Drugs-COVID-19: TNF Inhibitors Being Studied By More Experts To Treat COVID-19. University of Oxford Starting New Trial Involving Anti-TNF Drug Adalimumab

Drugs-COVID-19: Anti-tumour necrosis factor (anti-TNF) drugs or TNF inhibitors are now being explored by numerous researchers to treat COVID-19 after recent studies of patients with COVID-19 have shown that patients already taking anti-TNF drugs for inflammatory bowel disease and inflammatory arthritis are less likely to be admitted to hospital. The same was not observed for patients taking other anti-inflammatory drugs. https://ard.bmj.com/content/79/9/1156?utm_term=consumer&utm_content=062020covid&utm_campaign=covidtrendmd&utm_medium=cpc&utm_source=trendmd
 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474894/
 
https://academic.oup.com/ibdjournal/article/26/7/e73/5831990
 
https://www.karger.com/Article/Abstract/508740
 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7258834/


 
A group of rheumatology experts, writing in the journal The Lancet Rheumatology, say that study of TNF inhibitors to treat COVID-19 ought to be prioritized. These medications ought to be familiar to individuals with rheumatic disease and other autoimmune conditions. https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30309-X/fulltext#%20
 
TNF inhibitors or anti-TNF drugs include such drugs as:
- Adalimumab (Humira)
- Certolizumab pegol (Cimzia)
- Etanercept (Enbrel)
- Golimumab (Simponi)
- Infliximab (Remicade)
 
These drugs 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 is growing reasons to believe these drugs might be helpful for certain COVID-19 patients as well. In article 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.
 
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.
 
Typically this hyperinflammatory response in COVID-19 is characterized by elevated concentrations of serum TNF, interleukin (IL)-6, and IL-8, but relatively little IL-1. (latest studies show tha other interleukins and cytokines are also involved). TNF inhibitors also have some bonus benefits in that they also “downregulate” interleukins and other inflammatory proteins.
 
Furthermore, 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.  Those are other kinds of biologic medications also used to treat such conditions as rheumatoid arthritis.
 
Although 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.
 
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 another study mentioned in that lancet article, examining data from 600 rheumatic disease patients, found that “the use of anti-TNF therapy, either alone or in combination with other immunomodulatory drugs, compared with no disease-modifying anti-rheumatic drugs, was associated with a lower rate of hospital admission for COVID-19.”
 
The Australian researchers in the lancer article said, “The potential of anti-TNF therapy as a treatment for COVID-19 is supported by both biological plausibility and observational clinical data. 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.”
 
However although anti-TNF therapy could be useful clinically, it is possible that it may not outweigh the cost: benefit ratio given that in diseases such as Ulcerative Colitis, the annual cost of therapy can range from US$13,000–US$18,000 in the UK. In all, more research is needed to determine the potential of anti-TNF therapy in patients with COVID-19.And If truly beneficial, cheaper generic versions should be explored from India.
 
Meanwhile researchers at the University of Oxford are starting a new study to explore the effectiveness of the anti-tumour necrosis factor (anti-TNF) drug adalimumab as a treatment for patients with COVID-19 in the community, especially care homes.
 
The new AVID-CC trial, which will be conducted by Oxford Clinical Trials Research Unit (OCTRU), will enroll up to 750 patients from community care settings throughout the UK.
 
The trial is funded by the COVID-19 Therapeutics Accelerator, an initiative set up by Wellcome, the Bill and Melinda Gates Foundation and Mastercard, with support from an array of public and philanthropic donors.
 
It was reported that residents of care homes were particularly hard hit by the first wave of COVID-19 in the UK and other countries. Research has identified limited treatments that are effective for patients in hospital with COVID-19, but no effective treatments have yet been identified for those in the community care settings, many of whom may have severe symptoms.
 
Importantly the availability of biosimilar versions of biological treatments has been an important step forward in driving down costs, making the anti-TNF treatment affordable and accessible if the trial is successful.
 
Dr Duncan Richards, Professor of Clinical Therapeutics, University of Oxford who will be leading the research told Thailand Medical News,  ”The observed potential of anti-TNF drugs has prompted us to conduct a study in patients in community care to see whether treatment with the anti-TNF drug adalimumab reduces the progression to severe or critical disease or death in COVID-19 patients. We think anti-TNF drugs could be an important treatment for COVID-19 and are very grateful for the support of the COVID-19 Therapeutics Accelerator, which will allow us to find out. I would also like to thank Sandoz Ltd for provision of adalimumab. We are also looking forward to working with Sensyne Health to collect additional information on patients' clinical status through their app. Subject to the necessary approvals we hope to start recruiting patients in late October."
 
The clinical study will be delivered by Hospital at Home teams around the UK. Hospital at Home is a relatively new service in which hospital-based teams reach out into the community to deliver more complex treatment interventions while avoiding the need for admission to hospital. This study sits therefore in a unique niche between the existing national platform therapeutic studies PRINCIPLE (primary care) and RECOVERY (hospitals).
 
Dr Dan Lasserson, Professor of Acute Ambulatory Care, University of Warwick who also works as a clinician in a Hospital at Home service for Oxford University Hospitals NHS Foundation Trust, commented, This is the first drug trial designed for Acute Hospital at Home services and it could not come at a more important time. We need to determine the best treatments for COVID-19 that can be given to older people with frailty who are in care homes or living in their own homes. This grant from the COVID-19 Therapeutics Accelerator not only helps us determine whether anti-TNF drugs could improve outcomes, but the trial itself will help the development nationally of acute hospital at home services."
 
Dr Adam Gordon, Professor of Care of Older People at the University of Nottingham, and Consultant Geriatrician, added,  "We have seen lots of examples, earlier in the COVID pandemic, of older people in care homes being disadvantaged regarding access to treatments simply because of where they live. This study is an exciting opportunity to open up promising treatments to this most vulnerable, and underserved, group of people. It is an important step forward as we investigate how to manage COVID, and more generally in terms of bringing research to the frailest older people."
 
Oxford Hospital at Home Service receives support from the Oxford NIHR Biomedical Research Centre.


 
There are also currently 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.
 
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