From the Guidelines
Granulomatosis with polyangiitis (GPA) should be treated with a combination of corticosteroids and immunosuppressants, with rituximab (RTX) being the preferred remission induction therapy over cyclophosphamide (CYC) for active severe GPA, as recommended by the 2021 American College of Rheumatology/Vasculitis Foundation guideline 1.
Treatment Overview
The treatment of GPA typically involves two phases: induction and maintenance. The induction phase aims to achieve remission, while the maintenance phase focuses on preventing relapses.
- Induction therapy usually lasts 3-6 months and may include high-dose prednisone (1 mg/kg/day, maximum 60-80 mg daily) combined with RTX (375 mg/m² weekly for 4 weeks) or CYC (either oral at 2 mg/kg/day or intravenous at 15 mg/kg every 2-3 weeks) 1.
- Maintenance therapy follows with less potent agents like azathioprine (2 mg/kg/day), methotrexate (20-25 mg weekly), or mycophenolate mofetil (2 g/day) for at least 18-24 months 1.
Key Recommendations
- For active severe GPA, RTX is recommended over CYC for remission induction, with a reduced dose of glucocorticoids (GC) being preferred over standard dose GC 1.
- For active non-severe GPA, GC + RTX is recommended for remission induction, with GC + methotrexate (MTX) being an alternative option 1.
- For remission maintenance, RTX is the preferred therapy, followed by MTX or azathioprine, and then mycophenolate mofetil or leflunomide 1.
Monitoring and Prevention
- Regular monitoring of kidney function, complete blood counts, and ANCA levels is essential to assess disease activity and potential toxicity from treatment 1.
- Patients should receive Pneumocystis pneumonia prophylaxis with trimethoprim-sulfamethoxazole during treatment to prevent infections 1.
From the Research
Definition and Characteristics of GPA Vasculitis
- GPA vasculitis, also known as granulomatosis with polyangiitis, is a systemic vasculitis characterized by involvement of the upper airways, lungs, and kidneys 2.
- It shares many features with microscopic polyangiitis (MPA), and recent trials have included both vasculitides 2.
- GPA is a type of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which frequently affects the peripheral nervous system 3.
Treatment Options for GPA Vasculitis
- The current treatment of GPA is stratified based on severity, with methotrexate and glucocorticoids used to induce and maintain remission in non-severe cases 2.
- For patients with severe disease, options include glucocorticoids combined with either cyclophosphamide or rituximab 2.
- Rituximab has been found to be as effective as cyclophosphamide in inducing remission of severe active GPA 2.
- A combination of glucocorticoids and immunosuppressive agents such as cyclophosphamide, rituximab, methotrexate, or mycophenolate mofetil is used to induce remission, while a combination of low-dose glucocorticoids and azathioprine, rituximab, methotrexate, or mycophenolate mofetil is used to maintain remission 3.
Outcomes and Prognosis
- The efficacy and safety of rituximab induction and maintenance therapy for GPA have been demonstrated in a single-centre cohort study, with 2-year relapse-free survival and rituximab retention rates of 85% and 78%, respectively 4.
- GPA patients have a higher relapse rate compared to microscopic polyangiitis (MPA) patients, with 41.3% of GPA patients experiencing relapse compared to 25.9% of MPA patients 5.
- Renal events, such as end-stage kidney disease or a persistent drop in estimated glomerular filtration rate (eGFR), occur more frequently in MPA patients treated with rituximab compared to cyclophosphamide 5.