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

Table 6 Summary of the pediatric studies on the efficacy and safety of dual-biologic therapy

Ref.	Number of cases	Details of case	Medications used	Efficacy-clinical remission	Adverse events
	Median age (years); IQR
Dolinger et al[89], retrospective	16 (CD 7, UC 9)	All failed ≥ 2 biologics	VDZ + TOFA 9, VDZ + UST 4, UST + TOFA 3	75% at 6 months	6.25% (arthritis, deep vein thrombosis)
	15.9; 13.5-16.8
Wlazło et al[90], retrospective	14 ( CD 4, UC 10)	All failed single biologic	UST + ADA 5, VDZ + ADA 5, IFX + VDZ 3, VDZ + ADA/UST + ADA-1	73% at 4 months	7% (mild infection)
	11.7; 3-17
Yerushalmy-Feler et al[91], retrospective	62 (CD 35, UC 27)	All failed 1 biologic, 76% failed ≥ 2 biologics	IFX + VDZ 18, IFX + UST 8, ADA + UST 11, ADA + VDZ 11, VDZ + UST 8, TOFA + IFX 2, TOFA + VDZ 1	35% at 3 months, 50% at 6 months, 63% at 1 year	47% (7% serious, infection, thrombosis)
	15.5; 13-16.8
Olbjørn et al[92], retrospective	13 (9 CD, 4 UC)	All failed anti-TNFα agents	IFX + VDZ 8 (4 CD, 4UC), IFX + UST 5 (all CD)	IFX + VDZ, 75% remission at 6 months in UC, 25% in CD, IFX + UST 100% remission at 2 year	IFX + VDZ 2/8 (25%), IFX + UST 1/5 (20%)
	8; 4-17.5
Goyal et al[93], retrospective	9 children with CD	All failed anti-TNFα agents	IFX + VDZ + metho 1, IFX + anakinra 1, ADA + VDZ 1, ADA + VDZ+ PEN 1, ADA + VDZ + metho 3, UST + VDZ 2	Complete response 45%, partial response 22% at 4 months	3/9 (33%), skin infection, bleeding, fracture, unrelated
	16; 8-19
Wlazlo et al[94], retrospective	14 (CD 4, UC 10)	All failed anti-TNFα agents	ADA + VDZ 5, ADA + UST 6, IFX + VDZ 3	73% CRes by 4 months	Not reported
	11.7; 3-17

IQR: Interquartile range; CD: Crohn’s disease; UC: Ulcerative colitis; VDZ: Vedolizumab; TOFA: Tofacitinib; UST: Ustekinumab; IFX: Infliximab; ADA: Aadalimumab; Metho: Methotrexate; PEN: Partial enteral nutrition; TNFα: Tumor necrosis factor-alpha.