THU0434 LEFLUNOMIDE CO-THERAPY WITH PEGLOTICASE IN UNCONTROLLED GOUT

Background: Pegloticase is a PEGylated biologic for uncontrolled gout that has well-established efficacy. However, anti-drug antibody (ADA) development causes many patients to discontinue treatment before receiving the full therapeutic course. 1 ADAs bind to the pegloticase molecule, leading to reduced therapeutic efficacy and discontinuation of therapy. 2 Emerging data indicates that co-treatment with pegloticase and immunomodulating agents may prevent ADA development, allowing more patients to receive a full course of treatment. Prior case reports describe the results of pegloticase treatment with methotrexate, azathioprine or cyclosporine 3-6 ; however, the literature does not contain information on the use of leflunomide with pegloticase. Objectives: To evaluate overall pegloticase responder rate in uncontrolled gout patients co-treated with leflunomide. Methods: This retrospective study was conducted in a rheumatology practice where an immunomodulatory agent is typically used in conjunction with pegloticase. Patients co-treated with oral leflunomide (20 mg/day) and pegloticase (8 mg/infusion) were included. Extracted data included demographics, gout characteristics, pegloticase therapy parameters (serum uric acid [sUA], number of infusions), leflunomide therapy parameters (timing with respect to the first pegloticase infusion, dose, route), adverse events (e.g., gout flare, infusion reactions), and safety information (clinical laboratory parameters). Prior to each infusion all patients were administered a standard prophylaxis regimen of fexofenadine the night before and day of infusion, solumedrol day of infusion. The primary outcome was the proportion of pegloticase responders, defined as those receiving ≥12 infusions. Results: At data collection, 10 patients (5 male, 72.7 ± 12.5 years old, baseline sUA = 6.59 ± 3.15 mg/dL) had been co-treated with pegloticase and leflunomide. 4 patients (40%) received ≥12 infusions of pegloticase; 2 patients began treatment but were lost to follow-up, though neither of these patients experienced a rise in sUA during therapy. Of the 6 patients described, 4 met the primary outcome for a responder and 2 were lost to follow-up, resulting in 4/6 or 66% response rate. The 4 remaining patients had not reached their 12 th infusion at time of data cutoff and were ongoing with a mean of 8.0 ± 1.6 infusions (range: 6-10 infusions). No new safety concerns emerged. One patient had 3 gout flares during treatment and 1 patient required emergency care because of loss of consciousness and wooziness prior to pegloticase infusion due to pre-medication with solumedrol. No clinically meaningful laboratory value changes occurred, with the exception of a mild and transient ALT rise in 1 patient. Conclusion: Preliminary evidence suggests that low-to-moderate immunomodulation can minimize or prevent ADA formation against pegloticase and increase the number of patients fully benefitting from pegloticase. No prior studies have examined the effect of leflunomide on pegloticase responder rates. The current study indicates that oral leflunomide may be a viable immunomodulator for patients with uncontrolled gout undergoing pegloticase therapy. References: [1]Sundy JS, et al. JAMA , 2011;306(7):711-720 [2]Lipsky PE, et al. Arthritis Res Ther 2014;16:R60. [3]Botson J and Peterson J. Ann Rheum Dis. 2019; 78: A1289. [4]Berhanu AA, et al. Semin Arthritis Rheum , 2017;46(6):754-758 [5]Hershfeld MS, et al. Arthritis Res Ther , 2014;16(2):R63 [6]Bessen MY, et al. Int J Clin Rheum , 2019;14(6):238-245 Disclosure of Interests: : Karim Masri Shareholder of: Horizon Therapeutics, Corbus Pharmaceuticals, Gilead, Lineage Cell Therapeutics, Speakers bureau: Horizon Therapeutics, Pfizer, Novartis, Lilly, Kevin Winterling Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Brian LaMoreaux Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics