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Treatment of chronic gouty arthritis: it is not just about urate-lowering therapy
1Division of Rheumatology, Department of Medicine, UMDNJ/RWJMS, New Brunswick, NJ, USA. schlesna@umdnj.edu
Insights
Initiating urate-lowering therapy (ULT) for gout can increase flares. Prophylaxis with colchicine or NSAIDs helps, but safety concerns exist. Interleukin-1 inhibitors like rilonacept and canakinumab may offer alternatives for gout flare prevention.
Area of Science:
- Rheumatology
- Immunology
- Pharmacology
Background:
- Gouty arthritis management focuses on acute flare pain and inflammation, and preventing future flares and urate crystal deposition.
- A significant challenge in gout management is the increased risk of acute flares during the initial months of urate-lowering therapy (ULT), regardless of the specific ULT used.
- This flare increase is often linked to suboptimal patient adherence to ULT, highlighting a need for effective flare prophylaxis strategies.
Purpose of the Study:
- To enhance awareness regarding the critical role of gouty arthritis flare prophylaxis when initiating ULT.
- To review current recommendations and clinical evidence on the efficacy and safety of existing and novel therapies for gout flare prevention during ULT initiation.
Main Methods:
- This review synthesizes the pathophysiology of acute gouty arthritis flares occurring during ULT initiation.
- It examines existing literature on the use of anti-inflammatory prophylaxis for mitigating these flares.
Main Results:
- Chronic inflammation may persist in gout patients even when asymptomatic, suggesting the need for chronic anti-inflammatory therapy alongside ULT.
- Prophylaxis with colchicine or nonsteroidal anti-inflammatory drugs (NSAIDs) during ULT initiation significantly reduces gout flare incidence and severity.
- However, potential safety concerns with colchicine and NSAIDs may restrict their clinical application.
Conclusions:
- Interleukin-1 (IL-1) inhibitors, specifically rilonacept and canakinumab, show promise as alternative agents for preventing gout flares when colchicine and NSAIDs are not suitable.
- Rilonacept targets IL-1α, IL-1β, and IL-1RA, while canakinumab selectively inhibits IL-1β, offering distinct mechanisms within the IL-1 pathway for therapeutic intervention.
Objectives:
The management of gouty arthritis is focused on treating pain and inflammation associated with acute flares and preventing further acute flares and urate crystal deposition. A challenge associated with the successful management of gouty arthritis is an increased risk of acute flares during the first months after initiation of urate-lowering therapy (ULT). This increase in flare frequency can occur regardless of the choice of ULT and is linked to suboptimal patient adherence to ULT. Current treatment recommendations for the use of prophylaxis are limited. There are no definitive recommendations as to which agents should be used or for how long therapy is beneficial after starting ULT. This article aims to improve awareness of the importance of gouty arthritis flare prophylaxis when initiating ULT and to summarize current recommendations and clinical findings related to the efficacy and safety of currently available and investigational new therapies.
Methods:
This review discusses the pathophysiology of acute gouty arthritis flares during initiation of ULT and examines the literature on the use of anti-inflammatory prophylaxis for reduction of these flares.
Results:
It has recently become clear that, even when the patient is asymptomatic, chronic inflammation is often present in patients with chronic gouty arthritis. Chronic anti-inflammatory therapy should therefore be added to chronic ULT. Prophylaxis with colchicine as well as with nonsteroidal anti-inflammatory drugs (NSAIDs) during ULT initiation can reduce the incidence and severity of gouty arthritis flares substantially; however, safety concerns associated with colchicine and NSAIDs may limit their use.
Conclusion:
When colchicine and NSAIDs are contraindicated or poorly tolerated, rilonacept and canakinumab, interleukin-1 inhibitors in trials, may prove to be useful alternatives for flare prevention. (Of note, although both inhibit the IL-1β pathway, rilonacept also binds to IL-1α and IL-1RA, in contrast to canakinumab, which binds selectively to IL-1β.).
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