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2020 ; 2
(6
): e358-e367
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Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic
lymphohistiocytosis or macrophage activation syndrome
#MMPMID32373790
Mehta P
; Cron RQ
; Hartwell J
; Manson JJ
; Tattersall RS
Lancet Rheumatol
2020[Jun]; 2
(6
): e358-e367
PMID32373790
show ga
The term cytokine storm syndromes describes conditions characterised by a
life-threatening, fulminant hypercytokinaemia with high mortality. Cytokine storm
syndromes can be genetic or a secondary complication of autoimmune or
autoinflammatory disorders, infections, and haematological malignancies. These
syndromes represent a key area of interface between rheumatology and general
medicine. Rheumatologists often lead in management, in view of their experience
using intensive immunosuppressive regimens and managing cytokine storm syndromes
in the context of rheumatic disorders or infection (known as secondary
haemophagocytic lymphohistiocytosis or macrophage activation syndrome
[sHLH/MAS]). Interleukin (IL)-1 is pivotal in hyperinflammation. Anakinra, a
recombinant humanised IL-1 receptor antagonist, is licenced at a dose of 100 mg
once daily by subcutaneous injection for rheumatoid arthritis, systemic juvenile
idiopathic arthritis, adult-onset Still's disease, and cryopyrin-associated
periodic syndromes. In cytokine storm syndromes, the subcutaneous route is often
problematic, as absorption can be unreliable in patients with critical illness,
and multiple injections are needed to achieve the high doses required. As a
result, intravenous anakinra is used in clinical practice for sHLH/MAS, despite
this being an off-licence indication and route of administration. Among 46
patients admitted to our three international, tertiary centres for sHLH/MAS and
treated with anakinra over 12 months, the intravenous route of delivery was used
in 18 (39%) patients. In this Viewpoint, we describe current challenges in the
management of cytokine storm syndromes and review the pharmacokinetic and safety
profile of intravenous anakinra. There is accumulating evidence to support the
rationale for, and safety of, intravenous anakinra as a first-line treatment in
patients with sHLH/MAS. Intravenous anakinra has important clinical relevance
when high doses of drug are required or if patients have subcutaneous oedema,
severe thrombocytopenia, or neurological involvement. Cross-speciality management
and collaboration, with the generation of international, multi-centre registries
and biobanks, are needed to better understand the aetiopathogenesis and improve
the poor prognosis of cytokine storm syndromes.