P0810Selecting Advanced Therapy by Pretreatment Serum Leucine-rich Alpha-2 Glycoprotein Level in Patients with Ulcerative Colitis: A Multicentre Prospective Cohort Study

Abstract Background Serum leucine-rich alpha-2 glycoprotein (LRG) is a biomarker reflecting endoscopic activity in patients with ulcerative colitis (UC) and, may serve as treatment target for advanced therapy (AT), like C-reactive protein (CRP). However, unlike CRP, serum LRG is produced also by intestinal epithelium in response to stimulation not only by Interluekin-6 (IL-6) but also tumor necrosis factor (TNF) and IL-22. Therefore, a certain number of cases exist where serum LRG is elevated even when CRP is negative. This study aimed to investigate the optimal selection of AT based on serum LRG levels in patients with UC with serum CRP-negative. Methods This was a multicentre prospective cohort study including 259 patients with UC who received AT from January 2019 to March 2024 at 16 hospitals. Among them, 134 patients with UC with CRP-negative who received one of four classes of AT—anti-TNF, vedolizumab (VDZ), ustekinumab (UST), or Janus kinase inhibitor (JAKi)—were included in the present analysis anti-TNF, n = 27; VDZ, n = 41; UST, n = 42; JAKi, n = 24. The effectiveness and safety of AT was assessed by comparing the proportion of clinical remission (CR) at week 52 and the incidence rate of adverse events (AE) requiring discontinuation of AT using the person-year (PY) method. We defined CR as a partial Mayo score ≤2, with each subscore ≤1 and no-bleeding, CRP-negative as 0.20 mg/dL and the low-LRG group as 14.0 μg/mL, the high-LRG group as ≥ 14.0 μg/mL. Results Among 134 patients with UC who had negative CRP (female, 43%; pancolitis, 73%; AT exposure, 38%), 59 patients (44%) were classified as the high-LRG group. At week 0, median serum LRG and CRP levels were 13.1 μg/mL Interquartile range (IQR) 10.7-17.9 and 0.04 mg/dL IQR 0.00-0.09. Concomitant corticosteroids and immunomodulators were used in 65 (49%) and 47 (35%) patients. In high-LRG group, the proportion of patients achieved CR at week 52 tended to differ among the four AT classes and that in patients received VDZ was only 50% (P = 0.091; anti-TNF, 88%; VDZ, 42%; UST, 60%; JAKi, 75%), and there was no difference in the incidence rate of AEs (anti-TNF, 0; VDZ 0.9; UST, 3.0; JAKi, 0 per 100PY). In low-LRG group, the proportion of CR at week 52 was significantly different among the four AT classes and that in patients received VDZ or UST was 70% (P = 0.013; anti-TNF, 39%; VDZ, 75%; UST, 73%; JAKi, 33%), and there was no difference in the incidence rate of AEs (anti-TNF, 0; VDZ 0.9; UST, 3.0; JAKi, 0 per 100PY) Conclusion For AT selection in CRP-negative UC patients, ATs other than VDZ can be prioritized in the high-LRG group, whereas VDZ and UST are appropriate in the low-LRG group. Conflict of interest: Dr. Amano, Takahiro: No conflict of interest Yoshihara, Takeo: No conflict of interest Sakakibara, Yuko: No conflict of interest Yamada, Takuya: No conflict of interest Hiyama, Satoshi: No conflict of interest Murayama, Yoko: No conflict of interest Ogiyama, Hideharu: No conflict of interest Uema, Ryotaro: No conflict of interest Tsujii, Yoshiki: No conflict of interest Inoue, Takahiro: No conflict of interest Shinzaki, Shinichiro: Shinichiro Shinzaki has received grant support from AbbVie, EA Pharma, Nippon Kayaku, advisor fees from AbbVie, EA Pharma, Gilead Sciences, Janssen Pharmaceutical, Sekisui Medical and Takeda Pharmaceutical and honoraria from AbbVie, EA Pharma, Gilead Sciences, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma, Nippon Kayaku, Pfizer, Sekisui Medical, and Takeda Pharmaceutical. Iijima, Hideki: No conflict of interest Hayashi, Yoshito: No conflict of interest