Updated ACR Gout Management Guideline Features Higher Quality Evidence Supporting Treat-to-Target Recommendations

Earlier this year, the American College of Rheumatology (ACR) published an updated version of its guideline for the management of patients with gout. This guideline features 42 recommendations, including 16 strong recommendations, the most prominent of which concerned indications for and use of pharmacologic urate-lowering therapy (ULT) “for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares.”1 The revised treatment recommendations are supported by new evidence from clinical trials that have concluded since the publication of the last gout treatment guideline in 2012.

In their introduction, the ACR noted that although gout is the most common form of inflammatory arthritis, and previous guidelines also recommended treat-to-target strategies for the use of ULT, utilization of ULT remained unchanged and adherence to treatment was generally low.1

In light of the new data available, a team of rheumatologists and other experts and patient representatives developed a set of 57 population, intervention, comparator, and outcomes (PICO) questions to address:

  • Indications for ULT
  • Approaches to initiating ULT
  • Ongoing ULT management
  • Gout flares
  • Lifestyle and other medication strategies in patients with gout
  • Lifestyle and medication strategies in patients with asymptomatic hyperuricemia

The guidelines’ development team specified gout flare, serum urate concentration, and tophus as critical outcomes for all PICO questions specific to ULT. They identified pain as a critical outcome for all PICO questions specific to gout flare, which was identified as the only critical outcome for management of lifestyle factors. The team then conducted a systematic literature review to address each PICO question and evaluated the evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

The PICO questions and supporting evidence were used to draft treatment recommendations that were voted on by a panel of experts with patient input. A consensus of 70% of the voting panel was required for a recommendation to be included in the final guideline.

Recommendations in the guideline are rated as either “strong” or “conditional.” Strong recommendations “reflect decisions supported by moderate or high certainty of evidence where the benefits consistently outweigh the risks, and, with only rare exceptions, an informed patient and his or her provider would be expected to reach the same decision.” Conditional recommendations “reflect scenarios for which the benefits and risks may be more closely balanced and/or only low certainty of evidence or no data are available.”1

Strong Recommendations

The 2020 ACR Guideline for the Management of Gout contains the following strong recommendations.

Indications for Pharmacologic ULT

ULT should be initiated for patients with gout who have ≥1 subcutaneous tophi, evidence of radiographic damage (any modality) attributable to gout, or frequent (≥2 annually) gout flares.

Choice of Initial ULT

Allopurinol (Zyloprim) is the preferred first-line treatment for all patients with gout, including those with moderate-to-severe (stage ≥3) chronic kidney disease (CKD). Either allopurinol or febuxostat (Uloric) should be used instead of probenecid (Probalan) for patients with moderate-to-severe CKD. Pegloticase (Krystexxa) is not recommended as a first-line therapy for patients with gout. Initial therapy with allopurinol ≤100 mg daily is recommended for patients with gout, although patients with stage ≥3 CKD should be started at lower doses. Treatment with febuxostat should start at ≤40 mg daily with subsequent dose titration. Treatment with probenecid should be initiated at 500 mg 1 to 2 times daily with subsequent dose titration.

The guidelines strongly recommend the use of concomitant antiinflammatory prophylaxis therapy (eg, colchicine [Colcrys], nonsteroidal anti-inflammatory drugs [NSAIDs], prednisone/prednisolone) versus the use of no prophylactic therapy. Anti-inflammatory prophylaxis therapy should be continued for 3 to 6 months (instead of <3 months), with ongoing evaluation and continued prophylaxis as needed if the patient continues to experience gout flares.

Timing of ULT Initiation

For patients receiving ULT, a treat-to-target management approach that includes titration to meet target serum urate levels is recommended versus a fixed-dose strategy. Maintaining a serum urate target level of <6 mg/dL in patients with gout receiving ULT is also recommended versus treating with no set target in mind.

Changing ULT Strategy

Patients with gout receiving ULT should be switched to treatment with pegloticase, rather than continue with their current therapy, if treatment with xanthine oxidase inhibitors (XOIs), uricosurics, and other interventions have not achieved target serum urate levels, and if the patient continues to have frequent gout flares (≥2 flares/year) or has nonresolving subcutaneous tophi. However, the guidelines recommend against switching a patient from current ULT to pegloticase if treatment with XOIs, uricosurics, and other interventions has not achieved target serum urate levels but the patient has infrequent gout flares (<2 flares each year) and no tophi.

Gout Flare Management

For patients experiencing a gout flare, first-line treatment with colchicine, NSAIDs, or glucocorticoids (eg, oral, intraarticular, or intramuscular) is recommended versus treatment with interleukin-1 inhibitors or adrenocorticotropic hormone. Low-dose colchicine is recommended versus high-dose colchicine because it has similar efficacy with a lower risk for adverse effects. For patients with gout who are unable to take oral medications, treatment with glucocorticoids (eg, intramuscular, intravenous, or intraarticular) is recommended versus treatment with interleukin-1 inhibitors or adrenocorticotropic hormone.

Conditional Recommendations

The following are among the conditional recommendations contained in the 2020 ACR Guideline for the Management of Gout.

Indications for Pharmacologic ULT

Although some patients may prefer to receive ULT after their first gout flare, the updated guideline conditionally recommends against initiating ULT in these patients. Initiating ULT in patients with asymptomatic hyperuricemia is also recommended against.

Choice of Initial ULT

The guidelines conditionally recommend starting treatment with probenecid at doses of 500 mg 1 to 2 times daily, with subsequent dose titration, rather than initiating treatment at a higher dose.

Timing of ULT Initiation

If ULT is indicated in a patient with gout who is experiencing a flare, it is conditionally recommended that treatment be started during the flare rather than waiting until the flare has resolved to begin treatment.

Recommendations for Patients Receiving ULT Medications

The guideline conditionally recommends testing for the human leukocyte antigen (HLA)-B*5801 allele prior to starting allopurinol for patients of Southeast Asian descent and for African American patients, versus not conducting testing for the HLA-B*5801 allele in these patients. However, testing for the HLA-B*5801 allele prior to starting allopurinol is conditionally recommended against in patients of other ethnic or racial background.

Management of Lifestyle Factors

Patients with gout, regardless of disease activity, are conditionally recommended to limit their intake of alcohol, purine, and high-fructose corn syrup. Patients with gout, regardless of disease activity, who are overweight or obese are conditionally recommended to participate in a weight loss program (no specific program endorsed).

Conclusion

“With this update, we sought to look at new and emerging clinical evidence that would be beneficial for treating patients with gout,” said John FitzGerald, MD, PhD, Rheumatologist, University of California, Los Angeles, and Co-Principal Investigator of the ACR’s guideline. “The guideline now includes expanded indications for starting ULT, a greater emphasis to use allopurinol as the first line agent for all patients with gout that require urate lowering therapy including those patients with chronic kidney disease, and broadened recommendations about who needs HLA-B*5801 testing prior to starting allopurinol.”2

By incorporating data from updated literature and high-quality clinical trials and GRADE methodology, the 2020 ACR Guideline for the Management of Gout reinforces many of the previous 2012 ACR guideline recommendations, while resulting in “a more focused, less proscriptive document.”1

References

  1. FitzGerald JD, Dalbreth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken). 2020;72:744-760. Erratum in: Arthritis Care Res (Hoboken). 2020;72:1187.
  2. American College of Rheumatology. ACR releases gout management guideline with emphasis on treat-to-target strategy for urate lowering therapy. May 11, 2020. www.rheumatology.org/About-Us/Newsroom/Press-Releases/ID/1085. Accessed October 26, 2020.

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