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

Objective To evaluate the applicability of the 2016 EULAR/ACR/PRINTO macrophage activation syndrome (MAS) classification criteria in patients with Still's disease (sJIA‐SD) treated with IL‐1‐targeted therapy and to assess the incidence of MAS in this context. Methods We analyzed retrospective and prospective data from Dutch sJIA‐SD patients (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 sJIA‐SD patients treated with IL‐1‐targeted therapy (anakinra or canakinumab) with at least two year follow‐up were selected. Clinical and laboratory data was extracted from the electronic patient files. Results A total of 22 patients experienced 29 MAS episodes while on IL‐1‐targeted treatment. 7 patients had recurrent MAS episodes (not all on IL‐1 blockade). The 2016 criteria for MAS in sJIA‐SD were met for 28/29 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% (12/66 patients, with 11/12 while on IL‐1 inhibition). This incidence is comparable to that observed in historical corticosteroid‐treated patients. Half of MAS episodes occurred within 3 months after diagnosis and Epstein‐Barr virus was the most common identifiable trigger. Conclusion While first‐line anakinra in new‐onset sJIA‐SD has demonstrated high response rates, our data suggests 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 shows that the EULAR/ACR/PRINTO 2016 MAS classification criteria remain applicable to patients receiving IL‐1‐targeted therapy.