Journal Article

Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial

Berden, J.H.M., Ligtenberg, G., Bruijn, J.A., de Glas-Vos, J.W., for the Dutch Working Party on Systemic Lupus Erythematosus, Weening, J.J., van Houwelingen, H.C., Hagen, E.C., Derksen, R.H.W.M., van den Wall Bake, A.W.L., Assmann, K.J., Grootscholten, C., Bijl, M.

2006

Overview

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 (750mg/m2, 13 pulses in 2 years) combined with oral prednisone (CY) or to azathioprine (2mg/kg/day in 2 years) combined with intravenous pulses of methylprednisolone (3 × 3 pulses of 1000mg) 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.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Administration, Oral / Adolescent / Adult / Anti-Inflammatory Agents - administration & dosage / Anti-Inflammatory Agents - therapeutic use / Azathioprine - administration & dosage / Azathioprine - therapeutic use / clinical nephrology / clinical trial / Creatinine - blood / Cyclophosphamide - administration & dosage / Cyclophosphamide - therapeutic use / Drug Therapy, Combination / Female / Humans / immunosuppression / Immunosuppressive Agents - administration & dosage / Immunosuppressive Agents - therapeutic use / Injections, Intravenous / lupus nephritis / Lupus Nephritis - blood / Lupus Nephritis - drug therapy / Lupus Nephritis - pathology / Male / Methylprednisolone - administration & dosage / Methylprednisolone - therapeutic use / Middle Aged / Mycophenolic Acid - analogs & derivatives / Mycophenolic Acid - therapeutic use / Prednisolone - administration & dosage / Prednisolone - therapeutic use / randomized controlled trial / Remission Induction / Treatment Outcome