2022: Clinical Predictors of Macrophage Activation Syndrome and Treatment Outcomes in Adult-Onset Still’s Disease: A 24-Year Single-Center Experience

Background/Purpose: Adult-onset Still’s disease (AOSD) is a rare autoinflammatory disorder with heterogeneous manifestations. Its most severe complication, macrophage activation syndrome (MAS), occurs in up to 15% of cases and carries high mortality. Early identification of high-risk patients remains challenging and data on long-term outcomes are limited. This study aimed to identify clinical predictors of MAS and assess treatment outcomes and survival in a large AOSD cohort.

Methods: This retrospective study included 93 adults diagnosed with AOSD between 2000 and 2024 at a tertiary university hospital. All fulfilled Yamaguchi criteria and MAS was diagnosed per HLH-2004 and 2016 EULAR/ACR/PRINTO criteria. Demographic, clinical, laboratory and treatment data were included. Pouchot’s disease severity scores were calculated based on presenting symptoms. Associations with MAS were evaluated using univariate and multivariate logistic regression.

Results: The mean age at onset was 33.6 ± 14.4 years and 64.5% of the patients were female. Common symptoms are summarized in Table 1. MAS developed in 14.1% and was associated with younger age at onset (27.7 vs. 34.9 years; p=0.037) and higher baseline ferritin (p=0.0489). Multivariate analysis confirmed elevated ferritin (p=0.0489) and higher Pouchot’s scores (p=0.0204) as independent MAS predictors, as detailed in Table 2.

Diagnostic delay averaged 1.33 ± 2.8 (IQR, 25-75:0-1) years and was associated with lower methotrexate response (p=0.0457) and corticosteroid tapering success (p < 0.01). Patients with shorter delays achieved steroid-free remission more frequently (median 4 vs. 8 years; p< 0.01).

Glucocorticoids were prescribed to 93.3% of patients, methotrexate to 91.3% and anakinra to 47.2%. Tocilizumab (31.4%) and canakinumab (15.5%) were also used. JAK inhibitors achieved complete remission in all treated patients (3/3) including one with MAS. Steroid discontinuation was achieved in 37.8% of patients. Treatment responses are shown in Table 3. Overall survival was 94% with MAS accounting for two deaths.

Conclusion: Elevated ferritin and higher Pouchot’s scores independently predict MAS, supporting their use in early risk stratification. Diagnostic delay reduces treatment response and remission, highlighting the importance of prompt diagnosis. Although glucocorticoids remain the initial therapy, biologics such as anakinra and tocilizumab combined with JAK inhibitors are effective for remission in refractory cases. Early diagnosis and phenotype-guided treatment, favoring IL-1 inhibitors for systemic manifestations and IL-6 inhibitors for articular involvement, may further improve outcomes.