Post-Covid-19 Irritable Bowel Syndrome

Background and aim: The long-term consequences of COVID- 19 infection on the gastrointestinal tract remain unclear. Here we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction (DGBI) after hospitalization for SARS-CoV-2 infection. Material(s) and Method(s): GI-COVID19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were evaluated upon hospital admission and after 1, 6, and 12 months post-hospitalization. Gastrointestinal symptoms, anxiety, and depression were assessed using validated questionnaires, namely the Gastrointestinal Symptoms Rating Scale (GSRS), the Hanxiety and Depression Scale (HADS) and the Rome IV Diagnostic Questionnaire for Functional Gastrointestinal Disorders in Adults. Result(s): The study included 2183 hospitalized patients. The primary analysis included a total of 883 patients (614 COVID-19 patients and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrollment, gastrointestinal symptoms were more frequent among COVID-19 patients than in the control group (59.3% vs. 39.7%, P<0.001). At the 12-month follow- up, constipation and hard stools were significantly more prevalent in controls than in COVID-19 patients (16% vs. 9.6%, P=0.019 and 17.7% vs. 10.9%, P=0.011, respectively). Compared to controls, COVID- 19 patients reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% vs. 3.2%, P=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors, and presence of dyspnea. [Table presented] At the 6-month follow-up, the rate of COVID-19 patients fulfilling the criteria for depression was higher than among controls. Conclusion(s): Compared to controls, hospitalized COVID-19 patients had fewer complaints of constipation and hard stools at 12 months after acute infection. COVID-19 patients had significantly higher rates of IBS than controls. ClinicalTrials.gov number, NCT04691895.Copyright © 2023. Editrice Gastroenterologica Italiana S.r.l.

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).

Effect of upadacitinib on inflammatory markers and clinical outcomes in patients with Crohn's disease in the phase 3, U-EXCEL, U-EXCEED, and U-ENDURE studies

Background: Improvement in clinical outcomes and normalisation of objective markers of inflammation, high-sensitivity C-reactive protein (hs-CRP) and faecal calprotectin (FCP), are considered treatment targets per STRIDE-II guidelines.1 We evaluated the effect of the oral selective Janus kinase inhibitor upadacitinib (UPA) on changes in hs-CRP, FCP, and clinical outcomes in patients with Crohn's disease (CD). Method(s): In 2 phase 3, randomized, double-blind, placebo-controlled induction studies (U-EXCEL, NCT03345849;U-EXCEED, NCT03345836), patients with moderate-to-severe CD received 12-week treatment with UPA 45 mg (UPA45) once daily (QD) or placebo (PBO). Patients with clinical response to UPA45 were rerandomised in U-ENDURE (NCT03345823) to receive 52-week maintenance treatment with UPA 30 mg QD (UPA30), UPA 15 mg QD (UPA15), or PBO. Endpoints included marker normalisation (hs-CRP <= 5 mg/L, FCP <= 250 mug/g) in patients with elevated baseline marker levels, normal marker and clinical remission by Crohn's Disease Activity Index (CDAI < 150) or very soft/liquid stool frequency (SF)/abdominal pain score (APS) (average daily SF <= 2.8 and average daily APS <= 1, neither greater than baseline), and >= 50% reduction from baseline in marker values with a decrease of at least 100 points in CDAI from baseline. Median changes from baseline in marker levels were also evaluated. Non-responder imputation with no special data handling for missing data due to COVID-19 was used. Result(s): Of 1021 enrolled patients, 645 (63.2%) had elevated hs-CRP (> 5 mg/L) and 750 (73.5%) had elevated FCP (> 250 mug/g) levels at baseline. Significantly greater proportions of patients with elevated baseline marker levels achieved normalisation with UPA compared with PBO at week 12 (Fig 1A/B) and week 52 (Fig 2A/B;nominal P < .001 for all). Decreases in marker levels from baseline with UPA were observed as early as week 2 and were significantly greater than with PBO through week 12 (Fig 1C) and week 52 (Fig 2C;nominal P < .001 for all). Patients achieved clinical endpoints and improvements in markers at significantly higher rates with UPA45 vs PBO at week 12 (Fig 1D-F) and with UPA15 and UPA30 vs PBO at week 52 (Fig 2D-F;P < .001 for all). The safety profile of UPA in CD was previously reported and no new safety concerns were identified. Conclusion(s): Improvements in clinical endpoints and normalisation of objective markers of inflammation were achieved as early as week 2 with UPA45 induction and sustained with UPA15 and UPA30 maintenance therapy in patients with CD. Median changes in hs-CRP and FCP with UPA support continued improvement of inflammation up to week 52 .

Etrasimod 2mg Once Daily as Treatment for Moderately to Severely Active Ulcerative Colitis: Results from the Phase 3 Elevate Uc 52 and Elevate Uc 12 Trials

Introduction: Etrasimod (APD334), an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator, demonstrated efficacy in adults with moderately to severely active ulcerative colitis (UC) in the Phase 2 OASIS trial (NCT02447302). Here, we report data from 2 trials, ELEVATE UC 52 and ELEVATE UC 12, that evaluated the efficacy and safety of etrasimod 2mg for induction and maintenance in adults with UC. Aims & Methods: ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) were global, randomized, double-blind, placebo-controlled trials. In both trials, adults (16-80 years) with moderately to severely active UC (based on modified Mayo Score [MMS] of 4-9 with centrally read endoscopic subscore >=2 and rectal bleeding subscore >=1) and documented history of inadequate response, loss of response, or intolerance to >=1 treatment for UC were randomized 2:1 to once-daily treatment with etrasimod 2mg or placebo. Patients (pts) were stratified by previous exposure to biologic/Janus kinase inhibitor (JAKi) therapy, baseline corticosteroid use, and baseline disease activity (MMS 4-6 or 7-9). ELEVATE UC 52 utilized a treat-through design comprising a 12-week induction period followed by a 40-week maintenance period. Beginning at Week (Wk) 12, all pts could continue their randomized treatment;pts whose disease had not improved or had worsened compared to baseline (based on investigator judgement) could discontinue and enroll in an open-label extension study (NCT03950232). ELEVATE UC 12 comprised a 12-week induction period only. The primary efficacy endpoints were the proportion of pts achieving clinical remission (using the MMS) at Wk 12 and Wk 52 in ELEVATE UC 52, and at Wk 12 in ELEVATE UC 12. Safety was evaluated throughout the trials. Result(s): In ELEVATE UC 52, 433 pts were randomized (etrasimod, n=289;placebo, n=144) and 207 completed Wk 52. In ELEVATE UC 12, 354 pts were randomized (etrasimod, n=238;placebo, n=116) and 316 completed Wk 12. 62.6% of etrasimod-treated pts in both trials and 61.8% and 62.9% of placebo-treated pts in ELEVATE UC 52 and ELEVATE UC 12, respectively, were naive to biologic/JAKi therapy. All primary and key secondary efficacy endpoints were achieved with etrasimod vs placebo at both Wks 12 and 52 in ELEVATE UC 52 and Wk 12 in ELEVATE UC 12 (Table). Most commonly reported TEAEs (>=3% of etrasimod-treated pts and greater than placebo in either trial) were headache, nausea, COVID-19 infection, dizziness, pyrexia, arthralgia, abdominal pain and worsening of UC. Serious AEs were similar between treatment groups in both trials. The overall safety profile was consistent with previous studies. Conclusion(s): Treatment with etrasimod 2mg resulted in statistically significant and clinically meaningful improvements based on clinical, endoscopic, symptomatic, and endo-histologic endpoints at Wks 12 and 52 in adults with moderately to severely active UC. No new safety findings were observed with etrasimod 2mg treatment for up to 52 weeks.

Post-Infection Irritable Bowel Syndrome in Sars-Cov-2 Patients: The Gi-Covid19 Study

Introduction: SARS-CoV-2 infection, known as COVID-19, may lead to persistent gastrointestinal dysfunction resembling aspects of post-infection disorders of gut-brain interaction (DGBI). However, the long-term consequences of COVID-19 on the gastrointestinal tract remain unclear. Aims & Methods: We aimed to evaluate the prevalence of gastrointestinal symptoms and post-infection disorders of gut-brain interaction (DGBI) up to 12 months after hospitalization and the factors associated with their presence. The GI-COVID19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were assessed at hospital admission and followed up after 1, 6, and 12 months to assess gastrointestinal symptoms using the Gastrointestinal Symptoms Rating Scale, the Rome IV Diagnostic Questionnaire for Functional Gastrointestinal Disorders in Adults, and the hospital anxiety and depression scale. ClinicalTrials. gov number, NCT04691895. Result(s): The study included2183 hospitalized patients. After excluding patients with pre-existing gastrointestinal symptoms and/or surgery, a total of 883 patients (614 COVID-19 and 269 controls) were included in the primary analysis, of whom 435 COVID-19 and 188 controls completed 12 months of follow-up. At enrollment, gastrointestinal symptoms occurred more frequently in COVID-19 patients than in the control group (59.3% vs. 39.7%, P<0.001). Symptoms more frequently complained by COVID-19 patients at enrollment were nausea, diarrhea, loose stool, and urgency. At 1-month follow-up evaluation, nausea and acid regurgitation were significantly more prevalent in COVID-19 patients than in the control group (8.7% vs. 1.7%, P=0.015 and 8.4% vs. 2.1%, P=0.006, respectively). At 6 months, COVID-19 patients reported lower rates of flatus (17.6% vs. 19.1%, P=0.024), constipation (8.9% vs. 17.1%, P<0.001) and hard stools (9.6 vs. 17.2%, P=0.030) as compared with the control group. At 12 months, constipation and hard stools were significantly less prevalent in COVID-19 patients than in the control group (9.6% vs. 16%, P=0.019 and 10.9% vs. 17.7%, P=0.011, respectively). COVID-19 patients reported higher rates of DGBI during follow-up compared to controls (Table), although statistically significant differences were found only for irritable bowel syndrome (IBS) according to Rome III criteria (4.4% vs 1.1%, P=0.036) and Rome IV criteria (3.2% vs 0.5%, P=0.045). The rate of COVID-19 patients depressed at 6 months and with anxiety at 12 months was higher compared to controls (4.1% vs 2.7%, P=0.014 and 4.5% vs 1.1%, P=0.088, respectively). Factors significantly associated with IBS diagnosis were anamnestic allergies (OR 10.024, 95% CI 1.766-56.891, P=0.009), chronic intake of proton pump inhibitors (OR 4.816, 95% CI 1.447-16.025, P=0.010) and dyspnea (OR 4.157, 95% CI 1.336-12.934, P=0.014). Conclusion(s): Hospitalized COVID-19 patients complain less constipation and hard stools than control at 12 months after acute infection. COVID-19 patients are also more likely to develop IBS.

Oncophone20 study: patients perception of telemedicine during follow up visits

Goals: COVID 19 pandemy has compromised our health system and imposed a change in clinical managements of a lot of different pathologies (included neoplastic). As in a lot of part of the world, ambulatory visitswere interrupted in favour of phone calls. Our goals are: to analize the regular and multidisciplinary approach of follow up phone call visits after breast cancer;to highlight the improvement of the comunication between hospital doctors and territorial doctors;to estimate the emotional perception of the patients. Methods: A total of 267 women who experienced breast cancerwere enrolled during routinely follow up phone calls. Specific questionnaire about their experiences and their feelings about telemedicine in COVID 19 era were administered. We used SUTAQ questionnaire to highlight patients perception about telemedicine. The questionnaire consists of 22 items divided into different subscales: “Enhanced care” (EC), “Satisfaction” (ST), “Privacy and discomfort” (PD) and “Care personnel concerns” (CC) scales. Results: The median age of enrolled womenwas 67 years (63 women ≤55 yrs and 204 women ≥56 yrs);the majority of them (76.78%;n = 205) had a low educational level while 23.22% achieved a high school diploma or higher (n = 62). The oncologic treatment was chemotherapy, hormonal therapy or radiotherapy in 18%, 71% and 57% respectively. No significant differences were observed for age groups, with EC and ST showing moderate agreement and PD and CC approaching neutrality.Regarding educational level significant differences were observed. EC showed moderate positive perception (mean = 4.40) among patients with lower education level that was slightly lower among women with higher education level (mean = 4.14) with a significant difference (p = 0.034). ST had an opposite pattern: mean = 3.99 for low educational level and mean = 4.78 for high educational level, with a strong significant difference (p < 0.001). PD approached neutrality for low educational, while for higher educated women it the lower mean = 2,93 indicted a more positive perception (p = 0.007). CC showed moderate agreement with no statistical differences. No statistically significant evidences were observed in our sample according to oncologic treatment. Conclusion(s): Satisfaction about telemedicine was higher among patients with high educational level. Further analysis will be conduct in order to understand the oncologic and economic impact of telemedicine in term of recurrences rate and health costs. Conflict of Interest: No significant relationships.

WORLDWIDE POST-MARKETING SAFETY SURVEILLANCE EXPERIENCE WITH TOFACITINIB IN ULCERATIVE COLITIS

Background: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. First market authorization was received in the US in May 2018. Post-marketing surveillance (PMS) is an important part of monitoring adverse events (AEs). Here, we report an analysis of PMS case safety reports for tofacitinib in patients with UC.Methods: We analyzed the worldwide tofacitinib PMS reports received in the Pfizer safety database from May 30, 2018 to August 25, 2020. The type and estimated reporting rate (RR) of serious AEs (SAEs) of interest, incl. infection, vascular, respiratory, neoplasm, and cardiac events, were reviewed. Patient-years of exposure (PY) was estimated based on worldwide sales data and the calculated daily regimens of tofacitinib 5 or 10 mg twice daily, immediate or extended-release formulations.Results: During the 27-month reporting period, worldwide post-marketing exposure to tofacitinib was 8,916 PY. Overall, 4,226 case reports were received and included 12,103 AEs, of which 1,839 were SAEs. Among the cases reported, 1,141 (27.0%) included an SAE and 18 (0.4%) were fatal. Of cases with reported gender (88.1%) or age (81.6%), 46.5%occurred in men and the median age was 45 years (range 9–93). When analyzed by tofacitinib formulation, proportions of SAE cases were similar (Table 1). Table 2 presents a summary of AEs and SAEs by MedDRA system organ class. Among the 1,839 SAEs, RRs per 100 PY were 3.28 for infection events, 1.26 for vascular events, 0.74 for respiratory events, 0.55 for neoplasm events, and 0.50 for cardiac events. The most commonly reported serious infection events (MedDRA preferred term [PT] n≥8) were 2 PTs within the high level term (HLT) of Clostridia infections (C. difficile colitis/infection), pneumonia, COVID-19, cytomegalovirus, and herpes zoster. The most commonly reported serious vascular events (n≥10) included hemorrhage, thrombosis, and deep vein thrombosis. Most serious respiratory events were pulmonary embolism. The most commonly reported serious neoplasm events (n≥3) were 2 PTs within the HLT of breast and nipple neoplasms malignant (breast cancer female/breast cancer), colon cancer, lymphoma, malignant melanoma, neoplasm malignant, and prostate cancer. The most commonly reported serious cardiac events (n≥4) were 3 PTs within the HLT of ischemic coronary artery disorders (acute myocardial infarction/myocardial infarction, angina pectoris) and pericarditis.Conclusion: Based on this review of PMS data for tofacitinib in UC, the types of AEs and RRs were consistent with the known tofacitinib safety profile, with no new potential risks identified. Limitations of PMS reports, low numbers of case reports for extended-release formulation, and reliance on estimated RRs due to lack of precise values for exposure, required for incidence rate calculation, should be considered when interpreting these results.(Table Presented)(Table Presented)

SIGNIFICANTLY REDUCED MORTALITY IN COVID-19 PATIENTS WITH GASTROINTESTINAL MANIFESTATIONS

Background: Gastrointestinal (GI) symptoms are the most common extrapulmonary manifestation of coronavirus disease 2019 (COVID-19). Therefore, we sought to determine the impact of GI symptoms on disease outcomes and the systemic inflammatory response in COVID-19. Methods: In two large, independent cohorts of hospitalized COVID-19 patients in the United States (n=634) and Italy (n=287) we examined GI symptoms on admission and related them to mortality and circulating proteomic biomarkers. Disease severity defined by oxygenation and end organ damage was also examined as an outcome in the US cohort. In both cohorts, a multivariate logistic regression was performed to determine the association of GI symptoms (nausea, vomiting, and diarrhea) present on admission and outcomes adjusting for age, gender and examined comorbid diseases. A prediction model was built based on the initial US cohort and validated with a distinct US cohort (n=242). In a subset of patients (n=238), circulating cytokines and chemokines were examined using a multiplexed proteomic assay (Olink) that simultaneously quantified 92 protein analytes. Results: A significant reduction in disease-associated mortality in COVID-19 patients presenting with GI symptoms was observed both in the US cohort (OR 0.54, 95% CI 0.34-0.86) and the Italian cohort (OR 0.33, 95% CI 0.13-0.67) which was independent of age, gender and comorbidities. A prediction model consisting of age and BMI with the addition of GI symptoms had a significantly improved ability to predict disease severity and mortality compared with age and BMI alone (median area under the curve (AUC) of 0.64 (age + BMI+ GI symptoms) vs 0.59 (age + BMI) for disease severity and 0.73 (age + BMI + GI symptoms) vs 0.70 (age + BMI) for mortality). The proteomic analysis revealed 6 clusters based on their co-segregation across all COVID-19 patients. Among these 6 clusters, clusters 4 and 5, which were enriched in the "Hallmark Inflammatory Response" and “KEGG JAK/STAT Signaling Pathway” respectively, and were reduced in patients with diarrhea. The observed mortality reduction in COVID-19 patients with GI symptoms was associated with lower circulating levels of key inflammatory proteins including IL-6, IL-8, IL-17A and CCL28 that are known to be associated with poor outcomes in COVID-19;while there was an increase in IL-7 and TRAIL, which both have important immunoregulatory functions. Conclusions: COVID-19 patients with GI symptoms have reduced inflammatory biomarkers and improved survival after adjusting for comorbidities, age and gender. These data highlight GI involvement as an important parameter for severity stratification in COVID-19 and point towards an immunomodulatory role of the GI tract in response to SARS-CoV-2 infection. (Figure presented)

Oncophone 20b: The Patients perception of telemedicine during follow up visits for gynecological cancers in COVID-19 pandemic

Objectives The spread of COVID-19 pandemic changed the approach in the management of neoplasms. Telemedicine was one of the tools we experienced to maintain the continuity of care for the patients. Our goal is to evaluate the impact of telemedicine in patients management during follow up visits and its emotional impact. Methods We enrolled 79 women with gynecological cancer. SUTAQ questionnaire was used to highlight patients perception about telemedicine. The questionnaire consists of 22 items divided into different subscales: 'Enhanced care'(EC), 'Satisfaction' (ST), 'Privacy and Discomfort'(PD), 'Care personnel concerns' (CPC), ' Increased accessibility' (IA) and ' Telemedicine as a Substitution' (TMS) scales Results Enrolled women had a mean age of 55 years (35 women ≤ 55 years and 44 women ≥ 55 years). The majority of them (61.54%;n=48) achieved a high school diploma or higher while (n=30) had a low educational level (middle school or lower);87.3% (n=69) were employed and 70.89% (n=56) lived with their partner. Younger women had a better perception towards telemedicine for TMS (mean=3.68) compared to older ones (mean=3.05). The difference was statistically significant (p=0.025). The PD subscale was in favor of higher educated women (mean=2.57) compared to lower educated ones (mean=3.28;p=0.042). No significant differences were observed between intensive and non intensive treatment. EC, ST, IA, and PD reached good responsiveness towards telemedicine, irrespectively of care level. Conclusions Telemedicine has been a well-evaluated tool, not only among younger and higher educated women but even by women needing intensive care.

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.

Inflammatory Bowel Disease Management During the COVID-19 Outbreak: The Ten Do's and Don'ts from the ECCO-COVID Taskforce.

Our knowledge of COVID-19 is changing and evolving rapidly, with novel insights and recommendations, almost on a daily basis. It behooves the medical community to provide updated information on a regular basis, on best practice to facilitate optimal care of infected patients and on appropriate advice for the general population. This is particularly important in the case of patients with chronic conditions, such as inflammatory bowel disease [IBD]. In this review, we have compiled existing evidence on the impact of COVID-19 in IBD patients and provide guidance on the most appropriate care to adopt during the pandemic. Our review highlights that IBD, per se, is not a risk factor for COVID-19. However, all IBD patients with symptoms should be tested for SARS-CoV-2 and the procedures for disease management should be carefully adapted: [i] in SARS-CoV-2-positive IBD patients, medical treatments should be re-evaluated [with a particular focus on corticosteroids] always with the purpose of treating active disease and maintaining remission; [ii] non-urgent surgeries and endoscopic procedures should be postponed for all patients; [iii] online consultancy should be implemented; and [iv] hospitalization and surgery should be limited to life-threatening situations.