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

Table 2 Mechanism of action, drug doses, route of administration, efficacy and side effects of biologics in children with inflammatory bowel disease

Characteristics	Infliximab	Adalimumab	Ustekinumab	Vedolizumab	Tofacitinib
Mechanism of action	Anti-TNFα antibody (chimeric)	Anti-TNFα antibody (humanized)	Anti-IL-12/23 antibody (humanized)	Anti-α4β7 integrin antibody (humanized)	JAK inhibitor
Route	IV; SCb	SC	IV (1st dose) followed by SC	IV	Oral
Dosea
Induction	5mg/kg	2.4 mg/kg, f/b 12 mg/kg	6 mg/kg if < 40 kg BW, 130 mg if > 40 kg BW	6 mg/kg < 40 kg BW, 300 mg > 40 kg BW	10 mg twice daily
Maintenance	5mg/kg	0.6 mg/kg	2 mg/kg if < 40 kg BW, 90 mg if > 40 kg BW	Same as induction dose	5 mg twice daily
Schedulea
Induction	0 week, 2 week, and 6 weeks	0 week, and 2 weeks	0 week	0 week, 2 weeks, and 6 weeks	Daily
Maintenance	8 weekly	2 weekly	8 weekly	8 weekly	Daily
Target drug level	Induction (week 6) ≥ 10-15 μg/mL; maintenance ≥ 5 μg/mL	Post-induction before 3rd dose ≥ 7.5 μg/mL	Target level not well defined	Target level not well defined	NR
	In patients at risk for accelerated drug clearance, target concentration ≥ 25 μg/mL at 2nd infusion and ≥ 15 μg/mL at 3rd infusion[13]	Maintenance ≥ 7.5 μg/mL[13]
Adverse events	Infection, reactivation of TB/ HBV; skin reaction (psoriasis)	Infection; headache, arthralgia, skin reaction	Infection; (GI most common), myalgia	Infection; (respiratory, GI); headache, myalgia	Varicella zoster infection, thrombosis, dyslipidemia, LFT, derangement
Use of concomitant immunomodulator (azathioprine/methotrexate)	Yes (initial 6-12 months)	If biological naive: No need	No	No	No
		Biological exposed: Can add

^aDose and ^aschedule: Standard dose may need to be changed to more frequent dosing or/and higher dose as per the therapeutic drug monitoring (see text); in children with weight < 30 kg, vedolizumab should be dosed by the child's body surface area (200 mg/m²) or weight (10 mg/kg)[50].

^bSC: Subcutaneous route tried in study and shown to be as effective[44,45]. Recommendations for drug level vary as per disease site and burden e.g. higher in perianal Crohn’s disease.

IV: Intravenous; SC: Subcutaneous; TNFα: Necrosis factor alpha; Anti-α4β7: Anti-alpha4beta7; IL: Interleukin; BW: Body weight; TB: Tuberculosis; HBV: Hepatitis B virus; LFT: Liver function test; GI: Gastrointestinal; NR: Not recommended.