Leucine-rich alpha-2 glycoprotein as a predictor of primary non-response to anti-TNF-α therapy in biologic-naïve Egyptian IBD patients

BACKGROUND: Anti-tumor necrosis factor-α (anti-TNF-α) agents are a cornerstone in inflammatory bowel disease (IBD) therapy, yet primary non-response remains a significant practical challenge. Leucine-rich alpha-2 glycoprotein (LRG) has been recognized as a promising marker for disease activity. This study aimed to evaluate the predictive significance of pre-treatment serum LRG for response to anti-TNF-α therapy in biologic-naïve Egyptian IBD patients. METHODS: In this prospective cohort study, 100 biologic-naïve IBD adult patients (50 Crohn's disease [CD], 50 ulcerative colitis [UC]) and 100 healthy controls were enrolled. Patients received induction therapy with adalimumab or infliximab. Clinical, biochemical, and endoscopic evaluations were conducted at baseline and at week 24. Response was defined by clinical indices and endoscopic improvement, while biochemical normalization was evaluated as a secondary, supportive parameter. RESULTS: IBD patients had significantly elevated baseline LRG levels compared to the healthy controls (p < 0.001). Responders' baseline LRG was substantially lower than that of non-responders in both UC (26.53 vs. 34.88 µg/mL; p = 0.008) and CD (26.03 vs. 35.07 µg/mL; p = 0.006). Receiver operating characteristic analysis revealed a cut-off of > 29 µg/mL for predicting non-response, yielding sensitivities of 74.2% and 80.0% with specificities of 69.57% and 65.71% for UC and CD, respectively and negative predictive values of 85.7% for UC and 88.5% for CD. Multivariate regression confirmed baseline LRG as an independent predictor of non-response. CONCLUSIONS: Baseline serum LRG levels > 29 µg/mL demonstrated moderate discriminatory ability for predicting primary non-response to anti-TNF-α therapy in Egyptian IBD patients. LRG may serve as a useful adjunctive biomarker for pre-treatment risk estimation and recognizing patients who may require alternative therapeutic strategies.