Recombinant Interleukin-1 Receptor Antagonist Is an Effective First-Line Treatment Strategy in New-Onset Systemic Juvenile Idiopathic Arthritis, Irrespective of HLA-DRB1 Background and IL1RN Variants.

التفاصيل البيبلوغرافية
العنوان:	Recombinant Interleukin-1 Receptor Antagonist Is an Effective First-Line Treatment Strategy in New-Onset Systemic Juvenile Idiopathic Arthritis, Irrespective of HLA-DRB1 Background and IL1RN Variants.
المؤلفون:	Erkens RGA; University Medical Center Utrecht and University of Utrecht, Utrecht, The Netherlands., Calis JJA; University Medical Center Utrecht and University of Utrecht, Utrecht, The Netherlands., Verwoerd A; University Medical Center Utrecht and University of Utrecht, Utrecht, The Netherlands., De Roock S; University Medical Center Utrecht and University of Utrecht, Utrecht, The Netherlands., Ter Haar NM; University Medical Center Utrecht and University of Utrecht, Utrecht, The Netherlands., Den Engelsman G; University Medical Center Utrecht and University of Utrecht, Utrecht, The Netherlands., Van der Veken LT; University Medical Center Utrecht and University of Utrecht, Utrecht, The Netherlands., Ernst RF; University Medical Center Utrecht and University of Utrecht, Utrecht, The Netherlands., Van Deutekom HWM; University Medical Center Utrecht and University of Utrecht, Utrecht, The Netherlands., Pickering A; Harvard Medical School, Boston, Massachusetts., Scholman RC; University Medical Center Utrecht and University of Utrecht, Utrecht, The Netherlands., Jansen MHA; University Medical Center Utrecht and University of Utrecht, Utrecht, The Netherlands., Swart JF; University Medical Center Utrecht and University of Utrecht, Utrecht, The Netherlands., Sinha R; Systemic Juvenile Idiopathic Arthritis Foundation, Cincinnati, Ohio., Roth J; University of Münster, Münster, Germany., Schulert GS; Cincinnati Children's Hospital and University of Cincinnati College of Medicine, Cincinnati, Ohio., Grom AA; Cincinnati Children's Hospital and University of Cincinnati College of Medicine, Cincinnati, Ohio., Van Loosdregt J; University Medical Center Utrecht and University of Utrecht, Utrecht, The Netherlands., Vastert SJ; University Medical Center Utrecht and University of Utrecht, Utrecht, The Netherlands.
المصدر:	Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2024 Jan; Vol. 76 (1), pp. 119-129. Date of Electronic Publication: 2023 Nov 06.
نوع المنشور:	Journal Article; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: Wiley Country of Publication: United States NLM ID: 101623795 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2326-5205 (Electronic) Linking ISSN: 23265191 NLM ISO Abbreviation: Arthritis Rheumatol Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Malden, MA : Wiley, [2014]-
مواضيع طبية MeSH:	Arthritis, Juvenile/drug therapy , Arthritis, Juvenile/genetics , Biological Products/therapeutic use , Eosinophilia/drug therapy, Humans ; Interleukin 1 Receptor Antagonist Protein/genetics ; Interleukin 1 Receptor Antagonist Protein/therapeutic use ; HLA-DRB1 Chains/genetics ; Prospective Studies ; Receptors, Interleukin-1/therapeutic use
مستخلص:	Objective: Human leukocyte antigen (HLA)-DRB115:01 has been recently associated with interstitial lung disease (LD), eosinophilia, and drug reactions in systemic juvenile idiopathic arthritis (sJIA). Additionally, genetic variants in IL1RN have been linked to poor response to anakinra. We sought to reproduce these findings in a prospective cohort study of patients with new-onset sJIA treated with anakinra as first-line therapy. Methods: HLA and IL1RN risk alleles were identified via whole-genome sequencing. Treatment responses and complications were compared between carriers versus noncarriers. Results: Seventeen of 65 patients (26%) carried HLA-DRB115:01, comparable with the general population, and there was enrichment for HLA-DRB111:01, a known risk locus for sJIA. The rates of clinical inactive disease (CID) at 6 months, 1 year, and 2 years were generally high, irrespective of HLA-DRB1 or IL1RN variants, but significantly lower in carriers of an HLA-DRB111:01 allele. One patient, an HLA-DRB115:01 carrier, developed sJIA-LD. Of the three patients with severe drug reactions to biologics, one carried HLA-DRB115:01. The prevalence of eosinophilia did not significantly differ between HLA-DRB115:01 carriers and noncarriers at disease onset (6.2% vs 14.9%, P = 0.67) nor after the start of anakinra (35.3% vs 37.5% in the first 2 years of disease). Conclusion: We observed high rates of CID using anakinra as first-line treatment irrespective of HLA-DRB1 or IL1RN variants. Only one of the 17 HLA-DRB115:01 carriers developed sJIA-LD, and of the three patients with drug reactions to biologics, only one carried HLA-DRB1*15:01. Although thorough monitoring for the development of drug hypersensitivity and refractory disease courses in sJIA, including sJIA-LD, remains important, our data support the early start of biologic therapy in patients with new-onset sJIA irrespective of HLA-DRB1 background or IL1RN variants. (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
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معلومات مُعتمدة:	LLP10 ReumaNederland; The Merel Stichting; The Systemic JIA foundation; The Van Dam van Os Stichting
المشرفين على المادة:	0 (Interleukin 1 Receptor Antagonist Protein) 0 (HLA-DRB1 Chains) 0 (Biological Products) 0 (Receptors, Interleukin-1) 0 (IL1RN protein, human)
تواريخ الأحداث:	Date Created: 20230720 Date Completed: 20231229 Latest Revision: 20240226
رمز التحديث:	20240227
DOI:	10.1002/art.42656
PMID:	37471469
قاعدة البيانات:	MEDLINE

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تدمد:	2326-5205
DOI:	10.1002/art.42656