The use of steroid therapy in Kawasaki disease (KD) has a long and complicated history. A recent well-designed randomised controlled trial (RCT) provides strong evidence that the addition of a prolonged course of steroids to the standard treatment of intravenous immunoglobulin (IVIG) and aspirin significantly improves coronary artery (CA) outcomes in Japanese children at high risk of IVIG non-response. Of 2014 KD patients, only the 248 (12%) at high risk of IVIG failure were included, based on the authors' severity score. The incidence of CA abnormalities during the study period was 4/121 (3%) in the steroid treatment group and 28/121 (23%) in the standard treatment group (P < 0.0001); number needed to treat (NNT) to prevent CA abnormalities was five. At week 4, the incidence of CA abnormalities was 4/120 (3%) in the steroid treatment group and 15/120 (13%) in the standard treatment group (P = 0.014); NNT was 10.
These are impressive results. Other findings also suggest that steroids may be of benefit in those at highest risk of IVIG non-response. A RCT of adjunctive primary steroids in an unselected KD population in the USA failed to show any benefit on CA outcomes (albeit with a shorter and different steroid regimen to the Japanese study). However, a post hoc subgroup analysis of those who subsequently required IVIG retreatment suggested a significant beneficial effect on CA outcomes.
Caution is warranted in generalising the RAISE study findings as there are important differences between the study population and KD patients outside Japan. Crucially, Japanese risk-scoring systems, including that used in the RAISE study, have reasonable specificity but unacceptably low sensitivity in non-Japanese populations. There are other potentially important differences in the RAISE study: treatment was commenced at a median of day 4, which is earlier than is usual in Australia and other non-Japanese populations. Finally, the steroid regimen is partly intravenous and relatively prolonged, potentially increasing inpatient costs.
The development of severity scores predictive of IVIG non-response in non-Japanese patients would allow further studies of adjunctive regimens, including steroids, in those with the most severe KD.