TNFi safer than other immune modulator therapies in RA patients with COVID


Findings of a large, international study support the continued use of TNF inhibitor monotherapy in patients with immune-mediated inflammatory disease (IMID)  during the COVID-19 pandemic.

Whether patients with IMIDs such as RA, IBD and psoriasis are at greater risk of SARS-CoV-2 infection or more severe COVID-19 outcomes is not yet fully understood, and many questions over the safety of anti-inflammatory drugs remain unanswered, according to investigators including Associate Professor Philip Robinson of the Royal Brisbane and Women’s Hospital.

Previous studies provided early data backing the continued use of TNF inhibitors in IMID patients with COVID, but now a pooled analysis of data from three international patient registries has provided more substantial data supporting their safety as monotherapy during the pandemic.

For the study, published in JAMA Network Open, researchers carried out a pooled analysis of data from three international COVID-19 registries that included people with rheumatic diseases, inflammatory bowel disease and psoriasis, to explore any association between treatment with TNF inhibitor monotherapy and the risk of COVID-19–associated hospitalisation or death versus other immunomodulatory treatment regimens in adults with IMIDs.

The analysis included 6,077 patients from 74 countries, of which 53% were from Europe, 59% were female, and the mean age was 48.8 years. In the study population, the most common IMID diagnoses were rheumatoid arthritis (35%) and Crohn disease (25.3%).

The results showed that after taking into account active disease and common comorbidities, the odds of hospitalisation or death among those who received TNF inhibitor combination therapies compared to TNF inhibitor monotherapy was dependent on what additional medication was part of the combination regimen.

Compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalisation or death were observed in patients whose TNF inhibitor combination regimen included azathioprine/6-mercaptopurine therapy (odds ratio [OR] 1.74), azathioprine/6-mercaptopurine monotherapy (OR 1.84), methotrexate monotherapy (OR 2.00), and JAK inhibitor monotherapy (OR 1.82).

Interestingly, individuals treated with TNF inhibitors in combination with methotrexate therapy had similar odds of hospitalisation or death compared than those given TNF inhibitors alone (OR 1.18), which suggests “that clinicians would benefit from weighing the risks vs benefits of de-escalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine”, the authors noted.

Other factors linked with higher odds of hospitalisation or death included older age (OR per 1 year increase in age, 1.04), active IMID at COVID-19 diagnosis (OR 1.27), obesity (OR 1.39), lung disease (interstitial: OR 1.81 and obstructive OR 2.34); cardiovascular disease (OR 1.58); diabetes (OR 1.54 and chronic kidney disease (OR 3.10). From a treatment perspective, concomitant use of sulfasalazine (OR 1.62), leflunomide (OR 1.89), or oral budesonide (OR 2.86), and higher daily prednisone-equivalent glucocorticoid dose (OR per 1mg increase in dose of 1.07), were also associated with a higher risk.

All-in-all, the findings indicate that in patients with IMIDs, treatment with TNF inhibitor monotherapy “may be associated with a lower risk of COVID-19-associated hospitalisation or death compared with other immunomodulatory treatment regimens,” and “support the continued use of TNF inhibitor monotherapy during the pandemic,” the authors concluded.

In an accompanying comment, Dr Licio A. Velloso, from the Department of Internal Medicine, School of Medical Sciences, at the University of Campinas in Brazil, highlighted that one of the greatest strengths of the research was its “inclusion of a large number of patients with distinct ethnic backgrounds and IMIDs”, which differed from prior, smaller studies that largely included patients from North America and Europe.

The findings, he said, offer a “new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients”.

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