Background: Non-responders to primary intravenous immunoglobulin (IVIG) therapy with aspirin are at risk of coronary artery lesions in Kawasaki disease (KD). A randomized controlled trial (the RAISE study) indicated that prednisolone + primary IVIG improves responsiveness to treatment and coronary artery outcomes in non-responders to IVIG predicted on the basis of Kobayashi score. The present study aimed to verify the efficacy and safety of prednisolone + primary IVIG in predicted non-responders to IVIG.
Methods: We conducted a multicenter, prospective cohort study at 30 hospitals in Japan from July 2012. All KD patients received primary IVIG therapy (2 g/kg/24 h) and, if febrile at diagnosis, oral aspirin (30 mg/kg/day) and were stratified by Kobayashi score into non-responders (score [[Unable to Display Character: ]]5) and responders (score ≤4). The required sample size to reach statistical significance was 1,500 for KD patients and 500 for non-responders.
Results: We enrolled 868 patients with KD by the end of 2013, including 545 (63%) predicted responders and 323 (37%) predicted non-responders. Within the non-responder group, 256 patients received IVIG + prednisolone and 67 patients IVIG alone. The non-response rate to IVIG was significantly lower (17% vs. 55%, p<0.001) and the incidence of coronary artery lesions (Japanese criteria; 5% vs. 11%, p=0.06) non-significantly lower in the IVIG + prednisolone group than the IVIG alone group. These results are similar to those of the RAISE study (non-response rate of 13% and coronary artery lesion rate in non-responders of 3%). There were 10 severe adverse events (i.e., aseptic meningitis 2, liver dysfunction 2, anaphylaxis 1, hypertension 1, ventricular tachycardia 1, bacteremia 1, drug eruption 1, and gait disorder 1) and no significant between-group difference in event rate.
Conclusion: Like the RAISE study, our study suggests that prednisolone added to IVIG therapy with oral aspirin reduces the non-response rate and incidence of coronary artery lesions in predicted non-responders to IVIG with KD.