Primary endpoint

42-percent 42-percent
42-percent

42% of patients had a complete response1

42% of patients had a complete response1

These patients maintained sUA levels below 6 mg/dL ≥80% of the time in Months 3 and 6 vs 0% for placebo (P<0.001). Approximately 24 hours after the first dose, mean sUA level in these patients was <1 mg/dL.1

Secondary endpoint

45 percent45 percent
45 percent

At 6 months 45% of patients (n = 62) achieved complete resolution of tophi (P<0.002)1

At 6 months 45% of patients (n = 62) achieved complete resolution of tophi (P<0.002)1

Safety data from pivotal clinical trials

  • 5% of patients who received KRYSTEXXA (4 out of 85) experienced severe infusion reactions (anaphylaxis) compared to 0% of patients who received placebo (0 out of 43)1‡
    • The majority of infusion reactions in the pivotal clinical trials were resolved by slowing or interrupting the infusion, and restarting at the same or a slower rate. No patients required intubation, mechanical ventilator support, or hospitalization.2

Adverse Reactions Occurring in 5% or More of Patients Treated With KRYSTEXXA Compared With Placebo1

ADVERSE REACTION (PREFERRED TERM) KRYSTEXXA
8 MG EVERY 2 WEEKS (N = 85) N* (%)
PLACEBO (N = 43) N* (%)
Gout flare 65 (77%) 35 (81%)
Infusion reaction 22 (26%) 2 (5%)
Nausea 10 (12%) 1 (2%)
Contusion or Ecchymosis 9 (11%) 2 (5%)
Nasopharyngitis 6 (7%) 1 (2%)
Constipation 5 (6%) 2 (5%)
Chest Pain 5 (6%) 1 (2%)
Anaphylaxis 4 (5%) 0 (0%)
Vomiting 4 (5%) 1 (2%)

*If the same subject in a given group had more than 1 occurrence in the same preferred term event category, the subject was counted only once.1

Most did not occur on the day of infusion and could be related to other factors (eg, concomitant medications relevant to contusion or ecchymosis, or insulin dependent diabetes mellitus).1

Post hoc analysis criteria defined using National Institute of Allergy and Infections Diseases/Food Allergy and Anaphylaxis Network Criteria.1,2

sUA: A biomarker that informs the safety and efficacy of KRYSTEXXA in clinical practice

Adapted with permission from Baraf HS et al. J Clin Rheumatol. 2014;20(8):427-432.

*Based on infusion reactions per patient.2

Monitoring protocol

Close monitoring of sUA within 48 hours prior to infusions can significantly reduce infusion reactions.1,3

sUA CAN HELP IDENTIFY PATIENTS AT RISK FOR INFUSION REACTIONS1,3

FOR USE AFTER
FIRST INFUSION

Patients Level Icons

Take a preinfusion serum uric acid measurement, preferably within 48 hours prior to each infusion.

Patients Level IconsPatients Level Icons

Continue treatment if the preinfusion sUA level is ≤6 mg/dL

Discontinue treatment if levels increase above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed

Please view the KRYSTEXXA MIRROR RCT safety and efficacy data on this site.

UNDERSTANDING THE SAFETY DATA

From pivotal clinical trials to clinical practice

Pivotal clinical trials: double-blind protocol masked the causes leading to higher infusion reaction risk2,3

  • During the pivotal clinical trials, the relationship among sUA levels, antidrug antibodies, and infusion reactions was unknown, and therefore it was not observed.
    • Antidrug antibodies are common to biologic therapies4
    • Identifying the development of antidrug antibodies is often difficult5
  • Antidrug antibodies can lead to decreased efficacy and an increased risk of infusion reactions4
    • In the pivotal clinical trials, an sUA >6 mg/dL often reflected the development of antidrug antibodies to pegloticase2,6

Types of infusion reactions in the pivotal clinical trials2

INFUSION REACTIONS FREQUENCY (%)
Hives 10.6
Chest discomfort 9.5
Chest pain 9.5
Reddening of the skin 9.5
Itching of the skin 9.5
Difficulty breathing 7.1

The majority of infusion reactions in the pivotal clinical trials were resolved by slowing or interrupting the infusion and restarting at the same or a slower rate2*

*Approximately 75% of infusion reactions with a recorded intervention.

Severity of infusion reactions in the pivotal clinical trials2†

Incidence of infusion reactions by severity in the RCT

INFUSION REACTION SEVERITY PEGLOTICASE BIWEEKLY (n = 85) N (%) PLACEBO (n = 43) n (%)
Mild 7 (8) 0
Moderate 11 (13) 2 (5)
Severe 4 (5) 0

These 4 cases of severe infusion reactions identified by investigators were retrospectively reclassified as anaphylaxis by the FDA (n = 85)2

Only the most severe episode is showing if a patient had more than 1 event.2

Thirty-nine of these patients entered the open-label extension and were treated with pegloticase.2

RCT, randomized controlled trials.

Characterization of severe infusion reactions: All were resolved on site2

PATIENT INFUSION REACTIONS TREATMENT OUTCOME
PATIENT 1 1 INFUSION REACTIONSDifficulty breathing, swelling of the tongue TREATMENTInfusion discontinued
(Benadryl®: 25 mg IV)
OUTCOMEInfusion reaction resolved
PATIENT 2 2 INFUSION REACTIONSDifficulty breathing, hives, elevated heart rate, elevated blood pressure TREATMENTInfusion discontinued
(Benadryl®, Ventolin®)
OUTCOMEInfusion reaction resolved
PATIENT 3 3 INFUSION REACTIONSFlushing, itchy skin, low blood pressure, elevated heart rate, hives§ TREATMENTInfusion discontinued
(Benadryl®, Demerol®)
OUTCOMEInfusion reaction resolved
PATIENT 4 4 INFUSION REACTIONSItchy eye, puffy eye, chest discomfort, throat irritation, joint pain, back pain TREATMENTInfusion discontinued OUTCOMEInfusion reaction resolved

§Patient did not take full premedication regimen.

Of the 4 cases reclassified as anaphylaxis, 3 likely would have been prevented using the KRYSTEXXA Monitoring Protocol

In the pivotal clinical trials, no patients with infusion reactions required intubation, mechanical ventilator support, or hospitalization. There were no infusion-related deaths

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Get more information on the
KRYSTEXXA Monitoring Protocol

Dedicated members of the KRYSTEXXA team are available to offer account and medical support.

Support for your patients

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Starting KRYSTEXXA

There are several steps that will help prepare patients for infusion and ensure proper administration of KRYSTEXXA.

Learn about patients who might benefit from KRYSTEXXA

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.

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.

  • KRYSTEXXA (pegloticase) [prescribing information] Horizon.
  • Baraf HSB, et al. J Clin Rheumatol. 2014;20;427-432.
  • Keenan RT, et al. Rheumatol Ther. 2019;6:299-304.
  • Strand V, et al. BioDrugs. 2017;31:299-316.
  • Lombardi G, et al. BMJ Open. 2016;6:1-7.
  • Sundy JS, et al. JAMA. 2011;306:711-720.
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