Granulomatosis with Polyangiitis: Drug Therapy

Therapeutic Objective

• Risk reduction or prevention of complications.

Therapy recommendations

• Therapy is stage- and activity-based.
• Localized stage
  • Induction therapy: methotrexate (MTX) (folic acid antagonist/immunosuppressant) and glucocorticoids (steroids); recommended for induction therapy in addition to cyclophosphamide in patients with critical organ involvement
  • Maintenance therapy: low-dose glucocorticoids and azathioprine (purine antagonists/immunosuppressants) or leflunomide (immunosuppressants) or methotrexate.
• Early systemic stage
  • Induction therapy: methotrexate or cyclophosphamide (alkylants) and steroids.
  • Maintenance therapy: low-dose glucocorticoids and azathioprine (purine antagonists/immunosuppressants) or methotrexate.
• Generalized stage
  • Induction therapy: high-dose glucocorticoids.
    • Severe course: corticosteroid bolus therapy and cyclophosphamide.
    • In the setting of induction therapy, consider the use of the following adjunctive therapies:
      • Bladder protection
      • Prophylaxis against Pneumocystis jiroveci: trimethoprim-sulfamethoxazole.
      • Oral antifungal therapy
      • Gastric protection
      • Calcium vitamin D supplementation
    • Reserve options: Rituximab (monoclonal antibody), infliximab (TNF-alpha blocker).
  • Maintenance therapy
    • Once remission occurs, therapy is switched to azathioprine (24 months) or leflunomide or methotrexate. In addition, prednisolone.
    • Rituximab in reduced dose (500 mg every 6 months) is superior to azathioprine in maintenance therapy after cyclophosphamide induction.
    • Second-line alternatives: leflunomide and mycophenolate mofetil.
• Severe, vital threatening generalization stage.
  • See generalization stage (possibly rituximab instead of cyclophosphamide).
  • In addition: plasmapheresis therapy (plasma exchange).
• Refractory stage
  • Induction therapy: antiplatelet globulin or rituximab, plasmapheresis.
  • Maintenance therapy: no consensus
• In patients with relapse, rituximab is superior to cyclophosphamide.

Further notes

• Remission induction:
  • Non-organ-threatening ANCA-associated vasculitis (AAV): glucocorticoids (GC, weekly 0.3 mg/kg bw) + methotrexate (MTX, max 25 mg/wk).
  • Organ threat: GC + cyclophosphamide or rituximab.
• Remission maintenance (therapy for at least 24 months):
  • MTX or azathioprine (AZA) equivalentIn case of contraindications, intolerances, or previous treatment failure: rituximab (500 mg i.v. every 6 mo), plus GC ≤ 7.5 mg/d if necessary.
• Recurrence treatment:
  • Recurrence with organ-threatening manifestation: renewed induction therapy with cyclophosphamide or rituximab, each plus GC (1 mg/kg bw, max 80 mg/d).
• Supportive therapy: treatment of comorbidities; vaccinations; tumor screening. Furthermore, treatment of cardiovascular risk factors / diseases.