Granulomatosis with polyangiitis medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Ali Poyan Mehr, M.D. [2]Associate Editor(s)-in-Chief: Krzysztof Wierzbicki M.D. [3]Cafer Zorkun, M.D., Ph.D. [4]Amandeep Singh M.D.[5]

In most cases, treatment consists of a combination of a glucocorticoid (a steroid) and a cytotoxic medicine. It includes glucocorticoids, cyclophosphamide, Rituximab, Methotrexate, Azathioprine and when needed with plasmapheresis.

Before steroid treatment became available, mortality within one year was over 90%, with average survival being 5 months. Steroids prolonged average survival to 8 months. The introduction of cyclophosphamide (CYC) in the 1970s was a major breakthrough.^[1][2]

• Parenteral regimen (pulse therapy)
  • Preferred regimen (1):Methylprednisolone 7-15 mg/kg IV q24h for 3 days (maximum, 500-1000 mg/kg/day)

• Oral regimen (follows parenteral pulse therapy)
  • Preferred regimen (1): Prednisone 1 mg/kg/day PO from Day 1 (maximum, 60-80 mg/day) tapered over 14 days with maximum of 20 mg/day

• Oral regimen
  • Preferred regimen (1):Cyclophosphamide 1.5-2 mg/kg PO q24h for 3-6 months or till remission is achieved (Check CBC for Neutropenia and administer Mesna for hemorrhagic cystitis)
• Parenteral regimen (pulse therapy)
  • Preferred regimen (1): Cyclophosphamide 15 mg/kg IV q2weekly for 3 doses and then q3weekly for 3-6 months (Check CBC for Neutropenia and administer Mesna for hemorrhagic cystitis)

• Patients using cyclophosphamide should also receive glucocorticoids.

• Parenteral regimen
  • Preferred regimen (1): Rituximab 375 mg/m² IV q1week for 4 doses
  • Alternative regimen (1): Rituximab 1g IV q2weekly for 2 doses

• Parenteral regimen^[3]
  • Preferred regimen (1): Methotrexate 7.5 mg IM/SQ q1weekly till 1 year or remission.

• Oral regimen
  • Preferred regimen (1): Methotrexate 7.5 mg PO q1weekly till 1 year or remission.
• It is used in patients without any end organ damage and no life threatening disease.^[4]
• Relapse rate are higher with Methotrexate.^[5]

• Patients using methotrexate should also receive glucocorticoids.

• Oral regimen
  • Preferred regimen (1): Azathioprine 2 mg/kg/day PO for 6 months

• Indications
  • Renal dysfunction due to glomerulonephritis
  • Positive Anti-glomerular basement membrane antibody
  • Pulmonary hemorrhage

• Plasma exchange accompanies the pharmacological treatment

Some guidelines for which drug to choose.^[1]

• In localized disease, treatment with the antibiotic co-trimoxazole is recommended, with steroids in case of treatment failure.^[6]
• In generalized non-organ threatening disease, remission can be induced with methotrexate and steroids, where the steroid dose is reduced after a remission has been achieved and methotrexate used as maintenance.
• In case of organ-threatening disease, pulsed intravenous cyclophosphamide with steroids is recommended. Once remission has been achieved, azathioprine and steroids can be used to maintain remission.
• In severe renal vasculitis, the same regimen is used but with the addition of plasma exchange.
• In pulmonary hemorrhage, high doses of cyclophosphamide with pulsed methylprednisolone may be used, or alternatively CYC, steroids, and plasma exchange.

In severe disease not responsive to previously mentioned treatment, mycophenolate mofetil, 15-deoxyspergualin, anti-thymocyte globulin, rituximab and infliximab; intravenous immunoglobulin (IVIG) and etanercept.^[1]

During the course of treating Wegener’s granulomatosis, doctors often give their patients other medicines to prevent medicine-related side effects. These include

• Trimethoprim/sulfamethoxazole (also called bactrim or septra) is given three times a week to prevent Pneumocystis carinii infection (a lung infection)
• A medicine regimen is often given to prevent prednisone-related bone loss (osteoporosis)
• Folic acid or folinic acid (also called leucovorin) are often given to people taking methotrexate

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