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 .

Early efficacy results of montelukast as add on treatment of hospitalized patient with COVID-19 pneumonia: An investigator-initiated open labelled randomized controlled ongoing clinical trial

Background: Leukotriene receptor antagonists might have a role in viral infections, either by improving lung injury and inflammation, or by acting on 3CL proteinase of the HCoV-19. Thus, we hypothesised that montelukast may be an adjuvant drug in HCoV-19 infection treatment. This study aims to evaluate the efficacy and safety of montelukast in the adjuvant treatment of COVID-19 pneumonia. Method: We are conducting a randomized, controlled, parallel, open-label trial involving hospitalized adult patients with confirmed COVID-19. Patients were randomly assigned in a 1:1 ratio to receive either montelukast 10 mg, once a day for 14 days, in addition to standard of care (SoC), or SoC alone. SoC follows the best practice for treating these patients, according to updated recommendations. The primary outcome is time to recovery. Participants are assessed using diary cards to capture data on treatment-related improvements in an 8-point ordinal scale (COVID-19 scale). Secondary endpoints include changes in NEWS (National Early Warning Score), respiratory and inflammatory parameters. Mann-Whitney U test for continuous variables and Ficher's exact test for categorical variables were used to compare differences between groups. This phase IV clinical trial takes place at the University Hospital of São João, Porto. EudraCT number: 2020-001747-21. Results: Eighteen patients (11 males, mean age 60 years, age range 42-89, table 1) enrolled and completed the trial. The trial is still open for the recruitment of participants. The participants from the active group spent less time hospitalized than control group [median (P25-75): 3.0 (3-6) vs 7.5 (4.75-17.75) days, p = 0.03]. The number of days to achieve 7 (not hospitalized, limitation on activities) or 8 points (not hospitalized, no limitations) in the COVID-19 scale was also statistically significant. The number of patients in need of supplemental high flux oxygen and the NEWS score followed the same trend (table 1). Conclusion: In conclusion, early efficacy results from this ongoing clinical trial suggest montelukast may have a role in treating COVID-19 patients as an adjuvant treatment by diminishing hospitalization days until discharge. Data were presented as median (25th percentile-75th percentile) unless otherwise states. Bpm: beats per minute;cpm: cycles per minute;NEWS: National Early Warning Score);SoC: standard of care. NEWS is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness), and is being used as an efficacy measure. Higher points represent higher risk of poor outcomes. COVID-19 scale is as follows: (1) Death;(2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO);(3) Hospitalized, on non-invasive ventilation or high flow oxygen devices;(4) Hospitalized, requiring supplemental oxygen;(5) Hospitalized, not requiring supplemental oxygen-requiring ongoing medical care (COVID-19 related or otherwise);(6) Hospitalized, not requiring supplemental oxygen-no longer requires ongoing medical care;(7) Not hospitalized, limitation on activities and/or requiring home oxygen;(8) Not hospitalized, no limitations on activities. (Figure Presented).

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.