Post-Authorisation Safety Study of Lesinurad

Study Overview
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Brief Summary
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Non-interventional population-based prospective cohort study in multiple databases comparing patients with gout who initiate lesinurad in combination with an existing xanthine oxidase inhibitor (XOI) (lesinurad+XOI cohort) to a propensity score-matched cohort of similar patients from the same data source who continue treatment with XOI monotherapy (XOI mono cohort). Study will characterize the cardiovascular safety of lesinurad in combination with XOI in patients with gout aged 18+ years compared with similar patients who continue XOI monotherapy. Primary objective: to assess the relative incidence of major adverse cardiac events plus hospitalization for unstable angina (MACE+ events) in patients with gout in both cohorts. Secondary objectives: to describe the characteristics of the cohorts prior to matching; to assess the relative incidence of hospitalisation for acute kidney injury between the matched cohorts; to assess the relative incidence of individual MACE+ components in the matched cohorts.

Official Title
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Post-Authorisation Safety Study of Lesinurad

Conditions
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Gout, Hyperuricemia

Intervention / Treatment
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* Drug: Zurampic®
* Drug: Control group: xanthine oxidase inhibitor monotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: More than one dispensing/prescription for an xanthine oxidase inhibotor (XOI) within the past 183 days prior to the index date and days' supply extending beyond the index date A coded diagnosis of gout at any time in the past or on the index date Age 18 years or older Continuous enrolment in the database for the past 183 days Exclusion Criteria: Patients on urate-lowering therapy medications within 6 months prior to the index date to manage gout (probenecid, benzbromarone, or pegloticase) other than an XOI (allopurinol, febuxostat) or lesinurad (not including medications to treat gout flares). Patients with severe renal impairment defined using clinical diagnostic codes (i.e., a diagnosis code of CKD stage IV, end-stage renal disease, or an indicator that eCrCl is < 30 mL/min at any time prior to the index date).

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 |
| --- | --- |
| Zurampic®<br>Patients exposed to Zurampic® plus a xanthine oxidase inhibitor (allopurinol or febuxostat) (lesinurad+XOI) | Drug: Zurampic®<br>* non-interventional study where patients are exposed to Zurampic® plus a xanthine oxidase inhibitor (allopurinol or febuxostat) during the normal course of clinical practice<br>* Other names: Substance (INN)*: lesinurad;|
| Control group: xanthine oxidase inhibitor monotherapy<br>Patients exposed to xanthine oxidase inhibitor monotherapy (allopurinol or febuxostat). | Drug: Control group: xanthine oxidase inhibitor monotherapy<br>* non-interventional study where patients are exposed to xanthine oxidase inhibitor monotherapy (allopurinol or febuxostat) during the normal course of clinical practice<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Cardiac Events (MACE+) | MACE+ is a composite endpoint comprised of: hospitalisation for non-fatal AMI, stroke, or unstable angina and cardiovascular (CV) death. CV death includes the following causes, occurring in or out of the hospital: AMI, sudden cardiac, heart failure, CV procedures, CV haemorrhage, stroke, underlying cerebrovascular cause, other CV causes. | 2 year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospitalisation for acute kidney injury (AKI) including renal failure (with AKI as the primary diagnosis) | Confirmed cases of AKI require all three of the following criteria: A diagnosis of renal injury or acute renal injury recorded as a primary hospital discharge diagnosis in the electronic database AND An increase in serum creatinine at hospital admission or within 48 hours of hospital admission defined as follows: Increase in serum creatinine by ≥ 1.5-fold from baseline where baseline is lowest value recorded within 1 year before the hospital admission date OR Decrease in estimated glomerular filtration rate (eGFR) or actual 24-hour GFR by ≥ 50% from baseline where baseline is highest value recorded within 1 year before the hospital admission date OR Estimated creatinine clearance (eCrCl) < 30 mL/min AND Absence of all the following contraindications for lesinurad patients at any time prior to the index date: A diagnosis code of chronic kidney disease stage IV or greater eCrCl < 30 mL/min recorded at any time prior to the index date | 2 year follow-up | 
| Each individual component of MACE+ | This can be the hospitalisation for non-fatal AMI, stroke, or unstable angina and cardiovascular (CV) death. | 2 year follow-up |