EULAR 2022 (VIRTUAL)—When it comes to inflammatory arthritis, most rheumatology providers would agree that gout is, by far, the most treatable type. However, most patients and primary care providers might disagree. Why the disconnect?
Gout therapies are effective … when properly prescribed. Therein lies the rub. At the 2022 Congress of the European Alliance of Associations for Rheumatology (EULAR), Thomas Bardin, MD, rheumatology department, Hôpital Lariboisière, Paris, and professor emeritus, Université de Paris Cité, shared his expertise on refractory gout and whether it should actually exist in 2022.
Definitions & Causes
Refractory gout is defined as the persistence of clinical manifestations of gout due to the inability to reduce the serum urate (SU) concentration below the target 6.0 mg/dL.1 It’s characterized by long disease duration and features of severe disease like frequent flares, polyarticular involvement, tophi, destructive arthropathy and/or chronic inflammatory arthritis. Refractory gout is also associated with many comorbidities and high economic costs.2,3 The U.S. Food & Drug Administration estimated, when approving pegloticase in 2009, that about 1% of gout patients had refractory disease, but this number is a moving target.4
“The cause of refractory gout is obviously mismanagement, and there are multiple sources,” Professor Bardin said. Insufficient prescription and dosing of urate-lowering therapy (ULT) remains a major culprit. Poor adherence to therapy results in lack of disease control, which is fueled in part by a general lack of patient and healthcare provider education about gout management. Drug intolerances and contraindications further complicate the picture.5,6 The list goes on.
Historically, intolerance to allopurinol— mainly due to cutaneous reactions—has been a source of refractory gout. However, Professor Bardin et al. demonstrated the majority of patients with cutaneous intolerance to allopurinol can tolerate febuxostat.7 He remarked, “Usually I wait for a month [after an allopurinol reaction]—a little longer in the case of drug rash with eosinophilia and systemic symptoms (DRESS)—and start febuxostat at a dose of 40 mg daily, increasing it slowly. In my experience, you can get the patient back to target [SU].”
In the rare cases of patients with skin and/or liver intolerance to both allopurinol and febuxostat, Professor Bardin recommended the use of uricosurics.
ULT Dosing & Chronic Kidney Disease
Many regulatory agencies across the world limit the maximum dosage of allopurinol according to creatinine clearance due to the increased risk of fatal skin reactions. Unfortunately, such restrictions translate into the failure to titrate allopurinol to a dose that reaches SU targets.8