What is the treatment for Granulomatosis with Polyangiitis (GPA)?

From the Guidelines

The treatment for Granulomatosis with Polyangiitis (GPA) should prioritize rituximab over cyclophosphamide for remission induction in patients with active, severe disease, as conditionally recommended by the 2021 American College of Rheumatology/Vasculitis Foundation guideline 1.

Induction Therapy

The choice of induction therapy depends on the severity of the disease. For active, severe GPA,

• rituximab is conditionally recommended over cyclophosphamide for remission induction, with a level of evidence ranging from very low to moderate 1.
• Either IV pulse glucocorticoids (GCs) or high-dose oral GCs may be prescribed as part of initial therapy, with a level of evidence ranging from very low to moderate 1.
• A reduced-dose GC regimen is conditionally recommended over a standard-dose GC regimen for remission induction, with a level of evidence ranging from very low to moderate 1.

Maintenance Therapy

For patients with severe GPA whose disease has entered remission after treatment with cyclophosphamide or rituximab,

• rituximab is conditionally recommended over methotrexate or azathioprine for remission maintenance, with a level of evidence ranging from very low to moderate 1.
• Methotrexate or azathioprine is conditionally recommended over mycophenolate mofetil for remission maintenance, with a level of evidence ranging from very low to moderate 1.
• The duration of non-GC remission maintenance therapy in GPA should be guided by the patient’s clinical condition, preferences, and values, with a level of evidence ranging from low to moderate 1.

Relapse and Refractory Disease

For patients with GPA who have experienced relapse with severe disease manifestations and are not receiving rituximab for remission maintenance,

• rituximab is conditionally recommended over cyclophosphamide for remission re-induction, with a level of evidence rated as low 1. For patients with severe GPA that is refractory to treatment with rituximab or cyclophosphamide for remission induction,
• switching treatment to the other therapy is conditionally recommended over combining the 2 therapies, with a level of evidence rated as very low 1.

From the FDA Drug Label

RITUXAN, in combination with glucocorticoids, is indicated for the treatment of adult and pediatric patients 2 years of age and older with Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA). The treatment for Granulomatosis with Polyangiitis (GPA) is Rituximab in combination with glucocorticoids.

• Key points:
  • Indicated for adult and pediatric patients 2 years of age and older
  • Used in combination with glucocorticoids
  • For the treatment of GPA (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA) 2 2

From the Research

Treatment Overview

• The treatment for Granulomatosis with Polyangiitis (GPA) typically involves a combination of corticosteroids and immunosuppressive agents 3, 4, 5.
• The goal of treatment is to induce remission and prevent relapses, with different medications used for induction and maintenance therapy 3, 4.

Induction Therapy

• Cyclophosphamide (CYC) and rituximab (RTX) are commonly used for induction therapy, with RTX shown to be at least as effective as CYC in some studies 4.
• Corticosteroids, such as methylprednisolone, are often used in combination with immunosuppressive agents for induction therapy 6.

Maintenance Therapy

• Methotrexate, azathioprine, and mycophenolate mofetil are used for maintenance therapy to prevent relapses 3, 5.
• Intravenous immunoglobulins (IVIG) may be used as an alternative adjuvant therapy in some cases 3.

Treatment of Refractory Cases

• Treatment-refractory cases of GPA may require individualized treatment regimens, including the use of plasmapheresis, hemodialysis, and low-dose cyclophosphamide 6.
• The use of a multipronged approach, including high-dose corticosteroids, rituximab, and low-dose cyclophosphamide, may be beneficial for treatment-refractory cases or patients with severe renal involvement 6.

Special Considerations

• Patients with mixed connective tissue disease (MCTD) may be at risk of developing GPA, and physicians should consider a surgical lung biopsy for diagnosis in suspected cases 7.
• The treatment of GPA with rapidly progressive glomerulonephritis requires a prompt and aggressive approach, with the use of pulse dose methylprednisolone, rituximab, and cyclophosphamide 6.