Gout & Its Comorbidities

Insight into Maladies of Major Importance, Racial Disparities & More

SAN DIEGO—During ACR Convergence 2023, a panel discussion, titled Optimizing Clinical Care in Gout, outlined the current best practices for treating gout flares, preventing future flares, lowering urate levels and managing comorbidities. Experts also highlighted persistent, documented racial inequities in gout treatment, disease burden and outcomes of treatment.

Gout & Its Comorbidities

Dr. Dalbeth

Nicola Dalbeth, MD, professor and head of the Department of Medicine at the University of Auckland, New Zealand, said the treatment paradigm for gout is well known to rheumatologists. That paradigm includes the use of anti-inflammatory agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, colchicine, interleukin 1 inhibitors and urate-lowering therapy, such as allopurinol.

The comorbidities accompanying gout, particularly cardiovascular disease (CVD), chronic kidney disease (CKD) and diabetes, also have important consequences for patients—as evidenced by a persistent premature mortality gap. Rheumatologists became even more aware of the comorbidities of gout during the COVID-19 era, Dr. Dalbeth said. People with gout have increased risk of poor outcomes in the setting of COVID-19, much of it related to coexisting cardiometabolic comorbidities.^1,2

One unanswered question highlighted by Dr. Dalbeth: Is gout-related hyperuricemia driving poor cardiovascular outcomes (e.g., acute myocardial infarction [MI] and stroke), as was once believed? Mendelian randomized studies and clinical trials, including the All-HEART study in a general population, have indicated that serum urate reduction has no major causal effect on cardiovascular events.³

“Are we actually looking in the wrong place for CVD risk?” she asked. Perhaps gout flare itself and its acute inflammation are contributing to increased cardiovascular risk—with the odds of an acute MI or stroke substantially higher in the first 120 days following a gout flare.

Anti-inflammatory agents used to manage gout also benefit cardiovascular risk in the general population. Colchicine is effective at preventing and treating gout flares when starting urate-lowering therapy. Cardiovascular benefits of low-dose colchicine are also seen in a non-gout population in patients post-MI and those with stable CVD.⁴ Canakinumab, an anti-inflammatory monoclonal antibody used to treat rheumatic conditions, is also effective for gout flares.

Treatment Strategies

Dr. Dalbeth emphasized the need for a more systematic program for the intensive management and risk reduction of CVD and CKD in patients with gout. That approach includes assessing for vascular risk factors and screening for CKD.

Treatments for these comorbidities that also potentially benefit gout management include:

• The DASH (Dietary Approaches to Stop Hypertension) diet;
• Losartan, an anti-hypertensive drug;
• Atorvastatin, a cholesterol-lowering drug;
• Calcium channel blockers; and
• SGLT-2 (sodium-glucose cotransporter 2) inhibitors, increasingly.

Managing patients with SGLT-2 inhibitors, which are approved for use along with diet and exercise to lower blood sugar in adults with type 2 diabetes, holds exciting potential for people with gout and its comorbidities, Dr. Dalbeth said. Effective gout management can enable patients to take control of other areas of their health while reducing exposure to NSAIDs and corticosteroids.

Dr. Schlesinger

“The future will tell us what role the SGLT-2 inhibitors will play in gout treatments for patients with those comorbidities,” said Naomi Schlesinger, MD, the session’s second speaker  and professor and chief of the Division of Rheumatology at the University of Utah School of Medicine, Salt Lake City.

Most patients with gout have multiple comorbidities, and this fact is even more common in women than in men, regardless of age. For optimal treatment outcomes, one needs to control inflammation—both during acute flares and in chronic gout—along with reducing the uric acid pool and addressing polypharmacy in patients, Dr. Schlesinger said.⁵

The Kidneys

What does the physician do for patients with gout and kidney disease when NSAIDs are contraindicated because they can exacerbate or cause acute renal injury or failure? Recommendations for the use of colchicine at this point are largely empirical, not based on randomized controlled trials, Dr. Schlesinger said. Physicians need to be aware that in patients with severe CKD, the half-life of colchicine is prolonged, and the risk of toxicity is greater than in those without CKD.

For patients on dialysis, the total recommended dose of colchicine is 0.3 mg twice weekly, with close monitoring. Another option: If the patient can’t tolerate colchicine, a short course of glucocorticoids can be prescribed.

Gout is also more common and severe in patients who have had a kidney transplant, and kidney stones are common in these patients. For patients experiencing their first gout flare with kidney stones, initiate urate-lowering therapy and address predisposing factors, such as smoking and obesity, Dr. Schlesinger said.

Racial Disparities

Dr. Singh

Jasvinder Singh, MD, MPH, of the University of Alabama, Birmingham, reviewed the literature on racial disparities and health inequities for gout incidence, treatment and outcomes. Black men have a higher rate of gout than white men, and Black women have a higher rate of gout than white women, according to ARIC (the Atherosclerosis Risk in Communities Study), a U.S. population-based cohort study of middle-aged adults enrolled between 1987 and 1989 with ongoing annual follow up through 2012.⁶ 

African Americans with gout report higher emergency department and hospitalization rates and higher burden of disease than white Americans with gout. They also have worse generic mental and emotional health-related quality of life, more functional limitations and lower rates of urate-lowering treatment adherence. The quality of care they receive as measured by whether they are prescribed allopurinol is also worse. 

Dr. Singh described a randomized controlled trial of a comprehensive intervention aimed at addressing these disparities conducted in 306 African American veterans at four sites in the Veterans Health Administration from 2016 to 2020.⁷ The intervention included culturally appropriate storytelling, information on improving adherence to gout therapy contained on a printed handout and a veteran-narrated PowerPoint, and a video. The study produced no documented improvement, even when data were broken down into a variety of factors, he said. Medical adherence went up briefly, and then down.

“We need to better understand what [factors] are modifiable and non-modifiable and then target and develop effective interventions,” Dr. Singh said.

What’s needed is to engage minorities in prospective gout studies. Also, design and test interventions in randomized controlled trials and real-world pragmatic studies, and then take the evidence back to those communities to engage them.

Larry Beresford is a medical journalist in Oakland, Calif.

References

1. Fisher MC, Rai SK, Lu N, et al. The unclosing premature mortality gap in gout: A general population-based study. Ann Rheum Dis. 2017 Jul;76(7):1289–1294.
2. Wang Q, Liu J, Shao R, et al. Risk and clinical outcomes of COVID-19 in patients with rheumatic diseases compared with the general population: A systematic review and meta-analysis. Rheumatol Int. 2021 May;41(5):851–861.
3. Mackenzie IS, Hawkey CJ, Ford I, et al. Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): A multicentre, prospective, randomised, open-label, blinded-endpoint trial. Lancet. 2022 Oct 8;400(10359):1195–1205.
4. Tardif JC, Kouz S, Waters DD, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019 Dec 26;381(26):2497–2505.
5. Zhu Y, Pandya BJ, Choi HK. Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007–2008. Am J Med. 2012 Jul;125(7):679–687.e1.
6. Maynard JW, McAdams DeMarco MA, et al. Racial differences in gout incidence in a population-based cohort: Atherosclerosis risk in communities study. Am J Epidemiol. 2014 Mar 1;179(5):576–583.
7. Singh JA, Joseph A, Baker J, et al. Storytelling to improve disease outcomes in gout (STRIDE GO): A multicenter, randomized controlled trial in African American veterans with gout. BMC Med. 2021 Nov 9; 19(1):265.