In a randomized trial the anti-TNF antibody infliximab did not reduce resistance to IVIG treatment in Kawasaki disease. But it did reduce adverse reactions and improve secondary outcomes while being well-tolerated.
Tremoulet AH, Jain S, Jaggi P, et al. Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet (2014) doi:10.1016/S0140-6736(13)62298-9 [Epub ahead of print]
Infliximab, an anti-TNF antibody, did not improve the primary outcome in this study: reducing treatment resistance in Kawasaki disease. It did, however, reduce adverse reactions to intravenous immunoglobulin (IVIG), improved other secondary markers, and was safe and well tolerated.
Coronary artery aneurysms occur in about 25% of untreated patients. IVIG reduces this to 5%. But 20-25% are resistant to IVIG, and develop fever and inflammation – the main risk factors for coronary artery aneurysms. IVIG resistance was defined as a fever of ≥38°C at 36 hours to 7 days after completion of the infusion. IVIG reaction was defined as fever with chills or hypotension that warranted interruption of the infusion.
The main rescue treatment is corticosteroids. This study examined infliximab, an anti-TNF antibody. Plasma concentrations of TNF and soluble TNF receptor are raised in acute Kawasaki disease and are associated with coronary artery aneurysms.
In this group of 196 patients randomized to infliximab (98) or placebo (98), infliximab had no effect on treatment resistance (11 patients in each group). However, it did eliminate IVIG reaction (13 patients in the placebo group vs none in the infliximab group).
A commentary explains the difficulty of doing randomized controlled trials on rare diseases. Only a few Kawasaki patients do not respond to IVIG, and even fewer develop coronary artery aneurysms, so many patients are required for adequate statistical power. Studies can identify patients at higher risk, or use inflammatory markers, but these strategies have problems. This study shows that randomized controlled trials can be done, but also shows how difficult it is to extrapolate from them to clinical recommendations.