Real-world inflammatory bowel disease-modification outcomes: A narrative review

Table 1 Outcome measures recommended by the selecting therapeutic targets in inflammatory bowel disease II and standard protocol items: Recommendations for interventional trials consensus for use in inflammatory bowel disease-modification trials

Regulatory endpoints: STRIDE II	Disease modification endpoints: SPIRIT
Intermediate targets	Outcome measures
	Midterm complications
Clinical response [at least 50% decrease in PRO2 (CD: Abdominal pain and stool frequency; UC: Rectal bleeding and stool frequency)]	Bowel damage in patients with CD (Lemann Index; 12-24 months)
Clinical remission [CD: PRO2 (abdominal pain ≤ 1 and stool frequency ≤ 3) or HBI < 5; UC: PRO2 (rectal bleeding = 0 and stool frequency = 0) or partial Mayo < 3 and no sub-score > 1]	IBD-related surgery [any colectomy (UC), any CD-related surgery, endoscopic balloon dilation, perianal surgery (CD); 24-36 months]
Normalization of C-reactive protein (values under the upper limit of normal) and fecal calprotectin (to 100-250 μg/g)	IBD-related hospitalizations (composite of number of hospitalizations and cumulative length of hospital stay; 12-24 months)
Long-term targets	Disease extension in UC (excluding patients with pancolitis) (macroscopic proximal disease extension; 2-5 years after diagnosis)
Restoration of normal growth in children	Extraintestinal manifestations (12-36 months)
Endoscopic healing (CD: SES-CD < 3 points or absence of ulcerations; UC: Mayo endoscopic sub-score = 0 points or UCEIS ≤ 1 point)	Permanent stoma
Absence of disability and normalization of HRQoL	Short-bowel syndrome (small-bowel length < 200 cm)
Adjunctive targets to endoscopic remission	Long-term complications
Histological remission	Dysplasia or cancer (5 years)
Transmural healing	Mortality (both IBD-related and non-IBD related mortality; 5 years)
	Impact on patient’s life
	Health-related quality of life (tool: Composite of IBDQ-36 and SF-36; every 6-12 months)
	Disability (IBD Disability Index; every 6-12 months)
	Fecal incontinence (excluding patients with isolated liminal ileal CD) (Cleveland score or Jorge-Wexner score; every 6-12 months)

STRIDE: Selecting therapeutic targets in inflammatory bowel disease; SPIRIT: Standard protocol items: Recommendations for interventional trials; PRO2: Patient-reported outcomes 2; CD: Crohn’s disease; UC: Ulcerative colitis; HBI: Harvey-Bradshaw index; SES-CD: Simple endoscopic score for Crohn’s disease; UCEIS: Ulcerative colitis endoscopic index of severity; HRQoL: Health-related quality of life; IBD: Inflammatory bowel disease; IBDQ-36: 36-Item Inflammatory Bowel Disease Questionnaire; SF-36: 36-Item Short-Form Health Survey.