Intravenous Immunoglobulin Treatment Failure Research Articles

Corticosteroids Added to Initial Intravenous Immunoglobulin Treatment for the Prevention of Coronary Artery Abnormalities in High-Risk Patients With Kawasaki Disease.

BACKGROUNDRandomized controlled trials previously provided different conclusions about the superiority of adding corticosteroids to initial intravenous immunoglobulin treatment for the prevention of coronary artery abnormalities in patients with Kawasaki disease (KD). To further assess this issue, we analyzed large‐scale data from nationwide KD surveys in Japan, where combination treatment (corticosteroids added to initial standard intravenous immunoglobulin treatment) has become commonly used for patients at high risk for KD.METHODS AND RESULTSStandard intravenous immunoglobulin treatment and combination treatment were compared using data from time periods with and without combination treatment. Outcome measures were coronary artery abnormalities and initial intravenous immunoglobulin treatment failure. Hospitals where ≥20% of patients received combination treatment were identified, and treatment and control groups were selected via matching by age, sex, illness day at initial treatment, and KD recurrence. Matched group selection and subsequent analyses were conducted 1000 times to minimize sampling bias and potential confounders (bootstrapping). From 115 hospitals, 1593 patients with KD in the treatment group and 1593 controls were selected for each of the 1000 sample iterations. The median proportion of patients who developed coronary artery abnormalities among the treatment group and controls were 4.6% (95% CI, 3.8%–5.8%) and 8.8% (95% CI, 7.5%–10.0%), respectively: an estimated risk ratio of 0.53 (0.41–0.67). A median of 14.1% (95% CI, 12.4%–15.9%) of the patients in the treatment group and 21.7% (95% CI, 19.8%–23.4%) in the controls had treatment failure: an estimated risk ratio of 0.65 (0.56―0.75).CONCLUSIONSCombination treatment reduced coronary artery abnormality risk by an estimated 47% and treatment failure by 35%. Multiple‐dose corticosteroids may provide benefit in selected patients at high risk for KD.

Infliximab Treatment for Intravenous Immunoglobulin-resistant Kawasaki Disease: a Multicenter Study in Korea.

Background and ObjectivesWe investigated the status of infliximab use in intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) patients and the incidence of coronary artery aneurysms (CAAs) according to treatment regimens.MethodsBetween March 2010 and February 2017, 16 hospitals participated in this study. A total of 102 (32.3±19.9 months, 72 males) who received infliximab at any time after first IVIG treatment failure were enrolled. Data were retrospectively collected using a questionnaire.ResultsSubjects were divided into two groups according to the timing of infliximab administration. Early treatment (group 1) had shorter fever duration (10.5±4.4 days) until infliximab infusion than that in late treatment (group 2) (16.4±4.5 days; p<0.001). We investigated the response rate to infliximab and the incidence of significant CAA (z-score >5). Overall response rate to infliximab was 89/102 (87.3%) and the incidence of significant CAA was lower in group 1 than in group 2 (1/42 [2.4%] vs. 17/60 [28.3%], p<0.001).ConclusionsThis study suggests that the early administration of infliximab may reduce the incidence of significant CAA in patients with IVIG-resistant KD. However, further prospective randomized studies with larger sample sizes are required.

The Validity of a Scoring System in Predicting Intravenous Immunoglobulin Treatment Failure in Children With Kawasaki Disease

Background: Between 10 and 20% of children with Kawasaki disease (KD) will not respond to intravenous immunoglobulin (IVIG) treatment, and are prone to coronary abnormalities. A variety of predicting scoring systems, including the Kobayashi system, have been proposed, but have not yet been evaluated using Iranian patients. Objectives: To evaluate the Kobayashi scoring system with regard to predicting response to IVIG treatment in Iranian children. Patients and Methods: All patients who received a final diagnosis of KD at Aliasghar children’s hospital between 1982 and 2013, and who met the inclusion criteria, were enrolled in this retrospective cohort study. We excluded patients with missing data, abnormal echocardiographic finding on admission, late admission, atypical or afebrile cases, and those who had received an insufficient amount of IVIG. We compared demographic and echocardiographic data before IVIG, and within 7 days of treatment, as well as C reactive protein (CRP), sodium, aspartate aminotransferase, platelet levels, neutrophil percentage, age of patients, and duration of fever before IVIG administration, in treatment responders and non-responders. Results: Of the 141 cases, 97 patients met the criteria and were enrolled. Of these, 19 (19.6%) did not respond to IVIG. A total of 61.8% of patients were male, and the mean patient age was 36.9 months (SD = 32.1 months). Echocardiographic evaluation revealed early coronary involvement in 15.3% of patients, and coronary abnormalities were diagnosed in 10% of patients within the first 10 days of presentation and concurrent with their IVIG treatment. A between-groups comparison of quantitative CRP, absolute neutrophil count, and platelet count showed that platelet count alone was significantly higher in nonresponders (P = 0.04). With regard to items of Kobayashi scoring system, data were present for just 41 cases, but a significant difference between the two groups was shown, with the treatment-refractory group having a significantly higher score (P = 0.002). Receiver-operating characteristic curve analysis revealed that the optimum cut-off point for our population would be 2, which makes the sensitivity of the test equal to 75%, with a specificity of 60%. Conclusions: This preliminary study showed that patients with KD and a high Kobayashi score are at greater risk of being unresponsive to IVIG treatment. Further studies, preferably multicenter evaluations, are required in order to understand the exact application of various scoring systems in the management of people with KD in Iran.

Clinical characteristics and prediction of Kawasaki disease unresponsive to initial dose of intravenous immunoglobulin

Objective To determine the prediction and clinical characteristics of intravenous immunoglobulin (IVIG)treated Kawasaki disease (KD)failure in initial dose. Methods Retrospective analysis was performed with the clinical data of 111 children with KD.The patients were divided into sensitive group and unresponsive group according to initial effect of IVIG.The clinical manifestations, laboratory examination and radiological features of the children were compared.Logistic regression analysis was performed in significant different indicators to determine independent correlation factors.In order to seek the reference indexes which indicate unresponsive to IVIG, a receiver operating characteristic (ROC)curve was made, of which the diagnostic cut-off was nine independent correlation factors while grouping was made according to patients' different responses to IVIG. Results (1)There were 90 cases (81.1%)in effective group and 21 cases (18.9%)in unresponsive group.(2)Compared with the sensitive group, hyperpyrexia cases[66.7%(14/21 cases) vs 34.4%(31/90 cases), χ2=7.334, P=0.007] and the chances of coronary artery lesions [47.6%(10/21 cases) vs 23.3%(21/90 cases), χ2=4.989, P=0.026] were significantly higher in the unresponsive group.(3)Compared with the children administered twice with gamma globulin, the children of single-dose treatment significantly reduced the unresponsive probability [12.5%(9/72 cases) vs 30.8%(12/39 cases), χ2=5.504, P=0.019], and there was no difference in the chances of coronary artery lesions[23.6%(17/72 cases) vs 30.8%(12/39 cases), χ2=0.672, P=0.412]. (4)Comparing the sensitive group and the unresponsive group, the percentage of neutrophils count[(0.72±0.06) vs (0.76±0.04), t=-2.84, P=0.005], platelet counts [(352.38±42.18)×109/L vs (373.14±36.93)×109/L, t=-2.076, P=0.040]and C-reactive protein (CRP) [(74.38±12.92) mg/L vs (92.05±11.17) mg/L, t=-5.780, P=0.000] were significantly higher in the unresponsive group, but the level of serum albumin[(34.09±3.19) g/L vs (31.61±2.03) g/L, t=4.442, P=0.000] was lower.(5) Multivariate Logistic regression analysis indicated that the percentage increase of neutrophils count (P=0.018), CRP(P=0.000) increase and serum albumin(P=0.040) decrease were independent risk factors for unresponsive treatment with gamma globulin.(6)After the area under the ROC curve was calculated, the percentage of neutrophils count, CRP and serum albumin could be effective predictors to IVIG treatment failure in initial dose, and the critical values were 0.72, 78.5 mg/L and 33.11 g/L, respectively. Conclusions Treatment with IVIG for the first time may be ineffective in some situations such as the percentage of neutrophils count≥0.72, CRP≥78.5 mg/L or serum albumin≤33.11 g/L. Key words: Intravenous immunoglobulin; Kawasaki disease; Unresponsive; Clinical characteristic; Prediction

Erratum to: N-terminal Pro-Brain Natriuretic Peptide (NT proBNP) as a Predictive Indicator of Initial Intravenous Immunoglobulin Treatment Failure in Children With Kawasaki Disease: A Retrospective Study

Erratum to: N-terminal Pro-Brain Natriuretic Peptide (NT proBNP) as a Predictive Indicator of Initial Intravenous Immunoglobulin Treatment Failure in Children With Kawasaki Disease: A Retrospective Study

N-terminal Pro-Brain Natriuretic Peptide (NT proBNP) as a Predictive Indicator of Initial Intravenous Immunoglobulin Treatment Failure in Children With Kawasaki Disease: A Retrospective Study

Intravenous immunoglobulin (IVIG) administered in the acute stage of Kawasaki disease (KD) is the standard therapy. Few reports describe nonresponders to initial treatment with IVIG in KD, which remains the most consistent risk factor for coronary artery lesions (CALs). This study aimed to investigate whether the serum level of N-terminal pro-brain natriuretic peptide (NT-proBNP) can be a predictive indicator for identifying patients with KD at higher risk of IVIG treatment failure. In this study, 135 patients with a diagnosis of KD admitted for IVIG treatment were retrospectively enrolled for analysis. Of these 135 patients, 22 were nonresponders who received additional rescue therapy because they had an elevated body temperature 36 h after completion of initial IVIG treatment. The NT-proBNP concentration was significantly higher in the nonresponder group (2,465.36 ± 3,293.24 pg/mL) than in the responder group (942.38 ± 1,293.48 pg/mL) (p < 0.05). The optimal sensitivity and specificity cutoff point for predicted nonresponders was 1,093.00 pg/mL or higher. The sensitivity and specificity for prediction of IVIG response were respectively 70.0 and 76.5 %. The findings show that NT-proBNP is a helpful marker in determining patients at risk for not responding to initial IVIG treatment. The authors suggest that patients with an NT-proBNP level of 1,093.00 pg/dL or higher are likely to fail initial IVIG and may require further rescue therapy.

629 Serum Albumin Level Predicts Initial Intravenous Immunoglobulin Treatment Failure in Kawasaki Disease

Objectives: Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are less than 5 years old. Intravenous immunoglobulin (IVIG) is the standard therapy for KD. However, many KD patients still show poor response to initial IVIG treatment. This study was conducted to investigate the risk factors for IVIG treatment failure in KD.Methods: Children who met KD diagnosis criteria and were admitted for IVIG treatment were retrospectively enrolled for analysis. Patients were divided into IVIG-responsive and IVIG-resistant groups. Initial laboratory data before IVIG treatment were collected for analysis.Results: A total of 131 patients were enrolled during the study period. At 48 h after completion of initial IVIG treatment, 20 patients (15.3%) had an elevated body temperature. Univariate analysis showed that patients who had initial findings of high neutrophil count, abnormal liver function, low serum albumin level (< 2.9 g/dL), and pericardial effusion were at risk for IVIG treatment failure. Multivariate analysis with a logistic regression procedure showed that serum albumin level was considered the independent predicting factor of IVIG resistance in KD patients (P = 0.006, OR = 40, 95% CI: 52.8- 562). There was no significant correlation between age, gender, fever duration before IVIG treatment, hemoglobin level, total leukocyte and platelet counts, C-reactive protein level, or sterile pyuria and initial IVIG treatment failure. The specificity and sensitivity for prediction of IVIG treatment failure in this study were 96% and 34%, respectively.Conclusion: Pre-IVIG treatment serum albumin levels are a useful predictor of IVIG resistance in KD patients.

Serum albumin level predicts initial intravenous immunoglobulin treatment failure in Kawasaki disease

Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are <5 years old. Intravenous immunoglobulin (IVIG) is the standard therapy for KD. However, many patients with KD still show poor response to initial IVIG treatment. This study was conducted to investigate the risk factors for initial IVIG treatment failure in KD. Children who met KD diagnosis criteria and were admitted for IVIG treatment were retrospectively enrolled for analysis. Patients were divided into IVIG-responsive and IVIG-resistant groups. Initial laboratory data before IVIG treatment were collected for analysis. A total of 131 patients were enrolled during the study period. At 48 h after completion of initial IVIG treatment, 20 patients (15.3%) had an elevated body temperature. Univariate analysis showed that patients who had initial findings of high neutrophil count, abnormal liver function, low serum albumin level (≤2.9 g/dL) and pericardial effusion were at risk for IVIG treatment failure. Multivariate analysis with a logistic regression procedure showed that serum albumin level was considered the independent predicting factor of IVIG resistance in patients with KD (p = 0.006, OR = 40, 95% CI: 52.8-562). There was no significant correlation between age, gender, fever duration before IVIG treatment, haemoglobin level, total leucocyte and platelet counts, C-reactive protein level, or sterile pyuria and initial IVIG treatment failure. The specificity and sensitivity for prediction of IVIG treatment failure in this study were 96% and 34%, respectively. Pre-IVIG treatment serum albumin levels are a useful predictor of IVIG resistance in patients with KD.

IL-1B Polymorphism in Association With Initial Intravenous Immunoglobulin Treatment Failure in Taiwanese Children With Kawasaki Disease

Approximately 8-38% of children with Kawasaki disease (KD) will have persistent or recrudescent fever after initial intravenous immunoglobulin (IVIG) treatment and are at increased risk for development of coronary artery abnormalities. Using genetic markers may be helpful to identify the high-risk group of IVIG-resistant patients for aggressive treatment. The aim of this study was to evaluate the associations between 4 potential polymorphisms in the interleukin (IL)-1 family of genes and initial IVIG treatment failure in KD children. A total of 156 KD children (136 with and 20 without a response to IVIG treatment) who were treated with high-dose IVIG (2 g/kg) within 10 days of fever onset were recruited. Polymerase chain reaction and Taqman assays were used for genotyping. A significant increase in IVIG resistance risk was observed for IL-1B -511 TT and IL-1B -31 CC genotypes (adjusted odds ratio (AOR) 5.27, 95% confidence interval (CI) 1.69-16.38, P=0.004; AOR 3.95, 95%CI 1.26-12.41, P=0.019, separately). The diplotype TC/TC (at IL-1B -511 and -31) also showed a significantly increased risk of IVIG resistance (AOR 4.32, 95%CI 1.36-13.71, P=0.013). The IL-1B -511 TT and IL-1B -31 CC genotypes or the TC/TC diplotype may be associated with initial IVIG treatment failure in Taiwanese children with KD.

The relationship of eosinophilia to intravenous immunoglobulin treatment failure in Kawasaki disease

To investigate the role of eosinophils in Kawasaki disease (KD) and the relationship to initial intravenous immunoglobulin (IVIG) treatment failure. A retrospective analysis of all children who were admitted and met the criteria of KD between 1999 and 2005. The patients were divided into IVIG-responsive and IVIG-resistant groups. A total of 185 patients were enrolled during the study period. A series of blood eosinophils and biochemistry studies were correlated to the effectiveness of IVIG. The neutrophils percentage before IVIG treatment (pre-IVIG), leukocyte counts within 3 days after IVIG treatment (post-IVIG), liver enzyme, albumin levels, and post-IVIG eosinophils percentage were all significantly different between the two groups in univariate analysis. Under multivariate analysis with logistic regression, post-IVIG eosinophilia [peripheral blood (PB) eosinophils >or=4%] had an inverse correlation to KD patients with IVIG-resistance (p = 0.003). Also, pre-IVIG hypoalbuminemia (albumin <or=3.0 g/dl) was positively correlated to IVIG-resistance (p = 0.018). Further analysis showed that the PB eosinophils was markedly increased in the acute stage and returned to normal 3 weeks after IVIG treatment (p < 0.001). Eosinophil levels are highly elevated in the acute stage of KD both before and after the IVIG treatment. Post-IVIG treatment eosinophilia has an inverse correlation to KD patients with IVIG-resistance and may indicate IVIG-responsive. This may be a valuable factor to survey for the necessity of a second dose IVIG treatment.

Incomplete and Atypical Kawasaki Disease in a Young Infant: Severe, Recalcitrant Disease Responsive to Infliximab

This report describes a 7-week-old infant with incomplete and atypical Kawasaki disease, an acute vasculitis that predominantly affects infants and children. The patient was refractory to 2 doses of intravenous immunoglobulin and to high-dose intravenous methylprednisolone. He became afebrile only after 2 doses of infliximab. His prolonged, recalcitrant course was complicated by the development of peripheral gangrene and giant coronary artery aneurysms. Infants with incomplete and atypical Kawasaki disease are prone to intravenous immunoglobulin treatment failure and are at risk for the development of coronary artery aneurysms. In such patients, we suggest that consideration be given to early aggressive therapy with corticosteroids or infliximab added to intravenous immunoglobulin.

Gammaglobulin Failure and Retreatment in Kawasaki Disease

Background: Several cases of Kawasaki disease, (KD), up to 15%, were unresponsive to the initial treatment with intravenous immunoglobulin (IVIG). We retrospectively analyzed all children admitted for KD to determine the occurrence and variables associated with the initial IVIG treatment failure. Methods: All patients who fulfilled the criteria for KD and were treated with a single dose (2g/kg) of IVIG between January 1995 and December 2000 were enrolled. An analysis of patients who had initially failed to respond to IVIG and patients who had coronary artery aneurysm (CAA) was conducted. Results: A total of 113 patients were enrolled during the study period. There were 65 boys (57.5%). Thirteen patients (11.5%) were found to be unresponsive to initial IVIG treatment. Patients who were anemic (Hb 12,000/mm3), and high neutrophil count (>75%) were at risk for failure to response to a single dose of IVIG. We found no correlation between age, gender, days of starting IVIG treatment and ESR with failure of initial IVIG treatment. There were 23 patients (20.3%) who developed CAA. Male gender, lower hemoglobin ( 75%), higher ESR (>100mm/hr), prolonged fever and failure to respond to a single dose of IVIG were associated with a higher risk of developing CAA. Conclusions: The failure of a single dose of IVIG treatment could be seen in up to 11.5% of our Kawasaki patients. We found that low hemoglobin ( 12,000/mm3) and high neutrophil counts (>75%) were associated with retreatment of a second dose of IVIG.