Phase II Open Label Study of Anakinra in Intravenous Immunoglobulin-Resistant Kawasaki Disease.
Antirheumatic Agents
/ therapeutic use
C-Reactive Protein
/ immunology
Child
Child, Preschool
Coronary Aneurysm
/ diagnostic imaging
Echocardiography
Female
Fever
Humans
Immunoglobulins, Intravenous
/ therapeutic use
Immunologic Factors
/ therapeutic use
Infant
Interleukin 1 Receptor Antagonist Protein
/ therapeutic use
Male
Mucocutaneous Lymph Node Syndrome
/ diagnostic imaging
Proof of Concept Study
Treatment Failure
Treatment Outcome
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
23
03
2020
accepted:
30
07
2020
pubmed:
12
8
2020
medline:
23
3
2021
entrez:
12
8
2020
Statut:
ppublish
Résumé
Anakinra has been shown to be successful in preventing and treating cardiovascular lesions both in experimental murine models of Kawasaki disease (KD) and in several studies on intravenous immunoglobulin (IVIG)- and steroid-resistant patients with KD. This study was undertaken to determine the safety of blocking interleukin-1 in patients with IVIG-resistant KD. Sixteen patients were included in the present study. Patients with KD who were not responsive to 1 or more courses of 2 mg/kg of IVIG received anakinra by subcutaneous daily injections. Starting doses were 2 mg/kg of IVIG (4 mg/kg in patients who were age <8 months and who weighed ≥5 kilograms), and the dose was increased up to 6 mg/kg every 24 hours if the patient's body temperature remained >38°C, indicative of a fever. Treatment duration was 14 days. The last visit was on day 45. Primary outcome was abatement of fever. Secondary measures included disease activity, coronary artery Z score, and C-reactive protein (CRP) levels. Seventy-five percent of patients in the intention-to-treat group and 87.5% in the per-protocol group became afebrile within 48 hours of the last escalation dose of anakinra. Reduction of disease activity by 50% was indicated on 93.3% (95% confidence interval [95% CI] 68.1-99.8%) of physician evaluations and on 100% (95% CI 73.5-100%) of parent evaluations. CRP values normalized by day 30. At the initial screening, 12 of 16 patients had a maximum coronary artery Z score of >2, and 10 of 16 patients had a maximum Z score of >2.5. At day 45, 5 of 10 patients (50% [95% CI 18.7-81.3%]) and 6 of 12 patients (50% [95% CI 21.1-78.9%]) had achieved coronary artery Z scores of <2.5 and <2, respectively. Five serious adverse events were observed in 3 patients, but no serious infections or deaths occurred. Anakinra was well tolerated in the study patients and may have some efficacy in reducing fever, markers of systemic inflammation, and coronary artery dilatation in individuals with IVIG-refractory KD.
Substances chimiques
Antirheumatic Agents
0
Immunoglobulins, Intravenous
0
Immunologic Factors
0
Interleukin 1 Receptor Antagonist Protein
0
C-Reactive Protein
9007-41-4
Banques de données
ClinicalTrials.gov
['NCT02390596']
EudraCT
['2014‐002715‐41']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
151-161Informations de copyright
© 2020, American College of Rheumatology.
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