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preferred anti-integrin for pediatric IBD patients who have failed anti-TNF therapy.
Thus far there have been two published studies reporting the early outcomes of 73
pediatric IBD patients treated with this therapy. A multicenter, retrospective study
by Singh et al. described the early experience with vedolizumab in 52 patients with
pediatric IBD, the majority of whom (90%) had failed anti-TNF therapy [ 73 ]. All
patients received vedolizumab at 0, 2, and 6 weeks and then every 8 weeks; most
patients (75%) received adult dosing of 300 mg, and the remaining received weight-
based dosing—11 patients (21%) received 6 mg/kg/dose and two patients (4%)
received 5 mg/kg/dose. By week 14, 42% of patients with CD were in remission,
while 76% of patients with UC were in remission; however, there was no significant
difference in corticosteroid-free remission at this time point between these two
patient groups. Corticosteroid use did decrease throughout the course of the study
from 56% at the time of vedolizumab initiation to 19% by week 14. Disease pheno-
type may play a role in response as patients with colonic-only disease were more
likely to achieve remission at 14 weeks compared to patients with small bowel
involvement, 70% versus 39%, respectively. In the small subset of patients who
were TNF naïve (n = 5), 80% achieved clinical remission by week 6, and remission
was maintained through 22 weeks. A second smaller prospective study evaluated
the clinical response to vedolizumab in 21 patients with refractory pediatric IBD,
the majority with Crohn’s disease. Patients received induction dosing with 300 mg
at 0, 2, and 6 weeks and then every 8-week maintenance therapy [ 74 ]. There was a
significant decrease in both PCDAI and PUCAI at every follow-up interval from
baseline to week 14, which persisted to week 22 (p < 0.05). Clinical response rates
for all patients, defined as a decrease in activity index score by at least 12.5 points
in CD patients and 20 points in UC/IBD-U, were 31.6%, 52.6%, and 57.9% at
weeks 6, 14, and 22, respectively. At week 14 and 22, 20% of patients (4 out of 20)
were in steroid-free remission, compared to 5% at 6 weeks. In both studies, vedoli-
zumab generally was well tolerated and no infusion reactions were reported. In the
study by Conrad et al., 12 patients did have serious adverse events resulting in hos-
pitalization, but it was unclear whether these were directly related to vedolizumab
or patient’s primary disease. A phase 2, randomized, double-blind, dose-ranging
study of vedolizumab to evaluate the safety and tolerability of in pediatric inflam-
matory bowel disease is anticipated to begin enrollment soon (ClinicalTrials.gov
identifier: NCT03138655), and a multicenter prospective cohort study is currently
underway (ClinicalTrials.gov identifier: NCT02862132).
There is limited experience of ustekinumab, the most recently FDA-approved
biologic for treatment of adult Crohn’s disease, in pediatric patients. This human-
ized monoclonal antibody binds to the common p40 subunit of IL-12 and IL-23,
inhibiting activity of these proteins. To date, only one case report and one small
retrospective chart review of use in pediatric CD have been published [ 75 , 76 ].
Bishop et al. examined the response of four adolescent patients with CD who had
received subcutaneous ustekinumab therapy at 0 and 4 weeks and then every
8 weeks for maintenance therapy; no IV doses were administered [ 76 ]. All patients
had received both infliximab and adalimumab therapy and were primary responders
to their first anti-TNF agent. Two patients had a sustained clinical response, were
S. Patel and J. Strople