Glucocorticoids exposure is strongly associated with the accrual of irreversible organ damage in systemic lupus erythematosus patients, independent of disease activity, researchers report.
“Our findings suggest that only extremely low doses of glucocorticoid can be considered free of association with damage accrual in patients with SLE,” write researchers in the Nov. 22 issue of Lupus Science and Medicine.
Glucocorticoids are a mainstay treatment in both acute and chronic systemic lupus erythematosus. Previous studies have demonstrated that damage accrual is associated with cumulative disease activity. However, more recent studies suggest that damage accrual may also be associated with systemic lupus erythematosus treatment. Approximately 60 percent of systemic lupus erythematosus patients experience permanent organ damage within seven years of being diagnosed with the disease.
Given that glucocorticoids are often used in the context of high disease activity, it has been challenging for researchers to tease out the independent effect of systemic lupus erythematosus treatment on damage accrual.
This was an observational study of 162 systemic lupus erythematosus patients — 75 percent of whom received glucocorticoids. The patients were observed for two to 4.7 years by Diane Apostolopoulos, M.D., of Monash University in Australia, and colleagues. They measured damage accrual finding that glucocorticoid patients were 42 percent more likely to have significantly more damage as compared to patients who were not prescribed glucocorticoids (42% vs 15%, p<0.01).
The observational nature of the study was one of the limitations of the study, yet, it is noteworthy, the researchers wrote.
“Given the limitations of observational studies in the face of confounding by indication, our findings suggest the urgent need for a randomized study comparing the effect on damage accrual of usual care with that of a strategy that stringently limits glucocorticoid dosing,” Dr. Apostolopoulos and colleagues wrote.
In an editorial that was published online April 7 in Lupus Science and Medicine, Maarten Boers, M.D., of VU University Medical Center in the Netherlands, conveys concerns of the medical community misinterpreting observational studies by limiting applications of a potentially life-saving treatment.
“The truth of the matter is that trials on glucocorticoid beneficial and adverse effects are not being done, and that observational studies (invariably only focusing on glucocorticoid adverse effects, both related and unrelated to the disease) are hopelessly and irretrievably confounded by indication,” wrote Boers. “In brief, patients with the most severe disease are preferentially treated with glucocorticoids, and this leads to the associations found in observational studies, regardless of the beneficial effects of glucocorticoids.”
- Glucocorticoid use is associated with harm in both domains of the (Systemic Lupus International Collaborating Clinics Damage Index (SDI) traditionally associated with glucocorticoid-induced harm (cataracts, osteoporotic fracture, avascular necrosis, diabetes mellitus) and the residual SDI domains not previously associated with glucocorticoid-induced harm.
- Even lower doses of glucocorticoid are associated with damage accrual in SLE. The threshold identified was a time-adjusted mean prednisolone of 4.4 mg per day.
- Cumulative prednisolone exposure was associated with overall damage accrual after controlling for ethnicity and disease activity and was significant at time-adjusted mean doses above 4.42 mg prednisolone per day.
- A dose-response relationship between cumulative prednisolone use and irreversible organ damage accrual was observed, with increasing odds ratios with each ascending quartile.
- Compared to patients in the lowest quartile, patients in the highest quartile of cumulative prednisolone had adjusted odds ratio of 13.46, 95 percent CI (3.59 to 50.4), p<0.01 for damage accrual.
- Of the demographic factors evaluated, only ethnicity was associated with damage accrual. Asian patients had reduced odds of damage accrual compared with Caucasians (adjusted OR=0.22, 95% CI (0.09 to 0.53), p<0.01).
“Our findings further emphasize the need for new, more effective treatments for SLE that minimize or eliminate the need for glucocorticoids,” wrote Apostolopoulos and team.
This research was supported by a grant from Eli Lilly.
Apostolopoulos D, Kandane-Rathnayake R, Raghunath S, et al. “Independent association of glucocorticoids with damage accrual in SLE,” Lupus Science and Medicine. Published online November 22, 2016. DOI: 10.1136/lupus-2016-000157.
Boers M. “Observational studies on glucocorticoids are harmful!” Lupus Science and Medicine. Published online April 7, 2017. DOI: 10.1136/lupus-2017-000219