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Since the COVID pandemic began, physicians and scientists have been struggling to figure out how to best treat people who become seriously ill with this novel virus. While a variety of drugs have shown some promise, there are no “official” treatments because so much more research is needed.
A group of rheumatology experts, writing in the journal The Lancet Rheumatology, say that study of TNF inhibitors ought to be prioritized. These medications ought to be familiar to people with rheumatic disease and other autoimmune conditions.
TNF inhibitors include such drugs as:
- Adalimumab (Humira)
- Certolizumab pegol (Cimzia)
- Etanercept (Enbrel)
- Golimumab (Simponi)
- Infliximab (Remicade)
These therapies work by targeting TNF (tumor necrosis factor), a specific inflammatory protein. In these patients, blocking TNF serves to dampen a hyperactive immune response and the excessive inflammation that goes along with it, so it stops damaging healthy tissue.
There’s reason to believe this mechanism might be helpful for certain COVID-19 patients as well. In The Lancet Rheumatology, Philip C. Robinson, a rheumatologist at University of Queensland in Australia and his co-authors explain that the evidence showing anti-TNF drugs help critically ill COVID patients is mounting and deserves further study.
In particular, early research has shown that these drugs can be used to combat the dreaded “cytokine storm” — which occurs when a COVID patient has such a disproportionately strong immune response to the virus and end up with out-of-control inflammation in their lungs or other vital organs. If the inflammation can’t be quickly controlled, it can be fatal.
“This hyperinflammatory response in COVID-19 is characterised by elevated concentrations of serum TNF, interleukin (IL)-6, and IL-8, but relatively little IL-1,” the authors explained. TNF inhibitors also have some bonus benefits in that they also “downregulate” interleukins and other inflammatory proteins.
Additionally, many COVID patients have been developing dangerous blood clots, and anti-TNF drugs also seem to quickly downregulate clotting factors (D-dimer and pro-thombin) in the blood. “The same is not documented for anti-IL-6 or anti-IL-1 therapies,” they noted. Those are other kinds of biologic medications also used to treat such conditions as rheumatoid arthritis.
While there is not yet research from randomized controlled trials that proves that TNF biologics should be used as a COVID-19 treatment, some observational studies suggest a protective benefit.
According to the paper’s authors, data from a research registry of people with inflammatory bowel disease indicates that “when patients with inflammatory bowel disease develop COVID-19, those on anti-TNF therapies do just as well and possibly better than those on alternative agents” and “anti-TNF therapy was found to be inversely associated with the composite outcome of death or hospital admission for COVID-19.”
In examining data from 600 rheumatic disease patients, a different study found that “the use of anti-TNF therapy, either alone or in combination with other immunomodulatory drugs, compared with no disease-modifying antirheumatic drugs, was associated with a lower rate of hospital admission for COVID-19.”
Small trials are underway in the U.S. and England. For example, one British study is currently investigating the use of infliximab (Remicade) in patients admitted to hospital with suspected COVID-19, but bigger trials should be prioritized, according to the paper’s authors.
“The potential of anti-TNF therapy as a treatment for COVID-19 is supported by both biological plausibility and observational clinical data,” the study authors write. “There is a long history of safe use of anti-TNF therapy in a diverse range of diseases, and supply is plentiful with many originator products available as well as many biosimilars. Anti-TNF therapy now has huge potential. We need to urgently investigate its value through prioritization of clinical trial resources worldwide.”
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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.