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20-06-2019 | Rheumatology | News | Article

KAWAKINRA results support further investigation of anakinra for Kawasaki disease

medwireNews: The interleukin (IL)-1 receptor inhibitor anakinra merits further investigation for the treatment of Kawasaki disease, suggest findings from a phase IIa trial presented at the EULAR 2019 congress in Madrid, Spain.

The proof-of-concept trial included 16 children with Kawasaki disease and persistent fever (≥38 oC) despite standard treatment with intravenous immunoglobulin (IVIG) who were treated with anakinra for 15 days. Dosing was based on bodyweight, with a standard starting dose of 2 mg/kg that could be increased by 2 mg/kg every 24 hours for participants with persistent fever, to a maximum standard dose of 6 mg/kg.

Isabelle Koné-Paut (CHU de Bicêtre, Paris, France) reported that 81% of participants met the primary endpoint of body temperature below 38 oC within 48 hours of the last escalation dose of anakinra. The median body temperature was 37.6 oC at the 3-day follow-up, and 37.2 oC after 7 days.

Moreover, all patients met the secondary endpoint of a reduction in polyglycolic acid levels of at least 50% between baseline and the 15-day follow-up, while 53.8% of participants achieved C-reactive protein (CRP) levels below 10 mg/L by day 14, and 93.0% met this endpoint by day 30. Median CRP measurements were 135 mg/L at baseline and 9.5 mg/L at the 1-week follow-up.

The KAWAKINRA investigators also found that 57% of 14 evaluable patients had coronary dilation – indicated by a maximum Z score of at least 2.5 mm – at study entry, decreasing to 36% at day 14 and 21% at day 45. The presenter noted that all patients except one experienced normalization or improvement in coronary Z scores by the 45-day follow-up.

Three serious adverse events leading to treatment discontinuation occurred in the trial, comprising one case each of anakinra overdose, macrophage-activating syndrome, and increased coronary dilation. Other adverse events included cytolytic hepatitis in two patients, and one case each of hypereosinophilia, injection site reaction, and pancreatitis.

Koné-Paut concluded that anakinra treatment, given early in the course of IVIG-resistant Kawasaki disease, “was rapidly effective on [Kawasaki disease] symptoms, biologic inflammation and coronary dilatations in almost all patients, with a good tolerability.”

She recommended that “further studies investigating early intervention with IL-1 blockade in [Kawasaki disease] are worthwhile.”

By Claire Barnard

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

Ann Rheum Dis 2019; 78: 149 (abstract)
European Congress of Rheumatology 2019; Madrid, Spain: 12–15 June

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