Plain language summary Are medicines that block interleukin‐6 (a protein involved when the body’s immune system overreacts) effective treatments for COVID‐19 and do they cause unwanted effects? Key messages We are very confident that tocilizumab (a medicine that blocks interleukin‐6 (IL‐6)) reduces the number of hospitalized people who die from COVID‐19 within 28 days of treatment. However, it probably results in little or no difference in clinical improvement (defined as leaving the hospital or improvement in COVID‐19 symptoms). Sarilumab probably results in little or no difference in clinical improvement. We found few studies assessing the other IL‐6‐blocking medicines. We are, therefore, uncertain about their effects. A small number of studies have not published any results. These studies treated relatively low numbers of people and their results would not change our current findings. What is IL‐6, and what is its role in COVID‐19? IL‐6 is a type of protein called a cytokine, which helps to regulate the body’s immune system. In particular, IL‐6 triggers inflammation to help the body recognize and fight infection to defend itself against harmful substances, such as viruses. When a person has COVID‐19 it can disrupt their immune system response, causing it to overreact. When the body continually makes IL‐6 as part of this response, it can produce high levels of inflammation that damage the body. This can lead to severe breathing difficulties, organ failure and death. What are IL‐6 blocking agents? IL‐6 blocking agents are medicines that stop the IL‐6 from working by blocking signals from IL‐6 to other parts of the immune system. This reduces inflammation and may help the immune system to fight COVID‐19. In turn, this may reduce the need for breathing support with a ventilator (a machine that breathes for a patient) and reduce the number of deaths from COVID‐19. These are already known to be safe and effective when they are used to treat conditions that involve an ‘overreactive’ immune system, such as rheumatoid arthritis. What did we want to find out? We wanted to know if IL‐6 blocking agents are effective treatments for people with COVID‐19, compared with standard care alone or with placebo (a dummy treatment that appears identical to the medicine being tested but without any active medicine). We were particularly interested in the effects of IL‐6 blocking agents on: ‐ whether people’s symptoms got better or worse; ‐ how many people died; and ‐ any unwanted effects and serious unwanted effects. What did we do? We searched for studies that tested if medicines that block interleukin‐6 can treat COVID‐19 effectively. We looked for randomized controlled studies in which the treatments people received are decided by chance. We compared and summarized the results of the studies. We used a standardized method to rate our confidence in the evidence. The confidence is based on study features such as study design and the number of people included. What did we find? We found 32 studies in 12,160 people with COVID‐19. The average age of people was 56 to 75 years, and 66% of the participants were men. The studies took place at hospitals in different countries around the world. Eight studies were funded by pharmaceutical companies. The medicines most tested were tocilizumab and sarilumab. We found 17 additional registered studies of IL‐6‐blocking medicines to treat COVID‐19; these studies have no published results. Ten of these studies have either been completed or are still in progress. Seven were terminated. What are the main results of our review? Compared to placebo or standard treatment, treatment with tocilizumab: ‐ reduces the number of people with COVID‐19 dying, of any cause, around 28 days; ‐ probably makes little or no difference on clinical improvement around 28 days; ‐ probably results in little or no difference in unwanted effects. We are uncertain about the effects of tocilizumab treatment on: ‐ clinical improvement around 60 days; ‐ severity of COVID‐19; that is, how many patients needed a ventilator or additional organ support or died of COVID‐19 around 28 days; ‐ how many patients die, of any cause, around 60 days. Compared to placebo or standard treatment, treatment with sarilumab: ‐ probably makes little or no difference in clinical improvement (defined as leaving the hospital or improvement in COVID‐19 symptoms) around 28 days. We are uncertain about the treatment effects and unwanted events of sarilumab, clazakizumab, olokizumab, siltuximab, and levilimab, compared to placebo or standard treatment. What are the limitations of the evidence? Our confidence in the results of clazakizumab, olokizumab, siltuximab, and levilimab is limited because of the low number of studies conducted and the small number of people included in these studies. We were unable to assess the variation in effects due to changes in the standard treatment provided, and we were also unable to see if effects were different in people of different ages or genders. Further, most of the studies included in the review were conducted before the waves of different variants of concern and before vaccination was rolled out on a large scale. How up to date is this evidence? The evidence is up to date to 7 June 2022.
【저자키워드】 COVID-19, Cytokines, COVID-19 drug treatment, interleukin-6, bias, humans, male, female, Aged, Middle aged,