Infliximab Holds Promise in Treating Kawasaki Disease

Kawasaki disease (KD), an acute febrile disorder that primarily affects children aged 5 years or younger and can cause coronary artery abnormalities and acquired heart disease in children. Suppressing acute inflammation within 10 days of the disease’s onset is critical to preventing coronary artery lesions (CAL) in these patients.

While intravenous immunoglobulin (IVIG) is the initial therapy for KD, and typically leads to rapid defervescence (and therefore lower incidence of CALs), approximately 20% of patients do not respond adequately to IVIG. Often, IVIG-refractory KD is treated with an additional dose of IVIG, though half of refractory patients may not respond to the added dose.

Because serum tumor necrosis factor (TNF) is high in patients with KD, infliximab, an anti-TNF agent, has been proposed as a potential treatment for IVIG-refractory KD, but few randomized trials have been conducted to demonstrate the efficacy and safety of using infliximab in this setting.

Results of a small study of infliximab versus an additional dose of IVIG for treatment-refractory patients with KD, recently published in Scientific Reports, showed that infliximab improved the defervescence rate within 48 hours compared to treatment with IVIG, and that infliximab was well tolerated.

The study began on May 2012 and ended in September 2014. Because only a small group of patients met eligibility criteria, the recruitment target was not reached. In total, 31 patients were enrolled and randomized to receive either infliximab in a single intravenous dose of 5 mg/kg (n = 16) or intravenous polyethylene glycol-treated human immunoglobulin (VGIH) at a dose of 2 mg/kg (n = 15). The study’s primary outcome was the defervescence rate within 48 hours after treatment, and safety was evaluated through day 56.

The researchers found that:

• The defervescence rate within 48 hours was significantly greater in the infliximab arm at 76.7% (95% CI: 56.6%-96.7%) versus the VGIH arm at 37.0% (95% CI: 11.9%-62.1%).
• The median febrile period from the start of the study drug administration was 16.0 hours in the infliximab arm and 56.1 hours in the VGIH arm.
• Axillary body temperature from 4 hours to 20 hours was significantly lower in the infliximab group than in the VGIH group.
• CALs were found in 1 patient in the infliximab arm and 3 patients in the VGIH arm through day 21, and no patient had a new CAL after day 21.
• Improvement and resolution of clinical symptoms other than fever were comparable between treatment groups.
• Adverse events (AEs) occurred in 93.8% of patients in the infliximab arm and 100% of patients in the VGIH arm, with 1 serious AE reported in the VGIH arm.
• The most commonly reported AEs were an increase in anti—double-stranded DNA IgM antibodies.

The study’s authors say that, as prevention of CALs is among the most important goals of treating KD, and as anti-TNF therapy directly improves endothelial cell function and reduces inflammation, treating KD with infliximab may contribute to preventing development of coronary artery abnormalities. Larger and longer studies may help to confirm these trial results and provide longer-term outcomes with infliximab.