Background/Purpose: Systemic Juvenile Idiopathic Arthritis (sJIA) is a severe inflammatory disease with auto-inflammatory characteristics. The introduction of targeted biologic therapies has revolutionized the treatment and as such improved outcomes for children with sJIA. The IL-1 receptor antagonist, anakinra, is used as first-line treatment for sJIA in the Netherlands since 2008 and has been shown to induce and sustain inactive disease with approximately 50% of patients being able to taper and stop within the first year of disease [Ter Haar 2019 PMID: 30848528]. However, also with this strategy, around 25-30% of patients experience a more refractory disease course, necessitating maintenance therapy. Multiple eposodes of Macrophage Activation Syndrome (MAS), a severe complication of sJIA, has been suggested to be one of the refractory sJIA phenotypes [Erkens 2021 PMID: 34635293]. The EULAR/ACR/PRINTO 2016 MAS classification criteria [Ravelli 2016 PMID: 26314788] have been developed to facilitate the diagnosis of MAS in sJIA. However, there is still a scarcity of data on their performance in sJIA patients treated with biologicals. Recent studies indicate that treatment of sJIA with biologicals might change some clinical and laboratory features of MAS [Schulert 2018 PMID: 28499329]. We therefore aimed to describe the (clinical and laboratory) characteristics of sJIA patients who developed MAS while treated with first-line anakinra and to evaluate whether the 2016 MAS classification criteria are still applicable in these patients.

Methods: In this cohort study, we used both retrospective data (2008-2016) as well as data from a nationwide, prospective multicentre cohort study (Early start of Targeted Treatment in Systemic JIA, ESTIS, 2017 onwards) selecting patients who developed MAS during treatment with first-line anakinra. In total, 15 patients were included with at least 1 year of follow up. We described the demographic, clinical, laboratory and immunologic features of MAS in patients started on recombinant IL-1RA therapy as first-line therapy for sJIA.

Results: We included fifteen patients, with a total of sixteen episodes of MAS. The estimated incidence of MAS was 15.6% in the first year after start of anakinra (7/45 in the prospective nationwide, multicentre cohort study ESTIS in the period 2017-2021). Eleven out of the fifteen patients were female. A significant share (11/16 episodes) of the MAS episodes occurred within 2 months after the onset of sJIA and four episodes (4/16, 25%) were triggered by a primo EBV infection at the onset of MAS. All episodes of MAS met the EULAR/ACR/PRINTO 2016 classification criteria for MAS in sJIA.

Conclusion: While first-line treatment with anakinra in sJIA results in high response rates and minimal corticosteroid use, this strategy does not seem to lower the risk or incidence of MAS in SJIA in the first year of disease. The EULAR/ACR/PRINTO 2016 classification criteria for MAS are applicable to patients treated with first-line anakinra. We recommend to closely monitor the laboratory features from the classification criteria in (female) patients within the first months after the onset of sJIA and suggest to test all patients at the onset of sJIA on EBV status.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/characteristics-of-macrophage-activation-syndrome-in-systemic-jia-patients-receiving-anakinra-as-first-line-treatment/