This is the current release of the guideline.

Chronic and recurrent gout

To manage chronic gout and to prevent recurrent disease exacerbations by reducing uric acid levels through pharmacological and lifestyle interventions thereby providing prompt termination of pain and disability

Adults with previously diagnosed gout

Treatment/Management

1. Prophylaxis against recurrent attacks
   • Non-steroidal anti-inflammatory drugs (NSAIDs) such as naproxen or indomethacin
   • Colchicine
2. First-line therapy with allopurinol or febuxostat
3. Second-line therapy with probenecid
4. Third-line therapy with pegloticase
5. Lifestyle modifications
   • Low purine diet
   • Increased low-fat dairy foods
   • Avoidance of alcohol ingestion-specifically beer and liquor
   • Regular exercise
   • Increased coffee intake
   • Avoidance of aspirin
   • Increased vitamin C intake
   • Weight reduction and lowered insulin resistance
6. Monitoring of serum uric acid levels and gout symptoms
7. Monitor for signs and symptoms of cardiovascular events

Searches were conducted via electronic databases including UpToDate, Cochrane Library, Evidence-based Approach, PubMed, CINAHL, and MEDLINE, using key words gout, treatment, uric acid, allopurinol, febuxostat and chronic. The literature search performed was for the past 5 years, 2007-12. However one study from 2004 was included because of its significance.

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Quality of Evidence

Not stated

Not stated

Strength of Recommendation (Based on U.S. Preventive Services Task Force [USPSTF] Ratings)

A: The USPSTF recommends the service. There is high certainty that the net benefit is substantial.

B: The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.

C: The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small.

D: The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.

I statement: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

A formal cost analysis was not performed and published cost analyses were not reviewed.

Not stated

Strength of recommendations (A, B, C, D, I) and quality of evidence (High, Moderate, Low) are defined at the end of the "Major Recommendations" field.

Prophylaxis Against Recurrent Attacks

Non-steroidal Anti-inflammatory Drugs (NSAIDs) and Colchicine

• Naproxen 250 mg orally twice daily (Gonzalez, 2012; Neogi, 2011; Schumacher et al., 2008) (Grade A, High).
• Indomethacin 50 mg orally three times per day (Epocrates Online, 2012) (Grade B, Low).
• Colchicine 0.6 mg orally once or twice daily (Borstad et al., 2004; Hamburger et al., 2011; Neogi, 2011) (Grade A, High).
• Prophylaxis should be considered during initiation and tapering of uric acid lowering therapy (ULT) and should be continued for 3 to 12 months after reaching the serum uric acid target level (Epocrates Online, 2012; Hamburger et al., 2011) (Grade B, Moderate).

First Line Therapy

Pharmacological

• Initiation of ULT is indicated if >2 acute attacks per year, chronic arthropathy, tophaceous deposits, nephrolithiasis, or radiographic changes of gout. Once it is started, lifelong treatment is recommended (Epocrates Online, 2012; Neogi, 2011; Terkeltaub, 2010) (Grade B, Moderate).
• ULT should not be started until at least 2 weeks after resolution of an acute gout attack (Hamburger et al., 2011; Epocrates Online, 2012) (Grade B, Moderate).
• Assess serum uric acid (SUA) level two weeks after an attack has resolved as it may be falsely low or normal during an attack (Hamburger et al., 2011) (Grade B, Moderate).

Allopurinol

Allopurinol 100 mg daily, increasing 100 mg daily every 2 to 4 weeks (maximum of 800 mg daily) until an SUA level <6.0 mg/dl is reached (Hamburger et al., 2011; Gonzalez, 2012) (Grade B, Moderate).

• Results from a randomized controlled trial (RCT) indicated an increase in treatment success from 29% to 78% when doubling the allopurinol dose from 300 mg/day to 600 mg/day (Reinders et al., "A randomised controlled trial," 2009) (Grade A, High).
• Discontinue allopurinol at the first signs of a rash (Gonzalez, 2012; Hamburger et al., 2011) (Grade B, Moderate).
• SUA level monthly until target SUA level <6.0 mg/dl is reached, then retest every 6-12 months (Hamburger et al., 2011) (Grade B, Moderate).

Febuxostat

If allopurinol intolerance, contraindication, lack of efficacy or impaired renal function serum creatinine level >1.5. (Schumacher et al., 2008) (Grade A, High):

• Febuxostat 40 mg daily; may increase after 2 weeks to 80 mg daily to achieve an SUA of <6.0 mg/dl (Gray & Walters-Smith, 2011) (Grade B, Moderate).
• "At all doses studied, febuxostat more effectively lowered and maintained serum urate levels <6.0 mg/dl than did allopurinol (300 or 100 mg) or placebo in subjects with hyperuricemia and gout, including those with mild to moderately impaired renal function" (Schumacher et al., 2008) (Grade A, High).
• Monitor for signs and symptoms of cardiovascular events. In clinical trials, those treated with febuxostat had higher rates of these events than allopurinol, but not statistically significant. Currently, phase III clinical trials are being conducted to evaluate the safety in patients with cardiovascular comorbidities (Gray & Walters-Smith, 2011) (Grade B, Moderate).

Second Line Therapy

Probenecid

• Begin at 250 mg twice daily, may titrate up monthly to a total of 3 g daily in twice daily divided doses to achieve SUA level <6.0 mg/dl (Hamburger et al., 2011) (Grade B, Moderate).
• Results from an RCT indicated a 65% success rate on probenecid 2000 mg/day (Reinders et al., 2009, "Efficacy") (Grade B, Moderate)
• Used with or as an alternative to allopurinol or febuxostat (Hamburger et al., 2011) (Grade B, Moderate).

Third Line Therapy

Pegloticase

• According to Sundy et al. (2011), pegloticase is indicated for "refractory chronic gout and baseline serum uric acid level of 8 mg/dl or greater and at least one of the following: 3 or more self-reported gout flares during the past 18 months; 1 or more tophi; and gouty arthropathy, defined clinically or radiographically as joint damage due to gout. Patients also had contraindication to treatment with allopurinol or failure to normalize SUA despite 3 or more months of treatment with the maximum medically appropriate allopurinol dose" (Grade B, Low).
• It is administered intravenously, 8 mg every 2 or 4 weeks for 6 months (Sundy et al., 2011) (Grade B, Low).
• Pegloticase has a significant risk profile. Candidates should be referred to a health care provider with expertise in the use of pegloticase (Sundy et al., 2011) (Grade B, Low).
• In roughly 3% of patients, conventional oral urate–lowering agents fail to achieve target uric acid levels of less than 6.0 mg/dL. Pegloticase was developed for this group of patients (Brooks, 2011) (Grade C, Low).

Lifestyle Modifications

• Avoidance of purine rich foods (liver, kidneys, shellfish and red meat) (Crittenden & Pillinger, 2011) (Grade B, Moderate)
• Avoidance of beer and liquor (Crittenden & Pillinger, 2011) (Grade B, Moderate)
• Soy beans, vegetable protein sources and cherries (Crittenden & Pillinger, 2011) (Grade B, Moderate)
• Low-fat dairy products, such as yogurt and skim milk reduce uric acid levels (Crittenden & Pillinger, 2011) (Grade B, Moderate).
• Coffee, both caffeinated and decaf, reduces uric acid levels (Crittenden & Pillinger, 2011) (Grade B, Moderate).
• Reducing fructose intake is an important to measure to prevent hyperuricemia (Choi & Curhan, 2008) (Grade B, Moderate).
• Avoidance of aspirin (Grade A, High)
• Increase vitamin C supplementation by an additional 500 mg daily (Grade B, Moderate).
• Weight reduction and lower insulin resistance (Grade A, High) (Zychowicz, Pope, & Graser, 2010)

Definitions:

Strength of Recommendation (Based on U.S. Preventive Services Task Force [USPSTF] Ratings)

A: The USPSTF recommends the service. There is high certainty that the net benefit is substantial.

B: The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.

C: The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small.

D: The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.

I statement: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

Quality of Evidence

None provided

The type of supporting evidence is specifically stated for each recommendation (see the "Major Recommendations" field).

Management of chronic gout symptoms and prevention of recurrence

Adverse Effects of Medications

• Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal side effects. Caution should be used in patients with concomitant anticoagulant use and cardiovascular disease.
• Colchicine is associated with nausea, vomiting, and diarrhea.

An implementation strategy was not provided.

Not applicable: The guideline was not adapted from another source.

University of Texas at Austin, School of Nursing, Family Nurse Practitioner Program

Not stated

Primary Authors: Michael Emery, RN, MSN, FNP; Jessica Mackert, RN, MSN, FNP; Candace Mattson, RN, MSN, FNP (c); Adrienne Miller, RN, MSN, FNP; Kim Zaydel, RN, MSN, FNP

Not stated

This is the current release of the guideline.

Electronic copies: None available.

Print copies: Available from University of Texas at Austin, School of Nursing. 1700 Red River, Austin, Texas, 78701-1499, Attn: Nurse Practitioner Program.

None available

None available

This NGC summary was completed by ECRI Institute on July 24, 2012.

This NGC summary is based on the original guideline, which may be subject to the guideline developer's copyright restrictions.