Publications by authors named "Feagan Brian"
Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies.
Lancet
December 2024
Background: Interleukin-23 inhibition is effective in treating ulcerative colitis. Guselkumab is a dual-acting, human IgG1, interleukin-23p19 subunit inhibitor that potently neutralises interleukin-23 and can bind to CD64. We aimed to evaluate the efficacy and safety of guselkumab as induction and maintenance therapy in patients with ulcerative colitis.
View Article and Find Full Text PDFBackground And Aims: Efmarodocokin alfa is an interleukin (IL)-22 agonist, with favorable pharmacokinetic (PK) properties and an acceptable safety profile. This study further explored the therapeutic potential of efmarodocokin alfa compared to vedolizumab in patients with ulcerative colitis (UC).
Methods: This randomized phase 2 trial evaluated the efficacy, safety, PK, and pharmacodynamics of 3 doses of efmarodocokin alfa administered intravenously every 4 weeks (30 μg/kg [n=43], 60 μg/kg [n=44], and 90 μg/kg [n=43]) compared with placebo (n=22) and with vedolizumab (n=43) in the treatment of moderate to severe UC.
Purpose: To evaluate correlation between terminal ileal (TI) stricture diagnosis at MR enterography (MRE) and ileocolonoscopy (IC) in patients with Crohn's disease (CD).
Methods: One hundred and four patients with CD (51% females; 41 ± 15 years) underwent IC and MRE within 3 months in this retrospective case-control study. Positive cases had TI strictures diagnosed by endoscopy (n = 35); or MRE (threshold small bowel dilation ≥ 3cm; n = 34).
Background: Approximately half of patients with Crohn's disease require ileocolonic resection. Of these, 50% will subsequently have endoscopic disease recurrence within 1 year. We aimed to evaluate the efficacy and safety of vedolizumab to prevent postoperative recurrence of Crohn's disease.
View Article and Find Full Text PDFBackground: High placebo responses have limited drug development in eosinophilic oesophagitis. The optimal configuration of trial outcomes is uncertain.
Aims: To inform more efficient future trial designs, to characterise clinical, endoscopic and histologic placebo responses in eosinophilic oesophagitis randomised controlled trials (RCTs).
Background And Aims: Normalization of high-sensitivity C-reactive protein [hs-CRP] and fecal calprotectin [FCP] are suggested Crohn's disease [CD] intermediate treatment targets. This analysis evaluates achievement of biomarker normalization and the relationship between improvements in biomarker concentrations and clinical and endoscopic outcomes among patients treated with risankizumab.
Methods: This post hoc analysis included patients with moderately to severely active CD and elevated baseline hs-CRP [> 5 mg/L] or FCP [> 250 µg/g] concentrations from the 12-week ADVANCE and MOTIVATE induction studies, and the 52-week FORTIFY maintenance study.
Article Synopsis
- Filgotinib, an oral medication for ulcerative colitis, has shown promising results in long-term treatment outcomes based on findings from the SELECTION trial.
- Researchers used group-based trajectory modeling to classify patients’ symptom responses over time, identifying five distinct patient groups based on their treatment responses.
- A majority of patients showed positive response trajectories, with factors such as recent diagnosis, usage of a higher filgotinib dose, and being biologic-naive linked to better outcomes and greater chances of achieving comprehensive disease control.
Background: Diagnostic imaging using CT enterography, magnetic resonance enterography, and intestinal ultrasound are important tools in evaluating stricturing Crohn's disease. Definitions of strictures have been developed for CT enterography and magnetic resonance enterography. However, expert recommendations for definitions and treatment response of strictures on intestinal ultrasound are not available.
View Article and Find Full Text PDFBackground & Aims: Understanding placebo rates is critical for efficient clinical trial design. We assessed placebo rates and associated factors using individual patient data from Crohn's disease trials.
Methods: We conducted a meta-analysis of phase 2/3 placebo-controlled trials evaluating advanced therapies in moderate to severe Crohn's disease (2010-2021).
Interpreting modern randomized controlled trials of medical therapy in inflammatory bowel disease.
Nat Rev Gastroenterol Hepatol
November 2024
Article Synopsis
- Treatment options for inflammatory bowel disease (IBD) have significantly increased, with new therapies like IL23p19 antagonists and Janus kinase inhibitors over the past decade.
- Landmark clinical trials, including head-to-head biologic comparisons, have been conducted, introducing new methodologies and endpoints to improve treatment evaluation.
- This review examines the evolution of these randomized controlled trials (RCTs) and their potential impact on clinical practice for IBD management.
Article Synopsis
- The study compares various scoring systems used to assess disease activity in patients with moderately to severely active ulcerative colitis (UC) after treatment with ustekinumab.
- It utilized data from the phase 3 UNIFI induction trial, calculating the responsiveness of different scores by measuring how much better treated participants performed compared to those receiving a placebo, known as win probability (WinP).
- The findings indicate that the UC-100 score showed the highest responsiveness, but the Mayo Clinic score and its modifications also performed well, suggesting that different scoring methods can be appropriate depending on specific circumstances and evaluation needs.
Article Synopsis
- Inflammatory bowel disease (IBD)-associated spondyloarthritis (SpA) is a common but complex condition that needs better understanding and management strategies.
- For diagnosing IBD-associated peripheral SpA (IBD-pSpA), collaboration with rheumatology is crucial for evaluating symptoms, physical exams, and imaging.
- Treatment should start with addressing the underlying IBD activity and may include advanced therapies, with a similar collaborative approach recommended for diagnosing and managing axial SpA (IBD-axSpA), using targeted medications as necessary.
Background: Tulisokibart is a tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody in development for the treatment of moderately to severely active ulcerative colitis. A genetic-based diagnostic test was designed to identify patients with an increased likelihood of response.
Methods: We randomly assigned patients with glucocorticoid dependence or failure of conventional or advanced therapies for ulcerative colitis to receive intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10) or placebo.
Background & Aims: Intestinal ultrasound (IUS) is increasingly used to assess Crohn's disease (CD) activity in clinical practice. However, application in clinical trials has been limited by heterogeneous scoring methods and concerns about reliability. We aimed to determine the inter- and intra-rater reliability of locally and centrally read IUS parameters for evaluating CD using prospectively performed scans.
View Article and Find Full Text PDFArticle Synopsis
- The study aimed to evaluate various instruments for assessing bowel preparation (BP) quality in patients with Crohn's disease, a condition where BP performance is not well understood.!
- Five different scales were used to analyze BP quality in videos from 40 patients, focusing on reliability and validity through statistical methods.!
- Results showed that most instruments demonstrated substantial reliability, with a negative correlation between BP quality and disease activity scores, indicating these tools are useful in clinical practice and research for Crohn's disease patients.!
Background Standardized methods to measure and describe Crohn disease strictures at CT enterography are needed to guide clinical decision making and for use in therapeutic studies. Purpose To assess the reliability of CT enterography features to describe Crohn disease strictures and their correlation with stricture severity. Materials and Methods A retrospective study was conducted in 43 adult patients with symptomatic terminal ileal Crohn disease strictures who underwent standard-of-care CT enterography at a tertiary care center at the Cleveland Clinic between January 2008 and August 2016.
View Article and Find Full Text PDFArticle Synopsis
- A study was conducted to evaluate the effectiveness of MR enterography in characterizing strictures caused by Crohn's disease and its correlation with stricture severity.
- The research involved a retrospective analysis of patient data collected from two major clinics, examining various MR enterography features through assessments by trained radiologists over a significant time period.
- Results indicated that certain features of strictures, like length and associated bowel dilation, showed strong reliability in measuring severity, which can help improve clinical decision-making and drug development for treating this condition.
Article Synopsis
- Histologic remission is an important treatment goal in ulcerative colitis (UC) and could lead to better long-term health outcomes, with etrasimod being an oral medication studied for its effectiveness in treating active UC.
- In a study, patients were given either etrasimod or a placebo, and their improvement in disease symptoms and histologic endpoints were evaluated at 12 and 52 weeks.
- Results showed that those on etrasimod had significantly better outcomes in terms of histologic and composite measures, with a higher percentage achieving clinical remission if they experienced disease clearance at the earlier 12-week mark.
Background: Filgotinib, an oral, once-daily, Janus kinase 1 preferential inhibitor, is an approved treatment for moderately to severely active ulcerative colitis.
Aims: The aim of this study is to assess the safety and efficacy of continued filgotinib therapy over ~4 years in the long-term extension of the phase 2b/3 SELECTION trial (SELECTIONLTE; NCT02914535).
Methods: In this interim analysis of SELECTIONLTE, SELECTION completers (week 10 responders to filgotinib who completed the maintenance study) continued their assigned treatment (double-blind filgotinib 200 mg [FIL200] or filgotinib 100 mg) and SELECTION week 10 non-responders received open-label FIL200.
Background And Aims: The ileum is the most commonly affected segment of the gastrointestinal tract in Crohn's disease (CD). We aimed to determine whether disease location affects response to filgotinib, a Janus kinase (JAK) inhibitor, in patients with moderate-to-severely active Crohn's disease (CD) and applying appropriate methods to account for differences in measuring disease activity in the ileum compared to the colon.
Methods: This post-hoc analysis of data from the FITZROY phase 2 trial (NCT02048618) compared changes in the Crohn's Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn's Disease (SES-CD) amongst patients with ileal-dominant and isolated colonic CD treated with 10 weeks of filgotinib 200 mg daily or placebo.
Background & Aims: Vedolizumab is indicated for the treatment of chronic pouchitis in the European Union. We assessed whether vedolizumab induced mucosal healing (MH) and if MH was associated with clinical improvements.
Methods: EARNEST, a randomized, double-blind, placebo-controlled study, evaluated vedolizumab efficacy and safety in adults with chronic pouchitis.