Background: Recently published randomised controlled trials of ustekinumab (USK) in Crohn's disease used intravenous induction therapy, achieving median USK concentrations of 3.6ug/ml. Unlicensed USK has been on-going in Ireland for several years with induction protocols which rely exclusively on subcutaneous (sc) USK. The aim of this study was to assess USK drug levels achieved with sc induction regimen and the relationship to clinical outcomes.
Methods: Patients commencing treatment with USK in a single academic centre were recruited. Patients received sc USK 180mg at Week 0 and 90mg at Weeks 1, 2 and 8. The standard maintenance dose of 90mg sc 8 weekly could be changed at the discretion of the treating physician. Prospective data, including patient demographics, Harvey-Bradshaw Index, body mass index (BMI), C-reactive protein (Crp), serum Albumin (Alb) and trough serum USK levels was collected at Weeks 0, 1, 2 & 8.
Results: 12 patients were recruited from June 2016; median HBI at inclusion=6 (Range 0–9). Patient and disease characteristics are included in Table 1.
The median duration of follow up=118 days. Median values for Crp, Alb and HBI as per Figure 1.
11 patients completed the study induction protocol and continued maintenance USK. At Week 8, 83% (n=10) patients were in clinical remission (HBI score ≤4). The median Crp at Wk 8 was 3mg/L and median change in HBI was −2 (range −7 to 2). There was a significant correlation between change in HBI and BMI (r=−0.754; p=0.019).
The median trough levels were 15 ug/ml (IQR 13–22ug/ml), 20 ug/ml (IQR15.25–29.25 ug/ml) and 4.5 ug/ml (IQR 3.9–9.9) at Weeks 1, 2 and 8 respectively. 86% were found to have Wk 8 USK trough levels >3.6ug/ml, which has previously been associated with higher rates of clinical remission. There was a significant correlation between trough USK levels at Wk 2 and trough USK levels at Wk 8 (r=0.906; p=0.005). There was a significant correlation between Wk 1 USK levels and Wk 8 HBI (r=0.803; p=0.05).
Conclusions: Optimal therapeutic USK levels have yet to be defined. Recent data suggest that higher serum USK levels following iv induction are associated with better outcomes. This may also apply in the case of a novel modified sc induction regimen. Our data suggest a relationship between early USK levels and clinical outcomes at Wk 8.