Australian Ustekinumab Real-world Observational Research - AURORA study

The participants will be enrolled into this study since they are about to start ustekinumab therapy for Crohn's disease regardless of this study participation. As part of usual care, participants will receive a single weight-based ustekinumab IV induction dose at week 0 (260mg for weight equal or less than 55kg; 390mg for weight >55kg and equal or less than 85kg; 520mg for weight >85kg). At week 8, and every 8 weeks thereafter, participants will receive standard dosing of ustekinumab 90mg subcutaneous maintenance through to the end of study period. Patients who have an inadequate response can undergo dose escalation of ustekinumab by the study team as per standard care via compassionate dosing. There will be six study visits, including the baseline visit, over 27 months’ follow-up period for participants who achieve and maintain clinical response to ustekinumab. All study visits will occur as per standard of care to conform to the Australian Pharmaceutical Benefits Scheme assessment criteria At each study visit, participants will receive standard clinical care by their inflammatory bowel disease treatment team, which may include clinical assessment and standard local laboratory pathology tests. Additionally, the study team and the participants are required to complete questionnaires to assess secondary outcomes, and additional blood samples will be collected at each study visit to assess pharmacokinetics/ immunogenicity and pharmacodynamic markers associated with response to ustekinumab. This will add additional 15-30min to their usual clinic visits. The questionnaires will be administered by the investigators at each site which can include both doctors or research assistants who have been delegated to this projects. Participants also have the option to participate in a biospecimen sub-study (no restriction on how many can participate) during which additional stool samples will be collected at baseline, at 3 months and 27 months post enrolment and endoscopy biopsy samples will be collected at the time of endoscopic procedures (which could vary according to practice pattern at each site but it will be 1-2 endoscopic procedures within 27 months follow-up) to evaluate the cellular and molecular mechanisms of action of ustekinumab. The aim of the sub-study is to explain interindividual variability to response and help identify population subgroups that respond differently to standard ustekinumab therapy. According to Australian standards of care, participants will be assessed by colonoscopy and/or intestinal imaging (CT/MRI or intestinal ultrasound) at baseline to confirm disease burden. There will be at least one colonoscopy between 9 and 15 months after enrolment to determine endoscopic response. This is considered a separate endoscopy visit. All intestinal imaging occurring during the study period will be documented and results recorded at each study visit.