title: Combination therapy of mycophenolate mofetil and tacrolimus in lupus nephritis.
abstract: Since most lupus nephritis patients have an incomplete response to mycophenolate mofetil, combination regimens may improve outcomes. Tacrolimus (FK506) has shown some benefit in lupus nephritis in small trials, and combined with mycophenolate mofetil is standard immunosuppression in transplant patients. We investigate the addition of FK506 to mycophenolate mofetil, in patients who were mycophenolate mofetil failures. All patients were part of a prospective cohort, but evaluated retrospectively. Seven lupus nephritis patients (mean age 27.1, 100% female, 42% Caucasian and 42% African American) were evaluated. Three patients had combined ISN class III and V, two ISN class IV, one ISN class V and II and one ISN class IV and V. Six were taking an ACE-inhibitor or angiotensin receptor blocker, 6 hydroxychloroquine and 5 prednisone (mean dose 11.5 mg; range 0-30 mg). Mean mycophenolate mofetil dose at time of tacrolimus addition was 2.8 g (range 2-3 g). Mean tacrolimus dose was 3.4 mg (range 2-8 mg) titrated to a mean level of 4.67 ng/dl (range 2.2-11.8 ng/dl) for a mean of duration of 16 months (range 2-54 months). Two patients continued both therapies, while five discontinued therapy. One patient achieved a complete renal remission, while three achieved partial remission with 82.9%, 77.1%, 55.3% reductions in proteinuria. Toxicity limited the use of combination therapy: diabetic ketoacidosis (one patient), pneumonia (two) and muscle pain (two). These data suggest that adding tacrolimus in patients refractory to mycophenolate mofetil might have some benefit, although complete responses were rare. Unfortunately, tacrolimus toxicity appeared to be prevalent in these systemic lupus erythematosus patients, limiting its long term use.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Lanata
authors.forename: T
authors.initials: T
authors.lastname: Mahmood
authors.forename: D M
authors.initials: DM
authors.lastname: Fine
authors.forename: M
authors.initials: M
authors.lastname: Petri
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000188:drug therapy*; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D012074:Remission Induction; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus