1.
The therapeutic window of intravenous immunoglobulin (IVIG) and its correlation with clinical outcomes in Kawasaki disease: a systematic review and meta-analysis
Li Z, Cai J, Lu J, Wang M, Yang C, Zeng Z, Tang Q, Li J, Tang W, Luo H, et al
Italian journal of pediatrics. 2023;49(1):45
Abstract
BACKGROUND The optimal therapeutic window to start intravenous immunoglobulin (IVIG) for Kawasaki disease (KD) is highly debatable. We aimed to summarize the existing literature to evaluate the therapeutic window of IVIG treatment and its correlation with clinical outcomes in KD patients. METHODS We searched the databases from inception to August 26, 2022, without language restrictions. The primary outcomes were initial IVIG resistance and coronary artery lesions (CALs) in acute phase. Secondary outcome was CALs during 1-2 months of follow-up. RESULTS 27 studies involving 41,139 patients were included in this study. Very low-quality evidence showed that the earlier IVIG treatment within 4 days had a higher IVIG-resistance rate (RR, 1.80; 95% CI, 1.50-2.15; P < .00001; I(2) = 75%) than the late treatment. Very low-quality evidence showed that IVIG treatment for more than 7 days was associated with a higher risk of CALs in acute phase(RR, 0.57; 95% CI, 0.40-0.80; P = .001; I(2) = 76%). There was a lower risk of CALs during 1-2 months follow-up for those who started IVIG administration within 10 days from the onset. CONCLUSIONS Overall, IVIG treatment within 7 days of illness seems to be the optimal therapeutic window of IVIG. IVIG treatment within 7 days is found to be effective for reducing the risk of coronary artery lesions and cardiac sequelae in KD patients. The early IVIG treatment within 4 days should be vigilant for the IVIG resistance although large multi-center randomized trials with well design are needed.
2.
Indirect-comparison meta-analysis of treatment options for patients with refractory Kawasaki disease
Chan H, Chi H, You H, Wang M, Zhang G, Yang H, Li Q
BMC pediatrics. 2019;19(1):158
Abstract
BACKGROUND There is limited information available regarding the clinical management of intravenous immunoglobulin-resistant Kawasaki disease (KD). We aimed to evaluate the optimal treatment options for patients with refractory KD by presenting an indirect-comparison meta-analysis. METHODS PubMed, EMBASE, Web of Science, and the Cochrane Database were searched on August 31, 2018. Unpublished studies were also searched in ProQuest Dissertations & Theses and through manual retrieval strategies. Randomized concurrent controlled trials (RCTs), high-quality non-randomized concurrent controlled trials (non-RCTs), and retrospective studies associated with AEs were included. The quality of all eligible studies was assessed using Cochrane collaboration's tool and non-randomized study guidelines. Risk ratios (RR) with 95% confidence intervals (CIs) for dichotomous outcomes were estimated in our analysis. GRADE profiler 3.6.1 was used to assess the evidence profile. RESULTS Twelve studies involving 372 immunoglobulin-resistant KD patients were identified and analyzed. Neither infliximab nor intravenous pulse methylprednisolone (IVMP) was significantly more effective than second IVIG infusion with respect to lowering coronary artery lesions (CALs) (infliximab, 0.85, 0.43-1.69; IVMP, 0.99, 0.52-1.88) and treatment resistance (infliximab, 0.43, 0.21-0.89; IVMP, 1.16, 0.33-4.13). No significant differences were found between infliximab and IVMP in the incidence rate of CALs (0.70, 0.27-1.81), the treatment resistance (0.37, 0.09-1.60), the rates of coronary artery aneurysm (4.13, 0.38-45.22) and the coronary artery dilatation (0.45, 0.10-1.99). Furthermore, compared with second IVIG infusion, both infliximab and IVMP showed significant effectiveness in antipyretic effects (infliximab, 1.52, 1.16-1.99; IVMP, 1.29, 0.77-2.15). However, Infliximab was noninferior to IVMP on antipyretic effects (1.18, 0.66-2.15). IVMP treatment showed significant association with fewer AEs than second IVIG infusion (0.49, 0.26-0.94) and infliximab (2.34, 1.07-5.09). No significant differences were noted between infliximab treatment and second IVIG infusion (1.06, 0.69-1.63). CONCLUSIONS Infliximab, IVMP, and second IVIG infusion showed no significant differences in the cardioprotective effect or the rate of treatment resistance. Infliximab and IVMP treatment were more effective than second IVIG infusion regarding antipyretic effects. IVMP treatment may have an advantage due to its lower total rate of AEs associated with drug infusion. TRIAL REGISTRATION The study has been registered on PROSPERO ( CRD42016039693 ).