A New View on Gout Flares and Treatments
New research is revealing further insights into the causes of gout and gout flares as well as the best gout treatments.
There’s no doubt, gout is a unique type of arthritis. Traditionally viewed as a form of inflammatory arthritis, gout treatment has primarily focused on controlling uric acid levels that cause crystals to form around joints, causing profound pain in patients. But is there more to gout than has traditionally met researchers’ eyes? In a research session presented at the American College of Rheumatology’s annual meeting, ACR Convergence 2022, researchers proposed a new perspective on gout in the sessions title, “Gout Is an Autoinflammatory Metabolic Disease.”
As such, the question was proposed — “Is gout an autoinflammatory syndrome?” — by the session’s moderator, Michael Pillinger, MD, Professor of Medicine and Biochemistry and Molecular Pharmacology at New York University Grossman School of Medicine. “In a strict sense,” said Dr. Pillinger, “the answer is clearly, yes. Gout is an inflammatory syndrome, and it is not driven — to anyone’s knowledge — by any autoimmune process. Like many of the autoinflammatory syndromes, gout is episodic, and while you make think you know why gout is episodic — relating to a release or appearance of uric crystals — it’s likely that the reason why gouty flares come on are more complicated than that.
“Gout is a genetic disease. The majority of genes that have been identified are related to the regulation of urate levels, which of course is also driven by diet, environment, renal function, etc.” explained Dr. Pillinger. “But we’re beginning to see the potential role of genes that regulate not just urate, but also inflammation, confirming gout as a genetic autoinflammatory disease. In fact, one of the ongoing mysteries of the condition is why in a world full of patients with hyperuricemia [elevated uric acid level in the blood] only some of them get gout. The possibility that progression from gout to gout flares may be driven by intrinsic genetic or epigenetic predilections to inflammation is intriguing and an idea we’re only now beginning to wrap our questions around.”
The session primarily focused on the autoinflammatory nature of gout and highlighted the inflammatory cytokine interlukin-1’s (IL-1) role in gout. “Gout is a disease — like so many of the autoinflammatory syndromes — in which IL-1 plays a central role,” said Dr. Pillinger.
“IL-1 is so potent it is perhaps the most potent cytokine that we know,” said the session’s first of two presenters, Charles Dinarello, MD. Dr. Dinarello, an expert on inflammatory cytokines, specifically IL-1, is a member of the National Academy of Sciences, distinguished professor of medicine-infectious disease at the University of Colorado at Denver and professor of experimental medicine at Radboud University Medical Center in the Netherlands.
Dr. Dinarello provided a biologist’s view of IL-1 inflammation in gout. Essentially, IL-1 “evokes a very strong inflammatory process,” explained Dr. Dinarello. A strong, proinflammatory signal is sent to the nucleus, which contains genes associated with disease, such as cytokines and cytokine receptors. The result of this inflammatory processing is clinical and includes systemic inflammation, local inflammation (gout flares), decreased pain threshold, tissue damage and more.
Perhaps the most profound implications of such refined understanding of gout, may be the impact it has on the future treatment and management of the disease.
Several IL-1 blockers, including injectables anakinra, canakinumab and rilonacept, as well as a recently added oral option, NLRP3 inflammasome, are not specifically FDA-approved for gout, but they are proven treatments for blocking IL-1, explained Dr. Dinarello.
“Clinical data from IL-1-blocking injectable biologics in fact have validated the role of IL-1-beta in the pathogenesis of gout flares. This has been the case with anakinra, with canakinumab and rilonacept. Approved drugs that have validated the role of IL-1 beta in the pathogenesis of acute gout — that’s no longer in question,” added Dr. Dinarello.
In fact, oral NLRP3 IL-1 beta inflammasome inhibitors can now be used to treat gout flares in patients where traditional drugs are contraindicated or poorly tolerated.
The second speaker, Naomi Schlesinger, MD, an expert on the clinical manifestations and the treatment of gout, focused on the evidence of treatment options. Dr. Schlesinger is a professor of medicine and incoming chief, Division of Rheumatology in the Spencer Fox Eccles School of Medicine at the University of Utah in Salt Lake City.
“Urate-lowering therapy together with anti-inflammatory therapy leads to optimal outcomes,” said Dr. Schlesinger. “One has to remember, when you treat gout it’s not a sprint, but rather a marathon. You don’t just treat acute flares; you have to treat gout chronically. And while doing so, remember to assess the patient’s polypharmacy and comorbidities.”
In one study, co-authored and presented by Dr. Schlesinger, showed ice — in addition to the traditional gout treatments — was effective in treating acute gout. Any nonsteroidal anti-inflammatory drug (NSAID) may also be used; however, studies have not shown which NSAID works best. When comparing colchicine to NASIDs (specifically naproxen), no difference in pain intensity was noticed. When comparing steroids to NSAIDs, both were equally effective. And when comparing steroids, there was no statistically significant difference in pain intensity.
Other evidence presented by Dr. Schlesinger also included the anti-inflammatory effect of low- and moderate-intensity exercise in mice. A physical activity questionnaire of gout patients also showed patients who exercised had fewer flares per year. She also studied the effects of cherry juice concentrate consumed by gout patients, which reduced flares as well.
What’s key, said Dr. Schlesinger, is “we need to treat gout as an autoinflammatory disease and not purely a metabolic disease.”
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