Anakinra for cryopyrin-associated periodic syndrome

Abstract

Cryopyrin-associated periodic syndrome (CAPS) is a very rare auto-inflammatory syndrome, which has recently served as a pure model of IL-1β-driven diseases. CAPS is caused by mutations into the NLRP3 gene that encodes crypoyrin, which serves as a receptor of the innate immunity that senses danger signals and pathogens. Constitutive activation of cryopyrin in CAPS leads to an excessive secretion of IL-1β. CAPS patients experience symptoms of systemic inflammation, intense fatigue and have poor quality of life. In the most severe forms, they may develop serious organ damage such as visual and hearing impairment, neurological deterioration and renal insufficiency. Anti-IL-1 drugs are effective in treating symptoms of almost all CAPS patients and have radically transformed their lives. We describe the history of the ‘revival’ of CAPS patients through anti-IL-1 treatments with a special focus on anakinra, the first drug used in cohorts with variable disease severity and number of patients.

Keywords::

• anakinra
• auto-inflammatory diseases
• canakinumab
• chronic infantile neurological cutaneous and articular syndrome
• cryopyrin-associated periodic syndrome
• familial cold urticaria
• familial cold auto-inflammatory syndrome
• IL-1
• Muckle–Wells syndrome
• neonatal-onset multisystem inflammatory disease
• rilonacept
• treatment

Financial & competing interests disclosure

I Koné-Paut has personally received consulting fees from Novartis Pharma, Pfizer, Abbott and Chugai. Her institution has received research fees from Chugai, Novartis, SOBI Biovitrum and 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Cryopyrin-associated periodic syndrome (CAPS) are very rare chronic debilitating diseases due to mutations in the NLRP3 gene, which encodes the NLRP3 protein (cryopyrin).

• CAPS are pure IL-1-driven diseases. Anti-IL-1 treatments are extremely active in patients with CAPS and have changed their lives.

• Anakinra, an analog of the natural IL-1 receptor antagonist of short half-life, was the first biologic used to treat CAPS patients with spectacular effect.

• Two other anti-IL-1 have been developed, canakinumab (a fully human anti-IL-1β monoclonal antibody) and rilonacept (a chimerical protein containing the extracellular domains of the IL-1RI and adaptor protein attached to a human IgG molecule 1), for which two pivotal studies have shown very high level of evidence for efficacy and safety in patients with all CAPS phenotypes.

• The choice of one treatment or another depends on the type of patients, the most documented experience in younger patients and most severe forms being with anakinra. Drugs with long half-life are very accurate for lifelong treatments.

• The full effect of anti IL-1 drugs on the prevention and reversibility of damaged organs needs still to be defined. Their long-term safety needs careful patients’ follow-up onto international collaborative registries.