The American College of Rheumatology (ACR) developed an updated set of guidelines in 2020 for the management of gout. The guideline includes indications and use of urate-lowering therapy (ULT), titration and treat‐to‐target approach, approaches following ULT failure, and treatment of gout flares.

Below are the strong recommendations from the update guidelines.

Indications for pharmacologic urate‐lowering therapy (ULT)

Initiating ULT is strongly recommended for gout patients with any of the following: ≥1 subcutaneous tophi; evidence of radiographic damage (any modality) attributable to gout; OR frequent gout flares, with frequent being defined as ≥2 annually.

There have been reports of initial hesitancy to start ULT; ULT has not been widely adopted by clinicians, and when prescribed, patient adherence was poor. However, these have changed with newer data from several large, recently conducted clinical trials which demonstrates improved control of inflammatory symptoms and tophi with ULT.

Recommendations for choice of initial ULT for patients with gout

Treatment with allopurinol as the preferred first‐line agent, over all other ULTs, is strongly recommended for all patients, including those with moderate‐to‐severe chronic kidney disease (CKD) (stage ≥3).

As per the panel, allopurinol is preferred due to its efficacy, tolerability and safety. The fact that it is an oral medication and less expensive are added benefits. Initiating allopurinol at a lower dose is recommended to reduce the risk of hypersensitivity syndrome.

1. The choice of either allopurinol or febuxostat over probenecid is strongly recommended for patients with moderate‐to‐severe CKD (stage ≥3).
2. The choice of pegloticase as a first‐line therapy is strongly recommended against.
3. Starting treatment with low‐dose allopurinol (≤100 mg/day and lower in patients with CKD [stage ≥3]) and febuxostat (≤40 mg/day) with subsequent dose titration over starting at a higher dose is strongly recommended.

Initiating treatment at lower doses with subsequent dose escalation of ULT reduces the risk of flare. While higher starting doses and CKD are associated with risk of hypersensitivity syndrome, to achieve the serum urate (SU) target patients with CKD may still require dose titration above 300 mg/day.

1. Administering concomitant antiinflammatory prophylaxis therapy (e.g., colchicine, nonsteroidal antiinflammatory drugs [NSAIDs], prednisone/prednisolone) over no antiinflammatory prophylaxis therapy is strongly recommended.
2. Continuing concomitant antiinflammatory prophylaxis therapy for 3–6 months over <3 months, with ongoing evaluation and continued prophylaxis as needed if the patient continues to experience gout flares, is strongly recommended.

Evidence from randomised clinical trials and observational studies support the use of antiinflammatory prophylaxis therapy when initiating ULT. Prophylaxis should be continued for at least 3–6 months as shorter prophylaxis may lead to flares upon stopping prophylaxis. If the patient continues to experience flares after stopping prophylaxis, monitor flare activity and continue antiinflammatory treatment.

Timing of ULT initiation

1. A treat‐to‐target management strategy that includes ULT dose titration and subsequent dosing guided by serial SU measurements to achieve a target SU, over a fixed‐dose ULT strategy, is strongly recommended for all patients receiving ULT.
2. Achieving and maintaining an SU target of <6 mg/dl over the use of no target is strongly recommended for all patients receiving ULT.

A treat‐to‐target management strategy is preferred over a fixed‐dose strategy to optimise patient outcomes. Maintaining an SU target of <6 mg/dl is recommended. Compared to a fixed‐dose strategy, treat‐to‐target protocol is associated with greater ULT adherence, lower SU concentrations, reduction in tophi, and a lower proportion of frequent (≥2) gout flares at 24 months.

To prevent “treatment inertia”, ULT should be titrated over an appropriate time frame (e.g., weeks to months, not years). Specific dose titration schedule should be individualized based on patient comorbidities and preferences.

Recommendations for patients receiving ULT medications

Allopurinol - Starting allopurinol in daily doses of ≤100 mg (and lower doses in patients with CKD) is strongly recommended over starting at a higher dose.

When to consider changing ULT strategy

1. Switching to pegloticase over continuing current ULT is strongly recommended for patients with gout for whom xanthine oxidase inhibitor (XOI) treatment, uricosurics, and other interventions have failed to achieve the SU target, and who continue to have frequent gout flares (≥2 flares/year) OR who have nonresolving subcutaneous tophi.
2. Switching to pegloticase over continuing current ULT is strongly recommended against for patients with gout for whom XOI treatment, uricosurics, and other interventions have failed to achieve the SU target, but who have infrequent gout flares (<2 flares/year) AND no tophi.

The harms and costs of administering pegloticase would likely be similar in patients with mild versus severe disease, resulting in limited benefit and appreciable harm along with very high costs. This conclusion, along with strong patient panel statements about not wanting to receive twice‐monthly infusions to prevent infrequent gout flares, resulted in the strong recommendation against using pegloticase for patients with mild disease.

Gout flare management

1. Using colchicine, NSAIDs, or glucocorticoids (oral, intraarticular, or intramuscular) as appropriate first‐line therapy for gout flares over IL‐1 inhibitors or adrenocorticotropic hormone (ACTH) is strongly recommended for patients experiencing a gout flare.
2. Given similar efficacy and a lower risk of adverse effects, low‐dose colchicine over high‐dose colchicine is strongly recommended when colchicine is the chosen agent.
3. Treatment with glucocorticoids (intramuscular, intravenous, or intraarticular) over IL‐1 inhibitors or ACTH is strongly recommended for patients who are unable to take oral medications.

For gout flares, colchicine, NSAIDs, or glucocorticoids are recommended as the preferred first‐line therapies due to their efficacy, relative low cost, and tolerability in flare management. The dosing and duration for each drug should be based on the severity of the flare; treatment selection should be driven by patient factors such as comorbidity, access, past experience. When oral dosing is not feasible, parenteral glucocorticoids are favored over alternative agents.