January 06, 2020
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Glucocorticoids linked to organ damage in SLE independent of disease activity

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Glucocorticoid treatments contribute to organ damage accrual in patients with systemic lupus erythematosus, independent of clinical or serological disease activity, according to data published in The Lancet Rheumatology.

“Glucocorticoid use and disease activity are closely linked in SLE; in the absence of safer or more effective medicines, glucocorticoids are prescribed for patients with active disease for their powerful immunosuppressant and anti-inflammatory properties,” Diane Apostolopoulos, MBBS, of Monash University, in Melbourne, Australia, and colleagues wrote.

“In studies of organ damage in SLE, therefore, the association of disease activity and glucocorticoid dose raises the issue of confounding by indication, such that it is difficult even with sophisticated statistical approaches to ascertain the direct contribution of glucocorticoid use to organ damage in a setting where such use accompanies active disease,” they added. “Another way to examine whether glucocorticoids contribute to organ damage accrual in SLE independently of disease activity is to study patients in whom the variable of disease activity is absent.”

To examine the impact of glucocorticoid use on damage accrual independent of SLE disease activity, Apostolopoulos and colleagues studied data from the Asia-Pacific Lupus Collaboration cohort, specifically focusing on patients without measurable disease activity. The cohort included adult patients with SLE recruited between May 1, 2013, and Dec. 31, 2016, from 13 centers in Australia, Indonesia, Japan, Malaysia, the Philippines, Singapore, Taiwan, and Thailand. Participants were followed longitudinally for a median period of 2.2 years.

 
Glucocorticoid treatments contribute to organ damage accrual in patients with SLE, independent of clinical or serological disease activity, according to data.
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Disease activity, based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Physician Global Assessment (PGA) scores, as well as treatment information was recorded during each visit, at least every 6 months. Organ damage was assessed annually using the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Glucocorticoid use was measured as any treatment with prednisolone, cumulative prednisolone exposure and time-adjusted mean daily prednisolone dose. Apostolopoulos and colleagues included 1,707 cohort participants in their analysis.

The researchers used multivariate survival analyses to study time-dependent links between glucocorticoid use and damage accrual, with an association defined as an increase of 1 or more on SDI. A SLEDAI-2K score of 0 denoted a lack of clinical and serological disease activity, with a subset of such participants defined by a time-adjusted mean SLEDAI-2K (AMS) score of 0.

According to the researchers, damage accrual events were recorded in 14.9% of included patients, while 82.3% of patients were exposed to prednisolone, with a median time-adjusted mean prednisolone dose of 5 mg per day (IQR = 1.9-8.8).

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Due to SLEDAI-2K and PGA scores being highly correlated, the researchers developed two multivariable models, each including one of these two variables. In the model including AMS score, baseline SDI damage, defined as an SDI score of more than 0, was independently associated with damage accrual (HR = 1.32; 95% CI, 1.01-1.73). In the second model, time-adjusted mean PGA score was independently associated with damage accrual (HR = 1.05; 95% CI, 1.02-1.08). Time-adjusted mean prednisolone dose, age at enrollment and ethnicity were independently associated with damage accrual in both models.

Among the included patients, 157 demonstrated no disease activity, based on an AMS score of 0. Of these participants with no disease activity, 65.6% used glucocorticoids, with a median time-adjusted mean prednisolone dose of 2 mg per day (IQR = 0-5). Irreversible organ damage was accrued in 13.4% of these patients. Such damage was independently associated with time-adjusted mean prednisolone dose (HR = 1.14; 95% CI, 1.03-1.26), time-adjusted mean PGA score (HR = 1.13; 95% CI, 1.03-1.23), and age at enrollment (HR = 1.04; 95% CI, 1.01-1.07), but not baseline SDI damage.

“Damage accrual occurs in patients who have no clinical or serological disease activity as captured by the SLEDAI-2K, and glucocorticoid use contributes independently to the risk of organ damage in these patients and in patients with SLE overall,” Apostolopoulos and colleagues wrote. “In the absence of more effective and safer treatments for SLE, glucocorticoid use remains essential in patients with significant disease activity. However, these findings suggest that unnecessary use of glucocorticoids should be avoided in the management of the disease where possible.” – by Jason Laday

Disclosure: The researchers report funding from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen and UCB Pharma. Please see the study for all other authors’ relevant financial disclosures.