Key Inclusion/Exclusion Criteria3

Inclusion

  • Adult patients ≥18 years old with diagnosis of gout
  • Uncontrolled gout, defined as (all required)
    • Serum uric acid (sUA) ≥7 mg/dL
    • Oral urate lowering therapy failure/intolerance
    • ≥1 ongoing gout symptom (≥1 tophus, ≥2 flares in the year prior to screening and/or chronic gouty arthritis)

Exclusion

  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • eGFR <40 mL/min/1.73 m2
  • MTX contraindication/known intolerance
  • Elevated LFTs, low albumin or low blood cell counts
eGFR, estimated glomerular filtration rate; LFTs, liver function tests; MTX, methotrexate.

Family history, health literacy, and socioeconomic environment are contributing factors to gout becoming uncontrolled18,19

Two major factors contribute to uric acid buildup and crystallization18,19

Genetics
Gout runs in the family
Kidney damage
Impaired uric acid elimination
Additional contributing factors include4,18,20,21:
  • Diet and lifestyle
  • Age
  • Comorbidities
  • Metabolism
Diet is not a substitute for treatment as dietary restrictions may reduce uric acid levels by only ~1 mg/dL13,22

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Mirror: STUDY DESIGN

MIRROR RCT investigated the use of KRYSTEXXA co-administered with methotrexate1-3

MIRROR, Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase; RCT, randomized controlled trial.
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The MIRROR RCT was a 52-week, randomized double-blind placebo-controlled trial conducted in adult patients with chronic gout refractory to conventional therapy to evaluate administration of KRYSTEXXA 8 mg Q2W coadministered with 15 mg oral methotrexate QW and 1 mg oral folic acid QD (n=100) vs KRYSTEXXA alone (n=52).1,2
KRYSTEXXA MIRROR RCT design, showing Screening (n=278) before Week -6; MTX tolerability period (n=159) at Week -6 through Week -4; Double-blind MTX/PBO run in period with oral MTX (15mg/week)(n=98) and weekly oral PBO for MTX (n=51) at Week -4 through Day 1; Double-blind Pegloticase + MTX/PBO treatment period with IV Pegloticase (8 mg) every 2 weeks + Oral MTX (15 mg/week)(n=96) and IV Pegloticase (8 mg) every 2 weeks + Weekly oral PBO for MTX (n=49) from Day 1 through Week 24, with IV Pegloticase (8 mg) every 2 weeks + Oral MTX (15 mg/week)completed treatment through Week 24 (n=70)and IV Pegloticase (8 mg) every 2 weeks + Weekly oral PBO for MTX completed treatment through Week 24 (n=19), and with IV Pegloticase (8 mg) every 2 weeks + Oral MTX (15 mg/week)completed treatment through Week 52 (n=58)and IV Pegloticase (8 mg) every 2 weeks + Weekly oral PBO for MTX completed treatment through Week 52 (n=16) KRYSTEXXA MIRROR RCT design, showing Screening (n=278) before Week -6; MTX tolerability period (n=159) at Week -6 through Week -4; Double-blind MTX/PBO run in period with oral MTX (15mg/week)(n=98) and weekly oral PBO for MTX (n=51) at Week -4 through Day 1; Double-blind Pegloticase + MTX/PBO treatment period with IV Pegloticase (8 mg) every 2 weeks + Oral MTX (15 mg/week)(n=96) and IV Pegloticase (8 mg) every 2 weeks + Weekly oral PBO for MTX (n=49) from Day 1 through Week 24, with IV Pegloticase (8 mg) every 2 weeks + Oral MTX (15 mg/week)completed treatment through Week 24 (n=70)and IV Pegloticase (8 mg) every 2 weeks + Weekly oral PBO for MTX completed treatment through Week 24 (n=19), and with IV Pegloticase (8 mg) every 2 weeks + Oral MTX (15 mg/week)completed treatment through Week 52 (n=58)and IV Pegloticase (8 mg) every 2 weeks + Weekly oral PBO for MTX completed treatment through Week 52 (n=16)
Study visits with pegloticase infusion at Day 1 and every 2 weeks through Week 50. Additional noninfusion visits at Weeks 21, 23, and 52.
*100 patients randomized to MTX co-therapy; 52 patients randomized to PBO co-therapy.1
†The primary endpoint was the proportion of Month 6 (Weeks 20, 21, 22, 23, and 24) responders, defined as subjects achieving and maintaining an sUA level of <6 mg/dL for at least 80% of the time during Month 6.1
Folic acid should be continued daily during treatment of methotrexate.1
IV, intravenous; MTX, methotrexate; PBO, placebo; QD, every day; QW, every week; Q2W, every 2 weeks; sUA, serum uric acid.

Trial patient characteristics (ITT population)3

KRYSTEXXA MIRROR RCT patient population (N=152)

PATIENT CHARACTERISTICS KRYSTEXXA WITH MTX (n=100) KRYSTEXXA ALONE (n=52)
Age, mean (SD), years 55.6 (12.7) 53.0 (12.1)
Sex, male, n (%) 91 (91) 44 (84.6)
BMI, (mean) (SD), kg/m2 32.7 (5.6) 32.7 (7.8)
# of flares in 12 months
prior to baseline, mean (SD)		 10.6 (12.9) 11.3 (16.7)
sUA, mean (SD), mg/dL 8.7 (1.6) 9.1 (1.7)
Time since 1st gout diagnosis,
mean (SD), years		 13.7 (10.6) 14.3 (10.8)
Presence of tophi, n (%), yes 74 (74.0) 41 (78.8)
Stage 3 CKD, n (%)‡ 33 (33.3)§ 16 (30.8)
‡Patients with eGFR <40 mL/min/1.73 m² were excluded from study participation.3
§Baseline eGFR was missing for 1 patient.4
BMI, body mass index; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; ITT, intent-to-treat; SD, standard deviation.

Review the Key Inclusion/Exclusion Criteria

See the Data

Interested in how KRYSTEXXA may help reduce sUA?

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Significant improvement

In the MIRROR RCT, KRYSTEXXA with MTX improved patient response during both Months 6 and 12.1∥

See the Data
∥The primary efficacy endpoint was the proportion of responders, defined as achieving and maintaining sUA <6 mg/dL for at least 80% of the time during Month 6. The secondary efficacy endpoint was the proportion of responders, defined as achieving and maintaining sUA <6 mg/dL for at least 80% of the time during Month 12.

Learn more about patients who might benefit from KRYSTEXXA

Actor portrayal of patient with no visible tophi

Michelle

Occupation:
Nurse

59-year-old with no visible tophi, but has pain and tenderness in her hands; diagnosed with gout 5 years ago

Actor portrayal, not actual patient.

Learn About Michelle
Actor portrayal of patient with pain who was diagnosed with gout years ago

Andrew

Occupation:
Real estate agent

56-year-old with hypertension and pain in hands and feet; diagnosed with gout 8 years ago

Actor portrayal, not actual patient.

Learn About Andrew
Real KRYSTEXXA patient, Bet

Bet

Occupation:
Stay-at-home parent

43-year-old diagnosed with gout over 20 years ago

Real patient.

Learn About Bet

KRYSTEXXA is not indicated for the treatment of pain.

IMPORTANT SAFETY INFORMATION

WARNING: ANAPHYLAXIS AND INFUSION REACTIONS, G6PD DEFICIENCY ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA

  • Anaphylaxis and infusion reactions have been reported to occur during and after administration of KRYSTEXXA.
  • Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours of the infusion. Delayed hypersensitivity reactions have also been reported.
  • KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions.
  • Premedicate with antihistamines and corticosteroids and closely monitor for anaphylaxis for an appropriate period after administration of KRYSTEXXA.
  • Monitor serum uric acid levels prior to each infusion and discontinue treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.
  • Screen patients at risk for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to starting KRYSTEXXA. Hemolysis and methemoglobinemia have been reported with KRYSTEXXA in patients with G6PD deficiency. KRYSTEXXA is contraindicated in patients with G6PD deficiency.

CONTRAINDICATIONS:

  • In patients with G6PD deficiency.
  • In patients with history of serious hypersensitivity reactions, including anaphylaxis, to KRYSTEXXA or any of its components.

WARNINGS AND PRECAUTIONS

Gout Flares: An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy, including KRYSTEXXA. Gout flare prophylaxis with a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended starting at least 1 week before initiation of KRYSTEXXA therapy and lasting at least 6 months, unless medically contraindicated or not tolerated.

Congestive Heart Failure: KRYSTEXXA has not been formally studied in patients with congestive heart failure, but some patients in the pre-marketing placebo-controlled clinical trials experienced exacerbation. Exercise caution in patients who have congestive heart failure and monitor patients closely following infusion.

ADVERSE REACTIONS

The most commonly reported adverse reactions (≥5%) are:

KRYSTEXXA co-administration with methotrexate trial:

KRYSTEXXA with methotrexate: gout flares, arthralgia, COVID-19, nausea, and fatigue; KRYSTEXXA alone: gout flares, arthralgia, COVID-19, nausea, fatigue, infusion reaction, pain in extremity, hypertension, and vomiting.

KRYSTEXXA pre-marketing placebo-controlled trials:

gout flares, infusion reactions, nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis, and vomiting.

INDICATION

KRYSTEXXA® (pegloticase) is indicated for the treatment of chronic gout in adult patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated.

Limitations of Use: KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia.

Please see Full Prescribing Information, including Boxed Warning.

  • References
    • KRYSTEXXA (pegloticase) [prescribing information] Horizon.
    • Botson JK, et al. Arthritis Rheumatol. 2023;75:293-304.
    • Botson JK, et al. ACR Open Rheumatol. 2023;5:407-418.
    • Abdellatif A, et al. Am J Kidney Dis. 2023;81(suppl 1):S67.

IMPORTANT SAFETY INFORMATION

WARNING: ANAPHYLAXIS AND INFUSION REACTIONS, G6PD DEFICIENCY ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA

  • Anaphylaxis and infusion reactions have been reported to occur during and after administration of KRYSTEXXA.
  • Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours of the infusion. Delayed hypersensitivity reactions have also been reported.
  • KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions.