Rilonacept in the management of cryopyrin-associated periodic syndromes (CAPS)

Abstract

Cryopyrin-associated periodic syndromes (CAPS) are a subgroup of the hereditary periodic fever syndromes, which are rare autoinflammatory and inherited disorders, characterized by recurrent inflammation and varying degrees of severity. CAPS are thought to be driven by excessive production of interleukin-1β (IL-1β), through over-activation of the inflammasome by gain of function mutations in the gene encoding cryopyrin (NLRP3). This conclusion is supported by the remarkable efficacy of IL-1β blockade in these conditions. Rilonacept (Arcalyst TM ; Regeneron) is the first uS Food and Drug Administration-approved treatment for familial cold autoinflammatory syndrome and Muckle-Wells syndrome and the first in a new line of drugs designed for longer-acting IL-1 blockade. Rilonacept has been associated with a decrease in disease activity, high-sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) in the treatment of CAPS. The clinical safety and efficacy of rilonacept in CAPS and non-CAPS populations will be summarized in this review. Rilonacept is also beneficial for patients who tolerate injections poorly, due to an extended half-life over the unapproved CAPS treatment, anakinra, requiring weekly rather than daily self-administration. Other autoinflammatory disorders may also benefit from rilonacept treatment, with clinical trials in progress for systemic onset juvenile idiopathic arthritis, gout and familial mediterranean fever.

Canakinumab (ACZ885, a fully human IgG1 anti-IL-1β mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS)

“…This supports every eight-week dosing in children as in adults, which was shown to produce sustained remissions in the phase III study which included four children. This compares favourably with the very short half-life of anakinra (four to six hours) [ 19 ] and half-life of 6.3 days in children and 7 days in the adult population for rilonacept [ 20 ]. As a result of its very short half-life, anakinra is administered once daily while rilonacept is administered once weekly.…”

Amyloid arthropathy associated with multiple myeloma: polyarthritis without synovial infiltration of CD20+ or CD38+ cells

“…Taken together, these findings allow us to speculate that MAA is mediated by innate immune mechanisms, specifically by activation of macrophage-associated inflammasomes, resulting in the chronic release of IL-1β and related cytokines in the synovial membrane. This would suggest that MAA is related to the arthritis resulting from certain autoinflammatory diseases such as systemic juvenile idiopathic arthritis or familial Mediterranean fever, which are also driven by IL-1β and respond well to IL-1β-directed treatments [ 18 , 19 ]. The pathogenetically most plausible disease-modifying treatment for MAA, then, would be inhibition of IL-1β with biologics such as anakinra or rilonacept.…”

Adverse effects of biologic anti-inflammatory agents on the respiratory system: A review

“…[33] Rilonacept is a synthetic protein containing the extracellular domains of IL-1R1 that behaves as a soluble decoy receptor for IL-1β, and binds with high affinity. [34] It is currently used for the treatment of cryopyrin-associated periodic syndromes (CAPS) in adults and children 12 years and older.…”