High SLE Disease Activity Over Time Warrants New Treatments, Study Asserts

The activity of systemic lupus erythematosus (SLE) is persistently high in a large proportion of patients, despite high rates of steroids and immunosuppressants use, according to a five-year study. The findings indicate gaps in effectiveness of current SLE treatments, new research has found.

The research, “Persistent Disease Activity Remains a Burden for Patients with Systemic Lupus Erythematosus,” was published in The Journal of Rheumatology.

A substantial proportion of SLE patients have persistently high disease activity, or less-than-acceptable disease control, despite receiving treatment. In the case of corticosteroids, it is associated with organ damage over time. Other options investigated recently have not been satisfactorily effective, according to the researchers’ premise.

Aiming to better understand the burden of persistently active SLE, the team from Canada conducted the 1000 Canadian Faces of Lupus study, which enrolled patients from 2005 to 2008 at 14 Canadian sites.

Specifically, researchers assessed the distribution of levels of disease activity in patients with SLE and correlated it with clinical characteristics. They also analyzed changes in disease activity over time and predictors of these changes.

Clinical manifestations of SLE were recorded at the initial visit. Blood tests to determine levels of autoantibodies — those targeting the body’s own tissues — and assessments of disease activity, including the SLEDAI-2K SLE activity scale, were performed annually. The patients’ current and past medications use, general health, income, age, sex and education level also were considered.

Patients were divided into four groups based on their SLEDAI-2K score at the start of the study, and at every yearly visit (over five years). The groups were: low (under 4); moderate (4 to 5); moderately high (6 to 9), and; very high (above 10).

Overall, the analysis, funded by GlaxoSmithKline, included a total of 2,019 patients (90% women, 63% white), with a mean age at study start of 42 years and mean age at diagnosis of 31 years. Follow-up data were available from 1,326, 580, 274, 186, and 148 patients at 1, 2, 3, 4, and 5 years, respectively.

The overall mean SLEDAI-2K score at first visit was 4.7. Mean disease duration at study start was slightly inferior in patients with very high disease activity — 9.1 years, compared to 11.7 in those with low disease activity.

Patients with very high disease activity also were more likely to have had renal manifestations and were more likely to have lower incomes, with 37.3% being paid less than $30,000 annually in comparison with  25% in the low disease activity group.

The correlation with income may reflect more difficulty accessing care, the researchers noted, and less private insurance coverage for prescription medications.

Use of the steroid prednisone was highest in the group with very high SLE activity (64%), although those with low activity also showed high use (40%). Immunosuppressants also were used more by patients with very high disease activity.

Mean daily dose of prednisone was 24 mg in the very highly active group, but only 11-13 mg in the other groups. Doses higher than 7.5 mg — known to predict increased damage over time — also were prescribed more often to cases in very high activity.

A total of 116 of 181 patients (64.1%) with moderately high or very high initial SLE activity, determined as clinically relevant SLE activity, and three years of follow-up, remained active at five years.

Subsequent analysis showed that patients with low activity had only a 30-50% likelihood of transitioning to more active disease. In turn, those initially with very high disease activity had a probability of achieving low disease activity inferior to 20%, and a 36% likelihood of continued very high disease activity one year later.

Across the years, patients with moderately high SLE activity had nearly 50% probability of maintaining moderately high or very high disease activity one year later; hose with low disease activity showed about 14–25% likelihood of progressing to at least moderately high activity.

The investigators also found that among patients with the same SLEDAI-2K score at study start, those with longer disease duration, highest income category, without arthritis, and female patients, had lower SLE activity at one year. Only higher initial SLEDAI-2K score was a significant predictor of SLEDAI-2K score during the follow-up.

“Our data, similar to others, suggest that optimal control of disease activity is often not achieved with available steroid-sparing treatment options, with more than half of patients taking prednisone, often at substantial doses,” the researchers wrote. “This highlights gaps in the optimal treatment of SLE and the need for additional therapies.”

Of note, two of the study’s authors are employees of GlaxoSmithKline, and a third author was an employee of GlaxoSmithKline at the time of the study.