SAN DIEGO – Intensifying primary therapy for Kawasaki disease by adding infliximab, an antibody to tumor necrosis factor–alpha, improves certain outcomes but not others, finds a phase III randomized trial reported at IDWeek.
The 196 children studied, all of whom were given intravenous immunoglobulin (IVIG), had a 22% lower erythrocyte sedimentation rate and a 50% or 1-day shorter duration of fever if they also received infliximab. But there was no effect on the rate of treatment resistance (the trial’s primary outcome) or the development of coronary aneurysms.
Susan London/IMNG Medical Media
Dr. Adriana Tremoulet
The findings "really beg the question of what is the role of infliximab in Kawasaki disease," commented Dr. Adriana Tremoulet, a pediatric infectious disease specialist at the Rady Children’s Hospital in San Diego.
"For primary therapy, what I would say is that it’s safe to use. The data do suggest a biological and clinical effect, but there is no reduction in treatment resistance or coronary artery abnormalities that we have proved to date," she said. "In addition, many of you may wonder what we will do about rescue therapy for IVIG resistance. Again, I think we definitely have enough data to say that it’s a safe alternative to a second IVIG [treatment], but that the efficacy is unproved at this time."
In the trial, children aged 4 weeks to 7 years with acute Kawasaki disease were randomized to infliximab (Remicade, 5 mg/kg) or placebo, each followed by IVIG (2 g/kg).
The children had a median age of 2.8 years (10% were younger than 1 year), and 62% were boys. The median duration of illness at trial enrollment was 6 days, according to data reported at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
Results showed that, compared with their counterparts in the placebo group, patients in the infliximab group had less inflammation, as indicated by lower levels of C-reactive protein at 24 hours (4.1 vs. 5.3 mg/dL; P = .01) and a lower absolute neutrophil count (2,271 mm3 vs. 2,706 mm3; P = .001) and erythrocyte sedimentation rate (36 vs. 46; P = .003) at 2 weeks.
On the other hand, the infliximab group had a higher absolute lymphocyte count at 2 weeks (3,630 vs. 2,996; P = .002). "This is something we do see in children as they are going from an acute to a subacute change in their illness," Dr. Tremoulet commented.
The median duration of fever after enrollment was 1 day in the infliximab group, compared with 2 days in the placebo group (P less than .0001). The rate of IVIG infusion reactions, despite premedication, was also lower in the infliximab group (0% vs. 13%).
However, the rate of treatment resistance – defined as presence of fever between 36 hours and 7 days after the end of the first IVIG infusion – did not differ significantly between the groups (11% vs. 11%). And the same was true of the rate of coronary aneurysms detected by echocardiography (4% vs. 6%).
"It was safe to use infliximab even in children less than 1 year of age. Infliximab was tolerated well, even in the infants," Dr. Tremoulet maintained. Rates of serious adverse did not differ between treatment groups.
The investigators are now evaluating levels of various inflammatory cytokines, such as alpha1-antitrypsin and tumor necrosis factor–receptors, to better understand the biological effects of infliximab in this population, she noted.
Dr. Tremoulet disclosed no relevant conflicts of interest. Infliximab was donated by Janssen Biotech, the manufacturer.