What is the management of systemic vasculitis?

From the Guidelines

Management of systemic vasculitis requires a multifaceted approach, with the most recent and highest quality study recommending a combination of immunosuppressive therapy and high-dose corticosteroids for rapid induction of remission 1.

Key Principles of Management

• Initial treatment should focus on rapid induction of remission with high-dose corticosteroids (prednisone 1 mg/kg/day, maximum 60-80 mg daily) combined with another immunosuppressant based on disease severity and type.
• For severe disease, cyclophosphamide (15 mg/kg IV every 2-3 weeks or 2 mg/kg/day orally) or rituximab (375 mg/m² weekly for 4 weeks) is recommended, as indicated by the 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of polyarteritis nodosa 1.
• Once remission is achieved, usually within 3-6 months, maintenance therapy should be initiated with less toxic agents such as azathioprine (2 mg/kg/day), methotrexate (15-25 mg weekly), or mycophenolate mofetil (2-3 g/day), as suggested by earlier studies 1.

Supportive Care and Monitoring

• Corticosteroids should be gradually tapered to the lowest effective dose.
• Maintenance therapy typically continues for 18-24 months, with longer durations for relapsing disease.
• Supportive care is essential, including pneumocystis pneumonia prophylaxis with trimethoprim-sulfamethoxazole (one single-strength tablet daily) when using significant immunosuppression.
• Regular monitoring of disease activity, medication toxicity, and organ function is crucial through clinical assessment, laboratory tests, and sometimes imaging studies, as emphasized by the European League Against Rheumatism (EULAR) recommendations for the management of ANCA-associated vasculitis 1.

Disease Severity and Treatment Decisions

• Patients with severe disease should be treated with cyclophosphamide and glucocorticoids, while those with nonsevere disease may be treated with alternative immunosuppressive agents and a glucocorticoid-sparing regimen, as recommended by the 2021 guideline 1.
• The use of diagnostic procedures such as angiography, electromyography/nerve conduction studies, and nerve and muscle biopsy is recommended to aid in diagnosis, but the use of routinely repeated procedures during periods of disease quiescence is discouraged.

Future Research Directions

• Further studies are needed to determine the role of longitudinal vascular imaging studies, the comparative effectiveness of nonglucocorticoid immunosuppressive agents, and the development of biomarkers to inform disease activity or treatment response, as highlighted by the gaps in current knowledge 1.

From the FDA Drug Label

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 In patients treated with cyclophosphamide (followed by azathioprine for maintenance of CR), 38% of patients achieved CR at 6 and 12 months, and 31% of patients achieved CR at 6,12, and 18 months By month 28, major relapse occurred in 3 patients (5%) in the non-U.S. -licensed rituximab group and 17 patients (29%) in the azathioprine group.

Management of Systemic Vasculitis:

• Rituximab can be used to manage systemic vasculitis, with 44% of patients achieving complete remission at 6 and 12 months.
• The use of rituximab has been shown to be effective in maintaining remission, with a lower rate of major relapse compared to azathioprine.
• The safety profile of rituximab in patients with GPA and MPA is consistent with its known safety profile in adult patients with RA, GPA, and MPA. 2 2

From the Research

Management of Systemic Vasculitis

• Systemic vasculitis can be categorized as primary or secondary, with primary disorders including polyarteritis nodosa, Churg-Strauss syndrome, and Wegener granulomatous, and secondary processes representing a complication from a connective tissue disorder, infection, medication, or malignancy 3.
• The diagnosis of vasculitic neuropathy is straightforward in patients with an established diagnosis of systemic vasculitis and classic features of mononeuritis multiplex, with laboratory tests often indicating features of systemic inflammation, such as an elevated sedimentation rate or positive anti-neutrophil cytoplasmic antibody 3.
• Treatment of vasculitic neuropathy requires long-term immunosuppressive therapies, with high-dose prednisone combined with intravenous pulse or oral daily cyclophosphamide as standard initial therapy 3, 4.
• 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, although evidence for the benefit of these agents is limited to case reports and small case series 3, 4.
• The combination of cyclophosphamide and prednisone is still regarded as the induction treatment of first choice for most types of generalized systemic vasculitis, but treatment-associated adverse events occur frequently and have a considerable negative effect on outcomes 5.
• New data indicate that targeted treatments such as rituximab might have the potential to replace cyclophosphamide in the future, and the cumulative dosage of cyclophosphamide can be reduced by pulse versus oral administration without losing efficacy 5.
• The use of cyclophosphamide in patients with nonsystemic vasculitic neuropathy (NSVN) is controversial, but recent retrospective data suggest that those treated with prednisone and cyclophosphamide from the outset fare better than those initially treated only with prednisone 4.
• Azathioprine can be safely substituted for cyclophosphamide after 3 months without an increased relapse rate, and other therapies such as interferon-alpha and intravenous immune globulin can be used to treat vasculitis associated with hepatitis B infection or other conditions 4, 6.