What are the benefits of Interleukin-1 (IL-1) inhibitors for autoinflammatory disorders?

From the Guidelines

Interleukin-1 (IL-1) inhibitors provide significant benefits for patients with autoinflammatory disorders by reducing inflammation, alleviating symptoms, and improving quality of life. The benefits of IL-1 inhibitors for autoinflammatory disorders are well-established, with these medications effectively targeting the underlying pathophysiology of these conditions, which are characterized by dysregulated IL-1 production 1. Specific IL-1 inhibitors include anakinra (Kineret), canakinumab (Ilaris), and rilonacept (Arcalyst), with anakinra typically administered as a daily subcutaneous injection of 100mg for adults (1-2mg/kg for children), and canakinumab given as a subcutaneous injection every 4-8 weeks at 150-300mg for adults (2-4mg/kg for children) 1. These medications are particularly effective for conditions like Familial Mediterranean Fever, CAPS (Cryopyrin-Associated Periodic Syndromes), Still's disease, and recurrent pericarditis, with benefits including rapid reduction in fever, rash, joint pain, and fatigue, as well as normalization of inflammatory markers like CRP and ESR 1. Long-term use of IL-1 inhibitors can prevent amyloidosis and organ damage, which are common complications of untreated autoinflammatory disorders 1. Side effects of IL-1 inhibitors are generally mild and include injection site reactions and increased risk of infections, with regular monitoring for infections and neutropenia recommended during treatment 1. IL-1 inhibitors work by blocking the pro-inflammatory cytokine IL-1, which plays a central role in the inflammatory cascade that drives these disorders, effectively interrupting the pathological immune response at its source. Key points to consider when using IL-1 inhibitors include:

• Monitoring for infection, particularly respiratory tract infections with Streptococcus pneumoniae and skin infections due to Staphylococcus 1
• Vaccination against pneumococcal disease, with pneumococcal vaccines recommended for patients receiving IL-1 inhibitors 1
• Consideration of the risk of disease flare during vaccination, although the benefits of vaccination generally outweigh the potential risks 1
• Regular monitoring of disease activity and adjustment of treatment as needed to achieve and maintain optimal disease control 1.

From the FDA Drug Label

ILARIS (canakinumab) is an interleukin-1β (IL-1β) blocker indicated for the treatment of the following autoinflammatory Periodic Fever Syndromes: Cryopyrin-Associated Periodic Syndromes (CAPS) ARCALYST (rilonacept) is an interleukin-1 blocker indicated for: Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS), and Muckle-Wells Syndrome (MWS) in adults and children 12 years and older

The benefits of Interleukin-1 (IL-1) inhibitors, such as canakinumab 2 and rilonacept 3, for autoinflammatory disorders include:

• Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS)
• Treatment of other autoinflammatory conditions, such as Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS), Hyperimmunoglobulin D Syndrome/Mevalonate Kinase Deficiency (HIDS/MKD), and Familial Mediterranean Fever (FMF) for canakinumab 2
• Maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) and treatment of recurrent pericarditis (RP) for rilonacept 3

From the Research

Benefits of IL-1 Inhibitors for Autoinflammatory Disorders

The use of Interleukin-1 (IL-1) inhibitors has been shown to be beneficial in the treatment of autoinflammatory disorders. Some of the benefits include:

• Reduction of clinical symptoms and normalization of laboratory parameters in patients with polygenic autoinflammatory diseases 4
• Rapid reduction of clinical symptoms and improvement in both systemic and musculoskeletal symptoms 4
• Ability to taper or withdraw corticosteroids in some cases 4
• Effective treatment of a wide range of inflammatory diseases, including hereditary autoinflammatory diseases, rheumatic diseases, and cardiovascular diseases 5, 6
• Excellent safety record compared to other cytokine blocking therapies 5

Specific Benefits for Different Conditions

Some specific benefits of IL-1 inhibitors for different conditions include:

• Treatment of cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), gout, macrophage activation syndrome, recurrent pericarditis, rheumatoid arthritis (RA), and systemic juvenile idiopathic arthritis (sJIA) with anakinra 7
• Treatment of CAPS, FMF, gout, hyper-IgD syndrome, RA, Schnitzler's syndrome, sJIA, and TNF receptor-associated periodic syndrome with canakinumab 7
• Treatment of CAPS, FMF, recurrent pericarditis, and sJIA with rilonacept 7
• Potential treatment of hidradenitis suppurativa with bermekimab 7

Mechanism of Action

IL-1 inhibitors work by blocking the activity of IL-1, a cytokine that plays a key role in the regulation of inflammatory processes. This can help to reduce inflammation and improve symptoms in patients with autoinflammatory disorders. The different types of IL-1 inhibitors, including anakinra, canakinumab, and rilonacept, have different mechanisms of action, but all work to block the activity of IL-1 in some way 5, 6, 8