Biologics in the management of pediatric inflammatory bowel disease: When and what to choose

Table 1 Recommendations of pediatric guidelines regarding biologic use in inflammatory bowel disease

Characteristics	ECCO-ESPGHAN guidelines CD, 2020[13], UC, 2018[14,15]	Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition PIBD Working Group, 2022[6]	Canadian association of Gastroenterology Guidelines, 2019[16]
Indications CD	Upfront biologics for the following: (1) Extensive disease and deep colonic ulcers; (2) Perianal disease; (3) Stricturing or penetrating disease; and (4) Growth failure	Upfront biologics if severe luminal or perianal disease	Upfront biologics if severe luminal or perianal disease
	As step-up therapy: Moderate to severe active CD not responding to conventional therapy	Step-up approach: Moderate to severe active CD not responding to conventional therapy	Step-up approach: Moderate to severe active CD not responding to conventional therapy
	1st line: Infliximab, adalimumab; 2nd line: Ustekinumab	1st line: Infliximab, adalimumab, ustekinumab, and vedolizumab - no consensus	1st line: Iinfliximab, adalimumab; 2nd line: Ustekinumab; no consensus on vedolizumab
Indications UC	Chronically active moderate to severe UC, not responding to conventional therapy; tofacitinib - no consensus	Chronically active moderate to severe UC, not responding to conventional therapy	NA
	ASUC if not responding to 5 days of intravenous steroid	ASUC if not responding to 5 days of intravenous steroid
	1st line: Infliximab; 2nd line: Vedolizumab	1st line: Infliximab; vedolizumab, tofacitinib - no consensus
Co-therapy with immune-modulator	Infliximab - consider combination therapy Adalimumab - no	Infliximab and adalimumab - consider combination therapy	Infliximab - NR (male), no recommendation for or against (female)
			Adalimumab - NR (male), no recommendation for or against (female)
			If considered, methotrexate for boys and thiopurine for girls
Screening before biologic	HBV/HCV/HIV	HBV/HCV/HIV	HBV/HCV/HIV
	TB: Mantoux or IGRA (BCG-vaccinated patients), chest X-ray, sputum	TB: Mantoux and IGRA, chest X-ray, sputum	TB: Mantoux or IGRA, chest X-ray, sputum
TDM	Yes, proactive preferred	Yes, reactive	Yes, reactive
Target trough level	Infliximab: Induction (week 6) ≥ 15 μg/mL; maintenance ≥ 5 μg/mL	Infliximab: Induction > 10-15 μg/mL; maintenance ≥ 3-7 μg/mL	NA
	Adalimumab: Induction (week 4) and maintenance ≥ 7.5 μg/mL	Adalimumab: Maintenance ≥ 5-8 μg/mL

ECCO-ESPGHAN: European Crohn’s and Colitis Organization-European Society of Pediatric Gastroenterology, Hepatology and Nutrition; CD: Crohn’s disease; UC: Ulcerative colitis; ASUC: Acute severe ulcerative colitis; PIBD: Pediatric inflammatory bowel disease; TDM: Therapeutic drug monitoring; NA: Not available; NR: Not recommended; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; TB: Tuberculosis; IGRA: Interferon gold release assay; BCG: Bacille Calmette-Guerin.