Consultant Gastroenterologist, Barts Health NHS Trust
Reader in Inflammatory Bowel Disease at Barts and
the London School of Medicine and Dentistry
Queen Mary University of London, United Kingdom
Crohn's disease results in chronic intestinal inflammation, which, if left untreated, can progress to stricturing and penetrating disease, resulting in complications that often mandate surgery. Patients with active disease have an impaired health-related quality of life and reduced work productivity. Traditional treatment goals in CD have been clinical response and steroid-free clinical remission rather than a systematic drive for long-term mucosal healing. Results from recent pivotal trials have highlighted a disconnect between relief from clinical symptoms and endoscopic mucosal healing.1 Evidence from both cohort studies and long-term follow-up from clinical trials suggest that mucosal healing is associated with improved long-term outcome.2
Our therapeutic objective is evolving to include both clinical remission and mucosal healing, with the long-term overarching aim to modify the natural history of the disease.2,3 The appropriate objective and surrogate endpoints for clinical trials and routine practice are still being defined. It is clear that there is a therapeutic window of opportunity to intervene and change the disease course prior to disease progression and irreversible intestinal damage. The appropriate therapeutic paradigm for an individual patient will depend on disease prognosis and other patient factors. However, a durable clinical benefit and good tolerability profile are important factors to consider when choosing an appropriate therapeutic strategy. Finally, it is essential that the impact of therapy is monitored and timely optimization is implemented to maintain remission.
Head, Inflammatory Bowel Disease Center
The Tel Aviv Sourasky Medical Center
Tel Aviv, Israel
The advent of biologics has greatly expanded treatment options for patients with moderate to severe CD and dramatically impacted the way clinicians treat their patients. Despite the success of biologics, clinicians still face challenges in optimizing the management of CD. We will discuss these treatment challenges and potential approaches to overcome each challenge and enable patients to achieve their therapeutic goals.
The biologic agents currently available either systemically inhibit the pro-inflammatory cytokine TNFα, or selectively target lymphocyte trafficking in the gut (anti-integrin). With the availability of several agents, choosing a first-line biologic can be challenging, and both drug- and patient-related factors should be taken into consideration.1 Drug-related factors may include the efficacy and safety of the biologic,2 its ability to combine with other medical therapy, cost, and immunogenicity. Patient-related factors may include their expectation of the therapy, preference for drug administration route, presence of comorbidities, and other factors such as patient's body mass index and albumin levels.
Primary nonresponse and loss of response over time are common in patients receiving anti-TNF therapies. The challenge for clinicians is to determine the best course of action when this occurs. Depending on the reason for nonresponse/loss of response to anti-TNFs, one option may be to switch out of the drug class or use a biologic with a different mechanism of action.1 This approach has the potential to circumvent the primary resistance seen with anti-TNFs and the biologic escape developed during secondary resistance. Similarly, managing drug intolerance or safety issues is another common problem in clinical practice.
These and other treatment challenges will be discussed and practical insights that may help optimize management of patients with CD will be offered.