735 Crohn's Disease Patients Who Do Not Qualify for Clinical Trials Have Similar Clinical and Endoscopic Response Rates to Ustekinumab to Those Who Qualify for Clinical Trials

Abstract

INTRODUCTION: The UNITI clinical trial demonstrated ustekinumab (UST) safety and efficacy for moderate to severe Crohn's disease (CD) patients. However, exclusion criteria preclude enrollment of complex patients impacting external validity of the findings. The aim of this study was to evaluate UST response in active CD patients who would not have qualified for the randomized controlled trials (RCTs). METHODS: A retrospective cohort study of UST-treated CD patients who would not qualify (DNQ) and who would qualify (Q) for RCTs from 2016 to 2018 was performed. Inclusion criteria included symptomatic luminal CD activity (defined as abdominal pain and stool frequency), induction with UST infusion at CD dosing and ≥1 clinic visit post-induction. Criteria for DNQ patients were extracted from the published UNITI study protocol. The primary outcome of interest was week 8 clinical response rates (>50% improvement in abdominal pain and stool frequency from baseline) between Q vs DNQ groups. Secondary outcomes were endoscopic response, corticosteroid free clinical remission, dose escalation and adverse events between the two groups. RESULTS: 201 patients (Q = 111; DNQ = 90) with a median 6 months follow up (IQR 4-9 months) were included. The DNQ cohort had lower hemoglobin levels, more active perianal disease, upper tract disease, ileocolonic disease, and prior surgeries (Table 1). Week 8 clinical response rates were similar between Q and DNQ (64.0% vs 60.0%; P = 0.56). Clinical response, remission and steroid-free remission rates during maintenance were also similar between the two groups (Table 2). However, more patients in the DNQ group required dose escalation (64.4%) compared to the Q group (46.8%), P = 0.01, especially after induction dosing. Endoscopic response rates were similar between Q and DNQ groups, with complete mucosal healing achieved in 13.2% vs 13.6% of Q and DNQ patients (P = 0.94) (Table 2). CONCLUSION: These findings suggest that ustekinumab is equally efficacious for complex CD patients who would not have qualified for RCTs. Adverse events were infrequent for all UST treated patients. The majority of DNQ patients required dose escalation during their treatment course, suggesting more intensive therapy may be warranted for this patient subgroup. Further studies are needed to determine durable clinical and endoscopic response from dose escalation in this complex CD group.