Background Ustekinumab (UST) has been shown to effectively induce and maintain remission in inflammatory bowel disease (IBD). Only a few studies thus far have focused on UST pharmacokinetics suggesting that both, trough levels after i.v. induction as well as trough levels during stable maintenance might be associated with clinical and endoscopic response to UST. Data from real-world cohorts in this setting are scarce. Therefore, the aim of our study was to assess whether clinical response to UST was associated with a specific pharmacokinetic pattern. Methods All IBD patients treated with UST in one tertiary IBD centre between January 2017 and August 2020 were retrospectively retrieved from the database. Disease activity was assessed by Harvey-Bradshaw index (HBI) and partial Mayo score in Crohn’s disease (CD) and ulcerative colitis (UC) pts; respectively. Clinical response was defined as a decrease of HBI of ≥2 points or partial Mayo score ≥3 points. Patients not responding to therapy by week 16, or loosing original response received dose escalation from 90mg s.c. every 8 weeks to 90mg every 4 weeks. UST through levels were assessed by commercially available ELISA kit (IDKmonitor®) at week 8 after i.v. induction and/or during maintenance therapy after a minimum period of 16 weeks of treatment. Results In total, 61 IBD patients were included (mean age 38 years, range 22–70; 38 women; 54 CD/6 UC/1 IBD-U). All patients were antiTNF experienced, minority (11; 18%) had also been treated with vedolizumab prior UST. Thirty-nine pts (64%) were responders, out of these 15 pts (38%) required dose escalation at some point of the treatment due to secondary loss of response. UST through levels at week 8 were significantly higher than the maintenance levels (mean 5.6±SEM 0.7µg/mL vs. 2.2±0.3µg/mL; p<0.001). There were no significant differences between responders and non-responders neither in trough levels after induction (5±0.8µg/mL vs. 6.4±1.1µg/mL, p=n.s.), nor in trough levels during maintenance therapy (2.3± 0.4µg/mL vs. 1.9 ±0.4µg/mL, p=n.s.). Patients requiring dose escalation did not differ from stable responders in maintenance trough levels (2.4±0,6 µg/mL vs. 2,3 ±0,4 µg/mL). Conclusion In this limited size real-world cohort of IBD patients, we found no difference in pharmacokinetics between reponders and non-reponders to ustekinumab.

Background Vedolizumab (VDZ), an anti-integrin monoclonal antibody has demonstrated its efficacy in inducing and maintaining response in patients with luminal Crohn`s disease (CD). Postoperative recurrence (POR) affects over half of the patients with CD and currently, majority of these patients undergo surgery due to primary or secondary failure of anti-tumor necrosis factor (antiTNF) biologics. Thus, data on efficacy of other agents in this setting are needed. Considering the slow onset of action of VDZ together with its favorable safety profile in older and co-morbid patients, VDZ would represent a good candidate for preventing and treating POR but the data on its efficacy in this specific clinical situation are scarce. Therefore, the aim of this study was to evaluate the efficacy of VDZ in preventing and treating of Crohn`s disease postoperative recurrence. Methods In this retrospective single-center cohort study, we included all patients with CD treated with VDZ between May 2015 and August 2020. Patients who started with VDZ immediately postoperatively or continued from the pre-operative period (prevention of POR) or patients who started VDZ because of clinical or endoscopic POR (treatment of POR) with a minimal follow-up of one year were eligible for further analysis. The effect of VDZ was determined by Harvey-Bradshaw Index ≤ 4 in case of prevention of POR, or as any decrease of 3 or more points in case of treatment of POR. Endoscopic response was evaluated by Rutgeerts` score as any decrease of the score. All patients underwent the colonoscopy at 6 months postoperatively and further follow-up colonoscopy one year after treatment adjustment. Results In the defined period, a total of 54 patients with Crohn`s disease were treated with VDZ. Of these 54 patients, sixteen (11 women; median age 57 years, range 25–75) receive VDZ for prevention (6) or treatment (10) of postoperative recurrence. Six patients received first-line VDZ due to high risk profile for systemic biologics (age and/or co-morbidities), the remaining ten patients all had previously failed at least one anti-tumor necrosis factor biologic agent. During the median follow-up of 24 months (range 12 to 70), thirteen patients (81%) had clinical response or achieved remission, eleven (69%) had endoscopic response. Three patients with no response had to change the treatment to another biologic. Out thirteen responders, seven (54%) necessitated intensification of dosing regimen to every 4 or 6 weeks in order to achieve clinical and/or endoscopic response. Conclusion Vedolizumab is effective in preventing and treating of Crohn`s disease postoperative recurrence in a difficult-to-treat population of patients.