POS0936 PRE-INFUSION GLUCOCORTICOID REDUCTION/ELIMINATION IN PATIENTS WITH UNCONTROLLED GOUT TREATED WITH PEGLOTICASE AND METHOTREXATE: EXPERIENCE OF ONE COMMUNITY RHEUMATOLOGY PRACTICE
Authors: J. Albert, T. Marcal, Z. Vranic, L. Padnick-Silver, B. Lamoreaux
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Gout is a progressive, systemic, inflammatory arthritis resulting from chronically elevated serum urate levels (SU). Both American<sup>[1]</sup> and European<sup>[2]</sup> rheumatology society treatment guidelines recommend SU be maintained &lt;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<sup>[3,4]</sup> and tophi shrinkage.<sup>[5]</sup> 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<sup>[6]</sup> to attenuate antidrug antibody (ADA) development and decrease infusion reaction (IR) risk.<sup>[7]</sup> 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. <h3>Objectives:</h3> 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. <h3>Methods:</h3> 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 &lt;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. <h3>Results:</h3> 12 gout patients (91.7% male, age: 60.3 ± 11.0 years, BMI: 29.6 ± 7.5 kg/m<sup>2</sup>, 92% visible tophi, gout duration: 13.9 ± 8.9 years) were included. All patients had a pre-treatment SU &gt;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; <b>Figure 1, Top</b>). 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; <b>Figure 1, Bottom</b>). Response was not recaptured in the single patient with GC re-initiation. No IRs were observed in any patient. <h3>Conclusion:</h3> 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 &gt;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. <h3>REFERENCES:</h3> [1] FitzGerald JD, et al. <i>Arthritis Rheumatol</i> 2020;72:879-95. [2] Richette P, et al. <i>Ann Rheum Dis</i> 2017;76:29-42. [3] Dalbeth N, et al. <i>Rheumatology (Oxford</i>) 2022;61:4898-904. [4] Dalbeth N, et al. <i>Ann Rheum Dis</i> 2023;82 (suppl 1). [5] Mandell BF, et al. <i>Arthritis Res Ther</i> 2018;20:286. [6] Pegloticase [packare insert]. Horizon Therapeutics; 2022. [7] Botson JK, et al. <i>Arthritis Rheumatol</i> 2023;75:293-304. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> 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.