Registry Analysis Questions Comparability of Early Surgery vs TNF Inhibitors in Crohn’s Disease

A nationwide Swedish registry study examining early ileocecal resection (ICR) versus tumor necrosis factor inhibitor (TNFi) therapy in Crohn’s disease (CD) highlights the limitations of real-world data in replicating randomized trial findings.

The study aimed to replicate findings from the randomized LIR!C trial and a prior Danish registry analysis, both of which supported early ICR as a viable alternative to TNFi therapy in patients with nonstricturing ileocecal CD. Using linked Swedish national registers, investigators identified adult patients diagnosed with CD between 2007 and 2021 and compared outcomes among those receiving early ICR or TNFi.

When applying definitions similar to the Danish study, early ICR appeared associated with improved outcomes, with an adjusted hazard ratio of 0.72 for a composite endpoint including hospitalization, corticosteroid use, surgery, or perianal disease. However, when stricter criteria were used to better reflect the original LIR!C trial population, the difference between groups was no longer statistically significant (adjusted hazard ratio, 0.78).

The discrepancy reflects differences in patient selection. Patients undergoing ICR were more likely to have localized or surgically amenable disease, while those receiving TNFi often had more extensive or complex disease. The authors noted that “patients were not randomly assigned to ICR or TNFi, but instead received treatment based on their physician’s clinical judgment,” introducing confounding by indication.

They concluded that “the Danish and Swedish register-based remakes of the LIR!C trial should be interpreted with caution,” emphasizing that real-world comparisons are limited without detailed clinical data to ensure comparable patient populations.

Reference
Wewer MD, Söderling J, Ludvigsson JF, Myrelid P, Burisch J, Olén O. Early ileocecal resection or tumor necrosis factor inhibitor in crohn's disease: replication in a Swedish cohort. Clin Gastroenterol Hepatol. 2026;24(4):1185-1187. doi:10.1016/j.cgh.2025.07.046