Glucocorticoid Therapy and the Risk of Infection in Patients With Newly Diagnosed Autoimmune Disease

Abstract

Glucocorticoid (GC) therapy is associated with the risk of life-threatening adverse events in patients with autoimmune disease. To determine accurately the incidence and predictors of GC-related adverse events during initial GC treatment, we conducted a cohort study. Patients with autoimmune disease who were initially treated with GCs in Japan National Hospital Organization (NHO) hospitals were enrolled. Cox proportional hazard regression was used to determine the independent risks for GC-related serious adverse events and mortality. Survival was analyzed according to the Kaplan-Meier method and was assessed with the log-rank test.The 604 patients had a total follow-up of 1105.8 person-years (mean, 1.9 year per patient). One hundred thirty-six patients had at least 1 infection with objective confirmation, and 71 patients had serious infections. Twenty-two cardiovascular events, 55 cases of diabetes, 30 fractures, 23 steroid psychosis events, and 4 avascular bone necrosis events occurred during the follow-up period. The incidence of serious infections was 114.8 (95% confidence interval, 95.7Y136.6) per 1000 person-years. After adjustment for covariates, the following independent risk factors for serious infection were found: elderly age (hazard ratio EHR^, 1.25/10-yr age increment; p = 0.016), presence of interstitial lung disease (HR, 2.01; p = 0.011), high-dose GC use (Q29.9 mg/d) (HR, 1.71; p = 0.047), and low performance status (Karnofsky score, HR, 0.98/1-score increment; p = 0.002). During the follow-up period, 73 patients died, 35 of whom died of infection. Similarly, elderly age, the presence of interstitial lung disease, and high-dose GC use were found to be significant independent risk factors for mortality. The incidence of serious and life-threatening infection was higher in patients with autoimmune disease who were initially treated with GCs. Although the primary diseases are important confounding factors, elderly age, male sex, the presence of interstitial lung diseases, high-dose GCs, and low performance status were shown to be risk factors for serious infection and mortality.(Medicine 2013;92: 285Y293) Abbreviations: AE = adverse event, CI = confidence interval, CMV = cytomegalovirus, CT = computed tomography, GC = glucocorticoid, GI = gastrointestinal, HR = hazard ratio, IR = incidence rate, NHO = National Hospital Organization, RR = relative risk, SLE = systemic lupus erythematous, SOC = System Organ Class.

Cumulative Burden of Glucocorticoid-related Adverse Events in Patients with Systemic Lupus Erythematosus: Findings from a 12-year Longitudinal Study

“…Our finding that the likelihood of developing certain GC-related AE (including myopathy, glaucoma, nausea/ vomiting, fatty liver, tuberculosis, fungal infection, and cardiovascular disease) was associated with high-dose GC therapy is also consistent with previous studies 8,26 . Our study showed that the risk of bacterial infection increased with the GC daily dose 28,29,30 . In addition, our findings supported previous results that opportunistic infections 7,23,31 such as tuberculosis and fungal infections were associated with GC use in a dose-response relationship 32 .…”

Sarcoidosis Increases Risk of Hospitalized Infection. A Population-based Study, 1976–2013

“…An increased risk of both pyogenic and opportunistic infection has been observed in several immune-mediated disorders such as rheumatoid arthritis, system lupus erythematosus, idiopathic inflammatory myositis, and vasculitis (1)(2)(3)(4). Use of immunosuppressive agents and immune dysregulation are believed to play a pivotal role in the pathogenesis of the increased risk (5).…”

Incidence of Symptomatic Vertebral Fractures Among Newly Diagnosed Autoimmune Diseases Initiating Glucocorticoid Therapy

“…Patients were eligible for the study if they were initially treated with GCs for a recently diagnosed (within 4 weeks prior to study entry) autoimmune disease using established criteria. 10 The cohort start date was defined as the time of initiation of the first GC prescription. The autoimmune diseases registered in this study were as follows: rheumatic diseases—systemic lupus erythematosus, mixed connective-tissue disease, polymyositis, dermatomyositis, vasculitis, Behçet disease, systemic scleroderma, adult-onset Still disease, Sjögren syndrome, rheumatoid arthritis, autoimmune bullous diseases, and anaphylactoid purpura; neurological diseases—multiple sclerosis, myasthenia gravis, and chronic inflammatory demyelinating polyneuropathy; gastrohepatobiliary diseases—ulcerative colitis, autoimmune hepatitis, autoimmune pancreatitis, and primary biliary cirrhosis.…”

“…In the present study, we investigated the risk factors of symptomatic vertebral fracture, analyzing the database of cohort study conducted on patients with recently diagnosed autoimmune disease in the National Hospital Organization (NHO) hospitals between 2006 and 2008. 10 …”