Dr. Sammaritano explained the preference for triple over dual therapy. She noted that the best current randomized controlled trials on the topic, such as the BLISS-LN study with belimumab and the AURORA trial with voclosporin, show improved outcomes with the addition of another immunosuppressant without greater adverse events.4,5
“Nephron loss continues throughout a person’s lifetime, and every episode of lupus nephritis changes the course of that decline for the worse,” Dr. Sammaritano said. “So we feel we can’t wait for nephron loss to implement what has been shown to be the most efficacious therapy.”
Typically, these additional immunosuppressives should be:
- MMF—or an analog, such as mycophenolic acid—plus belimumab;
- MMF with a calcineurin inhibitor (e.g., voclosporin, tacrolimus and cyclosporine); or
- Low-dose cyclophosphamide— as established in the Euro- Lupus Nephritis Trial—plus belimumab, with MMF switched in after the initial course of cyclophosphamide is complete.6
Also, MMF-based regimens are conditionally recommended over cyclophosphamide-based regimens in patients with class III or class IV lupus nephritis, which Dr. Sammaritano explained is largely due to safety concerns. For patients with extra-renal disease, triple therapy containing belimumab is the conditional recommendation. If cyclophosphamide is used, it should be the lower dose protocol.
Another specific, conditional recommendation is for MMF plus a calcineurin inhibitor plus corticosteroids to be used if proteinuria is greater than 3g/g creatinine in class III, class IV nephritis or if over 1g/g creatinine in class V (membranous) nephritis, which is less common. Dr. Sammaritano explained that was due to the stabilizing effects of calcineurin inhibitors on the podocyte cytoskeleton.
“We do not specifically recommend cyclophosphamide with a calcineurin inhibitor as one of our options because this combination has not been studied in randomized controlled trials,” said Dr. Sammaritano. “But this does not mean that this combination cannot be used when indicated.”
Corticosteroids
In line with other recent ACR guidelines, this guideline attempts to limit doses of glucocorticoids and their consequent toxicities. Therefore, pulse IV glucocorticoids followed by low to moderate doses of oral glucocorticoids (i.e., 0.5 mg/kg/day with a max dose of 40 mg/day, tapering to a target dose of less than 5 mg/day by six months) are conditionally recommended.
Dr. Sammaritano described a recent meta-analysis that found that pulse glucocorticoids followed by a lower dose of oral glucocorticoids maximized complete renal response while minimizing toxicity.7 Moreover, she noted that patient panel participants strongly desired lower glucocorticoid doses if possible.
