The diagnostic and evaluation value of plasma interleukin 9 in the mucosal healing in patients with inflammatory bowel disease treated with biological agents

Abstract

Objective: To investigate the diagnostic and evaluation value of plasma interleukin 9 (IL9) in the mucosal healing (MH) in patients with inflammatory bowel disease (IBD) treated with biological agents. Methods: Cohort study. IBD patients (137 cases) treated in the Affiliated Suzhou Hospital to Nanjing Medical University (Suzhou Municipal Hospital) from September 2019 to January 2022 were prospective selected. Each patient was treated with biological agents [Infliximab (IFX, 56 cases), Adalimumab (ADA, 20 cases), Ustekinumab (UST, 18 cases), Vedolizumab (VDZ, 43 cases)]. According to different therapeutic drugs, the IFX, ADA, UST, and VDZ group were divided. Clinical symptoms, inflammatory indicators and imaging examinations etc. were evaluated every 8 weeks, and the degree of MH was evaluated by endoscopy at the 54th week. The expression of plasma IL9 was detected by ELISA after initial enrollment (W 0) and 8 weeks of biological treatment (W 8). Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of IL9 for MH. Select the cut off value for the optimal ROC threshold based on the highest value of the Youden index. Spearman's rank correlation was used to analyze the correlation between IL9 and Simple Endoscopic Score for CD (SES-CD) and Mayo Endoscopic Score (MES), so as to evaluate the predictive value of IL9 for MH in IBD patients treated with biologic agents. Results: Among the 137 patients, there were 97 Crohn's disease (CD) patients, 53 males and 44 females, aged (31.6±10.3) years (18-60 years). There were 40 ulcerative colitis (UC) patients, 22 males and 18 females, aged (37.5±14.7) years (18-67 years). Among the CD patients, 42 cases (43.3%) achieved MH on endoscopy at the 54th week, and 60 patients (61.9%) achieved clinical remission. Among the UC patients, 22 cases (55.0%) achieved MH and 30 cases (75.0%) achieved clinical remission. At W 0, the relative expression of IL9 in patients in IBD patients who achieved MH after 54 weeks of biological treatment was lower than that in the non-MH patients [x¯±s, (127.42±34.43) vs (146.82±45.64) ng/L, (113.01±44.88) vs (146.12±48.66) ng/L, respectively, both P<0.05]. At W 8, the relative expression of IL9 in the MH group was lower than that in the non-MH patients (both P<0.05). The relative expression of IL9 in the MH patients after IFX treatment was lower than that in the non-MH group (P<0.05). There was no significant difference among the other groups between MH and non-MH patients (all P>0.05). IL9 at W 8 showed high value in predicting MH in IBD [CD patients: area under curve (AUC)=0.716(95%CI: 0.616-0.817, P<0.001), sensitivity and specificity were 80.77%(95%CI:67.64%-88.45%) and 48.89%(95%CI: 35.53%-64.47%), respectively; UC patients: AUC=0.821, sensitivity and specificity were 77.78% and 72.73%, respectively]. At W 8, the cut off values for CD and UC patients were IL9>80.77 ng/L and IL9>77.78 ng/L, respectively. IL9 was positively correlated with endoscopic MH score parameters [M(Q1,Q3),SES-CD: 3.0(8.5, 18.5); MES: 2.0(1.0, 3.0)] (r=0.55, 0.72, respectively, both P<0.001) at W8. Conclusion: The plasma IL-9 at the week 8 after biological agents treatment can be used to diagnose and evaluate the MH of patients with IBD.