Health for life

AstraZeneca and Ardea Biosciences today presented results from a large study of allopurinol, a treatment commonly used to lower uric acid in patients with gout. The LASSO (Long-term Allopurinol Safety Study evaluating Outcomes in gout patients) study was a multinational, 6-month, open, prospective observational study involving 1,735 patients with gout and was designed to evaluate the safety and efficacy of medically appropriate doses of allopurinol. Results of the LASSO study showed no new safety signals with allopurinol doses of approximately 300mg/day. The study also revealed that at the time of last dose fewer than half (43%) of patients taking allopurinol achieved the target serum uric acid (sUA) level of <6.0 mg/dL, the level recommended by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). Results of the LASSO study were presented today at the ACR Annual Meeting in San Diego, CA.

Allopurinol, the most commonly used treatment to lower blood uric acid levels in gout, is a generic treatment that has been available for more than 50 years. It is a xanthine oxidase inhibitor, a class of drugs intended to reduce the bodys production of uric acid. Allopurinol is recommended at doses between 100mg and 900mg per day, depending upon disease severity. The LASSO study encouraged investigators to increase, or titrate, the dose of allopurinol over the six months of the study to a medically appropriate dose. There was a high rate of adherence to therapy (97% across doses) and the most commonly used dose was 300mg. Approximately 45% of patients finished on the same dose as their baseline dose. Results show that even among patients titrated to final doses above the most commonly used dose of 300mg/day, approximately 46% did not reach target sUA levels of <6.0 mg/dL.

"Gout is a painful form of arthritis that is often misunderstood and inadequately treated. The LASSO study demonstrates that many patients with gout fail to reach the recommended treatment goal," said study co-author Nicola Dalbeth, MD of the University of Auckland. "Failing to reach the recommended sUA target leaves patients with gout at risk for further disease progression and long-term consequences of gout."

The results of this large, multinational, prospective observational study of gout are consistent with published literature confirming many patients do not reach sUA targets with allopurinol therapy as currently used.

Specific findings from LASSO include:

- The study revealed no new safety signals with allopurinol (approximately 300mg/day).
- There were no cases of allopurinol hypersensitivity syndrome in this study.
At the time of last dose 43% of all patients in the study achieved target sUA levels of <6.0 mg/dL.
- Of patients in the study at final doses above 300mg/day, approximately 54% achieved target sUA levels of <6.0 mg/dL.
- Gout is the most common form of inflammatory arthritis with a prevalence of 8 million in the U.S. Gout is commonly misrepresented as a lifestyle disease. While diet can contribute to elevated levels of uric acid, the majority of uric acid is produced by the bodys naturally occurring processes, and gout is most often caused by the inefficient excretion of uric acid by the kidneys.
- In patients with gout, abnormally high levels of uric acid in the blood known as hyperuricemia lead to deposition of needle-like crystals in joints and soft tissues throughout the body, causing inflammation. Hyperuricemia results when the kidneys do not efficiently remove enough uric acid, or when the body produces too much. A persons genetics play a significant role in their risk of developing gout. The most common symptom of gout is extremely painful arthritis. Over time, the deposits of uric acid crystals may lead to joint damage, visible nodules called tophi, and impaired quality of life. Additionally, gout has been associated with serious health problems including cardiovascular disease, diabetes and kidney damage.

What did that study show?

In yesterdays post on the role of telephonic disease management for obesity, the Disease Management Care Blog pointed out that POWER was a landmark study that demonstrated that remote lifestyle counseling performed as well as traditional face-to-face counseling.

A New England Journal of Medicine editorial accompanying the POWER article points out that there may have been an additional factor that explained the results: patient attendance at the in-person counseling sessions dropped off precipitously as the trial progressed (an average of only 2 out of 24 scheduled visits after the seventh month), while the telephonic approach achieved 16 out of 18 scheduled contacts.

The DMCB agrees and suggests this is an additional virtue of remote telephonic disease management.  While in-person counseling may have more of an individual impact, it does little good if  patients no-show.  In contrast, "high volume" telephonic counseling may have more of a population-based effect, because a lower intensity intervention has greater absolute impact if its delivered to more persons.

NIH scientist Susan Yanovskis editorial falls short on capitalizing on that insight.  While it grudgingly points out that POWER shows "PCPs can deliver safe and effective weight-loss interventions in primary care settings," it neglects to mention the two important implications of POWER:

1) non-physician team members acting collaboration with PCPs are an important resource in the national battle against obesity and

2) offering a variety of communication channels increases reach and gives more patients new and effective options to access anti-obesity programs.