Gout: A Prevalent Disease and an Unmet Medical Need |

Gout afflicts 10 million people in the U.S. (1). The global incidence of gout has doubled in the past 10 years and is expected to re-double in the next decade (2). Despite its prevalence, current treatment is a throwback to drug discovery in the 1960s (3). More than 50 years later, allopurinol remains the established first-line, single-agent treatment for gout. Recent Phase 3 trials show that only 25% of gout patients treated with allopurinol actually achieve “target levels” of uric acid that is believed to be beneficial.

Not only has the number of suffering patients increased, but treatment stagnation in gout has markedly increased morbidity and costs. For example, gout is the most common form of inflammatory arthritis, and rheumatoid arthritis (RA) is the next most common.

The introduction of effective RA treatment (so-called “Disease-Modifying Anti-Rheumatic Drugs”) have reduced RA-related hospitalizations by two-thirds over 10 years. Total healthcare costs for RA were reduced by one-third over 20 years. Over the same periods, hospitalizations for gout have doubled and overall costs have risen 68%. Adherence to ineffective drugs has dual effects of failing to relieve patient suffering and increasing overall costs.

Causes and Complications of Gout |

Gout is associated with a sustained elevation of uric acid in the blood. Uric acid is produced by the breakdown of natural substances found in normal tissues and foods. As it accumulates, uric acid is normally filtered by the kidney and excreted in urine. Thus, there exists a natural balance between the production of uric acid and its excretion. In patients with gout, this balance is altered, such that uric acid increases to abnormally high levels in blood.

Gout occurs when excess uric acid falls out of solution and form crystals. A classic gout attack is characterized by severe pain in one or more joints, leading to an excruciating attack of arthritis (or “flare”). In addition to immediately relieving pain and inflammation, gout treatment involves longer-term measures to reduce the risk of recurrent flares and deformities (4).

Gout tends to be a chronic, lifelong condition. Without treatment of hyperuricemia, flares related to crystallized uric acid can recur and lead to a destructive and deforming arthritis. These crystals can deposit in the kidney, leading to renal failure as well as painful stones comprised of crystalline uric acid. Accelerated cardiovascular disease has also been linked to sustained hyperuricemia.

Treatment of Gout: General Concepts |

Patient treatment focuses on two major areas: relief of pain and acute inflammation (“acute gout”) and prevention of recurrent attacks and complications (“chronic gout”). Acute gout is managed with pain-killers and standard anti-inflammatory drugs (such as ibuprofen, colchicine, etc.). Several new anti-inflammatory drugs are also being investigated. Management of chronic gout focuses on reducing uric acid in the blood, with a goal of reducing the overall body content of uric acid, so that the risks of future attacks and complications are minimized. In general, drugs for chronic gout work by one of two general mechanisms: either reducing uric acid production or increasing its excretion (5).

Recent advances in molecular biology and genetics, nucleotide and proteomic profiling, and metabolomics (understanding the complexity of metabolic interactions and pathways) (6) have led to rapid advances in our understanding of heretofore highly complex disorders. The Acquist Gout Program is focused on the discovery and development of novel drugs that alter both sides of the urate production/excretion equilibrium.

References |

1. Dubchak N, Falasca GF.: New and improved strategies for the treatment of gout. Int J Nephrol Cardiovasc Dis. 3:145-66, 2010. doi: 10.2147/IJNRD.S6048

2. Zhu Y, Pandya BJ, Choi HK: Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arth Rheum. 63:3136-41, 2011. doi: 10.1002/art.30520.;jsessionid=8A2DBBA138AF7D05EB73186EC2165271.f01t03

3. Rundles RW, Wyngarden JB, Hitchings GH, et al.: Effects of a xanthine oxidase inhibitor on thiopurine metabolism, hyperuricemia, and gout. Trans Am Assoc Physicians 76:126-40, 1963.

4. VanItallie TB: Gout: epitome of painful arthritis. Metabolism Clinical and Experimental 59 (Suppl 1);S32–S36, 2010.

5. Khanna D, FitzGerald JD, Khanna PP, et al.: 2012 American College of Rheumatology Guidelines for Management of Gout Part I: Systematic Non-pharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res. 64:1431–46, 2012. doi: 10.1002/acr.21772

6. Suhre K, Shin SY, Petersen AK, et al.: Human metabolic individuality in biomedical and pharmaceutical research. Nature 477:54-60, 2011. doi: 10.1038/nature10354

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