Caution should be exercised when treating systemic lupus erythematosus (SLE) with even low-dose oral corticosteroids (OCS), as their use may be associated with potential harm among this patient population, according to study findings published in Rheumatology.
Organ damage can result from systemic inflammation due to active SLE (primarily affecting women), as well as from treatment with OCS. Prior studies examining acceptable and safe low doses of OCS to be used for treatment of SLE have proven inconclusive.
Investigators assessed treatment with OCS following diagnosis of SLE and evaluated the association between OCS dose and development of comorbidities, infections, malignancies and mortality.
An observational cohort study was conducted using data from the Swedish National Patient Register and the National Prescribed Drug Register (PDR) to identify all incident cases of SLE in Sweden from July 2005 through December 2019. Patients aged at least 18 years were matched 1:5 by sex, age, and county of residence with members of a population control group.
Oral corticosteroid doses were categorized as low- (>0.0 to <5.0 mg/day), medium- (5.0-7.5 mg/day), and high-dose (>7.5 mg/day).
A total of 5309 patients with SLE (84.6% women; mean age, 49.9 years) were included in the analysis, along with 26,545 patients in the control group.
During the first year after diagnosis, median OCS dose was 8.3 mg/day. Almost half (n=160) of patients were taking a median OCS dose of 5.7 mg/day, 15 years after diagnosis.
Within a year of SLE diagnosis, almost two-thirds of patients were taking OCS, more than 40% of whom were taking at least 10 mg/day.
The investigators found that patients with SLE taking low-, medium-, or high-dose OCS vs no OCS were associated with development of hypertension, cataracts, gastroduodenal ulcers, osteonecrosis, osteoporosis, infections (influenza, pneumonia, herpes zoster, and urinary tract infections), and mortality with a significantly increased probability (all P <.05).
Analysis revealed that OCS doses less than 5.0 mg/day were associated with lower hazard ratios (HRs) for development of comorbidities, infections, and impaired survival vs higher OCS doses.
Patients with SLE were at increased risk of developing infections vs the control group, with the highest HRs noted for influenza (HR, 7.57; 95% CI, 4.34-13.23) and herpes zoster (HR, 7.17; 95% CI, 5.74-8.96). The largest cumulative incidence difference among infections was for pneumonia, affecting 22% of patients with SLE vs 7% of the control group.
Patients with SLE were also at increased risk of developing other comorbidities, with the highest HR noted for osteonecrosis (HR, 7.24; 95% CI, 5.15-10.19). The largest cumulative incidence difference among comorbidities was for hypertension, affecting 36% of patients with SLE vs 19% of the control group.
Patients diagnosed with SLE from 2011 to 2015 showed a small reduction in OCS treatment 5 years after diagnosis compared with patients diagnosed from 2006 to 2010 (46% vs 49%; P =.039).
Overall, 873 patients died during follow-up, with the most common cause for mortality among patients with SLE being circulatory diseases (30.8%). Patients receiving OCS in a given year were at an increased risk for mortality in the following year vs patients not receiving OCS (HR for high-dose OCS, 3.75; medium-dose OCS, 2.19; low-dose OCS, 1.59).
Study limitations included the inception cohort design, which left few patients with follow-up data beyond 10 years. Additional limitations included use of prescriptions as a proxy for treatment adherence, as well as missing data on disease activity and ethnicity.
“These results highlight the potential harm also associated with low OCS dose treatment in SLE and the need to judiciously use OCS at the lowest possible dose to maximize efficacy and minimize harm. Consequently, there is a need for new treatments to prevent organ damage and premature death in SLE,” the study authors concluded.
Disclosure: One or more study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Frodlund M, Jönsen A, Remkus L, Telg G, Söderdahl F, Leonard D. Glucocorticoid treatment in SLE is associated with infections, comorbidities, and mortality- a national cohort study. Rheumatology (Oxford). Published online July 13, 2023. doi:10.1093/rheumatology/kead348