Background/Purpose: Treatment for patients with Kawasaki Disease (KD) refractory to standard therapy is controversial. Most experts recommend a second dose of IVIG [1], and for IVIG-resistant cases, infliximab is frequently used. However, there is limited evidence for the efficacy of infliximab and data has been primarily from Asian populations [1,2]. Patients with refractory KD are at risk for higher morbidity and mortality and have an increased risk of coronary artery aneurysms (CAA). For high-risk patients with CAAs on initial echocardiogram, the evidence for effective treatment for halting progression or achieving resolution of the CAAs is limited to a few retrospective studies. Infliximab, corticosteroids, and anakinra have shown some promise in reversal of CAAs though data is limited [3-5].  Here we report on four cases of refractory KD, where ongoing infliximab therapy was safe, well-tolerated and effective in resolution of clinical symptoms, laboratory abnormalities and coronary changes. 

Methods: This is a retrospective case series of four patients with refractory KD who were treated with ongoing infliximab infusions. Patients were all male, and ages: 7 months, 17 months, 19 months, and 6 years. All patients received initial treatment with high dose aspirin and two doses of IVIG, and developed CAAs within the first 2 weeks of presentation. The mean of the coronary artery z-scores was 8.06 (range 5.14-11). Due to recurrence of fever and elevated inflammatory markers, patients were started on oral steroids in addition to infliximab (5 mg/kg). Infliximab was given at time 0 and at 2 weeks, and then monthly until patients were tapered off of oral steroids at which point infliximab was also tapered off. All patients were first tapered off of steroids and subsequently off of infliximab and had full resolution of CAAs.

Results: The duration of infliximab infusions ranged from 12 to 24 months and steroid treatment from 2.5 to 8 months. Ongoing monthly infliximab led to normalization of inflammatory markers and thus allowed for tapering off of steroids in all cases. Coronary artery abnormalities resolved between 2 to 14 months. All patients had full remission based on clinical symptoms and echocardiogram findings and had additional angiography which excluded other systemic vasculitides.

Conclusion: Long-term Infliximab treatment, ranging up to 2 years in our study, was a safe, well-tolerated, and effective treatment for our patients with refractory KD. Ongoing infliximab led to full resolution of clinical symptoms, ability to taper off of oral steroids, and resolution of CAAs. Larger, prospective randomized clinical trials are needed to evaluate whether infliximab is effective in reversal of CAAs, and whether it should be used in all refractory KD cases and continued long-term for persistent KD.

References: 
1. Mccrindle BW et al. Circulation. 2017;135(17):e927-e999
2. Mori M et al. Sci Rep. 2018;8:1994
3. Nagamoto Y et al. Int J Cardiol. 2018;271:317-321
4. Tremoulet AH et al. Contemp Clin Trials. 2016;48:70-5
5. Dionne A et al. Pediatrics. 2019;143(6):e20183341

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/resolution-of-coronary-artery-changes-in-patients-with-refractory-kawasaki-disease-with-prolonged-course-of-infliximab-a-case-series/