People with systemic lupus erythematosus (SLE) experienced significantly higher rates of first severe infections, a higher number of severe infections overall, and greater infection-related mortality, compared with controls, based on data from a population-based cohort study of more than 30,000 individuals.
Infections remain a leading cause of morbidity and early mortality in patients with SLE, wrote Kai Zhao, MSc, of Arthritis Research Canada, Richmond, and colleagues. However, “limitations from existing studies including selected samples, small sizes, and prevalent cohorts can negatively affect the accuracy of both the absolute and relative risk estimates of infections in SLE at the population level,” they said.
In a study published in Rheumatology, the researchers identified 5,169 people newly diagnosed with SLE between Jan. 1, 1997, and March 31, 2015, and matched them with 25,845 non-SLE controls using an administrative health database of all health care services funded in British Columbia during the time period. The investigators said the study is the first “to evaluate the risk of severe infections in a large population-based and incident SLE cohort.”
The average age of the patients was 46.9 at the time of their index SLE diagnosis, and 86% were women. The average follow-up period was approximately 10 years.
The primary outcome was the first severe infection after the onset of SLE that required hospitalization or occurred in the hospital setting. A total of 955 (18.5%) first severe infections occurred in the SLE group, compared with 1,988 (7.7%) in the controls, for incidence rates of 19.7 events per 1,000 person-years and 7.6 events per 1,000 person-years, respectively, yielding an 82% increased risk of severe infection for SLE patients after adjustment for confounding baseline factors.
Secondary outcomes of the total number of severe infections and infection-related mortality both showed significant increases in SLE patients, compared with controls. The total number of severe infections in the SLE and control groups was 1,898 and 3,114, respectively, with an adjusted risk ratio of 2.07.
As for mortality, a total of 539 deaths occurred in SLE patients during the study period, and 114 (21%) were related to severe infection. A total of 1,495 deaths occurred in the control group, including 269 (18%) related to severe infection. The adjusted hazard ratio was 1.61 after adjustment for confounding baseline variables.
The risks for first severe infection, total number of severe infections, and infection-related mortality were “independent of traditional risk factors for infection and the results remain robust in the presence of an unmeasured confounder (smoking) and competing risk of death,” the researchers said. Reasons for the increased risk are uncertain, but likely result from intrinsic factors such as immune system dysfunction and extrinsic factors such as the impact of immunosuppressive medications. “Future research can focus on quantifying the relative contributions of these intrinsic and extrinsic factors on the increased infection risk in SLE patients,” they added.
The study findings were limited by several factors linked to the observational design, including possible misdiagnosis of SLE and inaccurate measure of SLE onset, the researchers noted. In addition, no data were available for certain confounders such as smoking and nonhospitalized infections, they said.
However, the results were strengthened by the large size and general population and the use of sensitivity analyses, they noted. For SLE patients, “increased awareness of the risk of infections can identify their early signs and potentially prevent hospitalizations,” and clinicians can promote infection prevention strategies, including vaccinations when appropriate, they added.
Based on their findings, “we recommend a closer surveillance for severe infections in SLE patients and risk assessment for severe infections for SLE patients after diagnosis,” the researchers emphasized. “Further studies are warranted to further identify risk factors for infections in SLE patients to develop personalized treatment regimens and to select treatment in practice by synthesizing patient information,” they concluded.
The study was supported by the Canadian Institutes for Health Research. The researchers had no financial conflicts to disclose.