The use of arthritis drugs, especially tocilizumab, against coronavirus has been the subject of debate through the pandemic, emerging as a choice at times and falling out of favour at other times.
Two arthritis drugs, tocilizumab and sarilumab, have re-emerged as possible treatment options for Covid-19 with the UK government recommending their use based on a new study. The use of arthritis drugs, especially tocilizumab, against coronavirus has been the subject of debate through the pandemic, emerging as a choice at times and falling out of favour at other times. The latest study, which is on a preprint server (which means that it is yet to be peer-reviewed), its results — unlike those of previous trials — suggest that tocilizumab and sarilumab could help save lives among Covid-19 patients admitted to an intensive care unit (ICU).
The study
Last week, the portal MedRxiv published results of the REMAP-CAP trial, which assessed 803 Covid-19 patients in ICU. Of them, 353 were administered tocilizumab within 24 hours of ICU admission, another 48 were given sarilumab within the same time-frame, and the remaining 402 were administered standard care minus these two drugs (the control arm).
While 64.2% ICU patients survived in the control arm, 72% survived when administered tocilizumab and 77.8% survived when given sarilumab.
The researchers found that the two arthritis drugs, now repurposed for Covid treatment, also helped reduce the need for organ support. Those given tocilizumab required organ support after 10 days on an average, those on sarilumab required after 11 days, and those in the control arm required organ support system in a single day.
What this could mean
“This trial shows the drugs cannot be written off so easily,” said Dr Shashank R Joshi, who has been part of another study to assess arthritis drug itolizumab’s role in Covid-19 treatment. Joshi said despite multiple trial studies yielding unfavourable conclusions for immunosuppressants’ use against Covid-19, they have found tocilizumab (marketed as Actemra by Roche) effective if used at the correct time. “In clinical practice we have observed that if a patient is on high flow nasal cannula and put on steroids, and if his condition deteriorates within next 24 hours in ICU, an immunosuppressant drug can be the correct intervention at that point. We have seen several patients turn around towards recovery,” Joshi said.
In India, three immunosuppressant drugs — tocilizumab, sarilumab, and itolizumab — are used to treat rheumatoid arthritis. These drugs work against a protein called IL-6, which plays a key role in the body mounting a cytokine response (when the immune system attacks the body’s own cells) after the virus infects the body. By suppressing IL-6, these repurposed drugs are supposed to stop the self-damaging cytokine response in severe Covid-19 infections.
Red flags
The Indian Council of Medical Research has previously warned against indiscriminate use of drugs such as remdesivir and tocilizumab in Covid-19 patients as they can do more harm than good. Four months before the UK approved use of the arthritis drugs, Maharashtra had removed tocilizumab from its Covid-19 treatment protocol. Several trials and studies had led to this decision. The most crucial one came from tocilizumab manufacturer Roche in July 2020: it published phase-III trial results that found tocilizumab did not meet the primary endpoint of clinical improvement or the secondary endpoint of reduction in mortality.
In October 2020, the New England Journal of Medicine published a study on 243 patients that found tocilizumab was not effective in preventing death in moderately ill, hospitalised Covid-19 patients.
In September 2020, pharma giant Sanofi halted its trial on sarilumab stating it did not work against Covid-19 after testing it on 420 patients. That July, Sanofi had halted a similar trial in the US after assessing 194 patients. In fact, Sanofi had said sarilumab was associated with a 3% higher risk of adverse events in comparison to the placebo group.
Unsettled debate
Why are the latest findings so contradictory? Intensivist Dr Rahul Pandit, who was himself treated with tocilizumab for Covid-19 last year, said he has completely stopped use of the drug. “We cannot rush into a conclusion with this one new research. We need to look at bigger data,” Pandit said.
Pandit stopped use of tocilizumab and itolizumab five months ago. “There was no evidence of improvement or reduction in mortality. Patients are at risk of secondary infection with this drug,” he said.
But as Dr Joshi puts it, “Each clinical trial has a different yardstick to measure the endpoint. This is only a year-old illness. We need to wait for more data before writing off drugs.”
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