Approach
The goals of therapy are threefold:
To achieve disease remission
To prevent disease recurrence
To minimise toxicity associated with drug therapy.
Exact treatment is dependent on the specific diagnosis and on the severity of the clinical manifestations. For more details on specific disorders see:
Granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis)
Eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome)
Goodpasture’s disease (also known as anti-glomerular basement membrane disease)
Cryoglobulinaemia (also known as cryoglobulinaemic vasculitis)
IgA vasculitis (formerly known as Henoch-Schonlein purpura)
Presumptive therapy for giant cell arteritis
Giant cell arteritis is the one form of systemic vasculitis for which it is standard to initiate therapy prior to establishing a definitive diagnosis, because it can lead to irreversible blindness. Giant cell arteritis should be treated with corticosteroids immediately when suspicion is high.[9][10] See Giant cell arteritis for detail on further management.
Remission-inducing therapy for granulomatosis with polyangiitis or microscopic polyangiitis
Rapid recognition of disease and subsequent instigation of induction therapy is important to minimise morbidity and mortality.
Patients will generally receive an initial course of high-dose corticosteroids with an immunosuppressant.
Screening and preventive measures against corticosteroid-induced osteoporosis should be instituted, along with monitoring and treatment for other complications of corticosteroid treatment (e.g., hypertension, diabetes mellitus, dyslipidaemia).[11] See Osteoporosis.
Life-threatening disease or involvement of vital organ
Corticosteroids plus immunosuppressive agents such as cyclophosphamide or rituximab are used to induce remission for patients with vasculitis that threatens life, or the function of a vital organ.[12][13] Examples of vasculitis that threatens vital organ function include pulmonary capillaritis, glomerulonephritis, and mononeuritis multiplex.[12][13]
Rituximab (an anti-CD20 monoclonal antibody) is recommended as first-line treatment for remission induction because it is considered less toxic than cyclophosphamide.[12][13] Rituximab is approved in the US and Europe for the treatment of GPA and MPA. The approval was based on one randomised clinical trial of 197 patients with severe GPA or MPA, which demonstrated that rituximab is non-inferior to cyclophosphamide for remission induction after 6 months of follow-up.[14]
Cyclophosphamide is associated with bone marrow suppression, infertility, haemorrhagic cystitis, and bladder cancer. Cyclophosphamide may be used when patients have active disease despite rituximab treatment or when rituximab is contraindicated.[12]
Cyclophosphamide or rituximab are used only for a limited time for remission induction: 3 to 6 months and 2 to 4 weeks (depending on the regimen used), respectively.
Either an intravenous-pulsed corticosteroid, or a high-dose oral corticosteroid, may be considered as part of the initial treatment for patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA); however, reduced-dose corticosteroid regimens are becoming more common.[12] Reduced-dose corticosteroid regimens are non-inferior to standard-dose corticosteroid regimens with respect to all-cause mortality or end-stage renal disease. Reduced-dose regimens are associated with a decreased risk of infection compared with standard-dose regimens.[15]
As part of the strategy to reduce exposure to corticosteroids, avacopan, a complement C5a receptor inhibitor, may be considered as an adjunctive therapy for patients treated with rituximab or cyclophosphamide, for induction of remission.[13]
Not life-threatening disease and no involvement of vital organ
Corticosteroids plus immunosuppressants (e.g., methotrexate, azathioprine, mycophenolate, rituximab) are used for the treatment of systemic vasculitis that does not threaten life or the function of a vital organ.[12][13] The use of immunosuppression facilitates tapering corticosteroids and reduces the risk of disease recurrence.
The American College of Rheumatology recommends methotrexate with a corticosteroid as first-line treatment for patients with active, non-severe GPA.[12] Alternative options for these patients include azathioprine or mycophenolate with a corticosteroid.[12] Rituximab may be considered, in conjunction with a corticosteroid, in certain clinical situations, e.g., in patients with hepatic or renal dysfunction, patients who have recurrent relapses on methotrexate, or when adherence to methotrexate is a concern.[12]
The European League Against Rheumatism recommends corticosteroids and rituximab, methotrexate, or mycophenolate for remission induction of GPA or MPA that does not threaten life or organs.[13] There are no trials comparing use of rituximab with other agents in non-organ threatening GPA or MPA, but trials of rituximab for induction therapy have included this patient group, and their safety and efficacy outcomes were non-inferior compared with patients who had more severe baseline disease.[13]
Avacopan may be considered as an adjunctive therapy for patients treated with rituximab for induction of remission.[13]
Remission maintenance
Once remission is achieved, corticosteroids are usually tapered according to clinical response and as tolerated by the patient to limit drug-induced toxicity. If patients have been receiving therapy with an immunosuppressant, they may be continued on this treatment for remission maintenance according to local protocols. Duration of maintenance therapy will vary according to the type of vasculitis and distribution of organ involvement.
For patients with severe GPA/MPA whose disease has entered remission after treatment with cyclophosphamide or rituximab, the following can all be used for remission maintenance: rituximab, methotrexate, and azathioprine.[12][13]
For patients with non-severe GPA whose disease has entered remission, the American College of Rheumatology recommends methotrexate or azathioprine for remission maintenance.[12] The European League Against Rheumatism recommends rituximab for remission maintenance. Azathioprine or methotrexate can be used if rituximab is contraindicated.[13]
Treatment-resistance
In patients who do not respond to treatment, consider the possibility that the patient is not having a disease flare. Infectious complications are common among patients who are chronically immunosuppressed, and can mimic many of the manifestations of vasculitis. Re-biopsy and culture of the affected organ can be invaluable to confirm the diagnosis, and to ensure that continued immunosuppression is appropriate. If not already under specialist care, it is important to consider referral to a rheumatologist or another consultant at this stage.
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