What is the mechanism of action of Anakinra (anakinra) in Hemophagocytic Lymphohistiocytosis (HLH)?

From the Guidelines

Anakinra is an interleukin-1 receptor antagonist used in the treatment of Hemophagocytic Lymphohistiocytosis (HLH), and its mechanism of action is to block the action of interleukin-1 (IL-1), a pro-inflammatory cytokine that plays a key role in the pathogenesis of HLH 1.

Key Mechanism of Action

• By binding to the IL-1 receptor, anakinra prevents the activation of downstream inflammatory pathways, thereby reducing the excessive immune activation and tissue damage characteristic of HLH.
• The use of anakinra in HLH is supported by studies that demonstrate its efficacy in reducing inflammatory cytokine levels and improving clinical outcomes in patients with HLH 1.

Dosage and Administration

• The recommended dose of anakinra in HLH is typically 2-6 mg/kg/day, administered subcutaneously, with treatment duration individualized based on clinical response and disease activity 1.
• Anakinra has been used in combination with other therapies, such as corticosteroids and IL-6 antagonist therapy, to treat HLH in patients with refractory disease 1.

Clinical Considerations

• The diagnosis of HLH can be challenging, and anakinra should be used in conjunction with other diagnostic criteria and clinical evaluation to guide treatment decisions 1.
• Anakinra has been shown to be effective in reducing the incidence of HLH-associated mortality and improving clinical outcomes in patients with HLH 1.

From the Research

Mechanism of Action of Anakinra in HLH

The mechanism of action of Anakinra in Hemophagocytic Lymphohistiocytosis (HLH) involves the blockade of interleukin-1 (IL-1) receptors, which play a crucial role in the cytokine storm associated with HLH.

• Anakinra, a recombinant IL-1 receptor antagonist, has been shown to effectively treat macrophage activation syndrome (MAS) and secondary HLH (sHLH) 2, 3, 4, 5, 6.
• The use of anakinra in HLH has been associated with improved outcomes, including higher response rates and longer survival, compared to traditional therapies such as etoposide-based treatments 6.
• The efficacy and safety of anakinra in HLH have been demonstrated in various studies, with fever resolution and decreased CRP and ferritin levels observed in patients treated with anakinra 2, 5.

Administration and Dosage

Anakinra can be administered subcutaneously or intravenously, with the latter being proposed for critically unwell patients.

• Subcutaneous dosing regimens have been widely described, with doses ranging from 6-10 mg/kg/day divided over four doses 2.
• Intravenous dosing has been shown to be effective in severe sHLH, with a wide therapeutic dosing range and tolerability 3, 4.

Clinical Outcomes

The use of anakinra in HLH has been associated with improved clinical outcomes, including:

• Higher response rates, with cumulative incidence of response at 30 days ranging from 83.3% to 90.5% 5, 6.
• Longer survival, with overall survival at 1 year ranging from 63% to 77.8% 4, 6.
• Reduced relapse rates, with cumulative incidence of relapse at 1 year ranging from 0% to 50% 6.