The American College of Rheumatology (ACR) developed an updated set of guidelines in 2020 for the management of gout, which includes indications and use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and medication recommendations. The full report was published in Arthritis Care & Research.1

According to the 2012 ACR guidelines for the management of gout, ULT was recommended as the first-line approach for a majority of patients with gout. However, ULT has not been widely adopted by clinicians, and when prescribed, patient adherence was observed to be poor.2,3 The ACR guidelines subcommittee determined that the 2012 recommendations were often disregarded because of a lack of strong evidence supporting the treat-to-target strategies, which has been addressed by newer evidence from several large, recently conducted clinical trials.

Updated ACR Guidelines for the Management of Gout

Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and patient input, the 2020 update of the ACR guidelines includes 16 strong recommendations and 34 other recommendations to support clinical decision-making for the treatment of gout.

Indications for Pharmacologic ULT

  • In line with the 2012 ACR guidelines for gout management, ULT is still the preferred treatment for most patients with gout. 
  • The guidelines subcommittee has included strong evidence to support initiating ULT in patients with gout who have any 1 of the following signs, including subcutaneous tophi (≥1), evidence of radiographic damage by any modality that appears to be due to gout, and frequent gout flare occurrence (>2 times/y).
  • Recommendations for initiation of ULT were noted to be conditional for patients with a previous history of infrequent gout flares (<2 flares/y).
  • The subcommittee has conditionally recommended against the initiation of ULT for patients who experience their first gout flare.
  • In cases involving urolithiasis, stage ≥3 chronic kidney disease (CKD), and/or serum urate (SU) concentration >9 mg/dL, ULT can be conditionally recommended.
  • The subcommittee has conditionally recommended against initiating pharmacologic ULT in patients with asymptomatic hyperuricemia (SU, >6.8 mg/dL and no previous gout flares or subcutaneous tophi), including those with comorbid CKD, cardiovascular disease, urolithiasis, or hypertension.

Choice of Initial ULT

  • Allopurinol has been strongly recommended as the preferred first-line agent for the treatment of all patients with gout, including those with moderate to severe CKD.
  • Xanthine oxidase inhibitors (XOI) allopurinol or febuxostat have been strongly recommended over probenecid for patients with moderate to severe CKD, with pegloticase recommended against as a first-line therapy.
  • Allopurinol may be strongly considered at starting doses of ≤100 mg per day, and at lower doses for patients with stage ≥3 CKD.
  • For febuxostat, starting doses of ≤40 mg per day with dose escalation to reach optimal dosing has been strongly recommended as the second choice to allopurinol.
  • When used as an initial therapy for gout, probenecid has been conditionally recommended at doses of 500 mg 1 to 2 times daily, with titration to higher therapeutic doses.
  • The guidelines subcommittee has strongly recommended concomitant prophylaxis anti-inflammatory therapy with colchicine, nonsteroidal anti-inflammatory drugs, or glucocorticoids, such as prednisone or prednisolone, over no prophylactic treatment.
  • Continuing anti-inflammatory prophylaxis has been recommended for 3 to 6 months over <3 months, with regular evaluation as long as gout flares persist.

Timing of ULT Initiation

  • Once ULT has been indicated for gout, clinicians may initiate treatment at the time of a flare rather than starting treatment after the flare has been resolved.
  • The subcommittee has strongly recommended a treat-to-target strategy with titration to reach target SU over a fixed-dose approach for patients with gout receiving ULT.
  • Achieving a stable SU target of <6 mg/dL vs no target for patients receiving ULT has been strongly recommended.
  • Augmenting the ULT treatment protocol with the supplementation of patient education, shared decision-making, and treat-to-target incentives by nonphysician providers has been conditionally recommended.

Duration of ULT

  • The guidelines subcommittee has conditionally recommended continuing ULT indefinitely over stopping therapy.

Patients Receiving ULT

Allopurinol

  • Because the HLA-B*5801 gene may be associated with a markedly elevated risk for allopurinol hypersensitivity reactions, testing for the HLA-B*5801 allele in patients with gout of Southeast Asian or African American descent has been conditionally recommended; however, universal testing for the allele was conditionally recommended against in patients of other ethnic backgrounds.
  • Among patients with gout who cannot or are unable to be treated with other oral ULT agents and who have had a prior allergic reaction to allopurinol, desensitization to allopurinol has been conditionally recommended.

Febuxostat 

  • For patients with gout receiving febuxostat with a new or history of a cardiovascular event, the subcommittee has conditionally recommended to switching to an alternative oral ULT drug.

Uricosurics

  • For patients receiving uricosuric treatment, it has been conditionally recommended against checking urinary acid levels prior to prescribing.
  • It has also been conditionally recommended against to alkalinize the urine of patients receiving uricosuric medications.

Switching to New ULT Strategies

  • The subcommittee has offered conditional recommendations for switching from a first XOI therapy to a second XOI in patients whose SU levels consistently remain >6 mg/dL and those who experience ≥2 flares yearly, or who have persistent tophi despite maximum therapeutic doses of the original drug. Switching to a second XOI may be preferred to adding a uricosuric agent.
  • Patients with gout whose treatment has failed to reach the SU target and those who continue to have frequent flares or unresolved tophi despite treatment with XOIs, uricosurics, or other drug therapies have been strongly recommended to switch to pegloticase rather than continuing with current ULT.
  • It has been strongly recommended against to switch to pegloticase over continuing current ULT when other drugs have failed to achieve the SU target but gout flares are less frequent (<2 flares/y) and no tophi are present.

Flare Management

  • Colchicine, nonsteroidal anti-inflammatory drugs, or glucocorticoids (oral, intra-articular, or intramuscular) vs interleukin (IL)-1 inhibitors or adrenocorticotropic hormone (ACTH) have been strongly recommended as first-line therapy for gout flares.
  • All doses of colchicine deliver similar efficacy; however, low-dose colchicine may have reduced risk for adverse effects, and therefore, has been strongly recommended.
  • The subcommittee has strongly recommended that in cases where patients cannot or are unable to receive oral therapies, other delivery forms of glucocorticoids (including intramuscular, intravenous, or intra-articular routes) are preferred over IL-1 inhibitors or ACTH.
  • The use of IL-1 inhibitors over no therapy may be recommended for patients in whom anti-inflammatory drugs are ineffective, poorly tolerated, or contraindicated.
  • As an adjuvant measure, topical ice may be used over no therapy at all for patients experiencing gout flares.

Managing Concurrent Medications

  • The guidelines subcommittee has conditionally recommended that patients with gout receiving hydrochlorothiazide switch to alternate antihypertensive therapy, regardless of disease activity.
  • Losartan has been conditionally recommended as an antihypertensive agent when feasible.
  • For patients with gout receiving low-dose aspirin therapy for appropriate indications, it has been conditionally recommended against stopping this medication, regardless of disease activity.
  • For patients receiving cholesterol-lowering therapy, it has been conditionally recommended against to add or switch to fenofibrate, regardless of disease activity.

Lifestyle Management

  • As with previous guidelines, patients with gout have been conditionally recommended to limit their intake of alcohol, purine, and high fructose corn syrup, regardless of disease activity. 
  • Adding vitamin C supplements to patients’ daily diet has been conditionally recommended against, regardless of disease activity. 
  • Weight loss (using any program) has been conditionally recommended for patients with gout who are overweight or obese, regardless of disease activity.

References

1. FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology guideline for the management of gout. Arthritis Care Res (Hoboken). 2020;72(6):744-760.


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2. Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431-1446.

3. Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 American College of Rheumatology Guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken). 2012;64(10):1447-1461.

This article originally appeared on Rheumatology Advisor