1711 study, a multicenter randomized trial, evaluated the safety and efficacy of adali-
mumab in pediatric CD [ 36 ]. Similar to the REACH clinical trial, patients received
open-label weight-based induction adalimumab (two doses), followed by double-
blind maintenance dosing regimens—high dose compared to low dose (high dose,
40 kg received 40 mg every other week and <40 kg received 20 mg every other
week; low dose, >40 kg received 20 mg every other week and <40 kg received
10 mg every other week). One hundred and ninety-two patients with moderate to
severe Crohn’s disease (PCDAI >30) received induction therapy, and 188 patients
were randomized based on clinical response to induction dosing (decrease and
PCDAI ≥ 15) and prior exposure to infliximab therapy (approximately 44% of
study participants). After induction (week 4), 155 patients (82.4%) had a clinical
response, and 52 patients (27.7%) were in clinical remission. At week 26, 53.7%
of patients had a clinical response, and 33.5% of patients were in clinical remis-
sion; 28.2% and 35.1% had a clinical response and were in clinical remission at
52 weeks, respectively. A higher proportion of patients in the high-dose regimen
were in remission at both of these time points, although the difference was not
statistically significant. Of the 71 patients that were on steroid therapy at baseline,
65.8% of patients in the low-dose group and 84.8% of patients in the high-dose
group had successfully discontinued this therapy. The proportion of patients expe-
riencing fistula improvement and closure was also higher in the high-dose group.
Finally, in the high-dose group, infliximab-naïve patients had higher remission and
response rates at both week 26 and 52 compared to patients who had previously
been treated with this therapy.
Analogous to experience with infliximab, in the IMAgINE 1 trial, 50.5% of
patients in the low-dose adalimumab therapy and 37.6% of patient in the high-dose
adalimumab therapy required dose escalation to weekly therapy after week 12 due
to nonresponse or disease exacerbation [ 36 ]. Efficacy of dose escalation was evalu-
ated in this subpopulation at 52 weeks [ 37 ]. Of the 83 patients who escalated to
weekly therapy, 51.8% had a clinical response and 24.1% achieved clinical remis-
sion, with a higher proportion of patients in the high-dose group achieving these
end points (57.1% and 31.4%, respectively). Patients on immunomodulator therapy
and patients randomized to the high-dose group were less likely to require dose
escalation to weekly therapy. Long-term efficacy of adalimumab was evaluated in
the IMAgINE 2 study [ 38 ]. One hundred patients who responded to adalimumab at
any time during IMAgINE 1 were enrolled in this open-label extension and fol-
lowed through 240 weeks. Overall 41% who entered IMAgINE 2 were in remis-
sion, and 48% had achieved response at 240 weeks, and for patients who entered
IMAgINE 2 in remission, remission was maintained in 45% at week 240.
Corticosteroid use continued to decrease during the course of this study, and among
patients who were on corticosteroids at time of entry into IMAgINE 1, corticoste-
roid-free remission increased from 40.5% at enrollment into IMAgINE 2 (week 52)
to 63.2% at week 240.
Adalimumab is not FDA approved for the treatment of pediatric ulcerative coli-
tis, and there is limited published data regarding the use of adalimumab therapy in
children with ulcerative colitis, but in clinical practice, adalimumab therapy is used
11 Biologic Therapy in Pediatric Inflammatory Bowel Disease