Letters
Eligibility for and Prescription of Urate-Lowering Treatment in Patients With Incident Gout in England Gout is caused by urate crystal deposition secondary to persistent hyperuricemia. Current guidelines recommend uratelowering 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 uratelowering treatment following first gout diagnosis and factors associated with prescription. Methods | 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 KaplanMeier 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). Results | 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, 2684
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). Discussion | A total of 44% of patients fulfilled indications for uratelowering 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
Figure. Cumulative Probability of Eligibility and Receipt of Prescription for Urate-Lowering Treatment Eligible
Not eligible
Not prescribed
Not prescribed
Prescribed
Prescribed
100
Cumulative Probability of Eligibility and Receipt of Prescription for Urate-Lowering Treatment, %
RESEARCH LETTER
80
60
40
20
0 0
1
2
3
JAMA December 24/31, 2014 Volume 312, Number 24
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a University of St. Andrews Library User on 05/13/2015
4
5
6
7
8
9
10
Years From First Diagnosis of Gout
jama.com
Letters
Table. Baseline Characteristics and Factors Associated With Prescription for Urate-Lowering Treatment No. (%) at Baselinea Follow-up, median (IQR), y Received prescription Age at diagnosis, mean (SD), y
Adjusted HR (95% CI)b
Cox proportional models were adjusted for age, sex, quintiles of index of multiple deprivation, calendar year of diagnosis (not shown), Charlson Comorbidity Index score, and indications for treatment. Similarities of patients within practices were considered by using a marginal model with robust sandwich estimate. The proportional hazards assumptions were verified through examination of log-log plots.
c
Based on recordings by practitioners; this variable was reported because there is a large racial difference in the prevalence and incidence of gout.
d
This is an overall measure of poverty in England based on the assessment of 7 domains for each area: income; employment; health and disability; education, skills, and training; barriers to housing and services; living environment; and crime. Data from 2004 were used for this analysis.
e
Includes myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, rheumatologic disease, peptic ulcer disease, mild liver disease, moderate or severe liver disease, diabetes mellitus, diabetes mellitus with chronic complications, renal diseases, any malignancy (including leukemia and lymphoma),metastaticsolidtumor,and human immunodeficiency virus infection. We calculated the Charlson ComorbidityIndexscoreforeachstudy person at diagnosis by adding scores assigned to each specific diagnosis.
f
Acute gout attack was defined as having a consultation for gout and being prescribed nonsteroid anti-inflammatory drugs, colchicine, or corticosteroid at least 3 months apart after the first diagnosis of gout. The presence of tophi and urolithiasis was based on physician diagnosis. Chronic kidney disease was defined by physician diagnosis or by renal function impairment with an estimated glomerular filtration rate (estimated by the abbreviated Modification of Diet in Renal Disease formula) of less than 60 mL/min on 2 separate occasions. Diuretic use was based on prescription.
g
Reference group is patients without an acute gout attack during the first year from diagnosis.
62.5 (15.2) 1855 (3.56)
1 [Reference]
9482 (18.18)
0.91 (0.84-1.00)
50-64
15 906 (30.49)
0.74 (0.68-0.80)
≥65
24 921 (47.77)
0.63 (0.58-0.68)
38 272 (73.37)
1.36 (1.31-1.41)
Racec 25 629 (49.13)
1 [Reference]
Black
406 (0.78)
1.24 (1.07-1.43)
Asian
190 (0.36)
0.93 (0.73-1.17)
Other
5925 (11.36)
0.97 (0.92-1.01)
20 014 (38.37)
0.87 (0.83-0.91)
10 390 (19.92)
1 [Reference]
Unknown
Unless otherwise indicated.
b
17 101 (32.78)
35-49
White
a
6 (4-9)
Eligibility for and Prescription of Urate-Lowering Treatment in Patients With Incident Gout in England Gout is caused by urate crystal deposition secondary to persistent hyperuricemia. Current guidelines recommend uratelowering 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 uratelowering treatment following first gout diagnosis and factors associated with prescription. Methods | 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 KaplanMeier 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). Results | 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, 2684
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). Discussion | A total of 44% of patients fulfilled indications for uratelowering 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
Figure. Cumulative Probability of Eligibility and Receipt of Prescription for Urate-Lowering Treatment Eligible
Not eligible
Not prescribed
Not prescribed
Prescribed
Prescribed
100
Cumulative Probability of Eligibility and Receipt of Prescription for Urate-Lowering Treatment, %
RESEARCH LETTER
80
60
40
20
0 0
1
2
3
JAMA December 24/31, 2014 Volume 312, Number 24
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a University of St. Andrews Library User on 05/13/2015
4
5
6
7
8
9
10
Years From First Diagnosis of Gout
jama.com
Letters
Table. Baseline Characteristics and Factors Associated With Prescription for Urate-Lowering Treatment No. (%) at Baselinea Follow-up, median (IQR), y Received prescription Age at diagnosis, mean (SD), y
Adjusted HR (95% CI)b
Cox proportional models were adjusted for age, sex, quintiles of index of multiple deprivation, calendar year of diagnosis (not shown), Charlson Comorbidity Index score, and indications for treatment. Similarities of patients within practices were considered by using a marginal model with robust sandwich estimate. The proportional hazards assumptions were verified through examination of log-log plots.
c
Based on recordings by practitioners; this variable was reported because there is a large racial difference in the prevalence and incidence of gout.
d
This is an overall measure of poverty in England based on the assessment of 7 domains for each area: income; employment; health and disability; education, skills, and training; barriers to housing and services; living environment; and crime. Data from 2004 were used for this analysis.
e
Includes myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, rheumatologic disease, peptic ulcer disease, mild liver disease, moderate or severe liver disease, diabetes mellitus, diabetes mellitus with chronic complications, renal diseases, any malignancy (including leukemia and lymphoma),metastaticsolidtumor,and human immunodeficiency virus infection. We calculated the Charlson ComorbidityIndexscoreforeachstudy person at diagnosis by adding scores assigned to each specific diagnosis.
f
Acute gout attack was defined as having a consultation for gout and being prescribed nonsteroid anti-inflammatory drugs, colchicine, or corticosteroid at least 3 months apart after the first diagnosis of gout. The presence of tophi and urolithiasis was based on physician diagnosis. Chronic kidney disease was defined by physician diagnosis or by renal function impairment with an estimated glomerular filtration rate (estimated by the abbreviated Modification of Diet in Renal Disease formula) of less than 60 mL/min on 2 separate occasions. Diuretic use was based on prescription.
g
Reference group is patients without an acute gout attack during the first year from diagnosis.
62.5 (15.2) 1855 (3.56)
1 [Reference]
9482 (18.18)
0.91 (0.84-1.00)
50-64
15 906 (30.49)
0.74 (0.68-0.80)
≥65
24 921 (47.77)
0.63 (0.58-0.68)
38 272 (73.37)
1.36 (1.31-1.41)
Racec 25 629 (49.13)
1 [Reference]
Black
406 (0.78)
1.24 (1.07-1.43)
Asian
190 (0.36)
0.93 (0.73-1.17)
Other
5925 (11.36)
0.97 (0.92-1.01)
20 014 (38.37)
0.87 (0.83-0.91)
10 390 (19.92)
1 [Reference]
Unknown
Unless otherwise indicated.
b
17 101 (32.78)
35-49
White
a
6 (4-9)
