Gout treatment focuses on rapidly controlling acute flares and preventing future attacks through long‑term urate lowering and lifestyle modification. Effective management requires matching therapy to comorbidities, using a treat‑to‑target serum urate strategy, and providing prophylaxis during urate‑lowering initiation.
Pathophysiological basis for treatment
Gout is an inflammatory arthritis caused by monosodium urate crystal deposition in and around joints, driven by sustained hyperuricaemia. When serum urate exceeds its solubility threshold, crystals form, triggering innate immune activation, particularly via NLRP3 inflammasome and interleukin‑1, and resulting in intense joint inflammation. Long‑standing hyperuricaemia leads to tophi, structural joint damage, and urate nephropathy, so treatment must both suppress inflammation and reduce the total body urate burden. This dual pathophysiological focus underpins the division of therapy into acute flare management and chronic urate‑lowering therapy.
Management of acute gout flares
Acute flares should be treated as early as possible, ideally within the first 24 hours of symptom onset, to shorten duration and reduce pain. First‑line options with broadly similar efficacy are non‑steroidal anti‑inflammatory drugs (NSAIDs), colchicine, and systemic or intra‑articular glucocorticoids, with the choice determined by comorbidities, contraindications, and patient preference
NSAIDs such as naproxen, indomethacin, or sulindac are effective when given at full anti‑inflammatory doses until at least one to two days after complete resolution of the flare. They are often avoided in patients with advanced renal impairment, peptic ulcer disease, heart failure, or significant cardiovascular disease, and gastroprotective strategies may be necessary in higher‑risk individuals. Colchicine, using modern low‑dose regimens (for example 1.2 mg followed by 0.6 mg one hour later, or 0.5–0.6 mg two to three times daily), offers similar pain relief to NSAIDs while reducing gastrointestinal toxicity compared with older high‑dose protocols. Dose reduction and careful monitoring are required in renal or hepatic impairment and when patients are taking interacting drugs such as certain macrolides or statins.
Systemic glucocorticoids, such as oral prednisolone 30–35 mg once daily for about five days, provide an alternative when NSAIDs and colchicine are contraindicated or not tolerated. Intra‑articular corticosteroid injection is particularly useful for monoarticular flares when septic arthritis has been excluded. Where standard therapies are unsuitable, interleukin‑1 blockade (for example anakinra) can be considered for refractory or complex flares, especially in the acute medical setting, although cost and availability limit use. Combining NSAIDs or glucocorticoids with colchicine may be necessary for very severe attacks, but concurrent use of oral NSAIDs and glucocorticoids is generally avoided because of increased gastrointestinal bleeding risk.
Urate‑lowering therapy and treat‑to‑target approach
Long‑term management aims to prevent further attacks, resolve tophi, and halt structural damage by achieving and maintaining target serum urate levels. Contemporary guidelines advocate a treat‑to‑target strategy: most patients should aim for serum urate below 360 µmol/L, with a more stringent target below 300 µmol/L in those with tophi, frequent flares, or severe chronic gouty arthropathy. Urate‑lowering therapy (ULT) is strongly recommended for patients with recurrent flares, tophi, urate nephrolithiasis, or radiographic damage, and many guidelines now support offering ULT earlier, including after a first flare in high‑risk individuals with very high urate or significant comorbidities.
Allopurinol, a xanthine oxidase inhibitor, is the preferred first‑line ULT for most patients because of its effectiveness, cost, and long experience of use. Standard practice is to “start low and go slow”, typically initiating at 50–100 mg daily (lower in advanced chronic kidney disease) and titrating every few weeks until the target serum urate is achieved. Screening for HLA‑B*5801 is recommended in some populations, particularly those of East Asian ancestry, because of the higher risk of allopurinol hypersensitivity syndrome in carriers. Febuxostat, another xanthine oxidase inhibitor, is an alternative when allopurinol is contraindicated, not tolerated, or insufficient at maximally tolerated doses; it reduces serum urate more effectively than standard‑dose allopurinol in many trials, including in patients with renal impairment.
Uricosuric agents, which enhance renal urate excretion, such as probenecid or benzbromarone (availability varies by jurisdiction), may be used as second‑line therapy or in combination with xanthine oxidase inhibitors for difficult‑to‑control disease. In severe, refractory tophaceous gout, intravenous pegylated uricase (for example pegloticase) offers rapid urate lowering and tophus resolution but is reserved for selected patients because of cost, infusion reactions, and the need for specialist supervision. Whatever agent is chosen, achieving and maintaining the serum urate target over the long term is more important than the specific drug, and lifelong therapy is often required.
Flare prophylaxis when starting ULT
Initiation of ULT can paradoxically precipitate gout flares as changing serum urate destabilises existing crystal deposits. To mitigate this, guidelines recommend concurrent prophylactic anti‑inflammatory therapy for at least three to six months after starting or escalating ULT. Low‑dose colchicine (for example 0.5–0.6 mg once or twice daily) is generally preferred where tolerated, with dose adjustment in renal or hepatic impairment and attention to drug interactions. Alternatives include low‑dose NSAIDs, such as naproxen 250–500 mg once or twice daily, or low‑dose prednisolone around 5 mg daily when colchicine and NSAIDs are unsuitable. Continuing prophylaxis until serum urate has been at target for several months reduces early flare burden and supports adherence to ULT.
Lifestyle and comorbidity management
Non‑pharmacological measures complement drug treatment but rarely suffice alone in established gout. Dietary advice typically emphasises limiting purine‑rich meats and seafood, reducing alcohol (especially beer and spirits), avoiding excess fructose‑sweetened beverages, and encouraging weight loss in people with obesity. Adequate hydration, choosing low‑fat dairy products, and increasing vegetable intake may help modestly lower serum urate and improve metabolic health. Optimising associated conditions such as hypertension, chronic kidney disease, diabetes, metabolic syndrome, and heart failure is essential, since these comorbidities both predispose to gout and influence the safety profile of gout medications.
Patient education and shared decision‑making are central to successful long‑term management. Explaining that gout is a chronic, curable crystal deposition disease rather than an inevitable consequence of ageing improves motivation for sustained urate‑lowering therapy. Structured follow‑up to monitor serum urate, assess adherence, adjust therapy, and reinforce lifestyle advice supports durable control and can ultimately lead to complete resolution of flares and tophi for many patients.