Efficacy of Second-Line Advanced Therapy in Patients with Crohn’s Disease After Failure of a First Anti-TNF: A Descriptive Analysis

Introduction: Sequencing therapy for Crohn’s disease (CD) is currently being intensively discussed due to the development of novel drugs and lack of standardized criteria for drug positioning in first- and further-line treatment. The aim of this study was to compare the efficacy of a second-line advanced therapy in Romanian patients with CD who have failed an anti-TNF agent. Methods: We performed a multicenter retrospective study that included adult patients with CD who had secondary loss of response after an initial response with an anti-TNF drug. The main outcome was clinical remission at 12 weeks of second-line treatment (CDAI < 150). The secondary outcomes included clinical response (decrease in CDAI ≥ 70 points), persistence of therapy at 1 year and rates of adverse events. Results: From 2008 to 2024, 216 patients were either switched to another anti-TNF or swapped to another therapeutic class, due to the failure of a first anti-TNF drug. Secondary lines of treatment included infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ), ustekinumab (UST). The highest rate of clinical remission (81%) was obtained with the sequence ADA-IFX in 26/32 (81%) patients and ADA-UST in 62/82 (76%) patients, followed by IFX-UST in 22/33 (67%) and IFX-ADA 34/51 (67%). Persistence in therapy at 1 year was better for the sequence ADA-UST (73%) and IFX-UST (67%) and ADA-IFX (63%) compared to IFX-ADA (59%) and IFX-VDZ (44%) (p < 0.001). Conclusions: There were significant baseline differences between the treatment groups, so this study represents an unadjusted comparison between the results obtained with different biologics in second-line treatment for Crohn’s disease. In patients with CD who have failed a first anti-TNF, the highest rate of clinical remission at 12 weeks was obtained with second-line IFX and UST whilst vedolizumab showed lower efficacy. UST demonstrated the most favorable long-term treatment persistence at 1 year.