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TNF Biologics COVID-19 Treatment

If you’re taking a type of medication known as tumor necrosis factor inhibitors, also called anti-TNF or TNFis, you may be wondering how these drugs could impact your chances of contracting COVID-19, or having more severe complications from it. After all, the common cold or other upper respiratory tract infections can be more common in people taking anti-TNF inhibitors.

On the other hand, some rheumatologists are pointing out that TNF biologics may actually be protective against COVID-19 inflammation — and they are calling for more clinical trials to study these drugs as a potential COVID treatment.

No wonder there is confusion and anxiety among the people who take these medications to manage conditions like rheumatoid arthritis, psoriasis, and Crohn’s disease.

While more research is needed to fully understand the impact of these medications on COVID-19, at least there is some preliminary data from the first few months of the pandemic, which is helping doctors and researchers make decisions help keep you healthy and safe.

We talked with top rheumatologist to help quell your fears and answer your questions. Read on to learn about how anti-TNF biologics work in the body, what the latest coronavirus research says, and how to best manage your inflammatory condition and minimize your risk of COVID-19.

How Anti-TNF Biologics Work in the Body

Anti-TNF biologics include some commonly prescribed medications for inflammatory and autoimmune conditions. They include:

  • Adalimumab (Humira)
  • Certolizumab pegol (Cimzia)
  • Etanercept (Enbrel)
  • Golimumab (Simponi, Simponi Aria)
  • Infliximab (Remicade)

These medications help control disease activity in patients with inflammatory conditions such as rheumatoid arthritis, axial spondyloarthritis, inflammatory bowel disease (Crohn’s and ulcerative colitis), psoriasis and psoriatic arthritis, and juvenile arthritis.

TNF inhibitors work by targeting and blocking a protein called tumor necrosis factor (TNF), which acts as a messenger that sends signals through your body, eventually leading to inflammation that causes swelling, pain, and stiffness. By inhibiting (or stopping) TNF, these medications can tamp down your immune response and decrease inflammation.

As with other biologic medications, you may be able to give yourself a TNFi biologic via a “self-injection,” or receive it via an infusion in a hospital or outpatient infusion center.

“Biologics are administered as injections or infusions because the chemical structure of the drug is too large to be adequately absorbed when taken by mouth,” explains rheumatologist Angus Worthing, MD, a clinical assistant professor of medicine at Georgetown University Medical Center in Washington, D.C.

These drugs are considered immunosuppressive, which means they can suppress your immune system and make you more susceptible to infections, says Vinicius Domingues, MD, a rheumatologist in Daytona Beach, Florida. Yet questions remain as to whether or what degree this includes coronavirus or its complications.

What the Research Says About TNF Biologics So Far

TNF inhibitors, like most treatments for inflammatory arthritis, are associated with more frequent upper respiratory infections compared to placebo, possibly because of their immune-suppressive effect, notes Dr. Worthing.

But initial studies on people who had been taking TNF biologics and then got infected with COVID-19 are so far more comforting than alarming.

“Luckily, we’re starting to get some reassuring data,” Dr. Worthing says.

An analysis of 600 rheumatic disease patients from 40 countries, which was published in the journal Annals of the Rheumatic Diseases, showed that patients who were regularly taking TNF inhibitors and who got infected with COVID-19 were less likely to require hospitalization compared to other types of medications.

A study of people with inflammatory bowel disease published in the journal Gastroenterology also found that, unlike corticosteroids, taking TNF biologics did not increase the risk of severe COVID-19 and complications.

Another review, published in the journal Current Opinion in Rheumatology, reported that “immune-mediated inflammatory disease (IMID) patients are not at higher risk of developing COVID-19 than individuals without IMID and that most patients recover, including those on biologic therapies, which provides reassurance to both patients and providers.”

“People who take biologic drugs can be reassured by the data that they don’t need to stop the drugs that are helping them feel good, but don’t let down your guard,” says Dr. Worthing. “Continue to maintain social distancing, wear your mask, and wash your hands frequently.”

Can TNF Biologics Actually *Help* Treat COVID-19?

Studies are underway to determine whether TNF inhibitors might be protective against COVID-19 complications.

“Even though COVID-19 starts as an upper respiratory tract infection, data is suggesting that TNF biologics might protect people from severe forms of COVID-19,” he says. “This could be because TNF is one of the cytokines [proteins] that can cause a cytokine storm, a dangerous overactive immune response in critically ill patients with COVID-19, and TNF blockers might prevent or treat that. It’s an open question.”

Whether medications like TNF inhibitors are helpful or harmful in COVID-19 may be a question of timing and other factors. Take steroids, for example.

“It’s true that taking steroids regularly prior to a COVID-19 infection — at least 10 mg or more of prednisone — is associated with more severe cases of COVID-19, but it’s also true that high doses of certain steroids can be lifesaving for people who are hospitalized with severe respiratory distress from COVID-19,” explains Dr. Worthing.

Could it be a similar situation with TNF inhibitor biologics?

“It could be related to timing — that they’re helpful in small subsets of people who need ICU care because of inflammation from COVID-19, but they may worsen risks if taken prior to infection,” says Dr. Worthing.

“The science of these meds is complex and research is ongoing,” says Phillip Robinson, a rheumatologist in Brisbane, Australia, who is among those calling for more research on TNF drugs as a COVID-19 treatment. “[Although] it seems like hyperinflammation is a big problem in COVID-19 and drugs that suppress the immune system may well have a role in treating COVID-19.”

The Importance of Continuing to Take Your TNF Biologic

Stopping TNF biologics can have serious ramifications for the management of your condition and your immune system. “If you were to stop a TNF inhibitor preemptively, you may return to an inflamed state — with telltale sore and swollen joints — and that is an immunocompromised state where you are more at risk for a number of infections,” says Dr. Worthing.

“There are probably multiple ways that having highly active inflammatory arthritis increases people’s risk of infections,” he adds. “During disease flares, a person’s immune system may be relatively more focused on inflaming joints than fighting germs, but also the immobility due to joint pain worsens risks of respiratory infections and urinary tract infections. Finally, infections are more likely if people must use steroids to calm down their inflammation.”

That last point is an important one: If your disease flares, you’ll not only be uncomfortable, but you may need to take corticosteroids like prednisone, which can be more immunosuppressing than TNF inhibitors and which have been linked to a more severe course of COVID-19.

Dr. Domingues agrees that most patients should continue taking anti-TNF inhibitors — unless they are exposed to coronavirus, develop symptoms of COVID-19, or test positive for COVID-19, which aligns with the latest clinical guidance from the American College of Rheumatology.

“It’s very well-known and established that if you stop your medication, you may have a disease flare,” says Dr. Domingues. “On the other hand, nothing has been scientifically proven as to whether these medications are harmful — or helpful — if you catch COVID-19. I’d rather you stay on your biologic to control your disease and wear a mask, social distance, and use hygiene measures to try to avoid COVID-19.”

What If You Develop Coronavirus Symptoms While on TNF Biologics?

The guidance from the ACR advises that patients may temporarily stop this medication if they:

  • Develop COVID-19 symptoms
  • Test positive for COVID-19
  • Have a known exposure to the virus

“The CDC defines exposure as being within six feet of someone with COVID-19 for 15 minutes or more and not wearing a mask,” says Dr. Worthing. If exposure happens, if you develop symptoms of COVID-19, or if you test positive for COVID-19, talk to your doctor about what to do with your TNF biologic. It’s likely they will recommend you stop taking the medication temporarily.

Here is a quick summary of the ACR guidance regarding TNF biologics:

  • Patients in the absence of infection: Continue ongoing treatment
  • Patients who have been exposed (without symptoms related to COVID-19): Stop treatment temporarily, pending a negative test result for COVID-19 or after two weeks of symptom-free observation
  • Patients with uncomplicated COVID-19 infections (mild or no pneumonia and treated in the ambulatory setting or via self-quarantine): Restart rheumatic disease treatments within seven to 14 days of symptom resolution
  • Patients who test positive for COVID-19 but are asymptomatic: Restart rheumatic disease treatments 10 to 17 days after the COVID test is reported as positive
  • Patients recovering from more severe COVID-19 related illness: Decisions regarding timing of restarting rheumatic disease treatments should be made on a case-by-case basis

“Note that guidance is subject to change as we learn more about the use of treatments in rheumatic diseases during the pandemic,” says Dr. Worthing.

The bottom line: Never stop taking your TNF biologic on your own without first consulting your rheumatologist. If you have questions about your medications or concerns about the safety of the infusion suite, speak with your doctor.

“Give your doctor’s office a call and find out what they are doing to minimize the spread of COVID-19,” says Dr. Worthing. “Don’t just stay home and skip your appointment.”

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Brenner EJ, et al. Corticosteroids, But Not TNF Antagonists, Are Associated With Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results From an International Registry. Gastroenterology. August 2020. doi: https://doi.org/10.1053/j.gastro.2020.05.032.

Gianfrancesco M, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Annals of the Rheumatic Diseases. July 2020. doi: https://doi.org/10.1136/annrheumdis-2020-217871.

Gianfrancesco M, et al. Epidemiology and outcomes of novel coronavirus 2019 in patients with immune-mediated inflammatory diseases. Current Opinion in Rheumatology. September 2020. doi: https://doi.org/10.1097/BOR.0000000000000725.

Interview with Angus Worthing, MD, a clinical assistant professor of medicine at Georgetown University Medical Center in Washington, D.C.

Interview with Phillip Robinson, a rheumatologist in Brisbane, Australia

Interview with Vinicius Domingues, MD, a rheumatologist in Daytona Beach, Florida

Kilian A, et al. Acute respiratory viral adverse events during use of antirheumatic disease therapies: A scoping review. Seminars in Arthritis & Rheumatism. October 2020. doi: https://doi.org/10.1016/j.semarthrit.2020.07.007.

Mikuls TR, et al. American College of Rheumatology Guidance for the Management of Rheumatic Disease in Adult Patients During the COVID‐19 Pandemic: Version 2. Arthritis & Rheumatology. July 30, 2020. doi: https://onlinelibrary.wiley.com/doi/10.1002/art.41437.

Robinson P, et al. Accumulating evidence suggests anti-TNF therapy needs to be given trial priority in COVID-19 treatment. The Lancet Rheumatology. September 4, 2020. doi: https://doi.org/10.1016/S2665-9913(20)30309-X.

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