Table 4

Study outcome measures and definitions

Study outcome measures	Disease activity in the adult population: Harvey-Bradshaw Index54 (HBI) for CD and Simple Clinical Colitis Activity Index55 (SCCAI) for UC and IBD-U Disease activity in the paediatric population: abbreviated Paediatric CD Activity Index for CD56 (abbPCDAI) and Paediatric UC Activity Index57 for UC and IBD-U (PUCAI)
	Endoscopic activity: Mayo Endoscopic Score58 in UC and SES-CD59 60 in CD patients All endoscopic assessments will be recorded prospectively.
	Cross-sectional imaging activity/severity will be assessed using the Lemann Index, Magnetic Resonance Index of Activity (MaRIA), and Short MaRIA for MR. IBUS-SAS and Lemann Index will be used for IUS.47 61 Transmural remission defined as bowel wall thickness less than 3 mm without colour Doppler signal62 All IUS assessments will be recorded prospectively.
	Impairment of growth in paediatric-onset IBD using the Paris classification63
	Delayed puberty in paediatric-onset IBD
	Distribution of imaging findings of EIMs in peripheral and axial joints and entheses, assessed by validated scores for inflammation and structural damage
	Musculoskeletal symptoms and signs, assessed by clinical examination, PROs and imaging
	Occurrence of dental disease (ie, periodontal diseases, caries, endodontic lesions) and tooth loss
Study outcome definitions	Abdominal surgery: IBD-related surgery including resection, colectomies, balloon dilatation, strictureplasty, stoma surgery and perianal surgery
	Perianal surgery: any perianal procedure related to fistula or abscesses in the perianal area
	Clinical disease activity, defined as follows: Adult CD: HBI (scores ≤4: clinical remission; scores 5–7: mild disease; scores 8–16: moderate disease; scores >16: severe disease)54 64 Paediatric CD: abbPCDAI (scores 0–9: inactive disease; scores 10–15: mild disease; scores 16–25: moderate disease; scores >25: severe disease) Perianal disease in CD: Perianal Disease Activity Index (scores ≤4: clinical remission; scores >4: active disease)65 Adult UC: SCCAI (scores ≤2: clinical remission; scores 3–5: mild disease; scores 6–11: moderate disease; scores ≥12: severe disease) Paediatric UC: PUCAI (scores 0–9: inactive disease; scores 10–34: mild disease; scores 35–64: moderate disease; scores 65–85: severe disease)
	Endoscopic disease activity, defined as follows: CD: SES-CD (scores <2: endoscopic remission; scores 3–6: mild endoscopic activity; scores 7–15: moderate endoscopic activity; scores >15: severe endoscopic activity)59 60 UC: Mayo Endoscopic Score (scores >1: active disease)58
	Non-response/loss of response to medical treatment: either no change or an increase in disease activity following treatment initiation
	Malignancy: Any malignancies will be registered
	Mortality: All-cause mortality will be registered
	Biological treatment including time to this end-point and indicated hereof: Treatment of IBD or IMIDs with biological therapies, including antibodies against TNF-α, integrin α4β7, IL12/23, JAK inhibitors and future anti-IBD targets and small molecules
	In paediatric IBD: Growth impairment, as defined by the Paris classification63
	In paediatric IBD: Delayed onset of puberty defined as no breast development at age 13 in girls or a bilateral testis volume of less than 3 mL at age 14 in boys
	Occurrence of gingivitis or periodontitis according to the current classification system,66 67 occurrence of caries, occurrence of endodontic lesions, and occurrence and reason for tooth loss, occurrence of peri-implantitis68

CD, Crohn’s disease; EIMs, extra-intestinal manifestations; IBD, inflammatory bowel disease; IMIDs, immune-mediated inflammatory diseases; IUS, intestinal ultrasonography; PROs, patient-reported outcomes; SES-CD, Simple Endoscopic Score for Crohn Disease; UC, ulcerative colitis.