Background/Purpose:

Gout is a
common chronic inflammatory condition due to hyperuricemia. Gout patients
typically have the clinical manifestation of acute painful flare attacks. While
the role of lowering serum uric acid (sUA) levels in the prevention of flares
is clearly recognized in recent gout care guidelines, only a limited number of
published studies exist about the association. To provide further evidence on
the topic, we sought to assess the risk of flares in patients with gout
according to detailed categories of sUA levels in a US managed care population.

Methods:

We
conducted a retrospective cohort study using administrative claims data from a
large US health plan of commercially insured and Medicare Advantage enrollees.
Patients were required to have evidence of gout (ICD-9-CM code 274.xx) based on
medical and pharmacy claims between January 2009 and April 2012. The 12 months
prior to the index gout claim were used to assess baseline sUA levels and patient
characteristics. Gout flares were assessed during a variable observation period
which lasted up to 2 years following the index gout claim; patients who
initiated urate-lowering therapy (ULT) in the follow-up period were censored
after the first claim for ULT. Flares were identified based on diagnoses for
gout or joint pain followed within 7 days by claims for NSAIDs, colchicine,
corticosteroids, or joint aspiration/drainage. Patients were assigned to
cohorts determined by baseline sUA level. Incidence rate ratios were calculated
for occurrence of first gout flare (using a sUA < 5.0 mg/dL reference cohort
as denominator). A Kaplan-Meier analysis and a Cox proportional hazards model were
used to assess the relationship between baseline sUA levels and risk of flares.

Results:

This
study included 18,008 patients (mean age = 55 years; 78 % male) with
gout. Patients were assigned to cohorts as follows: sUA < 5.0 mg/dL (N=1,953,
reference); sUA 5.0 to 5.9 mg/dL (N=2,046); sUA 6.0 to 6.9 mg/dL (N=2,739); sUA
7.0 to 7.9 mg/dL (N=3,487); sUA 8.0 to 8.9 mg/dL (N=3,677); and sUA ≥ 9.0
mg/dL (N=4,106). The incidence rate ratios for gout flares during the
observation period were 1.0 (reference), 1.3, 1.9, 2.4, 3.4, and 5.0,
respectively (all p < 0.01 in comparison to the reference cohort). In a Cox
proportional hazards model that adjusted for baseline characteristics, cohorts
with baseline sUA ≥ 6.0 mg/dL had a significantly higher risk of flares (HRs
ranged from 1.7 to 3.9, all p<0.001 in comparison to reference cohort). The
time to first flare in a Kaplan-Meier analysis was shorter for cohorts with
higher baseline sUA levels (Figure 1).

Conclusion:           

This
large contemporary study of gout patients in a managed care setting confirms
that patients with sUA levels ≥ 5.0 mg/dL (unadjusted analysis) or ≥
6.0 mg/dL (multivariate analysis) are at an increased risk of experiencing a
gout flare with rising sUA levels. These findings underscore the need to treat
to target as recommended by recent gout care guidelines.