Table 20Summary of prior knowledge, findings from the systematic review, and strength of evidence, by KQ

Key QuestionPrior Knowledge Used in Determining Strength of EvidenceSources of Evidence Included in This Systematic ReviewStrength of Evidence
KQ1 Acute Gout Treatment
Colchicine reduces painN/A
  • 2 placebo-controlled RCTs (N=45 and N=184) both with low risk of bias
High
Low-dose colchicine is as effective as higher dose for reducing pain, with fewer side effectsN/A
  • 1 head-to-head RCT with low risk of bias (N=184)
Moderate
NSAIDs reduce gout pain
  • Biologic rationale (anti-inflammatory action)
  • Placebo-controlled RCT evidence that NSAIDs provide temporary pain relief for numerous conditions
  • 1 placebo-controlled RCT with high risk of bias (N=30)
  • High strength observational data (NSAID use as prophylaxis against gout flare) (see below under KQ3)
High
No difference between NSAIDs in effectiveness
  • Equivalence in effectiveness among NSAIDs in numerous other conditions
  • 16 head-to-head RCTs
Moderate
Systemic corticosteroids reduce pain
  • Biologic rationale (anti-inflammatory action)
  • No placebo-controlled RCTs
  • Equivalence to NSAIDs in 4 RCTs (N=27, N=90, N=120, and N=60).Three of four RCTs had low risk of bias.
High
Animal-derived ACTH formulation reduces pain
  • Biologic rationale (anti-inflammatory action)
  • No placebo-controlled RCTs
  • Equivalence to NSAIDs and intramuscular steroids in RCTs (one RCT of each, N=76 and N=31 both at high risk of bias)
Moderate
Differences stratified by patient demographic, comorbid conditions, disease severity, clinical presentation, or laboratory valuesN/ANone of the included RCTs presented data stratified by these variables.Insufficient
KQ2 Diet and lifestyle management
Specific dietary changes (including reducing intakes of dietary purines, protein, or alcohol; increasing intakes of cherries, modified milk products, or supplemental vitamin C; or achieving weight loss) in gout management may affect symptomatic outcomesN/A
  • 3 RCTs (two at high risk of bias) (N=67, N=120, N=40)
  • 3 observational studies (N=20, N=120, N=633)
Insufficient
Gout-specific dietary advice (counseling about reducing red meat; avoiding offal, shellfish, and yeast-rich foods and beverages or increasing low-fat dairy products, vegetables, and cherries) compared with nonspecific dietary advice (counseling about the importance of weight loss and reduced alcohol intake) for reducing serum urate levels in patients with goutN/A
  • 1 RCT with high risk of bias (N=30)
Insufficient
Effectiveness of Traditional Chinese Medicine (TCM) (acupuncture, herbal mixtures, moxibustion) on symptomatic outcomesN/A
  • 86 RCTs, all of idiosyncratic therapies, with conflicting results
Insufficient
KQ3 Management of hyperuricemia
Urate lowering therapy does not reduce the risk of acute gout attacks within the first 6 monthsN/A
  • 2 placebo-controlled RCTs,with low risk of bias (N=1,072 and N=57)
High
Urate lowering therapy reduces the risk of acute gout attacks after 1- year
  • Acute gout attacks are caused by elevated serum urate concentrations
  • No placebo-controlled RCTs assess long-term risk of acute gout attacks
  • RCTs with low risk of bias show that ULT reduces serum uric acid
  • Open label extension study of ULT RCT shows reduced risk of acute gout attacks over time, plateauing at less than 5% at about 1 year
Moderate
Urate lowering therapy reduces serum urateN/A
  • 4 placebo-controlled RCTs all with low risk of bias (N=1,072, N=96, N=153, and N=57)
High
40 mg febuxostat and 300mg allopurinol show no differences in serum urate loweringN/A
  • 1 head-to-head RCT with low risk of bias (N=2,269)
High
Effectiveness and comparative effectiveness of allopurinol and febuxostat depending on the presence of tophiN/A
  • Subgroup analyses of included trials did not report consistent results when stratified on the presence of tophi.
Insufficient
Age and race (Caucasian vs. African-American) do not affect the efficacy of febuxostat or allopurinol.N/A
  • Subgroup analyses of 1 head-to-head RCT with low risk of bias (N=2,269)
Low
Prophylactic therapy with low-dose colchicine or low-dose NSAIDs when beginning urate lowering therapy reduces the risk of acute gout attacksN/A
  • 1 placebo-controlled RCT of colchicine with low risk of bias (N=43)
  • Strong observational evidence across 3 RCTs with low risk of bias that included different durations of prophylaxis (N=762, N=2,269, and N=1,072)
High
Longer durations of prophylaxis with colchicine or NSAIDs (> 8 weeks) are more effective than shorter duration when initiating urate lowering therapyN/A
  • Indirect evidence from comparisons across 3 RCTs of differing durations of prophylaxis
  • 1 RCT with high risk of bias (N=190)
Moderate
Specific gout-dietary advice to reduce red meat, shellfish, etc. while increasing low-fat dairy products, vegetables, and cherries does not add to the effectiveness of urate lowering therapy for reducing serum urateN/A
  • 1 RCT with high risk of bias (N=30)
Insufficient
KQ4 Treatment Monitoring
Serum urate monitoring improves outcomesN/A
  • No direct evidence
  • An argument can be made indirectly, based on the evidence that elevated serum urate levels cause gout
Insufficient
Treating to a specific target serum urate level reduces the risk of gout attacksLower serum urate levels are associated with reduced risk of gout attacks
  • No RCT evidence
  • Variable targets proposed or assessed in the literature
Low
KQ5 Criteria for discontinuation of pharmaceutical management
Hyperuricemia
Urate lowering therapy may be discontinued in gout patients with 5 years of urate lowering therapy keeping serum urate levels <7mg/dl, with subsequent annual off-urate lowering therapy-serum urate levels <7mg/dl		N/A
  • 3 prospective cohort studies (N=211, N=33, N=100)
Insufficient
Prophylaxis
Prophylaxis for acute gout when initiating urate lowering therapy with low-dose colchicine or NSAIDs should be longer than 8 weeks		N/A
  • Indirect evidence from comparisons across 3 RCTs with low risk of bias of differing durations of prophylaxis (N=762, N=2,269, and N=1,072)
Moderate

FDA = Food and Drug Administration; N/A = not applicable; NSAID = nonsteroidal anti-inflammatory drug; RCT = randomized controlled trial; ULT = urate lowering therapy

From: Discussion

Cover of Management of Gout
Management of Gout [Internet].
Comparative Effectiveness Reviews, No. 176.
Shekelle PG, FitzGerald J, Newberry SJ, et al.
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