Intravenous Anakinra May Be Useful in the Treatment of Cytokine Storm Syndromes

intravenous antibiotics
intravenous antibiotics
Authors of this viewpoint described the current challenges in the management of cytokine storm syndromes and reviewed the safety profile of intravenous anakinra.

Intravenous anakinra may be useful in the management of cytokine storm syndromes, according to a viewpoint published in Lancet Rheumatology.

Clinical presentations of hemophagocytic lymphohistiocytosis (HLH) can be described as cytokine storm syndromes, which represent a significant interface between rheumatology and general internal medicine. Cytokine storm syndromes have a high mortality rate, and therefore, early diagnosis and initiation of treatment is vital to improve patient outcomes. Interleukin (IL)-1 is pivotal to the etiopathogenesis of hyperinflammation; however, subcutaneous dosing is often challenging in these patients because of the unreliable absorption and multiple daily injections needed to achieve high doses during critical illness.

According to the authors, some of the current challenges in the management of cytokine storm syndromes include:

  • Lack of a unified nomenclature and cross-specialty collaboration to pool resources and expertise.
  • Etiopathogenesis of cytokine storm syndromes not fully elucidated but thought to involve a failure of the normal perforin-dependent cytolytic function of natural killer cells and cytotoxic CD8 T cells and defective clearance of antigenic stimuli resulting in continuous activation and proliferation of macrophages hemophagocytes, and an autocrine loop of proinflammatory cytokines.
  • Missed and delayed diagnoses because of clinical criteria and potential confounders.
  • Selection of treatment, which is largely based on expert consensus and extrapolated from familial HLH, and the benefits of potentially life-saving treatments balanced against potential risks for immunosuppression.

Anakinra, a recombinant humanized IL-1 receptor antagonist, is the recommended treatment option for HLH; however, there is no guidance on the route of administration. Intravenous anakinra is already in clinical use in cases of secondary hemophagocytic lymphohistiocytosis or macrophage activation syndrome (sHLH/MAS), despite its offlicense indication, lack of efficacy, and issues in administration route.

The report states that the frequency of intravenous anakinra compared to subcutaneous delivery in clinical practice remains unknown; however, among 46 patients admitted to 3 international tertiary centers for sHLH/MAS and treated with anakinra for 12 months, 18 (39%) received the medication via the intravenous route. Furthermore, safety profiles from clinical trials of intravenous anakinra (24-48 mg/kg/d) in sepsis, and long-term safety profiles for anakinra in rheumatoid arthritis (3 years) and cryopyrin-associated periodic syndromes (5 years) have proven the effectiveness of the drug. Pharmacokinetic analysis of anakinra revealed that intravenous vs subcutaneous dosing of anakinra enabled the achievement of a higher and faster maximal plasma concentration. Intravenous anakinra may be the preferred method in cases where subcutaneous administration is relatively contraindicated, such as among patients who have severe thrombocytopenia, hemorrhagic complications, subcutaneous skin edema, or neurologic symptoms.

“Cross-specialty management and collaboration, with the generation of international, [multicenter] registries and biobanks, are needed to better understand the [etiopathogenesis] and improve the poor prognosis of cytokine storm syndrome,” the authors concluded.


Mehta P, Cron RQ, Hartwell J, Manson JJ, Tattersall RS. Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome [published online April 23, 2020]. Viewpoint. Lancet Rheumatol. doi:10.1016/S2665-9913(20)30096-5