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

Abstract

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.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.).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.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.