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

Study Overview
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Brief Summary
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The primary purpose of this study is to observe patients being treated with pegloticase in a standard healthcare setting in order to evaluate the frequency and severity of infusion reactions, anaphylaxis and immune complex related events. Additionally, serious adverse events associated with pegloticase therapy will be identified.

Detailed Description
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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.

Official Title
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Observational Study of the Use of KRYSTEXXA® (Pegloticase) in Adult Hyperuricemic Patients With Gout Refractory to Conventional Therapy

Conditions
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Refractory Chronic Gout

Intervention / Treatment
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* Biological: Pegloticase


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pegloticase<br>Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician. | Biological: Pegloticase<br>* Pegloticase 8 mg intravenous every 2 weeks<br>* Other names: KRYSTEXXA®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Infusion Reactions | 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. | 52 weeks | 
| Number of Participants With Anaphylaxis | 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: Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia). 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). | 52 weeks | 
| Number of Participants With Immune Complex-related Events | 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. | From first dose of study drug to the end of the 12-week follow-up period (63 weeks). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Normalization of Serum Uric Acid at Week 24 and Week 52 | Normalization of serum uric acid was defined as serum uric acid value less than 6 mg/dL. | Week 24 and week 52 | 
| Change From Baseline in Number of Gout Flares | 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. | Baseline, week 24 and week 48 | 
| 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 | Gout tophi are nodular deposits of urate crystals and inflammatory cells in joints, soft tissues, bones, and in some organs. | Baseline and weeks 24 and 52 |