For patients with chronic gout refractory to conventional treatments to address the significant urate burden

OPEN THEM TO THE POSSIBILITY OF COMPLETE RESOLUTION IN MONTHS, NOT YEARS¹

In the pivotal clinical trials for KRYSTEXXA® (pegloticase)*

  • 42% of patients had a complete sUA response and met the primary endpoint of maintaining sUA <6 mg/dL for 80% of the time in months 3 and 6¹
  • 45% of patients had complete resolution of at least 1 target tophus, with no new or progressive tophi¹

*See trial design in “Results With KRYSTEXXA” section.

Mechanism of Action

KRYSTEXXA offers a unique mechanism of action for treating chronic gout refractory to conventional therapy

Clinical manifestations of chronic gout and its progression are directly related to the total body burden of urate, caused by an inherent lack of uricase in patients.² Uricase converts urate to allantoin, an inert water-soluble purine metabolite readily excreted by the kidneys.¹,² Current oral ULT agents target a patient’s sUA levels by addressing the production or excretion of urate.² KRYSTEXXA works differently, by catalyzing the conversion of uric acid to allantoin, resulting in rapid elimination of urate.¹

KRYSTEXXA is not indicated for the treatment of asymptomatic hyperuricemia.

Selected Important Risk Information

Hemolysis and methemoglobinemia have been reported with KRYSTEXXA in patients with G6PD deficiency. Do not administer KRYSTEXXA to these patients.

KRYSTEXXA is not indicated in patients with asymptomatic hyperuricemia.

Results with KRYSTEXXA

KRYSTEXXA is proven to reduce uric acid compared to placebo in refractory gout patients¹

KRYSTEXXA was studied in 2 randomized, double-blind, placebo-controlled trials (N=85) lasting 6 months followed by an open-label extension. KRYSTEXXA 8 mg was administered every 2 weeks by infusion.¹

  • A complete responder was a subject who completed the study AND achieved a pUA <6 mg/dL for at least 80% of the time during months 3 and 6
  • Incomplete responders were those subjects who did not complete the study OR did not meet the primary endpoint

Primary endpoint: Achievement of statistically significant plasma uric acid (pUA) response (P<0.001)¹

Significant pUA complete response (P<0.001)¹

42% (36/85) of KRYSTEXXA patients achieved a complete pUA response vs 0% (0/43) of placebo patients (P<0.001)1,4

  • Mean baseline sUA was 10 mg/dL¹
  • Within 24 hours following the 1st infusion, mean uric acid levels were 0.7 mg/dL in patients treated with KRYSTEXXA vs 8.2 mg/dL treated with placebo¹

PRIMARY ENDPOINT: Pooled analysis if the ITT population from 2 replicate 6-month, multicenter, randomized, double-blind, placebo-controlled trials of KRYSTEXXA 8 mg by IV infusion every 2 weeks. 47% (20/43) and 38% (16/42) of KRYSTEXXA subjects met the primary endpoints vs 0% of placebo subjects (0/20 [P<0.001] and 0/23 [P=0.001], respectively.)1,4

Selected Important Risk Information

Monitor serum uric acid levels prior to infusions. KRYSTEXXA should be discontinued if levels increase to >6 mg/dL after 2 consecutive levels are observed.

In the pivotal trials, the most common serious adverse reactions were: gout flares, infusion reactions, and anaphylaxis.

Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours.

KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions.

Proven to resolve tophi within 6 months

Baseline tophus

In the pivotal trials, ∼70% of patients had at least one clinically apparent tophus (ie, detectable via physical exam) at baseline.¹

SECONDARY ENDPOINT: Pivotal trials consisted of 2 replicate, 6-month, multicenter, randomized, double-blind, placebo-controlled trials of KRYSTEXXA 8 mg by IV infusion every 2 weeks. Pooled results of ITT population receiving KRYSTEXXA 8 mg by IV infusion every 2 weeks.1,4

Phase 3 patients receiving KRYSTEXXA 8 mg q2wks who met the secondary endpoint (100% tophus resolution at 6 months). Individual presentations and results may vary.1,4

Selected Important Risk Information

Concomitant use of KRYSTEXXA and oral urate-lowering agents may blunt the rise of sUA levels. Patients should discontinue and not initiate oral urate lowering agents while taking KRYSTEXXA.

Gout flare incidence and frequency

Baseline flares

Frequency of flares was high in all groups, but more so with KRYSTEXXA during the first 3 months of treatment. Frequency diminished during the subsequent 3 months of treatment.¹

In the pivotal trials at baseline, subjects reported a mean of 10 gout flares over the prior 18 months (7 in the past 12 months).¹

§Pooled results of the ITT population receiving KRYSTEXXA 8 mg every 2 weeks.

Safety & Administration

ANAPHYLAXIS AND INFUSION REACTIONS

As with other infusion therapies, anaphylaxis and infusion reactions have been reported to occur during and after administration with KRYSTEXXA.¹

  • Anaphylaxis may occur with any infusion, including a first infusion, and generally manifest within 2 hours of the infusion. However, delayed-type hypersensitivity reactions have also been reported¹
  • KRYSTEXXA should be administered in healthcare settings and by clinicians prepared to manage these events¹
  • Patients should be pre-medicated with antihistamines and corticosteroids to minimize the risk of IRs and closely monitored for an appropriate period of time after administration of KRYSTEXXA¹

Serum urate level (sUA) can be used as a marker for predicting when a patient is losing response to KRYSTEXXA¹

Discontinuation of subsequent treatment should be considered if uric acid levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.¹

Monitor sUA before each infusion to mitigate the risk of infusion reactions.

KRYSTEXXA Administration Guidance¹††

  • It is recommended that before starting KRYSTEXXA treatment, patients discontinue oral urate-lowering medications (ULT) and not institute treatment with an oral ULT while patients are on KRYSTEXXA treatment
  • Pre-medicate patients with antihistamines and corticosteroids
  • Slowly infuse KRYSTEXXA over no less than 120 minutes
    • In the event of an infusion reaction, the infusion should be slowed, or stopped and restarted at a lower rate
    • If a severe infusion reaction occurs, discontinue infusion and institute treatment as needed
  • No dose adjustment required for sex, age, weight, or renal impairment

††For complete administration guidance, please see Full Prescribing Information and the Medication Guide.

KRYSTEXXA Connect

KRYSTEXXA Connect is our comprehensive patient support website designed to help your patients access a wide range of services throughout their treatment with KRYSTEXXA. These include:

  • A reimbursement hotline to help access therapy
  • On-call patient support specialists, offering bi-weekly reminders and general assessment
  • The KRYSTEXXA Connect Co-pay Reduction Program
  • Downloadable resources to help you prepare and administer KRYSTEXXA

IMPORTANT SAFETY INFORMATION and INDICATION

INDICATIONS AND USAGE

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.

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

IMPORTANT SAFETY INFORMATION

WARNING: ANAPHYLAXIS AND INFUSION REACTIONS

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. However, delayed-type hypersensitivity reactions have also been reported. KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions. Patients should be premedicated with antihistamines and corticosteroids. Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA. Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.

The risk of anaphylaxis and infusion reactions is higher in patients who have lost therapeutic response.

Concomitant use of KRYSTEXXA and oral urate-lowering agents may blunt the rise of sUA levels. Patients should discontinue oral urate-lowering agents and not institute therapy with oral urate-lowering agents while taking KRYSTEXXA.

In the event of anaphylaxis or infusion reaction, the infusion should be slowed, or stopped and restarted at a slower rate.

Inform patients of the symptoms and signs of anaphylaxis, and instruct them to seek immediate medical care should anaphylaxis occur after discharge from the healthcare setting.

CONTRAINDICATIONS: G6PD DEFICIENCY ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA

Screen patients for G6PD deficiency prior to starting KRYSTEXXA. Hemolysis and methemoglobinemia have been reported with KRYSTEXXA in patients with G6PD deficiency. Do not administer KRYSTEXXA to these patients.

GOUT FLARES

An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy, including treatment with KRYSTEXXA. If a gout flare occurs during treatment, KRYSTEXXA need not be discontinued. 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 studied in patients with congestive heart failure, but some patients in the clinical trials experienced exacerbation. Exercise caution when using KRYSTEXXA in patients who have congestive heart failure and monitor patients closely following infusion.

ADVERSE REACTIONS

The most commonly reported adverse reactions in clinical trials with KRYSTEXXA are gout flares, infusion reactions, nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis and vomiting.

Please see Full Prescribing Information and Medication Guide for more information.

IMPORTANT SAFETY INFORMATION and& INDICATION

INDICATIONS AND USAGE

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.

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

IMPORTANT SAFETY INFORMATION

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. However, delayed-type hypersensitivity reactions have also been reported. KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions. Patients should be premedicated with antihistamines and corticosteroids. Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA. Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.

The risk of anaphylaxis and infusion reactions is higher in patients who have lost therapeutic response.

Concomitant use of KRYSTEXXA and oral urate-lowering agents may blunt the rise of sUA levels. Patients should discontinue oral urate-lowering agents and not institute therapy with oral urate-lowering agents while taking KRYSTEXXA.

In the event of anaphylaxis or infusion reaction, the infusion should be slowed, or stopped and restarted at a slower rate.

Inform patients of the symptoms and signs of anaphylaxis, and instruct them to seek immediate medical care should anaphylaxis occur after discharge from the healthcare setting.

CONTRAINDICATIONS: G6PD DEFICIENCY ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA

Screen patients for G6PD deficiency prior to starting KRYSTEXXA. Hemolysis and methemoglobinemia have been reported with KRYSTEXXA in patients with G6PD deficiency. Do not administer KRYSTEXXA to these patients.

GOUT FLARES

An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy, including treatment with KRYSTEXXA. If a gout flare occurs during treatment, KRYSTEXXA need not be discontinued. 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 studied in patients with congestive heart failure, but some patients in the clinical trials experienced exacerbation. Exercise caution when using KRYSTEXXA in patients who have congestive heart failure and monitor patients closely following infusion.

ADVERSE REACTIONS

The most commonly reported adverse reactions in clinical trials with KRYSTEXXA are gout flares, infusion reactions, nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis and vomiting.

INDICATIONS AND USAGE

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.

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

Please see Full Prescribing Information and Medication Guide for more information.

References

  1. KRYSTEXXA Prescribing Information. Horizon Pharma plc; 2016.
  2. Edwards NL. Crystal-induced joint disease. In: Rheumatology. London, UK: Decker Intellectual Properties Inc. 2012;1-16.
  3. ZURAMPIC Prescribing Information. Ironwood Pharmaceuticals, Inc. and AstraZeneca; 2016.
  4. Sundy JS, Baraf HSB, Yood RA, et al. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment. JAMA. 2011;306(7):711-720.

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