Procalcitonin levels predicting the infliximab response of immunoglobulin resistant Kawasaki disease

Abstract

To search the predictive factors of infliximab resistance in intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) patients. Study design. Twenty-seven patients with KD who received infliximab after 4-5 g/kg of IVIG therapy from 2013 to 2015 were consecutively recruited in this study. They were divided into two groups: patients who responded to infliximab (infliximab-responsive group, n = 15) and patients who required additional therapy for the disease control (infliximab-resistant group, n = 12). We analyzed the clinical and laboratory parameters just before the infliximab treatment including serum levels of procalcitonin and cytokines with respect to the infliximab response. Results: Serum procalcitonin concentration (P = 0.017), neutrophils to lymphocytes ratio (P = 0.013), and % neutrophils (P = 0.004) were higher, and serum sodium concentration (P = 0.017) was lower in infliximabresistant group than those of infliximab-responsive group, respectively. Multivariate logistic regression analyses indicated that higher procalcitonin concentration (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.00-5.00, P = 0.046) and lower sodium levels (OR 0.64, 95% CI 0.32-1.00, P = 0.047), but not other variables, were associated with infliximab-resistance. Serum procalcitonin concentrations positively correlated with the serum levels of interleukin-6, soluble tumor necrosis factor receptor type 1 and type 2, respectively. Analyses of the receiver operating characteristic (ROC) curve showed that the cutoff value of procalcitonin 2.0 ng/ml had 58.3% of sensitivity and 93.3% of specificity. ROC analysis yielded an area under the curve (AUC) of 0.739 to predict infliximab-resistance. Conclusion: Serum procalcitonin might be an effective biomarker to predict infliximab resistance in severe KD patients who are refractory to IVIG treatment.

Prediction of repeated intravenous immunoglobulin resistance in children with Kawasaki disease

“…The pre-IVIG regression model showed PCT > 1.81ng/ml before initial IVIG treatment was an independent predictor of repeated IVIG resistance in KD. Comparing with CRP as well as the other inflammation indicator, PCT may reflect uncontrollable hypercytokinemia faster along with the involvement of TNF-α signaling pathway in KD, based on the characteristics of early elevation and shorter half time [23]. Pre-IVIG NT-proBNP yielded the highest specificity, but it failed to predict repeated IVIG resistance, the reason may be due to relatively low sensitivity of 45.00 %.…”

Combination of S100A12/TLR2 signaling molecules and clinical indicators in a new predictive model for IVIG-resistant Kawasaki disease

“…Many studies have suggested using PCT levels to predict the occurrence of IVIG-resistant KD. Research investigations by Yoshikawa et al 36 , Dominguez et al 37 , Nakashima et al 38 , and Nakamura et al 39 demonstrated that the critical value of PCT for predicting IVIG-resistant KD ranged from 0.5 to 4.3 ng/mL, confirming the crucial role of PCT in drug resistance in KD. In support of this finding, the present study also found that PCT level might serve as a predictor of IVIG-resistant KD at a critical value of 0.845 ng/mL, consistent with the previous studies.…”

Current knowledge of TNF-α monoclonal antibody infliximab in treating Kawasaki disease: a comprehensive review

“…Nakashima et al. ( 71 ) aimed to develop a clinical prediction model for IFX responsiveness in patients with IVIG-refractory KD. Several studies ( 72 , 73 ) proposed procalcitonin as a biomarker to predict the severity of KD.…”