Reviewing the treatment
Gout therapies fall into two categories: those used to treat the acute flare and those used to lower serum uric acid and prevent future flares.
Treating the acute flare: Acute gout is very painful. Patients with the condition cannot bear weight on an affected joint. Pain management must be the clinician’s first focus. A number of therapies will induce a quick response if initiated in a timely manner. Be aware of comorbidities before choosing a treatment. Gout is more common in persons with hypertension, diabetes, and renal disease. These conditions may dictate which therapy is the most appropriate.
• Nonsteroidal anti-inflammatory drugs (NSAIDs): Long the mainstay in the treatment of acute gout, nearly any short-acting NSAID in a high enough dose will be effective. Indomethacin 150 mg twice daily for three days is a popular approach. This can be lowered to 75 mg twice daily for an additional three days if necessary. IM ketorolac (Toradol) 50 mg is widely used in ED settings. It is followed by several more days of oral NSAIDs (e.g., naproxen 500 mg twice a day). Recent small studies show celecoxib (Celebrex) is non-inferior to indomethacin and may be easier on the stomach. Celecoxib does not affect platelets the way nonselective NSAIDs do.9
• Colchicine: While colchicine has successfully treated both acute and chronic gout for ages, clinicians must be judicious about dosing. No one should be dosing patients with acute gout “to the onset of GI toxicity.” Use no more than six 0.6-mg tablets of colchicine per day in divided doses (every four hours) for the first day. Drop down to four tablets a day for two days and then twice a day for one week.
Because of profound myelosuppression, the use of IV colchicine has been abandoned. This product is set to be removed from the market by the FDA.
Colchicine 0.6 mg one to two times a day also has a role in preventing gout flares, especially during the initiation of urate-lowering therapy (ULT).
When using colchicine in older patients, be aware that chronic kidney disease increases both the risk of myelosuppression and neuromyopathy. Once-daily or alternate-day regimens should be used in persons with decreased creatinine clearances.
• Corticosteroids: These agents can be used as initial or adjunctive therapy in acute gout. Caution is required when prescribing to persons with poorly controlled diabetes, heart failure, or hypertension.
Burst doses prescribed as methylprednisolone (Medrol Dosepak) are highly effective and well tolerated. A one-week course is usually sufficient, but refractory cases may require up to two weeks. If the flare initially recedes but returns midway through the Dosepak it may be necessary to begin another Dosepak at once. Start at the six-tablets-a-day row all over again. IM depo steroids, such as triamcinolone (Kenalog), in a single 60-mg dose are also effective. For hospitalized persons, equivalent IV steroid formulations are used. Intra-articular (IA) corticosteroid injections have the most rapid onset of action and little systemic effect. For gout patients with large effusions, arthrocentesis followed by IA steroids will relieve the discomfort of the effusion and provide rapid pain relief.
• Opioids: Opioids have no primary role in the treatment of acute gout pain. Pain medications with no anti-inflammatory properties are generally reserved for chronic tophaceous gout. Trials of simple analgesics, such as acetaminophen (Tylenol), tramadol (Ultram), or propoxyphene (Darvon), are attempted first.
• Alternative and pipeline therapies: Synthetic adrenocorticotropic hormone (ACTH) 80 units subcutaneously is an alternative to the above medications and is especially well tolerated despite renal function or diabetes.10 The high cost of ACTH gel has made it no longer a practical therapy.
Interleukin (IL)-1 inhibition is under development for treatment of acute gout. IL-1 is a cytokine that plays a prime anti-inflammatory role in this condition. Anakinra (Kineret) is an IL-1 inhibitor approved by the FDA for rheumatoid arthritis and might be a viable alternative for gout when other therapies are contraindicated.11
Lowering serum uric acid: Not all patients with hyperuricemia and one or two gout flares require ULT, but many do.
Two therapeutic approaches to lowering urate are available. The problem of uric acid overproduction can be effectively countered by blocking xanthine oxidase with allopurinol. In theory, uricosuric agents, such as probenecid and sulfinpyrazone, are ideal agents to reverse underexcretion of uric acid by the kidney.
Allopurinol is far and away the most popular agent for lowering uric acid levels and is generally regarded as safe and effective. While severe toxicities are rare and true allergic reactions requiring the permanent discontinuation of this drug are seen in only 2% of users, adequate dosing of allopurinol to achieve a target serum uric acid level <6.0 mg/dL is disturbingly uncommon.12 Concerns about potential hypersensitivity and renal toxicities led to widely published (but not validated) guidelines for adjusting the dose of allopurinol based on creatinine clearance.13 Recent studies have shown that allopurinol dosing adjusted in this manner does not adequately treat hyperuricemia or reduce the risk of toxicity.14
Concerns about toxicity have also dampened enthusiasm for the use of probenecid, the only remaining uricosuric available in the United States. The dosing schedule is also problematic when viewing probenecid as a lifelong therapy for urate lowering. Unlike allopurinol, which can and should be given once daily, probenecid generally works best when used b.i.d. or t.i.d. Most importantly, probenecid loses virtually all of its uricosuric activity when the glomerular filtration rate drops below 30 mL/min/1.73 m2.