Kawasaki disease - Emerging treatments

Intravenous immune globulin (IVIG) plus corticosteroid (all patients)

One multicenter phase 3 clinical trial across Europe is currently exploring the hypothesis that a corticosteroid used as adjunctive treatment may reduce the frequency of refractory KD and thus may improve coronary outcomes in unselected KD cases: the Kawasaki disease coronary artery aneurysm prevention (KD-CAAP) trial, (ISRCTN71987471). Given that coronary artery aneurysm (CAA) complication rates seen in the UK and across Europe are higher than historically perceived (16% to 42%), all KD patients are arguably at high-risk of CAA despite IVIG and could therefore potentially benefit from adjunctive corticosteroids as primary treatment. KD-CAAP will therefore determine the efficacy and safety of adjunctive prednisone combined with IVIG and aspirin for prevention of CAA in unselected KD patients across Europe, compared with IVIG and aspirin alone. The primary outcome is CAA frequency within 12 weeks.[47]

Statins

Although the American Heart Association (AHA) Kawasaki disease guidelines (2017) recommend consideration of statin therapy, the authors of this topic report that use of statins in acute and long-term management of patients with KD has not become widespread US clinical practice and remains clinician dependent. Moreover, a 2019 scientific statement from the AHA states, "data are still limited regarding the role of statin therapy in patients with CAAs [coronary artery aneurysms]".[75] The potential utility of statin therapy is based on statins' generalized anti-inflammatory effect and their effect on myointimal proliferation in the arterial wall.[76]

Low-dose aspirin (as initial treatment)

Low-dose aspirin with IVIG for the initial treatment of KD may be as effective as the current practice of higher-dose aspirin with IVIG and could decrease adverse events. European guidelines state that future guidelines may recommend this approach but note a prospective controlled clinical trial has not yet been conducted. One retrospective cohort study of 358 patients showed no significant benefits of high-dose aspirin versus low-dose aspirin in terms of coronary artery aneurysm development, IVIG resistance, or disease recurrence. Coronary ectasia rate and length of hospital stay were significantly greater in the high-dose aspirin group.[77] One meta-analysis of 12,176 patients showed no significant difference in the incidence of coronary artery aneurysms in patients treated with high-dose versus low-dose aspirin. Patients in the high-dose aspirin treatment group had a slightly faster resolution of fever, but there were no differences in the rates of IVIG resistance or the length of hospital stay between the two treatment groups.[78]