P660 Serum Leucine-rich Alpha-2 Glycoprotein Can be a Biomarker for Selecting Anti-Cytokine Biologics in Patients with Inflammatory Bowel Disease: A Multicentre Prospective Cohort Study

• Published in: Journal of Crohn's and colitis Vol. 18; no. Supplement_1; p. i1258
• Main Authors: Amano, T, Yoshihara, T, Shinzaki, S, Sakakibara, Y, Yamada, T, Osugi, N, HIyama, S, Murayama, Y, Ogiyama, H, Nagaike, K, Tujii, Y, Asakura, A, Tashiro, T, Tani, M, Otake-Kasamoto, Y, Inoue, T, Yonezawa, A, Iijima, H, Hayashi, Y, Takehara, T
• Format: Journal Article
• Language: English
• Published: 24.01.2024
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjad212.0790

Abstract Background Serum leucine-rich alpha-2 glycoprotein (LRG) is a biomarker reflecting endoscopic activity in patients with inflammatory bowel disease (IBD). However, it remains unclear whether serum LRG can predict the effectiveness of anti-cytokine biologics (biologics) in patients with IBD. This study aimed to evaluate whether serum LRG could predict the effectiveness and serum trough concentrations of biologics in patients with IBD. Methods This was a multicentre prospective cohort study including patients with IBD (including ulcerative colitis [UC] or Crohn’s disease [CD]) who received the biologics [ustekinumab (UST), anti-tumor necrosis factor (anti-TNF)] from January 2019 to March 2023 at 15 hospitals participating in the Osaka Gut Forum. The effectiveness of biologics was evaluated by clinical remission (CR) at week 8. We defined CR as a partial Mayo score of 2 or lower, with each subscore of 0 or 1 for UC and a CD activity index of < 150 for CD. Factors associated with CR at week 8 such as backgrounds, disease activities and concomitant medications at week 0 were analyzed by Cox proportional hazards model. For each biologic, we compared the effectiveness of biologics in the high LRG group with that in the low LRG group divided by the median serum LRG levels at week 0 (cut-off = 18.2 μg/mL). Results A total of 184 patients with IBD (UC, 80; CD, 104) were enrolled (UST/ anti-TNF, 119/ 65; biologic exposure, 31.5%; median disease duration, 6 years [Interquartile range (IQR) 1-14]). Median serum LRG levels at week 0 and serum C-reactive protein levels at week 0 were 18.2 μg/mL [IQR 12.5-28.1] and 0.19 mg/dL [IQR 0.03-0.77], respectively. At week 0, 63 (34.2%) and 64 (34.8%) patients concomitantly received corticosteroids and immunomodulators, respectively. In 184 patients with IBD, multivariate analysis revealed that serum LRG level at week 0 < 18.2 μg/mL was extracted as a significant factor for CR at week 8 (Odds ratio: OR 2.70, 95% confidence interval: CI 1.22-5.96). In patients who received UST, the proportion of CR at week 8 in the low-LRG group (76.9%) was significantly higher than that in the high-LRG group (59.3%, P = 0.038). In patients who received anti-TNF, however, the proportion of CR in the low-LRG group (84.6%) was not differ from that in the high-LRG group (82.1%, P = 0.781). Median serum trough concentrations of UST at week 8 in the low-LRG group (10.9 μg/mL, IQR 6.7-13.4) was significantly higher than that in the high-LRG group (5.3 μg/mL, IQR 2.4-8.3, P < 0.001). Conclusion Serum LRG could predict the effectiveness and serum trough concentrations of UST and be a biomarker for selecting biologics in patients with IBD.