Background: Gout patients are at increased risk for developing chronic kidney disease (CKD) ¹ and hyperuricemia is an independent risk factor for CKD worsening, ^2,3 particularly in women. ³ As a result, renal function is of concern in uncontrolled gout patients. Pegloticase, a recombinant PEGylated uricase, can rapidly decrease serum uric acid levels (sUA) in uncontrolled gout patients, but with pegloticase monotherapy <50% have sustained urate-lowering during Month 6 of treatment. ⁴ Pegloticase treatment response rate is markedly higher when immunomodulating therapies such as methotrexate (MTX) are co-administered, ^5,6 but MTX use can be limited by renal impairment. Clinical trials excluded CKD patients, but real-world published cases of immunomodulation-pegloticase co-therapy have included patients with a pre-therapy eGFR <60 ml/min/1.73 m ² .

Objectives: This study examined pooled case data from prior studies, focusing on renal function changes during MTX-pegloticase co-treatment in patients with and without pre-therapy CKD.

Methods: This retrospective study examined deidentified case data collected for prior retrospective studies. ^7-9 All patients who underwent MTX-pegloticase co-therapy were included and categorized as CKD (baseline eGFR <60 ml/min/1.73 m ² ) or non-CKD (baseline eGFR ≥60 ml/min/1.73 m ² ). sUA, renal function, blood cell counts, and liver function were closely monitored during therapy. Patient characteristics, pegloticase treatment parameters, proportion of treatment responders (≥12 infusions received and sUA <6 mg/dL at infusion 12 [ongoing patients with <12 infusions excluded]), renal function changes (eGFR, CKD stage), and adverse events were examined.

Results: 15 uncontrolled gout patients with CKD (9 stage 3a, 4 stage 3b, 2 stage 4; pre-therapy mean[±SD] eGFR: 43.2±11.3 ml/min/1.73 m ² , sUA: 8.5±2.2 mg/dL) and 27 without CKD (pre-therapy eGFR: 82.9±19.0 ml/min/1.73 m ² ; sUA: 9.5±1.7 mg/dL) were included. Patient characteristics and comorbidity profiles were similar, but CKD patients were older (72.0±9.9 vs. 52.3±14.3 yrs) and more often female (33% vs. 7%). On average, MTX was initiated ~4 wks before pegloticase in both CKD status groups. MTX dose was lower in CKD patients (14.8±5.8 vs. 19.3±4.9 mg/wk). Pegloticase treatment was similar between groups (CKD: 14.7±8.1 infusions over 28.5±17.1 wks, non-CKD: 14.1±7.1 infusions over 27.9±15.1 wks), with similar urate-lowering response rate (92% vs. 86%). eGFR increased during therapy in 60% and 44% of CKD and non-CKD patients, respectively, with mean eGFR increase of 11.5±20.9 and 4.2±15.0 ml/min/1.73m ² , respectively. In the CKD group, CKD stage either improved or was stable in 13/15 patients (87%). The 2 patients with CKD progression both moved from stage 3a to 3b, and both stage 4 CKD patients had an eGFR increase, improving to stage 3a. In the non-CKD group, 3 patients developed stage 3 CKD (2 stage 3a, 1 stage 3b). 7/15 (47%) CKD and 13/27 (48%) non-CKD patients had ≥1 AE noted, with gout flare most reported (47% vs. 41%). A mild infusion reaction and pancytopenia occurred in 1 non-CKD patient each.

Conclusion: In this retrospective real-world review of a limited number of cases, MTX-pegloticase co-therapy resulted in sustained sUA lowering in uncontrolled gout patients with and without CKD. Close monitoring of renal function indicated stability or improvement during therapy in 86% of uncontrolled gout patients with CKD. Further study is needed to better understand therapy tolerance and treatment response rates of uncontrolled gout patients with CKD undergoing MTX-pegloticase co-therapy.

REFERENCES:

[1]Roughley MJ et al. Arthritis Res Ther 2015;17:90

[2]Edwards NL. Cleve Clin J Med 2008;75:S13-6

[3]Iseki K et al. Am J Kidney Dis 2004;44:642-50

[4]Sundy et al. JAMA 2011;306:711-20

[5]Botson J et al. J Rheum 2021;48:767-74

[6]Keenan RT et al. Semin Arthritis Rheum 2021;51:347-52

[7]Albert J et al. Rheumatol Ther 2020;7:639-48

[8]Broadwell A et al. Arthritis Rheumatol 2021;73 (suppl 10)

[9]Masri KR et al. Ann Rheum Dis 2020;79:450

Disclosure of Interests: John Albert Speakers bureau: Horizon Therapeutics, Consultant of: Horizon Therapeutics, Aaron Broadwell Speakers bureau: Horizon Therapeutics, Consultant of: Horizon Therapeutics, Karim Masri Shareholder of: Horizon Therapeutics, Speakers bureau: Horizon Therapeutics, Consultant of: Horizon Therapeutics, Lissa Padnick-Silver Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Brian LaMoreaux Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics