P0762 - Correlation of Ustekinumab Trough Levels With Outcomes in Inflammatory Bowel Disease

Jessica C. Petrov, MD, MSc¹, Sean Fine, MD, MS², Raneem Alzahrani, ³, Gamal Mohamed, PhD³, Badr Al-Bawardy, MD^4
1Yale School of Medicine, New Haven, CT; ²Warren Alpert Medical School of Brown University, Providence, RI; ³King Faisal Specialist Hospital, Riyadh, Ar Riyad, Saudi Arabia; ⁴King Faisal Specialist Hospital and Research Center, Riyadh, Ar Riyad, Saudi Arabia

Introduction: Therapeutic drug monitoring (TDM) is an important tool for managing patients with inflammatory bowel disease (IBD) receiving anti-tumor necrosis factor (anti-TNF) agents. Ustekinumab (UST), an anti-interleukin 12/23 monoclonal antibody, is associated with lower immunogenicity rates compared to anti-TNFs and data regarding the utility of TDM with UST are sparse. Our aim was to determine the correlation of UST trough levels with outcomes in a cohort of patients with IBD.

Methods: This was a multicenter, retrospective study of all IBD patients who received UST from 1/1/2014 to 3/1/2022. The primary outcomes were the correlation of UST level with clinical remission (per physician global assessment), endoscopic healing (absence of ulcers/erosions in Crohn’s disease (CD) and Mayo endoscopic score ≤ 1 for ulcerative colitis (UC)), and normal serum C-reactive protein (CRP) (≤ 5 mg/L). Secondary outcomes included defining optimal UST trough levels associated with favorable outcomes.

Results: A total of 71 patients (74.6% with CD; 57.7% female) had UST trough levels measured. The median age was 39.5 years [interquartile range (IQR): 26 – 52] and 12.6% were on combination therapy with immunomodulators (4 thiopurine; 5 methotrexate). UST was administered every 8 weeks in 23.9%, every 6 weeks in 18.3%, and every 4 weeks in 57.8% of patients.

The median UST level in the cohort was 4.1µg/ml (IQR: 2.3-7.8). Median UST level was 4.7 µg/ml (IQR: 2.3-10) in the clinical remission group (n=42) vs. 3.6 µg/m (IQR: 2.6-4.7) in those without clinical remission (p=0.083). UST trough levels were significantly higher in patients who achieved endoscopic healing (n=25) [5.4 µg/ml (IQR: 3.5-11) vs. 3.5 µg/ml (1.8-5.5); p=0.035] and normal CRP (n=39) [5.5 µg/ml (IQR: 3.5-10) vs. 3.1 µg/ml (IQR: 2.05-4.1); p=0.002]. Quartile analysis (Figure 1) demonstrated higher rates of favorable outcomes in the 4^th quartile of UST levels. A cutoff UST level of 4.8 µg/ml yielded the highest area under the curve (AUC) of 0.73 (95% CI: 0.61-0.80) to predict a normal CRP followed by a level cutoff of 3.5 µg/ml which yielded an AUC of 0.66 (95% CI: 0.52- 0.81) to predict endoscopic healing (Table 1).

Discussion: In our cohort, UST trough levels were significantly higher in patients who achieved endoscopic healing and normal CRP. A cut-off UST level of 4.8 reliably predicted CRP normalization. Further, prospective studies evaluating dose escalation based on trough levels in patients with IBD treated with UST are needed.




Disclosures:


Jessica C. Petrov, MD, MSc¹, Sean Fine, MD, MS², Raneem Alzahrani, ³, Gamal Mohamed, PhD³, Badr Al-Bawardy, MD⁴. P0762 - Correlation of Ustekinumab Trough Levels With Outcomes in Inflammatory Bowel Disease, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.