Disease and personal characteristics influencing the efficacy and safety of advanced therapies in moderate to severely active Crohn’s disease: Meta-analysis of individual patient data from randomized controlled trials

Inflammatory bowel disease (IBD) is a common chronic condition of inflammation to the gastrointestinal (GI) tract, impacting over 6.8 million people worldwide. The two types of IBD include ulcerative colitis (UC) and Crohn’s disease (CD). UC causes inflammation and sores (ulcers) in the lining of the lower part of the GI tract, whereas CD can affect any part of the GI tract and multiple layers of the intestinal wall. Physicians assess disease activity to provide comprehensive treatment plans based on use of different measurements such as clinical indicators, symptoms and blood tests.

The treatment of CD is complex and response can be influenced by several disease-related characteristics including disease location and the history of each patient such as whether they have undergone surgery, the location of the inflammation in the colon, or the types of treatments received. Understanding how these prior history factors impact treatment response can help in tailoring appropriate treatment strategies. However, knowledge of the impact of different characteristics of a patients history on treatment is limited. For example, despite the evidence that a significant proportion of patients with CD will require bowel surgery during their life and are at increased risk of future bowel surgeries, it is unknown if these patients may respond differently to new therapies compared to those who have not undergone bowel surgery. Similarly, we have little understanding on how patients will respond to new medications based on how they responded to other medications in the past. As patients enter clinical trials with complex histories, it is important to understand how a persons past may influence their future response.

Adding to treatment complexity is that CD is impacted by a person's age, sex, and race, and these characteristics interact reflecting the unique sociocultural, environmental, and genetic factors of an individual. Within clinical trials, the examination of age, sex, and race from an intersectionality approach has yet to be conducted. An intersectionality approach acts on complex social inequalities that emerge from the entangled social identities. While there have been calls for the inclusion of an intersectionality approach to clinical trials, and clinical science as a whole, very few studies have taken such an approach to the analysis of clinical trial data. As such, there is limited evidence on the impact of intersectional personal characteristic on treatment response in CD.

This research is important because, by understanding how a patient's unique history and social characteristics impact treatment, we are better able to design clinical studies and provide treatment plans with a higher chance of successfully controlling or resolving Crohn's disease for each patient. Ultimately, this could lead to better care and outcomes for people living with CD.