Subcutaneous Infliximab After A Previous Intravenous Dose Optimization

Inflammatory bowel diseases (IBD) are a group of immune mediated disorders primarily targeting the gastro-intestinal tract and consist of two distinct phenotypes: Crohn's disease (CD) and ulcerative colitis (UC) that share similarities in both clinical presentation, pathophysiology and treatment. A small proportion of IBD patients cannot be correctly characterized in one of those categories and is referred to as IBD type unclassified (IBDU), which is often classified under UC for clinical research purposes. TNF inhibitors are one of the most frequently prescribed biological therapies and remain an important part of the therapeutic arsenal with international guidelines recommending their use in moderate-to-severe CD and UC when conventional treatments have failed.

Infliximab, a chimer monoclonal antibody against tumor necrosis factor (TNF), was the first anti-TNF agent to be approved for treating IBD as early as 1999. After losing its product patent in 2013, several biosimilars of infliximab have been commercialized including CT-P13. Originally only available in an intravenous (IV) formulation, a subcutaneous (SC) formulation of CT-P13 has been registered for treating moderate-to-severe CD and UC as well. However, many questions on the use of these subcutaneous formulations of infliximab in daily clinical practice remain unanswered, especially in patients who previously required IV dose optimization of infliximab.

The primary objective of the AMARETTO trial is to compare clinical and biological outcome between a regimen with SC infliximab every week and SC infliximab every other week among patients who were in clinical and biological remission with an optimized IV schedule when they switched to SC infliximab.

The secondary objectives of this study are:

• To compare treatment optimization and discontinuation between a regimen with SC inflixmab every week and SC infliximab every other week among patients who were in clinical and biological remission with an optimized IV schedule when they switched to infliximab SC.

• To evaluate the willingness and the experience of patients switching to SC infliximab.

• To compare clinical and biological outcome, as well as treatment optimization and discontinuation between a regimen with SC infliximab (every week or every other week) and IV infliximab among patients who were in clinical and biological remission with an optimized IV schedule.

This study is a national, multicenter, randomized, open-label, prospective, pragmatic trial in Belgium. The trial design is as follows:

• All subjects will undergo screening procedures. The screening visit of eligible patients will include the review of inclusion and exclusion criteria, and the informed consent form procedure. After screening, if the patient fulfils all inclusion and none of the exclusion criteria, and is willing to participate, the gastroenterologist will record the characteristics of patients and of the disease, medical and surgical history, current and past IBD treatments physical examination, the PRO-2 score about the last 3 days before the visit, blood analysis, stool analysis and patients will be asked to fill in a questionnaire about health-related quality of life.

• Afterwards the patients will visit the gastroenterologist 4 times in one year (week 0, week 8, week 24 and week 52, however the specific weeks can vary depending on the IV dosing schedule). During these visits a physical examination will be done, the PRO-2 score based on the 3 previous days before the visit will be calculated, a blood analysis and stool analysis will be done, the concomittant medication will be collected and patients will be asked to answer the questionnaire about the health related quality of life.

NOTE: patients that switch to subcutaneous infliximab will be asked to collect all at home administrations in a diary and to additionnaly answer a questionnaire about the satisfaction of switching to subcutaneous infliximab.