SAFETY RESULTS

Review safety results from the pivotal clinical trials for KRYSTEXXA.

These results were obtained before the Stopping Rules were established using sUA levels as a predictive biomarker for infusion outcomes.

Post hoc analysis criteria defined using National Institute of Allergy and Infectious Diseases and Food Allergy Research and Education criteria.28

SCROLL FOR MORE

PHASE 3 SAFETY SUMMARY: ADVERSE EVENTS3

The sUA Stopping Rules were not in place during phase 3 trials

Most Common Serious Adverse Reactions Occurring in ≥5% Of Patients Treated With KRYSTEXXA3

Adverse reaction KRYSTEXXA
(n=85) na (%)
Placebo
(n=43) na (%)
Gout flares 65 (77) 35 (81)
All infusion reactions 22 (26) 2 (5)
Severe infusion reactions (anaphylaxis)28b 4 (5) 0 (0)

aIf the same subject in a given group had more than 1 occurrence in the same preferred term or event category, the subject was counted only once.3

bPost hoc analysis criteria defined using National Institute of Allergy and Infectious Diseases and Food Allergy Research and Education criteria.28

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 reported3

KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions3

Patients should be premedicated with antihistamines and corticosteroids3

Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA3

Other most common adverse reactions occurring in at least 5% of patients treated with KRYSTEXXA: nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, and vomiting3

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

In the pivotal clinical trials, no patients with infusion reactions required intubation, mechanical ventilator support, vasopressors, or hospitalization. There were no infusion-related deaths.28

GOUT FLARES OCCURRED IN BOTH KRYSTEXXA AND PLACEBO PATIENTS3

In months 4 to 6, flares in the KRYSTEXXA study arm were significantly reduced compared with months 1 to 3.2,3

In 2 pivotal clinical trials,

77%

of KRYSTEXXA
patients

81%

of placebo
patients

experienced at least 1 flare3

KRYSTEXXA (n=65/85); placebo (n=35/43)

An increase in flares is typical at the beginning of any effective antihyperuricemic treatment3

Gout flares were common in the study patients before randomization to treatment, with patients experiencing an average of 10 flares in the preceding 18 months prior to study entry3

Because of the observed initial drop in sUA with KRYSTEXXA, it is recommended to take steps to proactively manage gout flares (eg, NSAIDS, colchicine, or prednisone). It is recommended to start prophylactic treatment at least 1 week before initiation of KRYSTEXXA therapy and to continue it for at least 6 months, unless medically contraindicated or not tolerated2,3

Percentage of patients with ≥1 gout flare per 3-month period*

Uncontrolled Gout Patients

Both the KRYSTEXXA and placebo groups received chronic gout flare prophylaxis throughout the trial3

*Pooled results of the intent-to-treat population receiving KRYSTEXXA 8 mg by IV infusion every 2 weeks.

P=0.02

P=0.007

96% of patients who completed the pivotal clinical trials chose to continue receiving KRYSTEXXA in an open-label extension study.28

References
  1. Baraf HS, Becker MA, Gutierrez-Urena SR, et al. Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy. Arthritis Res Ther. 2013;15(5):R137.
  2. Sundy JS, Baraf HS, Yood RA, et al. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA. 2011;306(7):711-720.
  3. KRYSTEXXA [prescribing information]. Horizon Pharma Rheumatology LLC. September 2016.
  4. Thiele RG, Schlesinger N. Diagnosis of gout by ultrasound. Rheumatology (Oxford). 2007;46(7):1116-1121.
  5. Rees F, Hui M, Doherty M. Optimizing current treatment of gout. Nat Rev Rheumatol. 2014;10(5):271-283.
  6. Naredo E, Uson J, Jiménez-Palop M, et al. Ultrasound-detected musculoskeletal urate crystal deposition: which joints and what findings should be assessed for diagnosing gout? Ann Rheum Dis. 2014;73(8):1522-1528.
  7. Dalbeth N, House ME, Horne A, Taylor WJ. Reduced creatinine clearance is associated with early development of subcutaneous tophi in people with gout. BMC Musculoskelet Disord. 2013;14:363.
  8. Dalbeth N, Pool B, Gamble GD, et al. Cellular characterization of the gouty tophus: a quantitative analysis. Arthritis Rheum. 2010;62(5):1549-1556.
  9. Doghramji PP, Wortmann RL. Hyperuricemia and gout: new concepts in diagnosis and management. Postgrad Med. 2012;124(6):98-109.
  10. Bongartz T, Glazebrook KN, Kavros SJ, et al. Dual-energy CT for the diagnosis of gout: an accuracy and diagnostic yield study. Ann Rheum Dis. 2015;74(6):1072-1077.
  11. Schett G, Schauer C, Hoffmann M, Hermann M. Why does the gout attack stop? A roadmap for the immune pathogenesis of gout. RMD Open. 2015;1:(suppl 1):e000046.
  12. Edwards NL. Gout A. Clinical features. In: Klippel JH, Stone JH, Crofford LJ, White PH, eds. Primer on the Rheumatic Diseases. 13th ed. New York, NY: Springer; 2008:241-249.
  13. Edwards NL. Crystal-induced joint disease. In: Nabel EG. ACP Medicine: A Publication of the American College of Physicians. Hamilton, Ontario: Decker Intellectual Properties; 2012:1-16.
  14. Yu KH, Lien LC, Ho HH. Limited knee joint range of motion due to invisible gouty tophi. Rheumatology (Oxford). 2004;43(2):191-194.
  15. Dalakas MC. Inflammatory muscle diseases. N Engl J Med. 2015;372:1734-1747.
  16. Ianuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007;357:2153-2165.
  17. Parsad K, Rath D, Kundu BK. Arthritis Robustus: review of a case of an "abnormal" rheumatoid. Springerplus. 2014 Oct 16;3:606.
  18. Rada B. Neutrophil extracellular traps and microcrystals. J Immunol Res. 2017;2017:2896380.
  19. McQueen FM, Doyle A, Reeves Q, et al. Bone erosions in patients with chronic gouty arthropathy are associated with tophi but not bone oedema or synovitis: new insights from a 3 T MRI study. Rheumatology (Oxford). 2014;53(1):95-103.
  20. Choi HK, Al-Arfaj AM, Eftekhari A, et al. Dual energy computed tomography in tophaceous gout. Ann Rheum Dis. 2009;68(10):1609-1612.
  21. Park JJ, Roudier MP, Soman D, Mokadam NA, Simkin PA. Prevalence of birefringent crystals in cardiac and prostatic tissues, an observational study. BMJ Open. 2014;4(7):e005308.
  22. Popovich I, Dalbeth N, Doyle A, Reeves Q, McQueen FM. Exploring cartilage damage in gout using 3-TMRI: distribution and associations with joint inflammation and tophus deposition. Skeletal Radiol. 2014;43(7):917-924.
  23. Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431-1446.
  24. Perez-Ruiz F. Treating to target: a strategy to cure gout. Rheumatology (Oxford). 2009;48(suppl 2):ii9–ii14.
  25. Araujo EG, Bayat S, Petsch C, et al. Tophus resolution with pegloticase; a prospective dual-energy CT study. RMD Open. 2015;1(1):e000075.
  26. Schumacher HR, Becker MA, Wortmann RL, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum. 2008;59(11):1540-1548.
  27. Data on file. Horizon Pharma Rheumatology LLC; 2016.
  28. Baraf HS, Yood RA, Ottery FD, Sundy JS, Becker MA. Infusion-related reactions with pegloticase, a recombinant uricase for the treatment of chronic gout refractory to conventional therapy. J Clin Rheumatol. 2014;20(8):427-432.
  29. McDonagh EM, Thorn CF, Callaghan JT, Altman RB, Klein TE. PharmGKB summary: uric acid-lowering drugs pathway, pharmacodynamics. Pharmacogenet Genomics. 2014;24(9):464–476.
  30. Terkeltaub R, Bushinsky DA, Becker MA. Recent developments in our understanding of the renal basis of hyperuricemia and the development of novel antihyperuricemic therapeutics. Arthritis Res Ther. 2006;8(suppl 1):S4.
  31. Yood RA, Ottery FD, Irish W, Wolfson M. Effect of pegloticase on renal function in patients with chronic kidney disease: a post hoc subgroup analysis of 2 randomized, placebo-controlled, phase 3 clinical trials. BMC Res Notes. 2014;7:54.
  32. Levey AS, Bosch JP, Lewis JB, et al. Ann Intern Med. 1999;130(6):461-470.
  33. Levey AS, Stevens LA, Schmid CH, et al; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) [published correction appears in Ann Intern Med. 2011;155(6):408]. Ann Intern Med. 2009;150(9):604-612.
  34. Michels WM, Grootendorst DC, Verduijn M, et al. Clin J Am Soc Nephrol. 2010;5(6):1003-1009.
  35. Poggio ED, Wang X, Greene T, et al. J Am Soc Nephrol. 2005;16(2):459-466.
  36. Bleyer AJ, Wright D, Alcorn H. Pharmacokinetics and pharmacodynamics of pegloticase in patients with end-stage renal failure receiving hemodialysis. Clin Nephrol. 2015;83(5):286-292.
For U.S. Healthcare Professionals  |  Patient Site

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.

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.

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.

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.