Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease

Abstract

Objective: To investigate the safety, tolerability, and pharmacokinetics of the anti-tumor necrosis factor-alpha monoclonal antibody infliximab in subjects with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD).

Study design: We conducted a multicenter, randomized, prospective trial of second IVIG infusion (2 g/kg) versus infliximab (5 mg/kg) in 24 children with acute KD and fever after initial treatment with IVIG. Primary outcome measures were the safety, tolerability, and pharmacokinetics of infliximab. Secondary outcome measures were duration of fever and changes in markers of inflammation.

Results: Study drug infusions were associated with cessation of fever within 24 hours in 11 of 12 subjects treated with infliximab and in 8 of 12 subjects retreated with IVIG. No infusion reactions or serious adverse events were attributed to either study drug. No significant differences were observed between treatment groups in the change from baseline for laboratory variables, fever, or echocardiographic assessment of coronary arteries.

Conclusions: Both infliximab and a second IVIG infusion were safe and well tolerated in the subjects with KD who were resistant to standard IVIG treatment. The optimal management of patients resistant to IVIG remains to be determined.

Figures

Figure 1

Flow chart of subjects after randomization. Numbers in parentheses indicate number of subjects. The two subjects who failed to respond to the second study treatment were treated off-protocol with steroids.

Figure 2

A, Concentration of infliximab versus time curves for each individual subject. B, Median (± standard error of the median) infliximab concentrations versus time after dose in infants and children.

Figure 2

A, Concentration of infliximab versus time curves for each individual subject. B, Median (± standard error of the median) infliximab concentrations versus time after dose in infants and children.

Figure 3

Time course of serum cytokine and soluble TNF receptors in subjects treated with IVIG (solid lines) or infliximab (dashed lines). The analysis after the 24h time point excludes those patients who crossed over to receive other study drug (n=5). The asterisk (*) denotes timepoints for which the difference between median values for the two treatment groups was significant. Abbr. IL, interleukin; sTNFR, soluble tumor necrosis factor-α receptor; Pre-Rx, before study drug treatment.