Corticosteroid Use in Randomized Clinical Trials of Biologics and Small Molecules in Inflammatory Bowel Disease: A Systematic Review.

Background And Aims: This systematic review aims to elucidate the use of corticosteroids in randomized clinical trials (RCTs) evaluating biologics and small molecules for inflammatory bowel disease (IBD). We analyzed corticosteroid use during both the induction and maintenance phases, highlighting areas needing standardization and improvement in clinical research.

Methods: We selected placebo-controlled phase 3 RCTs involving adults with moderate to severe IBD.

Adaptive Steroid Tapering Impedes Corticosteroid-free Remissions Compared with Forced Tapering in Clinical Trials of Ulcerative Colitis.

Introduction: It is unclear if steroid tapering protocols can affect clinical trial outcomes in ulcerative colitis [UC], particularly fixed versus adaptive steroid tapering. Fixed steroid tapering involves incremental dose decreases at prespecified intervals, and adaptive steroid tapering uses investigator discretion as determined by the patient's response.

Methods: In this post-hoc analysis from six clinical trials of UC [VARSITY, ACT 1, PURSUIT, GEMINI1, OCTAVE, and ULTRA2], responders to induction therapy with baseline corticosteroid use were considered as the primary population of interest.

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.

Ozanimod Differentially Impacts Circulating Lymphocyte Subsets in Patients with Moderately to Severely Active Crohn's Disease.

Background: Ozanimod showed efficacy and safety in the phase 2 STEPSTONE study conducted in patients with moderately to severely active Crohn's disease.

Aims: This analysis assessed the effects of ozanimod on circulating lymphocytes in Crohn's disease.

Methods: Patients received ozanimod 0.

Tissue-specific reprogramming leads to angiogenic neutrophil specialization and tumor vascularization in colorectal cancer.

Neutrophil (PMN) tissue accumulation is an established feature of ulcerative colitis (UC) lesions and colorectal cancer (CRC). To assess the PMN phenotypic and functional diversification during the transition from inflammatory ulceration to CRC we analyzed the transcriptomic landscape of blood and tissue PMNs. Transcriptional programs effectively separated PMNs based on their proximity to peripheral blood, inflamed colon, and tumors.

The Disease Severity Index for Inflammatory Bowel Disease Is a Valid Instrument that Predicts Complicated Disease.

Background: The disease severity index (DSI) for inflammatory bowel disease (IBD) combines measures of disease phenotype, inflammatory activity, and patient-reported outcomes. We aimed to validate the DSI and assess its utility in predicting a complicated IBD course.

Methods: A multicenter cohort of adults with IBD was recruited.

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.

Persistent perineal sinus following proctocolectomy in the inflammatory bowel disease patient.

Prolonged perineal wound healing following proctocolectomy in patients with inflammatory bowel disease (IBD) is a frustrating result for the medical team and patients who were hoping for improved quality of life. Prolonged healing, which lasts more than 6 months following proctocolectomy, is termed persistent perineal sinus (PPS) and typically necessitates further surgical management. Healing of the PPS is difficult due to the resulting "dead space" following proctocolectomy, necessitating the need to fill the void with viable tissue in an area with anatomic constraints.

Post-traumatic stress disorder symptoms are frequent among inflammatory bowel disease patients of South Asian descent-A case-control study.

Background: Post-traumatic stress (PTS) is the psycho-physiological response to a traumatic or life-threatening event and is implicated in inflammatory bowel disease (IBD). IBD-PTS is present in up to 30% of white, non-Hispanic patients. The rates of IBD in Asian populations are expanding, making the exploration of IBD-PTS in this population imperative.

Neuroimmune Modulation Through Vagus Nerve Stimulation Reduces Inflammatory Activity in Crohn's Disease Patients: A Prospective Open-label Study.

Background And Aims: Crohn's disease [CD] is a debilitating, inflammatory condition affecting the gastrointestinal tract. There is no cure and sustained clinical and endoscopic remission is achieved by fewer than half of patients with current therapies. The immunoregulatory function of the vagus nerve, the 'inflammatory reflex', has been established in patients with rheumatoid arthritis and biologic-naive CD.

The importance of predicting patient responses to monoclonal antibodies for Crohn's disease.

Introduction: Crohn's disease (CD) is a chronic immune-mediated inflammatory bowel disease that results in relapsing and remitting symptoms but progressive transmural bowel damage leading to significant morbidity. CD results from dysregulation of the immune system related to genetic and environmental factors. While the use of monoclonal antibodies targeting cytokines and adhesion molecules has been shown to improve outcomes in CD patients, their widespread use has been limited due to high costs as well as variable access.

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.

The evolving role of JAK inhibitors in the treatment of inflammatory bowel disease.

Introduction: Janus Kinase inhibitors (JAKi) are a new class of oral therapies for the treatment of moderate-severe ulcerative colitis with additional potential for the treatment of moderate-severe Crohn's disease. In contrast to biologic therapies JAKi provide the opportunity for non-immunogenic once or twice daily oral therapies.

Areas Covered: Janus Kinase inhibitors for the treatment of ulcerative colitis and Crohn's disease based on mechanism of action, pharmacokinetics, clinical trial and real-world data regarding safety and efficacy; focusing on regulatory approvals in the U.

COVID-19 and Inflammatory Bowel Disease.

The COVID-19 pandemic caused by the SARS-CoV-2 virus represents an unprecedented global health crisis. Safe and effective vaccines were rapidly developed and deployed that reduced COVID-19-related severe disease, hospitalization, and death. Patients with inflammatory bowel disease are not at increased risk of severe disease or death from COVID-19, and data from large cohorts of patients with inflammatory bowel disease demonstrate that COVID-19 vaccination is safe and effective.