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

Table 5 Summary of the studies on the efficacy and safety of vedolizumab, ustekinumab and tofacitinib in children

Ref.	CD				UC
	Number of cases	Details of cases	Efficacy	Adverse event	Number of cases	Details of cases	Efficacy	Adverse event
	Age (years), mean ± SD/median age (years); IQR				Age, (years) mean ± SD/median age (years); IQR
Vedolizumab
Singh et al[47], retrospective	30	87% anti TNFα agent exposed	Clinical remission 42% at week 14	14.3%	22	95% anti TNFα agent exposed	Clinical remission 76% at week 14	Nil
	15.2; 7-17				14.3; 7-17
Hyams et al[49], HUBBLE trail	45	Refractory to steroid, immunomodulator and/or anti-TNFα agents; biologic exposed 64%	CRes 33%-63%; remission 16%-54% at week 14	90% (serious 30%)	44	Refractory to steroid, immunomodulator and/or anti-TNFα agents; biologic exposed 34%	CRes 40%-69%; remission 30%-60% at week 14	82% (serious 22%)
	2-17				2-17
Atia et al[50], VEDOKIDS	65	Refractory to steroid, immunomodulator and/or anti-TNFα agents	Clinical remission 32% at week 14	28% (none serious)	77	Refractory to steroid, immunomodulator and/or anti-TNFα agents	Clinical remission 49% at week 14	18% (none serious)
	15 ± 2.3				14.2 ± 2.9
Fang et al[51], systematic review	216	Refractory to steroid, immunomodulator and/or anti-TNFα agents	Clinical remission 18%-37% at week 14; 36%-57% at 1 year	serious 6%a	239	Refractory to steroid, immunomodulator and/or anti-TNFα agents	Clinical remission 31%-65% at week 14; 35%-54% at 1 year	Serious; 6%a
	< 21				< 21
Ustekinumab
Turner et al[53], UniStar study, Prospective	34	Moderate to severe CD, 94% anti-TNFα exposed	Clinical remission 41% at week 48	88% (serious 14.7%)	-	-	-	-
	13; 12-16
Yerushalmy-Feler et al[54], ESPGHAN Porto group, retrospective	69	98.6% anti-TNFα exposed	CRes 67% at week 12; remission 42% at week 12	8.7% (none serious)	-	-	-	-
	15.8; 13.8-16.9
Koudsi et al[55], GETAID, retrospective	48	All anti-TNFα exposed	PCDAI reduced from 28.7 to 18.7 at week 12	17%a	5	Refractory, all anti-TNFα exposed	PUCAI 47 to 25 at week 12	17%a
	15.0; 8.7-18				15.0; 8.7-18
Fang et al[56], systematic review	204	Refractory CD, 90% anti-TNFα exposed	Clinical remission 34% at week 8-16, 46% at 1 year	3.5%a	166	Refractory UC, 86% anti TNFα exposed	Clinical remission 24% at week 8-16, 46% by 1 year	3.5%a
Tofacitinib
Moore et al[57], retrospective	-	-	-	-	21	20 exposed to infliximab, 9 to adalimumab, 2 to ustekinumab, 13 to vedolizumab	CRes 43% at week 12; clinical remission 33% at week 12, 41% at week 52	71% (serious 52%, possibly non-drug related)
					18.4; 15-19.9
Ledder et al[58], retrospective	-	-	-	-	101	All at least 1 biologic exposed; 36% exposed to 3 biologics	CRes 46% at week 8; clinical remission 16% at week 8, 23% at week 24	3% (herpes zoster, dyslipidemia)
					12.8 ± 2.8

^aAdverse event rate reported for combined group of patients with Crohn’s and ulcerative colitis.

Adverse events: (1)Vedolizumab: Infection (respiratory tract infection, pneumonia, gastrointestinal tract), headache, arthralgia, muscle spasm, skin (rash, eczema), hepatic injury, hypersensitivity reaction, worsening of underlying disease; (2) Ustekinumab: Headache, arthralgia, nausea, abdominal pain, upper respiratory tract infection, and nasopharyngitis, gastroenteritis, abscess, intestinal obstruction, C. difficile; and (3) Tofacitinib: Fever, infections-viral, C. difficile, candida, pharyngitis, pneumonia, vaginitis/abdominal pain, constipation, dermatitis, headache, vomiting, ocular complaints.

CD: Crohn’s disease; UC: Ulcerative colitis; CRes: Clinical response; TNFα: Tumor necrosis factor-alpha; PCDAI: Pediatric Crohn’s disease activity index; PUCAI: Pediatric ulcerative colitis activity index; NA: Not available; IQR: Interquartile range.