What is the initial treatment approach for patients with vasculitis?

From the Guidelines

The initial treatment approach for patients with vasculitis typically involves corticosteroids, often starting with high-dose prednisone (1 mg/kg/day, usually 60-80 mg daily) to rapidly control inflammation, combined with immunosuppressive agents such as rituximab (375 mg/m² weekly for 4 weeks) for severe disease, as it is now often preferred due to fewer side effects 1.

Key Considerations

• For less severe disease, methotrexate (15-25 mg weekly), azathioprine (2 mg/kg/day), or mycophenolate mofetil (2-3 g/day) may be used.
• Treatment duration typically involves 3-6 months of intensive therapy followed by maintenance therapy for 1-2 years or longer.
• Patients should receive pneumocystis prophylaxis with trimethoprim-sulfamethoxazole (one single-strength tablet daily) while on immunosuppression.
• Regular monitoring of complete blood counts, kidney function, and inflammatory markers is essential.
• The choice of treatment should be tailored to the specific type of vasculitis, disease severity, organ involvement, and patient factors, as recommended by recent guidelines 1.

Recent Guidelines and Recommendations

• The KDIGO 2024 clinical practice guideline for the management of ANCA-associated vasculitis recommends a combination of glucocorticoids and either rituximab or cyclophosphamide for induction of remission in patients with new-onset or relapsing GPA or MPA with organ-threatening or life-threatening disease 1.
• The EULAR recommendations for the management of ANCA-associated vasculitis suggest that rituximab is preferred in relapsing disease, and that avacopan in combination with rituximab or cyclophosphamide may be considered for induction of remission in GPA or MPA, as part of a strategy to substantially reduce exposure to glucocorticoids 1.

Important Considerations for Treatment

• The dose and duration of glucocorticoids should be carefully considered, as high doses can increase the risk of serious infections, and a reduced dose regimen may be beneficial in reducing this risk 1.
• Plasma exchange may be considered as part of therapy to induce remission in GPA or MPA for those with a serum creatinine >300 µmol/L due to active glomerulonephritis, but its routine use is not recommended 1.

From the FDA Drug Label

Following 2 years of treatment with RITUXAN + MTX, 57% of patients had no progression of structural damage. 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. 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 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

The initial treatment approach for patients with vasculitis includes the use of rituximab or cyclophosphamide.

• Rituximab is administered at a dose of 375 mg/m2 once weekly for 4 weeks.
• Cyclophosphamide is administered at a dose of 2 mg/kg daily for 3 to 6 months. Both treatments are used in the remission induction phase, with the goal of achieving complete remission at 6 months, defined as a BVAS/GPA of 0 and off glucocorticoid therapy 2.

From the Research

Initial Treatment Approach for Vasculitis

The initial treatment approach for patients with vasculitis depends on the type and severity of the condition.

• For severe granulomatosis with polyangiitis or microscopic polyangiitis, rituximab is as effective as cyclophosphamide followed by azathioprine at 18 months 3.
• The standard induction therapy for these conditions consists of cyclophosphamide plus a corticosteroid, which significantly prolongs survival but has burdensome adverse effects 3.
• For cutaneous vasculitis, treatment includes avoidance of triggers and exclusion of vasculitis-like syndromes, and may involve leg elevation, avoidance of standing, and therapy with NSAIDs 4.
• For mild recurrent or persistent cutaneous vasculitis, colchicine and dapsone are first-choice agents, while severe cutaneous disease requires treatment with systemic corticosteroids or more potent immunosuppression 4.
• For renal vasculitis, plasma exchange as adjunctive therapy significantly reduces the risk of end-stage kidney disease at 12 months, and cyclophosphamide is standard induction treatment 5.
• Azathioprine, methotrexate, and leflunomide are effective as maintenance therapy for renal vasculitis, and rituximab is an effective remission induction agent 5, 6.

Treatment Options

Treatment options for vasculitis include:

• Cyclophosphamide combined with glucocorticoids for remission induction in generalized ANCA-associated vasculitis 6.
• Plasmapheresis treatment in severe cases 6.
• Biologic drugs, such as rituximab, for refractory disease 6.
• Medications suitable for remission maintenance, including azathioprine, methotrexate, leflunomide, and mycophenolate mofetil 5, 6.

Diagnostic Approach

The diagnostic approach to vasculitis should involve a systemic approach to diagnosis and classification of disease, evaluation of the extent of organ system involvement, and an exclusion of underlying treatable diseases 7.

• The diagnosis of small vessel vasculitis should preferably rely on both clinical findings and histopathological examination of the organ involved 6.
• A biopsy extending to the subcutis taken from the most tender, reddish or purpuric lesional skin is the key to obtaining a significant diagnostic result, and serial sections are often required for identifying the main vasculitic lesion 4.