Cruces’ Recipe
“Our scheme revolves around brief methylprednisolone pulses,” said Dr. RuizIrastorza. “We believe this approach allows rapid remission with very low toxicity cost to the patient.” By using only brief, highdose pulses, they aim to maximize the nongenomic effects of glucocorticoids, while avoiding the toxic genomic effects that accrue with longer time on prednisone doses upward of 30 mg daily.
After the methylprednisolone pulses of one to three days’ duration, the prednisone taper starts at a maximum dose of 20–30 mg daily, and is decreased to 5 mg daily by 12 weeks.6 For example, in an SLE patient with mild-to-moderate disease manifestations (e.g., arthritis, serositis), Dr. Ruiz-Irastorza and colleagues treat with a three-day, 125 mg methylprednisolone pulse, followed by 5–10 mg of prednisone for two to four weeks, and resumption of 5 mg of prednisone daily thereafter.
For major organ manifestations (e.g., lupus nephritis), they treat with a three-day, 250–500 mg methylprednisolone pulse, followed by a fixed prednisone taper scheme that begins at a maximum of 30 mg daily for seven days down to 5 mg daily within 12 weeks. They also administer single 125 mg doses of methylprednisolone every two weeks alongside Euro-Lupus cyclophosphamide dosing.6
“The methylprednisolone doses are for increasing the nongenomic effects, while decreasing the genomic effects from the oral prednisone taper as quickly as possible,” he explained.
Dr. Ruiz-Irastorza continued, “For lifethreatening SLE flares, we do almost the same thing, but add rituximab [and/or other agents]. We keep the prednisone tapering scheme the same, and continue to give methylprednisolone pulses with the Euro-Lupus protocol.”
‘There’s growing evidence that lower doses of prednisone work well, especially in lupus nephritis.’ —Guillermo Ruiz-Irastorza, MD, PhD
Their Evidence
In 2019, Dr. Ruiz-Irastorza et al. published observational data that speaks to the success of their glucocorticoid dosing approach.7 They compared their SLE cohort with a cohort at the University of Bordeaux and found statistically significant differences in clinical remission on treatment at year one (84% vs. 43%, P<0.001), as well as prolonged remission at year one to five (70% vs. 28%, P<0.001).
In 2021, they published further observational data regarding the addition of 125 mg of methylprednisolone to the Euro-Lupus protocol for lupus nephritis. Additional methylprednisolone pulses improved complete renal response rates above 80% at 12 months and reduced the need for oral glucocorticoids.8 Of note, the AURORA 1 trial that led to approval of voclosporin for the treatment of lupus nephritis used a similar prednisone tapering scheme, but achieved lower remission rates.9
