PMID- 37471469
OWN - NLM
STAT- MEDLINE
DCOM- 20231229
LR  - 20240226
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Linking)
VI  - 76
IP  - 1
DP  - 2024 Jan
TI  - 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.
PG  - 119-129
LID - 10.1002/art.42656 [doi]
AB  - OBJECTIVE: Human leukocyte antigen (HLA)-DRB1*15:01 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-DRB1*15:01, comparable with the general population, 
      and there was enrichment for HLA-DRB1*11:01, 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-DRB1*11:01 allele. One patient, an HLA-DRB1*15:01 
      carrier, developed sJIA-LD. Of the three patients with severe drug reactions to 
      biologics, one carried HLA-DRB1*15:01. The prevalence of eosinophilia did not 
      significantly differ between HLA-DRB1*15:01 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-DRB1*15:01 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.
CI  - (c) 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC 
      on behalf of American College of Rheumatology.
FAU - Erkens, Remco G A
AU  - Erkens RGA
AUID- ORCID: 0000-0002-3962-7228
AD  - University Medical Center Utrecht and University of Utrecht, Utrecht, The 
      Netherlands.
FAU - Calis, Jorg J A
AU  - Calis JJA
AD  - University Medical Center Utrecht and University of Utrecht, Utrecht, The 
      Netherlands.
FAU - Verwoerd, Anouk
AU  - Verwoerd A
AD  - University Medical Center Utrecht and University of Utrecht, Utrecht, The 
      Netherlands.
FAU - De Roock, Sytze
AU  - De Roock S
AD  - University Medical Center Utrecht and University of Utrecht, Utrecht, The 
      Netherlands.
FAU - Ter Haar, Nienke M
AU  - Ter Haar NM
AD  - University Medical Center Utrecht and University of Utrecht, Utrecht, The 
      Netherlands.
FAU - Den Engelsman, Gerda
AU  - Den Engelsman G
AD  - University Medical Center Utrecht and University of Utrecht, Utrecht, The 
      Netherlands.
FAU - Van der Veken, Lars T
AU  - Van der Veken LT
AD  - University Medical Center Utrecht and University of Utrecht, Utrecht, The 
      Netherlands.
FAU - Ernst, Robert F
AU  - Ernst RF
AD  - University Medical Center Utrecht and University of Utrecht, Utrecht, The 
      Netherlands.
FAU - Van Deutekom, Hanneke W M
AU  - Van Deutekom HWM
AD  - University Medical Center Utrecht and University of Utrecht, Utrecht, The 
      Netherlands.
FAU - Pickering, Alex
AU  - Pickering A
AD  - Harvard Medical School, Boston, Massachusetts.
FAU - Scholman, Rianne C
AU  - Scholman RC
AD  - University Medical Center Utrecht and University of Utrecht, Utrecht, The 
      Netherlands.
FAU - Jansen, Marc H A
AU  - Jansen MHA
AD  - University Medical Center Utrecht and University of Utrecht, Utrecht, The 
      Netherlands.
FAU - Swart, Joost F
AU  - Swart JF
AD  - University Medical Center Utrecht and University of Utrecht, Utrecht, The 
      Netherlands.
FAU - Sinha, Rashmi
AU  - Sinha R
AD  - Systemic Juvenile Idiopathic Arthritis Foundation, Cincinnati, Ohio.
FAU - Roth, Johannes
AU  - Roth J
AD  - University of Munster, Munster, Germany.
FAU - Schulert, Grant S
AU  - Schulert GS
AUID- ORCID: 0000-0001-5923-7051
AD  - Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 
      Cincinnati, Ohio.
FAU - Grom, Alexei A
AU  - Grom AA
AD  - Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 
      Cincinnati, Ohio.
FAU - Van Loosdregt, Jorg
AU  - Van Loosdregt J
AD  - University Medical Center Utrecht and University of Utrecht, Utrecht, The 
      Netherlands.
FAU - Vastert, Sebastiaan J
AU  - Vastert SJ
AD  - University Medical Center Utrecht and University of Utrecht, Utrecht, The 
      Netherlands.
LA  - eng
GR  - LLP10/ReumaNederland/
GR  - The Merel Stichting/
GR  - The Systemic JIA foundation/
GR  - The Van Dam van Os Stichting/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231106
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Biological Products)
RN  - 0 (Receptors, Interleukin-1)
RN  - 0 (IL1RN protein, human)
SB  - IM
MH  - Humans
MH  - *Arthritis, Juvenile/drug therapy/genetics
MH  - Interleukin 1 Receptor Antagonist Protein/genetics/therapeutic use
MH  - HLA-DRB1 Chains/genetics
MH  - Prospective Studies
MH  - *Biological Products/therapeutic use
MH  - *Eosinophilia/drug therapy
MH  - Receptors, Interleukin-1/therapeutic use
EDAT- 2023/07/20 19:14
MHDA- 2023/12/29 06:43
CRDT- 2023/07/20 13:54
PHST- 2023/06/07 00:00 [revised]
PHST- 2023/03/26 00:00 [received]
PHST- 2023/07/07 00:00 [accepted]
PHST- 2023/12/29 06:43 [medline]
PHST- 2023/07/20 19:14 [pubmed]
PHST- 2023/07/20 13:54 [entrez]
AID - 10.1002/art.42656 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2024 Jan;76(1):119-129. doi: 10.1002/art.42656. Epub 2023 
      Nov 6.