Does Starting Allopurinol Prolong Acute Treated Gout?
Does Starting Allopurinol Prolong Acute Treated Gout?
Background Traditionally, allopurinol is not initiated during an acute gout attack to avoid prolonging the painful arthritis. The 2012 American College of Rheumatology Guidelines for the Management of Gout suggest that urate-lowering therapy can be started during an acute attack, based on "consensus opinion of experts, case studies, or standard of care."
Objective The aim of this study was to determine whether initiating allopurinol will adversely affect the resolution of acute, treated gout.
Methods We conducted a 28-day, placebo-controlled, double-blind study of allopurinol initiation in patients with acute gout. Patients with crystal-proven gout by arthrocentesis were enrolled if they presented to the rheumatology clinic with an acute gout attack within 72 hours from initial therapy. The patients were also required to meet at least 1 additional criterion for urate-lowering therapy including (1) the presence of gouty tophi, (2) more than 1 acute gout attack per year, (3) a history of nephrolithiasis, or (4) urate overproduction (>1000 mg in 24-hour urine collection). Patients were excluded from the study if they had a glomerular filtration rate of less than 50 or liver function test of greater than 1.25 times the upper limit of normal. The treating physician determined therapy for the acute gout attack. Standard prophylaxis, with colchicine or nonsteroidal anti-inflammatory drugs, was prescribed. Allopurinol or placebo was initiated at 100 mg daily for the first 14 days and then increased to 200 mg daily for the next 14 days. The primary end point was protocol defined days to resolution of acute gout, incorporating patient-rated joint pain and physician examination. Secondary measures included Physician Global Assessment, patient-rated pain, adverse effects of therapy, and serum uric acid.
Results Thirty-one patients (17 on placebo, 14 on allopurinol) completed the study. Both intent-to-treat and completer analyses showed only a statistically insignificant difference in days to resolution (15.4 days in the allopurinol group completers vs 13.4 days in the placebo group; P = 0.5). The secondary measures revealed that the acute phase of pain rapidly improved in both groups.
Conclusions We initiated allopurinol at low doses during an acute gout attack in patients who met criteria for starting urate-lowering therapy and did not have abnormal kidney or liver function. In this cohort, allopurinol did not prolong the acute, treated attack.
An estimated 8 million Americans have been diagnosed with gout, and its prevalence is increasing. However, studies suggest that only a minority of gout patients receive adequate treatment. The yearly outpatient costs in the United States associated with gout are estimated to be as high as $1 billion annually, with a third of these costs directly attributed to acute gouty arthritis attacks. Patients 65 years or older with a diagnosis of gout have higher health care utilization and health care costs than similarly matched patients. Following diagnosis, many patients continue to experience recurrent acute gout attacks because of lack of effective urate-lowering therapy and various triggers.
For over 30 years, allopurinol has been the mainstay of preventive treatment for recurrent gout. Traditionally, urate-lowering therapy, including allopurinol, is not initiated during an acute episode to avoid prolongation of the painful gout attack. This common practice is widely accepted among rheumatologists and primary care physicians. Standard medical references recommend delaying the initiation of urate-lowering drugs during an acute gout attack because of the hypothesized potential for a change in serum uric acid level to precipitate an acute attack or substantially worsen an ongoing attack.
Initiation of allopurinol during an acute gout attack has the potential to reduce the number of outpatient visits required, thereby increasing patient convenience and decreasing health care costs, as well as increasing adherence to long-term uric acid–lowering therapy. The 2012 American College of Rheumatology (ACR) Guidelines for the Management of Gout recommended that pharmacologic urate-lowering therapy could be started during an acute gout attack. However, this recommendation was graded evidence level C based on the consensus opinion of experts, case studies, or standard of care. To address this question, we conducted a 28-day, placebo-controlled, double-blind study of allopurinol initiation in patients receiving treatment for an acute gout attack. We designed this study to compare initiation of allopurinol during the acute attack to use of a placebo under real-world treatment conditions and included patients with various treatment regimens already in progress. The liberal use of corticosteroids for the acute attack and titrated dosing of allopurinol were not allowed in previous studies.
Abstract and Introduction
Abstract
Background Traditionally, allopurinol is not initiated during an acute gout attack to avoid prolonging the painful arthritis. The 2012 American College of Rheumatology Guidelines for the Management of Gout suggest that urate-lowering therapy can be started during an acute attack, based on "consensus opinion of experts, case studies, or standard of care."
Objective The aim of this study was to determine whether initiating allopurinol will adversely affect the resolution of acute, treated gout.
Methods We conducted a 28-day, placebo-controlled, double-blind study of allopurinol initiation in patients with acute gout. Patients with crystal-proven gout by arthrocentesis were enrolled if they presented to the rheumatology clinic with an acute gout attack within 72 hours from initial therapy. The patients were also required to meet at least 1 additional criterion for urate-lowering therapy including (1) the presence of gouty tophi, (2) more than 1 acute gout attack per year, (3) a history of nephrolithiasis, or (4) urate overproduction (>1000 mg in 24-hour urine collection). Patients were excluded from the study if they had a glomerular filtration rate of less than 50 or liver function test of greater than 1.25 times the upper limit of normal. The treating physician determined therapy for the acute gout attack. Standard prophylaxis, with colchicine or nonsteroidal anti-inflammatory drugs, was prescribed. Allopurinol or placebo was initiated at 100 mg daily for the first 14 days and then increased to 200 mg daily for the next 14 days. The primary end point was protocol defined days to resolution of acute gout, incorporating patient-rated joint pain and physician examination. Secondary measures included Physician Global Assessment, patient-rated pain, adverse effects of therapy, and serum uric acid.
Results Thirty-one patients (17 on placebo, 14 on allopurinol) completed the study. Both intent-to-treat and completer analyses showed only a statistically insignificant difference in days to resolution (15.4 days in the allopurinol group completers vs 13.4 days in the placebo group; P = 0.5). The secondary measures revealed that the acute phase of pain rapidly improved in both groups.
Conclusions We initiated allopurinol at low doses during an acute gout attack in patients who met criteria for starting urate-lowering therapy and did not have abnormal kidney or liver function. In this cohort, allopurinol did not prolong the acute, treated attack.
Introduction
An estimated 8 million Americans have been diagnosed with gout, and its prevalence is increasing. However, studies suggest that only a minority of gout patients receive adequate treatment. The yearly outpatient costs in the United States associated with gout are estimated to be as high as $1 billion annually, with a third of these costs directly attributed to acute gouty arthritis attacks. Patients 65 years or older with a diagnosis of gout have higher health care utilization and health care costs than similarly matched patients. Following diagnosis, many patients continue to experience recurrent acute gout attacks because of lack of effective urate-lowering therapy and various triggers.
For over 30 years, allopurinol has been the mainstay of preventive treatment for recurrent gout. Traditionally, urate-lowering therapy, including allopurinol, is not initiated during an acute episode to avoid prolongation of the painful gout attack. This common practice is widely accepted among rheumatologists and primary care physicians. Standard medical references recommend delaying the initiation of urate-lowering drugs during an acute gout attack because of the hypothesized potential for a change in serum uric acid level to precipitate an acute attack or substantially worsen an ongoing attack.
Initiation of allopurinol during an acute gout attack has the potential to reduce the number of outpatient visits required, thereby increasing patient convenience and decreasing health care costs, as well as increasing adherence to long-term uric acid–lowering therapy. The 2012 American College of Rheumatology (ACR) Guidelines for the Management of Gout recommended that pharmacologic urate-lowering therapy could be started during an acute gout attack. However, this recommendation was graded evidence level C based on the consensus opinion of experts, case studies, or standard of care. To address this question, we conducted a 28-day, placebo-controlled, double-blind study of allopurinol initiation in patients receiving treatment for an acute gout attack. We designed this study to compare initiation of allopurinol during the acute attack to use of a placebo under real-world treatment conditions and included patients with various treatment regimens already in progress. The liberal use of corticosteroids for the acute attack and titrated dosing of allopurinol were not allowed in previous studies.
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