What are the treatment options for Gout (Gouty Arthritis)?

From the Guidelines

Gout treatment should prioritize urate-lowering therapy (ULT) with allopurinol as the first-line treatment, aiming to maintain serum uric acid (SUA) levels at <6 mg/dL (360 mmol/L) and <5 mg/dL (300 mmol/L) in those with severe gout, as recommended by the 2016 updated EULAR evidence-based recommendations for the management of gout 1. For acute gout attacks, treatment options include colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), oral or intra-articular steroids, or a combination of these, with the goal of providing immediate relief and reducing inflammation.

• Key considerations for acute treatment include:
  • Colchicine, which can be effective when started early
  • NSAIDs, which are commonly used for their anti-inflammatory properties
  • Oral corticosteroids, which may be used in patients who cannot take NSAIDs or colchicine In addition to pharmacological treatments, lifestyle modifications play a crucial role in managing gout, including:
• Weight loss if overweight
• Limiting alcohol consumption, especially beer
• Avoiding purine-rich foods like organ meats and shellfish
• Staying well-hydrated For long-term management, urate-lowering therapy with allopurinol is recommended as the first-line treatment, with febuxostat, uricosurics, or a combination of these considered if the target SUA level cannot be achieved with allopurinol alone 1.
• The dosage of allopurinol should be adjusted according to renal function to minimize the risk of adverse effects.
• Pegloticase is recommended for patients with refractory gout, offering an alternative treatment option for those who do not respond to conventional therapies.

From the FDA Drug Label

14 CLINICAL STUDIES The efficacy of KRYSTEXXA was studied in adult patients with chronic gout refractory to conventional therapy in two replicate, multicenter, randomized, double-blind, placebo-controlled studies of six months duration: Trial 1 and Trial 2.

The primary endpoint in both trials was the proportion of patients who achieved plasma uric acid (PUA) less than 6 mg/dL for at least 80% of the time during Month 3 and Month 6.

As shown in Table 2, a greater proportion of patients treated with KRYSTEXXA every 2 weeks achieved urate lowering to below 6 mg/dL than patients receiving placebo

Although the 4 week regimen also demonstrated efficacy for the primary endpoint, this regimen was associated with increased frequency of anaphylaxis and infusion reactions and less efficacy with respect to tophi.

The effect of treatment on tophi was a secondary efficacy endpoint and was assessed using standardized digital photography, image analysis, and a Central Reader blinded to treatment assignment.

Approximately 70% of patients had tophi at baseline.

A pooled analysis of data from Trial 1 and Trial 2 was performed as pre-specified in the protocols

At Month 6, the percentage of patients who achieved a complete response (defined as 100% resolution of at least one target tophus, no new tophi appear and no single tophus showing progression) was 45%, 26%, and 8%, with KRYSTEXXA 8 mg every 2 weeks, KRYSTEXXA 8 mg every 4 weeks, and placebo, respectively

The difference between KRYSTEXXA and placebo was statistically significant for the every 2 week dosing regimen, but not for the every 4 week dosing regimen.

Gout Treatment Options:

• Pegloticase (IV): Effective in lowering uric acid levels and resolving tophi in patients with chronic gout refractory to conventional therapy 2.
• Indomethacin (PO): Relieves the pain, reduces the fever, swelling, redness, and tenderness of acute gouty arthritis 3.
• Probenecid (PO): Treats hyperuricemia associated with gout and gouty arthritis 4.

Key Considerations:

• Pegloticase is administered via IV every 2 weeks, with a significant proportion of patients achieving urate lowering and tophi resolution.
• Indomethacin is an oral NSAID that provides relief from acute gouty arthritis symptoms.
• Probenecid is an oral medication that treats hyperuricemia associated with gout and gouty arthritis.

From the Research

Gout Treatment Overview

• Gout is a common form of acute inflammatory arthritis caused by the deposition of monosodium urate crystals within the synovium of joints, leading to severe pain and reduced quality of life for patients 5.
• The treatment of gout includes both acute flares and urate-lowering therapy, with a focus on a treat-to-target strategy to prevent gout flares 5, 6.

Acute Gout Flare Treatment

• Standard pharmacotherapies for gout flares include colchicine, NSAIDs, and oral or intramuscular corticosteroids, with IL-1 inhibitors as an option for flare refractory to standard therapies 5, 7.
• First-line agents for gout flares are NSAIDs, colchicine, and glucocorticoids, while IL-1β antagonists are highly effective but often used as salvage therapies due to cost-effectiveness concerns 7.

Urate-Lowering Therapy

• Urate-lowering therapies aim to prevent gout flares, with an emphasis on treat-to-target strategy and escalation of therapies until the target serum uric acid is reached 5, 6.
• Initial treatments include allopurinol and febuxostat, with uricosuric agents such as probenecid, sulfinpyrazone, and benzbromarone as adjuncts 5, 6.
• Allopurinol is an agent of first choice for urate-lowering therapy, but screening for HLA*B58:01 mutation is recommended in certain populations to decrease the occurrence of allopurinol hypersensitivity syndrome 7.
• Febuxostat is another efficacious urate-lowering therapy, but has received a U.S. FDA black box warning for cardiovascular safety 7.

Emerging Therapies and Clinical Considerations

• Novel uricosurics, such as verinurad and arhalofenate, are in development and show promise for future treatment options 7.
• Pegloticase is effective for patients with recalcitrant gout, but its immunogenicity can threaten sustained urate-lowering responses 7, 8.
• When prescribing gout medications, important factors to consider include pharmacokinetics, pharmacodynamics, population specifics, benefits, and contraindications 8.
• A comparative effectiveness study found that allopurinol and febuxostat achieved serum urate goals in patients with gout, with allopurinol being noninferior to febuxostat in controlling flares 9.