A Retrospective Cohort Study of Intravenous Immunoglobulin Therapy in the Acute Phase of Kawasaki Disease: The Earlier, the Better?

Abstract

Background: Although intravenous immunoglobulin (IVIG) is expected to prevent coronary artery abnormalities of Kawasaki disease (KD) in the acute phase, the timing and effectiveness of IVIG remain to be determined. The association of timing of IVIG administration in KD patients with coronary artery abnormalities is evaluated in this cohort study.

Methods: We systematically studied KD patients from two participating institutions between 2015 and 2017. To reveal the effectiveness of IVIG treatment, these patients were classified into four groups regarding the time of IVIG treatment. Primary outcome was coronary artery abnormalities by echo at diagnosis and 12 months follow-up; secondary outcomes included inflammatory markers.

Results: A total of 1281 patients were included in this study. The best time of IVIG treatment cut-off values in 12 months follow-up for predicting coronary artery abnormalities was days 7.5 of illness onset. According to the best time of IVIG treatment cut-off values, all patients were classified into 4 groups. Group 1 was defined as earlier IVIG treatment administration on days ≤4 of the illness (n = 77). Group 2 was defined with days 5-7 (n = 817), group 3 with days 8-10 (n = 249), group 4 with days >10 (n = 138). A greater proportion of IVIG-resistant KD patients were group 4 than the other three groups, and there were significant differences (p < 0.05). The incidence of coronary artery lesions (CALs) and coronary artery aneurysms (CAAs) in group 3 and group 4 was higher than that in group 1 (p < 0.05) and group 2 (p < 0.05) during a 12-month follow-up. Additionally, the incidence of CALs in group 1 was higher than that in group 2 but without statistical significance (p > 0.05). The OR was significantly higher for those who started IVIG administration more than 7 days from the onset was positively associated with the occurrence of CALs (OR, 5.3; 95% CI, 2.0-13.9) and CAAs (OR, 13.5; 95% CI, 2.9-14.1) 12 months after initial onset. Multivariate regression revealed that the timing of IVIG treatment and IVIG-resistance was independent risk factors of CALs.

Conclusions: IVIG treatment less than 7 days after illness onset are found to be sufficient for preventing developing coronary artery abnormalities in KD patients. Earlier IVIG treatment administration within 4 days may not increase the higher incidence of coronary artery abnormalities and IVIG resistance (Chinese Clinical Trial Registry:ChiCTR1800015800).

Figure 1

The time of IVIG treatment and the patients with coronary artery abnormalities due to Kawasaki disease in 12 months follow-up. Shown are receiver-operating-characteristic (ROC) curves for days of illness with IVIG treatment and coronary artery abnormalities in 12 months follow-up with KD cohorts. The best days of IVIG treatment cut-off values for predicting coronary artery abnormalities were 7.5 days. The area under the curve (AUC) was 0.80 (95% CI, 0.76 to 0.84).