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Scary Side Effects of Immune-Modulating Drugs

Drugs to dampen the immune system are BIG sellers. Humira and Enbrel make billions. How safe are these immune-modulating drugs during COVID?
Scary Side Effects of Immune-Modulating Drugs
High or low immunity symbol. Doctor turns a block and changes words ‘low immunity’ to ‘high immunity’. Beautiful white background. Medical, high or low immunity concept. Copy space.

Immune-modulating drugs have revolutionized the treatment of rheumatoid arthritis, psoriasis, inflammatory bowel disease and several other hard-to-treat conditions. Many of the ads you see on TV for such drugs warn that they can “lower your ability to fight infections including tuberculosis…” How do such drugs affect the body’s ability to deal with COVID-19?

TNF Blockers are Immune-Modulating Drugs:

TNF stands for tissue necrosis factor. It is a cytokine made by white blood cells and leads to inflammation. Drug companies have identified tissue necrosis factor as an enemy. That is why pharmaceutical manufacturers have developed so many TNF blockers.

There is a perception that the body screwed up by making this stuff. But this inflammatory protein “is also important for resistance to infection and cancers” (Microscopy Research and Technique, Aug. 1, 2000). 

This reminds us a bit of the way drug companies have perceived acid in the stomach. They approach this natural substance as if it were a biological misstep. Even though virtually all animals make strong stomach acid, drug companies have created medicines to counteract mother nature. They have done the same thing to combat TNF.

Making Billions with Immune Modulating Drugs:

TNF blockers are among the most hard to pronounce drugs in the world. Try wrapping your tongue around certolizumab, adalimumab, golimumab or infliximab. Then there are other biological agents such as risankizumab-rzaa and ixekizumab. Many of these drugs have become big best sellers on the pharmaceutical hit parade.

According to the FDA:

“TNF blockers suppress the immune system by blocking the activity of TNF, a substance in the body that can cause inflammation and lead to immune-system diseases, such as Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis. The drugs in this class include Remicade (infliximab), Enbrel (etanercept), Humira (adalimumab), Cimzia (certolizumab pegol) and Simponi (golimumab).”

Some of the most expensive drugs in the world are used to dampen down the immune system. The top seller for years has been adalimumab (Humira). It brought in about $20 billion in worldwide sales last year and has been a perennial money maker for the manufacturer.

Humira is prescribed for rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis and a few other inflammatory conditions. Similar drugs such as etanercept (Enbrel), certolizumab (Cimzia), golimumab (Simponi) and infliximab (Remicade) are also big money makers. These are all TNF-alpha blockers.

The Pros and Cons of Immune-Modulating Drugs:

When a doctor offers to prescribe one of these medications, weighing the potential benefit against the risks is challenging. That’s because they can be very helpful in controlling dreadful symptoms of hard-to-treat diseases. On the other hand, they can also cause some serious complications.

In one TV commercial, a father is missing too many events in his young daughter’s life. The voice-over announces that:

“Humira is for people who still have symptoms of Crohn’s disease after trying other medications, and the majority of people on Humira saw significant symptom relief and many achieve remission in as little as four weeks.”

That certainly sounds appealing to someone suffering with this severe bowel disorder.

Perhaps you’ve seen golfer Phil Mickelson in another television commercial for Enbrel.

He lets you know that:

“I’ve been fortunate to win on golf’s biggest stages. But when joint pain and stiffness from psoriatic arthritis hit, even the smallest things became difficult.”

Phil closes the commercial suggesting:

“Get back to the things that matter most. Ask your rheumatologist if Enbrel is right for you.”

Tinkering with the Immune System:

Both ads contain a long list of frightening side effects. Tinkering with the immune system can stir up some pretty scary problems even though it helps others at the same time.

For example, some Humira ads caution:

“Humira can lower your ability to fight infections. Serious and sometimes fatal infections including tuberculosis and cancers including lymphoma have happened as have blood, liver and nervous system problems, serious allergic reactions and new or worsening heart failure.”

This is not a complete list. We recently received a note about a little-known adverse effect.

Immune-Modulating Drugs and MS?

“Our daughter is currently taking leflunomide for MS and ankylosing spondylitis. Before her MS was diagnosed, she was taking Humira for ankylosing spondylitis. It worked well for controlling symptoms, until it didn’t. A couple of physicians speculate that Humira may have been a factor in causing her MS.”

In fact, the official prescribing information for Humira warns that it has been associated with demyelinating disease, including multiple sclerosis. When we reviewed the medical literature, we found numerous case reports of multiple sclerosis beginning after a person had been taking one of the TNF-alpha blockers (Therapeutic Advances in Neurological Disorders, Jan. 2, 2020). 

Such cases are rare, but for the individuals involved, they can be life-altering. People are more likely to be warned about the possibility of serious infections, including tuberculosis and hepatitis B. In addition, patients are at higher risk for certain cancers. There’s also the chance of heart failure.

What About Immune-Modulating Drugs and COVID?

We have been surprised that there isn’t more research to answer the question about the pros and cons of immune-modulating drugs and COVID-19. You would think that with so many people on such medications this would be a priority research topic.

We have seen a few articles.

Some suggest caution (Australaslan Journal of Dermatology, May 3, 2020): 

“There is currently insufficient evidence to determine whether patients on systemic immunomodulators are at increased risk of developing COVID-19 disease or more likely to have severe disease. As such, clinicians need to assess the benefit-to-risk ratio on a case-by-case basis. In patients with suspected or confirmed COVID-19 disease, all immunomodulators used for skin diseases should be immediately withheld, with the possible exception of systemic corticosteroid therapy, which needs to be weaned. In patients who develop symptoms or signs of an upper respiratory tract infection, but COVID-19 is not yet confirmed, consider dose reduction or temporarily cessation for 1–2 weeks.”

Then there is this comment about biologics such as TNF blockers (Dermatologic Therapy, Dec. 23, 2020): 

“There are few studies on how patients with psoriasis who are on biologic therapy are affected by the COVID-19 pandemic…Our findings suggest that biologic treatment for moderate-to-severe psoriasis would not pose an additional risk for COVID-19 infection and its life-threatening complications, even in the presence of a high frequency of cardiometabolic comorbidities, provided that all patients are informed and necessary pandemic-directed precautions are well adopted by the patients.”

And this from about a year ago (Journal of Cutaneous Medicine and Surgery, Aug. 6, 2020): 

“Currently, there is insufficient evidence to discontinue biologic therapy in patients with psoriasis who have not tested positive for COVID-19. The decision to pause biologic therapy should be considered on a case-by-case basis in patients in higher risk populations, and should take into account individual risk and benefit. Until more is known about the impact of biologic therapy on COVID-19 outcomes, we recommend patients with psoriasis who test positive for COVID-19 be instructed to discontinue or postpone biologic treatment until they have recovered from infection.”

We are disappointed that there is not clear information about the use of biologics like TNF blockers in the middle of a pandemic. This should be an absolute priority. Do these drugs have any impact on the risk of catching COVID or surviving an infection with SARS-CoV-2? As far as we can tell, there are no definitive answers. 

Final Words:

The benefits of immune-modulating drugs are very tangible. Who wouldn’t want to get back to “the things that matter most,” to quote Phil Mickelson? The risks, on the other hand, seem remote—until one happens.

What’s Your Experience with Immune-Modulating Drugs?

Have you taken Cimzia, Humira, Enbrel, Remicade, Simponi or any other biologic? Please share your story in the comment section below.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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