Precise infliximab exposure and pharmacodynamic control to achieve deep remission in paediatric Crohns 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. In response, our team has developed a personalised and scalable infliximab dosing intervention that starts with dose selection and continues throughout maintenance to optimise drug exposure. We hypothesise that a precision dosing strategy starting from induction and targeting dose-specific pharmacokinetic and pharmacodynamic endpoints throughout therapy will significantly improve outcomes compared with a conventional dosing strategy. Methods and analysis Conduct a clinical trial to assess rates of deep remission between Crohn’s disease patients receiving infliximab with precision dosing (n=90) versus conventional care (n=90). Patients (age 6–22 years) will be recruited from 10 medical centres in the USA. Each centre has been selected to provide either precision dosing or conventional care dosing. Precision dosing includes the use of a clinical dec...
Source: BMJ Open - Category: General Medicine Authors: Tags: Open access, Gastroenterology and hepatology Source Type: research