| Abstract |
Background
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, the treatment of which includes conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biologic DMARDs (bDMARDs). RA is known to be associated with an increased risk of serious infections and the use of bDMARDs almost doubles this risk. Serious infections can lead to sepsis, a life-threatening condition manifested by organ failure caused by a dysregulated host response to a pathogen. Biologic agents target proinflammatory cytokines which mediate the inflammation cascade activated both in RA and sepsis. However, very few data exist regarding the incidence of sepsis in patients with a serious infection while on treatment with bDMARDs.
Aims
This study aimed to evaluate the outcomes of sepsis and death in RA patients having a serious infection and to compare these outcomes in patients on bDMARD treatment versus those not treated with bDMARDs. Secondary aims were the comparison of subgroups of patients treated with different bDMARD classes [Tumor necrosis factor inhibitor (TNFi) versus non-TNFi] and subgroups based on age (geriatric versus younger patients).
Methods
Single center retrospective analysis of adult RA patients registered in the University of Crete Rheumatology Clinic Registry (UCRCR), who were hospitalized for ≥1 serious infection between 2004-2020. Patients were assigned to “bDMARD group” if they were receiving bDMARDs at the time of serious infection or “Control group” if there was no bDMARD exposure at least 3 months before the serious infection. Demographics, RA characteristics and comorbidities were retrieved from UCRCR database, while details regarding hospitalization were sought in the patients’ electronic and paper files. Apart from the Sequential Organ Failure Assessment (SOFA) criteria at admission and 76-92 hours of hospitalization, used to define the diagnosis of sepsis, the duration of hospitalization, the pathogen responsible (if isolated), the criteria of septic shock and in-hospital mortality were also registered.
Results
A total of 117 hospitalizations for serious infection in RA patients were included; 66 in patients receiving bDMARDs and 51 in the control group (65% bDMARD-naive and 35% bDMARD-experienced). The majority of the patients (76%) were women in both groups, however patients on bDMARDs were younger than control patients [70 (IQR 62-77) and 78 (IQR 68-82) years old respectively, p=0.002]. Other demographics, disease characteristics, disease activity at baseline and comorbidities did not differ between the two groups, except for a higher prevalence of a secondary rheumatologic diagnosis and of ≥1 previous hospitalization for infection in patients on bDMARDs.
During hospitalization, 14 patients (12%) died. Mortality was significantly higher in the control group (19.6% of patients) compared to the bDMARD group (6%) (p=0.025). Sepsis criteria were fulfilled in 56 patients (47.9%) at admission and/or at 76-92 hours of hospitalization. Sepsis was marginally more frequent in the control group versus the bDMARD group (56.9% and 40.9% respectively, p=0.087). In the subgroup analysis based on the type of bDMARD, no statistical difference was found for the outcomes of sepsis or death between patients on TNFi versus those on non-TNFi. However, in the subgroup of patients ≥65 years old, there was a tendency for lower incidence of adverse outcomes in patients on TNFi compared to those on non-TNFi or the control group.
Receiver operating characteristic (ROC) analysis indicated older age (p<0.001), higher SOFA score at admission (p<0.001), septic shock at 76-92 hours (p<0.001) and non-exposure to TNFi (p=0.040) as predictors of in-hospital death. However, in multivariable logistic regression analysis, older age was the only significant predictor of sepsis and death during hospitalization.
Conclusions
In the present study we found a high incidence of sepsis (47.9%) and mortality (12%) in RA patients hospitalized for a serious infection. Older age is the most significant predictor of adverse outcomes, however, patients on bDMARD therapy showed lower mortality and a tendency for lower incidence of sepsis compared to the control group.
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