Observational Study of the Use of Pegloticase (KRYSTEXXA®) in Refractory Chronic Gout

This was a Phase 4, multicenter, open-label, single-arm observational study of pegloticase 8 mg administered intravenously every 2 weeks in adult hyperuricemic patients with gout refractory to conventional therapy. Study duration is approximately 63 weeks, including 51 weeks of treatment and 12 weeks of follow-up.

The design of this study follows the FDA-approved Full Prescribing Information for the use of pegloticase and allows for capturing additional data related to the safety and efficacy of pegloticase within the standard healthcare setting.

• Pegloticase (Biological), also known as KRYSTEXXA®: Pegloticase 8 mg intravenous every 2 weeks

Primary outcomes

• Number of Participants With Infusion Reactions [52 weeks]: Infusion reactions were defined as adverse events (AEs) or clusters of events, not attributable to another cause that occurred during or within 2 hours after the infusion of pegloticase. Any other case that occurred outside of the 2-hour window was categorized per Investigator discretion.
• Number of Participants With Anaphylaxis [52 weeks]: Anaphylaxis was defined using the National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria: Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized hives; pruritus or flushing; swollen lips, tongue, or uvula), and at least 1 of the following: 1. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia). 2. Reduced blood pressure (i.e., systolic blood pressure < 90 mm Hg or greater than 30% decrease from that patient's baseline) or associated symptoms of end-organ failure (e.g., hypotonia \[collapse\], syncope, incontinence).
• Number of Participants With Immune Complex-related Events [From first dose of study drug to the end of the 12-week follow-up period (63 weeks).]: Immune complex-related events were defined as any presumptive immune complex-related disorders that were confirmed by an appropriate investigation of the event and of complement markers (C3 and C4 levels). Clinical manifestations could have included skin rash, arthralgia, arthritis, proteinuria, serum sickness, and cryoglobulinemia.

Secondary outcomes

• Percentage of Participants With Normalization of Serum Uric Acid at Week 24 and Week 52 [Week 24 and week 52]: Normalization of serum uric acid was defined as serum uric acid value less than 6 mg/dL.
• Change From Baseline in Number of Gout Flares [Baseline, week 24 and week 48]: The number of gout flares occurring in the 2 weeks prior to each visit. Baseline number of flares was calculated as the average number of flares that occurred in the 6-month baseline period divided by 12 weeks.
• Number of Swollen Joints Over Time [Baseline and weeks 24 and 52]
• Number of Tender Joints Over Time [Baseline and weeks 24 and 52]
• Number of Palpable Tophi Over Time [Baseline and weeks 24 and 52]: Gout tophi are nodular deposits of urate crystals and inflammatory cells in joints, soft tissues, bones, and in some organs.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Adults (age 18 years or more) with chronic gout refractory to conventional therapy, defined as patients who have failed to normalize SUA 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.
* Patients who have made the decision, along with their treating physician, to begin treatment with KRYSTEXXA.
* Patients who are willing and able to give informed consent and adhere to visit/protocol schedules.

Exclusion Criteria:

* Glucose-6-phosphate dehydrogenase (G6PD) deficiency
* Non-compensated congestive heart failure
* Pregnancy or breast feeding
* Prior treatment with pegloticase or another recombinant uricase
* Known allergy to urate oxidase
* Prior treatment or concomitant therapy with a polyethylene glycol (PEG)-conjugated drug
* Recipient of an investigational drug within 4 weeks prior to study drug administration or plans to take an investigational agent during the study

Participant flow

Outcome results

• Number of Participants With Infusion Reactions (Primary), Count of participants, Participants: Pegloticase 42
• Number of Participants With Anaphylaxis (Primary), Count of participants, Participants: Pegloticase 5
• Number of Participants With Immune Complex-related Events (Primary), Count of participants, Participants: Pegloticase 3
• Percentage of Participants With Normalization of Serum Uric Acid at Week 24 and Week 52 (Secondary), Number, percentage of participants: Pegloticase 27.7
• Change From Baseline in Number of Gout Flares (Secondary), Mean, flares: Pegloticase -0.83 +/- 0.88
• Number of Swollen Joints Over Time (Secondary), Mean, swollen joints: Pegloticase 8.60 +/- 10.847
• Number of Tender Joints Over Time (Secondary), Mean, tender joints: Pegloticase 9.33 +/- 11.715
• Number of Palpable Tophi Over Time (Secondary), Mean, tophi: Pegloticase 13.58 +/- 18.999

Adverse events

Time frame: From first dose of study drug to the end of the 12-week follow-up period (63 weeks).

Serious adverse events by term

Other adverse events by term

• Sundy JS, Baraf HS, Yood RA, Edwards NL, Gutierrez-Urena SR, Treadwell EL, Vazquez-Mellado J, White WB, Lipsky PE, Horowitz Z, Huang W, Maroli AN, Waltrip RW 2nd, Hamburger SA, Becker MA. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA. 2011 Aug 17;306(7):711-20. doi: 10.1001/jama.2011.1169. PMID 21846852

• Study Protocol (PDF, 2011-07-11)
• Statistical Analysis Plan (PDF, 2018-03-25)

• Jeffery Nieves, PharmD, Study director, Horizon Pharma Rheumatology LLC