Gout treatment

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Gout Treatment

Gout management has two distinct phases: (1) treating the acute flare and (2) long-term urate-lowering therapy (ULT) to prevent recurrence and complications.

Pathophysiology (quick recap)

Hyperuricemia leads to sodium urate crystal deposition in joints. Neutrophils phagocytose these crystals, release hydrolytic enzymes after lysosomal rupture, and drive acute inflammation. Treatment targets either this inflammatory cascade or the urate production/excretion imbalance.

1. Acute Flare Treatment

An untreated attack resolves spontaneously over several days, but prompt treatment can abort it within hours. All three agents below are considered first-line options - choice depends on patient-specific factors.

Agent	Dose	Indications	Contraindications
NSAIDs (indomethacin 50 mg TID, naproxen 500 mg BID, ibuprofen 800 mg TID, meloxicam 15 mg daily)	Full anti-inflammatory dose until flare resolves	First-line; most effective	CKD, peptic ulcer history, anticoagulation
Colchicine	1.2 mg PO, then 0.6 mg 1 hour later (1.8 mg total); most effective within first 36 hours	Can't take NSAIDs	CKD; avoid with carvedilol or grapefruit juice (raises colchicine levels); CYP3A4/P-gp inhibitors (clarithromycin, verapamil)
Intra-articular corticosteroids (triamcinolone/methylprednisolone)	40 mg for large joints; 10-20 mg for small joints	Monoarticular attack + contraindications to NSAIDs/colchicine; effective in 90% within 24 hours	Rule out septic arthritis first
Oral prednisone	40-60 mg daily until improvement, then taper over 7-10 days	Failed or contraindication to NSAIDs and colchicine	Poorly controlled diabetes
IL-1 inhibitor (anakinra)	100 mg SQ daily x 3 days (every other day if CrCl <30)	Refractory or contraindication to all standard therapies	Active infection

Key colchicine point: Low-dose colchicine (1.8 mg total) is equally effective to high-dose but far better tolerated. EULAR guidance allows up to 3 x 0.5 mg tablets per 24 hours as an alternative. - Rheumatology, 2-Volume Set (Elsevier, 2022)

2. Colchicine - Mechanism of Action

Colchicine binds tubulin and causes microtubule depolymerization, which:

Impairs neutrophil mobility and migration into inflamed joints
Blocks release of leukotrienes and other inflammatory mediators
Blocks cell division (binds mitotic spindles)

Adverse effects: GI toxicity (diarrhea, nausea, vomiting) is most common. Chronic use can cause myopathy (proximal > distal, elevated CK), neutropenia, aplastic anemia, alopecia. Overdose: bone marrow depression (nadir ~1 week), cardiac arrhythmia, hepatotoxicity. Colchicine is poorly dialyzable.

Lippincott Illustrated Reviews: Pharmacology

3. Urate-Lowering Therapy (ULT)

Indications

Initiate ULT when:

≥2 acute flares per year
Presence of tophi
Urate nephropathy or radiographic damage
First flare with uric acid >9 mg/dL, nephrolithiasis, or CKD ≥ stage 3

Uric Acid Targets

No tophi: serum urate <6 mg/dL
Tophi present: serum urate <5 mg/dL

Timing

Start ULT at least 2 weeks after the flare has resolved
If already on ULT during a flare, do not stop it - abrupt changes in uric acid levels can worsen or prolong the attack
Once target uric acid is reached, continue ULT indefinitely

ULT Drug Options

Xanthine Oxidase Inhibitors (First-Line)

Allopurinol - preferred first-line agent

Start 100 mg/day PO; start 50 mg/day in CKD stage 4+
Titrate by 100 mg increments (50 mg in CKD) every 2-5 weeks to goal
Doses up to 800 mg/day may be required
Screen for HLA-B*5801 in African American and Southeast Asian patients (risk of severe cutaneous reaction / allopurinol hypersensitivity syndrome - 25% mortality)
Blocks metabolism of azathioprine and 6-mercaptopurine - reduce those drugs by 60-75% if co-prescribed
Side effects: diarrhea, nausea, transaminitis, rash (1-5% develop severe allopurinol hypersensitivity syndrome)

Febuxostat - second-line

40-80 mg daily; 40 mg is roughly equivalent to 300 mg allopurinol
More expensive than allopurinol
Side effects: transaminitis; note higher rate of cardiovascular events (relevant in patients with established CVD)

Uricosuric Agents (for intolerance/failure of xanthine oxidase inhibitors)

Probenecid - first choice among uricosurics for monotherapy

Start 500 mg/day, titrate by 500 mg weekly to goal
Max dose 3,000 mg/day; most patients need 1-1.5 g/day in 2-3 divided doses
Side effects: rash, bone marrow suppression

Lesinurad - 200 mg/day (usually used in combination with allopurinol, not as monotherapy)

Uricase (Recombinant)

Pegloticase - for refractory, severe tophaceous gout

8 mg IV every 2 weeks
Converts uric acid to allantoin (a more soluble compound)
Reserved for patients failing or intolerant to all other ULT

4. Flare Prophylaxis During ULT Initiation

Initiating ULT commonly triggers an acute flare due to urate crystal remodeling. To prevent this:

Start low-dose colchicine (0.6 mg daily or BID), NSAIDs, or corticosteroids as prophylaxis
Ideally begin prophylaxis 1-2 weeks before starting ULT
Continue for at least 3-6 months after serum urate reaches target (longer if tophi are present)

5. Lifestyle and Risk Factor Management

Limit purine-rich foods (red meat, organ meats, shellfish)
Avoid or reduce alcohol (especially beer)
Increase hydration
Address comorbidities: hypertension, CKD, metabolic syndrome, diuretic use (thiazides/loop diuretics raise uric acid)
Consider switching losartan (mild uricosuric effect) or fenofibrate for patients on antihypertensives/lipid-lowering drugs

Recent Evidence

A 2024 meta-analysis (PMID: 39636389) found that urate-lowering therapy was associated with reduced all-cause and cardiovascular-specific mortality in gout and hyperuricemia. A 2025 network meta-analysis (PMID: 40709197) compared cardiovascular safety of benzbromarone vs. febuxostat vs. allopurinol, with no significant difference found between agents - this partially addresses the prior concern about febuxostat and CV events (the CARES trial concern).

Sources:

The Washington Manual of Medical Therapeutics
Lippincott Illustrated Reviews: Pharmacology
Rheumatology, 2-Volume Set (Elsevier, 2022)
Firestein & Kelley's Textbook of Rheumatology

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