From the Guidelines
Vasculitis treatment should prioritize 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, as recommended by the most recent EULAR guidelines 1.
Key Considerations
- The treatment approach should be based on the severity and type of vasculitis, with ANCA-associated vasculitis requiring specific consideration of rituximab as a first-line therapy alongside corticosteroids.
- Induction therapy typically lasts for 3-6 months to achieve remission, followed by maintenance therapy with lower doses of immunosuppressants.
- Regular monitoring for disease activity and medication side effects is crucial, including complete blood counts, kidney function, and urinalysis.
- Prophylaxis against Pneumocystis pneumonia with trimethoprim-sulfamethoxazole is recommended during immunosuppressive therapy.
Treatment Options
- Glucocorticoids, such as prednisone, starting at 1 mg/kg/day to rapidly reduce inflammation.
- Immunossuppressants like cyclophosphamide, methotrexate, or rituximab, depending on the specific type and severity of vasculitis.
- Rituximab (375 mg/m² weekly for 4 weeks) has become a first-line therapy alongside corticosteroids for ANCA-associated vasculitis.
Management
- Multidisciplinary management by centers with specific vasculitis expertise is recommended for AAV, as these diseases are rare, heterogeneous, and potentially life-threatening 1.
- Accurate diagnosis, assessment of disease severity, and differentiation between active vasculitis, infection, and other complications or comorbidities require rapid and low-threshold access to multidisciplinary diagnostic evaluation and treatment.
- Dedicated vasculitis centers can provide bundled services, including access to novel drugs within clinical trials, support from trained nurses and other healthcare providers, and education for patients.
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 The study demonstrated non-inferiority of RITUXAN to cyclophosphamide for complete remission at 6 months In the RITUXAN group, 44% of patients achieved CR at 6 and 12 months, and 38% of patients achieved CR at 6,12, and 18 months
Vasculitis treatment with Rituximab:
- Rituximab is used to treat Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA), two forms of ANCA Associated Vasculitides.
- The study demonstrated non-inferiority of RITUXAN to cyclophosphamide for complete remission at 6 months.
- 44% of patients achieved complete remission at 6 and 12 months, and 38% of patients achieved complete remission at 6,12, and 18 months 2
From the Research
Definition and Classification of Vasculitis
- Vasculitis refers to a pathologic condition defined by inflammatory cell infiltration and destruction of blood vessels 3
- Systemic vasculitis is classified as primary or secondary, with secondary vasculitis associated with connective tissue disorders, infections, medications, and rarely, as a paraneoplastic phenomenon 3, 4
Clinical Manifestations of Vasculitis
- Neuropathy is a common complication of systemic vasculitis and is related to ischemic nerve fiber damage with axon loss 3
- Peripheral neuropathy may be the sole manifestation of vasculitis, a condition termed nonsystemic vasculitic neuropathy (NSVN) 3, 4
- Vasculitis can present with life-threatening lung-kidney syndromes, such as diffuse alveolar hemorrhage and severely impaired glomerular filtration rates 5
Diagnosis of Vasculitis
- The diagnosis of vasculitis should be established by tissue (preferably nerve) biopsy 3
- Laboratory tests often indicate features of systemic inflammation, such as an elevated sedimentation rate or positive anti-neutrophil cytoplasmic antibody 4
Treatment of Vasculitis
- High-dose prednisone is the standard platform therapy for patients with systemic and NSVN 3, 4
- Cyclophosphamide is often used in combination with prednisone, with intravenous pulse or oral daily administration 3, 4, 6, 7
- Other agents, such as azathioprine, methotrexate, intravenous immunoglobulin, mycophenolate mofetil, plasma exchange, and rituximab, can be offered to patients who are intolerant or have a contraindication to cyclophosphamide 3, 4, 6, 7
- Plasma exchange as adjunctive therapy significantly reduces the risk of end-stage kidney disease at 12 months 6, 7
- Rituximab is an effective remission induction agent, and azathioprine, methotrexate, and leflunomide are effective as maintenance therapy 6, 7