Exploring Dual-Targeted Therapy in the Management of Moderate to Severe Inflammatory Bowel Disease: A Retrospective Study.

Abstract

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), often results in significant morbidity among patients with moderate to severe forms. While biologics and small molecules are effective in inducing remission, many patients experience refractory disease or extraintestinal manifestations. This study assesses the safety and efficacy of dual-targeted therapy in IBD patients treated at the Inflammatory Bowel Disease Center.

Methods: This retrospective cohort study examined 79 patients with UC or CD who received dual-targeted therapy at the University from October 2018 to August 2023. Data collected included demographics, disease characteristics, previous treatments, and clinical outcomes. Primary outcomes were endoscopic, radiographic, and patient-reported clinical improvements, with secondary outcomes focusing on safety profiles.

Results: Among the 79 patients (42 UC, 37 CD), 97 dual-targeted therapy cases were analyzed, primarily involving a biologic combined with a JAK inhibitor (90.7%). The median therapy duration was 39.1 weeks. Endoscopic improvement occurred in 69% of matched samples, with significant differences between pre- and postdual-targeted therapy Mayo scores for UC (P = .002) and Simple Endoscopic Score for CD (SES-CD) scores for CD (P = .018). The median pre- and postdual-targeted therapy Mayo scores across matched samples were 3 (range 1-3) and 1 (range 0-3), respectively, and for SES-CD scores were 12 (range 0-36) and 4 (range 0-20), respectively. Clinical improvement was reported by 73.2% of patients, with notable reductions in ESR (median 19 [range 2-124] mm/h to 9 [range 0-116] mm/h, P = .006), CRP (median 8.0 [range 0.2-78.5] mg/L to 3.0 [range 0.2-68.2] mg/L, P < .001), and albumin levels (4.0 [range 2.2-4.9] mg/dL to 4.2 [range 3.4-5.2], P < .001). Non-obesity was associated with both more endoscopic improvement (P = .002) and clinical improvement (P = .007). Adverse events occurred in 37 cases, predominantly upper respiratory tract infections and dermatologic issues, with no thromboembolic events reported.

Conclusions: Dual-targeted therapy demonstrated efficacy in improving clinical and endoscopic outcomes in patients with severe, refractory IBD and exhibited an acceptable safety profile. Despite the promising results, further research is needed to confirm these findings and determine optimal therapy combinations.