Association of Bile Acid Diarrhea with Symptoms and Disease Activity in Crohn’s Disease: Post-Hoc Clinical Trial Analysis of Serum 7a-hydroxy-4cholestern-3-one, C4, in Patients with Active Crohn’s Disease

Abstract Background and Aims In Crohn’s disease (CD), symptomatic and endoscopic assessments often show poor correlation. Bile acid malabsorption (BAM) is a common comorbidity in these patients and often results in bile acid diarrhea (BAD). This post-hoc clinical trial analysis evaluated BAD presence and association with symptoms and disease activity in patients with active CD. Methods The bile acid precursor, serum 7a-hydroxy-4cholestern-3-one (C4), was analyzed before and after adalimumab in patients with moderate to severe CD. Patients were stratified by C4 concentration to evaluate the association of BAD with symptomatic and endoscopic disease activity. Results Elevated baseline serum C4 (C4≥48.3 ng/ml) was present in 37.1% of patients with active CD, was most frequently associated with isolated ileal disease, and persistent in many patients after treatment. Compared to C4 maintained within the normal range, persistent C4≥48.3 ng/mL was associated with reduced stool frequency/abdominal pain score (SF/APS) clinical remission (23.9% vs. 55.9%, p<0.001), and SF remission (28.3% vs. 67.7%, p<0.001), but not endoscopic remission (43.5% vs. 53.1%). In patients with endoscopic remission, those with C4≥48.3 ng/ml demonstrated reduced SF/APS clinical remission (28.0% vs 51.0%) and SF remission (36.0% vs 67.7%), but similar AP remission (72.0% vs 70.8%) compared to those with normal C4 concentration. Conclusions In active CD, BAD was prevalent, particularly in isolated ileal disease, and associated with persistent diarrhea, but not endoscopic remission after treatment. These findings shed light on the discordance between symptomatic and endoscopic assessments observed in CD clinical trials and the challenges in treating isolated ileal disease. ClinicalTrials.gov NCT02065570