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. 2020 Mar;72(3):499-505.
doi: 10.1002/art.41130. Epub 2020 Jan 28.

Impact of IL1RN Variants on Response to Interleukin-1 Blocking Therapy in Systemic Juvenile Idiopathic Arthritis

Claas Hinze  1 , Sabrina Fuehner  1 , Christoph Kessel  1 , Helmut Wittkowski  1 , Elke Lainka  2 , Melanie Baehr  2 , Boris Hügle  3 , Johannes-Peter Haas  3 , Gerd Ganser  4 , Elisabeth Weißbarth-Riedel  5 , Annette Jansson  6 , Dirk Foell  1
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Impact of IL1RN Variants on Response to Interleukin-1 Blocking Therapy in Systemic Juvenile Idiopathic Arthritis

Claas Hinze et al. Arthritis Rheumatol. 2020 Mar.

Abstract

Objective: 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.

Methods: 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.

Results: 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).

Conclusion: 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).

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References

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