Gout: When Allopurinol Fails to Achieve the Serum Uric Acid Target

Clinical Scenario

This protocol addresses patients with gout who are on allopurinol-based urate-lowering therapy but have not reached the recommended serum uric acid (SUA) target — either because allopurinol at an adequate dose has been insufficient, or because it cannot be tolerated.

Why Escalation Is Needed

First-line therapy with allopurinol (titrated to target, alongside prophylactic colchicine or naproxen and lifestyle measures) has not brought SUA below 6 mg/dL (360 mmol/L). For patients with severe gout — tophi, chronic arthropathy, or frequent attacks — the more stringent target of 5 mg/dL (300 mmol/L) has also not been reached. This protocol defines the next step.

Treatment Approach (Partial Overview)

When allopurinol does not achieve the SUA target, switching to a different class of urate-lowering agent or adding uricosuric therapy is among the strategies considered. The complete agent selection, sequencing, and monitoring approach is in the full protocol.

Treatment Targets

Serum uric acid <6 mg/dL (360 mmol/L) — maintained lifelong
Serum uric acid <5 mg/dL (300 mmol/L) for patients with severe gout, until total crystal dissolution

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1136/annrheumdis-2016-209707

If the SUA target cannot be reached by an appropriate dose of allopurinol, allopurinol should be switched to febuxostat or a uricosuric, or combined with a uricosuric.
Febuxostat or a uricosuric are also indicated if allopurinol cannot be tolerated.
Febuxostat is a potent non-purine selective XOI approved at daily doses of 80 and 120 mg in Europe.
Benzbromarone (50–200 mg/day) is a more potent uricosuric as compared with probenecid (1–2 g/day).
For patients on ULT, SUA level should be monitored and maintained to <6 mg/dL (360 mmol/L).
A lower SUA target (<5 mg/dL; 300 mmol/L) to facilitate faster dissolution of crystals is recommended for patients with severe gout (tophi, chronic arthropathy, frequent attacks) until total crystal dissolution and resolution of gout.

View source ↗