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

Abstract

ObjectiveHLA‐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 new‐onset sJIA patients treated with anakinra as first‐line therapy.MethodsHLA and IL1RN risk alleles were identified via whole genome sequencing. Treatment responses and complications were compared between carriers versus non‐carriers.ResultsSeventeen of 65 patients (26%) carried HLA‐DRB1*15:01, comparable to 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 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 non‐carriers at disease‐onset (6.2% vs 14.9%, p=0.67) nor after the start of anakinra (35.3% versus 37.5% in the first 2 years of disease).ConclusionWe 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 3 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 biological therapy in new‐onset sJIA patients irrespective of HLA‐DRB1 background or IL1RN variants.image

Comparative efficacy and safety of different drugs in patients with systemic juvenile idiopathic arthritis: A systematic review and network meta-analysis

“…Anakinra is an IL-1 receptor antagonist that is non-glycosylated and created through genetic recombination. [ 7 ] Tocilizumab is a monoclonal antibody that humanizes the anti-human IL-6 receptor, which prevents IL-6 signaling. [ 8 ] Canakinumab, on the other hand, is a monoclonal antibody that is fully human and anti-IL-1β, selectively binding to IL-1β and preventing its signaling.…”