Gout & Metabolic Syndrome Save

Good day and welcome. My name is John Fitzgerald. I'm from the UCLA and VA. And thank you for tuning in to hear about gout. As a gout researcher, one of my most detested sayings is "it's just gout." We know so much about gout and we have both effective anti-inflammatory and urate lowering treatments that many providers, not just rheumatologists, feel that gout is easily managed. Gout has even been referred to as the curable disease. But unfortunately, it's also one of the most poorly managed diseases. The progression to tophaceous and erosive gout is largely preventable. Yet, we still see patients with advanced disease due to preventable treatment gaps.

So, briefly on why the curable disease is so rarely cured, adherence is frequently cited and it is important, but it is also important not to be patient blaming in our management. The most common reason for stopping urate lowering therapy is that the patient has had a flare and feels like the medication is either not working or making their gout worse, which in a sense it is.

For years, I used to try and fight back against the "it's just gout" mentality. But to patients and their providers, it often is just gout as diabetes, hypertension, hyperlipidemia, cardiovascular disease compete for attention. However, rather than competing with these diseases, gout should be evaluated as part of the metabolic syndrome. Newer pluripotent medications that treat both gout and the other cardiometabolic conditions make the bundling of gout into the metabolic syndrome more practical.

Based on separate studies, both using NHANES 2011 to 2018 data, the prevalence of gout and the metabolic syndrome has been rising. And while gout is not formally part of the metabolic syndrome definition, gout and metabolic steatosis of the liver are both considered consequences of the insulin resistance syndrome. Mendelian studies have demonstrated that insulin resistance leads to hyperuricemia and gout and not in the other direction.

Separate authors using separate databases came to the same conclusion. Looking at SNPs — genetic SNPs associated with insulin and type 2 diabetes — were associated with urate outcomes but not in the reverse. These other authors showed the same findings.

In addition to cardiovascular disease being part of the metabolic syndrome, the inflammatory pathway associated with gout is an important independent risk factor. As a reminder, several studies demonstrated that treatment with anti-inflammatories lowered cardiovascular risk. These included methotrexate, canakinumab, and importantly colchicine. Treatment with colchicine lowered cardiovascular risk, leading to an FDA indication for the prevention of cardiovascular disease. And it should be noted that during these trials, while there were higher reported rates of GI side effects, there were no significant myopathies despite 95% of patients on concurrent statin therapy. However, despite the indication, uptake of colchicine for cardiovascular disease has been slow. But the indication has lowered my threshold for preferencing colchicine in managing our patients with gout.

An important 2022 study found that cardiovascular risk increased in the first 60 days after a gout flare before returning to baseline levels after 180 days.

As mentioned, gout and metabolic steatosis liver disease are both manifestations of the insulin resistance syndrome. The association between fructose intake and hyperuricemia likely further contributes to fatty liver disease.

Switching now to therapies. The SGLT2i medications have shown benefit in many cardiometabolic conditions and there are several direct benefits for patients with hyperuricemia and gout.

To highlight a few key therapeutic points in managing gout: when starting anti-inflammatory options with your patients, these can include daily prophylaxis, pill-in-pocket strategies, or start low and go slow urate lowering titrations. This is the original febuxostat slow titration schedule that has been updated with an allopurinol titration schedule. Interestingly, in this study, even after 6 months of low-dose colchicine, a small spike in gout flares was noted at 6 months.

Finally, allopurinol titration is impacted by starting dose and dose needed to get serum urate less than 6 milligrams per deciliter. This easy allopurinol dosing schedule was developed by New Zealand researchers and they developed this target dose chart. You'll note that body weight has a significant impact on final target dose, as does starting urate levels. Renal function surprisingly has little impact.

So the recommendations for dose to target would be: start low — 100 milligrams, lower in patients with renal disease — and titrate up to the target, then check a urate, and then you could titrate up or down. Doses should be lowered for patients with renal disease. An even easier allopurinol dosing schedule is
to consider you need about 100 milligrams for every 1 milligram per deciliter of change needed. The starting dose of allopurinol is important also. We start low to limit the risk of allopurinol hypersensitivity syndrome and this is available in the data. And finally, we have gout patient education programs available online at the UCLA and the Greater Los Angeles VA rheumatology websites. Thanks again for tuning in and to hear more about gout, check out RheumNow.