Higher steroid dose improves lupus nephritis renal outcomes, raises mortality risk
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Key takeaways:
- Higher glucocorticoid doses improved lupus nephritis treatment response but increased serious infections and death.
- Pulses led to greater rates of response and death, but not serious infection.
Patients with lupus nephritis who receive higher initial doses of glucocorticoids demonstrate improved renal outcomes, albeit with increased serious infection and mortality risks, according to data published in Arthritis & Rheumatology.
“Glucocorticoids are a cornerstone in lupus nephritis therapy, and it is known that in combination with immunosuppression they can improve kidney outcomes, but can also increase the risk for infections,” Gabriel Figueroa-Parra, MD, an assistant professor of rheumatology at the Autonomous University of Nuevo León, in Mexico, told Healio. “There is remarkable lack of evidence to inform the appropriate dosing of glucocorticoids during the initial therapy of lupus nephritis. Appropriate tailoring of glucocorticoids is critically important.”
To examine the impact glucocorticoid regimens have on renal response, infections and mortality in patients with lupus nephritis, Figueroa-Parra and colleagues conducted a systematic review and meta-analysis. The researchers analyzed 50 control arms from 37 randomized controlled trials — featuring a total of 3,231 patients with biopsy-proven lupus nephritis — and evaluated protocolized regimens of glucocorticoids with mycophenolic acid analogs or cyclophosphamide.
The primary outcomes were complete response — defined as proteinuria under 0.5 grams during a period of 24 hours and stabilization of serum creatinine — as well as serious infections and all-cause death. The starting glucocorticoid dose was analyzed as a continuous variable via meta-regression.
According to the researchers, the meta-regression predicted that starting at 25 mg per day of oral prednisone, without methylprednisolone pulses, would yield a complete response rate of 19.5% (95% CI, 7.3-31.5) at 6 months. The prediction increased to 34.6% (95% CI, 16.9-52.3) when starting at 60 mg per day without pulses.
However, the 60 mg prednisone dose also increased the predicted serious infection rate to 12.1% (95% CI, 9.3-14.9), vs. 3.2% (95% CI, 2.4-4) with the 25 mg dose, and the predicted death rate to 2.7% (95% CI, 0-5.3), vs. 0.2% (95% CI, 0-0.4) with the lower dose.
Meanwhile, the addition of glucocorticoid pulses resulted in greater rates of complete response and death, but not serious infections, according to the researchers.
“This study is relevant for clinical practice because it showed the trade-offs of treating lupus nephritis with glucocorticoids when used with mycophenolate mofetil or cyclophosphamide — the standard of care,” study co-author Ali A. Duarte-Garcia, MD, of the Mayo Clinic, told Healio. “Higher doses of glucocorticoids result in higher rates of complete renal response but also higher rates of infection and death.”
Figueroa-Parra added that the results represent “the best available evidence to inform decision-making regarding the initial dose of glucocorticoids in patients with lupus nephritis.”
“Our results confirm what is known, higher glucocorticoid doses are more effective and carry a higher risk of infection,” he said. “However, we did not expect that mortality would also be increased or show a dose-response gradient. We neither expected that the use of IV pulses was going to be an effect modifier for mortality.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
At the 2019 American College of Rheumatology meeting, an abstract was presented that reviewed 64 studies regarding the safety of high-dose pulse intravenous corticosteroids, with 18 comparing them to oral steroids and 46 comparing them to placebo. Their conclusion was that pulse was not associated with an increased risk for serious adverse effects.
This contrasts with my personal observations, which have included serious infections, avascular necrosis (multiple sites in one patient), and steroid psychosis.
To quote a recent article by John Cush, MD, Arthur Kavanaugh, MD, and Michael Weinblatt, MD: “Pulse corticosteroid therapy is rarely, if ever, indicated in the management of RA. Pulse therapy is administered as three daily IV infusions of methylprednisolone 1,000 mg. Pulse therapy is usually reserved for those with life-threatening complications, such as vasculitis, severe cytopenia, or pericardial tamponade.”
They additionally noted that the long-term results for RA without life-threatening complications were no better with pulse than with oral steroids.
In the present study, a dose-response relationship was observed between the initial glucocorticoid dose and the rates of complete remission, serious infections, and death at six months. Higher initial glucocorticoid doses correlated with increased rates of all three outcomes. Those receiving pulse steroids did not have an increased rate of infections.
Seventy years after the discovery of cortisone, medicine is still trying to find the safest and most effective way to use them.
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