From the Journals

Glucocorticoids linked to damage accrual in SLE regardless of disease activity



The use of glucocorticoids was associated with damage accrual independent of serologic or clinical disease activity in patients with systemic lupus erythematosus (SLE), according to recent findings published in The Lancet Rheumatology.

“Disentangling the potential contribution of glucocorticoid use to organ damage in SLE is confounded, in most studies, by the fact that glucocorticoid use is usually associated with active disease. Our study showed that organ damage accrual occurred in a similar proportion of patients without disease activity as in the overall cohort, and that glucocorticoid use was a significant risk factor for damage,” wrote Diane Apostolopoulos, MBBS, of Monash University, Melbourne, and colleagues.

The longitudinal cohort study prospectively enrolled 1,707 patients with SLE from May 2013 to December 2016. Study participants were recruited from 13 institutions throughout Australia and Asia. The researchers defined glucocorticoid use as any exposure and cumulative exposure to prednisolone, in addition to mean time-adjusted daily prednisolone dose. Follow-up assessment occurred at least once every 6 months and varied depending on clinical necessity. At baseline, the researchers collected various demographic information, including smoking status, age, and education level, among others. The primary endpoint measured was organ damage accrual, which was assessed at baseline and annually thereafter. In addition, disease activity was evaluated in two multivariable models using Physician Global Assessment (PGA) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores.

After a median duration of 2.2 years, the researchers found that 82.3% of patients were exposed to prednisolone, and 14.9% of patients had experienced a damage accrual event. In the PGA model, mean time-adjusted PGA score (based on a 0- to 1-unit increase) was associated with damage accrual independent of clinical or serologic disease activity (hazard ratio, 1.05; P = .0012).

In the SLEDAI-2K model, baseline damage scores were independently associated with damage accrual (hazard ratio, 1.32; P = .0427).

In both models, ethnicity (Asian vs. non-Asian), age at study enrollment, and mean time-adjusted prednisolone dose were parameters independently associated with damage accrual.

“Novel findings from this study were that Asian ethnicity was protective when compared with any non-­Asian ethnicity, and that antimalarial usage was not protective for damage accrual,” the researchers wrote.

Despite the novel results, the researchers acknowledged that the protective effects of antimalarials could have gone undetected because of the short duration of follow-up.

In a related editorial, Guillermo Ruiz-Irastorza, MD, PhD, of University of the Basque Country in Bizkaia, Spain, said that the study provides novel data highlighting that glucocorticoid use has the potential to negatively affect the clinical progression of patients with SLE (Lancet Rheumatol. 2019 Nov 25. doi: 10.1016/S2665-9913(19)30132-8).

One question that remains from the current study is how to effectively reduce glucocorticoid-related adverse events, while still managing the disease, he further explained.

“These findings suggest that unnecessary use of glucocorticoids should be avoided in the manage­ment of the disease where possible,” the investigators concluded.

The study was funded by UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca. The authors reported financial affiliations with Abbott, AbbVie, Astellas, Ayumi Pharmaceutical, Bristol-Myers Squibb, Novartis, Pfizer, and several others.

SOURCE: Apostolopoulos D et al. Lancet Rheumatol. 2019 Nov 25. doi: 10.1016/S2665-9913(19)30105-5.

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