Factors predictive of serious infections over time in systemic lupus erythematosus patients: data from a multi-ethnic, multi-national, Latin American lupus cohort

Abstract

Aim The aim of this study was to identify factors predictive of serious infections over time in patients with systemic lupus erythematosus (SLE). Methods A multi-ethnic, multi-national Latin American SLE cohort was studied. Serious infection was defined as one that required hospitalization, occurred during a hospitalization or led to death. Potential predictors included were sociodemographic factors, clinical manifestations (per organ involved, lymphopenia and leukopenia, independently) and previous infections at baseline. Disease activity (SLEDAI), damage (SLICC/ACR Damage Index), non-serious infections, glucocorticoids, antimalarials (users and non-users), and immunosuppressive drugs use; the last six variables were examined as time-dependent covariates. Cox regression models were used to evaluate the predictors of serious infections using a backward elimination procedure. Univariable and multivariable analyses were performed. Results Of the 1243 patients included, 1116 (89.8%) were female. The median (interquartile range) age at diagnosis and follow-up time were 27 (20–37) years and 47.8 (17.9–68.6) months, respectively. The incidence rate of serious infections was 3.8 cases per 100 person-years. Antimalarial use (hazard ratio: 0.69; 95% confidence interval (CI): 0.48–0.99; p = 0.0440) was protective, while doses of prednisone >15 and ≤60 mg/day (hazard ratio: 4.18; 95 %CI: 1.69–10.31; p = 0.0019) and >60 mg/day (hazard ratio: 4.71; 95% CI: 1.35–16.49; p = 0.0153), use of methylprednisolone pulses (hazard ratio: 1.53; 95% CI: 1.10–2.13; p = 0.0124), increase in disease activity (hazard ratio: 1.03; 95% CI: 1.01–1.04; p = 0.0016) and damage accrual (hazard ratio: 1.22; 95% CI: 1.11–1.34; p < 0.0001) were predictive factors of serious infections. Conclusions Over time, prednisone doses higher than 15 mg/day, use of methylprednisolone pulses, increase in disease activity and damage accrual were predictive of infections, whereas antimalarial use was protective against them in SLE patients.

Differential Parameters between Activity Flare and Acute Infection in Pediatric Patients with Systemic Lupus Erythematosus

“…However, our result con rmed that renal involvement is signi cantly associated with active infection in the multivariate GEE analysis, in consistent to previous study [40]. Of note, our data is in consistent with Pimentel et al that any increase in the SDI was associated with the occurrence of serious infections [39]. We also showed that compared to PCT, CRP is a more sensitive and speci c marker for diagnosing bacterial infections in SLE [41].…”

“…Multivariate GEE analysis showed that SDI score, fever temperature, CRP level, PCT levels, lymphocyte percentage, NLR, Hb levels, and SLEDAI 2K renal score are independent parameters for predicting acute infection in SLE patients (Table 3b). Renal disease, despite being associated with infections in the univariate analysis, has not retained the statistical signi cance in the multivariate analysis in some series [38,39]. However, our result con rmed that renal involvement is signi cantly associated with active infection in the multivariate GEE analysis, in consistent to previous study [40].…”

“…Infection itself was reported to both potentially facilitate or protect against the development of SLE [10,46]. Results from a adult lupus cohort study in Latin America also showed that increased disease activity and damage accumulation were predictive of infection [39]. One study demonstrated that there is a positive correlation between SDI score and the number of recurrent major infections in pediatric-onset SLE [47].…”

American College of Rheumatology Guidance for the Management of Rheumatic Disease in Adult Patients During the COVID‐19 Pandemic: Version 1

“…Conducted primarily in the context of rheumatoid arthritis, studies examining tapering or discontinuation of biologics or JAK inhibitors suggest that a large proportion of patients experience rheumatic disease flare (78)(79)(80)(81). This is relevant because underlying inflammation or disease activity has been implicated as a risk factor for infection (82,83), a risk that may be heightened further in the context of "rescue" glucocorticoids. Although biologic therapies are associated with an increased risk of hospitalization due to serious infection, at least one report in rheumatoid arthritis has suggested that they are associated with a reduced risk of sepsis or fatal outcome, as compared to nonbiologic DMARDs, among patients developing serious infection with these therapies (84).…”

Monitoring and long-term management of giant cell arteritis and polymyalgia rheumatica

“…In this record-linkage study, however, no effort was made to adjust the results for confounding by indication. This approach is necessary because glucocorticoid doses are linked to clinical activity, and increased disease activity is associated with an increased risk of infections in several rheumatic diseases [142][143][144][145][146][147] .…”