42
Pediatric Efficacy
Similar to the adult population, anti-TNFs have been effective in inducing and
maintaining remission in pediatric IBD. The REACH (Randomized, Multicenter,
Open-Label Study to Evaluate the Safety and Efficacy of Anti-TNF alpha Chimeric
Monoclonal Antibody in Pediatric Subjects with Moderate to Severe CD) study
assessed the efficacy of a three-dose induction on reducing the signs and symptoms
of CD in children. 84% of subjects had a clinical response at week 10 with 58.9%
in clinical remission. Improvements were seen in quality of life, steroid use, and
height among those with evidence of growth delay. Other studies have validated the
effect of IFX on children with CD in respect to mucosal healing and promoting
growth [ 55 , 56 ]. Within the REACH cohort, infliximab was able to rapidly reduce
symptomatic perianal disease [ 57 ]. Similar results for induction and maintenance of
remission were noted with adalimumab [ 58 ].
Top-Down or Step-Up
Trials for anti-TNFs typically include moderate to severe CD and are often limited
to those with medically refractory disease to standard therapy. Anti-TNFs became
the “top” of the treatment pyramid following immunomodulators and steroids.
However, if anti-TNFs are the most effective therapy (as SONIC data suggests)
[ 14 ], then perhaps they should be used earlier in the course of the disease prior to a
moderate to severe flare. The difficulty of this strategy is that not all patients will
progress to moderate to severe disease. A population-based study from Denmark
determined that 50% of patients will be in remission 1 year from CD diagnosis with
only one third having active disease [ 59 ]. Aggressive early therapy may over-
immunosuppress a portion of the population who would otherwise not need immu-
nosuppression. However, a large European randomized controlled trial (top-down)
assessed early combination IFX with azathioprine versus steroids and sequential
azathioprine followed by IFX [ 60 ]. All patients were diagnosed within 4 years and
were naïve to steroid, immunomodulators, or anti-TNFs. Early combined therapy
resulted in a greater proportion of remission at weeks 26 (60% vs. 36%, p < 0.006)
and 52 (62% v. 42%, p < 0.03).
While both the top-down trial and SONIC suggested that early combined immu-
nosuppression for CD was superior to sequential therapy, concerns about side
effects, infections, and cost appear to limit this strategy [ 61 , 62 ]. The REACT trial
attempted to measure the benefits of early combined therapy (i.e., a top-down
approach) through a large open-label cluster randomized trial [ 63 ]. Of the 41 prac-
tices randomized, the primary outcome of steroid-free remission was similar
between the two strategies; however, the 2-year composite outcome of surgery, hos-
pitalization, or serious disease-related complication was lower in the early com-
bined immunosuppression group. An individual patient’s needs/risk factors may
therefore dictate the decision for initial therapy; however, the available data favors
a top-down (or early aggressive) approach on the whole.
B. P. Va u g h n