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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DISEASE STATE

Gout is a
systemic disease1,2

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About Uncontrolled Gout

Graphic showing how gout can affect the kidneys, heart, and spine

Gout is a type of arthritis associated with high amounts of uric acid, also known as hyperuricemia.3,4

  • When uric acid builds up, it can turn into crystals that cause painful flares, tophi, and other symptoms of gout1
  • Urate crystals can deposit almost anywhere in the body, in organs like the kidneys, heart, joints, and bones5-10
Visible buildup from gout in hand picture
Visible buildup from gout in hand picture

Urate crystal buildup isn’t always visible from the outside.

Up to 75% of the urate burden may not be detected upon physical examination11-13

Images courtesy of Dr Jürgen Rech. Green areas indicate urate crystal buildup. Individual patient presentations may vary.

Identifying uncontrolled gout in your patients14,15

Identifying patients with uncontrolled gout is the first step to getting them appropriate treatment.

Evaluate Your Gout Patients Using “STOP”2

sUA>6
Is their uric acid level >6 mg/dL?
TOPHI
Do they have nonresolving tophi?
ORAL ULT FAILURE
Have they been taking the maximum medically appropriate dose of ULTs?
PAINFUL FLARES
Have they had 2 or more painful flares in the past year?
Click to rotate
Uncontrolled gout is not defined by having all of the criteria above. KRYSTEXXA is not indicated for the treatment of pain.
sUA, serum uric acid; ULT, urate-lowering therapy.

Treating Uncontrolled Gout

While diet can help manage flares, it won’t treat the underlying cause of gout16,17

Only one-third of uric acid in the body comes from what patients eat.16,17 For many patients, urate crystal buildup is primarily due to
Gout genetics icon
Genetics
Some people are naturally prone to retaining higher levels of uric acid18
Renal icon
Renal issues
Chronic kidney disease (CKD) can make it harder for the body to remove uric acid1,19
Even an improvement in diet can lower uric acid levels by only ~1 mg/dL.20

Pharmacologic strategies to manage gout

Oral gout treatments focus on either addressing acute symptoms or reducing urate crystal levels but may not be sufficient for patients with uncontrolled gout.
acute
Acute21-23
Reduce the risk of flares
  • Antigout anti-inflammatory agent
  • Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Corticosteroids
Chronic gout icon
Chronic14,21,22
Lower uric acid levels
  • Xanthine oxidase inhibitors (XOIs)
  • Uricosurics
  • Uricase-based therapy
A marble representing the size of tophi
Tophus resolution may require years of oral therapy24

Even with a uric acid level of 5.4 mg/dL, it would take 2 years to dissolve a lump of uric acid the size of a small marble.24*

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

Help patients understand the impact of reducing their urate levels

To reduce urate crystal buildup, a patient’s sUA must be low enough for crystals to dissolve.
Graphic showing uric acid levels above 6 mg/dL are associated with increased risk of future flares and joint damage, while uric acid levels below 6 mg/dL are associated with decreased risk of future flares and joint damage
Graphic showing uric acid levels above 6 mg/dL are associated with increased risk of future flares and joint damage, while uric acid levels below 6 mg/dL are associated with decreased risk of future flares and joint damage
  • Treat-to-target guidelines recommend lowering the sUA level to a minimum of <6 mg/dL15
  • Lowering the sUA level to <5 mg/dL may be needed to more rapidly dissolve urate crystals and reduce flare frequency23,25
    • Lower sUA levels have been shown to increase the speed of tophus resolution and reduce the frequency of flares, suggesting that a lower sUA target may be preferred for patients with more severe gout23,26
The lower the sUA level, the faster urate crystal buildup will dissolve15,23

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
    • Doghramji PP, et al. Postgrad Med. 2012;124:98-109.
    • Dalbeth N, et al. Lancet. 2016;388:2039-2052.
    • Roddy E, et al. Arthritis Res Ther. 2010;12:223.
    • Edwards NL. Arthritis Rheum. 2008;58:2587-2590.
    • Aung T, et al. Patient Prefer Adherence. 2017;11:795-800.
    • Nickeleit V, et al. Nephrol Dial Transplant. 1997;12:1832-1838.
    • Klauser AS, et al. JAMA Cardiol. 2019;4:1019-1028.
    • Khanna PP, et al. J Clin Med. 2020;9:3204.
    • Pecherstorfer C, et al. ACR Open Rheumatol. 2020;2:565-572.
    • Ao J, et al. Clin Exp Ophthalmol. 2017;45:73-80.
    • 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.
    • KRYSTEXXA (pegloticase) [prescribing information] Horizon.
    • FitzGerald JD, et al. Arthritis Care Res (Hoboken). 2020;72:744-760.
    • Kang DH, et al. Electrolyte Blood Press. 2014;12:1-6.
    • Major TJ, et al. BMJ. 2018;363:k3951.
    • Doherty M. Rheumatology (Oxford). 2009;48(suppl 2):ii2-ii8.
    • Krishnan E. PLoS One. 2012;7:e50046.
    • Burns CM, et al. Ther Adv Chronic Dis. 2012;3:271-286.
    • Becker MA, et al. Semin Arthritis Rheum. 2015;45:174-183.
    • Becker MA, et al. N Engl J Med. 2005;353:2450-2461.
    • Perez-Ruiz F. Rheumatology (Oxford). 2009;48(suppl 2):ii9-ii14.
    • Perez-Ruiz F, et al. Arthritis Rheum. 2002;47:356-360.
    • Shoji A, et al. Arthritis Rheum. 2004;51:321-325.
    • Araujo EG, et al. RMD Open. 2015;1:e000075.

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.