Real-world data are reshaping the treatment of Crohn’s disease (CD), offering insights beyond the controlled conditions of clinical trials. From treatment effectiveness in diverse patient populations to long-term safety and biosimilar adoption, this article explores how the addition of real-world evidence can improve clinical decision making.

Patients in registration trials are often cherry-picked. They represent the perfect patient with CD and no other significant medical issues. These trials are designed to test therapies in the cleanest, most controlled way possible. That means that they exclude patients with common comorbidities, including people with overlapping cardiovascular issues, pulmonary issues, or even recent infections.

It is really important that we have real-world data so that we can understand the efficacy and effectiveness of therapies in people who are not cherry-picked. For example, some patients with CD may experience flares triggered by infections, requiring treatment for both issues. Others fall just outside of trial age limits. In addition, most patients have tried multiple therapies and are not treatment naive. That is why real-world data are important to understand the practicality of use and positioning of therapeutic agents. In addition, a registration trial may include around, say, 400 patients, which is the same number of patients I see in just 6 months of practice. However, real-world studies involve thousands of patients, providing a clearer picture of what truly works outside the laboratory.

For years, we suspected that infliximab was more effective than adalimumab in perianal CD, but we did not have the data. A recent 10-year, real-world, longitudinal study of patients in the UK IBD BioResource database demonstrated the superior effectiveness of infliximab compared with adalimumab for perianal CD, confirming that one therapy choice may be better in these patients. We also now know that if a patient fails a TNF inhibitor, switching to a different TNF inhibitor is not as effective as switching drug classes altogether. These are the kinds of real-world data that actually change practice.

Registration trials often aim for the highest bar, such as endoscopic remission. However, patients just want to feel better. They do not care as much about what their colonoscopy looks like; they care about symptoms such as urgency. In the United States, the US Food and Drug Administration (FDA) is now putting more emphasis on including these types of patient-related outcomes data. This is important, particularly in CD, because you can have all sorts of different outcomes based on the phenotype and location of the disease.

When it comes to safety, real-world studies can track a larger pool of patients than clinical trials for many years, some of whom have comorbidities and may not be taking their medications as prescribed. Examining the results of real-world studies is how we find new safety signals—things that maybe did not show up in the clinical trials.

Real-world data on biosimilars are the actionable data for these therapies. Since biosimilar FDA approval is often based on studies in rheumatoid arthritis rather than in CD, and pharmacokinetic data are typically used to receive approval, it raises an important question about whether new biosimilars will be effective for patients with CD. Another key consideration is whether patients will tolerate switching from the original molecule. Data from Europe and Asia, where biosimilars have been used for years, help answer this. The good news is that current data show similar effectiveness with no major safety concerns.