Background Nephritis is a serious manifestation of Systemic Lupus erythematosus (SLE), occurring in up to roughly half of patients. Intravenous cyclophosphamide (IVC) is widely used as an effective but also toxic regimen that enables a high rate of disease remission and preserves kidney function. Therapeutic strategies developed to reduce the toxicity of IVC have shown similar efficacy compared with the traditional NIH IVC regimen. All regimens include moderate to high oral or intravenous glucocorticoids. However, the optimal glucocorticoid dose needed for successful induction treatment in lupus nephritis has not been defined in randomized studies. Glucocorticoids themselves are known to be associated with severe side effects and attribute to about 25% of long-term damage in lupus patients.
Objectives We evaluated the efficacy of IVC without increased glucocorticoids in 40 patients with a first episode of lupus nephritis (duration <6 months).
Methods Forty Caucasian SLE patients with lupus nephritis [mean duration of nephritis 1.7 (1-6) months; WHO class III: n=17; class IV: n=19; class IV/V: n=2; no biopsy: n=2] received IVC (6 monthly pulses for induction, 6 quarterly pulses for remission maintenance). Prednisone was exclusively administered and dose-adjusted to control extra-renal manifestations. Response to treatment was defined as normalization of creatinine level, inactive urinary sediment, and proteinuria less than 0.2 g/day (complete response [CR]) or less than 0.5 g/day (partial response [PR]).
Results All patients completed the entire course of therapy with statistically significant reductions in the baseline of SLAM scores, hemoglobin, proteinuria, complement and anti-DNA levels. After 24 months, 25 (62.5%) patients met the criteria for CR and 8 (20%) patients for PR. The mean daily starting dose of prednisone was 23.9±23.8 mg/day. To further explore any prednisone effect, we separately analysed patients initially treated with prednisone doses ≥20 mg/day (A, n=19) or <20 mg/day (B, n=21). CR was achieved in 10 patients in group A (52.6%) vs. 15 (71.4%) in group B (p 0.37), PR was achieved in 5 (26.3%) vs. 3 patients (14.3%) respectively (p 0.58). Renal outcome was irrespective of initial prednisone doses as determined by Pearson’s chi-squared-test of independence (p 0.46). Long-term follow up was available in 37 patients (8.53±2.97 years). Fourteen (37.8%) patients experienced a renal flare. Thirty (81%) patients had normal serum creatinine, 5 (13.5%) showed increased serum creatinine (>2 mg/dl) and 2 (5.4%) developed end-stage renal disease.
Conclusions The rates of CR, PR and also the long-term outcomes are comparable with most published rates after treatment with a combination of IVC and Methylprednisolone Pulses. The current data clearly warrant randomized controlled trials evaluating the impact of high-dose compared to low-dose glucocorticoids or individualized dosing in order to minimize side effects.
Disclosure of Interest None Declared
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