Francesco Baldo, Greta Rogani, Remco G A Erkens, Mao Mizuta, Claudia Bracaglia, Dirk Foell, Marco Gattorno, Marija Jelusic, Jordi Anton, Paul Brogan, Scott Canna, Shanmuganathan Chandrakasan, Randy Q Cron, Fabrizio De Benedetti, Alexei Grom, Merav Heshin-Bekenstein, AnnaCarin Horne, Raju Khubchandani, Seza Ozen, Pierre Quartier, Angelo Ravelli, Masaki Shimizu, Grant Schulert, Christiaan Scott, Rashmi Sinha, Nicolino Ruperto, Joost F Swart, Sebastiaan Vastert, Francesca Minoia, PReS MAS/sJIA Working Party and the Paediatric Rheumatology International Trial Organisation (PRINTO)
MAS management remains highly heterogeneous worldwide. While glucocorticoids remain foundational, reducing steroid reliance through equitable access to immunomodulatory therapies and advancing mechanism-based strategies represent critical priorities in optimizing MAS care.
OBJECTIVE: Macrophage Activation Syndrome (MAS) is a rare, life-threatening hyperinflammatory condition complicating rheumatologic diseases, most commonly Still's disease (SD). Despite increasing awareness and emerging recommendations, MAS treatment remains heterogeneous worldwide. The METAPHOR project aimed to describe real-life therapeutic strategies for MAS, exploring differences across underlying diseases, geographic regions, physician subspecialties, and drug availability.
METHODS: An international web-based survey was developed by a multidisciplinary expert panel together with a patient representative, following a systematic literature review. The survey was anonymously completed through PReS/PRINTO and the Histiocyte Society networks (October-December 2023). Treatment strategies for MAS across different rheumatologic contexts were explored. Responses were analyzed descriptively and stratified by geography, subspecialty, clinical experience, and underlying disease.
RESULTS: A total of 287 physicians from 64 countries completed the survey, the majority being pediatric rheumatologists with more than 5 years of experience. Glucocorticoids, particularly intravenous methylprednisolone, were consistently identified as 1st-line therapy across all MAS subtypes (for 44% of clinicians as monotherapy). Anakinra, ciclosporin, and intravenous immunoglobulins were the most frequently combined agents. However, their use varied markedly by underlying disease and geographical region, with anakinra preferentially used in SD-MAS. Striking global disparities in drug availability, particularly for anakinra and emapalumab, significantly influenced treatment choices and were associated with increased reliance on steroid monotherapy.
CONCLUSION: MAS management remains highly heterogeneous worldwide. While glucocorticoids remain foundational, reducing steroid reliance through equitable access to immunomodulatory therapies and advancing mechanism-based strategies represent critical priorities in optimizing MAS care.