CellCept in p-ANCA Vasculitis
CellCept in p-ANCA Vasculitis
Microscopic polyangiitis (MP) is a primary systemic vasculitis predominantly affecting small
 blood vessels. Following the widespread introduction of ANCA testing, the primary systemic
 vasculitis (SV), Wegener?s granulomatosis (WG) and microscopic polyangiitis (MP) appear to be
 more frequent than was previously thought (see definitions in Appendix 6). In addition, the
 existence of early and organ-limited forms of these diseases, such as renal-limited
 vasculitis (RLV) is now clearly recognized. Their annual incidence exceeds 20 per million per
 year and they account for at least 5 % of the causes of end stage renal failure. The two
 diseases share many features of their histology, serology and response to treatment, pointing
 to similarities in their pathogenesis, which have justified a common approach to their
 management. The standard treatment with corticosteroids (CS) and cyclophosphamide (CYC) is
 usually effective at controlling active disease but continued treatment is necessary to
 prevent disease relapse. Due to the cumulative toxicity associated with CYC treatment,
 alternatives have been looked for. Mycophenolate mofetil (MMF) has been used to treat
 patients with a variety of immune-mediated nephritides, including ANCA-associated vasculitis,
 with less toxicity than CYC but with variable outcome. The present trial will examine whether
 substitution of oral CYC with oral MMF is equally efficient for induction of remission with
 less adverse effects in cases of MP with mild to moderate renal involvement. All patients
 will receive the same regimen of oral prednisone + MMF. Prednisone will be tapered to a stop
 after 24 weeks but MMF will continue for a total of 18 months unless there is worsening or
 persistent disease. The trial ends after 18 months.
1. Patients will receive I.V. methylprednisone, or I.V. dexamethazone, oral prednisone and
 oral MMF therapy as outlined in table 2.

 2. MMF will be initiated within the first 1-2 weeks of the start of steroids. Patients will
 receive CellCept, 750 mg po b.i.d for the first week. Dose will be increased to 1000 mg
 po b.i.d for the second week, and thereafter, according to blood levels and patient
 tolerance. Target blood levels are 1 ? 3.5 &#61549;g/ml. Treatment will be for a total
 of 18 months. This is based on the published dose-dependent adverse effect profiles in
 transplant patients (31-32) and on reports that lower doses are ineffective and shorter
 courses (less then 6 months) result in relapses or failure of therapy (25). Dose will be
 reduced in patient who can not tolerate MMF at the above dose.

 2) Relapse treatment to follow guidelines for relapse regimens. 3) After 18 months, all
 medications will be tapered to a full stop unless disease is active or grumbling.

 4) Pneumocystis pneumonia prophylaxis will be used during the trial (with
 sulfamethoxazole/trimethoprim, or Dapsone or Mepron if allergic to sulfa).
1. Active microscopic polyangiitis

 2. Active urinary sediment (>25 rbc/hpf, red cell casts or dysmorphic red cells)

 3. Renal biopsy compatible with the diagnosis of microscopic polyangiitis, or diagnosis
 demonstrated by the presence of hematuria, proteinuria, and dysmorphic red blood
 cells, and / or red blood casts when biopsy is contraindicated.

 4. Positive p-ANCA (MPO ELISA)

 5. Serum creatinine < 3.0mg/dl.

 6. Age 18 years or over.