TOPLINE:

A high initial dose of glucocorticoids in the treatment of patients with lupus nephritis (LN) showed a positive association with complete responses (CRs), serious infections, and mortality in a meta-analysis.

METHODOLOGY:

• LN is a severe manifestation of systemic lupus erythematosus and a significant cause of morbidity and mortality. Understanding the optimal glucocorticoid dosing can improve renal outcomes and minimize the risk for infection and death.
• This meta-analysis of 37 randomized controlled trials included 3231 patients with LN (mean age, 31.2 years; 88% women) who were treated with glucocorticoids in combination with mycophenolic acid analogs or cyclophosphamide.
• Of the 50 treatment arms in the trials, 12 used an initial dose of ≤ 30 mg/d (n = 633) and 38 used an initial dose of > 30 mg/d (n = 2598).
• The outcomes included CR, serious infections, and all-cause mortality.

TAKEAWAY:

• At 6 and 12 months, the overall CR rates were 29.8% and 33.9%, respectively, while serious infection rates were 10.1% and 11.7% and mortality rates were 1.9% and 2.2%, respectively.
• At 6 months, the initial glucocorticoid dose showed a positive association with the rates of CR (β-coefficient, 0.023; P = .003), serious infections (0.041; P = .01), and mortality (0.076; P = .006).
• Compared with a low starting dose, a high starting dose was associated with similar CR rates (29.8% vs 29.7%) but numerically higher rates of serious infections (10.4% vs 6.3%) and mortality (2.0% vs 0.8%) at 6 months. However, the associations were not statistically significant.

IN PRACTICE:

The authors wrote, “A higher dose of glucocorticoids is more likely to be effective but at the cost of serious infections and early mortality.” The authors further added, “Clinicians must weigh the benefits and harms that higher doses of glucocorticoids confer in the first 6 months of LN treatment.”

SOURCE:

The study was led by Gabriel Figueroa-Parra, MD, Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, and was published online on May 24 in Arthritis & Rheumatology.

LIMITATIONS:

The study was limited by the lack of head-to-head comparisons of various starting doses of glucocorticoid and information around the time to event. Outcomes beyond 12 months were not reported. The estimated dose or category may not have corresponded with extreme weights or protocol deviations.

DISCLOSURES:

This study was supported by an award from the Rheumatology Research Foundation. Two authors declared receiving grants from various sources, and one author served as a consultant for various pharmaceutical companies. The other authors did not report any conflicts of interest.