HLA DQA1*05 and risk of anti-TNF treatment failure and anti-drug antibody development in children with Crohn's Disease: HLA DQA1*05 and Pediatric Crohn's Disease.

Objectives: HLA DQA1*05 has been associated with the development of anti-drug antibodies (ADA) to tumor necrosis factor antagonists (anti-TNF) and treatment failure among adults with Crohn's disease (CD). However, findings from other studies have been inconsistent with limited pediatric data.

Methods: We analyzed banked serum from patients with CD < 21 years of age enrolled in COMBINE, a multi-center, prospective randomized trial of anti-TNF monotherapy vs.

Low Anti-Tumor Necrosis Factor Levels During Maintenance Phase Are Associated With Treatment Failure in Children With Crohn's Disease.

Background: Higher drug levels and combination therapy with low-dose oral methotrexate (LD-MTX) may reduce anti-tumor necrosis factor (TNF) treatment failure in pediatric Crohn's disease. We sought to (1) evaluate whether combination therapy with LD-MTX was associated with higher anti-TNF levels, (2) evaluate associations between anti-TNF levels and subsequent treatment failure, and (3) explore the effect of combination therapy on maintenance of remission among patients with therapeutic drug levels (>5 µg/mL for infliximab and >7.5 µg/mL for adalimumab).

De Novo Crohn's Disease Diagnosed in the Setting of Acute SARS-Cov-2 Infection Requiring Escalation of Infliximab Therapy Guided by Personalized Pharmacokinetics.

Here, we describe a 7-year-old girl who was diagnosed with an early-onset Crohn's disease in the setting of COVID-19 illness. Her disease process responded poorly to standard infliximab dosing, necessitating repeat hospitalizations and red blood cell transfusions. Remission was subsequently induced using a personalized infliximab pharmacokinetic profile based on therapeutic drug monitoring.

Precise infliximab exposure and pharmacodynamic control to achieve deep remission in paediatric Crohn's disease (REMODEL-CD): study protocol for a multicentre, open-label, pragmatic clinical trial in the USA.

Introduction: The only biologic therapy currently approved to treat moderate to severe Crohn's disease in children (<18 years old) are those that antagonise tumour necrosis factor-alpha (anti-TNF). Therefore, it is critically important to develop novel strategies that maximise treatment effectiveness in this population. There is growing evidence that rates of sustained corticosteroid-free clinical remission, endoscopic healing and drug durability considerably improve when patients receive early anti-TNF dose optimisations guided by reactive or proactive therapeutic drug monitoring and pharmacodynamic monitoring.