Publications by authors named "Allegretti J"

Objectives: 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.

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Article Synopsis
  • Interleukin-23 inhibition is a promising treatment for ulcerative colitis, and guselkumab serves as a potent inhibitor targeting this pathway, aiming to assess its safety and effectiveness for patients who have not responded to traditional therapies.
  • The study included two phase 3 trials where adults with moderate to severe active ulcerative colitis were randomly assigned to receive guselkumab or a placebo, with a focus on clinical remission as the main outcome at specific time points.
  • Results showed that a significantly higher number of patients receiving guselkumab achieved clinical remission compared to those on placebo, highlighting its potential as an effective therapy for managing ulcerative colitis.
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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.

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There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value.

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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.

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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.

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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.

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Article Synopsis
  • * Current gaps in IBD research include understanding the needs of underserved patient groups, validating biomarkers for early diagnosis, and optimizing treatment sequences for better patient outcomes.
  • * Implementing inclusive pragmatic research is essential to close these gaps and improve overall care and outcomes for all individuals affected by IBD.
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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.

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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.

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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.

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Fecal microbiota transplantation (FMT) has been demonstrated to be efficacious in preventing recurrent Clostridioides difficile (C. difficile) infections, and is being investigated for treatment of several other diseases including inflammatory bowel disease, cancer, obesity, liver disease, and diabetes. To speed up the translation of FMT into clinical practice as a safe and standardized therapeutic intervention, additional evidence-based technical and regulatory guidance is needed.

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  • A randomized placebo-controlled trial involved 61 patients, with 30 receiving FMT plus bezlotoxumab and 31 receiving FMT plus a placebo.
  • Results showed that 8% of participants had CDI recurrences (13% in the treatment group vs 3% in the placebo group), indicating no significant benefit of combining FMT with bezlotoxumab.
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Introduction: The comparative effectiveness of upadacitinib and tofacitinib for ulcerative colitis (UC) is poorly understood.

Methods: In this retrospective cohort study, we compared steroid-free clinical remission (SFCR) and endoscopic response/remission at 52 weeks among adults initiating upadacitinib or tofacitinib for UC.

Results: A total of 155 patients initiated upadacitinib (n = 81; 30% prior tofacitinib exposure) or tofacitinib (n = 74; 0% prior upadacitinib exposure).

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  • Adalimumab (ADL), a biologic treatment for chronic inflammatory diseases, is expensive, prompting the emergence of more affordable biosimilars that perform similarly.
  • This review highlights how factors like formulation, injection volume, and device design affect patients' experiences with injection-site pain (ISP).
  • In the USA, the availability of biosimilars includes designations of interchangeability, impacting how these products can be substituted at pharmacies, with varying degrees of regulation and clinical evaluation in progress.
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Introduction: Clostridioides difficile infection (CDI) causes symptoms of varying severity and negatively impacts patients' health-related quality of life (HRQL). Despite antibiotic treatment, recurrence of CDI (rCDI) is common and imposes clinical and economic burdens on patients. Fecal microbiota, live-jslm (REBYOTA [RBL]) is newly approved in the USA for prevention of rCDI following antibiotic treatments.

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Research and innovation around Clostridium difficile infection (CDI) has been a multidisciplinary endeavor since discovery of the organism in 1978. The field of gastroenterology has contributed to our understanding of CDI as a disease caused by disruptions in the gut microbiome and led to advances in therapeutic manipulation of gut microbiota, including fecal microbiota transplantation. The high incidence of CDI in patients with inflammatory bowel disease and treatment of the infection in this population have been of particular interest to gastroenterologists.

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Background And Aim: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis. These post hoc analyses evaluated early improvement in patient-reported outcomes with tofacitinib 10 mg twice daily (BID) in OCTAVE Open among patients with ulcerative colitis who experienced treatment failure with placebo (retreatment subpopulation) or tofacitinib 5 mg BID (dose escalation subpopulation) during maintenance.

Methods: Endpoints based on Mayo subscores (rectal bleeding improvement, stool frequency improvement, and symptomatic [both rectal bleeding and stool frequency] improvement) were analyzed overall and by prior tumor necrosis factor inhibitor (TNFi) failure status from month (M)1-M6 in OCTAVE Open.

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