Role of Interleukin‐1 Inhibitors in the Management of Gout

Abstract

Interleukin-1 (IL-1) inhibitors potentially have a role as antiinflammatory agents in refractory gout or for patients who are unable to tolerate conventional therapy, such as nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, or glucocorticoids, for acute attacks. Additionally, IL-1 inhibitors may also help patients with polyarticular and tophaceous gout by making them less vulnerable to breakthrough attacks during initiation of chronic urate-lowering treatment, the mainstay of gout therapy. Because evidence highlights the role of proinflammatory cytokine IL-1 in the inflammation process during an acute gouty attack, IL-1 inhibitors are used to modulate the pathogenesis of a variety of autoinflammatory diseases, providing support for its potential role in the inflammatory process of gout. After NSAIDs, colchicine, and steroids, IL-1 inhibitors are beneficial as fourth-line therapy for acute gout attacks due to their high cost and limited clinical experience. The IL-1 inhibitors used in gout are anakinra, canakinumab, and rilonacept. Based on published evidence, anakinra has limited support in the form of anecdotal case reports to justify its use for treating gout. Canakinumab's toxic profile in clinical trials precludes its use in treating patients for gout, and rilonacept shows promise with a few well-designed studies to support its use in gout patients initiating urate-lowering treatment. When combined with current traditional therapies, these newer agents present clinicians and patients with more potential treatment options in the difficult-to-treat gout population.

Contribution of Mast Cell–Derived Interleukin‐1β to Uric Acid Crystal–Induced Acute Arthritis in Mice

“…These results support the conclusion that MCs are locally activated during acute attacks of gout in humans. In addition, synovial fluid samples from gout patients had significantly higher levels of IL‐1β than did those from RA patients (Figure D), which is consistent with the known central role of this cytokine in gouty inflammation ().…”

Management of Gout and Hyperuricemia in CKD

“…IL-1 antagonism with canakinumab is an approach approved by the EMA for management of gout flares, but not yet approved in the US. 83–85 Anakinra is occasionally used off-label in the US in patients for whom the other therapies cannot be used. Regardless of which therapeutic approach is used, the earlier the treatment is started, the faster the flare is brought under control.…”

Pharmacokinetics considerations for gout treatments

“…It is a high-affinity human anti-IL-1b monoclonal antibody that neutralizes the bioactivity of the proinflammatory cytokine [29,30]. This activity inhibits the urate crystal-induced IL-1 signaling pathway [31] that occurs via activation of the NALP3 inflammasome [32]. Canakinumab is administered as a single 150-mg dose subcutaneously for gouty arthritis.…”