Key Inclusion/Exclusion Criteria2

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 include4,20:
  • 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/dL9,10

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Graphic of a shield showing that KRYSTEXXA has been approved for 14 years
URATE BURDEN

Urate crystal burden may not be visually apparent1-3

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Urate crystals can accumulate almost anywhere in the body without visible indication4,5

4X more urate deposits were found using DECT vs on clinical exam3

Drag the slider to see deposition
Deposition of monosodium urate crystals detected using DECT (displayed in green). Images courtesy of Dr Jürgen Rech. Individual patient presentations may vary.
urate-crystal-slider-2
urate-crystal-slider-1

Target sUA to a normal (<6 mg/dL) level

The lower the serum uric acid (sUA) level, the faster urate burden can resolve6,7

Even at an sUA level of 5.4 mg/dL, it would take 2 years to dissolve a tophus the size of a small marble.8,*
Changes in diet cannot adequately address the underlying cause of gout.9,10
Limitations of Diet

*According to a long-term follow-up of 24 patients receiving a mean daily dose of 320 mg allopurinol.8

KRYSTEXXA has not been studied to reverse damage to any of the body’s organs.

REDUCTION OF URATE DEPOSITION
ONGOING URATE DEPOSITION
  • 0-4.0
    mg/dL6,7
  • 4.1-5.9
    mg/dL6,11
  • >6.0
    mg/dL4,12,13

0-4.0 mg/dL6,7

Potential to

  • Resolve tophi faster
  • Expedite the reduction of urate burden
  • 0-4.0
    mg/dL6,7
  • 4.1-5.9
    mg/dL6,11
  • >6.0
    mg/dL4,12,13

4.1-5.9 mg/dL6,11

  • Slow resolution of tophi
  • Decrease flare frequency
  • 0-4.0
    mg/dL6,7
  • 4.1-5.9
    mg/dL6,11
  • >6.0
    mg/dL4,12,13

>6.0 mg/dL4,12,13

  • Urate continues to deposit in the joints and tissues, including organs
  • Flares can increase in frequency

Many patients fail to reach target sUA level of <6 mg/dL with oral ULTs14,15

 

2020 ACR Guidelines: When treating, ULT titration should occur over a reasonable timeframe (eg, weeks to months, not months to years) to prevent treatment inertia1,16,†

Allopurinol may have a
threshold effect that
impacts treatment
outcomes
Threshold Effects

†Treatment inertia is when adjustments are not made to current therapy when it fails to meet patient treatment goals.17

‡The primary efficacy endpoint was an sUA concentration of <6 mg/dL at each of the last 3 monthly measurements.15

The Febuxostat versus Allopurinol Controlled Trial (FACT) study was a phase 3, randomized, double-blind, 52-week, multicenter trial that compared the safety and efficacy of febuxostat with the safety and efficacy of allopurinol in adult subjects with gout who had sUA levels of at least 8 mg/dL.15

ACR, American College of Rheumatology; DECT, dual-energy computed tomography; ULTs, urate-lowering therapies.

Percentages of patients treated with allopurinol or febuxostat who failed to reach a target sUA level of <6 mg/dL 15,‡

check-list

300 mg allopurinol/day for 52 weeks (n=251)

80 mg febuxostat/day for 52 weeks (n=255)

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Identifying patients

See if your patients fit the criteria for uncontrolled gout.

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Learn more about patients who might benefit from KRYSTEXXA

Actor portrayal of gout patient, Linda

Linda

Occupation:
Accountant

55-year-old with hypertension diagnosed with gout 4 years ago

Actor portrayal, not actual patient.

Learn About Linda
pat-james

James

Occupation:
Middle school teacher

52-year-old with diabetes diagnosed with gout 15 years ago

Actor portrayal, not actual patient.

Learn About James
patient-bet

Bet

Occupation:
Stay-at-home parent

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

Real patient.

Learn About Bet

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 include4,20:
  • 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/dL9,10

Allopurinol may have a threshold effect that impacts treatment outcomes1421

Even at the highest doses, a proportion of patients may not benefit from increased doses of allopurinol1421

Proportion of patients with sUA <6 mg/dL categorized by their final daily allopurinol dose

Chart showing proportion of patients with sUA <6.0 g/dL by their final daily dose of allupurinol. Chart showing proportion of patients with sUA <6.0 g/dL by their final daily dose of allupurinol.

While XOIs can limit the production of uric acid, they do not actively remove saturated urate from the body1522

XOI, xanthine-oxidase inhibitor.

The efficacy analysis was performed post hoc to determine the proportion of patients who met the sUA target of <6 mg/dL when categorized by final allopurinol dose rather than the highest dose during the study.14 Analysis is exploratory and has not been adjusted for multiple comparisons. No clinical or statistical conclusions can be drawn.14

The efficacy analysis was performed post-hoc to determine the proportion of patients who met the sUA target of <6 mg/dL when categorized by final allopurinol dose rather than the highest dose during the study.21

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
    • Thiele RG, et al. Rheumatology (Oxford). 2007;46:1116-1121.
    • Bongartz T, et al. Ann Rheum Dis. 2015;74:1072-1077.
    • Choi HK, et al. Ann Rheum Dis. 2009;68:1609-1612.
    • Doghramji PP, et al. Postgrad Med. 2012;124:98-109.
    • Park JJ, et al. BMJ Open. 2014;4:e005308.
    • Perez-Ruiz F. Rheumatology (Oxford). 2009;48(suppl 2):ii9-ii14.
    • Araujo EG, et al. RMD Open. 2015;1:e000075.
    • Perez-Ruiz F, et al. Arthritis Rheum. 2002;47:356-360.
    • Kang DH, et al. Electrolyte Blood Press. 2014;12:1-6.
    • Burns CM, et al. Ther Adv Chronic Dis. 2012;3:271-286.
    • Shoji A, et al. Arthritis Rheum. 2004;51:321-325.
    • Maiuolo J, et al. Int J Cardiol. 2016;213:8-14.
    • Vargas-Santos AB, et al. Am J Kidney Dis. 2017;70:422-439.
    • Schumacher HR Jr, et al. Arthritis Rheumatol. 2008;59:1540-1548.
    • Becker MA, et al. N Engl J Med. 2005;353:2450-2461.
    • FitzGerald JD, et al. Arthritis Care Res (Hoboken). 2020;72:744-760.
    • Phillips LS, et al. Ann Intern Med. 2001;135:825-834.
    • Doherty M. Rheumatology (Oxford). 2009;48(suppl 2):ii2-ii8.
    • Schett G, et al. RMD Open. 2015;1(suppl 1):e000046
    • Major TJ, et al. BMJ. 2018;363:k3951.
    • Becker MA, et al. Semin Arthritis Rheum. 2015;45:174-183.
    • Graham G, et al. Br J Clin Pharmacol. 2013;76:932-938.

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.