Background Pulsed
cyclophosphamide or
mycophenolate mofetil for
lupus nephritis has limited efficacy. We previously reported a case of mixed-class IV + V
lupus nephritis successfully treated with
cyclophosphamide and
tacrolimus. This study assessed the efficacy and safety of multitarget
therapy with
cyclophosphamide and
tacrolimus for the treatment of
lupus nephritis. Methods In a prospective, single-arm, open label pilot study, we recruited 15 patients aged 18-64 years with active
lupus nephritis who met the American College of Rheumatology criteria for a diagnosis of
systemic lupus erythematosus (1997). The treatment protocol was a starting dose of
prednisolone of 0.6-1.0 mg/kg/day for 2 weeks and then tapered to a maintenance dose, intravenous
cyclophosphamide (500 mg biweekly for 3 months) and
tacrolimus (3.0 mg/day).
Tacrolimus was continued as maintenance
therapy. Complete remission was defined as a spot urine
protein/
creatinine ratio of < 0.5 g/gCr with no active urine casts and a serum
creatinine level that was either normal or within 30% of a previously abnormal baseline level. We retrospectively compared results for the study patients with those of 18 historical controls conventionally treated with
cyclophosphamide and
prednisolone. Results At baseline, the mean patient age was 41.5 ± 14.6 years (male:female ratio 2:13), urine
protein/
creatinine ratio 3.9 ± 2.3 g/gCr and serum
creatinine 84.6 ± 34.6 µmol/L.
Lupus nephritis classifications included classes IV ( n = 8), III + V ( n = 1), IV + V ( n = 5) and unclassified ( n = 1). Eleven patients completed the treatment protocol and four withdrew. At 6 months, 12 of 15 (80.0%) had achieved complete remission using intention-to-treat analysis, significantly more than historical controls (seven of 18 patients, 38.9%). A transient increase in serum
creatinine and gastric symptoms occurred in three cases. One patient withdrew due to cytomegalovirus antigenemia and severe diabetes, and one patient died of
thrombotic microangiopathy. Conclusions Multitarget
therapy with
cyclophosphamide and
tacrolimus can be a therapeutic option for
lupus nephritis. Clinical trials registration Combination
therapy of
tacrolimus and intravenous
cyclophosphamide for
remission induction of
lupus nephritis, UMIN: 000004893, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000005830&language=E . Date of registration: 18 January 2011.