Some science behind the scenes

TNFs

Tumor necrosis factor-alpha (TNFα) is a cytokine produced by monocytes and macrophages, two types of white blood cells. It mediates the immune response by increasing the transport of white blood cells to sites of inflammation.

TNFs inhibit this process.  Inhibition of its action by this class of drugs reduces the inflammatory response.

 TNFα is part of the immune system that protects the body from infection, as such treatment with these drugs will inevitably increase the risk of developing infections.  Latent infections can be reactivated, and the immune system may be unable to fight new infections. This has led to fatal infections.

A number of studies and reports have found adverse events in patients receiving these drugs, including serious and sometimes fatal blood disorders, serious infections caused by viruses, fungi, or bacteria, reports of lymphoma and solid tissue cancers, reports of serious liver injury, and reports of demyelinating central nervous system disorders, plus reports of cardiac failure.

The most famous drug within this category was Thalidomide, now renamed Thalomid

When Thalidomide was introduced in October 1957 it was proclaimed a "wonder drug" for insomnia, coughs, colds and headaches and was claimed to be an effective antiemetic which had an inhibitory effect on morning sickness. 

Thousands of pregnant women took the drug to relieve their symptoms.  Thalidomide was sold in a number of countries across the world from 1957 until 1961 when it was withdrawn from the market after being found to be a cause of birth defects in what has been called "one of the biggest medical tragedies of modern times". It is not known exactly how many worldwide victims of the drug there have been, although estimates range from 10,000 to 20,000.

In 1964 Jacob Sheskin, Professor at the Hebrew University of Jerusalem at Hadassah University Hospital administered thalidomide to a critically ill patient with  leprosy, in an attempt to relieve his pain in spite of the ban. It was found that thalidomide worked in leprosy by inhibiting tumor necrosis factor alpha. In 1997, Dr. Bart Barlogie reported thalidomide's initial effectiveness against multiple myeloma, and thalidomide was later approved in the United States by the FDA for use in this malignancy.

Myeloma is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies.  So as we can see, this class of drugs is targeted at the cancerous cells causing the problems.  If not treated, collections of abnormal cells accumulate in bones, where they cause bone lesions (abnormal areas of tissue), and in the bone marrow where they interfere with the production of normal blood cells. Most cases of myeloma also feature the production of a paraprotein, an abnormal antibody that can cause kidney problems and interferes with the production of normal antibodies leading to immunodeficiency. Hypercalcemia (high calcium levels) is also often encountered.

But it may now be interesting to read the observation.

Observations

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