Pos0936 Pre-Infusion Glucocorticoid Reduction/Elimination in Patients With Uncontrolled Gout Treated With Pegloticase and Methotrexate: Experience of One Community Rheumatology Practice

Background: Gout is a progressive, systemic, inflammatory arthritis resulting from chronically elevated serum urate levels (SU). Both American[1] and European[2] rheumatology society treatment guidelines recommend SU be maintained <6 mg/dL to improve gout signs/symptoms and to lower the acute gout flare rate. Patients with uncontrolled gout are intolerant of/refractory to oral urate-lowering therapies, experience frequent flares, and have persistent tophi. Pegloticase markedly lowers SU in these patients, leading to rapid monosodium urate crystal depletion[3,4] and tophi shrinkage.[5] Pre-infusion prophylaxis is administered with pegloticase including pre-infusion steroids, but these high dose glucocorticoids (GCs) can be particularly detrimental to the uncontrolled gout population with high morbidity burden including hypertension, renal disease, and diabetes. Methotrexate (MTX) co-therapy is now recommended with pegloticase[6] to attenuate antidrug antibody (ADA) development and decrease infusion reaction (IR) risk.[7] Increased response rate to pegloticase with immunomodulation co-therapy has given rise to the question of whether pre-infusion steroids can be reduced and eliminated. Objectives: To retrospectively examine one community rheumatology practice's experience with pre-infusion GC dose reduction in uncontrolled gout patients receiving pegloticase plus MTX co-therapy. Methods: This retrospective chart review included all patients who received pegloticase treatment (8 mg infusion with target dosing every 2 weeks) with MTX co-therapy and had a pre-infusion GC dose reduction during therapy. Data between 1 Jan 2020 and 1 Apr 2023 were included. The effect of GC dose reduction on continued pegloticase efficacy (SU <6 mg/dL) and IR rate were investigated. All patients began pegloticase therapy receiving standard IR prophylaxis, including 125 mg IV methylprednisolone. Patients were closely monitored with clinical examination and laboratory testing. Results: 12 gout patients (91.7% male, age: 60.3 ± 11.0 years, BMI: 29.6 ± 7.5 kg/m², 92% visible tophi, gout duration: 13.9 ± 8.9 years) were included. All patients had a pre-treatment SU >6 mg/dL (mean: 8.9± 1.9 mg/dL). Most common comorbidities included hypertension (58%), hyperlipidemia (33%), osteoarthritis (25%), and atrial fibrillation (25%). All patients began subcutaneous MTX prior to first pegloticase infusion (3.6 ± 0.9 weeks; 15 [n=10] or 10 [n=2] mg/week) and had received an average of 14.3 ± 4.2 infusions (83% ≥12 infusions) over 28.3 ± 9.3 weeks; Figure 1, Top). Pre-infusion GC dose reduction began at infusion 5 (11/12 [92%]) or infusion 6 (1/12 [8%]). Following initial GC reduction, 9 patients (75%) had continued SU-lowering (additional 11.7 ± 2.2 infusions received). The remaining 3 patients, had a rise in SU above 6 mg/dL and prematurely discontinued pegloticase (all had received 15 mg MTX/week; Figure 1, Bottom). Response was not recaptured in the single patient with GC re-initiation. No IRs were observed in any patient. Conclusion: These findings suggest that pre-infusion GC reduction and elimination is possible in some patients treated with pegloticase+MTX co-therapy. Most patients were able to successfully continue therapy after pre-infusion GC reduction, but some had an SU rise >6 mg/dL coinciding with steroid reduction. No IRs were observed following GC dose reductions, but further study is needed to better understand and verify these findings considering the small number of patients. REFERENCES: [1] FitzGerald JD, et al. Arthritis Rheumatol 2020;72:879-95. [2] Richette P, et al. Ann Rheum Dis 2017;76:29-42. [3] Dalbeth N, et al. Rheumatology (Oxford) 2022;61:4898-904. [4] Dalbeth N, et al. Ann Rheum Dis 2023;82 (suppl 1). [5] Mandell BF, et al. Arthritis Res Ther 2018;20:286. [6] Pegloticase [packare insert]. Horizon Therapeutics; 2022. [7] Botson JK, et al. Arthritis Rheumatol 2023;75:293-304. Acknowledgements: NIL. Disclosure of Interests: John Albert Horizon (now Amgen, Inc.), Horizon (now Amgen, Inc.), Tatiana Marcal Amgen, Inc., Amgen, Inc., Zana Vranic Amgen, Inc., Amgen, Inc., Lissa Padnick-Silver Amgen, Inc., Amgen, Inc., Brian LaMoreaux Amgen, Inc., Amgen, Inc.