All About Gout for Primary Care: Treating Acute Gout

Phagocytosis of monosodium urate (MSU) crystals becomes the inciting factor for acute gouty arthritis by activating a cascade of inflammatory cytokines.¹ Stopping this inflammatory process is the goal of therapy for acute gout. Therefore, the faster the attack is recognized and treated with medications-including NSAIDs, colchicine, and corticosteroids-the easier it is to control.[[{"type":"media","view_mode":"media_crop","fid":"57792","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_3342102284130","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7292","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 158px; width: 208px; border-width: 0px; border-style: solid; margin: 5px; float: right;","title":" ","typeof":"foaf:Image"}}]]

Pharmacological interventions for acute gout

NSAIDs: These are the preferred agent for treating acute gout for most patients. When used at a full anti-inflammatory dose, all NSAIDs appear equally effective at the population level.^2-5 Adequate dosing and duration are important; treatment should be continued until the flare has resolved and then reduced in tapered doses for at least 2 or 3 days after all overt signs of inflammation are gone.

Colchicine: The current recommended regimen of colchicine is 1.2 mg within 12 hours of the onset of the attack, followed by 0.6 mg 1 hour later. Ideally, patients will have a standing prescription for colchicine and initiate therapy as soon as possible. In practice, after the first 24 hours, patients can continue to take 0.6 mg colchicine daily until symptoms subside. Colchicine should be dose-reduced in patients who have an estimated glomerular filtration rate < 30 mL/min.

Steroids: Oral and intravenous steroids are effective and appropriate in patients who are experiencing polyarticular attacks and in those who have contraindications to colchicine and NSAIDs. Most rheumatologists prescribe a starting dose of 40 to 60 mg/d of prednisone with a taper over 10 to 14 days, which helps avoid rebound attacks after steroid withdrawal. Potential contraindications (eg, diabetes, hypertension, and heart failure) must still be considered.

Intra-articular corticosteroids may be useful in treating acute gout in a single joint or bursa and in cases in which systemic glucocorticoid load needs to be minimized. Care must be taken to rule out infection prior to injecting steroids into the joint; this may mean performing separate joint aspiration and injection.

Next: Doses, cautions, and comments

Doses, cautions, and comments

Following are doses, cautions, and comments for the pharmacological agents for acute gout⁶:

NSAIDs

Doses:

• Ibuprofen, 600-800 mg q 6-8 hours (max dose 3200 mg/24 hours)

• Naproxen, 500 mg q 12 hours (max dose 1250 mg/24 hours)

• Indomethacin, 50 mg q 8 hours (max dose 150 mg/24 hours)

Cautions: In older patients, history of peptic ulcers or NSAID-induced gastritis, liver disease, concomitant anticoagulants, hypertension, heart failure, and renal insufficiency.

Comments: Any NSAID at anti-inflammatory doses is effective; prescribe as scheduled rather than prn; continue for 2 or 3 days after resolution of symptoms; NSAIDs can be nephrotoxic and should be prescribed with caution to patients with renal insufficiency.

Colchicine

Dose: 1.2 mg at onset of symptoms followed by 0.6 mg 1 hour later.

Cautions: With concomitant use of strong CYP3A4 and P-glycoprotein inhibitors, in renal and liver disease (the medication is not nephrotoxic, but accumulation of drug can occur in the setting of renal insufficiency).

Comments: Best when started within 12-24 hours after onset; medication is not nephrotoxic, but accumulation of drug due to renal insufficiency can cause neuropathy and bone marrow suppression; a single dose can be given at any CrCl, but CrCl should be used to determine dose and frequency for repeat doses; in severe hepatic impairment, do not redose within 2 weeks; in severe renal impairment (CrCl < 30 mL/min), acute dosing not recommended if patient is already on prophylaxis (also dose adjusted).

Next: Corticosteroids

Corticosteroids

Doses:

• Prednisone, 40-60 mg daily for 2 days, then tapered over 10-14 days

Cautions: In diabetes, hypertension, heart failure.

Comments: Tapering doses slowly recommended to prevent rebound.

• Intramuscular methylprednisolone, 80-120 mg x1

Comments: Per oral or intramuscular steroids for oligo- and polyarticular flares.

• Intra-articular steroids: 20-80 mg (20 mg for small joints, 40 mg for medium joints, and 80 mg for large joints)

Cautions: Avoid injection in potentially septic joint.

Comments: Intra-articular for 1-2 joints.

Depot ACTH

Dose: 25-80 IU IM repeated 24-72 hours later, if necessary.

Cautions: Hypersensitivity, heart failure, active peptic ulcer, acute psychosis.

Comments: Concomitant use of colchicine 0.6 mg daily or BID recommended to prevent rebound flares; limited availability in United States.

Anakinra

Dose: 100 mg daily subcutaneous for 3 days.

Comments: Interleukin (IL)-1 receptor antagonist; not approved for this indication in the United States.

Rilonacept

Dose: 160-320 mg single subcutaneous injection.

Comments: IL-1β inhibitor; not approved for this indication in the United States.

Canakinumab (Phase 2 trials)

Dose: Single 150 mg subcutaneous injection.

Comments: IL-1β inhibitor; not approved for this indication in the United States; highly effective for prevention of recurrent attacks.

Next in this Special Report: Management of chronic gout, pharmacological interventions for chronic gout, prevention of future gout attacks, and referral to rheumatology.

References:

1. Martinon F, Petrilli V, Mayor A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440:237-241.

2. Janssens HJ, Janssen M, van de Lisdonk EH, et al. Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. Lancet. 2008;371:1854-1860.

3. Man CY, Cheung IT, Cameron PA, Rainer TH. Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial. Ann Emerg Med. 2007;49:670-677.

4. Terkeltaub RA. Colchicine update: 2008. Semin Arthritis Rheum. 2009;38:411-419.

5. Schumacher HR Jr, Boice JA, Daikh DI, et al. Randomised double blind trial of etoricoxib and indometacin in treatment of acute gouty arthritis. BMJ. 2002;324:1488-1492.

6. Eggeneen AT. Gout: an update. Am Fam Physician. 2007;76:801-808.