P1188 - Proactive Compared to Reactive Therapeutic Drug Monitoring Is Associated With Less Treatment Failure in Patients with Inflammatory Bowel Disease Treated With Adalimumab

Ajay Gade, MD¹, Alessandra Saraga, MD², Tina Deyhim, MD¹, Grace Geeganage, BSc¹, Samantha Zullow, MD¹, Loren Rabinowitz, MD¹, Laurie Grossberg, MD¹, Adam Cheifetz, MD, FACG¹, Konstantinos Papamichail, MD, PhD¹
1Beth Israel Deaconess Medical Center, Boston, MA; 2Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

Introduction: There are limited data regarding the role of proactive therapeutic drug monitoring (TDM) of adalimumab (ADM) in patients with inflammatory bowel disease (IBD). The primary aim of this study was to compare proactive to reactive TDM in patients with IBD treated with ADM in terms of treatment failure. A secondary outcome was to identify an ADM concentration threshold associated with treatment failure.

Methods: This single-center, retrospective, cohort study included consecutive patients with IBD who received maintenance ADM therapy and underwent TDM from January 2018 to March 2023. Patients with primary non-response to ADM and ileal pouch–anal anastomosis or stoma were excluded from the study. The proactive group consisted of patients who had at least one proactive TDM during the follow up time, while the reactive group consisted of patients who underwent only reactive TDM. A time-to-event analysis was performed for treatment failure, which was defined as drug discontinuation due to loss of response, serious adverse event, or need for surgery. Patients were followed from first TDM until treatment failure or the end of the follow up period (May 2024).

Results: The study population consisted of 277 patients with IBD (n=205, 74% with Crohn’s disease), who underwent either proactive (n=217) or reactive (n=60) TDM. Patients were followed for [median, interquartile range (IQR)] 39.5 (25.1-55.2) months. Kaplan-Meier analysis demonstrated less treatment failure in patients who underwent proactive compared to reactive TDM (p< 0.001, Figure 1). Multiple COX regression analysis identified proactive TDM to be associated with less treatment failure [hazard ratio (HR: 0.30, 95% confidence interval (CI): 0.16-0.55, p< 0.001], while elevated C-reactive protein (HR): 1.04, 95% (CI): 1.01-1.06, p=0.003] and antibodies to ADM at first TDM (HR: 3.2, 95%CI 1.6-6.5, p< 0.001] were associated with treatment failure. A receiver operating characteristic (ROC) analysis identified an ADM concentration threshold of 11.5 μg/mL distinguishing patients with or without treatment failure (area under the ROC curve: 0.656; 95%CI: 0.587-0.724; p< 0.001; sensitivity: 64%; specificity: 63%, Figure 2).

Discussion: In this large cohort study, proactive TDM, when compared to reactive TDM, was associated with less treatment failure in patients with IBD receiving ADM maintenance therapy. Future prospective studies are needed to confirm these findings.


Figure: Figure 1. Kaplan–Meier cumulative probability curves of treatment failure in patients with IBD undergoing either reactive (solid line) or proactive TDM (dotted line) treated with adalimumab.


Figure: Figure 2. Receiver operator curve analysis for adalimumab concentrations at start of therapeutic drug monitoring stratifying patients with or without treatment failure.

Disclosures:
Ajay Gade indicated no relevant financial relationships.
Alessandra Saraga indicated no relevant financial relationships.
Tina Deyhim 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.
Konstantinos Papamichail: Celltrion Inc – Advisory Committee/Board Member. Prometheus Laboratories Inc – Consultant, Speakers Bureau.

Ajay Gade, MD¹, Alessandra Saraga, MD², Tina Deyhim, MD¹, Grace Geeganage, BSc¹, Samantha Zullow, MD¹, Loren Rabinowitz, MD¹, Laurie Grossberg, MD¹, Adam Cheifetz, MD, FACG¹, Konstantinos Papamichail, MD, PhD¹. P1188 - Proactive Compared to Reactive Therapeutic Drug Monitoring Is Associated With Less Treatment Failure in Patients with Inflammatory Bowel Disease Treated With Adalimumab, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.