Starting with higher-dose prednisone boosts 1-year renal response in lupus nephritis
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An initial median prednisone dose of 45 mg per day achieved significantly better complete renal response rates at 1 year in patients with new-onset lupus nephritis, according to data published in Arthritis Care & Research.
“Given the numerous adverse events that may arise at any time after treatment initiation with glucocorticosteroids, current efforts are focused on minimizing their use in the management of [lupus nephritis (LN)],” Konstantinos Tselios, MD, PhD, of the Toronto Lupus Clinic, University Health Network, in Canada, and colleagues wrote. “In this context, a small observational study of 45 patients by the Cruces cohort in Spain reported that daily doses of prednisone as low as 20mg/day (15 patients, following methylprednisolone pulses) are not less effective than higher doses (30 patients, 50mg/day on average).
“Another small study from Germany (40 patients in total) reported that a mean daily dose of 8.7mg/day achieved at least comparable results with higher doses (19.2mg/day) in patients treated with cyclophosphamide pulses,” they added. “In these studies, patient matching by propensity score was not considered. These preliminary data call for further studies for the identification of the optimal dose of glucocorticosteroids for remission induction in LN.”
To compare the complete renal response rates associated with medium and high daily prednisone doses among patients with lupus nephritis, Tselios and colleagues examined data from the University of Toronto Lupus Clinic. According to the researchers, the clinic had, as of November 2019, enrolled 2,050 patients with lupus who are followed regularly at 2- to 6-month intervals. Demographic, clinical, immunological and therapeutic variables, as well as most co-morbidities, are recorded for each participant.
For their own study, Tselios and colleagues identified patients who had received remission induction therapy with either mycophenolate mofetil, cyclophosphamide or azathioprine in standard doses for new-onset lupus nephritis. Patients with end-stage renal disease at diagnosis were excluded.
A total of 206 patients with at least 1 year of follow-up prior to their lupus nephritis diagnosis and treatment initiation were included in the analysis. These participants were divided evenly into two groups: those receiving medium prednisone doses, or 30 mg or less per day, or a high amount, defined as 40 mg or more each day. In addition, they were matched based on baseline differences and followed for at least 1 year. Complete renal response was defined as a proteinuria level of less than 0.5 g per day, and no worsening of renal function. The researchers also tracked glucocorticoid-related damage.
According to the researchers, mean daily dosages for the medium- and high-regimen groups were 24.2 ± 4.6 mg and 48.6 ± 12.3 mg, respectively. At 1 year, the complete renal response rate in the high-dose group was 61.8%, compared with 38.2% in the medium-dose group (P = .024). This difference in response rates was reproduced for several subgroups, including concomitant immunosuppressive treatment and proliferative or non‐proliferative disease.
The researchers also noted that complete remission rates were higher at 2 years — 67.8% in the high-dose group, compared with 39% in the medium group (P = .002) — and 3 years — 64.9% compared with 49.1%, respectively (P = .025) — after lupus nephritis diagnosis. Meanwhile, cumulative glucocorticoid doses were comparable at 2 and 3 years, and glucocorticoid‐related damage was accelerated in both groups for the same period.
“Our findings indicate that treatment with initially high prednisone doses along with fast tapering according to the clinical response results in more favorable outcomes in new onset LN,” Tselios and colleagues wrote. “Despite the observation of better efficacy outcomes in patients treated with initially higher prednisone doses, the high rates of adverse event call for alternative strategies in the management of acute LN.”
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