1806: Characteristics and Comorbidity Burden of Phase 3 Clinical Trial Participants Who Did and Did Not Experience Acute Gout Flares During Biweekly Pegloticase Dosing

Naomi Schlesinger¹, Lissa Padnick-Silver², Katie Obermeyer² and Brian LaMoreaux², ¹Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, ²Horizon Therapeutics plc, Deerfield, IL

Background/Purpose: Acute gout flare often accompanies urate-lowering therapy initiation and is the most common adverse event associated with pegloticase, a recombinant pegylated uricase that rapidly lowers serum uric acid (sUA).¹ A recent case series of uncontrolled gout patients undergoing pegloticase plus methotrexate co-therapy found that patients who experienced acute gout flare during therapy were slightly older, more often obese, and had higher comorbidity burden at baseline than those that did not.² To better understand these findings, this analysis examined and compared phase 3 pegloticase trial participants with and without gout flare during treatment.

Methods: Patients with uncontrolled gout, sUA≥8 mg/dL, and allopurinol intolerance/recalcitrance who were administered biweekly 8 mg pegloticase infusions as part of the pegloticase phase 3 pivotal trials¹ were included. Patient baseline characteristics were compared in this post hoc analysis between participants who did and did not experience ≥1 acute gout flare during treatment.

Results: 66 patients (80.3% male, 57.0±15.12 years old, BMI: 33.0±7.42 kg/m²; sUA: 10.2±1.81 mg/dL) with ≥1 acute gout flare and 18 patients (77.8% males, 53.2±17.40 years old, BMI: 32.8±7.37 kg/m²; sUA=9.7±2.71 mg/dL) without acute gout flare were included. Patients who experienced ≥1 flare following pegloticase initiation had more acute gout flares in the 18 months prior to treatment (11.1±11.49 vs. 5.4±3.31 flares, p=0.040). Though many characteristics were similar, a larger proportion of flare patients were white (69.7% vs. 44.4%, p=0.057). 73.9% (207/280) of listed comorbidities were more prevalent in patients with ≥1 acute gout flare, indicating higher overall comorbidity burden; most notably, diabetes mellitus (30.3% vs. 16.7%; non-insulin dependent: 16.7% vs. 0%), renal failure (25.8% vs. 16.7%), and nervous system disorders (40.9% vs. 16.7%), but all p >0.05 (Figure). Additionally, more patients who experienced acute gout flares during treatment had insomnia (18.2% vs. 0) and depression (15.2% vs. 0) prior to treatment.

Conclusion: Findings of this post hoc analysis largely agree with those of a recent retrospective chart review study² suggesting higher comorbidity in patients who experience acute gout flares during pegloticase therapy. We also found possible differences in patient race and pre-treatment flare rate. This small study is hypothesis generating and further study is needed on a larger population. However, identifying possible risk factors for acute gout flare following ULT initiation would be beneficial for both patient and physician.

References:
1. Sundy JS, et al. JAMA 2011, 306:711-20.
2. Albert J, et al. Ann Rheum Dis 2022:81(Suppl 1):1644.
Figure. Comorbidities in phase 3 pegloticase pivotal trial participants who did and did not experience acute gout flare during biweekly pegloticase treatment. *noted as comorbidity, not based on BMI. †incudes benign and malignant neoplasms.
Disclosures: N. Schlesinger, Olatec Therapeutics, Novartis, Horizon Pharma, sobi, JW Pharma, LG Chem; L. Padnick-Silver, Horizon Therapeutics; K. Obermeyer, Horizon Therapeutics; B. LaMoreaux, Horizon Therapeutics.