40 - RISK FACTORS FOR CORONARY ARTERY ABNORMALITIES AND RESISTANCE TO IMMUNOGLOBULIN PLUS CICLOSPORIN A THERAPY IN SEVERE KAWASAKI DISEASE: SUBANALYSIS OF THE KAICA TRIAL

Background: To investigate risk factors for coronary arterial abnormalities (CAAs) and resistance to treatment in patients with KD receiving IVIG plus ciclosporin A (CsA) as the first-line treatment, we performed a subanalysis of baseline data of participants in the KAICA trial, a controlled, phase 3, randomized, open-label, blinded-endpoints trial (JMA-ILA00174).

Methods: All data of the patients enrolled in the KAICA trial, who had high predictive scores for IVIG unresponsiveness (Gunma score ≥5) at diagnosis and had been randomly assigned to either IVIG (2 g/kg/24 h) plus CsA (5 mg/kg/day for 5 days) (n = 86) or IVIG alone (n = 87), were subjected to this study. CAA was defined by a Z score ≥2.5 observed within 4 weeks after treatment initiation. Baseline data including basic characteristics, vital signs, clinical data before any treatments and genotypes of KD susceptibility genes (ITPKC and CASP3 SNPs) were compared between subgroups of patients for CAA or treatment response for each treatment group. Backward-forward stepwise logistic regression analyses were performed.

Results: In both treatment groups, 19 patients had CAAs, and the mean pre-Z-max, defined as the maximum among Z scores on four coronary artery branches before treatment, was significantly higher in those with CAA (p < 0.0001). Backward-forward stepwise multivariate logistic regression analyses revealed that pre-Z-max was the only significant predicted factor in IVIG plus CsA treatment group [odds ratio (OR) = 17.0]. As for the first-line treatment response, in the IVIG plus CsA group, treatment-resistant patients had a higher total bilirubin, higher ALT, and lower Na. Meanwhile, in the IVIG group, treatment-resistant patients had a higher Neutrophil % than treatment responders. In backward-forward stepwise multivariate logistic regression, treatment-resistant patients had a lower lymphocyte % and higher body temperature in both treatment groups. High serum total bilirubin levels were associated with a resistance to IVIG plus CsA treatment (OR =2.34), which were not associated with a response to IVIG alone. There were no significant differences in the other demographic, physical, hematological, and biochemical data or in the frequencies of risk allele carriers of ITPKC and CASP3 SNPs between those with and without CAAs in either group.

Conclusion: Coronary artery enlargement before treatment is a major determinant of CAA even in KD patients treated with initial IVIG treatment intensified by addition of CsA. Baseline serum total bilirubin level was a risk factor associated with resistance to IVIG plus CsA.