Evaluation of ustekinumab trough levels during induction and maintenance therapy with regard to disease activity status in difficult to treat Crohn Disease patients

Abstract Background Ustekinumab (UST) is approved for the therapy of moderate and severe Crohn disease (CD). Therapeutic drug monitoring (TDM) helps to monitor the therapeutic effect of biologics. Therefore, the aim of this study was to evaluate clinical outcomes of UST treated CD patients and to determine UST trough level (USTTL) with clinical and corticosteroid-free remission.Methods This retrospective study of CD included patients with moderate and severe active disease treated with a weight adapted induction dose of UST intravenously. The maintenance therapy consisted of 90 mg UST subcutaneously at week 8 and thereafter every 8 or 12 weeks depending on the clinical response. Clinical and corticosteroid-free remission, Harvey-Bradshaw-Index (HBI), USTTL and further laboratory parameters were measured just before the injection of UST at each follow-up evaluation until week 40.Results 37CD patients with a median HBI of 9 at week 0 were included. Starting from 24% at the beginning of the monitoring period and 38% of patients at the end of it, were treated with an 8-week interval (p = 0.18). There was a significant improvement of clinical (p = 0.0004) and corticosteroid-free remission (p = 0.03) as well as in HBI (p < 0.0001) from week 0 until the end of the observation period, respectively.The serum USTTL decreased significantly from 2.0 at week 8 to 0.3 in the maintenance therapy and 0.4 µg/mL at the end of it (p < 0.0001), respectively. Neither USTTL nor levels of CRP or faecal calprotectin were associated with disease outcome. Concomitant immunomodulator therapy did not appear to affect the USTTL or the clinical course.Conclusions UST is an effective treatment option in difficult to treat CD patients. USTTL may not be associated with treatment efficacy or predict treatment outcomes in CD patients. Further prospective randomized trials should be conducted to evaluate if USTTL is associated with treatment outcomes in CD patients.