169severe colitis showed that response to infliximab may decrease with time, and dose
escalation in this population was commonly needed, occurring in 62% of this cohort
[ 27 ]. Even after dose escalation, only 39% of these patients remained on infliximab
therapy after 1 and 2 years and 29% after 3 years. Lower BMI Z-score and serum
albumin as well as a higher ESR at baseline were associated with dose escalation,
but not infliximab failure.
There has been one randomized open-label prospective study evaluating the effi-
cacy and safety of infliximab in induction and maintenance therapy for moderately
to severely active pediatric UC [ 28 ]. Results of this study led to FDA approval of
infliximab for the treatment of pediatric UC in 2011. Sixty patients with medically
refractory, moderately to severely active UC were given 5mg/kg of infliximab at 0,
2, and 6 weeks, and those with response were then randomized to receive infusions
either 8 weeks or every 12 weeks. Forty-four patients (73%) responded to induction
therapy, and at week 8, 41 patients (68.3%) had achieved mucosal healing. Forty-
five patients were subsequently randomized to receive infliximab at 8-week or
12-week intervals. At week 54, 38.1% of patients receiving every 8-week infusions
were in remission compared to 18.2% receiving every 12-week dosing; a reduction
in corticosteroid use at 54 weeks was observed in patients receiving 8-week infu-
sions, but not in the 12-week infusion group. Similar to previous data, dose escala-
tion was common, and approximately 50% of patients required either an increase in
infliximab dose or more frequent infusions, with more patients requiring a step-up
in therapy in the every 12-week infusion group. Infliximab concentrations were
obtained at multiple points during the course of this study; higher concentrations at
week 8 were associated with clinical response and mucosal healing, and higher
median week 30 troughs were noted in patients receiving every 8-week dosing,
likely accounting for higher proportion of patients in this group who had sustained
efficacy [ 29 ]. In summary, this prospective randomized open-label study and addi-
tional retrospective and prospective observational cohorts clearly indicate that inf-
liximab is an effective therapy for moderate to severe UC with benefits in both
corticosteroid-dependent and corticosteroid-refractory disease and may help pre-
vent colectomy in pediatric UC patients.
Adalimumab for Pediatric Inflammatory Bowel Disease
Despite the promising outcomes associated with infliximab in the treatment of pedi-
atric IBD, historically, up to 50% of patients require dose escalation, and approxi-
mately 33% of patients discontinue infliximab therapy, most commonly due to loss
of response. The need for additional anti-TNF agents was recognized prompting the
development of adalimumab, a recombinant, fully human, monoclonal anti-TNF
antibody. Compared to infliximab, adalimumab provides an inherently decreased
risk of neutralizing antibody formation because of the therapy’s strictly human anti-
body components. Initial reports of adalimumab use in pediatric inflammatory
bowel disease focused on patients who had become intolerant to infliximab. Noe
11 Biologic Therapy in Pediatric Inflammatory Bowel Disease