Impact of IL1RN Variants on Response to Interleukin-1 Blocking Therapy in Systemic Juvenile Idiopathic Arthritis.
Adolescent
Antibodies, Monoclonal, Humanized
/ pharmacology
Antirheumatic Agents
/ pharmacology
Arthritis, Juvenile
/ drug therapy
Child
Child, Preschool
Cohort Studies
Female
Germany
Haplotypes
Humans
Infant
Interleukin 1 Receptor Antagonist Protein
/ genetics
Interleukin-1
/ antagonists & inhibitors
Male
Polymorphism, Single Nucleotide
/ drug effects
Registries
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:
03 2020
03 2020
Historique:
received:
13
03
2019
accepted:
03
10
2019
pubmed:
11
10
2019
medline:
14
7
2020
entrez:
11
10
2019
Statut:
ppublish
Résumé
To analyze the reported association of IL1RN polymorphisms with response to interleukin-1 (IL-1) blockade in a German cohort of patients with systemic juvenile idiopathic arthritis (JIA), and to assess the impact of other factors on treatment response. Sixty-one patients with systemic JIA who had received IL-1 blockade were identified within the German Autoinflammatory Disease registry DNA biobank. Response to IL-1 blockade was assessed according to 1) the clinical response (initially at least a transient response or good response compared to a poor response), 2) switch (or no switch) to anti-IL-6 receptor therapy following IL-1 blockade, 3) achievement of clinically inactive disease within 6 months of IL-1 blockade, 4) improvement in disease activity measured using the modified Juvenile Arthritis Disease Activity Score, and 5) achievement of a glucocorticoid-free state. In addition, basic demographic data, key features of the disease course, laboratory data, and IL1RN single-nucleotide polymorphisms (SNPs) were assessed. Six of 7 IL1RN SNPs reported to be associated with response to anakinra therapy were analyzed. These 6 IL1RN SNPs were inherited as haplotypes. An association of IL1RN haplotypes and SNPs with response to IL-1 blockade could not be confirmed in this cohort of patients with systemic JIA. Patients who received tocilizumab following IL-1 blockade had a longer duration from disease onset to diagnosis than those who did not receive tocilizumab (median 0.27 years versus 0.08 years). The results of this study could not confirm an impact of IL1RN SNPs on response to IL-1 blockade therapy with either anakinra or canakinumab in a cohort of patients with systemic JIA. However, a longer time frame from disease onset to diagnosis was associated with poorer long-term treatment response, thereby supporting the "window of opportunity" hypothesis that suggests improved long-term treatment response with shorter time from disease onset to diagnosis (and treatment).
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antirheumatic Agents
0
IL1RN protein, human
0
Interleukin 1 Receptor Antagonist Protein
0
Interleukin-1
0
canakinumab
37CQ2C7X93
tocilizumab
I031V2H011
Types de publication
Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
499-505Informations de copyright
© 2019 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.
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