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Background: It is well-known that gout negatively impacts patient quality of life (QOL). Uncontrolled gout has an even higher impact on patients QOL and disability, significantly influenced by gout flare frequency and the number of involved joints (tender, swollen, with tophi).1,2 QOL and joint improvements with pegloticase-induced urate-lowering have been reported,3,4 but the influence of tophi on these improvements has not yet been explored. Objectives: To examine patient-reported and clinical measures during 1-year of intensive urate-lowering with pegloticase in tophaceous and non-tophaceous gout patients. Methods: MIRROR RCT trial participants who received ≥1 pegloticase infusion were included in this post hoc analysis. All patients had uncontrolled gout (serum urate SU ≥7 mg/dL with oral ULT failure/intolerance and ongoing symptoms ≥1 tophus, ≥2 flares/year, or gouty arthropathy) and received ≤52 weeks of pegloticase treatment (8 mg infusion every 2 weeks) with or without MTX co-therapy (15 mg oral MTX/week). All patients completed a 2-week MTX tolerance period and a 4-week MTX or placebo run-in prior to first pegloticase infusion (Day 1). Because MTX has no known effects in gout, treatment groups were combined for this analysis. Observed values in Health Assessment Questionnaire (HAQ) measures (Health, Pain, Disability Index DI), tender joint count (TJC), swollen joint count (SJC), and Physician Global Assessment of Gout (PhGA) were examined during treatment and compared between patients with and without pre-treatment tophi. All included data were obtained while patients were on pegloticase treatment during sustained urate-lowering (treatment discontinued if 2 consecutive SU >6 mg/dL after Week 2). Results: 115 patients with pre-treatment tophi (91% male, age: 55.1±12.3 years, BMI: 32.0±5.6 kg/m2) and 37 without (81% male, age: 53.6±13.5 years, BMI: 35.1±8.1 kg/m2) were included. Prior to treatment (Week -6, prior to first MTX dose), all measures were worse in patients with tophi vs. those without (HAQ-Heath: 45.8±27.6 vs. 34.0±28.8, HAQ-Pain: 45.4±29.2 vs. 34.1±30.0, HAQ-DI: 0.79±0.73 vs. 0.59±0.68, TJC: 9.0±12.6 vs. 5.4±7.5, SJC: 7.6±10.4 vs. 2.7±5.1, PhGA: 5.8±2.0 vs. 4.5±2.2). All measures meaningfully improved by pegloticase treatment Week 24, with continued improvement through Week 52 in several measures, particularly among those with baseline tophi (Figure 1). Conclusion: Gout has a large impact on patient's QOL, with higher impact in patients with visible tophi, whose overall urate crystal burden is higher than patients without visible tophi.5 Sustained urate-lowering with pegloticase meaningfully improved all examined measures. However, full QOL improvements took longer in patients with tophi, presumably due to their higher urate burden at baseline. Prior publications have established that 52 weeks of pegloticase treatment results in near-total depletion of deposited urate.6,7 Therefore, the current findings clinically support the known association between tophi and quality of life impact,1,2 also suggesting that tophaceous gout patients in particular may benefit from a longer pegloticase treatment course. Further, this analysis highlights that, in the MIRROR RCT trial,3 attrition from treatment for any cause was very low after Week 24. REFERENCES: 1 Becker MA, et al. J Rheumatol 2009;36:1041-8. 2 Khanna PP, et al. Health Qual Life Outcomes 2012;10:117. 3 Botson JK, et al. Arthritis Res Ther 2022;24:281. 4 Strand V, et al. J Rheumatol 2012;39:1450-7. 5 Dalbeth N, et al. Ann Rheum Dis 2015;74:908-11. 6 Dalbeth N, et al. Arthritis Rheumatol 2023;74(suppl 9). 7 Dalbeth N, et al. Rheumatology (Oxford). 2022;61:4898-904. Acknowledgements: NIL. Disclosure of Interests: N. Lawrence Edwards Amgen, Inc., Lissa Padnick-Silver Amgen, Inc., Amgen, Inc., Katie Obermeyer Amgen, Inc., Amgen, Inc., Brian LaMoreaux Amgen, Inc., Amgen, Inc.
Edwards et al. (Sat,) studied this question.