Session Information
Date: Sunday, November 13, 2016
Session Title: Metabolic and Crystal Arthropathies - Poster I: Clinical Practice
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Numerous epidemiologic studies show that hyperuricemia and gout are associated with increased mortality while treatment with allopurinol is associated with reduced mortality. Studies examining surrogate markers of cardiovascular risk indicate that allopurinol may have a beneficial dose effect. Our objective was to determine whether allopurinol dose escalation is associated with decreased all-cause and cause-specific mortality relative to non-escalation.Methods:
In this 10-year observational, new user, active-comparator study of U.S. Veterans with gout and ≥ 40 years of age, we used propensity score matching with Cox proportional hazards and competing risks regression to compare all-cause and cause-specific mortality between allopurinol dose-escalators and non-escalators. National VA data was linked to the National Death Index to determine dose escalation and mortality outcomes.Results:
After matching, all characteristics were well balanced between groups. Among 6,009 dose escalators and 6,009 matched non-escalators, there were 2,133 deaths during observation corresponding to a mortality rate of 46.8 per 1,000 person-years. There were no differences between groups in all-cause mortality (HR 0.97; 95% CI 0.89 to 1.05, Figure 1), cardiovascular mortality (HR 0.99; 95% CI 0.87 to 1.12), or cancer mortality (HR 0.93; 95% CI 0.75 to 1.14). Dose escalation even among dose escalators was limited with only 10% of dose escalators receiving daily allopurinol doses above 300 mg (Table 1). Consistent with incomplete dose escalation, only 31% achieved serum urate (SU) < 6.0 mg/dL after 2-years (Table 2). Sensitivity analyses limited to those achieving SU goal and their matches showed an 8% reduction in cardiovascular mortality for dose escalators relative to non-escalators although this did not reach statistical significance (HR 0.92; 95% CI 0.75 to 1.14). Conclusion:
Although no association was found between allopurinol dose escalation and reduced mortality, the findings were likely limited by suboptimal dose escalation observed in practice even among dose escalators. Other study designs should be considered for further investigation of the potentially beneficial effect of allopurinol on mortality.
Table 1 Baseline and Follow-up Allopurinol Dosing by Group
|
Baseline |
|
Follow-up |
|||
| Allopurinol Dose* |
Dose Escalators (n = 6,009) |
Non-Escalators (n = 6,009) |
|
Dose Escalators (n = 6,009) |
Non-Escalators† (n = 6,009) |
|
≤ 100 |
75% |
76% |
|
1% |
78% |
|
> 100 & < 300 |
20% |
19% |
|
38% |
18% |
|
300 |
5% |
5% |
|
51% |
5% |
|
> 300 |
<1% |
<1% |
|
10% |
<1% |
| Totals may add to more than 100% due to rounding. * Dose represents the average daily dose with allopurinol equivalents used for febuxostat in follow-up calculations. † A small proportion of non-escalators (3.5%) had their dose decreased during the 2-year follow-up. | |||||
Table 2 Follow-up Serum Urate (SU) by Group
|
Dose Escalators (n = 6,009) |
Non-Escalators (n = 6,009) |
|
|
SU Tested |
91% |
77% |
|
At SU Goal < 6.0 mg/dL* |
31% |
12% |
|
Follow-up SU, mean mg/dL |
6.9 ± 1.9 |
7.6 ± 1.7 |
| Values are percentages and mean ± SD. Only the last value on record for follow-up was used if there were multiple. * Calculation includes those missing SU tests. Among only those with follow-up testing 34% of dos e escalators and 16% of non-escalators were at SU goal. |
||
Disclosure: B. W. Coburn, None; K. Michaud, None; D. A. Berman, None; T. R. Mikuls, None.
To cite this abstract in AMA style:
Coburn BW, Michaud K, Berman DA, Mikuls TR. Allopurinol Dose Escalation and Mortality Among Patients with Gout: A National Propensity-Matched Cohort Study [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/allopurinol-dose-escalation-and-mortality-among-patients-with-gout-a-national-propensity-matched-cohort-study/. Accessed March 23, 2023.« Back to 2016 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/allopurinol-dose-escalation-and-mortality-among-patients-with-gout-a-national-propensity-matched-cohort-study/