Early Treatment and IL1RN Single Nucleotide Polymorphisms Affect Response to Anakinra in Systemic Juvenile Idiopathic Arthritis

Marianna Nicoletta Rossi¹, Manuela Pardeo², Denise Pires Marafon², Emanuela Sacco², Chiara Passarelli³, Claudia Bracaglia², Chiara Perrone³, Anna Tulone⁴, Giusi Prencipe⁵ and Fabrizio De Benedetti⁶, ¹Laboratory of Immuno-Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Lazio, Italy, ²Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy, Rome, Italy, ³U.O.C. Laboratory of Medical Genetics, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy, ⁴Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy, ⁵Laboratory of Immuno-Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesu', Rome, Italy, ⁶Division of Rheumatology, Laboratory of Immuno-Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy, Rome, Italy

Meeting: ACR Convergence 2020

Keywords: Autoinflammatory diseases, cytokines, genetics, Juvenile idiopathic arthritis

Session Information

Date: Friday, November 6, 2020

Title: Pediatric Rheumatology – Basic Science Poster

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Systemic juvenile idiopathic arthritis (sJIA) represents 10-20% of all chronic arthritis during childhood. The interleukin 1 (IL-1) play a pivotal role in the pathogenesis of the disease. Indeed, several studies confirmed the therapeutic efficacy of anakinra (recombinant IL-1 receptor antagonist) in a significant portion of patients with sJIA, especially in the first phase of disease. The use of anakinra as first-line therapy can benefit from the so-called “window of opportunity”, for which the evolution of the disease can be modified preventing the onset of chronic arthritis. Despite a good response to anakinra in a high percentage of patients, there is a subset of non-responders. The early identification of non-responder patients is of primary importance to avoid the progression towards chronic arthritis. Some single nucleotide polymorphisms (SNPs) in IL1RN gene have been found associated with sJIA, and recently, a cluster of SNPs in the IL1RN non-translated region has been suggested as a possible predictor of non-response to anakinra. The aim of this study was to evaluate the impact of early treatment and genetic variants in IL1RN gene on the response to anakinra in sJIA.

Methods: Response to anakinra was considered as clinically inactive disease (CID) at 6 months, without glucocorticoids treatment. Demographic, clinical and laboratory characteristics of 56 patients were analyzed in univariate and multivariate analysis as predictors of response to treatment. Six SNPs in IL1RN gene were genotyped by qPCR or Sanger sequencing. Haplotype mapping was performed with Haploview software and IL1RN mRNA expression in whole blood from patients before anakinra initiation was assessed by qPCR.

Results: After 6 months of treatment, 73.2% of patients met the criteria for CID off glucocorticoids. In univariate analysis the variable strongly related with the response was disease duration from onset to anakinra initiation, with an optimal cut-off at 3 months. Patients who started anakinra after 3 months from disease onset had an 8-fold higher risk of non-response at 6 months. We confirmed that the 6 IL1RN SNPs were inherited as a common haplotype in our cohort of patients. We found that homozygosity for at least one high expression SNP correlates with higher IL1RN mRNA levels and was associated with a 6 fold higher risk of non-response, independently of disease duration.

Conclusion: Our results confirm the important role of early IL-1 inhibition and suggest that genetic IL1RN variants predict non-response to therapy with IL-1 blockade in patients with sJIA.

Disclosure: M. Rossi, None; M. Pardeo, None; D. Pires Marafon, None; E. Sacco, None; C. Passarelli, None; C. Bracaglia, SOBI, 8; C. Perrone, None; A. Tulone, None; G. Prencipe, None; F. De Benedetti, Novartis, 2, 8, Novimmune, 2, 9, Sobi, 2, 8, 9, Roche, 2, 8, Pfizer, 2, Sanofi, 2, AbbVie, 8.

To cite this abstract in AMA style:

Rossi M, Pardeo M, Pires Marafon D, Sacco E, Passarelli C, Bracaglia C, Perrone C, Tulone A, Prencipe G, De Benedetti F. Early Treatment and IL1RN Single Nucleotide Polymorphisms Affect Response to Anakinra in Systemic Juvenile Idiopathic Arthritis [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/early-treatment-and-il1rn-single-nucleotide-polymorphisms-affect-response-to-anakinra-in-systemic-juvenile-idiopathic-arthritis/. Accessed .

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