Multiple recent FDA approvals in pediatric rheumatology overcome ‘delayed’ trials
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SAN DIEGO — The recent approvals of belimumab, golimumab, tofacitinib, secukinumab and ustekinumab in children with rheumatic diseases, all within the past 4 years, have changed the landscape in pediatric rheumatology, noted a speaker here.
“Pediatric indications are always delayed,” Hermine Brunner, MD, MSc, MBA, of the University of Cincinnati and Cincinnati Children’s Hospital Medical Center, told attendees at the 2023 Congress of Clinical Rheumatology West. “This makes it even more difficult to treat children with arthritis.”
Part of the reason for the delay is that clinical trials in pediatric patients can only begin after studies in adult patients have reached phase 3, according to Brunner. Also, it must be determined whether the candidate medication is “safe and useful for children,” she added.
“Automatically, we are behind,” Brunner said.
In addition, if the candidate medication is determined to be “not feasible” in children, then it will not move forward for pediatric approval.
“This is one of the reasons why only a subset of medications that are approved for adults with arthritis or other autoimmune diseases make their way to pediatrics,” Brunner said.
Despite these hurdles, several recent approvals are providing rheumatologists with more options for treating pediatric populations.
In July 2022, belimumab (Benlysta, GlaxoSmithKline) became the first drug approved by the FDA for children with lupus nephritis, following its 2019 approval for pediatric systemic lupus erythematosus. Brunner highlighted data from the PLUTO trial, which included pediatric patients with SLE.
“The efficacy in children was similar as adults,” she said. “Children also experience a similarly robust reduction severe flare as compared with the adults.”
However, subcutaneous belimumab is not yet available for children.
Meanwhile, children with polyarticular juvenile idiopathic arthritis can now be treated on-label with the TNF inhibitor golimumab (Simponi Aria, Janssen), following an FDA approval in September 2020. However, the subcutaneous formulation of golimumab was not approved for children because it failed to meet its primary endpoint, according to Brunner.
That said, the study that led to approval of the 80 mg/m2 formulation should give rheumatologists a strong option for treating their patients, she added.
“The physicians thought the patient was better and the parents thought the patient was better,” Brunner said.
Patients with polyarticular JIA may also be treated on-label with tofacitinib (Xeljanz, Pfizer). The FDA made tofacitinib the first JAK inhibitor approved for polyarticular course JIA in another September 2020 decision.
Brunner encouraged attendees to review the safety profile of the medication in adults, describing the pediatric safety profile as comparable. The extended-release preparation is not yet approved for children.
Regarding secukinumab (Cosentyx, Novartis), open-label study results have demonstrated that pediatric patients with PsA improved “as early as 1 week” after receiving the first injection, according to Brunner. The trend continued in the double-blinded portion of the study, which contributed to its December 2021 FDA approval in this population.
“In essence, secukinumab injection led to reduction in flare of 72%,” Brunner said.
Lastly, the FDA approval of ustekinumab (Stelara, Janssen) for juvenile PsA, announced in August 2022, came as a result of extrapolation of adult data rather than from a specifically pediatric study, according to Brunner. The approval is for children aged older than 6 years.
“Basically, the patient is getting a starter dose and then 3 months of Stelara,” Brunner said.
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Brunner H. What’s New in Pediatric Rheumatology? Presented at The Congress of Clinical Rheumatology West; Sept. 7-10, 2023 (hybrid meeting).
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