From the Guidelines
For gout unresponsive to allopurinol, switch to febuxostat (Uloric) 40-80 mg daily or consider adding probenecid 250-500 mg twice daily to allopurinol if partial response was achieved. Before changing therapy, ensure patient adherence, adequate dosing (allopurinol often requires 300-600 mg daily), and rule out secondary causes like chronic kidney disease or medication interactions 1. During medication transitions, prescribe colchicine 0.6 mg once or twice daily for flare prophylaxis for 3-6 months 1. For severe cases unresponsive to oral medications, pegloticase (Krystexxa) 8 mg IV every two weeks may be necessary, though this requires monitoring for infusion reactions 1. Lifestyle modifications remain important, including:
- Weight loss if overweight
- Limiting alcohol (especially beer)
- Reducing purine-rich foods
- Staying well-hydrated Treatment-resistant gout often results from inadequate dosing, poor adherence, or underlying conditions affecting uric acid metabolism, so addressing these factors is essential for successful management 1. The 2020 American College of Rheumatology guideline for the management of gout recommends febuxostat as a suitable alternative to allopurinol in patients who are intolerant or unresponsive to allopurinol 1.
From the Research
Gout Unresponsive to Allopurinol
- 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 2.
- 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 2.
- Urate-lowering therapies, such as allopurinol and febuxostat, aim to prevent gout flares, with an emphasis on a treat-to-target strategy, escalating therapies until the target serum uric acid is reached 2, 3.
Alternative Treatments
- For patients unresponsive or allergic to allopurinol, alternative treatments include dietary changes, discontinuation of diuretic agents, and use of losartan or fenofibrate to treat concomitant hypertension or dyslipidemia 4.
- Uricosuric agents, such as probenecid, may be helpful in patients with normal or diminished urate excretion 4, 3.
- Rasburicase, an Aspergillus urate oxidase, may be indicated to prevent acute hyperuricemia induced by chemotherapy for hematological malignancies, but its use is limited by the need for parenteral administration and lack of validated treatment schedules 4.
Management of Gout
- Management guidelines emphasize the importance of a therapeutic serum urate target for effective gout management, and studies have identified safe and effective dosing strategies for allopurinol and other urate-lowering therapies 3, 5.
- Despite effective treatment, gout is often poorly managed, with missed opportunities to review and optimize gout management, particularly in patients with chronic kidney disease 6.
- Emerging therapies, including pegloticase, RDEA596, and interleukin-1 inhibitors, show promise for unmet needs in selected gout populations 3, 5.