medwireNews: Patients with new-onset lupus nephritis may be more likely to achieve a complete renal response if initially given a higher dose of prednisone than currently recommended, findings indicate.
The researchers also emphasize that the patients who were initially given a prednisone dose of at least 40 mg/day, which is higher than the 0.3–1.0 mg/kg per day recommended by the American College of Rheumatology (ACR) and EULAR, had a lower cumulative glucocorticoid dose over 3 years than those given a lower dose and were no more likely to experience glucocorticoid-related damage accrual.
Altogether, these “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 [lupus nephritis],” write Murray Urowitz (Centre for Prognosis Studies in Rheumatic Diseases, Toronto, Ontario, Canada) and colleagues.
Urowitz et al analyzed data from 103 patients with new-onset lupus nephritis enrolled in The University of Toronto Lupus Clinic who were initially given high prednisone doses (≥40 mg/day, mean 48.6 mg/day). These patients were matched using propensity scores for baseline clinical, demographic, laboratory, and therapeutic factors to an equal number of patients receiving a medium prednisone dose (≤30 mg/day, mean 24.2 mg/day).
At 12 months, 61.8% of patients in the high-dose group achieved a complete renal response (proteinuria <0.5 g/day, serum creatinine levels ≤120% of baseline values), which was significantly greater than the 38.2% of patients in the medium-dose group. The rate of complete and partial responses together also favored the high-dose group, at 66.7% versus 59.8% in the medium-dose group, but this was not a significant difference.
As reported in Arthritis Care & Research, similar results were observed in analyses of various subgroups, including patients with proliferative and non-proliferative disease, those who received mycophenolate mofetil or cyclophosphamide, and patients with sub-nephrotic proteinuria. On the other hand, there were significantly fewer complete responses in the high- versus medium-dose group among patients receiving remission induction therapy with azathioprine.
In a subgroup of 120 patients followed up for at least 3 years, complete remission rates remained higher in the high- than the medium-dose group, with significant differences seen at 2 years (67.8 vs 39.0%) and 3 years (64.9 vs 49.1%).
Interestingly, tapering of prednisone was more rapid among patients in the high-dose than the medium-dose group, the researchers note.
At 1, 2, and 3 years, patients in in the high-dose group were receiving lower mean doses of prednisone than the medium-dose group, as well as lower cumulative doses by the second and third year.
Moreover, the high-dose group “did not accrue significantly more glucocorticoid-related damage” than the medium-dose group, the team points out. The development of cataracts, osteoporosis, osteonecrosis, diabetes, and other events occurred at a similar rate in the high- and medium-dose groups at all timepoints, with a respective 5.8% versus 3.9% new events in the first year, 13.2% versus 13.2% in the second year, and 25.0% versus 20.3% in the third year.
But the researchers highlight that the “accelerated” rate of damage accrual seen in the late phases of disease (at 2 and 3 years) in both groups “underlines the importance of rapid prednisone tapering according to the clinical response that may be facilitated by the addition of other therapies.”
They conclude: “Despite the observation of better efficacy in patients treated with initially higher prednisone doses, the high rates of adverse event call for alternative strategies in the management of acute [lupus nephritis].”
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Arthritis Care Res 2021; doi:10.1002/acr.24592