Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Chronologic Age, Renal Function, and Comorbid Conditions (Physiologic Age) of Patients with Gout Did Not Increase Likelihood of Adverse Events (AEs): AGREE Study Post Hoc Analyses.

Furst1,  Daniel E., Maranian1,  Paul, Davis3,  Matthew W., Wason3,  Suman, Khanna1,  Dinesh, Terkeltaub2,  Robert

University of California Los Angeles, Los Angeles, CA
University of California San Diego, San Diego, CA
URL Pharma, Inc, Philadelphia, PA

Background:

Typical patients with gout have multiple comorbidities such as metabolic and cardiovascular (CV) disorders, hypertension, and kidney disease; concern for these conditions can make gout treatment conditions complex. This post hoc analysis was conducted to examine the relationship of age and comorbidities (renal, hepatic, CV function, and body mass index [BMI]) on the adverse event (AE) profile of patients with acute gout who were treated with colchicine.

Methods:

A phase 3 multicenter, randomized placebo-controlled trial (AGREE) compared safety and tolerability of 2 different colchicine regimens, low dose (2 × 0.6 mg initially, then 0.6 mg 1 hr later to 1.8 mg/day total) and high dose (2 × 0.6 mg initially, then 0.6 mg/hr to 4.8 mg/day total) versus placebo in patients with gout (N = 185). Data were pooled for the low-dose and high-dose groups. For the present analyses, logistic regression was undertaken using presence or absence of AEs as the dependent variable and the following as independent variables: creatinine clearance (>=60 mL/min); alanine aminotransferase and aspartate aminotransferase ([ALT, AST] above upper limit of normal [ULN]); albumin (<=3.5 g/L); alkaline phosphatase (>ULN); gout duration (years); BMI (>30); age (years); and presence or absence of CV history (eg, myocardial infarction, CV or cerebrovascular illness). Odds ratios (OR) were reported and compared. A Pearson chi-square P value <0.05 was used as the measure of statistical significance.

Results:

At baseline, patients had a mean age of 51.5 (standard deviation [SD]= 11.1) years, with a diagnosed gout duration of 10.5 (SD = 8.9) years, a BMI of 33.0 (SD = 5.7), and serum uric acid level of 8.8 (SD = 1.8) mg/dL, and had experienced >=2 acute gout flares in the 12 months before enrollment. Across the study, 83 patients (~45%) experienced an AE; most of these were mild to moderate gastrointestinal AEs (~73%). Incidence of AEs in patients treated with colchicine was not significantly affected by any of the independent variables analyzed in this study (Table). Additional sensitivity analyses using cutoffs of 3 × ULN for AST (n = 0), ALT (n = 0), and alkaline phosphatase (n = 1), and 3.0 g/L for albumin (n = 0), were not performed because numbers of patients meeting these criteria were negligible.

Table

Independent baseline variables analyzedPatients, n (%)Odds ratio95% Confidence intervalP value
Age (continuous)185 (100.0)1.000.97, 1.030.999
BMI >30125 (67.6)1.220.63, 2.370.548
Gout duration >8 years91 (49.2)1.240.68, 2.250.476
Cardiovascular history (yes/no)107 (57.8)1.130.60, 2.100.707
Creatinine clearance >=60 mL/min161 (87.0)0.870.34, 2.220.778
AST > ULN12 (6.5)1.190.31, 4.610.805
ALT > ULN31 (16.8)0.570.23, 1.440.236
Albumin <=3.5 g/L0
Alkaline phosphatase > ULN2 (1.1)1.040.06, 19.010.976

Conclusions:

In these regression analyses of 185 patients with gout in a randomized phase 3 study, there was no effect of chronologic age, gout duration, renal function (indicated by creatinine clearance), liver function (as assessed by AST, ALT, albumin, and alkaline phosphatase), presence of CV history, or obesity with the incidence of AEs following colchicine treatment (inclusive of all doses). Although additional studies would be needed to corroborate these results, these data offer reassurance regarding the safety of colchicine in patients with several comorbid conditions.

To cite this abstract, please use the following information:
Furst, Daniel E., Maranian, Paul, Davis, Matthew W., Wason, Suman, Khanna, Dinesh, Terkeltaub, Robert; Chronologic Age, Renal Function, and Comorbid Conditions (Physiologic Age) of Patients with Gout Did Not Increase Likelihood of Adverse Events (AEs): AGREE Study Post Hoc Analyses. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :147
DOI: 10.1002/art.27916

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