GAITHERSBURG, Maryland—The US Food and Drug Administration (FDA) arthritis advisory committee voted 15-1 on Wednesday to recommend approval of celecoxib (Celebrex®, Pfizer) for the treatment of juvenile rheumatoid arthritis (JRA).¹ The FDA isn't required to follow the panel's advice but usually does, and celecoxib is widely expected to join naproxen as an option for physicians who treat JRA.

The 16-member panel unanimously agreed that celecoxib is effective in JRA, however, they are divided over safety issues. Pfizer supported the request for a JRA indication with results of a 6-month noninferiority study that showed celecoxib was as effective as naproxen in treating JRA patients.

The safety debate focused on the cardiovascular (CV) and thromboembolic risks, which have been seen in adults taking selective cyclooxygenase (COX)-2 inhibitors. Pfizer's pediatric safety data extend only 6 months and include only 242 children. Postmarketing spontaneous adverse events reports are not available, and this agent was previously not approved for any pediatric use.

"No cardiovascular or thromboembolic events have been seen in the study of celecoxib in JRA, but it is nonetheless critical to consider the CV risk that children would have if they receive celecoxib or other NSAIDs long term," said Jeffrey Siegel, MD, medical team leader for the division of anesthesia, analgesia and rheumatology at the FDA's Center for Drug Evaluation and Research in Bethesda, Maryland.

Panel calls for registry to track long-term safety

To address the paucity safety data, the panel asked Pfizer to create a registry of JRA patients so it could further track safety of celecoxib in children with JRA.

Panel member Richard L. Gorman, MD, a pediatrician at Pediatric Partners in Ellicott City, Maryland, said that "a registry sounds like a great idea, but I don't think it should sit inside a pharmaceutical company. A simple registry might not give good information at all, and may give bad information at worst."

Panel member Christy Sandborg, MD, professor and chief of pediatric rheumatology at Stanford University School of Medicine in California, agreed. She said that the registry concept must be broad enough to pick up any CV signals in this population.

"It would not be helpful to follow 200 children," Dr. Sandborg contended. "We really need a wide-ranging, very large effort to be able to pick this thing up."

Pediatric Rheumatologists Need More Options for JRA

"We have no good data giving us the relative risks of celecoxib [versus] placebo. As best one can tell from all of the data provided, celecoxib itself doesn't seem to have a risk over NSAIDs," Kathleen A. Haines, MD, the section chief of pediatric immunology, pediatric rheumatology and immunology at Hackensack University Medical Center, in New Jersey, told CIAOMed. Dr. Haines also addressed the panel during the hearing.

Lauding the panel's decision, Dr. Haines said, "I was concerned they would be so worried about something in the future that they would forget that kids need these medications today, and the relative risks don't look higher than for naproxen, which is what kids are taking today."

An advantage of celecoxib, unlike naproxen, is that it does not inhibit platelet aggregation, she said.

Moreover, children have practical needs that adults do not, Dr. Haines noted. "They need medications with simple dosing schedules, because children go to school and most schools do not allow children to take medication or have nurses to distribute medications during the day," she said. Like naproxen, celecoxib is given twice daily.

Panel members and presenters also emphasized gastrointestinal safety as an important consideration, noting it as an issue in children as well as in adult patients; that children may experience loss of appetite, growth failure, and NSAID-induced gastritis with traditional NSAIDs. Although children may respond to proton pump inhibitors given with traditional NSAIDs for gastroprotection, panel members expressed concern about exposing young arthritis patients to two different classes of drugs with the potential for combined side effects.

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