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. 2025 Jan 1;64(1):32-44.
doi: 10.1093/rheumatology/keae391.

Current treatment in macrophage activation syndrome worldwide: a systematic literature review to inform the METAPHOR project

Francesco Baldo  1   2 , Remco G A Erkens  3 , Mao Mizuta  4 , Greta Rogani  3 , Federica Lucioni  1 , Claudia Bracaglia  5 , Dirk Foell  6 , Marco Gattorno  7 , Marija Jelusic  8 , Jordi Anton  9 , Paul Brogan  10   11 , Scott Canna  12 , Shanmuganathan Chandrakasan  13 , Randy Q Cron  14 , Fabrizio De Benedetti  5 , Alexei Grom  15 , Merav Heshin-Bekenstein  16 , AnnaCarin Horne  17   18 , Raju Khubchandani  19 , Seza Ozen  20 , Pierre Quartier  21   22 , Angelo Ravelli  23 , Masaki Shimizu  24 , Grant Schulert  15 , Christiaan Scott  25 , Rashmi Sinha  26 , Nicolino Ruperto  27 , Joost F Swart  3 , Sebastiaan Vastert  3 , Francesca Minoia  1 ; PReS MAS/sJIA Working Party and Paediatric Rheumatology International Trial Organization
Collaborators, Affiliations

Current treatment in macrophage activation syndrome worldwide: a systematic literature review to inform the METAPHOR project

Francesco Baldo et al. Rheumatology (Oxford). .

Abstract

Objective: To assess current treatment in macrophage activation syndrome (MAS) worldwide and to highlight any areas of major heterogeneity of practice.

Methods: A systematic literature search was performed in both EMBASE and PubMed databases. Paper screening was done by two independent teams based on agreed criteria. Data extraction was standardized following the PICO framework. A panel of experts assessed paper validity, using the Joanna Briggs Institute appraisal tools and category of evidence (CoE) according to EULAR procedure.

Results: Fifty-seven papers were finally included (80% retrospective case-series), describing 1148 patients with MAS: 889 systemic juvenile idiopathic arthritis (sJIA), 137 systemic lupus erythematosus (SLE), 69 Kawasaki disease (KD) and 53 other rheumatological conditions. Fourteen and 11 studies specified data on MAS associated to SLE and KD, respectively. All papers mentioned glucocorticoids (GCs), mostly methylprednisolone and prednisolone (90%); dexamethasone was used in 7% of patients. Ciclosporin was reported in a wide range of patients according to different cohorts. Anakinra was used in 179 MAS patients, with a favourable outcome in 83% of sJIA-MAS. Etoposide was described by 11 studies, mainly as part of HLH-94/04 protocol. Emapalumab was the only medication tested in a clinical trial in 14 sJIA-MAS, with 93% of MAS remission. Ruxolitinib was the most reported Janus kinase inhibitor in MAS.

Conclusion: High-dose GCs together with IL-1 and IFNγ inhibitors have shown efficacy in MAS, especially in sJIA-associated MAS. However, the global level of evidence on MAS treatment, especially in other conditions, is still poor and requires standardized studies to be confirmed.

Keywords: haemophagocytic lymphohistiocytosis; haemophagocytic syndromes; macrophage activation syndrome; treatment.

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Figures

Figure 1.
Figure 1.
Flowchart for the systematic literature review, including detailed exclusion criteria, and results of the selection process. aSeven case reports were exceptionally included after a discussion within the core team for the relevancy of the medication or the condition reported. CART-cell: chimeric antigen receptor T cell; HLH: haemophagocytic lymphohistiocytosis; HSCT: haematopoietic stem cell transplantation; MAS: macrophage activation syndrome
See this image and copyright information in PMC

References

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