TNF-Inhibitors: WTF

Back on April 6 of this year, I wrote a post  about an FDA report on medications used to treat inflammatory bowel diseases.  As a reminder:

“‘Drugs used to treat Crohn’s disease and other autoimmune disorders are among those with the greatest number of reported side effects filed with the U.S. Food and Drug Administration…’

It goes on to explain that, ‘Drugs which suppress the immune system to fight inflammation can cause serious and sometimes lethal infections including tuberculosis, and have been linked with blood disorders, including lymphoma, a blood cancer.’”

The FDA report examined Humira in detail, pointing out that the adverse events associated with its use are often severe (liver, blood, nervous system, cardiovascular problems…the list goes on and on), including 4,200 deaths a year.  Humira is in a class of pharmaceutical “biologics” (that also includes Remicade, Enbrel and several others) that reduce one of the body’s main pro-inflammatory chemicals, tumor necrosis factor (TNF).  However, as the name states, TNF is also very much responsible for protecting us from cancer (tumor necrosis = death of tumors), which is why these medications are associated with the development of diseases like lymphoma.

This morning, I read the following headline:  “Study to examine how tumor necrosis factor works to reduce intestinal inflammation.”[i]  Wait…what?!  I actually read it 3 times thinking I must be misunderstanding it.  But no, I had read it correctly.

“Tumor necrosis factor (TNF) is a cell signaling protein secreted by immune and other cells that affects cellular activity and controls inflammation and has been found to play a central role in the disease process of IBD. While anti-TNF therapies are part of the medical treatment regimen for many IBD patients, in the majority it is not an effective treatment in the long term. Many patients treated with anti-TNF biologics either do not respond or lose response within a year.”

Apparently, TNF does not have only pro-inflammatory effect.  It has two different receptors, TNFR1 and TNFR2.  The latter, when stimulated, “…drives a specific pathway that restricts inflammation.”

So now researchers at Children’s Hospital of Los Angeles are going to study this phenomena.  For the last 20 years or so, doctors have been liberally prescribing to the autoimmune community a class of irrefutably dangerous medications that potentially inhibit the production of the very chemical that ultimately may be necessary to heal.

My thoughts:

1. It is truly astounding – and terrifying – how many medications are on the market whose mechanisms of action is not truly understood.
2. Clinical trials, for the most part, are not long-term. As evidenced by these TNF inhibitors, the short-term action may be very different from the long-term action.
3. Doesn’t it just make you wonder how these medicines were deemed safe and appropriate by the FDA? How did they become the drug-of-choice to treat so many autoimmune diseases?  They very often have profoundly negative effect on humans; they can be deadly; they are frequently ineffective; even when they are effective, all too often they  are not effective in the long term.

I am really starting to wonder if TNF-inhibitors were, as I like to say, a big oopsie.

……………….

Oh..wait.  Well, hmmm….apparently they are not a big oopsie for everyone.  “The anti TNF Drugs (Humira, Remicade & Enbrel) for Rheumatic Disease have combined sales of more than US$ 30 Billion in 2015.  The Tumor Necrosis Factor Inhibitors Market & Clinical Pipeline Outlook 2022 report analyzes ongoing clinical and non-clinical trends in the global Tumor Necrosis Factor Inhibitors market. The anti TNF drugs are among the top 10 global block buster drugs and have dominated the global pharmaceutical market landscape for many years.”[ii]

I need a drink.

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[i] https://www.eurekalert.org/pub_releases/2017-11/chla-ste112017.php

[ii] https://globenewswire.com/news-release/2017/02/13/916536/0/en/30-Billion-Tumor-Necrosis-Factor-Inhibiotrs-Market-Clinical-Pipeline-Outlook-2022.html