POS0513 QUALITY OF LIFE AND CLINICAL GOUT ASSESSMENT CHANGES IN UNCONTROLLED GOUT PATIENTS UNDERGOING PEGLOTICASE THERAPY AS PART OF THE MIRROR RANDOMIZED CONTROLLED TRIAL

Background

Refractory/uncontrolled gout can severely limit physical function and impact patient quality of life ^[1,2]. Unfortunately, limited treatment options exist for patients intolerant of or refractory to oral urate-lowering therapies. Pegloticase can lower serum urate (SU) in these patients ^[3] with demonstrated quality of life and physical function benefits ^[4]. The MIRROR RCT trial showed increased SU-response rates (71.0% vs. 38.5%) with lower infusion reaction risk (4.2% vs. 30.6%) when pegloticase was co-administered with methotrexate (MTX) vs. placebo (PBO), but patient-reported outcomes (PROs) from this study have not been reported ^[5].

Objectives

To report the prespecified PROs and gout-related clinical measures through Month 12 of pegloticase + MTX/PBO co-therapy in MIRROR RCT trial participants.

Methods

Patients with uncontrolled gout (sUA≥7 mg/dL, ULT failure/intolerance, and ≥1 of the following: ≥1 tophus, ≥2 flares in past year, chronic gouty arthritis) were administered pegloticase (biweekly 8 mg infusion) plus either oral MTX (15 mg/wk) or PBO. The study included 2-wk MTX tolerance, 4-wk blinded MTX/PBO Run-in, and 52-wk pegloticase+MTX/PBO Treatment periods. Key exclusion criteria were being immunocompromised, G6PD deficiency, eGFR <40 ml/min/1.73m², or MTX contraindication. PROs included change from baseline (CFB) to Wk 52 in Health Assessment Questionnaire (HAQ) indices (secondary endpoints in ranked order: Disability [DI, score 0-3, MCID=0.22^4], Pain [score 0-100, MCID=10^4], Health [score 0-100, MCID=10^4]). Physician Global Assessment of Gout (PhGA; score 0-10, MCID=1⁴), and tender [68 count]/swollen [66 count] joint counts [TJC/SJC], with decreases in measures reflecting improvement. Analyses were performed on the intent-to-treat population (ITT; all randomized patients). Least-square mean (±SE) CFB to Wk 52 was analyzed using a mixed-model for repeated measures, adjusting for baseline score, baseline tophi presence, treatment group, visit, visit by treatment group interaction, and visit by baseline interaction.

Results

152 patients made up the ITT (100 randomized to MTX, 52 randomized to PBO). At baseline (before MTX exposure, Wk -6) HAQ scores indicated some disability, high pre-therapy pain, and somewhat poor overall health (mean [±SD] DI, Pain, Health: MTX: 0.7±0.7, 43.7±30.3, 44.9±28.6, respectively; PBO: 0.8±0.8, 40.5±28.6, 39.1±27.4, respectively). Baseline PhGA was similar between groups (MTX: 5.5±2.1, PBO: 5.4±2.2) but the MTX group had fewer affected joints (TJC: 6.7±8.4 vs. 11.0±15.9, SJC: 5.4±7.8 vs. 8.3±12.2). All HAQ measures progressively improved during treatment (Figure 1), but the treatment group difference in the Wk 52 CFB in HAQ-DI was not statistically significant, making further PRO analyses exploratory in nature. PhGA score improved (mean[±SE] Wk 52 CFB: -4.2±0.2 vs.-3.8±0.3), with a median observed score of 1.0 and 1.0 in the MTX and PBO groups, respectively, at Wk 52. TJC and SJC markedly declined during Treatment (mean[±SE] CFB TJC: -6.1±0.5 vs. -7.0±0.8, SJC: -5.1±0.4 vs. -6.0±0.6; MTX vs. PBO, both p >0.21), declining to a mean (±SD) TJC at Wk 52 of 1.4±4.6 and SJC of 1.4±4.5 in the MTX group and a TJC of 0.6±1.0 and SJC of 1.1±2.9 in the PBO group.

Conclusion

Pegloticase treatment resulted in meaningful improvements in both clinical measures and quality of life in patients with uncontrolled gout. Patients co-treated with MTX experienced greater improvements in HAQ-Pain and Health scores after 52 wks of therapy, likely reflective of the higher urate-lowering response rate observed in the presence of MTX immunomodulation ^[5].

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]Sundy JS et al. JAMA 2011;306:711-20. [4]Strand V et al. J Rheumatol 2012;39:7. [5]Botson J et al. Arthritis Rheumatol 2022 [Epub ahead of print].

Acknowledgements

This study was funded by Horizon Therapeutics plc.

Disclosure of Interests

John Botson Speakers bureau: Abbvie, Amgen, Aurinia, Chemocentryx, Horizon, Lilly, Novartis, Consultant of: Abbvie, Amgen, Aurinia, Chemocentryx, Horizon, Lilly, Novartis, Grant/research support from: Allena, Horizon, Radius Health, Katie Obermeyer Shareholder of: Horizon, Employee of: Horizon, Brian LaMoreaux Shareholder of: Horizon, Employee of: Horizon, Lissa Padnick-Silver Shareholder of: Horizon, Employee of: Horizon, Supra Verma Shareholder of: Horizon, Employee of: Horizon, Michael E. Weinblatt Consultant of: Abbvie, Aclaris, Amgen, Bayer, Bristol Myers Squibb, Corevitas, EQRx, Genosco, Glaxo Smith Kline, Gilead, Horizon, Johnson and Johnson, Novartis, Pfizer, Sanofi, Scipher, Set Point, Tremeau, Rani Therapeutics, Revolo, Sci Rhom, Grant/research support from: Aqtual, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Jeff Peterson Speakers bureau: Horizon, Lilly, Novartis, Consultant of: Horizon, Lilly, Novartis, Grant/research support from: Horizon (study site/investigator).