Speaking of Cures: Is there a new cure for gout?
The first new drug for gout in 40 years has shown promising results in a large trial.
Patients who got febuxostat had lower levels of serum uric acid than those getting allopurinol, the standard medication for the painful condition, according to a report in the Dec. 8 issue of the New England Journal of Medicine.
Maybe not:
"What hasn't been established is that the clinical benefits of febuxostat compared to allopurinol after one year were statistically significant," said study author Dr. Michael A. Becker, a professor of medicine at the University of Chicago Medical Center.
While the trial, which included 762 people with gout, was "the largest study of patients with gout I know of that has ever been done," Becker said, more studies are needed to show it reduces the number of gout flare-ups and other problems associated with the disease.
According to the study, the number of gout flare ups were the same whether people used the new drug, or the old drug, allopurinol. Gouty arthritis is caused by the preciptation of uric acid crystals in the joint fluid. Uric acid is one of the by-products of protein metabolism. It's normally excreted through the kidneys into the urine. Conditions that favor preciptation of the crystals include dehydration, an elevated uric acid level (from diet, genetic tendencies, obesity, or kidney problems), and some drugs, such as thiazide diuretics - commonly used to treat high blood pressure.
For some unknown reason, gout flare ups increase when drugs to reduce uric acid levels are first begun. This appears to be the main problem with the new drug mentioned in the news article. It was better at lowering uric acid levels, but patients had more attacks of gout in the first four weeks of taking it than those who used the older allopurinol. More patients taking the new drug also dropped out of the study because of side effects. Four patients died while taking it, though the researchers felt their deaths were unrelated to the drug. The paper, however, does not describe the causes of death, so we're asked to trust their judgement on that one.
The new drug may be better at lowering uric acid levels, but it remains to be seen whether it's actually a better treatment for gout. At this stage, it looks like it isn't.
(A more detailed description of gout and its treatment, including the types of foods to avoid, can be found here.)
There is increasing data showing uric acid to be an indpendent predictor of cardiovascular disease. While they will try to get a license for the treatment of gout the real important question is does reducing uric acid reduce cardiovascular risk?
ReplyDeleteMy dad got a horrible case of gout from taking one of those blood pressure medicines. He probably wouldn't want to take a medicine that causes more and more intense flare-ups either.
ReplyDelete(I like the comments!)
I am a kidney transplant recipient who suffers from gout. Gout is, to put it mildly, no fun at all.
ReplyDeleteGout is not uncommon in long-term kidney transplant. Unfortunately, one of the common transplant anti-rejection drugs (azathioprine/imuran) causes a potentially fatal interaction when taken with allopurinol. This is because azathioprine is also a purine analog not found in human nucleic acids. Allopurinol inhibits xanthine oxidase, which stops purine metabolism. The net result is that azathioprine builds up in the body and begins to interfere with the binding of nucleic acid purines (adenine and guanine). Nucleic acids can no longer be produced, with the result that mitosis stops. This can cause, among other things, aplastic anemia due to hematopoietic stem cells stopping their function.
To put it bluntly, allopurinol + azathioprine can stop all new blood cells from being made. This can often be fatal. Luckily, stopping either the allopurinol or the azathioprine causes the condition to reverse.
In my case (yes, I know about this because it happened to me) after 6 units of blood, packed cells, and platelets, and stopping allopurinol, I was fine. But left without the choice of allopurinol as an anti-gout drug, leaving only colchicine, which works well enough but is a rather nasty alkaloid.
A very controlled diet has spared me from any serious attacks for a couple years now.
A drug like this new one, which is a nonpurine selective inhibitor of xanthine oxidase, could be interesting because if it has a very high specificity for xanthine oxidase inhibition and is not itself a purine analog, it could conceivably be used concomitantly with azathioprine if the doses were tightly controlled.
Thanks for the article!