Organ damage risk doubled with daily doses of 20 mg prednisone.
Organ damage in patients with systemic lupus erythematosus (SLE) has various causes, but prominent among these is the use of high-dose corticosteroids, a large cohort study revealed.
The risk of developing any new organ damage over a mean period of 6.2 years more than doubled (HR 2.514, 95% CI 1.977-3.196, P<0.001) among patients whose mean prednisone dose was 20 mg/day compared with those whose mean dose was below 7.5 mg/day, according to Michelle Petri, MD, director of the Hopkins Lupus Center at Johns Hopkins University School of Medicine, and colleagues.
In addition, for each 1 mg/day increase in prednisone dose, the risk for any new organ damage rose by about 3% (HR 1.028, 95% CI 1.022-1.035, P<0.001) and by 15% (HR 1.150, 95% CI 1.112-1.188, P<0.001) with a 5 mg/day increase in dose, the researchers reported online in Lupus Science and Medicine.
It’s widely recognized that long-term steroid use is associated with organ damage in SLE, but the specific risks have not previously been quantified.
To explore this more fully, Petri and colleagues analyzed data from the Hopkins Lupus Cohort, which is a prospective longitudinal study initiated in 1987. Their analysis included 2,199 patients whose mean age at entry into the cohort was 38 and whose mean disease duration was slightly over 5 years. Almost all were women, 55% were white, and 38% were black.
Disease activity was assessed on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI), and irreversible damage was measured on the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI).
At the time of entry, 70% of patients were on hydroxychloroquine, and 53% were taking steroids, with 40% of those on steroids receiving doses of 7.5 mg/day or higher.
The average SELENA-SLEDAI score was 3.5, but one-quarter of patients had scores of 6 or higher. Mean SDI score at baseline was 1.2.
During the course of follow-up, 20.3% of patients developed musculoskeletal damage, 15.8% had ocular damage, and fractures relating to osteoporosis occurred in 12.4%.
Aside from prednisone dose, factors that were associated with elevated risk for any organ damage included SELENA-SLEDAI score during follow-up (HR 1.398, 95% CI 1.170-1.670, P<0.001), SDI at baseline (HR 1.064, 95% CI 1.023-1.106, P=0.002), and the use of immunosuppressant medications (HR 1.225, 95% CI 1.046-1.434, P=0.012).
In addition to calculating risks for any organ damage, the researchers also estimated risks for the specific organ systems for patients on doses of prednisone of 7.5 mg/day or higher compared with those on doses below 7.5 mg/day:
- Cataracts, HR 2.412 (95% CI 1.778-3.273, P<0.001)
- Osteoporotic fractures, HR 2.161 (95% CI 1.546-3.022, P<0.001)
- Cardiovascular damage, HR 1.544 (95% CI 1.018-2.341, P=0.041)
Renal damage was not associated with prednisone doses of 7.5 mg/day or higher (HR 1.440, 95% CI 0.863-2.403, P=0.163).
Other factors also were associated with damage to the individual organ systems. For instance, having a recent SELENA-SLEDAI score of 6 or higher increased the risk for cataracts (HR 1.475, 95% CI 1.008-2.157, P=0.045), which was notable as the cohort is relatively young.
For osteoporotic fractures, women had double the risk compared with men (HR 2.320, 95% CI 1.174-4.585, P=0.015), and being white versus black was associated with almost twice the risk (HR 1.89, P<0.001).
Moreover, an increase of 1 mg/day in prednisone dose led to increases of 3.8% for cataracts and 4.2% for fractures.
For the cardiovascular and renal damage domains, SELENA-SLEDAI of 6 or higher was associated with significantly higher risk (HR 2.737, 95% CI 1.780-4.209, and HR 4.079, 95% CI 2.521-6.600, respectively, P<0.001 for both).
“In conclusion, understanding the overall risk of organ damage and risk at individual organ systems associated with exposure to high-dose prednisone over time (i.e., 7.5 mg/day or more) and further understanding the risk imposed by an average of a 1 mg/day or 5 mg/day increase in prednisone dose would help clinicians better understand the long-term benefit gained from the use of corticosteroid-sparing therapies that are currently in development in SLE clinical trials,” Petri and colleagues concluded.
A limitation of the study was the lack of information on treatment adherence in the database.