medwireNews: Adding infliximab to standard therapy with high-dose intravenous immunoglobulin (IVIG) plus high-dose aspirin may decrease fever duration and prevent coronary artery lesions in children with Kawasaki disease (KD), study findings indicate.
The network meta-analysis (NMA) also revealed that “high-dose IVIG with pulse steroid therapy or cyclosporine therapy might have an additional effect on improving the decline in fever and lowering the incidence of [coronary artery lesions],” report Ping-Tao Tseng (Prospect Clinic for Otorhinolaryngology and Neurology, Kaohsiung, Taiwan) and co-authors in eBioMedicine.
They say that, at present, “the use of different adjunctive therapies remains controversial” in the management of KD.
To address this, the researchers reviewed data from 56 randomized trials that included a total of 6486 participants with KD aged 1.5 to 5.7 years (mean 2.6 years). Of these, 48 trials included 5904 children with acute KD receiving initial treatment. The remaining eight studies included 582 children with refractory KD who had failed to respond to standard treatment.
In patients with acute KD, the NMA compared high-dose IVIG (≥2 g/kg) plus aspirin with various doses of IVIG in combination with aspirin and either infliximab, clarithromycin, or pulsed-dose IV methylprednisolone.
The analysis showed that the shortest fever duration occurred among patients who received medium-dose IVIG (1 g/kg) plus aspirin and infliximab, but the difference of 1.76 days relative to high-dose IVIG plus aspirin was not statistically significant.
In fact, the only significant differences in fever duration versus standard therapy occurred among children who were given low-dose IVIG (100–400 mg) plus aspirin or aspirin alone. In these cases, fever was 1.47 days and 2.87 days shorter, on average.
Different treatments were used among the patients with refractory KD, and the researchers found that individuals who received IV pulsed steroid therapy had the fastest rate of fever decline, at a significant odds ratio (OR) of 0.04 versus standard treatment with high-dose IVIG.
The risk for failure to reduce fever was also significantly lower relative to standard therapy among patients who received high-dose IVIG plus IV pulse steroid therapy (OR=0.05), high-dose IVIG plus steroid therapy (OR=0.12), or infliximab monotherapy (OR=0.20). Conversely, individuals who received high-dose IVIG plus ciclosporin had a similar risk for fever failure to those in the reference group.
The researchers also looked at the impact of different treatments on incidence of coronary artery lesions. They found that incidence was lowest among children treated with medium-dose IVIG plus aspirin and infliximab for acute disease, and among those given high-dose IVIG plus cyclosporin for refractory disease.
Tseng et al conclude: “The infliximab plus standard therapy might be the best treatment for acute KD. Pulse methylprednisolone plus IVIG is the best choice for refractory KD.”
However, they add: “Because some of the findings of this NMA should be considered hypothesis-generating rather than confirmatory, further evidence from de novo randomised trials is needed to support our results.”
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