What is the treatment for ANCA (Antineutrophil Cytoplasmic Antibody) positive vasculitis with cavitary lesions?

From the Guidelines

Treatment for ANCA-positive vasculitis with cavitary lesions should involve a combination of high-dose corticosteroids and immunosuppressive agents, with rituximab being a preferred option for induction of remission, especially in relapsing disease, as recommended by the KDIGO 2024 clinical practice guideline 1. The initial regimen should include methylprednisolone 500-1000mg IV daily for 3 days, followed by oral prednisone 1mg/kg/day (maximum 60-80mg daily), with a gradual taper over 3-6 months.

• Concurrently, cyclophosphamide should be administered either as IV pulses (15mg/kg every 2-3 weeks) or orally (2mg/kg/day).
• Rituximab is an effective alternative, given as 375mg/m² weekly for 4 weeks, and is preferred in relapsing disease, as shown in the RAVE trial 1.
• For maintenance therapy after remission (usually 3-6 months), switch to less toxic agents like azathioprine (2mg/kg/day), methotrexate (20-25mg weekly), or mycophenolate mofetil (2g/day), with azathioprine being a recommended option for maintenance therapy, as per the EULAR recommendations 1. Some key points to consider:
• The European Alliance of Associations for Rheumatology (EULAR) also recommends rituximab over azathioprine and glucocorticoids for remission maintenance, with a recommended duration of maintenance therapy of at least 24–48 months following induction of remission 1.
• The KDIGO 2024 clinical practice guideline recommends that the duration of maintenance therapy should be tailored according to an individual’s risk of relapse and the drug used for maintenance, with a recommended interval of 18 months to 4 years following induction of remission 1.
• Trimethoprim-sulfamethoxazole prophylaxis (800/160mg three times weekly) should be added to prevent Pneumocystis pneumonia.
• Patients require close monitoring of renal function, complete blood counts, and inflammatory markers, as recommended by the KDIGO 2024 clinical practice guideline 1. This aggressive approach is necessary because ANCA vasculitis with cavitary lesions represents severe disease with potential for rapid deterioration of lung function and systemic complications if not promptly controlled, as highlighted in the KDIGO 2024 clinical practice guideline 1.

From the FDA Drug Label

A total of 197 patients with active, severe GPA and MPA (two forms of ANCA Associated Vasculitides) were treated in a randomized, double-blind, active-controlled, multicenter, non-inferiority study, conducted in two phases – a 6 month remission induction phase and a 12 month remission maintenance phase.

The main outcome measure for both GPA and MPA patients was achievement of complete remission at 6 months defined as a BVAS/GPA of 0, and off glucocorticoid therapy

Patients in both arms received 1,000 mg of pulse intravenous methylprednisolone per day for 1 to 3 days within 14 days prior to initial infusion. Patients were randomized in a 1:1 ratio to receive either RITUXAN 375 mg/m2 once weekly for 4 weeks or oral cyclophosphamide 2 mg/kg daily for 3 to 6 months in the remission induction phase

The treatment for ANCA positive vasculitis with cavitary lesions is Rituximab. The recommended dosage is 375 mg/m2 once weekly for 4 weeks. Patients may also receive 1,000 mg of pulse intravenous methylprednisolone per day for 1 to 3 days within 14 days prior to initial infusion.

• Key points:
  • Rituximab is used for the treatment of ANCA associated vasculitis.
  • The treatment is given in a remission induction phase.
  • Methylprednisolone may be given prior to the initial infusion.
  • The study demonstrated non-inferiority of RITUXAN to cyclophosphamide for complete remission at 6 months 2.

From the Research

Treatment Options for ANCA-Associated Vasculitis with Cavitary Lesions

• The treatment for ANCA-associated vasculitis with cavitary lesions typically involves immunosuppressive therapy, such as corticosteroids, to improve prognosis 3.
• However, immunosuppression can increase the risk of opportunistic infections, and close monitoring and prophylactic antifungal therapy should be considered 3.
• Rituximab has been shown to be effective in inducing remission in ANCA-associated vasculitis, with remission rates of 80-90% among patients with refractory disease 4, 5.
• Cyclophosphamide is also a common treatment for ANCA-associated vasculitis, but it can have unfavorable side effects, and alternatives such as mycophenolate mofetil may be considered 6, 7.
• Mycophenolate mofetil has been shown to be effective in inducing sustained remission in nonlife-threatening disease, but its efficacy compared to cyclophosphamide is still being studied 6, 7.

Specific Treatment Regimens

• A rituximab-based regimen was not superior to standard intravenous cyclophosphamide for severe ANCA-associated vasculitis, but it may be safer and more effective for relapsing disease 4, 5.
• Mycophenolate mofetil may be an alternative to cyclophosphamide for the treatment of selected patients with nonlife-threatening relapses 7.
• The choice of treatment regimen should be individualized based on the patient's specific condition and medical history.

Considerations for Cavitary Lesions

• Cavitary lesions can be a complication of ANCA-associated vasculitis, and treatment should be tailored to address this specific issue 3.
• The risk of opportunistic infections, such as fungal infections, should be considered when treating patients with cavitary lesions 3.
• Close monitoring and prophylactic antifungal therapy may be necessary to prevent severe complications 3.