Optimising the use of biological medications in inflammatory bowel disease

Abstract

Biological agents have revolutionised the management of inflammatory bowel disease (IBD) in the last fifteen years. As treatment choices increase, there is a need to differentiate between these agents to guide medication choice by gastroenterologists. As such, the aim of this thesis was to identify strategies to optimise the effectiveness of biological agents.

Key findings:

First, an updated epidemiological study was performed that demonstrated the prevalence of IBD is rising in Australia, particularly in the older population. Two common biological agents, infliximab and vedolizumab, were then compared in the management of ulcerative colitis. It was identified that vedolizumab had a longer treatment persistence when used as a first-line biological agent compared with infliximab, however not as a second-line agent.

To assist in achieving optimal outcomes in IBD, histological remission has emerged as a potential treatment endpoint. However its utility in clinical practice is unknown. In this thesis, a nationwide survey was performed that demonstrated that although histological activity is recognised as a potential treatment goal, there was poor knowledge by gastroenterologists and pathologists of its applicability in ulcerative colitis and associated histological scoring systems.

The VIEWS study was then designed to assess the impact of thiopurine therapy with vedolizumab. This was the first randomised controlled trial comparing the withdrawal or continuation of thiopurine therapy for patients with ulcerative colitis using vedolizumab who were in remission. Histological outcomes were also assessed. This trial demonstrated that although thiopurines do not affect vedolizumab trough levels, thiopurine withdrawal was associated with increased fecal calprotectin, histologic and histo-endoscopic activity. Histological activity and prior anti-tumour necrosis factor exposure predicted disease relapse upon thiopurine withdrawal for patients using vedolizumab for UC.