Rare diseases

Glucocorticoid use a risk factor for more severe outcomes in COVID-19

People with rheumatic disease who develop COVID-19 may be at risk of more severe disease, especially if they are on moderate- to high-dose glucocorticoids, a new study suggests.

However, the review of COVID-19 outcomes for patients with immune-mediated inflammatory disease (IMID) found that they are otherwise not at higher risk of developing COVID-19 and most patients recover, including those on biologic therapies.

The study investigators including Australian rheumatologists reviewed research covering 1400 patients with IMID across the fields of rheumatology, gastroenterology and dermatology. The  findings in Current Opinion in Rheumatology showed that patients who are older and those who have comorbidities such as hypertension, lung disease, diabetes or chronic renal impairment have poorer COVID-19 outcomes – similar to the risk profile among the general population.

People with rheumatic disease  had a higher likelihood of having severe outcomes from COVID-19, such as requirement for mechanical ventilation, the review found.  The COVID 19-Global Rheumatology Alliance physician registry, which has accumulated data from 600 patients found that 46%  were hospitalised and 9% died.

There was also a significant association between glucocorticoids and poorer outcomes from COVID-19. The risk of severe COVID-19 disease intensive care unit admission, ventilator use and/or death) was found to be almost 7-fold in patients with IBD on systemic glucocorticoids, while the risk of hospitalisation was two-fold in patients with rheumatic disease on prednisone ≥10 mg/day, compared to in patients not on steroids.

There was no association found between use of biologic or targeted synthetic DMARD therapy and more severe COVID-19 outcomes.

The study authors urged caution in interpreting the findings and called for more research into risks and outcomes of COVID-19 across various rheumatic disease and immunosuppressive drugs.

Co-author Associate Professor Philip Robinson, a rheumatologist at the Royal Brisbane Hospital is co-chair of the COVID-19 Global Rheumatology Alliance Steering Committee Steering Committee. He said the findings supported those of a separate study by the Alliance showing moderate- to high-dose glucocortiocoids were associated with higher odds of hospitalisation for COVID-19 in patients with rheumatic disease. That study found anti-TNF inhibitors were associated with decreased odds of hospitalisation in rheumatic disease patients.

Associate Professor Robinson said the risk of more severe COVID-19 disease in patients on glucocorticoids may be due to the therapy’s broad effect on downregulating the immune system, as opposed to other more targeted therapies.

And while it was important for all patients to heed infection control measures to reduce the risk of getting COVID-19, he said it would be prudent for those taking glucocorticoids to be particularly careful.

The Alliance Register of rheumatology patients with COVID-9 infections now has data recorded on more than 4200 cases globally, including 13 cases in Australia, he added.

“The register has been really invaluable in enabling us to work out what people’s outcomes are with specific disease and drugs – they are outcomes we really could not know without the register,” Associate Professor Robinson told the limbic.

He suggested that clinicians follow clinical guidance from EULAR and the American College of Rheumatology (ACR) regarding treating COVID-19 infection in patients with rheumatic disease.

The ACR recently updated its clinical guidance for COVID-19 in adult patients to include advice on the re-initiation of rheumatic disease treatments following COVID-19 infection.

Meanwhile, Associate Professor Robinson urged caution regarding findings on the use of IL-6 Receptor inhibition to treat complications of COVID-19 infection.

EULAR recently promoted findings of an observational study into the use of high dose glucocorticoids followed by IL-6 inhibition to treat patients with COVID-19-associated cytokine storm syndrome.

The study, which compared 86 patients in the Netherlands with a historical control group, found the experimental treatment protocol could reduce hospital mortality by 65%.

It came despite an announcement by Roche that its phase III trial of IL-6 inhibitor Actemra (tocilizumab) had failed to help patients with severe COVID-19-associated pneumonia.

Associate Professor Robinson said while there had been several publications that claimed IL-6 inhibitors improved outcomes in COVID-19, there were substantial problems with interpreting the published data, much of which was from observational studies.

Two randomised control trials had been announced, but were not yet published, he said.

“If I was making the decision, I would not try patients with IL-6 inhibitors because currently there is no high-quality evidence to support that,” he said.

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