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Abstract: SA-PO898

eGFR Changes in Uncontrolled Gout Patients Randomized to Receive Methotrexate or Placebo as Co-Therapy to Pegloticase: MIRROR RCT Findings

Session Information

Category: CKD (Non-Dialysis)

  • 2202 CKD (Non-Dialysis): Clinical‚ Outcomes‚ and Trials

Authors

  • Abdellatif, Abdul A., Baylor College of Medicine, Houston, Texas, United States
  • Botson, John K., Orthopedic Physicians Alaska, Anchorage, Alaska, United States
  • Obermeyer, Katie L., Horizon Therapeutics plc, Deerfield, Illinois, United States
  • LaMoreaux, Brian, Horizon Therapeutics plc, Deerfield, Illinois, United States
  • Marder, Brad Allan, Horizon Therapeutics plc, Deerfield, Illinois, United States
Background

The MIRROR RCT trial (methotrexate [MTX] or placebo [PBO] co-therapy to pegloticase) showed increased urate-lowering response rate (71.0% vs 38.5% during Month 6) and lower infusion reaction rate (4% vs 31%) in patients (pts) co-administered MTX. Because CKD is prevalent in gout pts and MTX is used cautiously in CKD pts, pegloticase+MTX co-therapy impact on renal function is of interest. Here we report eGFR changes in MIRROR RCT pts.

Methods

Uncontrolled gout pts (serum uric acid [sUA]≥7mg/dL, ULT failure/intolerance, ≥1 gout symptom) received pegloticase (biweekly 8mg infusion) and blinded oral MTX (15mg/wk) or PBO (2:1 randomization) following a 2-wk MTX tolerance test and 4-wk blinded MTX/PBO Run-in (eGFR<40ml/min/1.73m2 excluded). Baseline eGFR was measured before MTX exposure (Wk -6). Mean (SE) change from baseline (CFB) in eGFR was examined by treatment and baseline eGFR status (<60 and ≥60ml/min/1.73m2). Analyses were performed on all randomized pts (ITT).

Results

100pts were randomized to pegloticase+MTX (56±13 yrs, 91% men, eGFR=68.9±18.0ml/min/1.73m2) and 52pts to pegloticase+PBO (53±12yrs, 85% men, eGFR=71.1±17.6ml/min/1.73m2). eGFR was stable during MTX/PBO Run-in and after pegloticase initiation (Day1) in both treatment groups (Figure). At Wk24, eGFR CFB was +5.3±1.3 and +4.3±2.3ml/min/1.73m2 in the MTX (N=70; 69responders) and PBO (N=19, 19responders) groups, respectively. eGFR CFB at Wk24 did not differ between eGFR<60 and ≥60 groups in MTX (+4.1±2.4 [N=27], +6.3±1.7 [N=43] ml/min/1.73m2 respectively) or PBO (+2.5±5.6 [N=7],+7.8±4.1 [N=12] ml/min/1.73m2 respectively) pts (both p≥0.48).

Conclusion

eGFR did not appear to decrease after oral MTX initiation when administered as co-therapy with pegloticase. This was true for pts with and without pre-therapy eGFR <60ml/min/1.73m2. These findings suggest MTX co-therapy did not negatively impact renal function in MIRROR RCT trial participants.

Funding

  • Commercial Support – Horizon Therapeutics plc