Biologic agents for rheumatic diseases in the break of COVID-19: friend or foe?

ABSTRACT

BackgroundThe recent outbreak of COVID-19 has raised concerns in the rheumatology community about the management of immunosuppressive patients diagnosed with inflammatory rheumatic diseases. It is not clear whether the use of biologic agents may suppose a risk or protection against SARS-CoV2 infection however, it has been suggested that severe respiratory forms of COVID-19 occur as result of exacerbated inflammation status and cytokine production. This prompted the use of IL-6 (tocilizumab and sarilumab) and IL-1 inhibitors (anakinra) in severe COVID-19 disease and more recently JAK1/2 inhibitor (baricitinib). Therefore, patients with rheumatic diseases provide a great opportunity to learn about the use of biological agents as protective drugs against SARS-CoV2. ObjectivesTo estimate COVID-19 infection rate in patients treated with biologic agents for rheumatic inflammatory diseases, determine the influence of biologic agents treatment as a risk or protective factor and studying the prognosis of rheumatic patients receiving biologic agents compared to general population in a third level Hospital setting in Leon, Spain. MethodsWe performed a retrospective observational study including patients seen at Rheumatology department who received biological therapy for rheumatic diseases between December 1st 2019 and June 1st 2020 and analysed COVID-19 infection rate. All patients being attended at the rheumatology outpatient clinic with diagnosis of inflammatory rheumatic disease receiving treatment with biologic agents were included. Main variable was the hospital admission related to COVID-19. The covariates were age, sex, comorbidities, biologic agent and need for hospitalization. We performed a multivariate logistic regression model to assess risk factors of hospital admission. ResultsThere was a total of 3711 patients with COVID-19 requiring hospitalization. 30 patients out of a total of 820 patients (3.6%) receiving biological therapy had contracted COVID-19 and four required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 2.75%, and it was 0.48% among the group with underlying rheumatic diseases. A total of 423 patients died, 2 of which received treatment with biologic agents. Patients who tested positive for COVID-19 were older (female median age 61.8 IQR 46.5-75; male median age 68 IQR 48.5-72) than those who were negative for COVID-19 (female median age 58.4 IQR 48-69; male median age 55.9 IQR 46-66) and more likely to have cardiovascular disease (27 % vs 10%, OR 3. 41 (CI 1.47 - 7.94), p 0.004), be active smokers (13% vs 5%, OR 3.14 (CI 1.04-9.47), p 0.04) and receiving treatment with IL-12/23 inhibitors (6.7% vs 1.4%, OR 5.06 (CI 1.07-23.91) and rituximab (13% vs 2%, 2.66 (CI 1.03-7.27), p 0.04) and were less likely to be receiving treatment with IL-6 inhibitors (0% vs 14%, CI (0.006-0.97, p <0.05). When exploring the effect of the rest of the therapies between groups (affected patients vs unaffected), we found no significant differences in bsDMARD proportions. IL-1 inhibitors, IL6 inhibitors, JAK inhibitors and belimumab treated patients showed the lowest incidence of COVID-19 among adult rheumatic patients. We found no differences in sex or rheumatological disease between patients who tested positive for COVID-19 and patients who tested negative were found. ConclusionsOur findings suggest that use of biological therapy does not associate with severe manifestations of COVID-19, and it is likely to have a protective effect against them when compared to the general population.