All About Gout for Primary Care: Treating Chronic Disease

When a patient has had more than 1 acute gout attack, a secondary goal becomes preventing further acute attacks and decreasing the tophi burden. Both are achieved by lowering the patient’s serum urate level (SUL) to < 6 mg/dL and maintaining the SUL beneath this threshold.^{1[[{"type":"media","view_mode":"media_crop","fid":"57913","attributes":{"alt":"","class":"media-image media-image-right","height":"203","id":"media_crop_8742166948463","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7302","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":"border-width: 0px; border-style: solid; margin: 5px; float: right;","title":" ","typeof":"foaf:Image","width":"240"}}]]}

Managing chronic gout and preventing future attacks

The first step in managing patients who have gout is encouraging lifestyle changes, including weight loss, avoidance of purine-rich foods (organ meats and shellfish), avoidance of foods with high-fructose sweeteners, and reduction of alcohol consumption. Increasing vitamin C and low fat dairy intake may modestly decrease SULs.² Dietary changes often are insufficient and must be combined with pharmacologic management.

Diuretic drugs (eg, thiazides and loop diuretics) increase the risk of gout attacks, especially after initiation of urate-lowering therapy.³ When possible, patients who have a known history of gout should avoid these medications.

Urate-lowering agents frequently used to treat chronic gout include inhibitors of xanthine oxidase (allopurinol, febuxostat) and uricosuric agents (probenecid, sulfinpyrazone, benzbromarone, lesinurad); the latter category is used primarily as adjunctive therapy in the United States.

Prescribe simultaneous prophylaxis

Initiation of urate-lowering therapy briefly increases the risk of flare. It is therefore advisable to prescribe simultaneous prophylaxis with low dose colchicine (0.6 mg QD), prednisone (5-10 mg daily), or NSAIDs (eg, naproxen 250-500 mg BID). Prophylaxis should be continued for 3 to 6 months after goal uric acid is achieved on stable therapy.⁴ For the majority of patients, the goal is < 6 mg/dL; for patients with long-standing chronic gout or a large burden of tophi, the goal is often < 3 mg/dL.

Next: Pharmacological Intervention

Pharmacological intervention for chronic gout

Following are the main pharmacological interventions for chronic gout:

Allopurinol: This purine xanthine oxidase inhibitor is the most frequently used urate-lowering agent in the treatment of gout. Allopurinol is FDA approved for doses up to 800 mg/d.

In clinical practice, noncompliance with allopurinol therapy has been identified in about 50% of subjects in the first year of therapy.⁵ In addition, allopurinol is widely under-dosed in clinical practice. There is no goal dose of the medication; rather, the medication dose should be increased until the SUL target is achieved. Most patients can start at a dose of 100-200 mg once a day with an increase of 100 mg monthly until goal uric acid is achieved.

Although allopurinol is not nephrotoxic, it is renally cleared; in patients with chronic kidney disease (CKD), it is best to start with about 1.5 mg per unit of estimated glomerular filtration rate and increase by 50 mg monthly, until the target SUL  is achieved, all the while monitoring the patient for hypersensitivity-rash, cytopenias, transaminitis, and fever.⁶

Febuxostat: A potent, nonpurine, selective inhibitor of xanthine oxidase, febuxostat is primarily metabolized by the liver.⁷ Dosing is 40 mg or 80 mg daily, and dose adjustment is not needed in patients who have mild to moderate CKD.¹ Febuxostat 40 mg is roughly equivalent to allopurinol 300 mg.¹ Febuxostat is considered safe in patients who have a history of hypersensitivity to allopurinol.

Lesinurad: This urate transporter inhibitor (uricosuric) was recently FDA approved for urate lowering therapy when target SULs are not achieved with a xanthine oxidase inhibitor alone.⁸ Lesinurad is used at a dose of 200 mg QD, should be used only in conjunction with a xanthine oxidase inhibitor, and should be used with caution in patients who have CKD.

Next: Doses, Mechanisms, and More

Agents and doses, mechanisms, cautions, and comments

Following are doses, mechanisms, cautions, and comments for pharmacological agents for chronic gout:

Allopurinol

Dose: 50-800 mg daily; starting dose based on renal function.

Mechanism/cautions: Purine analogue that inhibits xanthine oxidase; avoid with azathioprine; interacts with coumadin; may precipitate acute attack.

Comments: Start after acute episode; titrate to serum uric acid < 6 mg/dL.

Febuxostat

Dose: 40-80 mg daily (approved at 80 mg and 120 mg doses in Europe).

Mechanism/cautions: Inhibits xanthine oxidase; avoid with azathioprine, mercaptopurine, and theophylline; caution in coronary artery disease and hepatic disease.

Comments: Safe in mild to moderate renal impairment, but limited data in severe renal disease and HD.

Probenecid

Dose: 500 mg twice daily.

Mechanism/cautions: Uricosuric, increases urate excretion by inhibition of URAT1 transporter in the proximal tubule                .

Comments: Normal renal function, high urine volumes, alkalinization of the urine required.

Pegloticase

Dose: FDA approval pending; up to 8 mg IV every 2 weeks.

Mechanism/cautions: Converts uric acid to allantoin; avoid in glucose 6 phosphate deficiency; caution in hyperlipidemia, anemia, congestive heart failure, and chronic kidney disease.

Comments: Submitted for FDA approval.

Lesinurad

Dose: 200 mg daily.

Mechanism/cautions: Lowers SUL via inhibition of URAT1 in the proximal tubule.

Comments: Use in combination with a xanthine oxidase.

Next: Referral

Referring patients to rheumatology

Although the majority of gout cases can be managed in the primary care setting, the care of a rheumatologist may be appropriate for patients with recalcitrant disease or who are difficult to manage because of comorbidities. In addition to the medications described above, gout management sometimes involves the use of pegloticase for chronic gout⁹ and canakinumab, anakinra, or adrenocorticotropic hormone for acute gouty arthritis; patients requiring these intravenous and subcutaneous medications are likely to benefit from a referral to rheumatology.