Interleukin‐1 antagonism in acute gout: Is targeting a single cytokine the answer?

Abstract

Despite the existence of effective treatments, persons with gout continue to experience acute attacks. Among those who had an attack during the previous year, the risk of having at least 1 recurrent attack in the following year is 69% (1). Not surprisingly, persons with gout experience diminished quality of life and work disability (2), related not only to these recurrent flares, but also to the presence of painful and at times disfiguring tophi. Given that gout is a common crystalinduced inflammatory arthritis, with up to 6.1 million US adults having gout at some point in their lifetime (3), this disease presents a substantial public health burden. Management of gout consists of the following 3 strategies: treatment of acute attacks; lowering of serum uric acid levels in order to prevent acute flares and tissue deposition of uric acid crystals (tophi); and prophylaxis against flares, particularly during the initiation of uratelowering therapy, and other strategies to prevent flares. Unfortunately, management of hyperuricemia in gout is suboptimal (4), and inappropriate treatment of acute attacks occurs frequently (1). The recommended options for management of acute attacks include agents that nonspecifically target inflammation, such as nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, corticosteroids, and possibly adrenocorticotropic hormone (ACTH) (5). Although NSAIDs and colchicine are accepted as effective treatments for gout attacks and are typically used as first-line agents for acute attacks (5), there are few placebo-controlled trials of these agents (6,7). In fact, despite its widespread use, oral colchicine was only recently (in 2009) approved by the Food and Drug Administration (FDA) for use in acute gout, an action supported by the results of a recent trial (7). While the relative efficacy of colchicine compared with NSAIDs is not known, the various NSAIDs appear to have similar benefits in acute gout. Unfortunately, NSAIDs and/or colchicine may be poorly tolerated or contraindicated in the presence of certain comorbidities. In such instances, intraarticular corticosteroids may be given for monarticular attacks, while systemic corticosteroids or ACTH may be used for polyarticular attacks or when sites not easily amenable to intraarticular injection are involved. However, the body of evidence for intraarticular corticosteroids and ACTH is poor (8). Systemic oral corticosteroids have recently been evaluated for the treatment of gout in 2 randomized placebo-controlled trials, with 1 trial evaluating prednisolone 30 mg daily and the other prednisolone 35 mg daily, both for 5 days. Both trials demonstrated equivalence to relatively standard regimens of NSAIDs (indomethacin and naproxen, respectively) (9,10). An alternate route for systemic administration of corticosteroids, intramuscular injection, was evaluated for acute gout in 2 studies (11,12). A 60 mg intramuscular triamcinolone dose with optional repeat administration demonstrated equivalent efficacy with its comparators, indomethacin and ACTH, respectively. However, both studies were small and of low quality (13). Most studies in acute gout have evaluated single drug regimens despite the regular use of combination therapies in clinical practice (8), suggesting that such practices merit further examination. While there are several effective management options for acute gout, refractory flares are a problem, particularly for persons with polyarticular and tophaceous gout. As such, multiple courses of corticosteroids are not infrequent among persons with chronic gout. Dr. Neogi’s work was supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant K23-AR-055127), an Arthritis Foundation Arthritis Investigator Award, an American College of Rheumatology Research and Education Foundation Junior Career Development Award in Geriatrics (T. Franklin Williams Scholar Award), and the Boston Claude D. Pepper Older Americans Independence Center (NIH grant P30-AG-031679). Tuhina Neogi, MD, PhD, FRCPC: Boston University School of Medicine and Boston University School of Public Health, Boston, Massachusetts. Address correspondence and reprint requests to Tuhina Neogi, MD, PhD, FRCPC, Boston University School of Medicine, Clinical Epidemiology Unit, 650 Albany Street, Suite X-200, Boston, MA 02118. E-mail: tneogi@bu.edu. Submitted for publication June 22, 2010; accepted in revised form June 24, 2010.