16 4
infliximab, with these patients having excellent response rates. Kugathasan et al.
reported outcomes of 15 consecutive children with medical refractory CD treated
with a single 5 mg/kg dose of infliximab [ 4 ]. Fourteen of these patients had improve-
ment after this single dose, and 10 of 15 children were in clinical remission (defined
as Pediatric Crohn’s Disease Activity Index (PCDAI) ≤ 15) by 10 weeks. Steroid
doses were also significantly lower at 4 and 10 weeks. Unfortunately, in a subse-
quent 52-week follow-up, 11 of the 14 responders experienced clinical relapse, with
patients with disease over 2 years having a shorter duration of response. A multi-
center study of 21 pediatric patients with moderate to severe CD randomized to
receive a single infusion of 1 mg/kg, 5 mg/kg, or 10 mg/kg of infliximab showed
similar results with 100% of patients achieving clinical response (≥10- point
improvement in PCDAI or ≥70 improvements in modified CDAI) and 48% achiev-
ing clinical remission, defined as a PCDAI < 10 or a modified CDAI <150, at some
point during the 12-week observation period [ 5 ]. Patients who received 5 mg/kg and
10 mg/kg doses of infliximab had higher rates of remission at the 12-week follow-
up evaluation compared to those who received 1 mg/kg. Nine patients had endo-
scopic assessment of disease prior to and 4 weeks after receiving infliximab.
Endoscopic lesion severity scores improved by a median of 7%, 69%, and 52% in
1, 5, and 10 mg/kg infliximab groups, respectively. Serum infliximab concentrations
were found to be similar in both pediatric and adult populations with duration of
detectable levels being proportional with dose—levels were detected through week
4 in 1 mg/kg group and compared through week 8 and week 12 in 5 and 10 mg/kg
groups, respectively. While the above studies assessed response to a single infusion
of infliximab, Cezard et al. prospectively evaluated the response of 21 children with
severe CD, most with corticosteroid-dependent disease, who received induction
dosing with 5 mg/kg infliximab on days 0, 15, and 45 [ 6 ]. Nineteen children were in
clinical remission (Harvey Bradshaw (HB) index <4) at day 4, and steroid use was
significantly decreased at 3 months. However, similar to the above studies, response
was not durable, and 19 of the patients (90%) experienced relapse despite continu-
ing immunosuppressive therapy, with 37% of relapses occurring before 3 months.
As highlighted above, the optimal frequency of medication administration was
not known during the early years of infliximab use in the pediatric population. It
was initially hypothesized that children could potentially develop a prolonged
response to infliximab compared to adults, obviating the need for regularly sched-
uled infusions; however, preliminary studies showed frequent relapse after single
dose or induction dosing. Episodic on-demand infliximab dosing, i.e., giving addi-
tional doses if patient relapsed, was another consideration in pediatric patients. This
strategy was further evaluated in a randomized, multicenter, open-label study by
Ruemmele et al. [ 7 ] Thirty-one children who were in remission after three inflix-
imab infusions (induction dosing) were randomized to scheduled infusions every
2 months or “on-demand” dosing. During the course of the trial, 92% of patients
who received episodic infliximab therapy experienced a relapse compared to 23%
of patients receiving scheduled infliximab therapy every 8 weeks. Additionally, the
time to relapse was shorter in patients who received episodic infliximab infusions
with an average time to relapse of 120 days compared to 150 days in the scheduled
S. Patel and J. Strople