Direct conversion of ustekinumab therapy is more beneficial than infliximab-optimized therapy in patients with Crohn's disease who develop secondary loss of response to infliximab.

Background: For patients with Crohn's disease (CD) who develop secondary loss of response (SLR) to infliximab (IFX), it remains unclear whether IFX optimization or direct conversion to ustekinumab (UST) offers better outcomes. This study aimed to identify risk factors for IFX optimization failure and to compare the clinical efficacy of IFX optimization versus UST conversion.

Methods: We retrospectively analyzed clinical data from patients with CD admitted to the First Affiliated Hospital of Wannan Medical College and the First Affiliated Hospital of the University of Science and Technology of China between January 2017 and January 2025. Rates of clinical, steroid-free, and endoscopic remission were assessed. Univariate and multivariate analyses were performed to identify independent risk factors for IFX optimization failure.

Results: In total, 65 patients with CD who developed SLR to IFX were included. The patients were divided into three groups: IFX optimization success (Group 1), IFX optimization failure followed by UST (Group 2), and direct UST conversion (Group 3). Of the 28 patients who received IFX optimization, only 6 achieved success, yielding a failure rate of 78.6%. Multivariate logistic regression showed that a baseline albumin concentration of < 40 g/L was an independent predictor of IFX optimization failure (p = 0.047, odds ratio: 15.00, 95% confidence interval: 1.031-218.300). When comparing UST-treated groups, the rate of clinical response at week 6 was significantly higher in Group 3 than in Group 2 (35.1% vs. 9.1%, p = 0.039). By week 52, clinical remission rates were similar (86.4% vs. 89.2%, p > 0.05).

Conclusions: Given the high failure rate of IFX optimization, direct conversion to UST may provide greater benefit and reduce treatment costs in patients with CD who develop SLR to IFX.