Subdomains of Post-COVID Syndrome (PCS) - a population-based study.

Purpose: 'Post-COVID Syndrome' (PCS), which encompasses the multifaceted sequelae of COVID-19, can be severity-graded by a previously defined score encompassing 12 different long-term symptom complexes. The PCS score was shown to have two main predictors, namely acute COVID-19 severity and individual resilience. The purpose of the present study was to verify these predictors and to assess their detailed relationship to the symptom complexes constituting the PCS score.

A Phase 2 Study of MORF-057, an Oral α4β7 Integrin Inhibitor in Moderately to Severely Active Ulcerative Colitis.

Background & Aims: MORF-057 is an orally administered small-molecule drug that inhibits α4β7 integrin-mediated recruitment of α4β7-expressing lymphocytes to the gut, a process implicated in the pathology of ulcerative colitis (UC). This study evaluated the efficacy, pharmacokinetics, pharmacodynamics, safety, and tolerability of MORF-057 in participants with moderately to severely active UC.

Methods: This open-label, phase 2a, single-arm, multicenter trial comprised a 6-week screening period, a 52-week active treatment period (including a 12-week induction period and 40-week maintenance period), and a 4-week safety follow-up period.

Nuclear spin hyperpolarization of pyruvate enables longitudinal monitoring of treatment response in intestinal tumor organoids.

Purpose: Colorectal cancer, a leading cause of death in the Western world, is increasingly affecting younger populations. The Warburg effect, characterized by enhanced lactate production, is a hallmark of this cancer type. Although F-FDG PET-CT is commonly used for diagnosis, MRI offers higher spatial and chemical resolution without the drawbacks of radiation.

Anti-TL1A antibody, afimkibart, in moderately-to-severely active ulcerative colitis (TUSCANY-2): a multicentre, double-blind, treat-through, multi-dose, randomised, placebo-controlled, phase 2b trial.

Background: TNF-like ligand 1A (TL1A) is an emerging therapeutic target for inflammatory bowel disease. We evaluated the safety and efficacy of multiple doses of afimkibart, a TL1A-directed antibody, in patients with moderately-to-severely active ulcerative colitis.

Methods: The multicentre, double-blind, treat-through, multi-dose, randomised, placebo-controlled, phase 2b, TUSCANY-2 trial was conducted at 114 centres in 23 countries across North America, Europe, Asia, Africa, Australia, and South America.

Comparison of the FDA and EMA guidance on drug development in ulcerative colitis: an expert panel review.

Background And Aims: The Food and Drug Administration (FDA) and European Medicines Agency (EMA) ensure the safety, efficacy, and security of treatments, including therapies for immune-mediated disorders such as inflammatory bowel disease (IBD). Their clinical trial guidelines aid sponsors in designing robust studies. While the EMA updated its guidelines for ulcerative colitis (UC) in 2018, the FDA issued new recommendations in April 2022.

Bowel Urgency in Crohn's Disease: Effects of Mirikizumab in a Randomized Controlled Phase 3 Study.

Background And Aims: Bowel urgency (BU) is an underrecognized and debilitating symptom of Crohn's disease. Mirikizumab, an interleukin-23p19 inhibitor, is efficacious for BU resolution in ulcerative colitis. We evaluated the efficacy of mirikizumab in achieving early BU response and remission among participants with Crohn's disease enrolled in the phase 3 VIVID-1 study.

Efficacy and Safety of Infliximab and Vedolizumab Maintenance Therapy in Patients with Crohn's Disease and Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Direct comparative data for infliximab and vedolizumab are limited due to lack of head-to-head trials. This systematic review and meta-analysis compared the efficacy and safety of infliximab and vedolizumab as intravenous or subcutaneous maintenance treatments for adults with moderately to severely active Crohn's disease or ulcerative colitis. Medical databases, PubMed, Embase, and the Cochrane Library were systematically searched from January 2010 to May 2024 to identify Phase 1 to 3 randomized controlled trials.

Broad Impact of Bowel Urgency in Ulcerative Colitis and Crohn's Disease: US, European, and Japanese Patient and Healthcare Professional Perspectives from the Communicating Needs and Features of IBD Experiences (CONFIDE) Survey.

Introduction: Bowel urgency affects the quality of life of patients with Crohn's disease (CD) and ulcerative colitis (UC). This study used data from the Communicating Needs and Features of IBD Experiences (CONFIDE) survey to explore patient and healthcare professional (HCP) perceptions on the broad impacts of bowel urgency on patients' emotions and daily lives.

Methods: Online, quantitative, cross-sectional surveys were conducted among patients with moderate-to-severe UC or CD (defined based on previous treatment, steroid use, and/or hospitalization) and HCPs specialized in gastroenterology in Europe (France, Germany, Italy, Spain, UK), United States (US), and Japan.

Impact of moderate-to-severe ulcerative colitis and Crohn's disease on sexual activity: United States and European patient perspectives from the communicating needs and features of IBD experiences (CONFIDE) survey.

Background: Ulcerative colitis (UC) and Crohn's disease (CD) negatively affect patients' quality-of-life, and their impact on patients' sexual health is rarely addressed. This study assessed the impact of moderate-to-severe UC and CD on sexual activity using United States (US) and European data from the Communicating Needs and Features of IBD Experiences (CONFIDE) survey.

Methods: Online, quantitative, cross-sectional surveys were conducted among patients with moderate-to-severe UC or CD and health care professionals (HCPs).

Oral Microcapsule Chromocolonoscopy With Patent Blue V Improves Adenoma Detection Safely and Effectively.

Background And Objective: Chromocolonoscopy significantly improves polyp/adenoma detection rates (PDR/ADR). However, its integration into routine clinical practice is hindered by its cumbersome mode of application. The objective was to develop an oral nutritional grade delivery system and to assess its efficacy for colonic release, mucosal staining and PDR/ADR as a proof of concept.

Bowel urgency in ulcerative colitis: effect of baseline urgency and change in urgency in response to mirikizumab.

Background: Mirikizumab has demonstrated efficacy in moderately to severely active ulcerative colitis. A 1-2-point change in Urgency Numeric Rating Scale (NRS) score can be meaningful for patients. In these post-hoc analyses, we evaluated the efficacy of mirikizumab compared to placebo by baseline Urgency NRS score groups (0-3, 4-6, and 7-10) and its effect on bowel urgency severity over time.

T and B cell responses against Epstein-Barr virus in primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is an idiopathic, progressive and incurable liver disease. Here, we aimed for systematic analyses of adaptive immune responses in PSC. By profiling the T cell repertoires of 504 individuals with PSC and 904 healthy controls, we identified 1,008 clonotypes associated with PSC.

Managing withdrawals and exclusions of study participants in COVID-19-research by NUKLEUS.

Background: This article describes how withdrawals and exclusions of study participants can be managed in COVID-19-cohort studies by NUKLEUS (German: NUM Klinische Epidemiologie- und Studienplattform), using NAPKON (German: Nationales Pandemie Kohorten Netz). The aim of this manuscript was to describe, how partial withdrawals can be performed so that most of the data and bio-samples can be kept for research purposes.

Methods: The study has taken all signed informed consents (ICs) of study participants into account in order to develop a method how partial withdrawals can be developed and installed.

Factors associated with response to filgotinib and the prognostic power of faecal calprotectin for ulcerative colitis in the phase 2b/3 SELECTION trial.

Background: Patients with moderately to severely active ulcerative colitis have distinct filgotinib response trajectories.

Aims: Evaluate factors associated with response to filgotinib over time.

Methods: Patients from SELECTION (NCT02914522) receiving filgotinib 200 mg (FIL200) or 100 mg (FIL100), or placebo were included.

US and European Patient and Health Care Professional Perspectives on Fatigue in Ulcerative Colitis and Crohn's Disease: Results From the Communicating Needs and Features of Inflammatory Bowel Disease Experiences Survey.

Background: Fatigue is a burdensome symptom of Crohn's disease (CD) and ulcerative colitis (UC). The Communicating Needs and Features of Inflammatory Bowel Disease Experiences (CONFIDE) study investigated how patients and health care professionals (HCPs) in the United States (US) and Europe (France, Germany, Italy, Spain, and the United Kingdom) perceived the experiences and impact of CD/UC-related symptoms.

Methods: Online, quantitative, cross-sectional surveys were conducted separately among patients with moderate-to-severe CD/UC (defined based on previous treatment, steroid use, and/or hospitalization) and HCPs who treated patients with CD/UC.

Fecal metaproteomics enables functional characterization of remission in patients with inflammatory bowel disease.

The gut microbiome is an important contributor to the development and the course of inflammatory bowel disease (IBD). While changes in the gut microbiome composition were observed in response to IBD therapy using biologics, studies elucidating human and microbial proteins and pathways in dependence on therapy success are sparse. Fecal samples of a cohort of IBD patients were collected before and after 14 weeks of treatment with three different biologics.

Nicotinamide modulates gut microbial metabolic potential and accelerates recovery in mild-to-moderate COVID-19.

Cellular NAD depletion, altered tryptophan metabolism and gut microbiome dysbiosis are associated with disease progression and unfavourable clinical outcomes in COVID-19. Here, we show that supplementing tryptophan metabolism with nicotinamide alleviates COVID-19 symptoms. We evaluate a 4-week intervention with a novel nicotinamide formulation (1,000 mg) in a prospective, double-blind, randomized, placebo-controlled trial in 900 symptomatic outpatients with PCR-proven COVID-19.

Deucravacitinib in patients with inflammatory bowel disease: 12-week efficacy and safety results from 3 randomized phase 2 studies in Crohn's disease and ulcerative colitis.

Background And Aims: Tyrosine kinase 2 is a downstream intracellular mediator of interleukin-23 signaling, which has a key role in the pathogenesis of inflammatory bowel disease. Deucravacitinib is a novel, oral, selective, allosteric tyrosine kinase 2 inhibitor currently approved for the treatment of adults with moderate to severe plaque psoriasis.

Methods: Here we describe 3 randomized, double-blind, placebo-controlled phase 2 studies of deucravacitinib in patients with moderately to severely active Crohn's disease (LATTICE-CD [NCT03599622]) or ulcerative colitis (LATTICE-UC [NCT03934216] and IM011-127 [NCT04613518]).

Long-term efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis: an interim analysis of the phase 3 U-ACTIVATE long-term extension study.

Background: The U-ACTIVATE long-term extension study aims to evaluate the long-term efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis. Here, we report interim results after 3 years of total treatment.

Methods: U-ACTIVATE is an ongoing, 288-week, phase 3, long-term extension study done at 307 centres across 43 countries (active sites on Dec 31, 2021, are presented as part of this interim analysis) and began on Jan 31, 2017.

Genome-wide association study of post COVID-19 syndrome in a population-based cohort in Germany.

If health impairments due to coronavirus disease 2019 (COVID-19) persist for 12 weeks or longer, patients are diagnosed with Post-COVID Syndrome (PCS), or Long-COVID. Although the COVID-19 pandemic has largely subsided in 2024, PCS is still a major health burden worldwide, and identifying potential genetic modifiers of PCS remains of great clinical and scientific interest. We therefore performed a case-control type genome-wide association study (GWAS) of three recently developed PCS (severity) scores in 2,247 participants of COVIDOM, a prospective, multi-centre, population-based cohort study of SARS-CoV-2-infected individuals in Germany.

Comparing Outcomes With Subcutaneous Infliximab (CT-P13 SC) by Baseline Immunosuppressant Use: A Post Hoc Analysis of the LIBERTY-CD and LIBERTY-UC Studies.

Background: Superior efficacy of subcutaneous infliximab (CT-P13 SC) over placebo for maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC) was demonstrated in the randomized LIBERTY-CD and LIBERTY-UC studies. The current post hoc analysis compared outcomes with CT-P13 SC by baseline immunosuppressant use.

Methods: Patients with moderately to severely active CD or UC randomized to the CT-P13 SC maintenance arm of the 54-week LIBERTY trials at week 10 and who were treated in the open-label extension (weeks 56-102) were included.

Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn's disease and ulcerative colitis: 2-year results from open-label extensions of two randomized controlled trials (LIBERTY).

Background And Aims: In the LIBERTY phase 3 studies in Crohn's disease (CD) or ulcerative colitis (UC), maintenance CT-P13 subcutaneous (SC) 120 mg was more effective than placebo after 1 year. Here we report 2-year data from the LIBERTY open-label extensions.

Methods: Two randomized, placebo-controlled, double-blind studies evaluated the efficacy and safety of CT-P13 SC maintenance in moderate-to-severe CD or UC.

Effect of Risankizumab Induction and Maintenance Therapy on the Rate of Hospitalization in Patients with Crohn's Disease.

Background And Aims: In phase 3 induction (ADVANCE and MOTIVATE) and maintenance (FORTIFY) trials, risankizumab was shown to benefit symptom and endoscopic defined outcomes in patients with Crohn's disease (CD). We examined the effects of risankizumab on the incidence of CD-related hospitalizations in these studies.

Methods: Patients with active CD were randomized to intravenous (IV) risankizumab 600 or 1200 mg, or placebo at weeks 0, 4, and 8 in the 12-week induction studies.

Corticosteroid-sparing effects of risankizumab efficacy and safety in patients with moderately to severely active ulcerative colitis.

Background And Aims: This post hoc analysis evaluated the corticosteroid-sparing effects of risankizumab (RZB) therapy in patients with moderate-to-severe ulcerative colitis in the phase 3 induction and maintenance studies, INSPIRE and COMMAND.

Methods: Patients were randomized (2:1) to 12 weeks of intravenous RZB or placebo (PBO) induction therapy; responders to intravenous RZB were randomized (1:1:1) to receive subcutaneous RZB 180 mg, 360 mg, or PBO (RZB withdrawal) maintenance therapy. Baseline corticosteroid doses were maintained during induction, with a mandatory taper beginning at maintenance week 0.

Real-world effectiveness of ustekinumab versus anti-TNF or vedolizumab in ulcerative colitis: induction and 12-month maintenance results from the prospective, observational RUN-UC study.

Background: Real-world evidence studies of ustekinumab (UST) in ulcerative colitis (UC) are needed because randomized controlled trials do not represent unselected patient populations in everyday clinical practice. Patients with UC were recruited when starting biologic therapy for the first time or switching to a new biologic therapy. This study assessed the effectiveness of maintenance therapy with UST in comparison to anti-TNF or vedolizumab (VDZ) at 12 months.