title: Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial.
abstract: Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001), we randomized 87 proliferative LN patients to either cyclophosphamide pulses (750 mg/m(2), 13 pulses in 2 years) combined with oral prednisone (CY) or to azathioprine (2 mg/kg/day in 2 years) combined with intravenous pulses of methylprednisolone (3 x 3 pulses of 1000 mg) and oral prednisone (AZA). After a median follow-up of 5.7 years (interquartile range 4.1-7.2 years), doubling of serum creatinine was more frequent in the AZA group, although not statistically significant (relative risk (RR): 4.1, with 95% confidence interval (95% CI): 0.8-20.4). Relapses occurred more often in the AZA group (RR: 8.8, 95% CI: 1.5-31.8). Creatinine and proteinuria at last visit did not differ between the two treatment arms. Moreover, 88.4% of the patients in the AZA arm were still free of cyclophosphamide treatment. During the first 2 years, the frequency of remission was not different, but infections, especially herpes zoster virus infections (HZV) were more frequent in the AZA group. Parameters for ovarian function did not differ between the two groups. In conclusion, in this open-label randomized controlled trial, cyclophosphamide was superior to azathioprine with regard to renal relapses and HZV. At last follow-up, there were no differences in serum creatinine or proteinuria between the two groups. However, since our study lacked sufficient power, longer follow-up is needed to reveal putative differences.
authors.affiliation: Division of Nephrology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. m.grootscholten@aig.umcn.nl
authors.forename: C
authors.initials: C
authors.lastname: Grootscholten
authors.forename: G
authors.initials: G
authors.lastname: Ligtenberg
authors.forename: E C
authors.initials: EC
authors.lastname: Hagen
authors.forename: A W L
authors.initials: AW
authors.lastname: van den Wall Bake
authors.forename: J W
authors.initials: JW
authors.lastname: de Glas-Vos
authors.forename: M
authors.initials: M
authors.lastname: Bijl
authors.forename: K J
authors.initials: KJ
authors.lastname: Assmann
authors.forename: J A
authors.initials: JA
authors.lastname: Bruijn
authors.forename: J J
authors.initials: JJ
authors.lastname: Weening
authors.forename: H C
authors.initials: HC
authors.lastname: van Houwelingen
authors.forename: R H W M
authors.initials: RH
authors.lastname: Derksen
authors.forename: J H M
authors.initials: JH
authors.lastname: Berden
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001379:Azathioprine / Q000008:administration & dosage / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008181:Lupus Nephritis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D011239:Prednisolone; D003404:Creatinine; D009173:Mycophenolic Acid; D001379:Azathioprine; D008775:Methylprednisolone