Gout Management: Past, Present, and Future Strategies

Research ongoing to target treatment-resistant gout.

According to the US Centers for Disease Control, gout is the most common form of inflammatory arthritis among men. It presents as hot, red, swollen joints and causes excruciating pain. Due to its unpredictable tendency to recur, the disease can cause substantial losses in both quality of life and productivity.

Recent estimates of gout prevalence in the United States, dating from 2007 to 2008, indicate that more than 8 million people, or nearly 4% of the population, have experienced at least 1 gout attack. These attacks result in at least 1 million hospitalizations yearly, and more than 2 million annual outpatient physician visits.

Current treatments are limited to drugs that help reduce the severity of pain, such as nonsteroidal anti-inflammatory drugs (NSAIDs), uricosuric agents, xanthine oxidase inhibitors, colchicine, and glucocorticoids. Dietary changes (limiting intake of purine-rich foods), may also have a role in treatment. However, despite these modalities, treatment remains suboptimal.

Juraschek and colleagues reported inconsistency between real world treatment of gout and guideline recommendations. For instance, of more than 4 million patients with gout in the United States, more than 2 out of 3 patients continue to have serum uric acid levels in excess of 6 mg/dL—higher than levels recommended by current American College of Rheumatology guidelines for patients with gout. Furthermore, only approximately half of patients with gout receive urate-lowering therapy.

Several investigational treatments, including targeted treatments, are under review for treatment of patients with gout—with an emphasis on treatment-resistant gout. These include the injectable interleukin 1 inhibitors canakinumab and anakinra. Efficacy data from past trials has already led to the approval of canakinumab for treatment of gout in the European Union. In addition, the medication is available in the United States, but only for treatment of rheumatoid arthritis and (unrelatedly) a rare form of neonatal inflammatory disease.

Canakinumab

In 2 phase 3 studies of canakinumab for patients with gout, researchers evaluated pain intensity 3 days after treatment with canakinumab for an acute gout attack using a 100-mm visual analog scale. Treatments in each trial were evaluated against intra-articular injection of the steroid triamcinolone acetonide.

Compared with the steroid injection, canakinumab reduced pain intensity by a significantly greater margin (25.0 mm vs 35.7 mm; P <.0001), with a more than 10-mm advantage in favor of canakinumab.

However, less encouragingly, serious treatment related adverse events were substantially more common in patients receiving the investigational treatment than in patients receiving the steroid injection (8.0% vs 3.5%). Among reported adverse events were infections, low neutrophil counts, and low platelet counts.

Anakinra

To date, investigation of the efficacy of anakinra in the treatment of gout has been more limited than treatment investigations involving canakinumab. A pilot study conducted in 2007 and a retrospective case series of 40 patients with gout are the totality of evidence supporting the efficacy of this drug for gouty arthritis.

Results of the pilot study indicate improvements in gout symptoms in 10 patients with treatment-resistant gouty arthritis who received the medication (100 mg daily for 3 days), and all of whom experienced a rapid response in terms of pain relief. Due to the small size of the trial, no adverse events were reported.

A 40-patient retrospective series with the drug conducted in 2013 indicates efficacy in 32 male patients treated for an average of 8.7 years for gouty arthritis. These patients were all unable to use conventional therapies due to contraindications or failure of 2 or more prior main-line treatment. Of these 32 patients, 90% experienced a good response, as indicated by a more than 40-point drop on pain scales, and a significant reduction in levels of the inflammatory marker C-reactive protein. Adverse events were limited to 7 infectious events that occurred in patients who had used anakinra for several years.

Targeted Therapy in Gout

With phase 3 trials of canakinumab, and with the treatment having already been approved in Europe, interleukin-1 antagonists may eventually become available in the United States, pending FDA approval. Already, an off-label targeted treatment is available in the United States—anakinra. Although this treatment is not specifically indicated for gouty arthritis, it has nevertheless already been used for nearly a decade in certain patients with resistant forms of the disease.

References

• Centers for Disease Control and Prevention. Gout. http://www.cdc.gov/arthritis/basics/gout.html. Accessed July 2015.
• Robinson PC, Dalbeth N. Advances in pharmacotherapy for the treatment of gout. Expert Opin Pharmacother. 2015;16(4):533-546.
• Juraschek SP, Kovell LC, Miller ER rd, Gelber AC. Gout, urate-lowering therapy, and uric acid levels among adults in the United States. Arthritis Care Res (Hoboken). 2015;67(4):588-592.
• Becker MA. http://www.uptodate.com/contents/treatment-of-acute-gout?topicKey=RHEUM%2F1666&elapsedTimeMs=0&view=print&displayedView=full. Accessed July 2015.
• Kineret (anakinra) [package insert]. Stockholm, Sweden: Swedish Orphan Biovitrum AB; October 2013.
• Schlesinger N, Alten RE, Bardin T, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis. 2012;71(11):1839-1848.
• So A, De Smedt T, Revaz S, Tschopp J. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther. 2007.
• Ottaviani S, Moltó A, Ea HK, et al. Efficacy of anakinra in gouty arthritis: a retrospective study of 40 cases. Arthritis Res Ther. 2013.