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. 2023 Sep;111(3):458-476.
doi: 10.1111/ejh.14029. Epub 2023 Jun 21.

Intravenous anakinra for the treatment of haemophagocytic lymphohistiocytosis/macrophage activation syndrome: A systematic review

James E G Charlesworth  1 , Akhila Kavirayani  2
Affiliations

Intravenous anakinra for the treatment of haemophagocytic lymphohistiocytosis/macrophage activation syndrome: A systematic review

James E G Charlesworth et al. Eur J Haematol. 2023 Sep.

Abstract

Background: Haemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) has a potentially high mortality rate. Anakinra, an interleukin-1 receptor antagonist, is now recommended early in HLH/MAS, with intravenous (IV) use proposed in critically unwell patients. This systematic review establishes the literature relating to IV anakinra in secondary HLH/MAS (sHLH/MAS).

Methods: We screened Embase, PubMed, and Medline, including all reports of IV anakinra for HLH or MAS. We extracted age, HLH/MAS trigger, continuous infusion or bolus dosing, and survival.

Results: Twenty-nine case reports/series identified 87 patients (median age 22 years, range 22 months to 84 years), all with sHLH. Amongst identifiable triggers, 43% were systemic infection, 33% rheumatological, 9% oncological. Children had predominantly a rheumatological trigger (48%), whilst adults were more commonly infection-driven (50%). Overall, rheumatologically triggered disease showed greater survival (83.3%), particularly compared with oncological triggers (42.9%). Children had a greater survival, particularly under 10 years (83%, vs. adults, 63%).

Conclusions: Despite IV anakinra recipients likely to be critically unwell, this cohort had similar disease triggers and survival compared to large historical cohorts, and enhances awareness of age and trigger-specific survival patterns. IV anakinra had a wide therapeutic dosing range and tolerability, regardless of trigger, demonstrating substantial utility in severe sHLH/MAS.

Keywords: HLH; IL-1 receptor antagonist; IV anakinra; MAS; cytokine storm; haemophagocytic lymphohistiocytosis; intravenous anakinra; macrophage activation syndrome.

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References

REFERENCES

    1. Crayne CB, Albeituni S, Nichols KE, Cron RQ. The immunology of macrophage activation syndrome. Front Immunol. 2019;10:119.
    1. Crayne C, Cron RQ. Pediatric macrophage activation syndrome, recognizing the tip of the iceberg. Eur J Rheumatol. 2020;7:13-20.
    1. Schulert GS, Grom AA. Pathogenesis of macrophage activation syndrome and potential for cytokine- directed therapies. Annu Rev Med. 2015;66:145-159.
    1. Steen EA, Hermiston ML, Nichols KE, Meyer LK. Digenic inheritance: evidence and gaps in hemophagocytic lymphohistiocytosis. Front Immunol. 2021;12:777851.
    1. Hines MR, von Bahr Greenwood T, Beutel G, et al. Consensus-based guidelines for the recognition, diagnosis, and Management of Hemophagocytic Lymphohistiocytosis in critically ill children and adults. Crit Care Med. 2021;50:860-872.

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