Managing gout: There’s more we can do

Responding to an acute attack

Whenever possible, initiate pharmacologic therapy within 24 hours of symptom onset, because this has been associated with decreased pain and shorter duration of an acute attack.^8,13 The choice of drug should be guided by the severity of the attack, as determined by both a pain score on a visual analog scale (VAS) and the number of affected joints; patient preference, prior response, and associated comorbidities are also important considerations (TABLE 2^8,13,14). When medications are prescribed for acute attacks or chronic gout, a discussion of adverse effects, drug interactions, contraindications, cost, and the importance of adherence is needed, as well.

For mild to moderate pain (≤6 out of 10 on a VAS) involving a few small joints or one or 2 large joints, monotherapy with a nonsteroidal anti-inflammatory drug (NSAID), a corticosteroid, or colchicine is recommended. For severe pain (>6 out of 10) and/or polyarticular involvement (≥4 joints in more than one region of the body), combination therapy is recommended (eg, colchicine and either an NSAID or a corticosteroid).¹³ Prednisone, methylprednisolone, and adrenocorticotropic hormone are options for patients who are NPO. Acute gout therapy should be continued until the attack resolves, which can range from 5 to 14 days.¹³

Colchicine considerations. The dose of colchicine recommended by the ACR for an acute gout attack (1.2 mg loading dose, followed by 0.6 mg one hour later, then followed after 12 hours, as needed, by up to 0.6 mg once or twice a day) is substantially lower than the dosing schedule used historically (1.0 mg loading dose, followed by 0.5 mg every 2-3 hours). Higher doses have not proven to be more effective, however, and typically led to gastrointestinal toxicity, causing patients to stop taking the drug before acute symptoms resolved.^8,13,22

Keep in mind, too, that colchicine therapy should not be initiated more than 36 hours after symptom onset, as therapy is less effective beyond this time frame.^8,13 In addition, concurrent use with P-glycoprotein and CYP3A4 inhibitors—eg, clarithromycin and erythromycin and some antifungals, antiretrovirals, calcium-channel blockers, immunosuppressants, and statins—may increase the risk of colchicine toxicity and should be avoided.

Treating chronic gout

Management of recurrent or progressive gout is aimed at reducing and maintaining serum urate levels <6.0 mg/dL, using ULT (TABLE 3^12,23-25) combined with anti-inflammatory prophylaxis to reduce the frequency of gout flares and the size and number of tophi.^12,23 Patients who meet one or more of the following criteria qualify for ULT:

• the presence of tophi

• ≥2 acute attacks per year
• chronic kidney disease (CKD) stages 2 through 5

• a history of urolithiasis.¹²

Both ULT and anti-inflammatory therapy should be started after an acute gout attack resolves, but patients already on prophylactic therapy should continue the regimen both during and after acute attacks to avoid more frequent exacerbations.^9,12 If gout symptoms persist despite a serum urate level of <6.0 mg/dL, increase the dose of ULT to achieve a target of <5 mg/dL to reduce the frequency of flares and the size and number of tophi.^12,26

Allopurinol, a xanthine oxidase inhibitor, is typically used as first-line ULT due to efficacy and low cost.¹³ Febuxostat, also a xanthine oxidase inhibitor, is an additional first-line option, although the US Food and Drug Administration issued a warning based on postmarketing reports of hepatic failure.²⁵ In the case of a xanthine oxidase allergy or intolerance, probenecid may be used as an alternative first-line therapy. First-line agents for anti-inflammatory prophylaxis include low-dose colchicine (0.6 mg once or twice daily) and low-dose NSAIDs. Oral corticosteroids (<10 mg/d) are considered second-line therapy.¹³

Allopurinol hypersensitivity. Although allopurinol is generally well tolerated, about 2% of patients develop a mild rash and up to 5% of patients stop taking it because of an adverse effect.²⁵ More importantly, allopurinol hypersensitivity syndrome (AHS) is rare but potentially fatal; in the United States, it is estimated that one in every 1000 patients treated with allopurinol will develop AHS.^12,27

Allopurinol hypersensitivity syndrome is rare, but potentially fatal. AHS is characterized by a rash (eg, Stevens-Johnson syndrome or toxic epidermal necrolysis), eosinophilia, leukocytosis, fever, hepatitis, and renal failure.^12,25 There is no cure; the mainstay of treatment is early diagnosis, withdrawal of allopurinol, and supportive care.²⁵ Because of the high mortality rate (20%-25%),^12,27 genetic screening for allele HLA-B*5801 prior to starting allopurinol therapy is recommended for patients in high-risk groups: Koreans with CKD (stage 3 or worse) and all Han Chinese and Thai patients, regardless of kidney function.¹² Alternative therapies should be used for patients who test positive for the allele.

Duration of therapy

Pharmacologic treatment of an acute gout attack should continue until the attack resolves, which can range from 5 to 14 days. The duration of treatment for chronic gout is far longer.