Dual-targeted Therapy for the Management of Refractory Crohn’s Disease: A Retrospective Cohort Study

Background: Crohn’s disease (CD) is a chronic relapsing autoimmune disease. Dual-targeted therapy (DTT) has been proven effective and safe in refractory inflammatory bowel disease (IBD), especially the combination of ustekinumab with vedolizumab (UST+VDZ). However, the efficacy and safety of DTT on refractory CD are still limited or insufficient. Aims: We aim to evaluate the efficacy and safety of DTT including ustekinumab combined with adalimumab (UST+ADA) and UST + VDZ in refractory CD patients. Methods: Refractory CD patients who failed at least two biologics from Xijing IBD Center were included. Clinical evaluation was performed by Crohn's Disease Activity Index (CDAI). Endoscopic data were assessed using Simple Endoscopic Score-Crohn's Disease (SES-CD). Other clinical indicators were also collected. Results: Totally, 23 patients were enrolled, and 20 completed 4-27 months of follow-up. Among these patients, there were significant post-treatment reductions in median SES-CD [14.5 to 5 (p＜0.005)] and CDAI [326.25 to 94.75 (p＜0.005)]. For UST + ADA (n=16), 68.75% reached endoscopic response, 56.25% achieved endoscopic remission, 75% clinical response occurred and 68.75% of patients achieved clinical remission. For UST + VDZ (n=4), 25% had endoscopic response, 50% had clinical response, and one achieved clinical remission. The regime of UST + ADA exhibited a more favorable performance during follow-up. 7 patients discontinued DTT due to no significant improvement or exacerbation, and no severe adverse events were observed. Conclusion: The study supports the effectiveness and safety of ACT for refractory CD, especially UST + ADA. Larger sample and randomized controlled trial (RCT) studies are needed for confirmation.