{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T11:08:35Z","timestamp":1789816115217,"version":"4.0.1"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,2]],"date-time":"2021-05-02T00:00:00Z","timestamp":1619913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the impact of early treatment and <jats:italic>IL1RN<\/jats:italic> genetic variants on the response to anakinra in systemic juvenile idiopathic arthritis (JIA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Response to anakinra was defined as achievement of clinically inactive disease (CID) at 6 months without glucocorticoid treatment. Demographic, clinical, and laboratory characteristics of 56 patients were evaluated in univariate and multivariate analyses as predictors of response to treatment. Six single\u2010nucleotide polymorphisms (SNPs) in the <jats:italic>IL1RN<\/jats:italic> gene, previously demonstrated to be associated with a poor response to anakinra, were genotyped by quantitative polymerase chain reaction (qPCR) or Sanger sequencing. Haplotype mapping was performed with Haploview software. <jats:italic>IL1RN<\/jats:italic> messenger RNA (mRNA) expression in whole blood from patients, prior to anakinra treatment initiation, was assessed by qPCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After 6 months of anakinra treatment, 73.2% of patients met the criteria for CID without receiving glucocorticoids. In the univariate analysis, the variable most strongly related to the response was disease duration from onset to initiation of anakinra treatment, with an optimal cutoff at 3 months (area under the curve 84.1%). Patients who started anakinra treatment \u22653 months after disease onset had an 8\u2010fold higher risk of nonresponse at 6 months of treatment. We confirmed that the 6 <jats:italic>IL1RN<\/jats:italic> SNPs were inherited as a common haplotype. We found that homozygosity for \u22651 high\u2010expression SNP correlated with higher <jats:italic>IL1RN<\/jats:italic> mRNA levels and was associated with a 6\u2010fold higher risk of nonresponse, independent of disease duration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings on patients with systemic JIA confirm the important role of early interleukin\u20101 inhibition and suggest that genetic <jats:italic>IL1RN<\/jats:italic> variants predict nonresponse to therapy with anakinra.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41612","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T10:10:07Z","timestamp":1607422207000},"page":"1053-1061","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Early Treatment and <i>IL1RN<\/i> Single\u2010Nucleotide Polymorphisms Affect Response to Anakinra in Systemic\u00a0Juvenile Idiopathic 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