POS1243 SERUM URATE LEVELS AND RECURRENT GOUT FLARE EVENTS AND GOUT-PRIMARY HOSPITALISATIONS: GENERAL POPULATION-BASED INCEPTION COHORT OF >62,000 NEWLY-DIAGNOSED GOUT PATIENTS

Background: Despite EULAR and other rheumatology guidelines' emphasis on treat-to-target-serum-urate levels (<6 or <5 mg/dL, urate crystal sub-saturation points), this pathophysiology-based recommendation is not accepted in primary care practice (where >90% of gout care occurs) or endorsed by the American College of Physicians. A recent investigation of 3,613 UK Biobank participants found that baseline urate levels were strongly associated with the risk of subsequent gout flares and rates of hospitalisation for recurrent gout, in a dose-dependent manner [ JAMA 2024 [1]]. However, as UK Biobank participants tend to be healthier with a better socioeconomic status (SES) than the general population, and that study only included patients with prevalent gout who were treated in primary care, the generalizability of those findings should be confirmed, especially for newly-diagnosed gout cases. Objectives: We evaluated the relation between baseline serum urate measurement and subsequent risk of acute gout flares, in reference to the target-serum-urate levels, in a general population-based inception cohort of 62,213 incident gout patients. Methods: This was a nationwide cohort study using the Clalit Health Services database, which includes electronic medical records data for approximately 5 million Israeli residents. We included people diagnosed with gout over the years 2001-2023, with at least one year of enrollment prior to gout diagnosis, one year of follow-up after gout diagnosis, and one baseline serum urate measurement around the time of the gout diagnosis. As done previously, [1, 2] flares occurring after gout diagnosis were ascertained by (1) hospitalisation or emergency department visit with gout (ICD-10 M10) as primary discharge diagnosis; (2) diagnosis of gout flare in outpatient records; or (3) diagnosis of gout in community clinics. Outpatient records and community clinics were counted only if prescriptions were issued within a week from diagnosis, for corticosteroids, colchicine, or non-steroidal anti-inflammatory drugs (NSAIDs). We also investigated flares requiring hospitalisation. Negative binomial regression was used to assess the relation between prior serum urate levels and rates of recurrent gout flares over 1, 5, and 10 years of follow-up. The multivariable models were adjusted for age, sex, SES, smoking, comorbidities (hypertension, ischemic heart disease, heart failure, chronic kidney disease, and peripheral vascular disease), and diuretic use. Results: We included 62,213 patients newly diagnosed with gout (mean age 61 years, 68% males), among whom we documented 24,663 recurrent gout flares over 465,917 person-years. Mean serum urate at baseline was 7.4 mg/dL. 97% and 99% of flares occurred among those with baseline serum urate ≥6 and ≥5 mg/dL, respectively. Age- and sex-adjusted rate ratios (RR) for flares with urate levels of ≤ 4.9, 5.0-5.9, 6.0-6.9, 7.0-7.9, 8.0-8.9, 9.0-9.9, and ≥10 mg/dL were 1.0, 1.8, 4.4, 8.8, 13.9, 19.1, and 26.9, respectively, during the first ten years of follow-up (Table 1). The associations persisted in the extended adjusted model, with corresponding RRs of 1.0, 1.5, 4.0, 7.9, 12.8, 17.0, and 23.4 (Table 1). Nearly all flares requiring hospitalisation (98%) occurred with baseline urate ≥6 mg/dL. The RR for hospitalised flares with urate levels of ≤ 4.9, 5.0-5.9, 6.0-6.9, 7.0-7.9, 8.0-8.9, 9.0-9.9, and ≥10 mg/dL were 1.0, 0.80, 4.9, 3.6, 9.9, 19.8, and 40.5, respectively. Conclusion: In this nationwide inception cohort of incident gout patients, almost all flares (97% and 99%) occurred among those with baseline urate ≥6 and ≥5 mg/dL, respectively, and higher serum urate levels were strongly associated with recurrent flares, with a striking dose-response relationship. These findings confirm those reported among UK Biobank participants with prevalent gout treated in primary care, but with greater generalizability and precision. Together, these replicated findings support the notion that nearly all cases of gout flares can be prevented by gout patients meeting these target urate levels. REFERENCES: [1] McCormick et al., JAMA 2024. PMID 38319333. [2] Cipolletta et al., JAMA 2022. PMID 35916846. Table 1. Rates and Rate Ratio (RR) for Recurrent Gout Flares According to Serum Urate Level and Follow-Up Time from Gout Diagnosis. Acknowledgements: NIL . Disclosure of Interests: Ran Abuhasira: None declared, Itai Hazan: None declared, Chio Yokose: None declared, Natalie McCormick: None declared, Hyon Choi Ani, Protalix, Horizon, LG Chem, and Shanton, Horizon, LG Chem. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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