Current treatment recommendations and considerations for cryopyrin-associated periodic syndrome

Abstract

Cryopyrin-associated periodic syndrome (CAPS) encompasses a spectrum of three phenotypes of increasing severity. The syndrome is due to dominant mutations in NLRP3, which encodes a key component of the innate immunity that regulates the secretion of IL-1β. CAPS manifests as systemic inflammation, which compromises quality of life and leads to serious complications and handicap. Anti-IL-1 drugs have shown remarkable efficacy in treating CAPS symptoms and have significantly changed patients’ lives. They have acceptable safety profiles but do have some differences. We review three drugs that are currently marketed for CAPS, give additional information for the practical use of these drugs, and provide some recommendations for management.

Keywords:

• anakinra
• autoinflammatory diseases
• canakinumab
• chronic infantile neurological cutaneous and articular syndrome
• cryopyrin-associated periodic syndrome
• familial cold autoinflammatory syndrome
• interleukin 1
• Muckle–Wells syndrome
• neonatal-onset multisystem inflammatory disease (NOMID)
• recommendations
• rilonacept
• treatment

Financial & competing interests disclosure

I Koné-Paut has personally received consulting fees from Novartis, SOBI, Pfizer, Abbvie and Chugai. Her institution has received research fees from Chugai, SOBI Biovitrum, and Novartis. C Galeotti has received an educational grant from Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• CAPS is a rare debilitating condition with symptoms and complications driven purely by excessive and dysregulated secretion of IL-1β.

• Three anti-IL-1 drugs are marketed: anakinra, canakinumab and rilonacept. All have sustained efficacy in controlling CAPS systemic inflammation. In addition, they have significantly improved quality of life.

• Most patients with treatment have shown improved or stabilized secondary complications such as uveitis, aseptic meningitis and cochlear inflammation.

• The whole spectrum of the possible efficacy of the drugs on secondary complications is incompletely assessed but could be increased by prompt initiation of treatment as soon as the first CAPS symptoms appear.

• The decision to treat CAPS must be made by an expert physician. All patients presenting active clinical symptoms and sustained biological inflammation should receive early treatment.

• Bacterial infections need to be carefully treated and prevented by accurate vaccination and patient education. Close monitoring of other potential side effects is also required.

• The choice of anti-IL-1 drug depends on its availability and affordability.

• Anakinra could be safe during pregnancy; however, close monitoring of possible renal malformation in fetuses is recommended.

• Despite their high cost, canakinumab and rilonacept have more convenient schemes of administration for the long term.

• Post-marketing registries are ongoing to better define the long-term efficacy and safety of anti-IL-1 drugs in CAPS.

Notes