What is the best steroid-sparing agent for maintenance of Granulomatosis with Polyangiitis (GPA)?

From the Guidelines

Rituximab is the best steroid-sparing agent for maintenance of Granulomatosis with Polyangiitis (GPA).

Key Points

• The American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis recommends rituximab over methotrexate or azathioprine for remission maintenance in patients with severe GPA/MPA whose disease has entered remission after treatment with cyclophosphamide or rituximab 1.
• The guideline also recommends methotrexate or azathioprine over mycophenolate mofetil or leflunomide for remission maintenance in patients with severe GPA/MPA 1.
• The 2022 EULAR algorithm for treatment of eosinophilic granulomatosis with polyangiitis (EGPA) suggests that AZA, MTX, or RTX can be used as alternatives for maintenance of remission if MEPO is not tolerated or ineffective 1.
• Rituximab has been shown to be non-inferior to cyclophosphamide and appeared more effective for relapsing disease in the RAVE trial 1.

Steroid-Sparing Agents

• Rituximab: recommended as the first-line steroid-sparing agent for maintenance of GPA, with a dose of 375 mg/m2 of body surface area, once a week for four infusions 1.
• Methotrexate: recommended as an alternative to rituximab, with a dose of 20-25 mg/week 1.
• Azathioprine: recommended as an alternative to rituximab, with a dose of 2-3 mg/kg/day 1.

Important Considerations

• The choice of steroid-sparing agent should be individualized based on patient preferences, values, and clinical condition 1.
• The duration of non-GC remission maintenance therapy in GPA/MPA should be guided by the patient’s clinical condition, preferences, and values 1.

From the Research

Steroid-Sparing Agents for Granulomatosis with Polyangiitis (GPA)

The following steroid-sparing agents have been studied for the maintenance of GPA:

• Rituximab: Studies have shown that rituximab is an effective maintenance treatment for GPA, with high rates of sustained remission and low rates of relapse 2, 3, 4, 5.
• Cyclophosphamide: Cyclophosphamide has also been used as a maintenance treatment for GPA, particularly for patients with severe or refractory disease 5, 6.

Efficacy of Rituximab as a Steroid-Sparing Agent

Rituximab has been shown to be effective in inducing and maintaining remission in GPA patients, with response rates ranging from 78.8% to 92% 2, 3, 4.

• A study published in 2014 found that rituximab maintenance therapy every 6 months resulted in a relapse rate of 11.2/100 patient-years 4.
• Another study published in 2019 found that rituximab induction and maintenance therapy resulted in a 2-year relapse-free survival rate of 85% and a 2-year rituximab retention rate of 78% 3.

Comparison of Rituximab and Cyclophosphamide

Both rituximab and cyclophosphamide have been shown to be effective in treating GPA, but rituximab may have a more favorable safety profile 5, 6.

• A study published in 2019 found that rituximab was effective in treating scleritis and uveitis associated with GPA, with no adverse side effects noted throughout the course of treatment 6.
• Cyclophosphamide, on the other hand, has been associated with a higher risk of adverse effects, such as transient leukopenia 6.

Recommendations for Steroid-Sparing Agents

Based on the available evidence, rituximab is a recommended steroid-sparing agent for the maintenance of GPA, particularly for patients with relapsing or refractory disease 2, 3, 4, 5.

• The use of cyclophosphamide may be considered for patients with severe or refractory disease, but its use should be carefully weighed against the potential risks of adverse effects 5, 6.