Safety and efficacy of oral febuxostat for treatment of HLA-B*5801-negative gout: a randomized, open-label, multicentre, allopurinol-controlled study

Figures & data

Figure 1. Disposition of patients used to evaluate the safety and efficacy of oral febuxostat for treatment of HLA-B*5801-negative gout.

Table 1. Demographic and baseline characteristics of enrolled gout patients after the washout period (safety analysis set *).

	Febuxostat n = 54	Allopurinol n = 55	p-value
Age (years)	46.0 ± 11.0	45.2 ± 12.0	0.722
Gender			1.000
Male	53 (98.1)	53 (96.4)
Female	1 (1.9)	2 (3.6)
Palpable tophus			0.340
No	29 (53.7)	24 (43.6)
Yes	25 (46.3)	31 (56.4)
Height (cm)	169.5 ± 7.0	169.3 ± 6.3	0.927
Weight (kg)	77.4 ± 13.4	80.0 ± 14.3	0.327
BMI (kg/m^2)	26.8 ± 3.7	27.8 ± 4.2	0.201
Alcohol use			0.173
Non-drinker	37 (68.5)	44 (80.0)
Ex-drinker	5 (9.3)	1 (1.8)
Drinker †	12 (22.2)	10 (18.2)
Concentration of preferred alcoholic beverage (n = 22)			0.065
< 10%	7 (13.0)	6 (10.9)
10–30%	0 (0.0)	3 (5.5)
> 30%	5 (9.3)	1 (1.8)
Tobacco use			0.564
Non-tobacco user	36 (66.7)	37 (67.3)
Ex-tobacco user	3 (5.6)	6 (10.9)
Tobacco user	15 (27.8)	12 (21.8)
Caffeine use			0.129
Non-caffeine user	45 (83.3)	38 (69.1)
Caffeine user ‡	9 (16.7)	17 (30.9)
Previous urate-lowering therapy			0.707
No	41 (75.9)	39 (70.9)
Yes	13 (24.1)	16 (29.1)
Uric acid in urine (mg/day)	704.4 ± 459.6	727.7 ± 401.4	0.791
Urine creatinine (mg/day/kg)	20.2 ± 12.0	20.3 ± 8.5	0.947
CrCl (mL/min)	103.6 ± 64.19	105.4 ± 50.41	0.879

BMI, Body mass index; CrCl, creatinine clearance rate.

* All randomized patients who took at least one dose of the study drug.

† Alcohol drinker: 0.5–8 drinks/week.

‡ Caffeine user: 1 drink/week to 3 drinks/day.

Values are given as mean ± standard deviation (sd) or number (percentage). Continuous variables are presented as mean ± sd and compared by Student’s t-test. Categorical variables were compared with a χ² test or Fisher’s exact test.

Figure 2. Percentage change in serum urate level (mean ± sd) of gout patients before and at various times after initiation of treatment (day 1), full analysis set. * Significant difference (p < 0.05) based on a χ² test.

Table 2. Number (percentage) of enrolled gout patients with a serum urate level less than 6.0 mg/dL at different times after initiation of treatment (full analysis set *).

	Febuxostat n (%)	Allopurinol n (%)	Treatment difference % (95% CI)	p-value †
All subjects
	n = 54	n = 54
Week 2	39 (72.2)	14 (25.9)	46.3 (27.7–64.9)	< 0.001
Week 4	34 (63.0)	12 (22.2)	40.7 (21.9–59.6)	< 0.001
Week 8	38 (70.4)	13 (24.1)	46.3 (27.8–64.8)	< 0.001
Week 12	32 (59.3)	6 (11.1)	48.2 (30.7–65.6)	< 0.001
Subjects without tophi
	n = 29	n = 23
Week 2	22 (75.9)	8 (34.8)	41.1 (12.3–69.9)	0.005
Week 4	21 (72.4)	9 (39.1)	33.3 (3.7–62.9)	0.024
Week 8	23 (79.3)	7 (30.4)	48.9 (21.1–76.7)	< 0.001
Week 12	20 (69.0)	5 (21.7)	47.2 (19.5–75.0)	< 0.001
Subjects with tophi
	n = 25	n = 31
Week 2	17 (68.0)	6 (19.4)	48.7 (22.1–75.2)	< 0.001
Week 4	13 (52.0)	3 (9.7)	42.3 (16.5–68.1)	0.001
Week 8	15 (60.0)	6 (19.4)	40.7 (13.3–68.0)	0.003
Week 12	12 (48.0)	1 (3.2)	44.8 (20.6–68.9)	< 0.001

CI, Confidence interval.

* All randomized patients who took at least one dose of study drug and had at least one post-dosing assessment.

† Significant difference (p < 0.05) based on a χ² test.

Table 3. Adverse events (AEs) of enrolled gout patients during the 12-week study period (safety analysis set).

	Febuxostat (n = 54)	Allopurinol (n = 55)	p-value
Overall AEs	38 (70.4)	35 (63.6)	0.587
Overall serious AEs	2 (3.7)	1 (1.8)	0.618
Overall deaths	0 (0.0)	0 (0.0)	–
Incidence of skin rash	3 (5.6)	9 (16.4)	0.124
Incidence of gout flare	22 (40.7)	19 (34.6)	0.556
Overall drug-related AEs	8 (14.8)	7 (12.7)	0.969
Liver function test abnormal	7 (13.0)	6 (10.9)	0.776
Hyperlipidaemia	1 (1.9)	0 (0.0)	0.495
Dizziness	1 (1.9)	0 (0.0)	0.495
Dysuria	1 (1.9)	0 (0.0)	0.495
Eosinophilia	0 (0.0)	1 (1.8)	1.000
Blood triglycerides increased	0 (0.0)	1 (1.8)	1.000
AE leading to discontinuation	0 (0.0)	2 (3.6)	0.495

Values given as n (%). Categorical variables were compared by a χ² test or Fisher’s exact test.

Table 4. Changes in serum creatinine (safety analysis set).

	Febuxostat (n = 54)	Allopurinol (n = 55)	p-value*
Baseline (day 1)	1.08 ± 0.18	1.09 ± 0.18	0.637
Week 4	1.06 ± 0.18	1.06 ± 0.17‡¶	0.532
Week 8	1.03 ± 0.15†§	1.03 ± 0.16‡¶	0.317
Week 12	1.01 ± 0.17†	1.04 ± 0.17‡¶	0.634

Data are given as mean ± standard deviation.

* p-value was from Student’s t-test.

†,‡ p < 0.05 indicates a statistical difference when comparing with the baseline creatinine level for the febuxostat group (†) and the allopurinol group (‡) separately. Change from baseline for each group was assessed by a paired t-test.

§ Missing data for one patient at week 8 in the febuxostat group.

¶ Missing data for one patient at weeks 4 and 12 and two patients at week 8 in the allopurinol group.