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Abstract: PUB035

Treatment Response in Patients with Uncontrolled Gout Co-Treated with Pegloticase and Leflunomide

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Masri, Karim Richard, Ben Secours Rheumatology Center, Richmond, Virginia, United States
  • Winterling, Kevin W., Horizon Therapeutics, Lake Forest, Illinois, United States
  • LaMoreaux, Brian, Horizon Therapeutics, Lake Forest, Illinois, United States
Background

Many patients with CKD develop gout with a prevalence ≤36% in later stage disease. Though oral urate-lowering therapies are used in CKD patients, some may not respond to or cannot tolerate them. Uncontrolled (refractory) gout can be treated with pegloticase (PEGylated uricase enzyme), however, anti-drug antibodies (ADAs) can cause loss of therapeutic efficacy. Compared with pegloticase alone, recent case series show markedly higher response rates with methotrexate/pegloticase co-therapy (42% vs. 80-100%). However, certain considerations with methotrexate use including significant renal or hepatic disease may not be as restricting with leflunomide. This study examined pegloticase response rate in patients co-treated with pegloticase and leflunomide.

Methods

This chart review study included uncontrolled gout patients treated with pegloticase (biweekly 8 mg infusions) and oral leflunomide (20 mg/day). Patient, disease, and treatment parameters were examined, along with safety data. Patients receiving ≥12 pegloticase infusions with a serum uric acid level (sUA) <6 mg/dL at infusion 12 were considered responders.

Results

10 patients were identified and included (5 men, 72.7±12.5 years, pre-therapy sUA: 7.1±2.4 mg/dL). Common comorbidities were CKD (90%), hypertension (70%), diabetes mellitus (60%), obesity (60%), congestive heart failure (50%), and coronary artery disease (20%). 7 patients (70%) met responder criteria (26.6±14.0 infusions, sUA at infusion 12: 0.9±1.5 mg/dL). 3 patients were lost to follow-up or discontinued therapy. Gout flare (1 patient, 3 flares), wooziness/loss of consciousness (1 patient; before pegloticase infusion, deemed solumedrol related), worsening of kidney/cardiac issues (1 patient, deemed unrelated to treatment), and mild, transient ALT/AST increases (2 episodes, 1 patient) were observed. All treatment-related AEs were known effects of pegloticase or leflunomide.

Conclusion

These findings suggest that leflunomide/pegloticase co-therapy can increase the proportion of pegloticase responders, likely due to attenuation of ADAs. While methotrexate has been shown to increase pegloticase response rates, many gout patients have advanced CKD and leflunomide potentially represents an alternative option for minimizing ADAs.

Funding

  • Commercial Support – Horizon Therapeutics