Long-term outcomes--mycophenolate mofetil treatment for lupus nephritis with addition of tacrolimus for resistant cases.
BACKGROUND
Although mycophenolate mofetil (MMF) is being increasingly used to manage lupus nephritis (LN), long-term experience is limited. Despite treatment, a significant proportion of patients will be refractory to this regime.


METHODS
We report, in this observational study, our long-term experience treating 70 patients with biopsy-proven LN, with MMF as continuous induction-maintenance therapy, who were followed up prospectively over a 5-year period. As rescue therapy for MMF-resistant cases, tacrolimus (0.075 mg/kg/day) was added. The study primary end point was complete response (CR). Secondary end points included partial response (PR), treatment failure, relapse and side effects. Predictor factors associated to renal outcome were analysed by Cox regression analysis.


RESULTS
Thirty-six MMF-treated patients (51%) remained in CR, and 23 (33%) failed treatment at last follow-up. Time to treatment failure was associated with persistent hypoalbuminaemia (hazard ratio (HR) = 0.87; 95%CI, 0.81-0.95; P = 0.001), higher proteinuria (HR = 1.29; 95%CI, 1.03-1.62; P = 0.030) and fewer early responses (HR 0.28; 95%CI, 0.10-0.77; P = 0.014). Renal relapse occurred in 24 (34%) patients. Time to flare was associated with persistent anti-dsDNA titres (HR = 1.001; 95%CI, 1.001-1.003; P = 0.005) and younger age at inclusion (HR = 0.36; 95%CI, 0.14-0.90; P = 0.029). Tacrolimus was added to 17 (24%) patients. A significant reduction of proteinuria was already observed at 3 months (P = 0.002). After 2 years follow-up, 12 (70%) of them achieved clinical response (six CR and six PR). Conclusions. MMF is an effective treatment for LN. Combination therapy with tacrolimus is an effective and safe alternative for MMF-resistant patients.
Systemic Autoimmune Diseases Research Unit, Internal Medicine Department, Vall d'Hebron Hospital, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain. jocortes@ir.vhebron.net
Josefina
J
Cortés-Hernández
María Teresa
MT
Torres-Salido
Alfonso Segarra
AS
Medrano
Miquel Vilardell
MV
Tarrés
Josep
J
Ordi-Ros
D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008181:Lupus Nephritis / Q000188:drug therapy*; D008297:Male; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D012044:Regression Analysis; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus