Abstract
OBJECTIVES: Pegloticase lowers serum urate (SU) but is limited by anti-drug antibodies. Methotrexate (MTX) co-administration increases urate-lowering response rate and decreases infusion reaction risk. This is of importance in uncontrolled gout patients who have few treatment options and highly impacted quality of life (QOL). Here, we report exploratory QOL/clinical endpoints of MIRROR RCT (NCT03994731). METHODS: Patients with uncontrolled gout (sUA ≥ 7 mg/dl, urate-lowering tehraoy (ULT) failure/intolerance, and ≥1 gout sign/symptom [≥1 tophus, ≥2 flares in past year, chronic gouty arthritis]) were administered pegloticase (biweekly 8 mg infusion; 52 weeks) with oral MTX (15 mg/week) or placebo co-therapy. Key exploratory outcomes included change from baseline (CFB) in Physician Global Assessment of Gout [PhGA, score: 0-10], CFB in tender/swollen joint counts [TJC/SJC, score: 0-68/0-66], and gout chronic response rate (GCR50, GCR70; 50%/70% reduction in ≥3 of TJC, SJC, HAQ-Health, HAQ-Pain). Least-square mean (±S.E.) CFB to week 52 was estimated using a mixed model for repeated measures. RESULTS: In total, 100 patients were randomized to pegloticase + MTX; 52 to pegloticase + PBO. At baseline, patients had poor overall health (HAQ-Health [MTX, PBO]: 44.9 ± 28.6, 39.1 ± 27.4; PhGA: 5.5 ± 2.1, 5.4 ± 2.2) and many affected joints (TJC: 5.4 ± 7.8, 6.7 ± 8.4; SJC: 8.3 ± 12.2, 11.0 ± 15.9). QOL progressively improved during treatment, with similar CFB at week 52 in MTX vs. PBO groups in PhGA (-4.2 ± 0.2 vs. -3.8 ± 0.3) and TJC/SJC (-6.1 ± 0.5 vs. -7.0 ± 0.8/-5.1 ± 0.4 vs. -6.0 ± 0.6). However, at week 52, more MTX patients met GCR50 (58.0% vs. 38.5%) and GCR70 (52.0% vs. 30.8%) criteria. CONCLUSION: In the MIRROR RCT, pegloticase treatment with or without MTX co-therapy led to meaningful clinical/QOL improvements in uncontrolled gout patients. However, patients receiving MTX co-therapy had greater benefits because of a higher sustained SU-lowering rate (60.0% vs. 30.8% in the PBO group at week 52). TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03994731.