Adalimumab safely induced and maintained remission in about one-third of pediatric patients with treatment-resistant Crohn’s disease, reported Dr. Jeffrey S. Hyams and his colleagues in the August issue of Gastroenterology.
In a phase III, multicenter, randomized trial consisting of an open-label induction followed by double-blind maintenance therapy (IMAgINE 1), Dr. Hyams of the Connecticut Children’s Medical Center, Hartford, studied 188 patients aged 6-17 years with a recent diagnosis of Crohn’s disease confirmed by endoscopy or radiology.
All patients were classified as having moderate to severe disease, with a Pediatric Crohn’s Disease Activity Index (PCDAI) of greater than 30 despite concurrent treatment with an oral corticosteroid and/or an immunomodulator such as azathioprine, 6-mercaptopurine, or methotrexate. The 45 sites were located in Canada, Europe, and the United States.
Patients received induction therapy for 4 weeks, and then were randomly assigned to high-dose or low-dose adalimumab as double-blind maintenance therapy for 48 weeks thereafter.
High-dose patients whose body weight was 40 kg or greater received 40 mg of the drug every other week; patients weighing less than 40 kg received 20 mg every other week. Low-dose patients with a body weight of 40 kg or greater received 20 mg every other week. Patients weighing less than 40 kg received 10 mg every other week (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.04.046]).
At week 12, patients who were nonresponders, defined as a change in PCDAI of less than 15 points, or who had a flare were switched to weekly dosing at the same dose. If at 8 weeks after increasing the frequency, patients were still nonresponders, they transitioned to open-label, high-dose therapy according to their weight.
Overall, 155 patients (82.4%) responded to induction (a PCDAI decrease of 15 or more points from baseline), and 52 patients (27.7%) were in clinical remission at the end of the 4-week induction period. At week 26, 33.5% of patients were in clinical remission, wrote the authors.
"A numerically higher proportion of patients in the high-dose adalimumab group were in clinical remission and clinical response compared with the low-dose group, but the differences did not achieve statistical significance," they added.
Looking at safety, the authors noted that 124 patients (66.0%) completed the entire 26-week study. The most common reasons for dropping out of the study were lack of efficacy and adverse events.
"In the open-label induction period, 101/192 (52.6%) of patients reported treatment-emergent adverse events, including two serious infections (one Yersinia infection and one viral infection; both events resolved and the patients completed the study)," wrote the authors. Eight serious infections were observed during the double-blind period.
"There were no cases of malignancy, congestive heart failure, demyelinating disease, lupus-like syndrome, or tuberculosis, and no deaths," they added. "No new safety signals were identified in this study."
Dr. Hyams pointed out that the lack of a placebo in this study is a potential limitation. However, "The design was considered appropriate for a pediatric trial because of ethical considerations after the principal evidence of efficacy had been established in adult patients with moderate to severe CD," he wrote.
The study was funded by Abbott Laboratories, maker of adalimumab. Several authors were also employees of Abbott, and several (including Dr. Hyams) disclosed financial relationships with Abbott as well as other pharmaceutical companies, including the makers of biologics.