165infusion study group. At week 60, 61% of patients on episodic infliximab therapy
were in remission compared to 83% of patients receiving scheduled infliximab.
The REACH study, a large multicenter, randomized, open-label trial, prospec-
tively evaluated the safety and efficacy of induction and maintenance of infliximab
in moderately to severely active pediatric CD and demonstrated superiority of every
8-week maintenance infliximab infusions compared to every 12-week infusion
schedule [ 8 ]. One hundred and twelve patients with moderate to severe CD despite
immunomodulatory therapy received three-dose induction regimen of infliximab
5 mg/kg. Responders were then randomized to receive maintenance infliximab
5 mg/kg every 8 or 12 weeks. After completion of induction therapy (week 10
assessment), 88% of patients had responded, defined as a decrease in PCDAI score
of at least 15 points, and 59% of patients were in clinical remission, defined as a
PCDAI <10. At week 54, 64% of patients receiving infliximab every 8 weeks had a
clinical response, and 56% were in clinical remission without the need for a dose
adjustment compared to a clinical response rate of 33% and clinical remission rate
of 23.5% in the every 12-week study group. Corticosteroid use significantly
decreased, and IMPACT III quality of life scores improved in both 8- and 12-week
groups over the course of the study. Sixty participants entered the REACH open-
label extension—33 patients receiving infliximab 5 mg/kg every 8 weeks, 12
patients receiving 10 mg/kg every 12 weeks, and 15 patients receiving 10 mg/kg
every 8 weeks [ 9 ]. In these patients receiving scheduled infliximab for up to 3 years,
most had sustained clinical benefit, with approximately 80% having no or mild
disease based on the physician global assessment (PGA) at assessments.
Additional studies have evaluated the long-term outcomes of infliximab therapy.
In one population-based retrospective study of 66 pediatric CD patients treated with
infliximab (five receiving episodic treatment) followed for a mean of 41 months,
prolonged clinical response was seen in approximately 70% of patients [ 10 ].
However, in patients considered infliximab dependent (n = 37), 57% had recurrence
of symptoms prior to the 8-week interval, requiring increased dose to 10 mg/kg or
shortened infusion intervals to maintain response. In a similar study by Crombe
et al. of 120 patients with pediatric CD, 54% had long-term efficacy of therapy; 27%
of the entire cohort required dose optimization (shortened interval and/or increased
dose) [ 11 ]. Forty-two percent of these patients were receiving episodic infusions,
which may account for the lower long-term response rate compared to other effi-
cacy studies. Finally, a multicenter cohort study of patients enrolled in the Pediatric
Inflammatory Bowel Disease Collaborative Research Registry evaluated long-term
outcomes of pediatric CD patients treated with infliximab maintenance therapy
[ 12 ]. In total, 202 of 729 patients received infliximab; the majority of whom received
infliximab early in their disease course, with 60 patients (30%) receiving infliximab
within 3 months of their diagnosis, 64 patients (32%) between 3 and 12 months
from diagnosis, 47 patients (23%) between 12 and 24 months from diagnosis, and
31 patients (15%) after 24 months from diagnosis. One hundred and twenty eight
patients were ultimately included in the outcome cohort with 121 patients receiving
continuous infliximab maintenance therapy. After 1 year of infliximab maintenance
therapy, 32% of patients had mild disease, and 54% had inactive disease as assessed
11 Biologic Therapy in Pediatric Inflammatory Bowel Disease