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  1. J. Botson1,
  2. P. M. Peloso2,
  3. K. Obermeyer2,
  4. B. Lamoreaux3,
  5. L. Zhao2,
  6. M. E. Weinblatt4,
  7. J. Peterson5
  1. 1Orthopedic Physicians Alaska, Medical, Anchorage, United States of America
  2. 2Horizon Therapeutics plc, Research and Development, Deerfield, United States of America
  3. 3Horizon Therapeutics plc, Medical Affairs, Deerfield, United States of America
  4. 4Brigham and Women’s Hospital, Division of Rheumatology, Immunology and Allergy, Boston, United States of America
  5. 5Western Washington Medical Group, Arthritis Clinic, Bothell, United States of America


Background: Gout development follows persistent serum uric acid (sUA) elevation. Patients who are refractory to or cannot tolerate oral urate lowering therapies (ULTs) have limited treatment options. Pegloticase is effective in treating refractory gout, but many patients develop anti-drug antibodies (ADAs), which are associated with loss of urate-lowering efficacy1-3 and infusion reactions (IRs).1,2 In phase 3 trials, the pooled pegloticase responder rate during Months 3 and 6 combined was 42% (8 mg infusion every 2 weeks), with high-titer ADA positive patients losing efficacy prior to 6 months.1 The 6-month results from the MIRROR open-label trial (79% response rate [11/14], 95%CI 49-95%)4 suggest that methotrexate (MTX) administered in conjunction with pegloticase increases treatment responder rate.

Objectives: To examine longer-term (12-month) exploratory endpoints from the MIRROR open-label trial, including joint, overall health, and gout global assessments. Serial dual-energy computed tomography (DECT) images were also examined when available.

Methods: Adult patients with uncontrolled gout (sUA ≥6 mg/dL with ≥1 of the following: sUA ≥6 mg/dL despite ULT use, intolerance to ULT, or functionally limiting tophaceous deposits) were included. Patients with immunocompromised status, G6PD deficiency, severe renal impairment, or MTX contraindication were excluded. Patients were administered oral MTX (15 mg/week) and folic acid (1 mg/day) 4 weeks prior to and throughout pegloticase therapy (8 mg biweekly infusion for up to 52 weeks). Exploratory outcomes included mean change from baseline (CFB) in number of affected joints (tophi, swollen, tender), Health Assessment Questionnaire (HAQ) scores (Disability Index [DI; score 0−3], Pain [score 0−100], Health [score 0−100]), and Gout Global Assessments (Patient, Physician; score 0−10). A decrease in these measures reflects clinical/patient-reported health improvement. Change in urate deposition volume, as measured on DECT imaging, was also examined as available. Analyses were performed on the modified intent-to-treat (mITT) population (≥1 pegloticase infusion received).

Results: 14 patients (all male, mean±SD age: 49.3±8.7 years) made up the mITT population. Mean±SD sUA prior to pegloticase treatment was 9.2±2.5 mg/dL and 13 patients had visible tophi. 3 patients discontinued due to 2 consecutive sUA levels >6 mg/dL and 1 patient completed the study at week 24 (pre-protocol amendment extending treatment from 24 to 52 weeks). 10 patients completed the 52-week study. Of these, 8 patients received 26 infusions and 2 patients received 12 infusions, discontinued pegloticase after meeting their treatment goal at 24 weeks, and started allopurinol while remaining in study under observation. At week 52 (n=10, sUA=1.1±2.5 mg/dL), the number of affected joints improved, along with HAQ measures (Figure 1). Global Assessments of Gout also improved (Physician: CFB=-5.7±2.6, Patient CFB=-4.6±2.1) and majority of subjects had a score of 0 or 1 (0=“excellent health”) at week 52 (Physician: 0.3±0.5, Patient: 1.1±1.3). Two patients had available DECT imaging. One received pegloticase/methotrexate co-therapy thru week 52 and had a marked reduction in total urate volume (baseline: 128.76 cm3, week 52: 1.33 cm3). The other received only 5 pegloticase infusions, but also showed total urate volume reduction (baseline: 59.20 cm3, week 10: 25.07 cm3). Both patients displayed improvement in bone erosion healing.

Conclusion: These 12-month exploratory endpoints of the MIRROR open-label trial suggest that MTX/pegloticase co-therapy results in meaningful changes in clinical evaluations (tophaceous, tender, and swollen joint counts), and patient-reported outcomes (pain, disability) in patients with uncontrolled gout.

References: [1]Sundy JS et al. JAMA 2011;306:711-20

[2]Baraf HS et al. J Clin Rheumatol 2014;20:427-32

[3]Lipsky PE et al. Arthritis Res Ther 2014, 16:R60

[4]Botson JK et al. J Rheum 2020 [Epub ahead of print]

Disclosure of Interests: John Botson Speakers bureau: Horizon Therapeutics, Celgene, Novartis, and AbbVie, Consultant of: Horizon Therapeutics, Celgene, Novartis, and AbbVie, Grant/research support from: Horizon Therapeutics and Radius Health, Paul M. Peloso Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Katie Obermeyer Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Brian LaMoreaux Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Lin Zhao Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Michael E. Weinblatt Shareholder of: Lycera, Can-Fite BioPharma, Scipher Medicine, Inmedix, and Vorso, Consultant of: Bristol Myers Squibb, Corona, Lilly, AbbVie, Amgen, Arena, GlaxoSmithKline, Gilead Sciences, Horizon Therapeutics, Lycera, Novartis, Pfizer, Roche, Samsung, Scipher Medicine, and Set Point, Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo Bioscience, Lilly and Sanofi, Jeff Peterson Speakers bureau: Horizon Therapeutics plc, Grant/research support from: Horizon Therapeutics plc.

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