Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or colchicine are recommended first-line treatments for patients experiencing a gout flare.[53][81][82] The choice between treatments should be guided by patient preference and potential risks and contraindications (e.g., renal impairment in the case of NSAIDs).[53][81]
NSAIDs halt the inflammatory cascade if they are started early. Also used to suppress gouty attacks when maintenance therapy with urate-lowering drugs is started.[81]
It is common to use indometacin, although there is no evidence to suggest that it is more effective than other NSAIDs.[84]
One Cochrane review reported, with moderate certainty, that NSAIDs and selective cyclo-oxygenase-2 (COX-2) inhibitors have similar efficacy for pain, swelling, treatment success, and quality of life in patients with gout.[85]
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The review found no difference between groups for function, but this result was based on low-certainty evidence. Higher withdrawal rates due to adverse events (mainly gastrointestinal) were seen with non-selective NSAIDs.[85]
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An additional systematic review concluded that although COX-2 inhibitors are equally as effective as non-selective NSAIDs for pain relief in patients with gout, COX-2 inhibitors may be more beneficial overall.[86]
Choice of NSAID should be guided by patient preference.[81]
In patients at high risk of gastrointestinal complications, a proton-pump inhibitor or misoprostol should be co-prescribed.
Proton-pump inhibitors should be considered for all patients who are taking an NSAID.[53]
COX-2 inhibitors may be safer than traditional NSAIDs in patients with a history of gastrointestinal bleeding or comorbidities.
Treatment course is generally 7 to 14 days. However, NSAIDs should be given for the shortest period possible, at the lowest effective dose.
Primary options
naproxen: 500 mg orally twice daily
OR
ibuprofen: 400-800 mg orally three to four times daily
OR
diclofenac potassium: 50 mg orally (immediate-release) three times daily
OR
meloxicam: 7.5 to 15 mg orally once daily
OR
indometacin: 25-50 mg orally three times daily
OR
celecoxib: 100-200 mg orally twice daily
corticosteroid
Corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), or colchicine are recommended first-line treatments for patients experiencing a gout flare.[53][81][82]
The choice between treatments should be guided by patient preference and potential risks and contraindications (e.g., renal impairment in the case of NSAIDs).[81]
Corticosteroids can be given either as an intra-articular injection for monoarticular acute gout or parenterally for oligoarticular or polyarticular acute gout.[81] Parenteral dose depends on the severity of the presentation; switch to oral dosing after 1-2 days and then taper oral dose as usual.
In the UK, off-label use of intra-articular or intramuscular injections of corticosteroids are only considered if NSAIDs and colchicine are contraindicated.[53]
Corticosteroids are probably more effective than colchicine for acute gout, although there are no head-to-head trials.[87]
Corticosteroids are associated with potentially serious adverse effects.
One Cochrane review reported moderate-certainty evidence that corticosteroids had similar efficacy for pain, inflammation, function, and treatment success when compared with NSAIDs for patients with gout.[85]
Should be avoided if septic arthritis has not been excluded.
How to aspirate synovial fluid from the knee and administer intra-articular medication using a medial approach.
How to aspirate synovial fluid from the shoulder and administer intra-articular medication. Video demonstrates a posterior approach to the glenohumeral joint and a lateral approach to the subacromial space.
Primary options
prednisolone: 1 mg/kg orally given as a single dose
MoreOR
prednisolone: 20-40 mg orally once daily initially, decrease by 5-10 mg/day decrements every 3 days until discontinuation; or 30 mg orally once daily for 5 days
OR
methylprednisolone acetate: small joint: 4-10 mg intra-articularly as a single dose; medium joint: 10-40 mg intra-articularly as a single dose; large joint: 20-80 mg intra-articularly as a single dose; consult specialist for guidance on parenteral dose
OR
triamcinolone acetonide: small joint: 2.5 to 10 mg intra-articularly as a single dose; larger joint: 5-40 mg intra-articularly as a single dose
febuxostat
Febuxostat is a non-purine selective xanthine oxidase inhibitor that reduces the production of uric acid.
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The US Food and Drug Administration recommends that febuxostat should only be prescribed for patients who have failed treatment with, or cannot tolerate, allopurinol and who have been counselled regarding the cardiovascular risk.[111]
American College of Rheumatology guidelines recommend that patients with gout who are taking febuxostat, and have a history of cardiovascular disease or a new cardiovascular event, should switch to another urate-lowering therapy, if available.[81]
The Medicines and Healthcare Products Regulatory Agency in the UK recommends that patients with pre-existing major cardiovascular disease (e.g., myocardial infarction, stroke, or unstable angina) should avoid treatment with febuxostat unless no other therapy options are available.[112]
Febuxostat is recommended as joint first line treatment with allopurinol in the UK, once the patients comorbidities and preferences are noted.[53] If the target serum urate level is not reached or first line treatment with febuxostat is not tolerated, switching to a second line treatment with allopurinol should be considered, taking into account any comorbidities or preferences.[53]
In randomised controlled trials of patients with hyperuricaemia or gout, febuxostat reduced serum urate level more effectively than allopurinol.[113][114] Open-label data suggest that this benefit is maintained for up to 40 months.[126] In these studies, however, allopurinol was administered at doses less than the maximum approved dose for this indication. A subsequent double blind non-inferiority trial demonstrated comparative efficacy for febuxostat and allopurinol in controlling flares when given at standard doses at 72 weeks.[116]
Commonly reported adverse effects of febuxostat therapy include elevated liver function tests, headache, hypertension, diarrhoea, and arthralgia/stiffness.[127][128]
Cardiovascular death and all-cause mortality were significantly more common among patients taking febuxostat than those taking allopurinol (4.3% vs. 3.2%, hazard ratio [HR] 1.34 [95% CI 1.03 to 1.73]; 7.8% vs. 6.4%, HR 1.22 [95% CI 1.01 to 1.47], respectively) in a multi-centre non-inferiority trial of patients with gout and cardiovascular disease.[119] Febuxostat was non-inferior to allopurinol with respect to a composite primary outcome of cardiovascular events.
Conversely, evidence from subsequent systematic reviews suggest that there is no significant association with high blood pressure, all cause mortality, myocardial infarction, or stroke for either febuxostat or allopurinol, and no significant difference between the two treatments for the composite outcome of major adverse cardiovascular events (including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and unstable angina with urgent coronary revascularisation) among adult patients with hyperuricaemia and/or gout.[120][121][122]
Febuxostat should not be started during an acute attack, as it might prolong the attack or precipitate more attacks.[129]
Goal is to reduce uric acid level <360 micromol/L (<6 mg/dL) to prevent supersaturation and crystal formation.
Adjust dose according to serum urate target level of 360 micromol/L (6 mg/dL).
Primary options
febuxostat: 40-80 mg orally once daily
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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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