Australian real-world effectiveness and safety of Ustekinumab for the treatment of Crohn's disease: results of the AURORA Study, including the ANZIBD Consortium

Background: Ustekinumab is an effective therapy for the management of Crohn's disease. Australia is unique, as ustekinumab can be prescribed as first-line biologic therapy, and there is high concomitant immunomodulator use. Aim: To evaluate the real-world efficacy and safety of ustekinumab in moderate to severe Crohn's disease. Methods: A multicentre prospective cohort study was conducted at 19 Australian centres between September 2019 and April 2022. Clinical assessments were performed at baseline, 3, 9 and 15 months. Logistic regression analyses were performed to identify predictors of clinical response and remission. Results: 197 patients (male 45.2%) were included: 58.9% were biologic-naïve and 50.0% were on concomitant immunomodulators. Clinical response rates were 75.4%, 75.5% and 72.3% at 3, 9 and 15 months, respectively with corresponding clinical remission rates of 45.8%, 51.6% and 55.5%. Clinical response and remission rates at 3 and 9 months were significantly higher in bio-naïve patients compared with biologic-exposed (p < 0.01); but no significant differences were seen with concomitant immunomodulator use. Dose escalation was required in 31.5% of patients. Ustekinumab was discontinued in 12.7% of patients. The cumulative probability of maintaining ustekinumab treatment at 15 months was 84.4%. Despite 161 adverse events reported, including 41 hospitalizations, only eight patients required treatment discontinuation due to adverse events. Conclusions: This real-world study on the use of ustekinumab in Crohn's disease showed that short-term clinical response and remission rates are higher in bio-naïve compared with bio-exposed patients, with a high persistence rate at 15 months. The addition of an immunomodulator did not significantly impact outcomes. Ustekinumab was found to be safe in most patients.