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by PGA; by 2 years, 21% of patients had mild disease and 67% had inactive disease;
and at 3 years of maintenance therapy, 30% had mild disease and 57% had inactive
disease. However, almost half (63/128) of the patients required anti-TNF dose
adjustments during their course on infliximab therapy. The above results emphasize
the long-term benefits and durability of infliximab therapy in pediatric CD, but also
the need for dose optimization to maintain response in a substantial proportion of
patients. Loss of response has been reported to be as high as 33–50% in pediatric
CD patients over a follow-up period of 3–5 years. With so many variables involved
in the treatment of pediatric inflammatory bowel disease, attempts have been made
to identify predictors of response to infliximab. Grover et al. studied 47 patients
with refractory, luminal CD who had an initial response to induction infliximab
therapy [ 13 ]. Twenty-eight patients (60%) developed a sustained primary response
for an average of 2.8 years, and 19 patients (40%) had a loss of response at a median
of 11 months. It was found that a loss of response was associated with a lower BMI
and lower height z-scores prior to infliximab induction and a higher CRP after
induction, which may be surrogates for severity of inflammation. Patients were
more likely to have a sustained primary response if immunomodulator therapy was
continued beyond induction therapy with infliximab, likely related to effects on
infliximab drug levels. In this study, duration of disease, time to infliximab therapy,
disease severity, disease location, complicating phenotypes, and steroid dependency
were not associated with loss of response.
As the incidence of pediatric inflammatory bowel disease has risen, there has
also been an increase in early-onset disease in patients younger than 8 years of age.
A retrospective study by Kelsen et al. evaluated the safety and efficacy of infliximab
in this subgroup of patients with early-onset disease [ 14 ]. Thirty-three patients with
either CD, ulcerative colitis (UC), or inflammatory bowel disease unclassified (IBD-
U) who had initiated infliximab therapy prior to 7 years of age were assessed. After
1 year of infliximab therapy, 10%, 25%, and 0% of patients with CD, UC, and IBD-
U, respectively, had a clinical response. Nineteen patients (58%) required either
dose escalation or a reduction in interval between infusions. The proportion of
patients who were maintained on infliximab steadily decreased over time with 36%
on infliximab maintenance after 1 year, 18% after 2 years, and 12% after 3 years. In
a subset of patients younger than 5 years of age, only 25% were continued on inflix-
imab after 1 year, and only 10% were maintained on infliximab after years 2 and 3
combined. Ultimately, it was found that children less than 7 years of age with early-
onset IBD were less likely to continue infliximab as maintenance therapy compared
to older pediatric patients assessed in the REACH trial. These findings may be
related to specific pharmacokinetics of infliximab in younger patients or potentially
related to the colonic-predominant phenotype seen in early-onset IBD.
Adult studies have demonstrated the efficacy of infliximab for treatment of peri-
anal CD, and several small studies have shown similar benefit of infliximab in pedi-
atric patients with this complicated phenotype [ 6 , 15 , 16 ]. Post hoc analysis
evaluated the effect of infliximab in a subpopulation of 31 patients with concurrent
perianal Crohn’s disease from REACH [ 15 ]. In 22 patients that had baseline peri-
anal disease, 41% had complete or partial response after a single dose of infliximab,
S. Patel and J. Strople