Although COVID-19 vaccines have recently been all the rage with the distribution of the approved Pfizer and Moderna vaccines, other non-vaccine, coronavirus treatments have also proved successful including a drug named tocilizumab. How does tocilizumab work? Many people with severe COVID-19 suffer from systemic or widespread inflammation due to the immune system overworking against the virus. Tocilizumab is a drug that reduces this inflammation. Although tocilizumab is commonly used to treat rheumatoid arthritis, researchers believe it can also be used to combat the coronavirus as the drug reduces inflammation, which is a common symptom in patients with severe COVID-19.
Multiple studies have been conducted that tested the efficacy of tocilizumab but each study produced varying results and reached different conclusions. One of these studies, published in December 2020 in the New England Journal of Medicine, tested the efficacy of tocilizumab in patients hospitalized with COVID-19. The researchers concluded that tocilizumab was not effective in preventing death in moderately ill hospitalized patients. However, a more recently conducted trial that also tested the efficacy of tocilizumab in hospitalized COVID-19 patients concluded that the drug was effective in preventing death and provided other benefits to patients. Why is there such a drastic difference in results? The initial study contained many caveats including a small sample size (243 participants) in comparison to a much larger sample size (4116 participants) in the later study. Additionally, a key difference between these two trials is that the larger, more recent trial administered tocilizumab to patients in addition to corticosteroids the patients were initially taking. The details of this tocilizumab trial were posted on February 11, 2021 in the medRxiv preprint. (The study has not yet been peer-reviewed). A summary is provided below.
About the Trial
The randomized and controlled trial was conducted at the University of Oxford between April 23 2020 and January 24 2021. A total of 4116 adult patients hospitalized with COVID-19 were enrolled; all were receiving oxygen and had evidence of systemic inflammation. Of the 4116 trial participants, 14% were receiving mechanical ventilation, 41% were receiving non-invasive respiratory support, and 45% were receiving only oxygen support. The participants were randomized into two groups: one group of 2022 patients received tocilizumab while another group of 2094 patients received usual care. 82% of patients from both groups were taking corticosteroids (drug that lowers inflammation in the body) and of these 82% of patients, a majority were specifically taking the corticosteroid dexamethasone.
Results
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| Patients receiving tocilizumab consistently had a lower mortality rate than patients receiving usual care |
Tocilizumab was also associated with a greater probability of discharge from the hospital (alive). Of the 2022 patients receiving tocilizumab, 54% left the hospital within 28 days while 47% of patients receiving usual care left the hospital within the same time frame. (See figure below)
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| A greater percentage of patients receiving tocilizumab were discharged compared to patients receiving usual care |
Patients who were not initially on invasive mechanical ventilation and received tocilizumab were less likely to progress to invasive mechanical ventilation or death (33%) than those who received usual care (38%). The study also states that "the benefits of tocilizumab were clearly seen among those receiving treatment with a systemic corticosteroid such as dexamethasone." In terms of mortality rate, tocilizumab was observed to be more effective in males, individuals of white ethnicity, and when administered 7 days within symptom onset. However, the drug was still beneficial in the overall number of participants. (See below)
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| 'Effect of allocation to tocilizumab on 28-day mortality rate by baseline characteristics' |
Conclusion
The trial results indicate that tocilizumab is an effective treatment for patients hospitalized with COVID-19 that have evidence of inflammation as well as hypoxia, or oxygen supply. The main benefits of tocilizumab treatment were a decreased mortality rate and increased probability of hospital discharge. Additionally, tocilizumab was significantly more effective with use of corticosteroids such as dexamethasone. Most patients who were not taking corticosteroids along with tocilizumab did not experience significant improvement.
Vaccines aren't the only coronavirus-related development making significant progress. Researchers estimate that 49% of hospitalized COVID-19 patients in the UK would benefit from this drug. While vaccines protect and reduce the risk of COVID-19 infection, drugs like tocilizumab will help treat COVID-19 and expedite the recovery process in those who have been infected.
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