01.04.2010 | Research article | Ausgabe 2/2010 Open Access

The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial
- Zeitschrift:
- Arthritis Research & Therapy > Ausgabe 2/2010
Electronic supplementary material
Competing interests
Authors' contributions
Introduction
Materials and methods
Subjects, study design, and procedures
Efficacy analyses
Primary efficacy endpoint
Determination of sample size
Secondary efficacy endpoints
Subgroup analyses of primary endpoint
Safety analyses
Results
Subject disposition and demographics
Variable
|
Febuxostat 40 mg daily
N = 757
|
Febuxostat 80 mg daily
N = 756
|
Allopurinol 200/300 mg daily
N = 756
|
---|---|---|---|
n (%)
|
|||
Gender
|
|||
Male
|
722 (95.4)
|
710 (93.9)
|
709 (93.8)
|
Female
|
35 (4.6)
|
46 (6.1)
|
47 (6.2)
|
Race
|
|||
American Indian or Alaska Native
|
6 (0.8)
|
10 (1.3)
|
6 (0.8)
|
Asian
|
26 (3.4)
|
25 (3.3)
|
37 (4.9)
|
Black or African American
|
83 (11.0)
|
78 (10.3)
|
67 (8.9)
|
Native Hawaiian or Other Pacific
|
|||
Islander
|
11 (1.5)
|
10 (1.3)
|
11 (1.5)
|
White
|
620 (81.9)
|
618 (81.7)
|
625 (82.7)
|
Other
|
11 (1.5)
|
15 (2.0)
|
8 (1.1)
|
Missing
|
0
|
0
|
2 (0.3)
|
Ethnicity
|
|||
Hispanic or Latino
|
47 (6.2)
|
49 (6.5)
|
53 (7.0)
|
Not Hispanic or Latino
|
710 (93.8)
|
707 (93.5)
|
702 (92.9)
|
Missing
|
0
|
0
|
1 (0.1)
|
Age (years)
|
|||
Mean ± SD
|
52.5 ± 11.68
|
53.0 ± 11.79
|
52.9 ± 11.73
|
Range
|
21 to 85
|
21 to 85
|
19 to 85
|
Body Mass Index (kg/m
2
)
|
|||
Mean ± SD
|
32.9 ± 6.37
|
32.9 ± 6.39
|
32.7 ± 6.23
|
Range
|
20 to 64
|
16 to 64
|
17 to 61
|
Alcohol Use
|
|||
Non-/Ex-drinker
|
242 (32.0)
|
243 (32.1)
|
235 (31.1)
|
Drinker (1 to 14 drinks/week)
|
515 (68.0)
|
513 (67.9)
|
521 (68.9)
|
Serum Urate (mg/dL)
|
|||
<9.0
|
283 (37.4)
|
280 (37.0)
|
274 (36.2)
|
9 to <10.0
|
225 (29.7)
|
222 (29.4)
|
252 (33.3)
|
10.0 to <11.0
|
162 (21.4)
|
159 (21.0)
|
133 (17.6)
|
11.0 to <12.0
|
58 (7.7)
|
67 (8.9)
|
64 (8.5)
|
≥12.0
|
29 (3.8)
|
28 (3.7)
|
33 (4.4)
|
Mean ± SD
|
9.6 ± 1.15
|
9.6 ± 1.20
|
9.5 ± 1.19
|
Range
|
8 to 14
|
8 to 15
|
8 to 15
|
Years with Gout
|
|||
Mean ± SD
|
12.0 ± 9.13
|
11.7 ± 9.64
|
11.2 ± 9.14
|
Range
|
0 to 53
|
0 to 51
|
0 to 48
|
Completed Previous Febuxostat Study
|
98 (12.9)
|
88 (11.6)
|
90 (11.9)
|
Renal Function
b
|
|||
Moderately Impaired
|
130 (17.2)
|
136 (18.0)
|
136 (18.0)
|
Mildly Impaired
|
349 (46.1)
|
367 (48.5)
|
365 (48.3)
|
Normal
|
278 (36.7)
|
253 (33.5)
|
255 (33.7)
|
Medical History
|
|||
Cardiovascular Disease (including hypertension)
|
421 (55.6)
|
440 (58.2)
|
436 (57.7)
|
Diabetes
|
89 (11.8)
|
113 (14.9)
|
110 (14.6)
|
Hypercholesterolemia
|
52 (6.9)
|
53 (7.0)
|
57 (7.5)
|
Hyperlipidemia
|
299 (39.5)
|
308 (40.7)
|
335 (44.3)
|
Use of Low-dose Aspirin (≤ 325 mg daily)
|
133 (17.6)
|
133 (17.6)
|
139 (18.4)
|
Efficacy analyses
Primary efficacy endpoint
Secondary efficacy endpoints
Subgroup analyses of the primary endpoint
Variable
|
Febuxostat 40 mg daily
N = 757
|
Febuxostat 80 mg daily
N = 756
|
Allopurinol 300/200 mg daily
N = 755
|
---|---|---|---|
% (n/N)
|
|||
Renal Function
a
|
|||
Moderately Impaired
|
43.1 (56/130)
|
71.3 (97/136)
|
31.6 (43/136)
|
Mildly Impaired
|
52.1 (182/349)
|
71.7 (263/367)
|
46.3 (169/365)
|
Normal
|
37.4 (104/278)
|
58.1 (147/253)
|
41.7 (106/254)
|
Baseline Serum Urate (mg/dL)
a
|
|||
<9.0
|
60.1 (170/283)
|
80.4 (225/280)
|
52.7 (144/273)
|
9.0 to <10.0
|
47.1 (106/225)
|
70.7 (157/222)
|
40.5 (102/252)
|
≥10.0
|
26.5 (66/249)
|
49.2 (125/254)
|
31.3 (72/230)
|
Baseline Tophus
a
|
|||
No
|
48.1 (284/591)
|
69.8 (414/593)
|
44.6 (271/607)
|
Yes
|
34.9 (58/166)
|
57.1 (93/163)
|
31.8 (47/148)
|
Completed Prior Febuxostat Study
a
|
|||
No
|
43.4 (286/659)
|
65.7 (439/668)
|
40.8 (271/665)
|
Yes
|
57.1 (56/98)
|
77.3 (68/88)
|
52.2 (47/90)
|
Gout flares
Safety Analyses
Rates of AEs and premature withdrawals
Febuxostat 40 mg daily
N = 757
|
Febuxostat 80 mg daily
N = 756
n (%)
|
Allopurinol 200/300 mg daily
N = 756
|
|
---|---|---|---|
Total Subjects with ≥ 1 AE
|
429 (56.7)
|
410 (54.2)
|
433 (57.3)
|
Total Subjects With at ≥ 1 Serious AE
|
19 (2.5)
|
28 (3.7)
|
31 (4.1)
|
Most Frequently (≥ 5%) Reported AEs
|
|||
Upper Respiratory Tract Infections
|
71 (9.4)
|
53 (7.0)
|
57 (7.5)
|
Liver Function Analysis
|
63 (8.3)
|
52 (6.9)
|
50 (6.6)
|
Rash
|
44 (5.8)
|
42 (5.6)
|
55 (7.3)
|
Diarrhea
|
45 (5.9)
|
47 (6.2)
|
57 (7.5)
|
Musculoskeletal and Connective Tissue Signs and Symptoms NEC
|
43 (5.7)
|
38 (5.0)
|
32 (4.2)
|
All APTC CV Events
|
|||
Number of Subjects with Events
|
0
|
3
|
3
|
Rate (%)
|
0.00
|
0.40
|
0.40
|
95% CI (%)
|
(0.000, 0.486)
|
(0.082, 1.155)
|
(0.082, 1.155)
|
APTC Events Summarized by Category
|
|||
CV Death
|
0
|
0
|
2 (0.26)
|
Nonfatal Myocardial Infarction
|
0
|
1 (0.13)
|
1 (0.13)
|
Nonfatal Stroke
|
0
|
2 (0.26)
|
0
|
All Non-APTC Events
|
|||
Number of Subjects with Events
|
10
|
9
|
7
|
Rate (%)
|
1.32
|
1.19
|
0.93
|
95% CI (%)
|
(0.635, 2.416)
|
(0.546, 2.248)
|
(0.373, 1.898)
|
Non-APTC Events Summarized by Category
|
|||
Angina
|
2 (0.26)
|
0
|
0
|
Coronary Revascularization
|
1 (0.13)
|
0
|
1 (0.13)
|
Transient Ischemic Attack
|
1 (0.13)
|
0
|
1 (0.13)
|
Cerebral Revascularization
|
0
|
0
|
0
|
Venous and Peripheral Arterial Vascular Thrombotic Event
|
0
|
2 (0.26)
|
0
|
Congestive Heart Failure
|
2 (0.26)
|
0
|
1 (0.13)
|
Arrhythmia, No Evidence of Ischemia
|
3 (0.40)
|
4 (0.53)
|
1 (0.13)
|
Other Non-APTC CV Events
|
1 (0.13)
|
3 (0.40)
|
3 (0.40)
|