SAN DIEGO, CA—Adding infliximab to standard intravenous immunoglobulin (IVIG) to reduce inflammation in acute Kawasaki disease (KD) is safe in children, even those younger than 1 year of age, according to a phase 3 randomized trial presented at IDWeek 2012.

Children receiving infliximab, a chimeric anti-TNFα monoclonal antibody, had less inflammation and fewer days of fever; however, no measurable effect on treatment resistance or rates of coronary artery outcome vs the placebo arm were observed, noted Adriana H. Tremoulet, MD, MAS, of Rady Children’s Hospital San Diego, and the University of California, San Diego, La Jolla, CA.

Between March 2009 and August 2012, the study randomized 196 children 4 weeks to 17 years of age with acute KD to infliximab (single dose 5mg/kg) plus standard therapy (IVIG 2g/kg) or IVIG 2g/kg alone. All subjects were treated with the same brand of IVIG and premedicated with acetaminophen and diphenhydramine. Follow-up occurred at 2 and 5 weeks.

The primary outcome measure was difference in rates of treatment resistance—defined as a fever ≥38.0°C 36 hours to 7 days after the end of the first IVIG infusion—between the two arms.

Randomization was stratified by age (<1 year and ≥1 year), sex, and study center. Patients were excluded if they were afebrile ≥48 hours at screening or had a history of tuberculosis. Baseline characteristics between the two arms were similar, including age, illness day, percent male, and levels of pretreatment erythrocyte sedimentation rate, C-reactive protein, and white blood cell count.

Median age of the patients was 2.8 years; 20 were younger than 1 year of age, 11 of whom received infliximab. Day 6 was the median day of illness at enrollment. A total of 62% were male.

Among the two treatment arms, the primary outcome was identical: 11% of patients had a fever 36 hours to 7 days after the end of the first IVIG infusion. In the infliximab arm, median day of fever was 1 day and, in the placebo arm, 2 days (P<0.0001), Dr. Tremoulet reported. In the infliximab arm, none of the subjects had an IVIG infusion reaction, defined as chills or hypotension requiring temporary interruption of IVIG infusion, whereas 13 patients (13%) in the placebo group has this clinical effect.

Laboratory values, including absolute neutrophil count at 2 weeks, absolute lymphocyte count at 2 weeks, C-reactive protein (mg/dL) at 24 hours, and erythrocyte sedimentation rate at 2 weeks, were all statistically significant (infliximab vs. placebo). On echocardiogram, read by a single, blinded cardiologist, 72.9% of the patients in the infliximab were normal; 22.9% dilated, and 4.2%, an aneurysm. These results in the placebo arm were 72.2%, 21.7%, and 6.1%, respectively. No difference was observed in serious adverse events between arms.

These data suggest one of the roles of infliximab in KD may be as rescue therapy for IVIG resistance; however, efficacy remains to be proven. To evaluate inflammation, the investigators will now measure banked plasma/serum for alpha-1 antitrypsin, sTNFR-alpha 1 and 2, IL-10, IFN-gamma, MMP-9, IL-17, and sIL6r, Dr. Tremoulet said.