BACKGROUND:Ustekinumab (UST), a human monoclonal antibody that binds the p40 subunit of interleukin 12 (IL-12) and IL-23, is licensed for induction and maintenance therapy of moderate to severe inflammatory bowel disease (IBD). To date, there is limited data published on any potential association between ustekinumab serum trough levels and mucosal healing in order to guide treatment strategies and appropriate dosing. AIM:This study aims to identify a relationship between maintenance ustekinumab serum trough levels and mucosal healing and/or response in patients with Crohn's disease in an observational cohort study. METHODS:Ustekinumab serum trough levels and antibody titres were analyzed in patients on maintenance drug using an ELISA drug-tolerant assay. Mucosal response (MR) was defined as ≥50% reduction in fecal calprotectin level (FC) and/or ≥50% reduction in the Simple Endoscopic Score for Crohn's Disease (SES-CD score). Mucosal healing (MH) was defined as FC ≤150 µg/mL and/or global SES-CD score ≤5. Median trough levels were analyzed using the Kruskal-Wallis test, and logistic regression was used to determine sensitivity and specificity of levels predicting mucosal response. RESULTS:Forty-seven patients on maintenance ustekinumab for Crohn's disease were included in this study. The majority were female (66%), with a median age of 40 years (21-78 years). The majority of patients were biologic-experienced (89.4%, n = 42). Patients with histologically confirmed Crohn's disease represented 100% (n = 47) of the cohort. Over one-third of patients (n = 18, 38.3%) were on higher than standard dosing of 90 mg every 8 weeks. Patients with mucosal healing (n = 30) had significantly higher mean serum ustekinumab levels (5.7 µg/mL, SD 6.4) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001). A serum ustekinumab trough level greater than 2.3 µg/mL was associated with MH, with a sensitivity of 100% and specificity of 90.6% (likelihood ratio 10.7). Similarly, for patients with MR (n = 40), we observed a higher mean serum ustekinumab trough level (5.1 µg/mL, SD 6.1) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001). Furthermore, a serum ustekinumab trough level greater than 2.3 µg/mL was associated with a 10-fold increased likelihood of mucosal response vs mucosal nonresponse (sensitivity 100%, specificity 90.5%, likelihood ratio 10.5). CONCLUSION:This study demonstrates that higher ustekinumab serum trough levels are associated with a greater likelihood of achieving mucosal healing and mucosal response in patients with Crohn's disease regardless of prior biologic exposure. Further prospective studies are required to correlate target maintenance trough levels and the optimal time to dose-escalate in order to improve patient outcomes.

Background and Aims: EUS-guided choledochoduodenostomy (EUS-CDD) with an electrocautery-enhanced lumen-apposing metal stent (EC-LAMS) has emerged as a viable method of establishing biliary drainage in patients with malignant distal biliary obstruction (MDBO). Our aim was to assess the efficacy, safety, and outcomes in patients with MDBO who underwent EUS-CDD with an EC-LAMS. Methods: A retrospective review of consecutive patients with MDBO who underwent EUS-CDD with EC-LAMSs at 8 tertiary institutions across the United Kingdom and Ireland between September 2016 and November 2020 was undertaken. Results: One hundred twenty patients (55% men) with a median age of 73 years (interquartile range, 17; range, 43-94) were included. The median follow-up period in 117 patients was 70 days (interquartile range, 169; range, 3869), and 23 patients (19.2%) were alive at the end of the follow-up. Three patients were lost to follow-up. Technical success was achieved in 109 patients (90.8%). Clinical success (reduction of serum bilirubin to <= 50% of original value within 14 days) was achieved in 94.8% of patients (92/97). The adverse event rate was 17.5% (n = 21). Biliary reintervention after initial technical success was required in 9 patients (8.3%). Conclusions: EUS-CDD with EC-LAMSs at tertiary institutions within a regional hepatopancreatobiliary network for treatment of MDBO was effective in those where ERCP was not possible or was unsuccessful. When technical failures or adverse events occur, most patients can be managed with conservative or endoscopic therapy.

Endoscopic ultrasound guided choledochoduodenostomy (EUS-CDD) with electrocautery enhanced lumen apposing metal stents (EC-LAMS) has recently emerged as a viable option in the management of patients with malignant distal biliary obstruction (MDBO). We conducted a multi-centre collaboration from the UK and Ireland with an aim to analyse the pooled efficacy, safety and long term outcomes of EUS-CDD for treatment of MDBO.

Introduction Endoscopic ultrasound guided choledochoduodenostomy (EUS-CDD) with electrocautery enhanced lumen apposing metal stents (EC-LAMS) has emerged as a viable option in the management of patients with malignant distal biliary obstruction (MDBO). We conducted a multi-centre collaboration from the UK and Ireland with an aim to analyse the pooled efficacy, safety and long term outcomes of EUS-CDD for treatment of MDBO. Methods Consecutive patients with MDBO who underwent EUS-CDD with EC-LAMS at 8 tertiary hepatopancreatobiliary institutions between September 2016 and September 2020 were retrospectively analysed. Recorded variables included patient demographics, procedural characteristics and follow-up data. Results 112 patients (59 male) were identified. The mean age was 72 years old (range 46 - 94 years old). Pancreatic adenocarcinoma was the commonest underlying malignancy in 63.4% (n=71). The indications for EUS-CDD were: an inaccessible papilla (n=49), tumour infiltration of papilla (n=29) and unsuccessful biliary cannulation/stricture impassable with guidewire (n=34). Technical success was achieved in 91.1% (n=102) of patients. Additional stenting with plastic pigtails through the EC-LAMS was performed in 26 patients at the discretion of the endoscopist to augment biliary drainage. Data for clinical success (reduction of serum bilirubin to ≤50% of original value at day 7) was available for 90 patients and was achieved in 94.4% of these (n=84). The adverse event rate was 16.9% (n=19) and further details are summarised in the table. The biliary re-intervention rate was 8.1% (n=8) in 99 patients with successful EUS-CDD (3 lost to follow-up), over a median follow-up of 70 days (range 3 - 761 days). Eight patients underwent attempted surgical resection of their primary tumour and in those who did, resection and formation of hepaticojejunostomy was successful. Conclusion We present the first collaborative data from the UK and Ireland demonstrating EUS-CDD in MDBO to be efficacious with a reasonable safety profile.

Aims Endoscopic ultrasound guided choledochoduodenostomy (EUS-CDD) with electrocautery enhanced lumen apposing metal stents (EC-LAMS) has recently emerged as a viable option in the management of patients with malignant distal biliary obstruction (MDBO). We conducted a multi-centre collaboration from the UK and Ireland with an aim to analyse the pooled efficacy, safety and long term outcomes of EUS-CDD for treatment of MDBO.