Mycophenolate mofetil for induction and maintenance of remission in microscopic polyangiitis with mild to moderate renal involvement--a prospective, open-label pilot trial

Abstract

Background and objectives: 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.

Design, setting, participants, & measurements: 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.

Trial registration: ClinicalTrials.gov NCT00405860.

Figure 1.

Treatment response at different points of follow-up. Patients who met the primary endpoint of remission (BVAS/WG = 0) with stable or improved renal function, black; had persistently active disease (BVAS/WG persistently >0), gray; or were counted as treatment failures (relapse, lack of response, or intolerance of MMF), white.

Figure 2.

Disease activity assessed by (A) BVAS/WG, (B) MPO-ANCA levels, (C) erythrocyte sedimentation rate, (D) C-reactive protein, (E) eGFR, and (F) proteinuria. Shown are the medians, interquartile range, and minimum/maximum values. The statistical analyses presented correspond to the comparisons between baseline and week 24 and between week 24 and the end of the trial (week 72). Data shown for each time point are based on patients remaining on protocolized therapy as indicated.