“In 60 years, we haven’t fully worked that out,” says Dr. Mikuls. “It’s not a debate about whether it’s the case; it’s a debate about the magnitude, about the relationship of a serum urate level on therapeutics.”
Whether or not to use a treat-to-target strategy for serum urate and the ideal target level have been debated vigorously in recent years. The American College of Physicians’ 2017 guideline did not recommend treating to a specific serum urate target using a serum urate-lowering therapy, such as allopurinol.11 In contrast, the ACR 2020 gout guideline recommends clinicians treat to a target serum urate of 6 mg/dL to reduce the risk of flares, based on some newer evidence.9
“To me,” adds Dr. Mikuls, “that is probably the most important concept in the 2020 ACR gout guideline.”
Another argument against the idea of uric acid’s role in gout flares 60 years ago was the marked hyperuricemia seen in some people without gout. “While we have some more thoughts on that now, the same question was raised in this JAMA article from 60 years ago,” says Dr. Mikuls. “We still don’t really have an answer.”
Others at the time argued that elevated uric acid could not be a potential trigger of gouty attacks, as lowering the serum uric acid by uricosuric drugs did not relieve acute attacks of gout. On the contrary, it was known the administration of these drugs might exacerbate an acute attack.
“By the time gout patients have their first flare, they have built up huge urate stores in their body, and it takes a long time to deplete those,” Dr. Mikuls explains. “That’s one thing we really understand that we probably didn’t 60 years ago, that you have to slowly empty that uric acid load, and that takes—with effective conventional therapy—probably a couple of years for most patients.”
Whether or not to use a treat-to-target strategy for serum urate & the ideal target level have been debated vigorously in recent years.
Similarly, it was known at the time that colchicine, a drug with no effect on uric acid levels, could effectively treat acute gout attacks. This was taken by some as partial evidence that uric acid did not play an important role.
The ACR gout guideline recommends using a prophylactic anti-inflammatory medication, such as colchicine, when first starting patients on urate-lowering medicines, such as allopurinol, to help prevent rebound flares.9 Dr. Mikuls also points out that many patients—and even some medical professionals—get confused about the different roles in the treatment of gout for anti-inflammatory medications vs. urate-lowering therapies, which can negatively influence medication adherence and flare prevention.
