However, researchers at IDWeek 2012 said that although the drug showed a biological and a clinical effect during a phase III study, it did not meet the primary efficacy outcome.
Researchers at IDWeek 2012 show that infliximab is safe for the treatment of Kawasaki disease. However, although the drug showed a biological and a clinical effect during a phase III study, it did not meet the primary efficacy outcome.
A phase III clinical trial that assessed the safety and efficacy of infliximab for the treatment of Kawaski disease in children failed to meet its primary outcome but did provide valuable safety data for future trials, according to a doctor involved in the study who presented results at IDWeek 2012, the first joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), HIV Medicine Association (HIVMA), and Pediatric Infectious Diseases Society (PIDS).
“We showed a biological and a clinical effect, but we did not meet our primary outcome, said Adriana Tremoulet, MD, of the Kawasaki Disease Research Center at Rady Children’s Hospital in San Diego. Infliximab did not meet the trial’s primary outcome because there was no measurable effect on treatment resistance, Tremoulet said.
Kawasaki disease is characterized by inflammation of blood vessels throughout the body that, if left untreated, can lead to heart damage. When children with the disease are treated with a standard intravenous therapy of immunoglobulin (IVIG) and aspirin, some will continue to have persistent fever that increases their risk of heart complications, said Tremoulet. The randomized, double-blind, placebo-controlled trial added a single dose of 5 mg/kg infliximab to standard therapy.
It took three years to enroll 196 children who had acute Kawasaki disease in the two-center study at Rady Children’s Hospital in San Diego and Nationwide Children's Hospital in Ohio. Children ranging in ages 1 month to 17 years, including 11 infants, took part in the trial that got underway earlier this year.
Study data indicates the drug was well tolerated and there were no serious adverse events related to the infliximab infusion, even among the 11 infants who were part of the trial, Tremoulet said. Lab results were similar between the treated children and those given placebo, she said.
Results indicated a decrease in inflammation and a drop in the number of days with a fever among the children who received active drug. However, “with our current data, it doesn’t change how we treat all children with Kawaski disease,” Tremoulet said.
Nevertheless, the safety data is “really critical” because of past concerns about giving infliximab, a monoclonal antibody, to babies, said Tremoulet. She noted that prolonged use can lead to resurgence of tuberculosis.
“Really, I think the safety profile of this treatment approach is now very, very solid,” she said. “Although we may not use it for primary therapy, it is certainly safe to use as rescue therapy” given to children when the first dose of IVIG fails and a fever persists.
In light of these results, Tremoulet said that it may be time to step away from past study designs that focused on the general population of children with the disease in favor of follow up studies with children whose conditions are more criticial. “That may be too much of a mix and we need to focus on the kids that are at higher risk and are the ones with heart disease,” she said.
Tremoulet said a large percentage of children have heart complications within a week of disease symptoms. “It doesn’t happen later it happens now,” she said. “So if we identify those kids then those are the kids that we can then go ahead and treat and add to their treatment.”