What is the treatment for recurrent ANCA (Anti-Neutrophil Cytoplasmic Antibody) positive, PR-3 (Proteinase 3) positive, crescentic glomerulonephritis?

From the Guidelines

The treatment for recurrent ANCA-positive, PR3-positive crescentic glomerulonephritis should involve rituximab as the first-line therapy, given its superior remission rate compared to cyclophosphamide, especially in patients with relapsing disease, as shown in the RAVE trial with an odds ratio of 3.57 (95% CI: 1.43–8.93) at 6 months 1.

Key Considerations

• The choice of rituximab is based on its effectiveness in achieving remission, particularly in the PR3-ANCA subgroup, with a lower rate of infectious complications compared to cyclophosphamide 1.
• Cyclophosphamide may still be considered in certain cases, but its use should be limited due to its potential for severe side effects and the availability of safer alternatives like rituximab.
• Glucocorticoids, such as prednisolone, are also essential in the treatment regimen but should be used at the lowest effective dose to minimize adverse events, with a goal to taper them off as soon as possible, ideally within 5 months 1.

Treatment Approach

• Induction therapy with rituximab at 375 mg/m² weekly for 4 weeks, along with prednisolone starting at 0.5 mg/kg/day, is a recommended approach for patients with recurrent ANCA-positive, PR3-positive crescentic glomerulonephritis 1.
• Maintenance therapy should be initiated after achieving remission, typically within 3-6 months, using rituximab (500 mg every 6 months) or other immunosuppressive agents like azathioprine (2 mg/kg/day) or mycophenolate mofetil (1-2 g/day) for at least 18-24 months 1.
• Regular monitoring of renal function, urinalysis, ANCA titers, and medication side effects is crucial to adjust the treatment plan as needed and prevent potential complications.

Additional Therapies

• Plasma exchange may be considered in severe cases with rapidly declining renal function or pulmonary hemorrhage, although its use should be based on individual patient needs and clinical judgment.
• Complement-targeted therapy, such as avacopan, may offer an alternative to glucocorticoid treatment in AAV, with potential benefits in reducing glucocorticoid exposure and improving kidney outcomes 1.

From the FDA Drug Label

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 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.

The treatment for recurrent ANCA positive, PR-3 positive, crescentic glomerulonephritis includes:

• Rituximab: 375 mg/m2 once weekly for 4 weeks or two 500 mg intravenous infusions separated by two weeks, followed by a 500 mg intravenous infusion every 6 months for 18 months.
• Cyclophosphamide: 2 mg/kg daily for 3 to 6 months in the remission induction phase.
• Methylprednisolone: 1,000 mg of pulse intravenous methylprednisolone per day for 1 to 3 days within 14 days prior to initial infusion.
• Prednisone: 1 mg/kg/day (not exceeding 80 mg/day) with pre-specified tapering 2 Key points to consider:
• The treatment regimen may vary depending on the patient's response and disease severity.
• Rituximab has been shown to be non-inferior to cyclophosphamide for complete remission at 6 months 2.
• The safety profile of rituximab in patients with GPA and MPA is consistent with the known safety profile in adult patients with RA, GPA, and MPA 2.

From the Research

Treatment for Recurrent ANCA Positive, PR-3 Positive, Crescentic Glomerulonephritis

• The treatment for recurrent ANCA positive, PR-3 positive, crescentic glomerulonephritis typically involves immunomodulatory and immunosuppressive therapies to induce remission, maintain remission, and treat relapses 3.
• In some cases, rituximab (RTX) may be used as remission induction (RI) treatment, and the absence of PR3- or myeloperoxidase (MPO)-ANCA positivity is highly predictive for remaining relapse-free 4.
• The implementation of ANCA and B-cell monitoring could guide therapeutic decision-making to prevent relapses in ANCA-associated vasculitis (AAV) patients treated with RTX 4.
• Steroid therapy may also be initiated to improve symptoms and reduce ANCA titers, as seen in a case report of a patient with PR3-ANCA-positive necrotizing glomerulonephritis 5.
• In cases where infectious endocarditis is associated with crescentic glomerulonephritis, antibacterial drugs and valve replacement surgery may be necessary to improve renal function and reduce ANCA levels 6.

Factors Influencing Treatment

• The presence of PR3-ANCA or MPO-ANCA positivity is a key factor in determining the treatment approach, as these antibodies are associated with distinct pathologic lesions and clinicopathologic variants 3.
• The serotype of ANCA (PR3-ANCA or MPO-ANCA) should be specified in the diagnosis, along with the clinicopathologic variant if possible 3.
• Age, racial/ethnic, and geographic influences may also impact the prevalence, serotype frequencies, and clinicopathologic phenotypes of ANCA vasculitis 3.