Treating Gout: Allopurinol Found Safe During Acute Attacks
When treating a patient with gout, lowering uric acid levels too quickly can cause adverse events, such as triggering an acute attack. This has led some physicians to caution against the use of Urate Lowering Therapy (ULT) until an acute attack subsides.1-4
However, a new study may dispel these claims. After comparing patients taking allopurinol, an xanthine oxidase inhibitor used for ULT, with a placebo given during an acute gout attack, researchers found a negligible difference in the amount of days the attack lasted (15.4 days for allopurinol group versus 13.4 days for control group).5 The two groups noted little difference in their experience of pain, as well.
Over the course of 4 weeks, patients with crystal-proven gout by athrocentesis (14 on allopurinol, 17 on placebo) were treated with standard prophylaxis of cochicine and nonsteroidal anti-inflammatory drugs. Some patients also received corticosteroids and/or analgesics. 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 treating physician determined therapy for the acute gout attack, wrote the authors.
The mean serum uric acid level did lower in the allopurinol group (6.42 mg/dL for allopurinol group, 8.25 mg/dL for placebo), yet both groups reported a significant drop in pain by day 3 or 4 of treatment. Pain remained similar between the two groups from onset of the attack through to the resolution.
Limitations of the study included small patient size. Patients were excluded from the study if they had a glomerular filtration rate of <50 or liver function test of >1.25 times the upper limit of normal.
The 2012 American College of Rheumatology taskforce on gout acknowledged that in clinical practice, preventing flares while lowering serum urate is an ongoing problem. Since ULT can precipitate a flare, patients often incorrectly assume that ULT is making their gout burden worse. Improving patient adherence to ULT is a significant concern for doctors as gout is a condition still largely undertreated in medical practice.1,6
Currently, there are four FDA-approved medications in the United States to lower UA levels. Allopurinol and febuxostat (Uloric), prevent the body from making urate by inhibiting xanthine oxidase, while probenecid (Probalan) and pegloticase (Krystexxa) help the body eliminate urate via the kidneys and metabolizing urate, respectively.
According to the 2012 American College of Rheumatology (ACR) Guidelines for the Management of Gout, indications for ULT include patients with any gouty tophus or tophi; patients who experience at least one attack along with continued renal impairment (chronic kidney disease II or higher); or if a patient has two or more attacks in a 12-month period.
Part 1 of the guidelines emphasizes the necessity of lowering serum urate to reduce a gout patient’s crystal burden even in the absence of clinically evident tophi; and regarded reducing and maintaining serum urate concentrations below a specific target, or “treating to target,”as paramount. The recommended target, based upon the physiological saturation of serum urate, is below 6 mg/dL, and less than 5 mg/dL in some cases when the crystal burden and associated morbidity is high.
This new research provides some evidence for the safety of such a practice, particularly in a context where corticosteroids are utilized.8 There has been anecdotal evidence, for example, that starting ULT is safe while the patient is hospitalized and on corticosteroids to assure initiation of the ULT and safe titration—after proper screening for allopurinol hypersensitivity syndrome (AHS).7 Although encouraging and consistent with anecdotal cases, initiation of ULT in all patients during an attack may not be appropriate.
But delaying treatment because of noncompliance is an issue, and initiating ULT during an acute attack could assure initiation, possibly improved compliance, and subsequently reduce the risk of future acute attacks, improving a patient's quality of life and protecting them from further pain, the study authors concluded.
The authors of the study declared no conflicts of interest.
Reporting by Thomas G. Ciccone.