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.

Oral Peptide Therapeutics as an Emerging Treatment Modality in Immune-Mediated Inflammatory Diseases: A Narrative Review.

Immune-mediated inflammatory diseases (IMIDs), such as psoriasis, psoriatic arthritis, and inflammatory bowel disease, encompass a heterogenous group of conditions associated with chronic inflammation. Systemic treatments for patients with IMIDs include parenterally delivered monoclonal antibodies (mAbs) that disrupt specific cytokine and cytokine receptor binding interactions, and orally delivered small molecules that inhibit certain enzymes involved in the regulation of inflammatory signaling. Many patients prefer oral alternatives to injectables, but currently available oral advanced therapies are less effective than mAbs and/or have tolerability concerns.

One-Year Efficacy of Guselkumab Versus Advanced Therapies for the Treatment of Moderately to Severely Active Crohn's Disease: A Network Meta-Analysis.

Introduction: This study used network meta-analysis (NMA) to evaluate the comparative efficacy of available advanced therapies for moderately to severely active Crohn's disease (CD) versus the IL-23 inhibitor guselkumab.

Methods: A systematic literature review was conducted to identify randomized controlled trials (RCTs) of advanced therapies in moderately to severely active CD. Bayesian NMAs were conducted for outcomes of clinical response, clinical remission, endoscopic response, and a combined outcome of clinical remission with endoscopic response, at the end of the maintenance phase (up to 1 year).

Assessment and Impact of Age on the Safety and Efficacy of Etrasimod in Patients With Ulcerative Colitis: A Post Hoc Analysis of Data From the ELEVATE UC Clinical Program.

Background: Patient age can impact the safety and efficacy of ulcerative colitis (UC) treatments. Etrasimod is an oral, once daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active UC. Here, we evaluate the impact of age on etrasimod safety and efficacy in patients with UC in the phase 3 ELEVATE UC clinical program.

Risk Factors for Antibiotic Exposure Post-Fecal Microbiota Transplantation for Recurrent Infection: A Prospective Multicenter Observational Study.

Background: Recurrent infection (CDI) is primarily driven by antibiotic-induced disruption of the indigenous intestinal microbiota. Restoration of microbiota through fecal microbiota transplantation (FMT) is effective in preventing subsequent CDI, although this effect is attenuated with additional antibiotic exposure. The aim of this study was to identify the risk factors for recurrent antibiotic administration after FMT.

Tolerability and Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists in Patients with Inflammatory Bowel Disease.

Purpose: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) have transformed obesity management, but their safety and efficacy in patients with inflammatory bowel disease (IBD) warrants further evaluation.

Methods: This retrospective cohort study included adults with obesity and a diagnosis of IBD who were treated with GLP-1 RA within a large healthcare network. Primary outcomes were ≥ 5% total weight loss (TWL) at 12-months post initiation, and IBD flares, comparing 12-months pre- and post-GLP-1 RA initiation.

Safety and Efficacy of Fecal Microbiota, Live-jslm (REBYOTA®), for the Prevention of Recurrent Clostridioides difficile Infection in Participants With Inflammatory Bowel Disease in PUNCH CD3-OLS.

Background: Fecal microbiota, live-jslm (RBL; REBYOTA®), is the first single-dose, broad consortia, microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care antimicrobials. Inflammatory bowel disease (IBD) is a common risk factor for rCDI, yet patients with IBD are often excluded from prospective trials. This subgroup analysis of PUNCH CD3-OLS (NCT03931941) evaluated the safety and efficacy of RBL in participants with rCDI and IBD.

Safety, Pharmacokinetics, and Clinical Efficacy of ADS051, a Neutrophil Modulator, in Ulcerative Colitis: Results of a Randomized Phase 1b Trial.

Introduction: Ulcerative colitis (UC) is characterized by colonic inflammation, with neutrophils playing a key role in UC activity, prognosis, and response to therapies. Current UC therapeutics can have significant side effects and limited efficacy. ADS051 is a novel, oral, gut-restricted small molecule that modulates neutrophil migration and activation without in vitro suppression of T-cell activation.

Etrasimod as a Monotherapy or With Concomitant Use of Corticosteroids and/or Aminosalicylates: Results From the ELEVATE UC Clinical Program.

Background: Etrasimod is an oral, once daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). We assessed the benefit of etrasimod monotherapy and the impact of concomitant corticosteroids (CS) and/or 5-aminosalicylates (5-ASA) therapy.

Methods: In ELEVATE UC 52 and ELEVATE UC 12, patients with moderately to severely active UC were randomized 2:1 to etrasimod 2 mg QD or placebo for 52 and 12 weeks, respectively.

Small-Molecule Neutrophil Modulator ADS051 is Safe and Well-Tolerated in a Phase 1 Single Ascending Dose Study.

Introduction: A need for better treatment options for moderate to severe ulcerative colitis (UC) persists because of the efficacy and safety limitations of current therapies. Neutrophil epithelial transmigration is associated with the characteristic colonic mucosal inflammation in and very likely involved with the pathogenesis and clinical symptoms of UC. ADS051 is a small-molecule inhibiting neutrophil migration and activation, which are potentially important therapeutic targets in UC.

Safety and Tolerability of CP101, a Full-Spectrum, Oral Microbiome Therapeutic for the Prevention of Recurrent Clostridioides difficile Infection: A Phase 2 Randomized Controlled Trial.

Background & Aims: Recurrent Clostridioides difficile infections (CDIs) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full-spectrum, oral microbiome therapeutic is unknown. This study aimed to determine the safety and efficacy of CP101, an orally administered microbiome therapeutic, to restore a diverse microbiome and prevent recurrent CDI in a broad population.

Diet and Microbiome-Directed Therapy 2.0 for IBD.

Inflammatory bowel disease (IBD) comprises chronic and relapsing disorders of the gastrointestinal tract, characterized by dysregulated immune responses to the gut microbiome. The gut microbiome and diet are key environmental factors that influence the onset and progression of IBD and can be leveraged for treatment. In this review, we summarize the current evidence on the role of the gut microbiome and diet in IBD pathogenesis, and the potential of microbiome-directed therapies and dietary interventions to improve IBD outcomes.

The Progression of Microbiome Therapeutics for the Management of Gastrointestinal Diseases and Beyond.

There has been an increased ability to investigate the human microbiota through next-generation sequencing and functional assessment. This advancement has rapidly expanded our ability to study and manipulate the gastrointestinal microbiome to mitigate disease. Fecal microbiota transplantation, a therapy that broadly transfers the entire intestinal ecosystem, has been explored as a potential therapeutic in a variety of gastrointestinal, hepatic, and extraintestinal conditions.

TCF1-LEF1 co-expression identifies a multipotent progenitor cell (T2-MPP) across human allergic diseases.

Repetitive exposure to antigen in chronic infection and cancer drives T cell exhaustion, limiting adaptive immunity. In contrast, aberrant, sustained T cell responses can persist over decades in human allergic disease. To understand these divergent outcomes, we employed bioinformatic, immunophenotyping and functional approaches with human diseased tissues, identifying an abundant population of type 2 helper T (T2) cells with co-expression of TCF7 and LEF1, and features of chronic activation.

Review article: The epidemiology and management of Clostridioides difficile infection-A clinical update.

Background: Clostridioides difficile is the most common cause of healthcare-associated infection, and severe cases can result in significant complications. While anti-microbial therapy is central to infection management, adjunctive therapies may be utilised as preventative strategies.

Aim: This article aims to review updates in the epidemiology, diagnosis, and management, including treatment and prevention, of C.