Gout Research from ACR Convergence 2024 at a Glance

‘My picks for the top research in gout presented at ACR Convergence 2024’

ACR CONVERGENCE 2024—Approximately 70 abstracts about gout from around the globe were accepted for presentation at ACR Convergence 2024. My picks reflect my passion and interests in improving gout management.

1. Abstract 0178

Are Participants in Gout Clinical Trials Representative of People with Gout in the General Population? Liu et al.¹

Industry-led clinical trials play an important role in drug development and regulatory approvals. As clinicians, we rely on clinical trial data to guide our treatment decisions and to develop treatment recommendations and consensus guidelines. However, clinical trial inclusion and exclusion criteria, which determine the trial population, may not reflect the real-world disease population. This may be especially true in gout clinical trials because people with gout have many co-morbidities, including chronic kidney disease, which is frequently an exclusion criterion for clinical trials.

In the study presented by Liu et al., demographics and comorbidity data from 12 phase 3 clinical trials of gout medications approved by the FDA from 2009 to 2023 were compared with published data from participants with gout in the 2007–08 and 2015–16 U.S. National Health and Nutrition Examination Survey (NHANES). Not surprisingly, there was under-representation of women, older individuals, non-white ethnicities and those with comorbid health conditions commonly experienced by people with gout including hypertension, prior myocardial infarction, nephrolithiasis and diabetes.

The under-representation of non-white ethnicities is troubling. Efforts have been made by funders such as the National Institutes of Health (NIH) to address this under-representation. The Revitalisation Act of 1993 requires the Director of the NIH to ensure that members of “minority” groups are included in clinical trials and that the trial is designed and carried out in a manner sufficient to provide for a valid analysis of whether the variables being studied in the trial affect members of minority groups differently than other trial participants.

Bias, conscious or unconscious, among healthcare professionals, researchers and the healthcare system likely also has an impact on recruitment of non-white ethnic groups into clinical trials.

The challenge for us as a community is to work in partnership with non-white populations to develop culturally appropriate, acceptable and effective systems to overcome disparities and enable a pathway to be involved in clinical trials and help achieve health equity.

In this regard, it was also pleasing to see a Meet the Panel session at ACR Convergence 2024 discuss this topic.

2. Abstract 2557

The Relation of Colchicine to Knee/Hip Replacement Among People with Gout. Wang et al.²

Current guidelines recommend anti-inflammatory prophylaxis for people with gout starting urate-lowering therapy for three to six months.^3,4 An exploratory post hoc analysis of the LoDoCo2 trial reported a lower incidence of total hip or knee joint replacement in people with cardiovascular disease who received colchicine than among those who received placebo.⁵ On the basis of this, Wang et al. undertook a propensity score-matched, population-based cohort study of people with gout to examine the effect of colchicine on joint replacement using data from the U.K. IMRD General Practice database.

The study identified ~32,000 incident colchicine users with gout and compared the risk of hip/knee replacement with ~32,000 propensity score-matched people with gout not starting colchicine. The authors reported a modest lower risk of hip/knee replacement in those who initiated colchicine, which remained similar after adjustment (HRadj 0.87 [95%CI 0.80 to 0.95]).

These data are of interest given previous negative trials of colchicine for treatment of osteoarthritis and suggest there may be some benefit for the use of colchicine in people with gout beyond prevention and treatment of gout flares.

3. Abstract 1071

Rapid Access Microscopy & Real-Time Case Discussion via a Secure Messaging App. Anouchka Lewis⁶

Acute crystal arthritidies including gout and calcium pyrophosphate deposition disease (CPPD) typically present as a painful, red, hot, swollen joint. Septic arthritis, which is considered a medical emergency given the risk of joint destruction, can also present as a painful, red, hot, swollen joint.

Synovial fluid analysis is the gold standard for diagnosis of both crystal arthritidies and septic arthritis. Visualization of monosodium urate or calcium pyrophosphate crystals in synovial fluid is operator dependent. A false-negative result for crystals in synovial fluid may result in a diagnosis of culture-negative septic arthritis, leading to patients being admitted to hospital, undergoing joint washout and receiving antibiotics unnecessarily.

In this abstract, Lewis et al. noted a high rate of culture-negative septic arthritis in their institution, suggesting a high rate of misdiagnosis. A hot-joint pathway providing a structured assessment for patients presenting with an acutely swollen joint included indications for joint aspiration, rapid access to rheumatology-led polarized light microscopy and a secure messaging app for coordination between ED physicians, rheumatologists and orthopedic surgeons.

With the introduction of the pathway cases of culture-positive septic arthritis increased, culture-negative arthritis cases were reduced and the diagnosis of crystal arthritis went up. Importantly, there was an increase in the number of people able to be discharged without the need for hospital admission and the average length of stay reduced by three days.

This study highlights an ongoing challenge in the diagnosis of crystal arthritis and the importance for both the patient and the healthcare system of an accurate diagnosis. The close collaboration via the messaging app allowed rapid, easy multidisciplinary input into these diagnostically challenging cases.

4. Abstract 0273

Barriers & Facilitators for Outpatient Follow-Up After an Acute Gout Flare. Lopez et al.⁷

It is well recognized that many people with gout present to the emergency department for flare management. However, successful long-term management of gout requires engagement between the patient and their usual healthcare provider to ensure urate-lowering therapy is instituted and target urate is achieved. Lopez et al examined the barriers and facilitators to outpatient follow-up for gout management after an ED visit for a gout flare. Importantly, 7/12 individuals interviewed were Black or African American.

Although the results may not be surprising to many of us, they highlight factors clinicians need to consider. Lack of reliable transportation and the impact of gout on an individual’s physical function to go to clinic were barriers for 75% and 67% respectively. The most important facilitator was the emergency department clinician providing information on gout, including emphasising the need to follow up in the outpatient setting (92%).

The interaction with the emergency department physician at the time of a gout flare is clearly important not only for managing the flare but also for referral to a primary healthcare provider or rheumatologist for ongoing management and education about the importance of long term treatment and follow-up.

Working with our colleagues in the emergency department to ensure that clear messaging is given to patients about the need for urate-lowering therapy and the importance of follow-up is just one piece of the puzzle. Overcoming system and financial barriers is more complex. Gout management guidelines are plentiful, but we need to consider in our own institutions’ settings and the unique populations that we serve how best to implement them.

5. Abstract 1100

Coronary DECT for the Detection of Monosodium Urate Crystal Deposition. Yokose et al.⁸

Advanced imaging techniques, such as ultrasound and dual-energy CT (DECT), have enabled visualization of monosodium urate (MSU) deposits in joints. DECT has also been used to visualise MSU deposits in other organs, such as the kidneys. In this study, Yokose et al. examined whether people with gout have a higher prevalence of MSU crystals in their coronary arteries than those without gout, using both the default and optimized post-processing DECT settings.

Data from 71 people with gout and 126 without gout revealed that those with gout had 3.1-fold higher odds (95% CI, 1.5 to 6.1) of having MSU-coded vascular lesions, which attenuated after age/sex-adjustment using the default settings. However, with the optimized settings, the OR was 3.9 (95% CI, 1.8 to 9.4), and although this attenuated, it remained significantly different after age/sex-adjustment. 

Given the higher risk of cardiovascular disease for people with gout, the association of gout with cardiovascular risk factors and the inflammatory nature of MSU crystals, these findings raise a number of questions. The contribution of MSU crystals in coronary vasculature to cardiovascular events and whether urate-lowering therapy alters the observed MSU deposition and any subsequent effects on cardiovascular events remain to be determined.

6. Abstract 2560

Continuous Reduction in Ultrasound Detected Crystal Depositions over 5 Years Follow-up. Hammer et al.⁹

Tophi are collections of MSU crystals together with chronic inflammatory tissue. Tophi can impair joint movement, cause pain, ulceration and result in joint damage. Tophus regression occurs around the concentration of 6 mg/dL (0.36 mmol/L) with more rapid reduction in tophus size occurring with lower serum urate concentrations. The study by Hammer et al examined the change in tophi using ultrasound over two to five years on urate-lowering therapy in people enrolled in the NOR-gout study.

During the first year of the NOR-gout study, urate-lowering therapy was adjusted to achieve target serum urate of <6 mg/dL (0.36 mmol/L) or 5 mg/dL (0.30 mmol/L) in those with tophi. After the first year, participants were followed by their primary care physician to maintain target urate with additional study visits at year 2 and 5. Ultrasound was undertaken at baseline, months 12, 24, and 60, with semi-quantitative scoring of MSU crystal deposits. Two hundred nine participants were included, and mean serum urate remained below target of <6 mg/dL at months 3, 6, 12, 24 and 60. The ultrasound revealed a corresponding reduction in the tophi and aggregates as well as the sum ultrasound score, which continued out to five years.

These data will be useful in talking to people with gout and, especially, those with tophi about the time it takes for tophi to dissolve and the need for adherence with long-term urate-lowering therapy to maintain serum urate below target to achieve crystal dissolution. Although benefits are seen in the first year, persistence with therapy will see even more reduction in tophus, even that which may not be visible to the naked eye.

Lisa Stamp, MBChB, PhD, is a rheumatologist and professor of medicine at the University of Otago, Christchurch, New Zealand and is the Clinical Lead Research for Health New Zealand. She has extensively researched the pathophysiology and management of gout.

References

1. Liu J, Gamble G, Dalbeth N. Are participants in gout clinical trials representative of people with gout in the general population? [abstract]. Arthritis Rheumatol. 2024;76(suppl 9).
2. Wang Z, Tilley S, Peloquin C, Petrow E, Clancy M, Neogi T. The relation of colchicine to knee/hip replacement among people with gout in a population-based cohort study [abstract]. 2024;76(suppl 9).
3. FitzGerald J, Dalbeth N, Mikuls T, , et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res. 2020;72(6):744–760.
4. Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017;76(1):29–42.
5. Heijman MWJ, Fiolet ATL, Mosterd A, et al. Association of low-dose colchicine with incidence of knee and hip replacements: Exploratory analyses from a randomized, controlled, double-blind trial. Ann Intern Med. 2023;176(6):737–742.
6. Lewis A, Stack J, Corish O, et al. Rapid access microscopy and real time case discussion via a secure messaging app improves diagnostic accuracy and management of acute hot swollen joints [abstract]. 2024;76(suppl 9).
7. Lopez E, Jackson L, Saag K, Danila M. Barriers and facilitators for outpatient follow-up after an acute gout flare: A qualitative research study [abstract]. Arthritis Rheumatol. 2024;76(suppl 9).
8. Yokose C, Pascart T, Randhawa M, et al. Coronary dual-energy computed tomography for the detection of monosodium urate crystal deposition in the arteries of individuals with and without gout (CORODECT): A multi-center prospective imaging study [abstract]. 2024;76(suppl 9).
9. Hammer H, Karoliussen L, Terslev L, et al. Continuous reduction in ultrasound detected crystal depositions over 5 years follow-up: Results from the NOR-Gout study [abstract]. 2024;76(suppl 9).