P1138 Curcumin-QingDai combination for patients with active Crohn’s disease: Initial real-world experience from a retrospective multi-center cohort study
Authors: Salomon N , Marom M , Odeh S , Molnar M , Shitrit A B G , Nayshool O , Ungar B , Ben-Horin S , Rainis T 
Published: January 2025

Abstract

Background
A combination of Curcumin and QingDai (CurQD) was shown to exert aryl-hydrocarbon-receptor (AhR) pathway activation and to be effective in ulcerative colitis. However, its benefit in Crohn’s disease (CD) has not been studied

Methods
A retrospective cohort study of patients with active CD treated with CurQD at three academic centers. Active disease was defined by PRO-2 SF≥2 and AP ≥1. The primary endpoint was the rate of clinical remission at the end-of-induction (weeks 8-12), PRO2 SF≤1 and AP=0. Secondary endpoints included biomarker response (FCP drop ≥50% in a patient with FCP &gt;250mcg/gr at baseline) and remission (FCP drop ≥50% and FCP&lt;250mcg/gr at end-of-induction) and CurQD retention. Public-domain GTEx dataset was explored for mRNA expression of the target AhR in colon versus small intestinal mucosa

Results
Thirty patients were identified for the safety dataset, of whom 13/30 (43%) were bio-experienced, and 25 were eligible for inclusion in the efficacy analysis,. Clinical PRO2 remission at the end of induction was achieved in 12/25 (48%) of patients and clinical response in 19/25 (76%), with an overall reduction in median PRO2 score from 15 (95%CI 13-19.7) to 4 (95%CI 2-8.7, p&lt;0.001). Biomarker remission and response were observed in 11/20 (55%) and 15/20 (75%), respectively, of patients with baseline FCP&gt;250mcg/gr, with an overall reduction in median FCP from a baseline 639 mcg/gr (95%CI 128-5480) to 138mcg/gr (95%CI 5-1470, p=0.001). Biomarker remission was observed in 8/11 (73%) of patients with colonic-involving L2/L3 disease versus 3/9 (33%) L1 extent (OR 4.5, 95%CI 0.8- 24, p=0.08). After 8-months’ median follow-up (range 2-26 months), 16/19 (84%) of responding patients were still taking CurQD. Three patients experienced headaches and three had abdominal pain/diarrhea. Two of the six stopped CurQD due to these symptoms. One patient had elevated liver transaminases X3/normal, which resolved upon halving CurQD dose.
To explore if the signal for a difference in efficacy in patients with or without colonic involvment relates to different expression of the target AhR in colon versus small bowel, an analysis of GTEx dataset was performed, which revealed comparable AhR mRNA expression levels in human colonic and terminal ileum segments.

Conclusion
In this first-reported real-world experience, the AhR-agonist CurQD was effective in inducing and maintaining clinical and biomarker remission in CD patients, including in biologic-experienced patients

References
1.Yanai H, Salomon N, Lahat A, Ungar B, Eliakim R, Kriger-Sharabi O, Reiss-Mintz H, Koslowsky B, Shitrit AB, Tamir-Degabli N, Dotan I, Zittan E, Maharshak N, Hirsch A, Ben-Horin S, Kopylov U. Real-world experience with Curcumin-QingDai combination for patients with active ulcerative colitis: A retrospective multicentre cohort study. Aliment Pharmacol Ther. 2023 Jul;58(2):175-181
2.Ben-Horin S, Salomon N, Karampekos G, Viazis N, Lahat A, Ungar B, Eliakim R, Kuperstein R, Kriger-Sharabi O, Reiss-Mintz H, Yanai H, Dotan I, Zittan E, Maharshak N, Hirsch A, Weitman M, Mantzaris GJ, Kopylov U. Curcumin-QingDai Combination for Patients With Active Ulcerative Colitis: A Randomized, Double-Blinded, Placebo-Controlled Trial. Clin Gastroenterol Hepatol. 2024 Feb;22(2):347-356