Urate-Lowering Takes Longer to Improve Quality of Life in Tophaceous Gout

Urate-lowering with pegloticase meaningfully improved quality of life but took longer in gout patients with tophaceous, found a study presented at the 2024 European Alliance of Association for Rheumatology (EULAR) from June 12 – June 15, in Vienna, Austria.¹

Gout impacts the quality of life as pain interferes with daily activities and mood swings affect family relationships.² Uncontrolled gout has an even greater impact on quality of life and disability. The influence is impacted by gout flare frequency and the number of involved joints that are either tender, swollen, or with tophi.

“Gout has a large impact on patient’s [quality of life], with higher impact in patients with visible tophi, whose overall urate crystal burden is higher than patients without visible tophi,” wrote investigators, led by N. Lawrence Edwards, MD, professor in the department of Medicine at the University of Florida Health in Gainesville.¹

Urate-lowering with pegloticase has been shown to improve joints and quality of life. However, tophi’s influence on these improvements has not yet been evaluated. Hence, investigators examined patient-reported and clinical measures during 1-year of urate-lowering with pegloticase in gout patients with and without tophaceous.

MIRROR included participants who received ≤ 52 weeks of pegloticase infusion (8 mg infusion every 2 weeks), had uncontrolled gout with a serum urate of ≥ 7 mg/dL, failed or had an intolerance to urate-lowering therapy, and experienced ongoing symptoms of either ≥ 1 tophus, ≥ 2 flares, or gouty arthropathy.

In the trial, all patients participated in a 2-week trial to see if they could tolerate methotrexate. Afterward, they entered a 4-week study period and were randomized to receive methotrexate or placebo. Following 6 weeks of preparation, participants began their treatment with pegloticase. Since methotrexate showed no effects on gout, the treatment groups of methotrexate and placebo were combined in this analysis.

The team also assessed health, pain, Disability Index, tender joint count, swollen joint count, and Physical Global Assessment of Gout using the Health Assessment Questionnaire (HAQ). The observed metric values were compared between patients who had tophi before starting the treatment and those who did not.

All data included in the analysis was collected when patients were on pegloticase treatment during urate-lowering therapy. Treatment was discontinued if participants had consecutive serum urate levels of > 6 mg/dL after week 2.

The study included 115 patients who had tophi before the treatment (91% male, age: 55.1±12.3 years, BMI: 32.0±5.6 kg/m2) and 37 who did not (81% male, age: 53.6±13.5 years, BMI: 35.1±8.1 kg/m2).

Before participants received their first methotrexate dose, investigators saw all measures were worse in patients with tophi than patients without (HAQ-Heath: 45.8±27.6 vs. 34.0±28.8, HAQ-Pain: 45.4±29.2 vs. 34.1±30.0, HAQ-Disability Index: 0.79±0.73 vs. 0.59±0.68, tender joint count: 9.0±12.6 vs. 5.4±7.5, swollen joint count: 7.6±10.4 vs. 2.7±5.1, Physician Global Assessment of Gout: 5.8±2.0 vs. 4.5±2.2). However, pegloticase treatment meaningfully improved all measures by week 24 and continued improvement through week 52 in several measures.

“Full [quality of life] improvements took longer in patients with tophi, presumably due to their higher urate burden at baseline,” investigators wrote. “Prior publications have established that 52 weeks of pegloticase treatment results in near-total depletion of deposited urate. Therefore, the current findings clinically support the known association between tophi and quality of life impact, also suggesting that tophaceous gout patients in particular may benefit from a longer pegloticase treatment course.”

References

1. ^{Edwards NL, Padnick-Silver L, Obermeyer K, et alAB0112 PATIENT-REPORTED QUALITY OF LIFE IN UNCONTROLLED GOUT AND CHANGES WITH INTENSIVE URATE-LOWERING: COMPARISON OF TOPHACEOUS AND NON-TOPHACEOUS PATIENTSAnnals of the Rheumatic Diseases 2024;83:1289-1290.}
2. ^{Díaz-Torné C, Pou MA, Rodríguez-Díez B, Pujol-Ribera E. Living with gout. Experiences, impact and challenges of the disease. Qualitative study through focus groups. Reumatol Clin (Engl Ed). 2023;19(3):150-158. doi:10.1016/j.reumae.2022.03.002}