METHYLPREDNISOLONE AND CYCLOPHOSPHAMIDE, ALONE OR IN COMBINATION, IN PATIENTS WITH LUPUS NEPHRITIS - A RANDOMIZED, CONTROLLED TRIAL

Background: Uncertainty exists about the efficacy and toxicity of bolu s therapy with methylprednisolone or of the combination of methylpredn isolone and cyclophosphamide in the treatment of lupus nephritis. Obje ctive: To determine 1) whether intensive bolus therapy with methylpred nisolone is an adequate substitute for bolus therapy with cyclophospha mide and 2) whether the combination of methylprednisolone and cyclopho sphamide is superior to bolus therapy with methylprednisolone or cyclo phosphamide alone. Design: Randomized, controlled trial with at least 5 years of follow-up. Setting: Government referral-based research hosp ital. Patients: 82 patients with lupus nephritis who had 10 or more er ythrocytes per high-power field, cellular casts, proteinuria (>1 g of protein per day), and a renal biopsy specimen that showed proliferativ e nephritis. Interventions: Bolus therapy with methylprednisolone (1 g /m(2) body surface area), given monthly for at least 1 year; bolus the rapy with cyclophosphamide (0.5 to 1.0 g/m(2) body surface area), give n monthly for 6 months and then quarterly; or bolus therapy with both methylprednisolone and cyclophosphamide. Measurements: 1) Renal remiss ion (defined as <10 dysmorphic erythrocytes per high-power field, the absence of cellular casts, and excretion of <1 g of protein per day wi thout doubling of the serum creatinine level), 2) prevention of doubli ng of the serum creatinine level, and 3) prevention of renal failure r equiring dialysis. Results: Renal remission occurred in 17 of 20 patie nts in the combination therapy group (85%), 13 of 21 patients in the c yclophosphamide group (62%), and 7 of 24 patients in the methylprednis olone group (29%) (P < 0.001). Twenty-eight patients (43%) did not ach ieve renal remission. By life-table analysis, the likelihood of remiss ion during the study period was greater in the combination therapy gro up than in the methylprednisolone group (P = 0.028). Combination thera py and cyclophosphamide therapy were not statistically different. Adve rse events were amenorrhea (seen in 41% of the cyclophosphamide group, 43% of the combination therapy group, and 7.4% of the methyl predniso lone group), cervical dysplasia (seen in 11% of the cyclophosphamide g roup, 7.1% of the combination therapy group, and 0% of the methylpredn isolone group), avascular necrosis (seen in 11% of the cyclophosphamid e group, 18% of the combination therapy group, and 22% of the methylpr ednisolone group), herpes tester (seen in 15% of the cyclophosphamide group, 21% of the combination therapy group, and 3.7% of the methylpre dnisolone group) and at least one infection (seen in 26% of the cyclop hosphamide group, 32% of the combination therapy group, and 7.4% of th e methylprednisolone group). Conclusions: Monthly bolus therapy with m ethylprednisolone was less effective than monthly bolus therapy with c yclophosphamide. A trend toward greater efficacy with combination ther apy was seen.