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P533 Ustekinumab therapeutic drug monitoring in Crohn’s disease patients with loss of response

V. Heron*1,2, T. Bessissow1, A. Bitton1, P. Lakatos1, E. Seidman1, A. Jain3, R. Battat1,4, P. Germain1, C. Lemieux1, W. Afif1

1McGill University Health Centre, Department of Gastroenterology, Montreal, Canada, 2Mayo Clinic, Division of Gastroenterology and Hepatology, Rochester, USA, 3Prometheus Laboratories Inc., San Diego, USA, 4University of California San Diego, Division of Gastroenterology, La Jolla, USA

Background

Crohn’s disease (CD) patients on ustekinumab (UST) may experience a partial or secondary loss of response (LOR). The aim of the study was to assess the role of UST therapeutic drug monitoring (TDM) in patients with a LOR.

Methods

In this prospective study, trough UST TDM was performed in CD patients experiencing either a partial response or a secondary LOR to UST based on clinical (HBI ≥5) and/or objective inflammation (CRP ≥5 or FCP ≥250 or SES-CD >2). Patients were treated at the discretion of the physician prior to the UST TDM results becoming available. Patients were reassessed for complete remission (HBI <5, CRP <5 and FCP < 250) or for response (HBI decrease by >3 points and a 50% decrease in CRP, FCP). UST drug and antibody concentrations were assessed using a liquid phase assay (Prometheus Laboratories Inc.).

Results

38 instances of clinical LOR were identified in 35 patients. The median age at LOR was 39 years (range 18–72), 57% were male and 91% were biologic experienced. The median follow-up visit occurred at 3.8 months (IQR 3.1–4.4 months). Treatment interventions and outcomes are listed in Table 1. When UST was dose escalated with q 4 week dosing or re-induction, patients with active inflammation achieved complete remission and response in 38% and 31%, respectively. When baseline TDM was available (n = 35), the mean UST concentration was significantly lower in patients with active biochemical or endoscopic inflammation (n = 31) compared with patients with no objective inflammation (n = 4): 5.21 vs. 18.74 μg/ml, p < 0.0001. In the 27 patients with active inflammation in whom UST treatment was continued (29 instances), the mean baseline UST concentration was higher in patients who achieved complete remission (n = 10), compared with those who did not (n = 19): 7.61 vs. 4.01 μg/ml, p = 0.01. The mean baseline FCP was significantly lower in patients who achieved complete remission, compared with patients who did not (414 vs. 993 μg/g, p = 0.03). The mean post treatment UST drug concentration was significantly higher in patients who achieved complete remission (n = 8), compared with those who did not achieve complete remission (n = 14): 13.04 vs. 8.57 μg/g, p = 0.03.

Treatment: n (%)Complete remission n (%)Response n (%)No response n (%)
No change: 4 (11)3 (75)1 (25)0 (0)
Q8 to Q4 weeks: 22 (58)10 (45)7 (31)5 (23)
IV/SQ re-induction: 7 (18)1 (14)2 (29)4 (57)
Immunosuppression added: 3 (8)0 (0)1 (33)2 (67)
Changed out of class: 2 (5)0 (0)1 (50)1 (50)

Treatment intervention and outcomes.

Conclusion

Overall, ustekinumab dose escalation or reinduction in CD patients with a LOR resulted in complete remission or response in 69% of patients. Baseline higher drug concentrations and low FCP were associated with significantly increased rates of complete remission. Higher post-treatment drug concentrations were significantly associated with increased rates of complete remission.