From the Journals

Various adjuncts to IVIg help treat coronary artery abnormalities in pediatric Kawasaki disease



Two studies published in Pediatrics add new information on potential therapies as adjuncts to intravenous immunoglobulin to treat coronary artery abnormalities in pediatric Kawasaki disease patients.

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In the phase 3, randomized, placebo-controlled EATAK (Etanercept as Adjunctive Treatment for Acute Kawasaki Disease) trial, Michael A. Portman, MD, and his colleagues examine the effects of adding etanercept to intravenous immunoglobulin (IVIg) to study IVIg resistance in children with Kawasaki disease.

The researchers enrolled 201 participants from eight pediatric centers who received an IVIg infusion followed immediately by either subcutaneous etanercept (0.8 mg/kg; n = 100) or placebo (n = 101) and then received two more weekly doses. They performed a subgroup analysis based on age, gender, and race. The participants were between 2 months and 18 years old with incomplete (10 etanercept, 12 placebo) or complete Kawasaki disease as determined by American Heart Association criteria and American Academy of Pediatrics 2004 criteria.

Of the 35 patients who showed IVIg resistance and received a second dose, the IVIg resistance rate for participants receiving etanercept was 13%, compared with 22% in the placebo group. The overall odds ratio for IVIg resistance was 0.54. While etanercept did not lower the rate of IVIg resistance in participants younger than 1 year old, it significantly reduced IVIg resistance in those older than 1 year.

IVIg fever response significantly differed by race, which ranged from Asian participants having a 7% resistance rate to African Americans having a resistance rate of 57%.

Forty-five of all participants had greater than 2.5 baseline coronary z scores, 23 in the etanercept group and 22 in the placebo group. While etanercept reduced change in coronary z score among participants with baseline dilation (P = .04) and without baseline dilation (P = .001), there was no improvement among participants in the placebo group. Etanercept additionally reduced progression of dilation, compared with the placebo group (P = .03). The researchers noted etanercept had a good safety profile, and there were no differences between the groups receiving the intervention or placebo.

“With these considerations, EATAK results reveal a reasonable risk/benefit profile for etanercept,” Dr. Portman of Seattle Children’s Research Institute, and his colleagues concluded. “Future clinical trials, conducted in these subgroups or stratified according to patient demographics or genotypes, will be necessary to validate our findings before wide clinical adoption.”

In a second study, Audrey Dionne, MD, of Boston Children’s Hospital, and her colleagues explored how corticosteroids or infliximab together with IVIg can reduce the progression of coronary artery aneurysms (CAA). They performed a retrospective study of 121 children (73% boys; median age, 3 years) with Kawasaki disease and CAA at three different centers who received corticosteroid and IVIg therapy (n = 30), infliximab and IVIg therapy (n = 58), or IVIg alone (n = 33). The children had a coronary z score greater than or equal to 2.5 and less than 10, and there were no significant differences between median z scores among the treatment groups (P = .39).

The researchers found that patients who received corticosteroids with IVIg therapy were protected against coronary size progression (coefficient, −1.31); in addition, those patients who received infliximab and IVIg therapy were protected against coronary size progression at follow-up (coefficient, −1.07), the researchers said. Those on placebo were not.

“Our data suggest that adjunctive treatment at the time of diagnosis may be beneficial in patients with CAA,” Dr. Dionne and colleagues concluded. “Future adequately powered, prospective randomized trials are needed to determine the best adjunctive treatment of patients with KD [Kawasaki disease] who present with coronary changes.”

The EATAK trial was funded by the Food and Drug Administration Office of Orphan Product Development, Amgen, and the National Institutes of Health. Dr. Portman and colleagues reported no relevant financial disclosures. The study from Dionne et al. received funding from the McCance Family Foundation and the Vella Fund. One of the authors reported being a paid expert witness for missed diagnoses of Kawasaki disease, which was unrelated to the study. The other authors said they had no conflicts of interest.

SOURCES: Portman MA et al. Pediatrics. 2019. doi: 10.1542/peds.2018-3675; Dionne A et al. Pediatrics. 2019. doi: 10.1542/peds.2018-3341.

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