Microscopic Polyangiitis Medication
- Author: Mehran Farid-Moayer, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Medication Summary
Treatment of microscopic polyangiitis (MPA) consists of 3 phases.
First phase - Remission induction with oral prednisone and cyclophosphamide
For induction of remission, 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 one month. If significant improvement is seen, the prednisone dose is decreased by 5 mg/wk. Once the dose of 10 mg/d is reached, the dose can be changed 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 2 rare vasculitis disorders: MPA and Wegener granulomatosis (WG). The safety and effectiveness of rituximab was demonstrated in a single controlled trial, in which 197 adults with MPA or WG 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.[8] 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.
Retreatment with rituximab for MPA or WG was not evaluated; therefore, the safety and efficacy of retreatment with subsequent courses of rituximab has not been established.
Second phase - Remission maintenance
The preference is to replace cyclophosphamide, which has high toxicity, with either methotrexate or azathioprine. If the serum creatinine concentration is greater than 2 mg/dL, methotrexate is no longer 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.
Although preliminary, the results from a small retrospective study suggest that systematic rituximab infusions as maintenance therapy was well tolerated but did not prevent all relapses in patients with granulomatosis with polyangiitis or microscopic polyangiitis who were in remission and taking conventional immunosuppressants or rituximab. An ongoing randomized controlled trial may or may not confirm these results.[9]
Third phase - Treatment of relapse
The treatment of relapse MPA is the same as that of remission induction (see First phase).
Other therapies include the following:
- The use of sulfamethoxazole/trimethoprim is controversial in the prevention of relapse. The use of this treatment for Wegener granulomatosis has shown promising results.[10, 11] 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.[12, 13, 14]
- Cyclosporine is used for maintenance therapy.
- Intravenous immunoglobulin has been used in treatment of refractory disease.
Pneumocystis carinii pneumonia (PCP) (Pneumocystis jiroveci) prophylaxis via low-dose sulfamethoxazole/trimethoprim given as one double-strength tablet 3 times weekly is prudent.[14]
Corticosteroids
Class Summary
First line of treatment for induction of remission and usually for maintenance. For induction of remission, use IV methylprednisolone. For maintenance, use prednisone.
Methylprednisolone (Adlone, Medrol, Solu-Medrol)
Steroids ameliorate effects immune reactions and may limit biphasic anaphylaxis.
Prednisone (Deltasone, Orasone, Sterapred)
Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.
Immunosuppressive agents
Class Summary
These agents inhibit immune reactions that result from diverse stimuli.
Cyclophosphamide (Cytoxan, Neosar)
Chemically related to nitrogen mustards.
As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Rituximab (Rituxan)
Chimeric murine/human monoclonal antibody directed against the CD20 antigen found on surface of B-lymphocytes.
Methotrexate (Folex PFS, Rheumatrex)
Should not be used if serum creatinine clearance is >2.0 mg/dL.
Unknown mechanism of action in treatment of inflammatory reactions; may affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust dose gradually to attain satisfactory response. An alternative form of less toxic therapy only for localized and nonaggressive disease is combination of MTX and prednisone.
Azathioprine (Imuran)
Immunosuppressive agent; antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.
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