Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France

Lequerré, Thierry; Quartier, Pierre; Rosellini, David; Alaoui, F.Z.; Bandt, M. De; Mejjad, O.; Koné‐Paut, Isabelle; Michel, Margot; Dernis, E.; Khellaf, Meheni; Limal, Nicolas; Job-Deslandre, C; Fautrel, Bruno; Loët, Xavier Le; Sibilia, Jean; Inflammation, Club Rhumatismes et

doi:10.1136/ard.2007.076034

Cited by 372 publications

(270 citation statements)

References 11 publications

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“…22 However, there is evidence that there may be at least two sJIA patient subpopulations: Anakinra-responsive and non-responsive; in a trial of French patients approximately half were responsive. 23 Comparable findings were also observed in an Italian cohort and also in a UK cohort (unpublished observations). Similar results have been seen with the receptor based IL-1 blocker, IL-1 TRAP (Rilonacept).…”

Section: Introductionsupporting

confidence: 54%

“…The observation that just under half of patients treated with Anakinra show a positive response 23 suggests that there may be at least two different populations of sJIA patients; in only some of whom the main underlying cause for disease is a defect in IL-1 regulation. This means that the associations observed in this study may only have a significant effect in those patients responsive to Anakinra, potentially confounding the results due to admixture.…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive association study of genetic variants in the IL-1 gene family in systemic juvenile idiopathic arthritis

et al. 2008

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Patients with systemic juvenile idiopathic arthritis (sJIA) have a characteristic daily spiking fever and elevated levels of inflammatory cytokines. Members of the interleukin-1 (IL-1) gene family have been implicated in various inflammatory and autoimmune diseases, and treatment with the IL-1 receptor antagonist, Anakinra, shows remarkable improvement in some patients. This work describes the most comprehensive investigation to date of the involvement of the IL-1 gene family in sJIA. A two-stage case-control association study was performed to investigate the two clusters of IL-1 family genes using a tagging single nucleotide polymorphism (SNP) approach. Genotyping data of 130 sJIA patients and 151 controls from stage 1 highlighted eight SNPs in the IL1 ligand cluster region and two SNPs in the IL1 receptor cluster region as showing a significant frequency difference between the populations. These 10 SNPs were typed in an additional 105 sJIA patients and 184 controls in stage 2. Meta-analysis of the genotypes from both stages showed that three IL1 ligand cluster SNPs (rs6712572, rs2071374 and rs1688075) and one IL1 receptor cluster SNP (rs12712122) show evidence of significant association with sJIA. These results indicate that there may be aberrant control of the activity of the IL-1 family in sJIA patients causing the increased susceptibility to the disease.

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Section: Introductionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Comprehensive association study of genetic variants in the IL-1 gene family in systemic juvenile idiopathic arthritis

et al. 2008

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“…A recent study in 20 patients with systemic-onset juvenile idiopathic arthritis reported that anakinra was effective in some patients, with 50% and 25% of patients achieving 30% and 50% improvements, respectively, in American College of Rheumatology (ACR) Fig. 3 Anakinra plasma concentrations pedi core set criteria [34]. Recent data also support anakinra as second-line therapy for systemic-onset juvenile idiopathic arthritis, with six of seven patients from a case series in the UK experiencing rapid early improvement in systemic symptoms and joint disease [35].…”

Section: Discussionmentioning

confidence: 99%

Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study

et al. 2008

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This study assessed the safety and preliminary efficacy of the interleukin-1 receptor antagonist anakinra in patients with polyarticular-course juvenile rheumatoid arthritis (JRA). Eighty-six patients entered a 12-week open-label run-in phase (1 mg/kg anakinra daily, ≤100 mg/day). Fifty responders were randomized to anakinra or placebo in a 16-week blinded phase, followed by a 12-month open-label extension (N=44). Due to low enrollment, the primary endpoint was changed from efficacy to safety. The incidence and nature of adverse events were similar across all study phases, with the exception of injection site reactions, which were mild to moderate and decreased with time. Anakinra produced a nonsignificant (P=0.11) reduction in disease flares compared with placebo. When normalized to 1 mg/kg dose, anakinra plasma concentrations were similar to values in adult patients with rheumatoid arthritis. These results indicate that anakinra 1 mg/kg once daily (≤100 mg/day) is safe and well tolerated in patients with JRA.

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“…Anakinra, an interleukin 1 receptor antagonist, has been shown to effectively treat sJIA 1,2,3,4,5 ; however, some patients may require multiple painful daily injections to control their disease. Another biologic, abatacept, selectively modulates the CD80/CD86:CD28 costimulatory signal necessary for T cell activation 6 and has been shown to be effective in treating patients with sJIA who have a polyarticular course 7 .…”

Section: To the Editormentioning

confidence: 99%

Combination Therapy of Abatacept and Anakinra in Children with Refractory Systemic Juvenile Idiopathic Arthritis: A Retrospective Case Series: Table 1.

Record¹,

Beukelman²,

Cron³

2011

J Rheumatol

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Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France

Cited by 372 publications

References 11 publications

Comprehensive association study of genetic variants in the IL-1 gene family in systemic juvenile idiopathic arthritis

Comprehensive association study of genetic variants in the IL-1 gene family in systemic juvenile idiopathic arthritis

Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study

Combination Therapy of Abatacept and Anakinra in Children with Refractory Systemic Juvenile Idiopathic Arthritis: A Retrospective Case Series: Table 1.

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