P3262 - 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

Tina Deyhim, MD¹, Alessandra Saraga, MD², Ajay Gade, MD¹, Grace Geeganage, BSc¹, Samantha Zullow, MD¹, Loren Rabinowitz, MD¹, Laurie Grossberg, MD¹, Adam Cheifetz, MD, FACG¹, Thierry Dervieux, PharmD, PhD³, Konstantinos Papamichail, MD, PhD¹
1Beth Israel Deaconess Medical Center, Boston, MA; 2Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; 3Prometheus Labs Inc, San Diego, CA

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 ≤i1for 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, Figure 1). Patients with ER had lower ADM CL compared to those without ER (Mann-Whitney U test, p< 0.001, Figure 2). 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.

Discussion: 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.


Figure: Correlation of adalimumab drug clearance with titers of antibodies to adalimumab


Figure: Adalimumab drug clearance with or without endoscopic remission. Box plots (5-95%) show the median (solid line within box), interquartile range (upper and lower box boundaries), standard deviation (whiskers) and outliers (black dots)

Disclosures:
Tina Deyhim indicated no relevant financial relationships.
Alessandra Saraga indicated no relevant financial relationships.
Ajay Gade indicated no relevant financial relationships.
Grace Geeganage indicated no relevant financial relationships.
Samantha Zullow: Johnson & Johnson – Advisory Committee/Board Member.
Loren Rabinowitz indicated no relevant financial relationships.
Laurie Grossberg: Pfizer – Advisory Committee/Board Member.
Adam Cheifetz: Abbvie – Consultant, Speakers Bureau. Adiso – Consultant. Aegirbio – Advisory Committee/Board Member. Artizan – Advisory Committee/Board Member. BMS – Consultant, Speakers Bureau. Celltrion Inc – Advisory Committee/Board Member, Consultant. Clario – Consultant. Eli Lilly – Consultant. Food is Good – Consultant. Fresenius Kabi – Consultant. Fzata – Consultant. Johnson and Johnson – Consultant, Speakers Bureau. Pfizer – Consultant. ProciseDx – Advisory Committee/Board Member. Prometheus – Advisory Committee/Board Member. Samsung – Consultant. Spherix – Consultant.
Thierry Dervieux: Prometheus Laboratories Inc – Employee.
Konstantinos Papamichail: Celltrion Inc – Advisory Committee/Board Member. Prometheus Laboratories Inc – Consultant, Speakers Bureau.

Tina Deyhim, MD¹, Alessandra Saraga, MD², Ajay Gade, MD¹, Grace Geeganage, BSc¹, Samantha Zullow, MD¹, Loren Rabinowitz, MD¹, Laurie Grossberg, MD¹, Adam Cheifetz, MD, FACG¹, Thierry Dervieux, PharmD, PhD³, Konstantinos Papamichail, MD, PhD¹. P3262 - 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, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.