Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis

Background: controlled trials in lupus nephritis have demonstrated that cyc lophosphamide therapy is superior to corticosteroid therapy alone. The long -term effectiveness and side-effect profiles of pulse immunosuppressive reg imens warrant further study. Objective: To define the long-term risk and benefit of monthly treatment wi th boluses of methylprednisolone, cyclophosphamide, or both. Design: Extended follow-up (median, 11 years) of a randomized, controlled t rial. Setting: U.S. government research hospital. Patients: 82 patients with proliferative lupus nephritis. Measurements: Rates of treatment failure (defined as need for supplemental immunosuppressive therapy or doubling of serum creatinine concentration, or death) and adverse events. Results: In an intention-to-treat survival analysis, the likelihood of trea tment failure was significantly lower in the cyclophosphamide (P = 0.04) an d combination therapy (P = 0.002) groups than In the methylprednisolone gro up. Combination therapy and cyclophosphamide therapy alone did not differ s tatistically in terms of effectiveness or adverse events. Of patients who c ompleted the protocol (n = 65), the proportion of patients who had doubling of serum creatinine concentration was significantly lower in the combinati on group than in the cyclophosphamide group (relative risk, 0.095 [95% Cl, 0.01 to 0.842]). Conclusion: With extended follow-up, pulse cyclophosphamide continued to sh ow superior efficacy over pulse methylprednisolone alone for treatment of l upus nephritis. The combination of pulse cyclophosphamide and methylprednis olone appears to provide additional benefit over pulse cyclophosphamide alo ne and does not confer additional risk for adverse events.