Microscopic Polyangiitis Treatment & Management

Updated: Jul 31, 2018
  • Author: Mehran Farid-Moayer, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Treatment

Approach Considerations

Treatment of microscopic polyangiitis (MPA) is principally with corticosteroids and other immunosuppressive agents and consists of induction and maintenance of remission.The treatment of relapsed MPA is the same as that of remission induction. Intravenous immunoglobulin has been used in treatment of refractory disease. [12]

MPA can manifest as a mild systemic vasculitis with mild renal insufficiency, or it can manifest as a full-blown acute disease with rapid deterioration of renal function and respiratory failure due to pulmonary capillaritis. The choice of medication depends in part on the extent of disease, the rate of progression, and the degree of inflammation.

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Induction of Remission

Induction of remission in MPA is customarily achieved with cyclophosphamide and prednisone. Cyclophosphamide is started at 1.5-2 mg/kg/d. The patient should be monitored for leukocytopenia and neutropenia. Prednisone is started at 1 mg/kg/d and is continued for 1 month. If significant improvement is seen, the prednisone dose is decreased by 5 mg/wk. Once the dosage of 10 mg/d is reached, the next taper can be to 10 mg every other day. After complete remission, the maintenance phase is started.

For induction of remission in patient with milder manifestations of MPA, a combination of methotrexate and prednisone can be used. However, a significantly higher relapse rate was observed with this combination than with the combination of cyclophosphamide and prednisone.

In cases involving life-threatening alveolar capillaritis with pulmonary alveolar hemorrhage, plasmapheresis in addition to intravenous cyclophosphamide and pulse doses of steroids may be used.

Glucocorticoid monotherapy is not recommended because of lower remission rates.

In April 2011, the US Food and Drug Administration (FDA) approved rituximab to treat MPA and granulomatosis with polyangiitis (Wegener granulomatosis; GPA). The safety and effectiveness of rituximab was demonstrated in a single controlled trial by the RAVE-ITN Research Group, in which 197 adults with MPA or GPA were randomly assigned to receive either rituximab (375 mg/m2/wk for 4 wk) plus daily prednisone, or cyclophosphamide (2 mg/kg/d) orally plus daily prednisone to induce remission. [13] Prednisone was tapered off. The primary endpoint was remission of disease without use of prednisone at 6 months. After 6 months, 64% of patients treated with rituximab had complete remission compared with 53% of those treated with cyclophosphamide. 

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Maintenance of Remission

For remission maintenance, the preference is to replace cyclophosphamide, which has high toxicity, with either methotrexate or azathioprine. [14, 15] However, if the serum creatinine concentration is greater than 2 mg/dL, methotrexate is not an option. At this phase, prednisone is continued and cyclophosphamide is replaced with azathioprine at 2 mg/kg/d for 12 months. After a year, the dose of azathioprine is decreased to 1.5 mg/kg/d. If methotrexate is used for maintenance treatment, it can be started at 0.3 mg/kg once a week, with the maximum dose of 15 mg/wk. This is increased by 2.5 mg/wk (maximum 20 mg/wk).

This phase is continued for 12-24 months. Prednisone can be continued at 10 mg/d or every other day.

Analysis of long-term outcomes in 112 patients enrolled in the WEGENT trial confirmed thatmethotrexate or azathioprine are comparable treatment options for maintaining remission of MPA. The 10-year overall survival rates were 75.1% in patients receiving azathioprine and 79.9% in those receiving methotrexate (P = 0.56), while relapse-free survival rates were 26.3% and 33.5% (P = 0.29), respectively. [16]

A followup study by the RAVE-ITN Research Group demonstrated that a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for inducing and maintaining remission for 18 months. At 18 months, 39% of the patients in the rituximab group had maintained complete remissions, compared with 33% of the patients who received cyclophosphamide for 3 to 6 months followed by azathioprine for 12 to 15 months. [17]

The French Vasculitis Study Group reported that rituximab was more effective than azathioprine for maintaining remission in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. In this study, 115 patients with newly diagnosed or relapsing GPA, MPA, or renal-limited ANCA-associated vasculitis in complete remission after a cyclophosphamide-glucocorticoid regimen were randomly assigned to receive either 500 mg of rituximab on days 0 and 14 and at months 6, 12, and 18 after study entry or daily azathioprine until month 22. At month 28, 17 patients (29%) in the azathioprine group had experienced major relapse, compared with three patients (5%) in the rituximab group (hazard ratio for relapse, 6.61; P = 0.002).17 On continued follow-up to 60 months, major relapse-free survival rates were 71.9% with rituximab versus 49.4% with azathioprine (P=0.003); overall survival rates were 100% with rituximab versus 93.0% with azathioprine (P=0.045). [18]

Another French Vasculitis Study Group trial compared fixed-schedule and individually tailored rituximab regimens for maintaining remission of ANCA-associated vasculitis, and found that relapse rates did not differ significantly between the two approaches, while patients on individually tailored regimens received fewer rituximab infusions. Patients on individually tailored regimens received an initial 500-mg rituximab infusion and then underwent testing every 3 months, with rituximab reinfusion only when CD19+ B lymphocytes or ANCA had reappeared or the ANCA titer rose markedly.  [19]

Other therapies include the following:

  • The use of trimethoprim-sulfamethoxazole (TMP-SMX) is controversial in the prevention of relapse. TMP-SMX has shown promising results in patients with GPA. [20, 21] The relationship between Staphylococcus aureus colonization and the relapse rate has shown a debatable correlation.
  • The use of mycophenolate mofetil in the treatment of MPA has been limited. In several small studies, mycophenolate mofetil was effective in maintaining remission in patients with MPA, even in those with moderate-to-severe renal impairment. [22, 23, 24]
  • The use of low-dose cyclosporine for maintenance therapy has been reported [25]
  • Pneumocystis jiroveci prophylaxis with low-dose TMP-SMX (one double-strength tablet three times weekly) is prudent. [24]
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Consultations

A rheumatologist would be the main consultant who helps with the diagnosis and immunosuppressive therapy. Additional consultations would be based\ on the specific organ system involvement, as follows:

  • Consult a pulmonologist for the management of hemoptysis due to pulmonary alveolar capillaritis; additionally, consult a pulmonologist to help with the management of respiratory failure associated with diffuse alveolar hemorrhage and with the diagnosis of pulmonary involvement

  • Consult a nephrologist for help with the diagnosis and management of renal involvement and possible need for dialysis

  • Consult a gastroenterologist, if necessary, for the management of gastrointestinal bleeding

  • Consult a surgeon in cases involving catastrophic events in gastrointestinal or other organ systems

  • Consult a hematologist if plasmapheresis is considered

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