Predictors of reaching a serum uric acid goal in patients with gout and treated with febuxostat

Figures & data

Table 1 Attrition table for study cohort

Criteria, n (%)	Subjects excluded	Subjects remaining
Inclusion criteria
History of a paid claim for a febuxostat prescription processed through the pharmacy benefit with a service date between February 1, 2009, and December 31, 2013		9,108 (100.0)
>1 medical claim with a gout diagnosis code (ICD9 code: 274.xx) in any position during the 12-month pre-index period or within 30 days after the index date	1,861 (20.4)	7,247 (79.6)
Continuous enrollment in a fully insured commercial or Medicare Advantage with Prescription Drug plan for 12 months pre- and post-index date	3,188 (35.0)	4,059 (44.6)
A valid serum uric acid test result at least 120 days after the index date	2,593 (28.5)	1,466 (16.1)
At least one valid serum creatinine test result during the 24-month observation period	38 (0.4)	1,428 (15.7)
Age 18–89 as of the index date	26 (0.3)	1,402 (15.4)
At least one baseline serum uric acid test result (on or before index)	259 (2.8)	1,143 (12.5)
Exclusion criteria
Patients with an allopurinol claim within 12 months after the index date	328 (3.6)	815 (8.9)
Patients with a cancer diagnosis receiving no other gout medications during the 24-month observation period	83 (0.9)	732 (8.0)
Evidence of stage 5 chronic kidney disease	37 (0.4)	695 (7.6)
Patients with organ transplantation	17 (0.2)	678 (7.4)
Patients who received pegloticase <2 months prior to index	0 (0.0)	678 (7.4)
A diagnosis (one inpatient or two outpatient nondiagnostic) of HIV/AIDS or use of an HIV specific medication	0 (0.0)	678 (7.4)
Final study sample		678

Abbreviations: AIDS, acquired immune deficiency syndrome; HIV, human immunodeficiency virus.

Table 2 Group means and counts for model variables by sUA goal attainment

Parameter	sUA level (<6 mg/dL) n=356	sUA level (≥6 mg/dL) n=322	p-valuea
Age, mean (SD), years	68.8 (11.0)	67.9 (11.4)	0.3037
Gender, n (%) Female	130 (36.5)	124 (38.5)	0.5925
Raceb
White	228 (64.0)	183 (56.8)	0.0549
Black	39 (11.0)	59 (18.3)	0.0064
Hispanic and Other	17 (4.8)	11 (3.4)	0.3745
Unknown	72 (20.2)	69 (21.4)	0.6997
Geographic region, n (%)
Northeast	0 (0.0)	c	0.1364
Midwest	37 (10.4)	40 (12.4)	0.4057
South	287 (80.6)	260 (80.7)	0.9665
West	32 (9.0)	20 (6.2)	0.1747
Index febuxostat dose (40 vs 80 mg), n (%)	243 (68.3)	247 (76.7)	0.0141
Febuxostat adherence following the index date (PDC), n (SD)	0.82 (0.21)	0.59 (0.30)	<0.0001
Days on febuxostat therapy prior to sUA lab value record, n (SD)	171 (71)	126 (77)	<0.0001
Patient out-of-pocket expenditures per febuxostat scriptd	$33 ($23)	$32 ($24)	0.421
Deyo–Charlson comorbidity index, n (SD)	2.3 (2.4)	2.4 (2.2)	0.7206
RxRisk-V comorbidity index, n (SD)	7.8 (3.2)	8.0 (3.1)	0.3596
Presence of chronic kidney disease, n (%)
Stage 1	c	c	0.2166
Stage 2	c	16 (5.0)	0.0555
Stage 3	111 (31.2)	91 (28.3)	0.4066
Stage 4	41 (11.5)	41 (12.7)	0.6277
Hypertension, n (%)	321 (90.2)	300 (93.2)	0.1599
Type 2 diabetes, n (%)	156 (43.8)	162 (50.3)	0.0908
Coronary artery disease, n (%)	123 (34.6)	115 (35.7)	0.7512
Congestive heart failure, n (%)	68 (19.1)	77 (23.9)	0.127
Stroke, n (%)	52 (14.6)	48 (14.9)	0.9124
Hyperlipidemia, n (%)	293 (82.3)	264 (82.0)	0.9146
Peripheral vascular disease, n (%)	44 (12.4)	47 (14.6)	0.3936
Number of gout flares during the pre-index period, n (SD)	1.2 (1.2)	1.2 (1.3)	0.8154
Number of symptomatic gout medications, n (SD)	5.1 (5.0)	4.7 (4.7)	0.331
Urate-lowering medications, n (%)	c	c	0.8494
Thiazide diuretics, n (%)	36 (10.1)	37 (11.5)	0.5631
Use of allopurinol in the pre-index period, n (%)	217 (61.0)	187 (58.1)	0.4453
Average daily dose of allopurinol in the pre-index period, n (SD)	54 mg (79 mg)	45 mg (70 mg)	0.2308
Indication of gouty tophi in the pre-index period, n (%)	15 (4.2)	11 (3.4)	0.5893
Baseline sUA level, n (%)	7.9 (2.3)	8.8 (2.3)	<0.0001

Notes:

a Based on either a t-test or nonparametric test for continuous measures and a chi-square test for categorical measures.

b Race is available only for the Medicare population.

c Suppressed because cell count <10 in accordance with Health Insurance Portability and Accountability Act privacy rules.

d Scripts converted to 30-day equivalents, for example, a 90-day febuxostat script was counted as three scripts. $= US dollars (USD).

Abbreviations: PDC, proportion of days covered; sUA, serum uric acid.

Table 3 Parameter estimates for multivariate model of sUA goal attainment (logistic model) in the training sample

	Parameter	Parameter estimate	Adjusted odds ratio (95% CI)	p-value
Initial model (n=453)	Age	0.021	1.02 (1.00, 1.05)	0.0853
	Gender, male	−0.053	0.90 (0.55, 1.46)	0.6656
	Racea
	Black (Ref=White)	−0.160	0.89 (0.48, 1.65)	0.6176
	Hispanic (Ref=White)	−0.342	0.74 (0.13, 4.29)	0.6386
	Other (Ref=White)	0.349	1.48 (0.42, 5.30)	0.5193
	Unknown (Ref=White)	0.200	1.28 (0.67, 2.43)	0.5416
	Presence of coronary artery disease	0.279	1.32 (0.77, 2.28)	0.3145
	Presence of stroke	0.030	1.03 (0.55, 1.92)	0.9241
	Presence of hyperlipidemia	0.009	1.01 (0.57, 1.79)	0.9744
	Presence of peripheral vascular disease	−0.131	0.88 (0.46, 1.67)	0.6906
	Presence of congestive heart failure	−0.498	0.61 (0.34, 1.09)	0.0922
	Presence of chronic kidney disease	−0.130	0.88 (0.56, 1.38)	0.5733
	Presence of hypertension	−0.352	0.70 (0.31, 1.59)	0.3992
	Presence of type 2 diabetes	−0.145	0.87 (0.55, 1.37)	0.5370
	Febuxostat adherence following the index date (PDC)	0.028	1.03 (1.02, 1.04)	<0.0001
	Days on febuxostat therapy prior to sUA lab value record	0.001	1.00 (1.00, 1.01)	0.7381
	Baseline sUA level	−0.170	0.84 (0.77, 0.92)	0.0002
	Index febuxostat dose=40 mg (Ref=80 mg)	−0.115	0.80 (0.49, 1.28)	0.3427
	Allopurinol use in the pre-index period	−0.358	0.70 (0.45, 1.08)	0.1056
	RxRisk-V Score	0.016	1.02 (0.94, 1.10)	0.7120
Final model (n=453)	Febuxostat adherence following the index date (PDC)	0.029	1.03 (1.02, 1.04)	<0.0001
	Baseline sUA level	−0.180	0.84 (0.77, 0.91)	<0.0001
	Allopurinol use in the pre-index period	−0.326	0.72 (0.48, 1.10)	0.1256
Final model (180 days pre-index; n=418)	Febuxostat adherence following the index date (PDC)	0.030	1.03 (1.02, 1.04)	<0.0001
	Baseline sUA level	−0.190	0.83 (0.75, 0.91)	<0.0001
	Allopurinol use in the pre-index period	−0.542	0.58 (0.38, 0.90)	0.0150

Note:

a Race is available only for the Medicare population.

Abbreviations: PDC, proportion of days covered; sUA, serum uric acid.

Table 4 Parameter estimates for multivariate linear model of sUA in the training sample

	Parameter	Parameter estimate	95% Confidence limits	p-value
Initial model (n=453)	Age	−0.033	(−0.054, −0.013)	0.0013
	Gender=Male (Ref=Female)	0.313	(−0.097, 0.723)	0.1341
	Race=White (Ref=Unknown)	0.463	(−0.088, 1.013)	0.0995
	Race=Black (Ref=Unknown)	0.299	(−0.379, 0.976)	0.3868
	Race=Hispanic (Ref=Unknown)	1.270	(−0.365, 2.905)	0.1275
	Race=Other (Ref=Unknown)	0.443	(−0.708, 1.593)	0.4501
	Presence of coronary artery disease	0.112	(−0.349, 0.573)	0.6337
	Presence of stroke	0.180	(−0.355, 0.716)	0.5083
	Presence of hyperlipidemia	−0.237	(−0.727, 0.253)	0.3423
	Presence of peripheral vascular disease	−0.015	(−0.564, 0.535)	0.9584
	Presence of congestive heart failure	0.377	(−0.110, 0.864)	0.1286
	Presence of chronic kidney disease	−0.047	(−0.433, 0.338)	0.8090
	Presence of hypertension	−0.264	(−0.951, 0.422)	0.4491
	Presence of type 2 diabetes	0.199	(−0.196, 0.594)	0.3221
	Febuxostat adherence following the index date (PDC)	−0.045	(−0.054, −0.035)	<0.0001
	Days on febuxostat therapy prior to sUA lab value record	0.002	(−0.001, 0.006)	0.2496
	Baseline sUA level	0.183	(0.107, 0.259)	<0.0001
	Index febuxostat dose=40 mg (Ref=80 mg)	−0.006	(−0.017, 0.004)	0.2252
	Allopurinol use in the pre-index period	0.258	(−0.108, 0.624)	0.1665
	RxRisk-V Score	0.014	(−0.057, 0.084)	0.7056
Final model (n=453)	Age	−0.025	(−0.041, −0.009)	0.0021
	Presence of congestive heart failure	0.512	(0.090, 0.935)	0.0175
	Febuxostat adherence following the index date (PDC)	−0.040	(−0.046, −0.033)	<0.0001
	Baseline sUA level	0.184	(0.111, 0.257)	<0.0001
	Allopurinol use in the pre-index period	0.253	(−0.102, 0.609)	0.1621
Final Model (180 days pre-index; n=418)	Age	−0.027	(−0.043, −0.010)	0.0015
	Presence of congestive heart failure	0.496	(0.022, 0.970)	0.0401
	Febuxostat adherence following the index date (PDC)	−0.040	(−0.047, −0.033)	<0.0001
	Baseline sUA level	0.170	(0.093, 0.247)	<0.0001
	Allopurinol use in the pre-index period	0.353	(−0.017, 0.722)	0.0614

Note: Race is available only for the Medicare population.

Abbreviations: PDC, proportion of days covered; sUA, serum uric acid.

Figure 1 ROC curves for the logistic model: training and validation samples.

Abbreviation: ROC, receiver operator characteristic.

Table 5 Performance measures for predicting sUA goal attainment

	Training (n=453)	Validation (n=225)
Logistic model
Goodness-of-fit statistic	2.92 (p=0.94)	3.82 (p=0.87)
C-statistic	0.725	0.776
Linear model
R-square	0.3107	0.3344
Adjusted R-square	0.3030	0.3192
F statistic	40.30 (p<0.01)	103.40 (p<0.01)

Abbreviation: sUA, serum uric acid.

Table S1 Baseline demographics for training and validation samples

Measure	Training sample (n=453)			Validation sample (n=225)
	sUA level (<6 mg/dL)	sUA level (≥6 mg/dL)	p-value	sUA level (<6 mg/dL)	sUA level (≥6 mg/dL)	p-value
n	238	215		118	107
Age, years (SD)	69.3 (11.4)	68.3 (11.0)	0.3269	67.6 (9.9)	67.0 (12.3)	0.5849
Age category, n (%)
18–34	b	b	0.4647	0 (0.0)	b	0.1635
35–44	b	b		b	b
45–54	18 (7.6)	18 (8.4)		12 (10.2)	b
55–64	32 (13.4)	36 (16.7)		18 (15.3)	19 (17.8)
65–74	94 (39.5)	85 (39.5)		62 (52.5)	42 (39.3)
75–84	68 (28.6)	62 (28.8)		18 (15.3)	27 (25.2)
85–89	16 (6.7)	b		b	b
Gender, n (%)
Male	151 (63.4)	132 (61.4)	0.6527	75 (63.6)	66 (61.7)	0.7713
Female	87 (36.6)	83 (38.6)		43 (36.4)	41 (38.3)
Racea, n (%)
White	149 (62.6)	124 (57.7)	0.5922	79 (66.9)	59 (55.1)	0.0304
Black	29 (12.2)	38 (17.7)		10 (8.5)	21 (19.6)
Hispanic	b	b		b	b
Other	b	b		b	0 (0.0)
Unknown	50 (21.0)	44 (20.5)		22 (18.6)	25 (23.4)
Geographic region, n (%)
Northeast	0 (0.0)	b	0.3684	0 (0.0)	0 (0.0)	0.1897
Midwest	29 (12.2)	26 (12.1)		b	14 (13.1)
South	185 (77.7)	171 (79.5)		102 (86.4)	89 (83.2)
West	24 (10.1)	16 (7.4)		b	b

Notes:

a Race is available only for the Medicare population.

b Suppressed because cell count <10 in accordance with Health Insurance Portability and Accountability Act privacy rules.

Abbreviation: sUA, serum uric acid.

Table S2 Baseline clinical characteristics for training and validation samples

Measure	Training sample (n=453)			Validation sample (n=225)
	sUA level (<6 mg/dL)	sUA level (≥6 mg/dL)	p-value	sUA level (<6 mg/dL)	sUA level (≥6 mg/dL)	p-value
N	238	215		118	107
Index febuxostat dose (40 mg), n (%)	167 (70.2)	161 (74.9)	0.2622	76 (64.4)	86 (80.4)	0.0077
Febuxostat adherence following the index date (PDC), n (SD)	0.82 (0.20)	0.62 (0.31)	<0.0001	0.83 (0.21)	0.55 (0.30)	<0.0001
Days on febuxostat therapy prior to sUA lab value record, n (SD)	169 (69)	129 (73)	<0.0001	176 (76)	121 (86)	<0.0001
Patient out-of-pocket expenditures per febuxostat script, n (SD)	$34 ($23)	$31 ($22)	0.2510	$32 ($22)	$34 ($28)	0.5502
Deyo–Charlson comorbidity index, n (SD)	2.5 (2.5)	2.6 (2.3)	0.6439	2.1 (2.1)	2.1 (1.9)	0.0531
Presence of chronic kidney disease stages 1–4, n (%)	111 (46.6)	108 (50.2)	0.4447	53 (44.9)	41 (38.3)	0.3163
Stage 1	a	0 (0.0)	0.1201	a	a	0.4810
Stage 2	a	a		a	a
Stage 3	75 (31.5)	67 (31.2)		36 (30.5)	24 (22.4)
Stage 4	30 (12.6)	27 (12.6)		11 (9.3)	14 (13.1)
Presence of hypertension, n (%)	211 (88.7)	201 (93.5)	0.0734	110 (93.2)	99 (92.5)	0.8390
Presence of type 2 diabetes, n (%)	108 (45.4)	108 (50.2)	0.3016	48 (40.7)	54 (50.5)	0.1407
Presence of coronary artery disease, n (%)	84 (35.3)	76 (35.3)	0.9903	39 (33.1)	39 (36.4)	0.5928
Presence of congestive heart failure, n (%)	52 (21.8)	57 (26.5)	0.2463	16 (13.6)	20 (18.7)	0.2943
Presence of stroke, n (%)	40 (16.8)	35 (16.3)	0.8801	12 (10.2)	13 (12.1)	0.6369
Presence of hyperlipidemia, n (%)	194 (81.5)	179 (83.3)	0.6271	99 (83.9)	85 (79.4)	0.3869
Presence of peripheral vascular disease, n (%)	33 (13.9)	31 (14.4)	0.8660	11 (9.3)	16 (15.0)	0.1942
Number of gout flares during the pre-index period, n (SD)	1.2 (1.1)	1.3 (1.3)	0.5699	1.2 (1.3)	1.0 (1.2)	0.6717
Number of symptomatic gout medications (colchicine,	4.8 (4.6)	5.0 (5.0)	0.7114	5.6 (5.6)	4.2 (4.1)	0.6972
NSAIDs, glucocorticoids), n (SD)
Presence of urate-lowering medications (probenecid or sulfinpyrazone)	a	a	0.8927	a	a	0.5046
Presence of thiazide diuretics, n (%)	23 (9.7)	19 (8.8)	0.7619	13 (11.0)	18 (16.8)	0.2070
Use of allopurinol in the pre-index period, n (%)	137 (57.6)	127 (59.1)	0.7454	80 (67.8)	60 (56.1)	0.0701
Average daily dose of allopurinol in the pre-index period, n (SD)	48 mg (75 mg)	45 mg (72 mg)	0.9869	65 mg (84 mg)	45 mg (68 mg)	0.4479
Indication of gouty tophi in the pre-index period, n (%)	10 (4.2)	a	0.7936	a	a	0.5620
Baseline sUA level, n (SD)	8.0 (2.3)	9.0 (2.4)	<0.0001	7.8 (2.2)	8.5 (2.1)	0.0233

Notes:

a Suppressed because cell count <10 in accordance with Health Insurance Portability and Accountability Act privacy rules. $= US dollars (USD).

Abbreviations: NSAIDs, nonsteroidal anti-inflammatory drugs; PDC, proportion of days covered; sUA, serum uric acid.