Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Allopurinol is the first-line urate-lowering therapy (ULT) for most people with gout, but target serum uric acid (sUA) levels of <6.0 mg/dL (recommended by current ACR guidelines) are often not achieved with doses up to 300 mg/day. Data on allopurinol dose titration and its efficacy are limited. The aim of this international, multicenter, prospective study was to evaluate the efficacy of allopurinol dose titration in a real-world setting (ClinicalTrials.gov Identifier: NCT01391325).
Methods: Adult patients meeting ARA criteria for the Classification of Acute Arthritis of Primary Gout and at least 2 gout flares in the preceding year were enrolled in this 6-month study. Patients who had received ULT other than allopurinol before the trial underwent a 7-day washout period before initiating or re-initiating allopurinol therapy, which was prescribed according to approved product labels and/or institutional standards of care. The study protocol encouraged upward titration of the allopurinol dose to an optimal, medically appropriate dose as determined by the investigator. The main efficacy endpoint was the proportion of patients with a sUA level of <6.0 mg/dL at the end of the study.
Results: Dosing and sUA Levels
Table 1. Final Allopurinol Dose by Baseline Dose
|
Baseline Dose (mg/day) |
Final Allopurinol Dose (mg/day) |
||||||
|
≤100 |
>100-200 |
>200-300 |
>300-400 |
>400-500 |
>500-600 |
>600 |
|
|
≤100 (n=591) |
40 (6.8) |
90 (15.2) |
361 (61.1) |
76 (12.9) |
11 (1.9) |
12 (2.0) |
1 (0.2) |
|
>100-200 (n=395) |
5 (1.3) |
129 (32.7) |
209 (52.9) |
31 (7.8) |
14 (3.5) |
5 (1.3) |
2 (0.5) |
|
>200-300 (n=662) |
1 (0.2) |
8 (1.2) |
557 (84.1) |
55 (8.3) |
19 (2.9) |
14 (2.1) |
8 (1.2) |
|
>300-400 (n=62) |
0 (0.0) |
0 (0.0) |
2 (3.2) |
34 (54.8) |
17 (27.4) |
7 (11.3) |
2 (3.2) |
|
>400-500 (n=11) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (9.1) |
8 (72.7) |
0 (0.0) |
2 (18.2) |
|
>500-600 (n=8) |
0 (0.0) |
0 (0.0) |
2 (25.0) |
0 (0.0) |
0 (0.0) |
5 (62.5) |
1 (12.5) |
|
>600 (n=3) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
3 (100) |
Shading: percentage of patients in same dose category at last visit as at baseline. Those above the diagonal were at a higher dose level and those below the diagonal were at a lower dose level.
Table 2. Levels of sUA by Final Daily Allopurinol Dose
|
sUA Response Categories (mg/dL) |
Final Allopurinol Dose (mg/day) |
|
||||||
|
≤100 (n=46) |
>100-200 (n=227) |
>200-300 (n=1131) |
>300-400 (n=197) |
>400-500 (n=69) |
>500-600 (n=43) |
>600 (n=19) |
Total (N=1732) |
|
|
<6.0 |
6 (13.0) |
77 (33.9) |
485 (42.9) |
111 (56.3) |
40 (58.0) |
19 (44.2) |
6 (31.6) |
744 (43.0) |
|
<5.0 |
1 (2.2) |
23 (10.1) |
152 (13.4) |
44 (22.3) |
16 (23.2) |
11 (25.6) |
3 (15.8) |
250 (14.4) |
|
<4.0 |
0 (0.0) |
2 (0.9) |
27 (2.4) |
8 (4.1) |
3 (4.3) |
6 (14.0) |
1 (5.3) |
47 (2.7) |
|
<3.0 |
0 (0.0) |
0 (0.0) |
2 (0.2) |
0 (0.0) |
1 (1.4) |
0 (0.0) |
0 (0.0) |
3 (0.2) |
As shown, 54.1% (937 patients) finished on a higher dose than at baseline, but only 15.8% of patients exceeded 300 mg/day (Table 1). Another 44.8% finished at the same dose as baseline. At the time of the last dose, only 43.0% of all patients had achieved target sUA levels <6.0 mg/dL (Table 2). Even at doses above 300 mg/day, approximately 46% did not reach target sUA levels of <6.0 mg/dL.
Conclusion: In this large, multinational, prospective observational study of gout, optimal allopurinol dose escalation occurred infrequently. Fewer than 50% of patients overall achieved target sUA level <6.0 mg/dL and the majority of those with a baseline dose ≥300 mg/day did not increase their dose. These data, consistent with published literature, likely reflect real-world circumstances in which a significant proportion of patients fail to reach sUA targets with allopurinol therapy as currently used.
Disclosure:
S. Baumgartner,
Stock options AstraZeneca,
1,
Full time employment Ardea Biosciences, a wholly owned subsidiary of AstraZeneca,
3;
H. Choi,
Savient, Takeda,
2,
Takeda, AstraZeneca,
5;
N. Dalbeth,
Ardea/AstraZeneca,
5;
D. Fitz-Patrick,
Ardea Biosciences,
2;
M. Cravets,
Full time employee of Ardea Biosciences, a wholly-owned subsidiary of AstraZeneca PLC,
3;
C. Storgard,
AstraZeneca,
1,
Ardea Biosciences, a wholly owned subsidiary of AstraZeneca,
3.
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