Rilonacept is an interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) cytokine trap. Rilonacept blocks IL-1 signaling by acting as a soluble decoy receptor that binds both IL1α and IL-1β and prevents its interaction with cell surface receptors. Rilonacept also binds interleukin-1 receptor antagonist (IL-1ra). The equilibrium dissociation constants for rilonacept binding to IL-1α, IL-1β, and IL-1ra were 1.4 pM, 0.5 pM, and 6.1 pM, respectively.

CAPS refers to rare genetic syndromes generally caused by mutations in the NLRP-3 [nucleotide-binding domain, leucine rich family (NLR), pyrin domain containing 3] gene (also known as Cold-Induced Autoinflammatory Syndrome-1 [CIAS1]). CAPS disorders are inherited in an autosomal dominant pattern with male and female offspring equally affected. Features common to all disorders include fever, urticaria-like rash, arthralgia, myalgia, fatigue, and conjunctivitis. In most cases, inflammation in CAPS is associated with mutations in the NLRP-3 gene, which encodes the protein cryopyrin, an important component of the inflammasome.

Cryopyrin regulates the protease caspase-1 and controls the activation of interleukin-1 beta (IL-1β). Mutations in NLRP-3 result in an overactive inflammasome, resulting in excessive release of activated IL-1β that drives inflammation. DIRA is an autoinflammatory, autosomal recessive disorder caused by loss of function mutations in the IL1RN gene, which encodes IL-1 receptor antagonist (IL-1ra), resulting in unopposed signaling of the proinflammatory cytokines IL-1α and IL-1β through the IL1 receptor. Interleukin-1 (IL-1) is a key cytokine that mediates the pathophysiology of many inflammatory processes, and it has been implicated as a causative factor in pericarditis.

IL-1α and IL-1β bind to the universally expressed cell surface receptor, IL-1 Receptor type-1, triggering a cascade of inflammatory mediators. Pre-formed IL-1α is released by damaged/inflamed pericardial cells and may contribute to the maintenance and amplification of inflammation via activation of the NLRP3 inflammasome, which then augments the inflammatory response by production of IL-1β in a cascade amplification system.

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.
• Maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) in adults and pediatric patients weighing 10 kg or more.
• Treatment of recurrent pericarditis (RP) and reduction in risk of recurrence in adults and children 12 years and older.

Administer by subcutaneous injection 

• CAPS, FCAS, MWS, and RP (2.2):
  • Adults:
    • Loading dose: 320 mg, delivered as two 160 mg (2 mL) injections.
    • Maintenance dose: 160 mg (2 mL) injection once weekly
  • Pediatric patients 12 years to 17 years:
    • oading dose: 4.4 mg/kg, up to a maximum of 320 mg, delivered as 1 or 2 injections (not to exceed 2 mL/injection).
    • Maintenance dose: 2.2 mg/kg, up to a maximum of 160 mg (2 mL) injection, once weekly.
• DIRA (2.3):
  • Adults and pediatric patients weighing 10 kg or more:
    • 4.4 mg/kg up to a maximum of 320 mg, delivered as 1 or 2 injections (2 mL/injection) once weekly.

The most common adverse reactions reported by patients with CAPS and RP treated with ARCALYST are injection-site reactions and upper respiratory tract infections. 

None. 

Serious Infections: Serious, life-threatening infections have been reported in patients taking ARCALYST.

• Do not initiate treatment with ARCALYST in patients with active or chronic infections. Discontinue treatment if a patient develops a serious infection. 
• Hypersensitivity Reactions: If a hypersensitivity reaction occurs, discontinue administration of ARCALYST and initiate appropriate therapy.
• Immunizations: Avoid live vaccines. Update recommended vaccinations prior to initiation of therapy per current guidelines.