Background/Purpose: Patients with uncontrolled or refractory gout have heavy disease burden,¹ but few treatment options. Pegloticase is effective for lowering serum urate (SU) in these patients, though efficacy is limited by anti-drug antibody development in some patients.² Administering pegloticase in conjunction with an immunomodulating therapy meaningfully increased the number of patients with sustained urate lowering while on treatment.³ However, case data in the literature remain limited. The current study reports experience from two busy rheumatology practices where immunomodulating therapy is routinely prescribed in patients undergoing pegloticase treatment.

Methods: Patients who underwent concomitant pegloticase/immunomodulation therapy (initiated 2017 or later) were included. Patient and treatment characteristics were examined, along with the proportion of patients who were considered pegloticase responders (≥12 pegloticase infusions and SU < 6 mg/dL at infusion 12). Patients who remained on therapy, but had not yet reached infusion 12 were not included in responder rate analyses. All patients received pre-infusion prophylaxis (125 mg IV methylprednisolone or 100 mg hydrocortisone, 180 mg oral fexofenadine or 25 mg IVP diphenhydramine). Estimated glomerular filtration rate (eGFR) was also examined before therapy and at last infusion. Data are presented as mean±SD or %.

Results: 34 patients (79% male, 62.4±16.3 years) with uncontrolled gout (SU = 9.1±2.0 mg/dL, 91% had tophi, 14.7±13.4 year gout history) were included. The most common comorbidities were hypertension (76%), obesity (71%), osteoarthritis (68%), and chronic kidney disease (CKD, 47%). Baseline eGFR was 65.4±25.2 ml/min/1.73 m² and 41% had eGFR< 60 ml/min/1.73 m². A mean of 14.6±7.1 pegloticase infusions were administered over 28.5±14.9 weeks. Immunomodulator co-therapy was initiated prior to (5.3±3.0 weeks, n=32) or at (n=2) first pegloticase infusion and included subcutaneous (subQ) methotrexate (MTX; 15.4±4.9mg/week [range: 10-25 mg/week], n=20), oral MTX (15.3±3.6 mg/week [range: 7.5-20 mg/week], n=9), oral mycophenolate mofetil (MMF; all 1000 mg/day, n=3), and oral azathioprine (AZA; all 100 mg/day, n=2). Overall treatment responder rate was 89.3% (n=28). Response rates were 93% for subQ MTX (n=14), 89% for oral MTX (n=9), 100% for MMF (n=3), and 50% for AZA (n=2). eGFR remained essentially unchanged during therapy (+10.3±16.9 ml/min/1.73 m²) and CKD stage remained stable or improved in 85% of patients (Stage 1 to 2 [n=1], Stage 2 to 3a [n=1], Stage 3a to 3b [n=2],). 34 gout flares occurred in 19 patients (56%), no infusion reactions or infections were noted, and no new safety concerns were identified.

Conclusion: These data provide further support for concomitant immunomodulator/pegloticase therapy, showing similar efficacy rates to both an open-label trial with oral MTX (79%)⁴ and a systematic literature review of all immunomodulators (83%).³

References:

1. Becker MA, et al. J Rheumatol 2009;36:1041-8.
2. Sundy JS, et al. JAMA 2011;306:711-20.
3. Keenan RT, et al. Semin Arthritis Rheum 2021;51:347-52.
4. Botson J, et al. Ann Rheum Dis 2020;79:442.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/concomitant-immunomodulation-and-pegloticase-therapy-experiences-with-a-variety-of-immunomodulatory-agents-in-two-community-rheumatology-practices/