Development of Damage Strongly Associated With Increased Mortality in SLE

Development of damage is strongly associated with increased mortality in systemic lupus erythematosus (SLE), according to study results published in Rheumatology.¹ Researchers indicated that patients with SLE at increased risk of developing damage included those who received high-dose steroids and immunosuppressants in the first 2 years of treatment.

Previous studies have showed that immunosuppressive agents and biologics have led to a considerable improvement in the 5-year survival rate of patients with SLE; however, patients with SLE who live longer often face the risk for long-term chronic organ damage and disability because of persistent disease activity and/or side effects from treatment.² Other studies have reported that patients with SLE who develop chronic damage within 1 year of disease onset have higher mortality, though there is a lack of long-term follow-up data from large cohorts.³

The objective of this study was to examine damage and mortality in 300 patients with SLE in London, United Kingdom, who were followed up for up to 40 years.

Researchers performed a retrospective analysis of medical records and scores from the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index to compare demographic, clinical, serologic, and treatment factors in 231 patients with damage (77%) with those in 69 patients who never developed damage. Kaplan-Meier analysis was used to assess survival and damage-free survival in both groups of patients.

Study results indicated that compared with patients without damage, patients with damage were more likely to have experienced kidney involvement (42.0% vs 15.9%; P <.001), central nervous system involvement (30.3% vs 14.5%; P =.009), and to have received steroids (82.5% vs 58.6%; P <.001) or various immunosuppressants. Risk factors of developing chronic damage were ethnicity (hazard ratio [HR] of 1.22 for patients of African or Caribbean ethnicity vs white patients; 95% CI, 1.00-1.50; P =.045), high doses of steroids (HR, 1.47; 95% CI, 1.08-1.99; P =.014), and early use of immunosuppressants (HR, 2.08; 95% CI, 1.53-2.82; P <.001).

Of the 87 patients who died during the 40-year follow-up period, 93.1% had damage compared with 70.4% of the patients who survived (P <.001). Sepsis was the main cause of death (26.4%), followed by cancer (25.3%) and cardiovascular events (19.5%). Compared with patients who survived, patients who died were older at the time of SLE diagnosis (29.4±9.77 years vs 33.6±12.03 years). Multivariable analysis showed that age at SLE onset, damage, positive antiphoshoplipid antibodies, serositis, and azathioprine treatment remained statistically significant in differentiating the 2 groups. Researchers found that the presence of any damage was associated with increased mortality (HR, 8.43; 95% CI, 2.64-26.9; P <.001), with age at SLE diagnosis and early use of high-dose steroids and immunosuppressants associated with death.

The main study limitation was the lack of data on disease activity.

“A move to treatment of severe SLE using less toxic drugs may begin to resolve this conundrum as well as achieving better outcomes for patients,” the researchers concluded.

References

1. Segura BT, Bernstein BS, McDonnell T, et al. Damage accrual and mortality over long-term follow-up in 300 patients with systemic lupus erythematosus in a multi-ethnic British cohort. Rheumatology (Oxford). 2020;59(3):524-533.

2. Wada Y, Hasegawa H, Saeki T et al. Long-term prognosis and factors associated with damage accrual in Japanese patients with systemic lupus erythematosus. Clin Exp Nephrol. 2018;22:597-602.

3. Conti F, Ceccarelli F, Perricone C, et al. The chronic damage in systemic lupus erythematosus is driven by flares, glucocorticoids and antiphospholipid antibodies: results from a monocentric cohort. Lupus. 2016;25:719-726.