Use of Glucocorticoids Linked to Organ Damage in SLE, Study Finds

These findings draw attention to the possible harmful effects of glucocorticoids — a type of corticosteroid hormone — and indicate that these therapies should be avoided by people with SLE when possible, the investigators said.

The study, “Factors associated with damage accrual in patients with systemic lupus erythematosus with no clinical or serological disease activity: a multicentre cohort study,” was published in the journal The Lancet Rheumatology.

Glucocorticoids such as prednisone are prescribed for patients with active disease due to their immunosuppressive and anti-inflammatory properties. 

While glucocorticoids work quickly to reduce inflammation, extended use has been associated with organ damage. This makes it difficult to determine if such damage seen in people with SLE is caused by active disease or the use of these treatments.

To better understand the source of organ damage in SLE patients on glucocorticoids, researchers from 13 centers collaborated to determine if these medications also are associated with organ damage in SLE patients without active disease. The 13 centers were located in Australia, Indonesia, Japan, Malaysia, the Philippines, Singapore, Taiwan, and Thailand.

Adults with SLE were identified from the Asia-Pacific Lupus Collaboration — a large, international partnership of lupus clinicians and researchers. 

Among the 1,707 patients recruited, 1,591 (93.2%) were women. Participants’ median age was 29 years and median SLE disease duration was 8 years.

Clinical information was collected at the study’s start. Follow-up visits were conducted at least once every six months for a median follow-up period of 2.2 years. 

Disease activity was determined using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), a tool based on 24 factors of disease activity in nine organ systems. A score of 0 in SLEDAI-2K represented no disease activity.

Clinicians collected information on prednisolone use at each visit. A Physician Global Assessment (PGA) was determined with a scale from 0 — for no disease activity — to 3, for maximally active disease. Organ damage was assessed using the Systemic Lupus International Collaborating Clinics Damage Index (SDI) at a minimum of one follow-up visit.

The results showed that 709 patients (41.5%) had irreversible organ damage at the start of the study (baseline). Over the study period, increased organ damage was reported in 255 participants (14.9%). 

The factors linked to organ damage included previous damage, SLEDAI-2K score (disease activity over time), the mean PGA score, current smoking, and both age and disease duration at study enrollment. Interestingly, people of Asian ethnicity showed protection against accumulation with organ damage compared with non-Asians.

However, organ damage was significantly associated with use of prednisolone, and both the mean dose and cumulative amount taken. 

During the study’s course, 157 patients (9.2%) showed no signs of disease activity. Yet, irreversible organ damage was reported in 21 (13.4%) of these participants.

This was a similar rate compared with the overall study group, the researchers noted. 

These findings support the link between glucocorticoids and damage accumulation in SLE, with a 14% increase in the risk of organ damage for each 1 mg increase in the mean daily dose of prednisolone, the scientists said.

While most patients were taking prednisolone during the study period, 302 (17.7%) participants had no exposure to oral glucocorticoids. Of these, 108 (35.8%) had organ damage before the study, and 31 (10.3%) developed such damage over the study period. This damage was linked to age, disease duration, and PGA score. 

“These findings add evidence in support of the harmful effects of glucocorticoids in SLE,” the team said.

“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,” the investigators added. 

Steve holds a PhD in Biochemistry from the Faculty of Medicine at the University of Toronto, Canada. He worked as a medical scientist for 18 years, within both industry and academia, where his research focused on the discovery of new medicines to treat inflammatory disorders and infectious diseases. Steve recently stepped away from the lab and into science communications, where he’s helping make medical science information more accessible for everyone.
José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.