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

Santos, Cristiana Sieiro; Fernandez, Xenia Casas; Morales, Clara Moriano; Diez, Elvira Alvarez; Castro, Carolina Alvarez; Robles, Alejandra Lopez; Sandoval, Trinidad Perez

Background: The recent outbreak of COVID19 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 SARSCoV2 infection however, it has been suggested that severe respiratory forms of COVID19 occur as result of exacerbated inflammation status and cytokine production. This prompted the use of IL6 (tocilizumab and sarilumab) and IL1 inhibitors (anakinra) in severe COVID19 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 SARSCoV2. Objectives: To estimate COVID19 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. Methods: We 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 COVID19 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 COVID19. 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. Results: There was a total of 3711 patients with COVID19 requiring hospitalization. 30 patients out of a total of 820 patients (3.6%) receiving biological therapy had contracted COVID19 and four required hospital care. Crude incidence rate of COVID19 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 COVID19 were older (female: median age 61.8 IQR 46.5 to 75; male: median age 68 IQR 48.5 to 72) than those who were negative for COVID19 (female: median age 58.4 IQR 48 to 69; male: median age 55.9 IQR 46 to 66) and more likely to have cardiovascular disease (27 % vs 10%, OR 3. 41 (CI 1.47 to 7.94), p 0.004), be active smokers (13% vs 5%, OR 3.14 (CI 1.04 to 9.47), p 0.04) and receiving treatment with IL-12/23 inhibitors (6.7% vs 1.4%, OR 5.06 (CI 1.07 to 23.91) and rituximab (13% vs 2%, 2.66 (CI 1.03 to 7.27), p 0.04) and were less likely to be receiving treatment with IL6 inhibitors (0% vs 14%, CI (0.006 to 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. IL1 inhibitors, IL6 inhibitors, JAK inhibitors and belimumab treated patients showed the lowest incidence of COVID19 among adult rheumatic patients. We found no differences in sex or rheumatological disease between patients who tested positive for COVID19 and patients who tested negative were found. Conclusions: Our findings suggest that use of biological therapy does not associate with severe manifestations of COVID19, and it is likely to have a protective effect against them when compared to the general population.