What is the preferred treatment, Methotrexate (MTX) or Azathioprine, for ANCA (Anti-Neutrophil Cytoplasmic Antibody)-associated vasculitis?

From the Guidelines

Azathioprine is the preferred treatment for ANCA-associated vasculitis, as it has been shown to be slightly more effective than Methotrexate (MTX) at preventing relapses in clinical trials 1. The dose of azathioprine recommended is 1.5–2 mg/kg/d at complete remission, until 1 year after diagnosis, then decreased by 25 mg every 3 months 1. Some key points to consider when choosing between azathioprine and MMF include:

• Azathioprine is generally preferred as first-line maintenance therapy for 18-24 months 1
• MMF can be used as an alternative at a dose of 1-1.5 g twice daily, particularly in patients who cannot tolerate azathioprine due to side effects or in those with poor response 1
• Clinical trials have shown that azathioprine is slightly more effective than MMF at preventing relapses in ANCA vasculitis 1
• MMF may be preferred in women of childbearing potential as azathioprine has more pregnancy concerns 1
• Both medications require regular monitoring of complete blood counts and liver function tests every 1-3 months 1
• Patients should also be on Pneumocystis pneumonia prophylaxis (typically with trimethoprim-sulfamethoxazole) while on these immunosuppressants 1
• The choice between these agents should be individualized based on patient factors, comorbidities, and disease characteristics 1

From the FDA Drug Label

The non-U.S.-licensed rituximab was administered as two 500 mg intravenous infusions separated by two weeks (on Day 1 and Day 15) followed by a 500 mg intravenous infusion every 6 months for 18 months. Azathioprine was administered orally at a dose of 2 mg/kg/day for 12 months, then 1.5 mg/kg/day for 6 months, and finally 1 mg/kg/day for 4 months; treatment was discontinued after 22 months.

The preferred treatment between Methotrexate (MTX) and Azathioprine for ANCA-associated vasculitis cannot be determined from the provided drug labels, as there is no direct comparison between these two treatments. However, the labels do provide information on the use of Azathioprine as a maintenance therapy after induction with cyclophosphamide or rituximab.

• Azathioprine is used as a maintenance therapy to prevent relapse in patients with GPA/MPA who have achieved remission with cyclophosphamide or rituximab.
• The labels do not provide a direct comparison between MTX and Azathioprine, and therefore, no conclusion can be drawn regarding the preferred treatment. 2 2

From the Research

Treatment Options for ANCA-Associated Vasculitis

The treatment options for ANCA-associated vasculitis include Methotrexate (MTX) and Azathioprine. However, the provided studies do not directly compare MTX and Azathioprine.

Comparison of Azathioprine and Rituximab

• A study published in 2014 3 compared rituximab with azathioprine for maintenance in ANCA-associated vasculitis and found that rituximab was more effective in maintaining remission.
• Another study published in 2023 4 found that the cumulative incidence of serious infections among patients who received rituximab was higher than among those who received azathioprine during maintenance.
• A study published in 2013 5 compared rituximab with cyclophosphamide followed by azathioprine and found that rituximab was as effective as conventional immunosuppressive therapy for the induction and maintenance of remissions.

Long-Term Follow-Up of Azathioprine and Cyclophosphamide

• A study published in 2014 6 compared azathioprine with cyclophosphamide for initial maintenance therapy in ANCA-associated vasculitis and found that the outcomes were still poor for this group of patients, and further research is required to determine the optimal timing of maintenance therapy.

Cost-Effectiveness of Rituximab and Azathioprine

• A study published in 2022 7 evaluated the cost-effectiveness of azathioprine, fixed-schedule rituximab, and tailored-dose rituximab for ANCA-associated systemic vasculitis and found that tailored-dose rituximab was the most cost-effective treatment.

Key Findings

• Rituximab may be more effective than azathioprine in maintaining remission in patients with ANCA-associated vasculitis 3, 5.
• The cumulative incidence of serious infections is higher among patients who receive rituximab than among those who receive azathioprine during maintenance 4.
• Tailored-dose rituximab may be the most cost-effective treatment for ANCA-associated vasculitis 7.