Adalimumab has received approval from the Food and Drug Administration for use in pediatric patients aged 5 years and older with moderately to severely active ulcerative colitis (UC), according to a press release from manufacturer AbbVie.
Approval was based on data from the phase 3 ENVISION 1 randomized, double-blind study (NCT02065557) in which 60% of patients receiving the higher induction dose showed clinical remission according to Partial May Score (PMS) at 8 weeks, 45% of whom were in remission according to Full Mayo Score (FMS) at 1 year. The approval means that children with UC and their families have the option of a subcutaneous biologic that can be administered at home.
In the ENVISION 1 study, clinical remission was defined as a PMS (based on stool frequency, rectal bleeding, and physician's global assessment) ranging from 0 to 3 at the end of the 8-week induction period or FMS (which adds endoscopy) at the end of 52 weeks as less than or equal to 2 points total, with no individual subscore greater than 1. The study included children aged 4-17 years with active UC who were randomized to a low-dose or high-dose group.
"Through week 8, patients in both dosage groups received 2.4 mg/kg (maximum of 160 mg) at week 0, 1.2 mg/kg (maximum of 80 mg) at week 2, and 0.6 mg/kg (maximum of 40 mg) at weeks 4 and 6. The higher-dosage group also received an additional dosage of 2.4 mg/kg (maximum of 160 mg) at week 1," according to the company press release. Between weeks 8 and 52, patients received double-blind placebo or 0.6 mg/kg adalimumab (maximum of 40 mg) every other week (maintenance standard dose) or every week (maintenance high dose).
No new adalimumab safety signals were noted in the study; headache and worsening UC were the most frequently reported treatment-emergent adverse events, and 22.6% of patients experienced a serious adverse event. "No deaths, malignancies, active tuberculosis or demyelinating disease were observed in this study," according to the company. Full prescribing information can be found on the FDA website.
Approval Expands Options
"The number of FDA-approved biologics to treat pediatric UC has been limited," said Atsushi Sakuraba, MD, PhD, an inflammatory bowel disease specialist at the University of Chicago, in an interview. "Infliximab is approved for pediatric UC and CD [Crohn's disease], but adalimumab was only approved for CD in pediatric patients, and vedolizumab and ustekinumab are approved for neither UC nor CD in pediatric patients," he said. "Thus, the addition of adalimumab as a treatment option for pediatric UC is of great benefit for pediatricians and patients."
The approval will impact clinical practice in several ways, Sakuraba said. "Adalimumab may be used for those who lose response to infliximab, but may also be used as a first-line biologic because it is self-injectable," he emphasized. Given that adalimumab is already in use for pediatric patients with Crohn's disease, Sakuraba said he does not see any barriers to implementation of its use for children with UC.
In addition, "the potential for better disease control, reduction of disease-related complications, and improved quality of life outweighs the risk of adverse reactions," Sakuraba said. "The news of no new safety concern in the 52-week study period further supports the safety of biologic treatment in pediatric patients," he added.
As for additional research: "It remains to be determined whether combination therapy with an immunomodulator would be more effective than monotherapy, and also whether there are any additional risks of adverse events with the addition of immunomodulators such as long-term risk of malignancy, especially lymphoproliferative disorders," Sakuraba noted. "Therapeutic options for pediatric [inflammatory bowel disease] are limited and lagging, compared to adult patients, so studies of non-TNF [tumor necrosis factor] biologics such vedolizumab and ustekinumab are also awaited," he said.
Sakuraba had no financial conflicts to disclose.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
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Cite this: Adalimumab Earns FDA Approval for Ulcerative Colitis in Children - Medscape - Mar 03, 2021.