Critically-ill coronavirus patient saved by quick-thinking doctor who gave him an arthritis drug

A critically-ill coronavirus patient was saved after getting a promising arthritis drug that is being trialled by doctors worldwide.

Leonard Whitehurst was admitted to the Royal Cornwall Hospital on March 16 with a confirmed case of COVID-19.

Over the course of his stay, his condition deteriorated until his prognosis was ‘very grim’, according to medics who treated him.

One of the 72-year-old’s doctors decided to give him tocilizumab on compassionate grounds, after it showed promise in treating COVID-19 patients in Italy

Tocilizumab, marketed as RoActemra or Actemra, is used to suppress the immune system of rheumatoid arthritis patients.

For COVID-19, it has the potential to stop the ‘cytokine storm’ that happens when the immune system goes into overdrive and starts attacking the body. 

As soon as Mr Whitehurst was given the drug as a last-ditch attempt, his condition began improving. He is now recovering at home.

Dr Giorgio Gentile believes he is the first to have tried the arthritis drug in the UK back in March following the advice of worldwide doctors.

Now, tocilizumab is part of three major trials involving British patients – with the first results expected by June or July. 

As soon as Leonard Whitehurst was given the drug tocilizumab, his condition began improving. He is now recovering at home (pictured with the nursing team at Royal Cornwall Hospital)

A critically-ill coronavirus patient was saved by a quick-thinking doctor, Dr Giorgio Gentile (pictured), who gave him an arthritis drug being trialled by doctors worldwide

A critically-ill coronavirus patient was saved by a quick-thinking doctor, Dr Giorgio Gentile (pictured), who gave him an arthritis drug being trialled by doctors worldwide

Tocilizumab, marketed as Actemra and made by Roche, is used to suppress the immune system of rheumatoid arthritis patients. But it may have potential for COVID-19

Tocilizumab, marketed as Actemra and made by Roche, is used to suppress the immune system of rheumatoid arthritis patients. But it may have potential for COVID-19

Dr Gentile, a consultant nephrologist from Italy, has worked at the Royal Cornwall Hospitals Trust since 2015, having moved here with his family. 

He revealed that Mr Whitehurst needed 19 litres of oxygen but had not been put on a ventilator. 

Dr Gentile said: ‘Leonard was deteriorating quickly and escalation to intensive care for ventilation was not an option.

‘As the patient wasn’t prepared to be artificially ventilated, the outlook was very grim.

‘I was desperate to try to save the patient. To me, tocilizumab seemed like the only viable option left to try and save his life.’

Dr Gentile had been regularly reviewing the medical literature of COVID-19 that was coming out from countries which battled the peak of their outbreaks before the UK.

He also maintained regular contacts with his network of colleagues involved on the frontline against COVID-19 in Italy – the only European country to record more deaths than the UK. 

WHAT IS TOCILUZUMAB? 

Tocilizumab is used to treat adults with rheumatoid arthritis, as well as certain types of childhood arthritis. 

It is typically marketed under the names of RoActemra and Actemra, produced by the Swiss pharmaceutical firm Roche.

RoActemra was hailed as the first innovation in the field of treating rheumatoid arthritis (RA) for ten years when it was approved by the NHS in 2012 after a long battle over pricing.

The prescription medicine works by reducing levels of IL-6 protein in the body, which people with rheumatoid arthritis or another autoimmune conditions have too much of.

If there is too much IL-6, it can cause inflammation and damage. Tocilizumab blocks the effects, and has become a go-to for inflammatory disease treatment. 

Doubts have been raised about the safety of tocilizumab, which has a long list of side effects including a cough or sore throat, blocked or runny nose, headaches or dizziness, mouth ulcers, high blood pressure, weight gain and stomach problems.

Tocilizumab has been shown to increase the risk of infections in patients with rheumatoid arthritis, including pneumonia and upper respiratory tract infections, according to Versus Arthritis.

Trials on patients with RA before approval were not designed to assess long-term efficacy and safety.

The Food and Drug Administration has received reports on 1,128 people who died after taking Actemra, according to a report by Stat News in 2017. It said the FDA declined to comment about Actemra.

Dr Gentile had become aware of multiple anecdotal reports of people in very severe conditions who had dramatically improved after treatment with tocilizumab. 

‘The AIFA, which is the Italian equivalent of the Medicines and Healthcare products Regulatory Agency, had just approved a large trial with tocilizumab and was actively recruiting people,’ added Dr Gentile.

‘The Italian experience seemed to mirror a preliminary yet promising experience from Chinese scientists, who used tocilizumab in 21 patients with very encouraging results.’ 

Another promising study of 20 patients in China, published in mid-March, claimed tocilizumab cured 95 per cent of critically ill patients.

The prescription medicine works by reducing levels of IL-6 protein in the body, which people with rheumatoid arthritis or another autoimmune conditions have too much of. 

If there is too much IL-6, it can cause inflammation and damage. Tocilizumab blocks the effects, and has become a go-to for inflammatory disease treatment.

It is hoped that tocilizumab will work to prevent an overreaction of the immune system seen in some coronavirus patients.

Called a ‘cytokine storm’, the body’s immune response can go into overdrive and produce inflammation and attack healthy tissue, which could be fatal.

It’s thought to play a role in a large majority of deaths – especially the elderly whose immune systems have aged.  

Dr Gentile said: ‘Our patient had all the laboratory signs of the so-called “cytokine storm”, which I was aware of thanks to a paper published in the peer-reviewed journal, The Lancet.

‘The same paper speculated that tocilizumab could be used to treat patients with severe COVID-19 pneumonia and hyper-inflammation, who are at high risk of progression towards acute respiratory distress syndrome and death. 

‘Luckily, we have brave, compassionate and open-minded leadership here at the RCHT. They gave me the green light to use tocilizumab on compassionate grounds. 

‘The patient agreed to receive the treatment, which was then quickly administered.’

WHAT IS THE RECOVERY TRIAL? 

More than 6,000 coronavirus patients in the UK have volunteered to take part in a drug trial run by the University of Oxford to find a treatment for COVID-19.

The programme is called the RECOVERY Trial (The Randomised Evaluation of COV-id19 thERapY) and is the world’s biggest single trial of drugs to treat the coronavirus.

The university got the support of Chief Medical Officer Professor Chris Whitty and put out a plea to doctors around the country to enrol patients in the voluntary trial.

Volunteers have since joined the trial from more than 160 NHS trusts around the country and scientists are hopeful more people will continue to sign up.

Medics have not put a number on the amount of people the trial needs in order to be successful but has said the more participants the trial has, the more likely it will be the team will find answers.

Participants will receive one of five drugs currently on the market — including the anti-malaria drug touted by Donald Trump, known as hydroxychloroquine.

The other drugs being looked at as a treatment for COVID-19 include a combination of Lopinavir and Ritonavir (known by the brand name Kaletra), which is used to treat HIV; low-dose Dexamethasone,a steroid used to reduce inflammation; azithromycin, a commonly used antibiotic which may have antiviral properties; and the steroid Tocilizumab.

Similar trials are being set up around the world, which run independently to the Recovery Trial, but none have garnered as many participants as the UK programme.

Mr Whitehurst received two infusions of tocilizumab 12 hours apart from nurses.

Before the infusion, his oxygen saturation was 75 per cent. A normal reading should be between 80 and 100.

After the infusion, Mr Whitehurst’s clinical conditions and his oxygen saturation improved very quickly, and then kept improving gradually and steadily over the subsequent days.

His oxygen requirement decreased gradually over time.

‘At the time, we were at the very beginning of the COVID-19 crisis in the UK and the national lockdown had just been declared. So, it is quite possible that the RCHT has been the first NHS trust in the UK to successfully treat a patient with tocilizumab,’ added Dr Gentile.

‘We’re certainly among the first. This kind of innovation and collaborative learning would not be possible without such a dedicated staff and our colleagues going above and beyond to provide the best care for our patients.’

Mr Whitehurst was discharged from hospital last week ‘smiling and overjoyed’, having spent more than a month in the hospital. 

Mr Whitehurst said: ‘I would like you to pass on my heartfelt thanks to all the staff on Wheal Prosper ward. 

‘I was quite overwhelmed on leaving the hospital, and I am truly grateful for everything the teams have done for me.’

Dr Gentile stressed that although tocilizumab worked for his patient, further evidence from rigorous randomised controlled trials is necessary to fully establish the role of the drug in COVID-19 pneumonia.

Tocilizumab is part of three major trials involving British patients – with the first results expected by June or July. 

One of those is the Recovery trial, which is also testing four promising treatments, including HIV, malaria and antibiotic medications.

It has recruited about 6,000 NHS patients, making it the largest study looking at repurposing existing therapies to treat the incurable virus.

Patients from almost every NHS trust in the country are taking part in the trial, which is being run by Oxford University.

The drug will be administered to patients whose lungs have become severely inflamed due to a dangerous immune reaction caused by the virus.   

Roche is also conducting a Phase III clinical trial of a targeted 330 hospitalised patients worldwide with severe COVID-19 pneumonia.

The pharma giant says that it is working with the Food and Drug Administration (FDA) to initiate the randomised, double-blind, placebo-controlled study, to evaluate the safety and efficacy of the drug in combo with standard of care. 

Overall fifteen registered trials in China, Europe and the US are testing it on COVID-19 patients, alone or in comparison to other therapies. 

Doctors in China were the first to try tocilizumab against the deadly coronavirus that causes COVID-19 in early February. Some patients in the trial were diagnosed at the First Affiliated Hospital of Nanchang University. Medics are pictured on an intensive care ward there

Doctors in China were the first to try tocilizumab against the deadly coronavirus that causes COVID-19 in early February. Some patients in the trial were diagnosed at the First Affiliated Hospital of Nanchang University. Medics are pictured on an intensive care ward there

CT scans also showed damage to the lungs reduced significantly around the fourth and fifth day of treatment. Pictured left, the lungs of a 55-year-old man, centre, a 82-year-old man and right, a 32-year-old patient

CT scans also showed damage to the lungs reduced significantly around the fourth and fifth day of treatment. Pictured left, the lungs of a 55-year-old man, centre, a 82-year-old man and right, a 32-year-old patient

Doctors in China were the first to try tocilizumab against the deadly coronavirus that causes COVID-19 in early February.

Patients, who were given routine therapies along with the drug, were diagnosed as severe or critical.

They were being treated at two separate hospitals in the eastern province of Anhui in China – The First Affiliated Hospital of University of Science and Technology of China and Anhui Fuyang Second People’s Hospital. 

Within a few days, patients’ fever returned to normal and all other symptoms improved remarkably, Dr Xiaoling Xu and colleagues report.

Fifteen of the 20 patients involved in the trial were able to have their oxygen intake lowered, while one patient was taken off completely.

Seventeen of the patients had seen levels of their white blood cells, called lymphocytes, drop. But on the fifth day, this returned to normal in ten of the patients.

Nineteen patients (95 per cent) were discharged after 13 and a half days. The other patient is recovering well, the study said.

CT scans also showed damage to the lungs reduced significantly around the fourth and fifth day of treatment. 

The authors concludes: ‘Tocilizumab is an effective treatment in severe patients of COVID-19, which provided a new therapeutic strategy for this fatal infectious disease.’

The researchers did not compare the drug to a placebo or any other drugs in the small study. The paper was published on ChinaXiv, a website which hosts scientific research which has not been peer-reviewed.  

Speaking on behalf of the Trust, chief executive Kate Shields said: ‘This brave clinical leadership helped to save a patient’s life. We are proud of Dr Gentile and everyone involved in making this innovative treatment possible and overwhelmed by the care, compassion and dedication of our colleagues during this difficult time.’ 

The MHRA said: ‘There is no licensed treatment for (COVID-19) related symptoms or to prevent infection.

‘Clinicians and prescribers may prescribe an unlicensed medicine for an individual patient outside of the clinical trials setting, where they consider that the possible benefits of treatment may outweigh any risks of using the unlicensed medicine.’