Gout Management—Need for Greater Attentiveness to Broader Treatment

Treating patients at risk for or diagnosed with type 2 diabetes should be closely monitored for gout-related disease, with treat-to-target therapy initiated early with ongoing monitoring, informed by new consensus statement, and clinical guidelines pending from the American College of Rheumatology.

with John FitzGerald, MD, Tuhina Neogi, MD, PhD, and David Bursill, MD

With gout and diabetes often coexisting, the onset of gout offers a strong and independent risk factor for development of type 2 diabetes (T2D); and, women who develop gout are at even higher risk of T2D than men with this arthritic condition.1

Patients with these coexisting conditions also share an unhealthy habit. "Patients with diabetes are known to have adherence issues with taking medications, and gout patients are among the poorest pill-takers," says John FitzGerald, professor of medicine at the David Geffen School of Medicine at the University of California at Los Angeles.

In addressing the prospect of medication adherence when new recommendations suggest stepped up care,''it is my belief that better patient education is needed," Dr. FitzGerald tells EndocrineWeb. "Patients must be informed to understand that [urate-lowering] medication may first cause an increased risk of flares before the benefits can be appreciated," but the long-term benefits will be welcomed as well as outweight the pain and disfigurement that is more likely should they avoid treatment.

Properly defining gout is a first-step to better treatment for many missed patients.

Further complicating both research and clinical care, there is a lack of standardization in the terms used to define and diagnose the range of diseases high uric acid gout. Now, endocrinologists and primary care the practitioners who care for these patients will have clearer guidance on the more efficacious approach to treatment given two recent developments:

  • A new consensus statement has been issued to provide consistency in labels and definitions for the disease states described as gout.2
  • Proposed treatment guidelines for gout were unveiled at the American College of Rheumatology (ACR) annual meeting,3 and submitted for publication in the next few months.

Dr. FitzGerald is co-principal investigator of the 2020 ACR Gout Guidelines (as well as the original guidelines issued in 2012), and a member of the Gout, Hyperuricemia and Crystal-Associated Disease Network.

G-CAN Consensus Statement—What Does Use of the Term “Gout” Really Mean?!

"Gout is part of the metabolic syndrome," Dr. FitzGerald says, and not one uncomplicated disease. "The key to efficiently managing this inflammatory pain condition is to manage hyperuricemia with urate-lowering medications. Since we cannot change the patient’s physiology, we need to address the crystal deposits that are the hallmark of gout," Dr. FitzGerald; as such, lowering the uric acid level is crucial.

Issuance of this much needed consensus statement culminates from an international effort by G-CAN to offer definitions and labels for an array of disease states represented as gout.

In the first phase of statement development, the writing group created labels and definitions to encompass all related disease elements. They identified 13 unique gout-related states and 63 unique identifiers in all. The group then prepared a consensus agreement to reflect eight disease state categories with definitions; 2 these include:

Asymptomatic Disease States

  • hyperuricemia
  • monosodium urate crystal deposition
  • hyperuricemia with monosodium urate crystal deposition

Symptomatic Disease States

  • gout (see classification below)
  • tophaceous gout
  • erosive gout
  • first gout flare
  • recurrent gout flares

The writing group also reached consensus as to the application of “gout” in patient management—it should be restricted to current or previously clinically evident disease caused by monosodium urate crystal deposition, including gout flare, chronic gouty arthritis, or subcutaneous tophus.2

These terms were selected to reflect clinical accuracy as well as to communicate concepts important for gout etiology, pathogenesis, and patient presentation, Dr. FitzGerald told EndocrineWeb. The new categories are designed to be used not only to gain consistency in the scientific literature but also to meet the goal of better attentiveness to diagnosis and more comprehensive treatment in clinical settings.

Highlighting Key Changes to Gout Management in Type 2 Diabetes, CKD

The proposed ACR gout guidelines indicate first-line therapy should be initiation of a low dose urate-lowering therapy, titrating up to achieve and maintain a serum urate level of less than 6 mg/dL to deliver an optimal patient response.3 The strategy, according to the authors, is to aim to mitigate the common treatment-related adverse side effects such as hypersensitivity, and to reduce the risk of flares often experienced when urate-lowering treatment is initiated.

Other notable changes in the proposed guidelines is to foster use of allopurinol as the preferred urate-lower treatment, particularly in patients with chronic kidney disease. "We come out much more strongly that allopurinol is the most desirable first-line agent to most effectively reduce urate levels," Dr. FitzGerald tells EndocrineWeb.

This reflects an update from the earlier guideline in which allopurinol and febuxostat (Uloric) had equal footing as a choice of treatment, he says, but not so in our updated guidelines. Rather, febuxostat is recommended for use as second-line urate-lowering therapy, even in those with cardiovascular disease.3 The change reflects consideration toward cost in making decisions for updating past recommendations, he says.

There is also a strong recommendation to prescribe prophylaxis anti-inflammatory (eg, colchicine, non-steroidal anti-inflammatories, prednisone/prednisolone) when planning to initiate urate-lowering therapy for at least three-to-six months, but not less than three months, with ongoing monitoring.3

Also, the guidelines will include indications for expanding treatment to have you consider starting urate-lowering therapy in patients with infrequent gout flares or after a first flare or in cases of moderate to severe chronic kidney disease (CKD)  (ie, stage 3 or higher), marked hyperuricemia, with serum urate over 9 mg/dl, or kidney stones.3

To address racial/ethnic variability in response to therapy, a recommendation has been expanded to more fully capture patients in whom there is a higher risk of allopurinol hypersensitivity. The allele HLAB-5801 has been linked to side effects in certain ethnic groups who take drugs such as allopurinol.4

This may be accomplished by ordering genotype blood testing for HLA-B5801 before initiating urate-lowering therapy. "[DNA testing] is recommended as before for patients of Asian descent, but is now similarly suggested for African-Americans," Dr. FitzGerald says. “Both population subgroups are known to have a higher likelihood of allergic reactions.”

Lastly, the guidelines writing group recognizes the value in permitting nonphysician practitioners to manage a urate-lowering dosing protocol to increase the ease and optimize implementation of the the treat-to-target strategy.

The proposed ACR gout guidelines will differ from those issued by the American College of Physicians (ACP) on at least one important point: The ACP guideline stops short of endorsing a treat-to-target approach, finding the evidence insufficient to conclude that the benefits of escalated dosing with urate-lowering medication and repeated monitoring outweighed possible harms.5

"Our hope is that with the improved evidence on the value of the treat to target approach and the value of serum urate <6mg/dL since the last 2012 guideline effort, that we are providing a more compelling reason for this management strategy," Dr. FitzGerald says. "Eventually, we hope treatment guidance will become more uniform."

Enhancing Treatment of Patients with Diabetes and Gout-Related Disease

"Gout management remains largely suboptimal due to so many providers responding just to the flares without also treating the underlying hyperuricemia that is the cause of gout, or starting a patient on a urate-lowering therapy medication without titrating the dose or monitoring the serum urate response to guide dose escalation," says Tuhina Neogi, MD, PhD, professor of medicine and of epidemiology at Boston University School of Medicine and Public Health in Massachusetts, in a statement issued by the ACR.3  She is the co-principal investigator of the guidelines.

She voiced optimism that the guidelines will help healthcare providers treat the range of gout-related conditions as a chronic disease and not just an acute pain problem.  

"Physicians should understand that urate is the pathophysiologic culprit behind the development of gout," Dr Neogi tells EndocrineWeb. “Without monosodium urate crystals, there would be no clinical manifestations of gout (gout flares and tophi) "

The central foundation of gout management, she says, is in reducing serum urate to under 6 mg/dL.1,2  In order to get patients to a symptom-free state, she says, clinicians must commit to following the recommendation to prescribe allopurinol—as first-line therapy—starting at a low dose and escalating the dosage over weeks or months until the target urate level is achieved.

"In the majority of patients, this means that a dose of more than 300 mg/dL will eventually be needed,” she says, “It may be necessary to continue to increase the dose above 300 mg/dL, which can be done safely in any patient so long as close monitoring continues, including in patients with renal impairment as there is no evidence that allopurinol is nephrotoxic."

The key clinical strategy, she says, aims to start low to reduce the risk of causing flares in the early phase of treatment, and to reduce the risk that the patient will develop allopurinol hypersensitivity syndrome.

As for the G-CAN consensus statement: "I think the G-CAN consensus statement on the disease elements of gout, and the updated guidelines on the disease elements of gout, provide important guidance for clinicians on how to communicate fundamental concepts of gout to their patients,” co-author David Bursill, MD, professor of medicine at the University of Adelaide in South Australia, tells EndocrineWeb. ”While it does not directly impact the existing deficiencies in the management of gout, providing consistent, accurate, and informative terminology is fundamental in clinical practice and in the scientific literature offers an important first step.”

Providing Clearer Treatment Mandate to Achieve Better Patient Outcomes

"In particular, attention has been given to developing concise terms and definitions that attempt to avoid perpetuating misconceptions about gout which can, in turn, act as treatment barriers," said Dr. Bursill. Consider the aftermath of inappropriate management of gout, he says. If patients who have the condition are not placed on urate-lowering therapy or are receiving an inadequate dose, the result is that our patients end up in rheumatologists’ offices to deal with damaged or destroy joints that will likely leave patients with functional limitations and chronic inflammatory disease.

"Patients are too often quite dismayed when they come to realize that the long-term manifestations of gout that could have been prevented by appropriate therapy if given when they first presented for treatment, but weren’t," Dr. Bursill says.

Dr. Neogi acknowledges that getting guidelines to be adopted takes time. "Professional societies that develop guidelines are now placing greater effort on implementation, including dissemination as well as ongoing education and outreach efforts," she tells EndocrineWeb, as there is recognition of the need for a more sustained, ongoing commitment to see that these guidelines are adopted by the vast majority of clinicians.

Neither Dr. FitzGerald, Dr. Neog, nori Dr. Bursill have any financial conflicts with regard to this content.

Continue Reading:
Anti-Inflammatory Therapy for CVD, Diabetes Risk Reduction
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