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Kuo C, Grainge MJ, Mallen C, Zhang W, Doherty M. Eligibility for and Prescription of Urate-Lowering Treatment in Patients With Incident Gout in England. JAMA. 2014;312(24):2684–2686. doi:10.1001/jama.2014.14484
Gout is caused by urate crystal deposition secondary to persistent hyperuricemia. Current guidelines recommend urate-lowering treatment to prevent crystal deposition and encourage crystal dissolution for patients with more severe gout or concomitant conditions.1,2 However, after the first diagnosis, it remains unclear when such treatment is appropriate. We investigated the timing of eligibility for and prescription of urate-lowering treatment following first gout diagnosis and factors associated with prescription.
Approvals with a waiver of informed consent were obtained from the Trent Multicenter Research Ethics Committee and the independent scientific advisory committee. Patients diagnosed with incident gout in 1997-2010 were identified using the Clinical Practice Research Datalink, containing anonymized information including patient demographics, diagnoses, examination findings, laboratory results, and prescribed medications from approximately 8% of the UK population.3 General practitioners in 486 English practices are trained to record these data and their recording quality has been validated.
All patients were followed up from the first date of diagnosis until death, transfer out, or August 31, 2013. Using Kaplan-Meier plots, we estimated cumulative probabilities of patients fulfilling current indications for urate-lowering treatment (multiple attacks, tophi, chronic kidney disease, urolithiasis, diuretic use)1,2 and receiving treatment. Gout diagnosis and treatment indications were ascertained using physician diagnosis, laboratory results, and prescriptions. Variations in prescription rates explained by patient-level factors (age, sex, race, individual socioeconomic status, diagnosis year, Charlson Comorbidity Index score) and practice-level factors (total and gout patient number, median birth year, sex ratio, practice region and socioeconomic status, and the proportion of patients having comorbidities included in the Charlson Comorbidity Index) were calculated using a 2-level linear model. Marginal Cox proportional hazards models allowed assessment of multiple factors (age, sex, year of diagnosis, Charlson Comorbidity Index score, and treatment indications) associated with prescription. A 2-sided P value of less than .05 was considered statistically significant. Analyses were performed using SAS version 9.3 (SAS Institute Inc).
Of 52 164 patients with incident gout, the mean age at diagnosis was 62.5 years and 73% were men. Median time to first treatment indication was 5 months (interquartile range, 0-29 months) and the cumulative probability of fulfilling any indication was 44.26% (95% CI, 43.83%-44.69%) at 0 years from diagnosis, 61.02% (95% CI, 60.60%-61.44%) at 1 year, 86.81% (95% CI, 86.49%-87.13%) at 5 years, and 94.27% (95% CI, 93.98%-94.56%) at 10 years. The cumulative probabilities for prescription at the same time points were 0%, 16.90% (95% CI, 16.58%-17.22%), 30.39% (95% CI, 29.90%-30.81%), and 40.52% (95% CI, 39.96%-41.08%) (Figure).
The median prescription rate for urate-lowering treatment among practices was 32.5% (interquartile range, 26.3%-39.3%; range, 0%-100%). Patient- and practice-level factors accounted for 7.82% and 13.49%, respectively, of total prescription variance.
Compared with not fulfilling each specific indication, most indications for treatment were associated with increased prescribing. The hazard ratio (HR) was 1.60 (95% CI, 1.55-1.65) for acute gout attacks during the first year following diagnosis, 1.87 (95% CI, 1.56-2.24) for tophi, 1.67 (95% CI, 1.60-1.74) for chronic kidney disease, and 1.57 (95% CI, 1.51-1.63) for diuretic use at diagnosis (Table).
A total of 44% of patients fulfilled indications for urate-lowering treatment at initial diagnosis, and 87% were eligible within 5 years of diagnosis. However, only a minority of those eligible were treated according to current recommendations.1,2
Examined patient- and practice-level factors accounted for only one-fifth of the variance in prescriptions. The unexplained variance may be accounted for by factors not available in the database. Recognized barriers to care include suboptimal patient and physician knowledge of gout, its treatment, and clinical recommendations, and patient and physician preferences for treatment.4,5
Study limitations include the use of general practitioner diagnosis to identify gout patients; however, gout diagnosis in this database has been validated previously.6 For modeling, we assumed that indications for treatment have equal importance, which may not be true.
In conclusion, our study supports including urate-lowering treatment in the information about gout provided to patients around the time of first diagnosis.
Corresponding Author: Weiya Zhang, PhD, Academic Rheumatology, City Hospital, Clinical Sciences Building, Nottingham NG51PB, England (firstname.lastname@example.org).
Author Contributions: Dr Kuo had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Zhang and Doherty are joint senior authors.
Study concept and design: Kuo, Zhang, Doherty.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Kuo, Zhang, Doherty.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Kuo, Grainge.
Obtained funding: Kuo, Zhang.
Administrative, technical, or material support: Mallen, Zhang, Doherty.
Study supervision: Grainge, Zhang, Doherty.
Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Zhang reported receiving personal fees from Daiichi Sankyo; and nonfinancial support from the National Institute for Health and Care Excellence, the European League Against Rheumatism, and the British Society of Rheumatology. Dr Doherty reported receiving personal fees from AstraZeneca, Menarini, Nordic Biosciences, Novartis, and Pfizer for work on gout and osteoarthritis advisory boards. No other disclosures were reported.
Funding/Support: This work was funded by the National Science Council of Taiwan project 103-2314-B-182A-070-MY2 and Chang Gung Memorial Hospital project CMRPG3A0624. The study methods and infrastructure were supported by the University of Nottingham. Dr Mallen is funded by an Arthritis Research UK clinician scientist award.
Role of the Funders/Sponsors: The sponsors of the study had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript and decision to submit the manuscript for publication.