Mycophenolate mofetil for induction and maintenance of remission in microscopic polyangiitis with mild to moderate renal involvement--a prospective, open-label pilot trial.
OBJECTIVE
Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA), often targeting myeloperoxidase (MPO). Cyclophosphamide (CYC) plus corticosteroids (CS) is considered standard therapy for patients with renal involvement, but treatment response is not satisfactory in all patients and CYC has well recognized toxicity. This prospective pilot trial explored whether mycophenolate mofetil (MMF) represents an effective alternative to CYC for induction and maintenance of remission in MPA with mild to moderate renal involvement.


METHODS
Seventeen P-ANCA/MPO-ANCA-positive patients with MPA with mild to moderate renal involvement received MMF (1000 mg orally, twice daily) and CS (intravenous methylprednisolone, 1 to 3 g, followed by oral prednisone at 1 mg/kg per day). Oral CS were discontinued by month 6; MMF was continued through month 18. The primary outcome measure was remission by month 6 and stable renal function. Secondary endpoints included major relapses necessitating a switch to CYC plus CS, minor relapses requiring an increase in CS dosage, and adverse events.


RESULTS
Thirteen of 17 patients enrolled achieved the primary outcome, and 4 failed because of insufficient response, relapse, or MMF intolerance. Twelve patients remained in remission through month 18, renal function remained stable, and proteinuria improved. Side effects of MMF were mild, transient, and responsive to dose adjustments in all patients except one.


CONCLUSIONS
MMF represents an alternative to CYC for induction and maintenance of remission in patients with MPO-ANCA-associated MPA with mild to moderate renal disease.
Silva
Francisco
F
Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55905, USA.
Specks
Ulrich
U
Kalra
Sanjay
S
Hogan
Marie C
MC
Leung
Nelson
N
Sethi
Sanjeev
S
Fervenza
Fernando C
FC
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007674:Kidney Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D055953:Microscopic Polyangiitis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D009195:Peroxidase / Q000276:immunology; D010865:Pilot Projects; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D019268:Antibodies, Antineutrophil Cytoplasmic; D007166:Immunosuppressive Agents; D009195:Peroxidase; D009173:Mycophenolic Acid; D011241:Prednisone; D008775:Methylprednisolone