Impact of Interleukin-1 Blockade on the Development of Macrophage Activation Syndrome in Still Disease: Incidence and Diagnostic Validity of the EULAR/ACR/PRINTO 2016 MAS Classification Criteria

  • Remco G A Erkens
  • , Greta Rogani
  • , Laura Huber
  • , Anouk Verwoerd
  • , Dieneke Schonenberg-Meinema
  • , J Merlijn van den Berg
  • , Wineke Armbrust
  • , G Elizabeth Legger
  • , Sylvia Kamphuis
  • , Ellen J H Schatorjé
  • , Esther P A H Hoppenreijs
  • , Joost F Swart
  • , Marc H A Jansen
  • , Jorg van Loosdregt
  • , Sebastiaan J Vastert

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objective: To evaluate the applicability of the 2016 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR)/Paediatric Rheumatology International Trials Organisation (PRINTO) macrophage activation syndrome (MAS) classification criteria in patients with Still disease and systemic juvenile idiopathic arthritis (sJIA-SD) treated with interleukin-1 (IL-1)–targeted therapy and to assess the incidence of MAS in this context. Methods: We analyzed retrospective and prospective data from Dutch patients with sJIA-SD (diagnosis 2008–2017, n = 54) and data from a nationwide prospective Dutch cohort and intervention study (diagnosis 2017–2022, n = 66). From these cohorts, MAS episodes developing in patients with sJIA-SD treated with IL-1–targeted therapy (anakinra or canakinumab) with at least two years of follow-up were selected. Clinical and laboratory data were extracted from the electronic patient files. Results: A total of 22 patients experienced 29 MAS episodes while receiving IL-1–targeted treatment. Seven patients had recurrent MAS episodes (not all while receiving IL-1 blockade). The 2016 criteria for MAS in sJIA-SD were met for 28 of 29 MAS episodes (97%). Within the prospective nationwide cohort starting anakinra as first-line monotherapy, the incidence rate of MAS in the first two years of disease was 18% (12 of 66 patients, with 11 of 12 while receiving IL-1 inhibition). This incidence is comparable to that observed in historical glucocorticoid-treated patients. Half of MAS episodes occurred within three months after diagnosis, and Epstein-Barr virus was the most common identifiable trigger. Conclusion: Although first-line anakinra in new-onset sJIA-SD has demonstrated high response rates, our data suggest the incidence of MAS in the first two years of disease is not reduced. Patients appear to be particularly at risk early in disease. Importantly, our data show that the EULAR/ACR/PRINTO 2016 MAS classification criteria remain applicable to patients receiving IL-1–targeted therapy.

Original languageEnglish
Pages (from-to)1784-1798
Number of pages15
JournalArthritis & Rheumatology
Volume77
Issue number12
Early online date26 May 2025
DOIs
Publication statusPublished - Dec 2025

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