Covid-19: Rheumatism medications could lead to a milder course of the disease
31.03.2024 17:42
Contrary to earlier fears, patients with rheumatoid arthritis do not experience more severe COVID-19 infections than other people in Germany. Some medications used in basic therapy may even have a positive effect on the course of the disease. This is shown by an analysis of the COVID-19-Rheuma.de registry of the German Society for Rheumatology (DGRh), which has now been published in Frontiers in Medicine.
At the beginning of the pandemic, rheumatism patients were classified as particularly vulnerable because they typically have to take medications that affect the immune system. These include glucocorticoids ("cortisone"), which can quickly reduce painful inflammation in the joints during a flare-up. They also receive so-called disease-modifying antirheumatic drugs (DMARDs), which inhibit inflammation in the long term and thus prevent progressive joint destruction. These medications also affect the immune system. "At the beginning of the COVID-19 pandemic, the fear was that the rheumatism medications would hinder the body's defense against the virus and that rheumatism patients would be particularly susceptible to severe COVID-19," recalls Professor Dr. Alexander Pfeil from Jena University Hospital.
Covid-19 disease progression: Comparison of two registries
A team led by PD Dr. med. Rebecca Hasseli-Fräbel from the University Hospital of Münster and Professor Pfeil has now analyzed the Covid-19-Rheuma.de registry of the German Society for Rheumatology (DGRh) to address this question. The Covid-19 registry is a collaborative project between the Justus Liebig University Giessen and the DGRh's Covid-19 Registry Commission, designed to investigate the pandemic's impact on rheumatology patients in greater detail. DGRh President Professor Dr. med. Christof Specker and Professor Dr. med. Ulf Müller-Ladner played a key role in the evaluation on behalf of the commission. The researchers compared the disease progression of 366 patients with an equally sized group of German patients from the LEOSS registry ("Lean European Survey on SARS-CoV-2"). These patients did not suffer from rheumatic diseases or other immune disorders and did not receive any therapy that could affect the immune system. Both patient groups required inpatient treatment due to Covid-19.
Of the rheumatoid arthritis patients, more than half (56) were treated with glucocorticoids. Most patients also received disease-modifying antirheumatic drugs (DMARDs). These included non-specific immunosuppressants such as methotrexate, which is now the first-line treatment for many diseases. Many patients also received biologics, which target the inflammatory reactions in the joints more precisely. Among these, 10 patients received drugs such as adalimumab, certolizumab, infliximab, etanercept, or golimumab, which inhibit tumor necrosis factor alpha (TNF), a substance involved in joint destruction. Approximately the same number of rheumatoid arthritis patients (11) received the antibody rituximab. This suppresses the B cells that produce rheumatoid factor and other antibodies that the overactive immune system forms when attacking the body's own cells.
Influence of drug classes on Covid-19 infections
The analysis revealed that these two drug classes have different effects on the course of a SARS-CoV-2 infection. Patients treated with rituximab were 2.5 times more likely to experience a severe course of Covid-19. "The drug also prevents the formation of antibodies against SARS-CoV-2 and therefore hinders the body's defense against the virus," reports Professor Pfeil.
In contrast, the use of TNF inhibitors was associated with less severe cases of Covid-19. According to PD Dr. Hasseli-Fräbel and Professor Pfeil, a possible explanation for this could be that TNF inhibitors effectively suppress disease activity without significantly inhibiting the immune system. This could therefore have a beneficial effect – including on the course of Covid-19, the experts suggest.
Rheumatism patients do not become more severely ill with Covid-19.
No negative influence of the presence of a rheumatic disease on the course of Covid-19 was apparent. However, previous analyses of the Covid-19 Rheumatism Registry had shown that high rheumatic disease activity negatively impacts the prognosis of a coronavirus infection. PD Dr. Hasseli-Fräbel points out that these analyses refer to the first two waves of the pandemic, before the introduction of vaccines, when Covid-19 was more frequently fatal. In the Rheumatism Registry, 17 of the hospitalized patients died from or with Covid-19. In the comparison group of the LEOSS Registry, the number was 15. The difference was not statistically significant.
Today, the disease is far less frequently fatal. Professor Pfeil explains: "This is partly due to the immunity that the population has built up through vaccinations or previous infections with SARS-CoV-2. But the pathogenicity of SARS-CoV-2 has also decreased in the new variants."„
Vaccination still makes sense
Nevertheless, all rheumatology patients are advised to get vaccinated. The mRNA vaccines are safe for them, even if they are being treated with TNF inhibitors or rituximab. According to the current STIKO (Standing Committee on Vaccination) recommendation, patients receiving basic antirheumatic therapy should be vaccinated annually in the fall with the adapted COVID-19 vaccines. Professor Specker explains: „It is more difficult to develop immunity against SARS-CoV-2 while undergoing treatment with rituximab. If possible, patients should be vaccinated before starting rituximab treatment, or, if already on therapy, shortly before the next dose, which is usually given every 6 to 12 months, to achieve the best possible immune response. This should be done in consultation with the treating rheumatologist.“
Original publication
Rebecca Hasseli et al. The protective effect of tumor necrosis factor-alpha inhibitors in COVID-19 in patients with inflammatory rheumatic diseases compared to the general population—A comparison of two German registries. Frontiers in Medicine 2024; DOI: 10.3389/fmed.2024.1332716
https://www.frontiersin.org/articles/10.3389/fmed.2024.1332716/full
https://pubmed.ncbi.nlm.nih.gov/38510457
Covid-19 rheumatism registry
https://www.covid19-rheuma.de