Rheumatism and COVID-19: How safe are TNF inhibitors?

Most rheumatism drugs can be used safely in SARS-CoV-2 infections. Some even seem to protect against severe cases, but individual drugs were associated with a complicated disease path.

Risk factors for severe COVID-19 cases investigated

The majority of rheumatism drugs can also be used safely in cases of infection with SARS-CoV-2. Some drugs even seem to protect against severe courses of COVID-19 disease. However, individual drugs against inflammatory rheumatic diseases are associated with complicated disease paths.

Drugs against inflammatory rheumatic diseases influence the immune system. Some increase the susceptibility to infections. This can also influence the course of a COVID-19 disease. For this reason, Dr. Anne Regierer and Dr. Martin Schäfer from the epidemiology program at the German Rheumatism Research Centre (German acronym: DRFZ) and Dr. Rebecca Hasseli, coordinator of the COVID-19 rheumatism register of the German Rheumatology Society (DGRh), examined the data of 2,000 patients with COVID-19 rheumatism. The DGRh presented the data of 2,274 patients with an inflammatory rheumatic disease and a SARS-CoV-2 infection. The register is a joint project of the DGRh and the University of Gießen (Germany). The current study by Dr. Regierer was also conducted within the framework of this commission.

The DRFZ and DGRh researchers categorised severe courses into three groups: treated as outpatients (1), admitted as inpatients (2) and invasively ventilated or deceased (3). "In the vast majority, the infection was fortunately uncomplicated," reports Dr Hasseli. This was 78 per cent. Unfortunately, 83 patients died of COVID-19, which is 3.6 per cent of those recorded in the registry at that time.

"For the rheumatism patients," explains Dr. Regierer, "it was shown that, as in those not affected by rheumatism, severe courses are often associated with older age, male gender and additional cardiovascular diseases". However, the activity of the rheumatic disease also has a considerable influence: patients with a medium to high disease activity had a significantly higher risk of a more severe COVID-19 course than those with a "stable" disease. Patients with high disease activity who were also taking glucocorticoids had an even higher risk of a complicated course of infection.

High vaccination rate of rheumatism patients could further increase safety

In the group of immunosuppressants used for the treatment of rheumatic diseases, some were slightly more frequently associated with a more severe COVID-19 course, while others were not. While the biologic rituximab was associated with a more severe course of COVID-19 and the JAK inhibitors appear to moderately increase this risk, the commonly used TNF inhibitors, on the other hand, were more associated with a milder course of SARS-CoV-2 infection. "We have to interpret these data cautiously, as this is a cross-sectional survey that does not allow any direct conclusions in the sense of if-then", emphasises Prof. Christof Specker, MD and a board member of the DGRh, who is a spokesperson of the commission. For example, he added, JAK inhibitors and rituximab are used more frequently in more complicated rheumatic courses.


The TNF inhibitors taken by many rheumatism patients are safe in the case of a COVID-19 infection. They could possibly even protect against severe courses. The most important thing is to control the activity of the disease. For this reason, patients should never stop taking medication on their own. The treating rheumatologist must carefully weigh up the therapy. This also includes consistent information about vaccination and the highest possible vaccination rate among rheumatism patients.

Regierer AC, Hasseli R, Schäfer M, et al: TNFi is associated with positive outcome, but JAKi and rituximab are associated with negative outcome of SARS-CoV-2 infection in patients with RMD.