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Publications

Journal Article Systematic Review Research Support, Non-U.S. Gov't Ppublish 6 citations

PubMed: 39058514 DOI: 10.1093/rheumatology/keae391

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

Rheumatology (Oxford) 64(1):32-44

Authors: Francesco Baldo, Remco G A Erkens, Mao Mizuta, Greta Rogani, Federica Lucioni, 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

Affiliations

  • Pediatric Immuno-Rheumatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
  • ASST Gaetano Pini, Milan, Italy.
  • Department of Pediatric Rheumatology and Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan.
  • Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
  • University Hospital Muenster, Muenster, Germany.
  • Reumatologia e Malattie Autoinfiammatorie, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
  • University Hospital Centre Zagreb, University School of Medicine, Zagreb, Croatia.
  • Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
  • Great Ormond Street Hospital for Children, London, UK.
  • University College London Institute of Child Health, London, UK.
  • Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Aflac Cancer and Blood Disorders Center Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.
  • University of Alabama at Birmingham, Birmingham, AL, USA.
  • Cincinnati Children's Hospital, Cincinnati, OH, USA.
  • Dana Dwek Children's Hospital, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel.
  • Department of Pediatrics, Karolinska University Hospital, Stockholm, Sweden.
  • Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
  • SRCC Childrens Hospital, Mumbai, India.
  • Department of Pediatrics, Hacettepe University, Ankara, Turkey.
  • Université Paris-Cité, Paris, France.
  • RAISE Reference Centre, Pediatric Immunology-Hematology and Rheumatology Unit, Necker-Enfants Malades Hospital, Paris, France.
  • Direzione Scientifica, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
  • Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
  • University of Ottawa, Ottawa, Canada.
  • Systemic JIA Foundation, Cincinnati, OH, USA.
  • Gaslini Trial Centre/Servizio Sperimentazioni Cliniche Pediatriche, PRINTO, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

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.

MeSH

Macrophage Activation, Prednisolone, Macrophages, Rheumatic Diseases, Metaphor, Therapeutics, Macrophage Activation Syndrome

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