-2 vaccination in those with Inflammatory Bowel Disease (IBD) has been consistently high in emerging research. Serological responses following a third dose have yet to be established. Aim: We aimed to quantify the serological response to a third dose of SARS-CoV-2 vaccines in those with IBD and compare to responses after a two-dose regimen. Methods: Individuals with IBD who have received at least two doses of a COVID-19 vaccine were assessed for serological response using the SARS-CoV-2 IgG II Quant assay to the receptor-binding domain of the SARSCoV- 2 spike protein at least eight weeks after second dose and then after third dose. The primary outcome was seroconversion defined as IgG levels of ≥50 AU/mL. Secondarily, we evaluated the geometric mean titer (GMT) with 95% confidence intervals (CI). Outcomes were stratified by prior COVID-19 history. A Wilcoxon rank sum test was used to compare antibody titres following 3rd dose vaccination and titres following 2nd dose vaccination. For patients with both post-2nd and post-3rd vaccination serology, the difference in antibody titres between doses was determined and the mean difference was tested using one-sample Student's t-tests. Results: Table 1 describes the characteristics of individuals with IBD (n = 271) with serological data following the corresponding dose for those with 2nd dose vaccination (n = 175) compared to those with a 3rd dose of vaccine (n = 96). Seroconversion following 3rd dose vaccination occurred for all individuals (100.0%), compared to a 94.4% seroconversion rate at least eight weeks following 2nd dose vaccination (range: 8 to 35 weeks post-2nd dose). GMT for the post-3rd dose cohort (16424 AU/mL [13437, 19411 AU/mL]) was significantly higher (p<0.0001) than the post-2nd dose cohort (3261 AU/mL [2356, 4165 AU/mL] (Table 1, Figure 1b). Individual titres as a function of time following 2nd dose vaccination are seen in Figure 1a for both 3rd dose and 2nd dose cohorts. For individuals with serology following both 2nd dose and 3rd dose vaccination (n = 82), seroconversion rates increased from 97.6% to 100.0% after the 3rd dose. GMT following post-3rd dose vaccination also increased with a mean difference in antibody titres between post-3rd dose and post-2nd dose vaccination of 11384 AU/mL (8541, 14228 AU/mL, p < 0.0001). This difference was significant for both individuals with prior COVID-19 history (11682 AU/mL [95% CI: 8618, 14746 AU/mL, p<0.0001]) and individuals without (8194 AU/mL [95% CI: 988, 15400 AU/mL]). Conclusion: Seroconversion rates and antibody response following third dose vaccination are substantially increased as compared to second dose in patients with IBD. Third dose vaccination can counter the decrease in antibody concentration over time following a two-dose regimen. (Table Presented) Table 1. Patient characteristics, vaccine type, seroconversion rates, and geometric mean titres by prior COVID-19 status for post-3rd dose and post-2nd dose cohorts

Serological responses to SARS-CoV-2 vaccination in patients with inflammatory bowel disease: A prospective cohort study

BACKGROUND: The immune response of SARS-CoV-2 vaccines is uncertain in those with Inflammatory Bowel Disease (IBD) due to a diverse array of immune-modifying therapies that vary in the mechanism of immunosuppression. AIM: We aimed to quantify the serological response to SARS-CoV-2 vaccines in those with IBD and determine antibody levels across varying therapeutic options. METHODS: Individuals with IBD who received first and/or second dose of a COVID- 19 vaccine (Pfizer-BioNTech, Moderna, and/or AstraZeneca) were assessed for serological response (2-4 weeks after first dose;2-8 weeks after second dose and 8-18 weeks after second dose) using the SARS-CoV-2 IgG II Quant assay to the spike protein of SARS-CoV-2. The cohort was stratified based on age, sex, vaccine received, IBD type, IBD therapeutic, and prior confirmed diagnosis of COVID-19. The primary outcome was seroconversion defined as IgG levels of ≥50 AU/mL. Secondarily, we evaluated the geometric mean titer (GMT) with 95% confidence intervals (CI). RESULTS: Table 1 describes the characteristics of individuals with IBD (n=464) with serological data following the first dose (n=266) and/or second dose (n=303) of a COVID-19 vaccine. After the first dose of the vaccine, 81.6% seroconverted, with the lowest first-dose conversion rates in patients taking anti-TNF monotherapy (79.7%), anti-TNF combination therapy (52.9%), and corticosteroids (50.0%) (Table 1). Overall, 98.4% of the cohort seroconverted within 2-8 weeks of the second dose, with 94.6% seropositive within 8-18 weeks of the second dose. Seroconversion after second dose was consistently high across all medication classes (range: 94.6%-100.0%), except for oral corticosteroids (62.5%). GMT levels significantly increased (p<0.0001) from first dose (1679 AU/mL) to second dose at 2-8 week (7943 AU/mL) but fell significantly (<0.0001) to 3565 AU/mL 8-18 weeks from second dose (Table 1, Figure 1). GMT levels 2-8 weeks after second dose were higher in those with prior COVID-19 (12,729 AU/mL), but lower in those receiving anti-TNF combination therapy (4231 AU/mL) and oral corticosteroids (5996 AU/mL) (Table 1). CONCLUSION: Seroconversion rates following fullregimen vaccination are high in patients with inflammatory bowel disease across all medication classes except for anti-TNF combination therapy and oral corticosteroids. Antibody titres and seroconversion rates tend to decrease after 8 weeks postfull vaccination, which is consistent across medication classes.

Efficacy of risankizumab induction and maintenance therapy by baseline Crohn's Disease location: Post hoc analysis of the phase 3 ADVANCE, MOTIVATE, and FORTIFY studies

Background: In Crohn's disease (CD), disease location affects treatment outcomes.1 This post hoc analysis assessed the efficacy of risankizumab (RZB), an interleukin 23 p19 inhibitor, by disease location. Methods: In ADVANCE (NCT03105128) and MOTIVATE (NCT03104413), patients with moderately to severely active CD and intolerance or inadequate response to conventional and/or biologic therapy (ADVANCE) or to biologic therapy (MOTIVATE) received intravenous (IV) RZB induction therapy or placebo (PBO) for 12 weeks. Patients achieving clinical response to IV RZB induction were re-randomised in a maintenance study (FORTIFY, NCT03105102) to receive subcutaneous (SC) RZB or SC PBO (ie, withdrawal) for 52 weeks. This post hoc analysis included patients who received RZB 600 mg IV in either ADVANCE or MOTIVATE and patients who received RZB 360 mg SC in FORTIFY. Clinical and endoscopic outcomes were evaluated in patient subgroups stratified by CD location at baseline (ileal only, colonic only, ileal-colonic) using non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19. Results: At week 12, significantly greater proportions of patients receiving RZB 600 mg IV achieved the co-primary endpoints CD Activity Index (CDAI) clinical remission and endoscopic response vs PBO in the colonic only (n = 190) and ileal-colonic (n = 252) subgroups (P < .001;Figure 1A-1B). At week 12, statistically higher proportions of RZB-treated patients achieved the composite endpoint CDAI clinical remission and endoscopic response, as well as endoscopic remission in the colonic only and ileal-colonic subgroups vs PBO (P < .001;Figure 1C-1D). At week 52, significantly greater proportions of patients receiving RZB 360 mg SC achieved the co-primary endpoints CDAI clinical remission and endoscopic response, composite CDAI clinical remission and endoscopic response, and endoscopic remission vs withdrawal (PBO SC) in the colonic only (n = 59) and ileal-colonic (n = 67) subgroups (P ≤ .05;Figure 2A-2D). In patients with endoscopic remission after 12 weeks of IV RZB (week 0 of maintenance), significantly more RZB-treated patients achieved sustained endoscopic remission at week 52 vs withdrawal (PBO SC) in the colonic only and ileal-colonic subgroups (P ≤ .01;Figure 2E). At weeks 12 and 52, efficacy rates were numerically lower in ileal only CD relative to colonic only and ileal-colonic CD. Results for ileal only CD are limited by the small number of patients in the subgroup (induction, n = 85;maintenance, n = 15). Conclusion: RZB induction and maintenance therapy was effective in patients with moderately to severely active CD with greater benefits observed in patients with any colonic involvement.

Shorter disease duration is associated with better outcomes in patients with moderately to severely active Crohn's Disease treated with risankizumab: Results from the phase 3 ADVANCE, MOTIVATE, and FORTIFY studies

Background: An association between shorter disease duration and improved clinical efficacy has been shown in post hoc analyses of clinical trial data with biological therapies in Crohn's disease (CD). The efficacy and safety of risankizumab (RZB) as induction and maintenance therapy have been recently reported. Here, the efficacy of RZB stratified by baseline CD duration is reported. Methods: In ADVANCE (NCT03105128) and MOTIVATE (NCT03104413), patients with moderately to severely active CD received intravenous (IV) RZB induction therapy or placebo (PBO) for 12 weeks. Patients with clinical response to RZB IV induction were re-randomised in a 52-week maintenance study (FORTIFY, NCT03105102) to receive subcutaneous (SC) RZB or PBO (ie, withdrawal). For this post-hoc analysis, patient subgroups were stratified by years of CD duration at baseline (< 2, 2-5, > 5-10, and > 10 years). Induction analyses focused on patients who received RZB 600 mg IV or PBO for 12 weeks. As all patients who entered maintenance responded to RZB IV induction, maintenance analyses were limited to those patients who responded to induction and then received RZB 360 mg SC for 52 weeks. Clinical and endoscopic outcomes were evaluated using nonresponder imputation incorporating multiple imputation to handle missing data due to impact of the COVID-19 pandemic. Safety was assessed throughout the studies. Results: The induction and maintenance analyses included 527 patients who received RZB 600 mg IV and 141 patients who received RZB 360 mg SC, respectively. At the end of induction (week 12), patients with CD duration of < 2 years achieved higher rates of endoscopic outcomes with IV RZB induction vs patients with longer durations of disease (Figure 1), and regardless of baseline CD duration, greater proportions of RZB-treated patients achieved clinical remission (defined by stool frequency and abdominal pain), endoscopic response, endoscopic remission, and ulcer-free endoscopy vs PBO (P ≤ .05). Clinical remission rates at week 12 were numerically higher in patients with CD duration of < 5 years vs > 5 years (Figure 1). Similar results for improved clinical and endoscopic outcomes associated with shorter disease duration were observed at week 52 with RZB 360 mg SC maintenance treatment (Figure 2). RZB was well tolerated with lower rates of serious adverse events and serious infections vs PBO in induction, across CD duration subgroups. Conclusion: RZB induction and maintenance therapy was effective and well tolerated with a safety profile generally similar across CD duration subgroups. Achievement of clinical and endoscopic endpoints were higher in patients with shorter duration of CD, suggesting that earlier introduction of RZB therapy may lead to improved outcomes.

IMPACT OF COVID-19 PANDEMIC IN IBD PATIENT CARE

BACKGROUND The COVID-19 pandemic is affecting patients and healthcare providersworldwide. During the first wave of the pandemic, healthcare delivery shifted from inpersonto virtual clinics. Non-urgent and some emergent procedures, including endoscopies,surgeries, and imaging, were delayed to limit the spread and divert resources to COVID-19. AIMS To assess the impact of the COVID-19 pandemic in care to IBD patients METHODSA survey study was conducted to assess the impact of the COVID-19 pandemic on IBDcare. All patients had a virtual clinic appointment between March to July 2020 at either:University of Alberta Hospital or the University of Calgary Clinic. A section of the surveyassessed patient experience of virtual clinics and delays in access to IBD care during theCOVID-19 pandemic. RESULTS A total of 1581 patients were contacted to complete thesurvey. 628 patients agreed to participate in the survey, however not all patients completedeach component. 423 patients reported which hospital they receive their care: 71.2% (301)were from the University of Alberta, 24.6% (104) were from the University of Calgary, and2.9% (18) did not list either hospital. 429 patients provided a postal code, where 71.8%(308) were from either the Calgary or Edmonton metropolitan area. The mean age of patientswho participated in the survey was 48 years (SD = 15.19). 408 patients responded tosatisfaction/future use questions: 84.3% (344) patients agree/strongly agree they were comfortablecommunicating to the physician using the remote system, 77.5% (316) of patientsagree/strongly agree that virtual clinic is an acceptable way to receive healthcare services,84.8% (346) of patients agree/strongly agree they would use virtual care services again, and82.6% (337) agree/strongly agree they were satisfied with the telehealth system. Table 1shows additional challenges experienced by patients. Overall, 17.3% of patients reportedsome type of delay in care by July 2020. Table 2 shows the proportion of patients with adelay by type of care and the median delay: 5.7% of patients with IBD had surgery delayedby a median of 10 weeks (8-16 weeks). Of note, 73.9% (51) of patients were from theUniversity of Alberta, 23.2 (16) were from the University of Calgary, and 2.9% (2) patientsdid not associate with either hospital. Additionally, 75.4% (52) of patients who experienceddelays live within the Calgary/Edmonton metropolitan area. CONCLUSION: While somedelays in healthcare delivery occurred during the first wave of the pandemic, overall 82.7%of patients with IBD maintained their care without disruption. Sustaining healthcare deliveryto the IBD community required adaptation to virtual care;however, patient satisfaction wasoverwhelming positive among patients with IBD.(Table Presented)Table 1: Additional Challenges Experienced by Patients (N = 228)(Table Presented)Table 2: Proportion of IBD Patients with delays in care (N=398)

Efficacy of upadacitinib induction therapy in patients with moderately to severely active ulcerative colitis by biologic inadequate responder status: Results from two randomized phase 3 studies

Introduction: Upadacitinib (UPA), an oral JAK inhibitor, showed significantly greater efficacy vs placebo (PBO) in induction treatment of patients (pts) with moderately-to-severely active ulcerative colitis (UC) in two phase 3 induction trials, U-ACHIEVE and U-ACCOMPLISH. We evaluated efficacy of UPA in pts who had an inadequate response (IR), loss of response, or intolerance to biologic therapies (Bio-IR) or were non-Bio-IR. Methods: U-ACHIEVE and U-ACCOMPLISH, multicentre, double-blind, placebo (PBO)-controlled trials, randomized pts with moderately to severely active UC to UPA 45 mg QD or PBO for 8 weeks (wks). Randomization was stratified by status of previous biologic failure, ie an inadequate response (IR), loss of response, or intolerance to biologic therapies (Bio-IR or bio-failure) vs non-Bio-IR (nonbio-IR or non-bio-failure), baseline corticosteroid use (yes or no), and baseline adapted Mayo score (≤7 or>7). Efficacy endpoints included primary endpoint of clinical remission (adaptedMayo score) at Wk 8 and ranked secondary endpoints of clinical response (partial adapted Mayo score at Wk 2 and adapted Mayo score at Wk 8), endoscopic improvement (Mayo endoscopic subscore 0 or 1), endoscopic remission (Mayo endoscopic subscore 0) and histologic-endoscopic mucosal improvement at Wk 8 (HEMI;endoscopic subscore ≤1 and Geboes score ≤3.1). Results using non-responder imputation incorporating multiple imputation for missing data due to COVID-19 are reported. Results: In both studies, approximately half the pts were Bio-IR (Table 1). In both Bio-IR and non-Bio-IR pts, significantly higher proportion of pts receiving UPA achieved primary endpoint of clinical remission versus PBO;the magnitude of clinical remission at Wk 8 was greater in non-Bio-IR pts (UPA, 35% vs PBO, 9%;treatment difference [95% CI]: 26.0% [16.0, 36.1]) versus Bio-IR (UPA, 18% vs PBO, 0%;17.5% [11.4, 23.6]) in U-ACHIEVE and non-Bio-IR (UPA, 38% vs PBO, 6%;31.6% [22.8, 40.5]) versus Bio-IR (UPA, 30% vs PBO, 2%;27.1% [19.6, 34.7];Table 1) in U-ACCOMPLISH. Results were generally similar for ranked secondary endpoints (Table 1). UPA 45 mg QD was well-tolerated and no new safety signals were observed. Conclusion: UPA 45 mg QD is an effective induction treatment for pts with moderately to severely active UC. A significantly higher proportion of pts in both Bio-IR and non-Bio-IR groups receiving UPA achieved primary and secondary endpoints versus PBO. The magnitude of difference was greater among pts who were non-Bio-IR versus Bio-IR.

Efficacy and safety of upadacitinib as induction therapy in patientswith moderately to severely active ulcerative colitis: Results from phase 3 u-accomplish study

Introduction: U-ACCOMPLISH is one of two phase 3 induction trials evaluating safety and efficacy of upadacitinib-45 mg once daily (UPA) in adults with ulcerative colitis (UC). Methods: U-ACCOMPLISH, a multicentre, randomized, double-blind, placebo-controlled trial (NCT03653026), enrolled patients (pts) with moderate-to-severe UC (defined as adapted Mayo score 5-9 with centrally read endoscopic score of 2-3) who had inadequate response, loss of response, or intolerance to aminosalicylates, immunosuppressants, corticosteroids and/or biologics. Pts were randomized 2:1 to UPA or placebo (PBO) for 8 weeks (wks). At wk 8, responders entered the maintenance phase and non-responders entered the extended treatment period to receive open-label UPA for additional 8 wks. Primary endpoint (clinical remission per adapted Mayo Score) and ranked secondary endpoints including symptomatic, endoscopic-histologic evaluations from 8-wk PBO-controlled period are reported here. Non-responder imputation incorporating multiple imputation for missing data due to COVID-19 are reported. Results: 522 pts were randomized (UPA, n = 345;PBO, n = 177);intent-to-treat population included 341 pts in UPA and 174 pts in PBO group. Baseline demographics and disease characteristics were similar between groups;50.7% and 51.1% were biologic inadequate responders in UPA and PBO groups, respectively (Table 1). A significantly higher proportion of pts receiving UPA (33.5%) versus PBO (4.1%) achieved primary endpoint (adjusted treatment difference: 29.0% [23.2, 34.7];P<0.001). A significantly higher proportion of pts receiving UPA versus PBO also achieved all ranked secondary endpoints (all P<0.001;Figure 1).Serious adverse events were reported by 3.2% and 4.5% of pts in UPA and PBO groups, respectively (Table 1). Similar rates of serious infection were observed in both groups (0.6%);2 events each of herpes zoster and opportunistic infection were reported in UPA group. No active tuberculosis, malignancy, adjudicated major adverse cardiovascular events, or deaths were reported. One pt with venous thromboembolism (deep vein thrombosis and pulmonary embolism) and 1 pt with gastrointestinal perforation were reported in the placebo group. Conclusion: UPA 45 mg QD induction treatment led to statistically significant improvements in clinical, endoscopic, and combined endoscopic-histologic endpoints. Treatment was well tolerated, and safety profile and AE prevalence were comparable with previous studies of UPA with no new safety signals identified.

Efficacy and safety of upadacitinib induction therapy in patients with moderately to severely active ulcerative colitis: Results from the phase 3 u-achieve study

Introduction: U-ACHIEVE is one of two phase 3 induction trials evaluating safety and efficacy of the selective JAK-1 inhibitor upadacitinib-45 mg once daily (UPA) in adults with ulcerative colitis (UC). Methods: U-ACHIEVE, a multicentre, double-blind, placebo (PBO)-controlled trial (NCT02819635) randomized patients (pts) with moderately-to-severely active UC 2:1 to UPA or PBO for 8 weeks (wks). Randomization was stratified by biologic inadequate responder (Biologic-IR) status (Biologic-IR vs non-biologic-IR), baseline corticosteroid use (yes or no), and baseline adapted Mayo score (≤7 or≥7). Primary endpoint was proportion of pts achieving clinical remission (per adapted Mayo Score) at wk 8. Ranked secondary endpoints included wk 8 endoscopic improvement, endoscopic remission, clinical response per adapted Mayo Score, and histologic-endoscopic mucosal improvement;and wk 2 clinical response per partial adapted Mayo Score. Non-responder imputation incorporating multiple imputations for missing data due to COVID-19 are reported. Safety was assessed through wk 8. Results: 474 pts were randomized (UPA, n=319;PBO, n=155). Baseline characteristics were well balanced between groups (Table 1). A significantly higher proportion of pts receiving UPA (26.1%) vs PBO (4.8%) achieved wk 8 clinical remission (adjusted treatment difference [95% CI]: 21.6% [15.8, 27.4];P<0.001;Figure 1a). For all ranked secondary endpoints, UPA was superior to PBO (P<0.001;Figure 1a). A significant difference vs PBO in clinical response favouring UPA was seen as early as wk 2 (60.1% vs 27.3%) and was sustained thereafter up to wk 8 (79.0% vs 41.6%;Figure 1b). Serious AEs, severe AEs, and AEs leading to study drug discontinuation were higher in PBO group (Table 1). Acne, creatine phosphokinase elevation, and nasopharyngitis were most common AEs with UPA and worsening UC and anaemia with PBO. Incidence of serious infection was similar between UPA and PBO. Neutropenia and lymphopenia were reported more frequently with UPA vs PBO (Table 1). No adjudicated gastrointestinal perforation, major adverse cardiovascular events, or thrombotic events, and no active tuberculosis, malignancy, or deaths were reported. Conclusion: In pts with moderately-to-severely active UC, UPA induction therapy was superior to PBO in inducing clinical and endoscopic remission/response, over 8 wks;responses were significant and rapid. UPA was well-tolerated;safety was comparable with the known safety profile of UPA, and no new safety signals were identified.