Predictive Model for Outcomes in Inflammatory Bowel Disease Patients Receiving Maintenance Infliximab Therapy.

Background: No models predict future outcomes in inflammatory bowel disease (IBD) patients receiving maintenance infliximab therapy. We created a predictive model for unfavorable outcomes.

Methods: Adult patients with IBD receiving maintenance infliximab therapy at 2 centers with matched serum infliximab concentrations and blinded histologic scores (Robarts Histopathologic Index [RHI]) were included.

A living organoid biobank of patients with Crohn's disease reveals molecular subtypes for personalized therapeutics.

Crohn's disease (CD) is a complex and heterogeneous condition with no perfect preclinical model or cure. To address this, we explore adult stem cell-derived organoids that retain their tissue identity and disease-driving traits. We prospectively create a biobank of CD patient-derived organoid cultures (PDOs) from colonic biopsies of 53 subjects across all clinical subtypes and healthy subjects.

Pathogenic strains can emerge from gut-resident commensals.

is a prominent member of the human gut microbiota, playing crucial roles in maintaining gut homeostasis and host health. Although it primarily functions as a beneficial commensal, can become pathogenic. To determine the genetic basis of its duality, we conducted a comparative genomic analysis of 813 strains, representing both commensal and pathogenic origins.

Pangenome comparison of genomospecies unveils genetic diversity and ecological insights.

Unlabelled: is a Gram-negative commensal bacterium commonly found in the human colon, which differentiates into two genomospecies termed divisions I and II. Through a comprehensive collection of 694 whole genome sequences, we identify novel features distinguishing these divisions. Our study reveals a distinct geographic distribution with division I strains predominantly found in North America and division II strains in Asia.

A global consensus on the definitions, diagnosis and management of fibrostenosing small bowel Crohn's disease in clinical practice.

Fibrostenosis of the small bowel is common in patients with Crohn's disease. No consensus recommendations on definition, diagnosis and management in clinical practice are currently available. In this Consensus Statement, we present a clinical practice RAND/UCLA appropriateness study on the definition, diagnosis and clinical management of fibrostenosing Crohn's disease.

Subcutaneous Infliximab (CT-P13 SC) as Maintenance Therapy for Inflammatory Bowel Disease: Two Randomized Phase 3 Trials (LIBERTY).

Background & Aims: CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. The LIBERTY studies aimed to demonstrate superiority of CT-P13 SC vs placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC).

Methods: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators.

Reliability and Responsiveness of Clinical and Endoscopic Outcome Measures in Crohn's Disease.

Background: Regulatory guidance for Crohn's disease trials recommends coprimary efficacy end points that evaluate both symptoms and mucosal inflammation. We aimed to characterize the operating properties of commonly used disease activity assessments alone and in combination.

Methods: Endoscopic and clinical data were available for 129 participants from the Study of Biologic and Immunomodulator Naïve Patients in Crohn's Disease trial.

Exposure-efficacy relationship of vedolizumab subcutaneous and intravenous formulations in Crohn's disease and ulcerative colitis.

Background And Aims: This posthoc analysis of the GEMINI and VISIBLE studies in ulcerative colitis (UC) and Crohn's Disease (CD) assessed exposure-efficacy of vedolizumab intravenous (IV) and subcutaneous (SC).

Methods: A previously described population pharmacokinetic model was used to predict average serum and trough concentrations at steady state (C, C) and simulate the transition from vedolizumab IV to SC. Efficacy was defined as clinical remission at week 52: complete Mayo score ≤ 2 points and no individual subscore > 1 point (UC), and CD activity index score ≤ 150 points (CD).

Efficacy of vedolizumab during intravenous induction therapy in ulcerative colitis and Crohn's disease: post hoc analysis of patient-reported outcomes from the VISIBLE 1 and 2 studies.

Background: Vedolizumab is an anti-α4β7 integrin antibody used to treat moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). This post hoc analysis of patient-reported outcomes (PROs) from the VISIBLE 1 (NCT02611830) and 2 (NCT02611817) phase 3 studies evaluated onset of treatment effect on patient-reported symptoms during 6-week vedolizumab induction.

Methods: Patient-reported stool frequency (SF) and rectal bleeding (RB) (UC Mayo score), and SF and abdominal pain (AP) in CD were collected via electronic diary from VISIBLE patients receiving one or more open-label intravenous (IV) vedolizumab induction doses (weeks 0 and 2).

Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis Through 5 Years in Crohn's Disease and 4 Years in Ulcerative Colitis.

Background And Aims: Previously published long-term safety data reported a favourable ustekinumab safety profile for the treatment of inflammatory bowel disease [IBD]. We present the final cumulative safety data from pooled ustekinumab IBD phase 2/3 clinical studies through 5 years in Crohn's disease [CD] and 4 years in ulcerative colitis [UC].

Methods: In phase 3 studies, patients received a single intravenous placebo or ustekinumab [130 mg or ~6 mg/kg] induction dose followed by subcutaneous maintenance doses of placebo or ustekinumab [90 mg q8w or q12w].

Clinical Trial Design in Ulcerative Colitis: Interpreting Evolving Endpoints Based on Post Hoc Analyses of the Vedolizumab Phase 3 Trials GEMINI 1 and VISIBLE 1.

Background: The 12-point total Mayo score including a Physician's Global Assessment (PGA) of disease activity has been used to assess outcomes in clinical trials for ulcerative colitis (UC). In 2016, the US Food and Drug Administration (FDA) issued guidance advising the removal of the PGA in future trials. We examined how endpoints in UC trials have evolved and conducted a post hoc analysis of the GEMINI 1 and VISIBLE 1 trials to understand how the use of a 9-point modified Mayo score, excluding PGA, compares with the total Mayo score.

Pangenome comparison of genomospecies unveil genetic diversity and ecological insights.

is a Gram-negative commensal bacterium commonly found in the human colon that differentiates into two genomospecies termed division I and II. We leverage a comprehensive collection of 694 whole genome sequences and report differential gene abundance to further support the recent proposal that divisions I and II represent separate species. In division I strains, we identify an increased abundance of genes related to complex carbohydrate degradation, colonization, and host niche occupancy, confirming the role of division I strains as gut commensals.

Efficacy and safety of 48 weeks of guselkumab for patients with Crohn's disease: maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial.

Background: Many patients with moderately to severely active Crohn's disease do not respond to available therapies or lose response over time. The GALAXI-1 study previously found that three intravenous guselkumab dosages showed superior clinical and endoscopic outcomes over placebo at week 12 in patients with moderately to severely active Crohn's disease. We report the safety and efficacy of subcutaneous guselkumab maintenance regimens to week 48 in the GALAXI-1 study.

Efficacy and Safety of the Anti-mucosal Addressin Cell Adhesion Molecule-1 Antibody Ontamalimab in Patients with Moderate-to-Severe Ulcerative Colitis or Crohn's Disease.

Background And Aims: Ontamalimab is a fully human immunoglobulin G2 monoclonal antibody against mucosal addressin cell adhesion molecule-1, developed as treatment for inflammatory bowel disease.

Methods: Six phase 3, multicentre, randomised, double-blind, placebo-controlled clinical trials compared efficacy and safety of ontamalimab [25 mg and 75 mg once every 4 weeks] with placebo in patients with moderate-to-severe ulcerative colitis or Crohn's disease [two induction studies and one re-randomised maintenance study per condition]. This clinical trial programme was discontinued in 2020 for reasons unrelated to drug safety/efficacy; Crohn's disease studies are described in the Supplementary data.

Efficacy and Safety of Ustekinumab for Ulcerative Colitis Through 4 Years: Final Results of the UNIFI Long-Term Maintenance Study.

Introduction: Ulcerative colitis (UC) is a chronic condition that may require long-term treatment. We report the final efficacy and safety results of the UNIFI long-term extension study of ustekinumab in patients with UC through 4 years.

Methods: Ustekinumab induction responders who completed 44 weeks of maintenance treatment and agreed to enter the long-term extension continued their subcutaneous maintenance therapy (90 mg ustekinumab every 8 or 12 weeks [q8w or q12w] or placebo).

Qualitative and psychometric evaluation of the PROMIS®-Fatigue SF-7a scale to assess fatigue in patients with moderately to severely active inflammatory bowel disease.

Background: This study evaluated the content validity and psychometric properties of the Patient-Reported Outcomes Measurement Information System® (PROMIS)-Fatigue Short Form 7a (SF-7a) v1.0 scale to determine its suitability in clinical trials to assess fatigue in patients with moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC).

Methods: A qualitative interview assessed patients' experience living with CD (N = 20) and UC (N = 19).

Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study.

Background & Aims: The QUASAR Phase 2b Induction Study evaluated the efficacy and safety of guselkumab, an interleukin-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) with prior inadequate response and/or intolerance to corticosteroids, immunosuppressants, and/or advanced therapy.

Methods: In this double-blind, placebo-controlled, dose-ranging, induction study, patients were randomized (1:1:1) to receive intravenous guselkumab 200 or 400 mg or placebo at weeks 0/4/8. The primary endpoint was clinical response (compared with baseline, modified Mayo score decrease ≥30% and ≥2 points, rectal bleeding subscore ≥1-point decrease or subscore of 0/1) at week 12.

Practical Primer Addressing Real-World Use Scenarios of Subcutaneous Vedolizumab in Ulcerative Colitis and Crohn's Disease: Post Hoc Analyses of VISIBLE Studies.

Background: Vedolizumab, an anti-αβ integrin approved for intravenous (IV) treatment of moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD), was evaluated as a subcutaneous (SC) formulation in maintenance therapy for UC and CD in phase 3 VISIBLE 1, 2, and open-label extension studies, and recently approved in Europe, Australia, and Canada. Our aim was to evaluate efficacy and safety of IV and SC vedolizumab in clinically relevant UC and CD scenarios.

Methods: Post hoc data analyses from VISIBLE trials examined: (1) whether baseline characteristics predict clinical response to 2 vs 3 IV vedolizumab induction doses; (2) efficacy and safety of switching during maintenance vedolizumab IV to SC in patients with UC; (3) vedolizumab SC after treatment interruption of 1-46 weeks; (4) increasing dose frequency of vedolizumab SC from every 2 weeks (Q2W) to every week (QW) after disease worsening.

Evolution of Symptoms After Ustekinumab Induction Therapy in Patients With Crohn's Disease.

Background & Aims: Ustekinumab is an effective treatment of Crohn's disease (CD). Of interest to patients is knowing how soon symptoms may improve. We analyzed ustekinumab response dynamics from the ustekinumab CD trials.

A randomised, double-blind, placebo-controlled study of the LAG-3-depleting monoclonal antibody GSK2831781 in patients with active ulcerative colitis.

Background: Selective depletion of T cells expressing LAG-3, an immune checkpoint receptor that is upregulated on activated T cells, has been investigated in pre-clinical models as a potential therapeutic approach in inflammatory and autoimmune diseases where activated T cells are implicated.

Aims: GSK2831781, a depleting monoclonal antibody that specifically binds LAG-3 proteins, may deplete activated LAG-3 cells in ulcerative colitis (UC).

Methods: Patients with moderate to severe UC were randomised to GSK2831781 or placebo.