S1758 Lower Drug Clearance Is Related to Proactive Therapeutic Drug Monitoring and Is Associated With Endoscopic Remission in Patients With Inflammatory Bowel Disease Treated With Adalimumab

Introduction: There are limited data regarding the association of adalimumab (ADM) clearance (CL) with clinical outcomes in patients with inflammatory bowel disease (IBD). The aim of this study was to identify variables related to drug CL and to investigate the association of drug CL with endoscopic remission (ER) in patients with IBD on maintenance ADM therapy. Methods: This single-center, retrospective study included consecutive patients with IBD who received maintenance ADM therapy and underwent therapeutic drug monitoring (TDM) with a drug tolerant assay (homogenous mobility shift assay) between January, 2018, and May, 2023. ER was defined as an endoscopic Mayo score ≤1 for ulcerative colitis, no ulcerations for patients with Crohn’s disease (CD) or a Rutgeerts score of ≤i1 for patients with an ileocolonic resection for CD and was evaluated within 3 months from the TDM. Drug CL was determined using a nonlinear mixed effect model with Bayesian priors. A per-sample analysis was performed. A multiple linear regression analysis was done to identify variables associated with ADM drug CL. Results: The study population consisted of 266 patients with IBD (n = 198, 74% CD) who underwent a total of 515 TDM tests (proactive, n = 388 and reactive n = 127). Proactive compared to reactive TDM was associated with lower drug CL [beta coefficients (β): -0.173, 95% confidence interval (CI): -0.180 to -0.088, P < 0.001], while variables associated with higher drug CL included body mass index (β: 0.125, 95% CI: 0.005-0.013, P < 0.001), prior biologic exposure (β: 0.087, 95% CI: 0.022-0.112, P = 0.004) and antibodies to ADM (ATA) (β: 0.676, 95% CI: 0.628-0.750, P < 0.001). Of note, there was a positive correlation of ATA titer with ADM drug CL (Spearman rho: 0.560, 95% CI: 0.358-0.712, P < 0.001). Patients with ER had lower ADM CL compared to those without ER (Mann-Whitney U test, P < 0.001). A receiver operating characteristic analysis (ROC) identified an ADM drug CL threshold of 0.301 L/day [area under the ROC curve (AUC): 0.731; 95% CI: 0.654-0.808; P < 0.001; sensitivity: 61%; specificity: 78%] in distinguishing patients with or without ER. Conclusion: This large retrospective study showed that proactive TDM was associated with lower drug CL, and that there is a positive correlation between ATA titers and drug CL in patients with IBD on ADM maintenance therapy. Moreover, lower ADM drug CL was associated with ER.