The APLAR Gout Registry: A Multinational Collaboration to Better Understand People with Gout in the Asia‐Pacific

Gout is the most prevalent inflammatory arthropathy in adults. The pathologic hallmark of gout is the continuous deposition of monosodium urate (MSU) crystals in and around the joints, which triggers inflammatory response (gout flares) and, if untreated, may progress toward articular destruction.1 Hyperuricemia is one of the primary risk factors for development of gout as well as the main target for gout treatment. Gout is treated by dissolving MSU crystals from the joint and surrounding tissues by continuously lowering serum urate to sub-saturation levels (below 6 mg/dL or 0.36 mmol/L).1 Gout has been associated with decline in health-related quality of life, decreased work productivity, work day loss, and increased healthcare expenditure,2 especially in people with uncontrolled gout, frequent gout flares, chronic arthritis and multiple tophi.3 Asia-Pacific countries have significant gout burden. Due to the large populations, estimated gout case counts were high in several Asia-Pacific subregions: 8.8 million cases in East Asia, 6.5 million cases in South Asia, 2.8 million cases in Southeast Asia and 0.5 million in Australasia.4 These numbers are comparable to those from regions traditionally regarded as having high gout prevalence, including North America (5.4 million) and Western Europe (5.0 million).4 The incidence rates of gout per 100 000 population in 2017 (percentage change between 1990 and 2017) were as follows: 84.9 (6.2) in East Asia, 90.4 (1.7) in South Asia, 88.5 (6.5) in Southeast Asia and 166.4 (11.1) in Australasia. Despite the high gout burden, people with gout living in Asia-Pacific countries have been relatively under-represented in gout research.5 This means that knowledge about gout and how to manage it have been largely derived from studies conducted among populations outside Asia-Pacific regions.6 Asia-Pacific is a highly diverse place in terms of ethnicities, cultures, comorbidities, and healthcare systems. These factors likely contribute to distinct characteristics of people with gout in the Asia-Pacific compared to other parts of the world (Figure 1). Ethnicities reflect genetic backgrounds, which influence levels of serum urate, the probability of developing gout and gout treatment outcomes. Mean serum urate concentrations varied widely among people of different ethnic backgrounds, ranging between 7.9 mg/dL (0.47 mmol/L) in Taiwanese Aborigines and 5.1 mg/dL (0.30 mmol/L) in people from rural Philippines.7 Local culture further contributes to how affected people perceive and cope with gout, as well as how they seek available local medical care—all of which can modify the characteristics and outcomes of gout.8 Recent studies suggested that comorbidities of people with gout appeared in clusters that were dependent on the population studied.9 Information on these different comorbidity profiles could also contribute to gout management and outcomes. Finally, Asia-Pacific countries have a wide variety of socio-economic backgrounds and healthcare systems, ranging from single-payer universal coverage to predominantly private insurance coverage.10 Socio-economic status and healthcare coverage translates to access and/or availability of specialist care, medications, technology (eg, telemedicine), and health education, which could further influence treatment outcomes of chronic diseases, including gout.11 We therefore hypothesize that people with gout living in Asia-Pacific countries may have distinct clinical characteristics and may also be facing a unique set of challenges to gout care. We started developing The Asia Pacific League of Associations for Rheumatology (APLAR) Gout Registry to gain deeper understanding of the challenges and characteristics of people with gout in our regions. The primary objective of the registry will be to characterize people with gout living in Asia-Pacific countries, especially where clinical characteristics of gout have not been explored and documented. The APLAR Gout Registry will be a longitudinal, multinational physician-reported registry of people with gout living in Asia-Pacific countries. The registry will be overseen by members of the APLAR Crystal-induced Arthritis Special Interest Group (the steering committee). One or 2 country managers will be assigned for each member country. Responsibilities of country managers will include formation of local research teams, researcher training, application for institutional ethics approval, data collection and communication with the steering committee. In addition to institutional ethics approval, memorandum of understanding between participating institutions and the APLAR Gout Registry steering committee regarding data sharing will be required before data collection can commence. The Registry will include all adults (18 years or older) diagnosed with gout who are under the care of and are being followed by reporting physicians. Both newly diagnosed and established gout cases will be eligible. Exclusion criteria will include people who were initially diagnosed with gout, but the diagnosis was later changed to another condition (eg, calcium pyrophosphate arthritis) and people who wish to withdraw from the Registry. In this Registry, participants will be considered as having gout when they have at least 1 episode of acute arthritis (gout flare) and are diagnosed as having gout by reporting physicians. Fulfillment of the 2015 American College of Rheumatology (ACR) / European League Against Rheumatism classification criteria for gout will not be required for inclusion in the registry, but items from the criteria will be recorded for subgroup analysis.12 Gout flare is defined as a clinically evident episode of acute joint swelling and tenderness which is judged to be induced by MSU crystals deposition by a reporting physician and which satisfies Gaffo's definition of gout flare.13 Data collection will begin after the participants have provided written informed consent for Registry participation. Researchers will gather data by interview, physical examination, and review of relevant laboratory data. Variables collected can be categorized into the following domains: demographics, comorbid conditions, gout history, gout treatments, serum urate levels, and gout flare (if present) (Table S1). Participants will be grouped into 1 of 9 clinical scenarios based on their clinical characteristics: participants with intermittent symptoms (scenarios 1–3), participants with stable tophus and intermittent symptoms (scenarios 4–6), and participants with tophus and chronic symptoms or those with unstable tophus (scenarios 7–9) (Table 1).14 The clinical scenarios were originally developed by the task force panel of the 2012 ACR Guidelines for Management of Gout to facilitate clinically based decision-making.14 The clinical scenarios contained key information comparable to what doctors typically encountered during clinical practice. Grouping gout patients into 1 of these clinical scenarios would help us visualize how our gout patients are faring in terms of disease severity and treatment outcomes. Data collection will be performed on recruitment day (first consultation) and on all subsequent clinical encounters, which include outpatient visits, emergency department visits and hospital admissions with gout as the primary diagnosis. All data will be anonymized, and each participant will be assigned a unique study number that cannot be traced back to their identities. Data will be entered into the Registry by participating researchers via an online portal on the APLAR website. The initial analysis of the APLAR Gout Registry is planned at the end of the first 12 months of participant recruitment. The first registry report will describe participants' clinical characteristics, with emphasis on clinical severity (presented as scenarios), comorbidity profile and treatment pattern. Subsequent analyses using longitudinal data (2 or more years of follow up) would allow exploration of factors associated with gout outcomes (eg, target serum urate achievement, gout flare, hospitalization), adjusting for demographics, comorbidities, and clinical characteristics. If the cohort size allows, we may also be able to perform cluster analysis of gout patients, where each cluster represents a subset of people with gout with distinct characteristics and prognosis. In order to provide the best care possible to our gout patients, we have to understand who they are and what challenges they are facing. We believe the APLAR Gout Registry will provide invaluable insights into how people living with gout in our regions are faring. Such knowledge may inform future research agendas on gout in Asia-Pacific people, as well as ensure that future gout guidelines are tailored for local populations. We anticipate that data collection will commence in early 2023. We encourage all interested rheumatologists from APLAR member national organizations to help contribute to the registry, especially those who are caring for under-represented gout populations. Conceptualiztion: all authors; Methodology: all authors; Visualization: K.J., Writing - Original Draft: K.J.; Writing - Review & Editing: all authors; Project administration: R.D.V., A.M.E., M.H.M.Z.S.; Supervision: J.P.L. None. All authors declare no conflict of interest. Data sharing is not applicable to this article as no new data were created or analyzed in this study. Table S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.