Background/Purpose: Gout is the most common form of inflammatory arthritis and is caused by elevated serum uric acid (sUA). Allopurinol is a first-line urate-lowering therapy for patients with gout and the American College of Rheumatology guidelines recommend allopurinol dose titration to lower and maintain sUA levels <6 mg/dL. Understanding the gap between treatment guidelines and real-world dose titration patterns in patients with gout may ultimately lead to better disease management and control. Hence, the aim of this study was to understand real-world allopurinol dose-titration patterns relative to sUA levels.

Methods: This was a retrospective study using de-identified Humedica electronic medical record data from 2007 to 2015. The study cohort included gout patients (International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM: 274.xx]), aged ≥18 years on the first gout diagnosis, with at least 1 sUA result and 2 allopurinol prescriptions. An sUA episode within the study cohort was defined as allopurinol initial dosage (ID) prior to (closest) and titrated dosage (TD) after (within 30 days of) an sUA test. Study measurements included dosage (strength/day) by imputing allopurinol strength, and dose frequency, dose titration was categorized as up-titration, down-titration, or no-dosage-change by comparing ID and TD for each episode (up-titration: ID < TD; down-titration: ID > TD, no-dose-change: ID = TD). Uncontrolled episodes were defined as episodes with sUA levels ≥6 mg/dL. Prescriber’s specialty was identified from the TD prescription. Descriptive episode-level and patient-level analyses were performed.

Results: All sUA episodes (n=64,609) selected in this analysis were from 40,143 unique patients (mean age of 64 years, 73% male, and 82% Caucasian). Of all sUA episodes, 57% were uncontrolled (sUA ≥6 mg/dL). A total of 71% uncontrolled episodes had no-dosage-change (n=26,123), 21% had up-titration (n=7,823), and 7% had down-titration (n=2,704). Among no-dosage-change sUA episodes, episodes with lower dosages were uncontrolled at higher rates. Seventy-eight percent of dosage-change episodes were uncontrolled, of which 100 to 300 mg/day was the most frequent (39%) dose titration. Overall, the most frequent TD was 300 mg/day (52%) followed by 100 mg/day (36%), >100 & <300 mg/day (8%), >300 mg/day (3%), and <100 mg/day (<1%). Prescriber specialty at the time of a TD prescription was mostly primary care (77%), followed by rheumatology (13%), others/unknown (9%), and nephrology (2%). Among uncontrolled episodes, rheumatologists dose-titrated allopurinol more often than other specialists (rheumatologists [46%], nephrologists [29%], others/unknown [29%], and primary care physicians [26%]).

Conclusion: Contrary to current guidelines from the American College of Rheumatology, allopurinol dose was generally not titrated, regardless of sUA levels. This current lack of titration suggests a need for more active management of patients with gout and uncontrolled sUA, including consideration of new treatment options in addition to allopurinol.