A Prospective Randomised Controlled Trial of Adults with Perianal Fistulising Crohn’s Disease and Optimised Therapeutic Infliximab Levels: PROACTIVE Trial

Abstract

Crohn’s disease can be complicated by perianal fistulising Crohn’s disease, a highly morbid condition which can cause perianal pain, sepsis, and faecal incontinence. Infliximab is the most effective medical treatment for perianal fistulising Crohn’s disease. In patients who lose response to infliximab or relapse, therapeutic drug monitoring allows doctors to decide whether to increase the infliximab dose or to switch to another drug. Therapeutic drug monitoring is a process that involves measuring infliximab drug levels in the blood and measuring the presence of antibodies against infliximab. How therapeutic drug monitoring can be used to prevent a relapse and sustain Crohn’s disease remission is currently not clear.

This research project aims to analyse whether optimal dosing strategy of infliximab to achieve fistula healing in patients with complex perianal fistulising Crohn’s disease by comparing two treatment arms: the standard care arm and the proactive therapeutic drug monitoring arm. We will compare rates of fistula healing, fistula closure, healing as seen on magnetic resonance imaging (MRI), patient-reported outcomes and quality of life between the two groups.

Patients will be screened for suitability for infliximab therapy by their gastroenterologist, who perform a number of examinations, tests and procedures, and will review your medical history. Eligible patients will be randomly allocated to either the proactive therapeutic drug monitoring arm or the standard care arm. Patients in the standard care arm will receive the standard dose of infliximab and patients in the proactive therapeutic drug monitoring arm will have infliximab dosing is adjusted based on the infliximab levels in their blood. Patients will be assessed for response based on their symptoms, physical examination of the perianal area, blood tests, imaging results including MRI and patient-reported outcomes including quality of life assessments. In both arms patients will be required to attend regularly for reviews, infliximab infusions and investigations. The maximum duration of this study will be approximately 54 weeks (1 year) from the time you decide to participate. At each study visit, patients will undergo a clinical evaluation, routine blood tests, blood collection for infliximab level testing, and/or a stool specimen collection for faecal testing.