Initiating allopurinol during an acute gout attack doesn't adversely affect the resolution of the attack, according to results of a new placebo-controlled, double-blind study.
The acute gout attack resolved after an average of 13.4 days in patients who received placebo and 15.4 days in those taking allopurinol, but the difference was not statistically significant (P=0.5), Erica H. Hill, DO, , San Antonio, Texas, and colleagues reported in the.
Action Points
- Allopurinol given during an acute gout attack does not adversely affect the resolution of the acute episode.
- Urate-lowering therapy during an acute gout attack should be accompanied by appropriate acute management.
Most patients in both groups had very low (PGA) scores, and patient-rated pain scores were relatively low for both groups even early into the study.
The results support the recommending that urate-lowering therapy can be started during an acute attack, provided patients receive effective acute management.
The analysis included patients with gout who were randomized to receive either placebo or allopurinol for 28 days. The drug was initiated at 100 mg daily (as per recommended by the ACR) for the first 14 days and then increased to 200 mg daily for the next 14 days.
The primary endpoint was time to resolution of the acute gout attack. Resolution was determined by what the authors called a "stringent" definition that included: physical examination findings of no swelling, no warmth, and tenderness of 1 or less on a 3-point Likert scale; a patient-rated pain score of 3 or less in the involved joint, or 50% reduction from study initiation; and no new inflammation in any other joints.
The primary physician was allowed to determine the appropriate treatment for the acute gout attack, based on its severity, joints involved, and patient preference.
Of the 37 patients randomized, two were excluded from the analysis, and of the remaining subjects, 31 completed the study: 17 in the placebo and 14 in the allopurinol groups.
In addition to the study drug, all patients were given prophylactic colchicine, except one placebo patient who took meloxicam.
In addition to a nonsignificant between-group difference in resolution of the gout attack, the analysis demonstrated that both groups had similar patient-rated pain scores at enrollment and at day 28. Both groups reported low pain scores by days 3 to 4, with a mean of 1.79 in the placebo group and 2.0 in the allopurinol group. The difference in PGA scores between the groups was not significant at any point during the study.
Allopurinol was well tolerated with one serious adverse event reported. One subject experienced recurrent epistaxis requiring nasal packing.
"Based on our results and clinical experience, we advocate starting allopurinol only if the patient meets the standard indications for beginning urate-lowering therapy and with the dose titration as recommended by the ACR 2012 guidelines," said the authors.
In the past, allopurinol was not started during an acute gout attack. It was thought that delaying initiation of urate-lowering drugs could prevent a change in serum uric acid level that might precipitate an acute attack or substantially worsen an ongoing attack.
Although the study wasn't designed to determine the benefits, if any, of initiating allopurinol concomitant with treatment for an acute attack, doing so has the potential to decrease healthcare costs, said the authors. An estimated 8 million Americans have been diagnosed with gout and its prevalence is increasing. The yearly outpatient costs in the U.S. associated with gout was estimated to be as high as $1 billion annually with a third of these costs directly attributed to acute gouty arthritis attacks.
A potential limitation to the study was the non-uniform approach to treating the acute gout attack. Since the study excluded certain groups -- for example, those with a glomerular filtration rate (GFR) of less than 50 mL/min and those with aspartate and alanine aminotransferases (AST/ALT) or alkaline phosphatase greater than 1.25 times the upper limit of normal -- results may not be generalizable to other populations or to those receiving initial drug doses of over 100 mg per day. As well, there could have been unblinding during the study (investigators correctly "guessed" patient randomization prior to unblinding 85% of the time).
Disclosures
The authors declare no conflict of interest.
Primary Source
Journal of Clinical Rheumatology
Hill EM, et al "Does starting allopurinol prolong acute treated gout? A randomized clinical trial" J Clin Rheumatol 2015; DOI: 10.1097/RHU.0000000000000235.