Sunday, April 4, 2021

You can teach an old dog new tricks!

Colchicine is one of the longest-used remedies in the modern medical armamentarium. It was mentioned in the Ebers Papyrus, dating from Egypt in 1500 BC, and its use to treat gout was described by the ancient Greeks. It is derived from the autumn crocus, scientifically named Colchicum autumnale. The active ingredient was isolated in the early 1800’s and it has been widely used to treat gout ever since.

When I was a pup, the dictum was to treat an acute gout attack by taking one colchicine tablet every hour until either the gout was resolved or the diarrhea was so bad that the patient did not care about the gout. In the intervening years we have learned a much more civilized approach. Lower doses work just as well and have much less GI side effects.

Readers of Prescription for Bankruptcy know that colchicine is also a sordid example of pharmaceutical company greed, with this ancient remedy manipulated into becoming a high cost branded product.

My focus here, however, is to note that this “one trick pony,” which 50 years ago was considered as useful only to treat gout has become a hot new product, with a rapidly expanding portfolio of uses.

Amazingly for a product of this lineage, the exact mechanism of action of colchicine is still being studied, but it clearly has strong anti-inflammatory properties, and works to reduce the effects of the body’s white blood cells. It is this anti-inflammatory property that is being exploited to treat a broad and growing range of diseases. The first new use was to treat a rare disease, Familial Mediterranean Fever, a disease whose victims suffer repeated attacks of fever, joint and abdominal pain, and many of whom go on to develop chronic kidney failure. Two trials published in 1974 showed that colchicine could dramatically reduce the frequency of acute attacks, and it was later shown that it largely prevented the kidney disease.

A variety of rare skin diseases characterized by local inflammation also respond to colchicine. More recently, colchicine has shown the ability to reduce recurrences of pericarditis, a non-fatal but very painful inflammation of the sac surrounding the heart.

As most of you know, the leading cause of death in the U.S. and most western countries is coronary disease. While we tend to simplistically think of heart attacks as caused by build up of cholesterol deposits in the coronary arteries, inflammation has long been felt to play a part. It is thus not surprising that several trials have looked at the effect of colchicine on heart attack. Two large trials, one in patients who had recently suffered an acute heart attack and one in patients with stable coronary disease found that daily low-dose colchicine reduced the risk of heart attacks, stroke, coronary surgery and cardiovascular death. Before we anoint colchicine the Fountain of Youth, it must be noted that overall death rates were not reduced, and may have even been a bit higher, in the colchicine group than in those taking placebos.

Finally, it would be remiss in 2021 not to note the potential role of colchicine in the fight against Covid-19. You may be aware that cortisone-type drugs, which have an anti-inflammatory effect, have been proven to improve outcomes in very sick Covid-19 patients, so a trial of colchicine was obvious. A small trial done in Brazil at the beginning of the year gave colchicine or placebo for 10 days to 72 patients hospitalized with Covid-19. Those given colchicine had shorter time in the hospital and less need for oxygen. While the small size of the trial prevented conclusions about the effect on survival, the only two deaths were in the placebo group.

A much larger trial was conducted by a group from Montreal. They studied 4159 patients not sick enough initially to be hospitalized. Half were given 0.5 mg of colchicine 3 times daily for three days and then once daily for another 27 days. Since this was a less sick group, the absolute numbers were not high in either group, but the patients given colchicine had reduced rates of needing to end up in the hospital, require a ventilator or die.

Just because a drug has been around for a long time, it can still be very useful, and there are always new things to learn about it.

Prescription for Bankruptcy. Buy the book on Amazon

4 comments:

  1. Does your book explain how this "...this ancient remedy [was] manipulated into becoming a high cost branded product"?

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  2. Yes, the dramatic increase in price, from a few cents a pill to several dollars a pill is a wonderful example of pharmaceutical greed coupled to poor regulations. I detail it in the book.

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