Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

suspected giant cell arteritis

1st line – corticosteroid

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INITIAL
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suspected giant cell arteritis
1st line – 

corticosteroid

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 (or temporal) arteritis should be treated with corticosteroids immediately when suspicion is high.[11][12]

See Giant cell arteritis for information on further management.

Primary options

prednisone: 1 mg/kg/day orally, maximum 80 mg/day

ACUTE

life-threatening or organ-threatening granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)

1st line – corticosteroid

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ACUTE
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life-threatening or organ-threatening granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
1st line – 

corticosteroid

Examples of vasculitis that threatens vital organ function include pulmonary capillaritis, glomerulonephritis, and mononeuritis multiplex.[9][14]

Corticosteroids plus immunosuppressive agents such are used to induce remission for patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).[9][14]

Either an intravenous-pulsed corticosteroid, or a high-dose oral corticosteroid, may be considered as part of the initial treatment for patients with severe GPA or MPA; however, reduced-dose corticosteroid regimens are becoming more common.[14] 

Reduced-dose corticosteroid regimens are noninferior 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.[16]

Oral corticosteroids are generally recommended until symptoms resolve or for 1 month, then gradually tapered over 6 months. However, tapering regimens vary and local guidance should be consulted.

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, dyslipidemia).[13] See Osteoporosis.

Primary options

methylprednisolone sodium succinate: 0.5 to 1 g intravenously every 24 hours for 3-5 days

OR

prednisone: 1 mg/kg/day orally, maximum 80 mg/day

Plus – immunosuppressant induction therapy

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ACUTE
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life-threatening or organ-threatening granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
Plus – 

immunosuppressant induction therapy

Treatment recommended for ALL patients in selected patient group

For patients with active, severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), rituximab (an anti-CD20 monoclonal antibody) is recommended as first-line treatment for remission induction because it is considered less toxic than cyclophosphamide.[14] Rituximab is approved in the US and Europe for the treatment of GPA and MPA. The approval was based on one randomized clinical trial of 197 patients with severe GPA or MPA, which demonstrated that rituximab is noninferior to cyclophosphamide for remission induction after 6 months of follow-up.[15]

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.

Cyclophosphamide is associated with bone marrow suppression, infertility, hemorrhagic cystitis, and bladder cancer. Cyclophosphamide may be used when patients have active disease despite rituximab treatment or when rituximab is contraindicated.[14]

Blood and urine should be monitored once weekly to once monthly for patients treated with cyclophosphamide, for evidence of adverse effects such as hemorrhagic cystitis or bone marrow suppression. In addition to an increased risk of infection, cyclophosphamide is associated with an increased risk of malignancy and infertility.

Rituximab is associated with infusion-related reactions. Patients should be premedicated with acetaminophen, intravenous methylprednisolone, and an antihistamine 30 minutes prior to each infusion.

Pneumocystis jiroveci (PCP) prophylaxis is recommended during rituximab treatment and for at least 6 months after treatment. PCP prophylaxis should also be considered for patients treated with cyclophosphamide.

Patients treated with cyclophosphamide or rituximab should not have live virus vaccines prior to or during treatment.

Primary options

rituximab: 375 mg/square meter of body surface area intravenously once weekly for 4 weeks; or 1000 mg intravenously on days 1 and 15

Secondary options

cyclophosphamide: 1-2 mg/kg/day orally; 15 mg/kg intravenously every 2 weeks for 3 doses, followed by 15 mg/kg every 3 weeks for at least 3 doses

Plus – immunosuppressant maintenance therapy

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ACUTE
|
life-threatening or organ-threatening granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
Plus – 

immunosuppressant maintenance therapy

Treatment recommended for ALL patients in selected patient group

For patients with severe granulomatosis with polyangiitis or microscopic polyangiitis whose disease has entered remission after treatment with cyclophosphamide or rituximab, the following can all be used for remission maintenance: rituximab, methotrexate, and azathioprine.[9][14]

Rituximab is associated with infusion-related reactions. Patients should be premedicated with acetaminophen, a corticosteroid, and an antihistamine 30 minutes prior to each infusion. Pneumocystis jiroveci prophylaxis is recommended during rituximab treatment and for at least 6 months after treatment. PCP prophylaxis should also be considered for patients treated with cyclophosphamide. Patients treated with rituximab should not have live virus vaccines prior to or during treatment.

Methotrexate and azathioprine are significantly less toxic than cyclophosphamide, but still require routine monitoring of complete blood count for adverse effects such as myelosuppression.

Methotrexate must be co-administered with folate to prevent toxicity.

Patients taking methotrexate should avoid alcohol. Not recommended for women of childbearing potential unless risks outweigh benefits and also contraindicated in the presence of renal insufficiency.Patients who are deficient in thiopurine methyltransferase are unable to tolerate azathioprine. All patients should be tested for thiopurine methyltransferase activity or genotype before starting azathioprine.

These treatments should only be used by an experienced provider in the appropriate clinical setting.

Primary options

rituximab: 500 mg intravenously every 6 months; or 1000 mg intravenously every 4 months

OR

methotrexate: 7.5 to 25 mg orally/subcutaneously once weekly on the same day each week

OR

azathioprine: 1-2 mg/kg/day orally

Consider – avacopan

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ACUTE
|
life-threatening or organ-threatening granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
Consider – 

avacopan

Treatment recommended for SOME patients in selected patient group

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.[9]

Primary options

avacopan: 30 mg orally twice daily

non-life-threatening, non-organ-threatening granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)

1st line – corticosteroid

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ACUTE
|
non-life-threatening, non-organ-threatening granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
1st line – 

corticosteroid

A corticosteroid plus an immunosuppressant is used for the treatment of systemic vasculitis that does not threaten life or the function of a vital organ.[9][14] Reduced-dose corticosteroid regimens are associated with a decreased risk of infection compared with standard-dose regimens.[16]

Primary options

prednisone: 1 mg/kg/day orally, maximum 80 mg/day

Plus – immunosuppressant induction therapy

Back
ACUTE
|
non-life-threatening, non-organ-threatening granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
Plus – 

immunosuppressant induction therapy

Treatment recommended for ALL patients in selected patient group

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.[14][17] The use of immunosuppression facilitates tapering corticosteroids and reduces the risk of disease recurrence.The American College of Rheumatology recommends methotrexate with a corticosteroid is recommended first-line treatment for patients with active, nonsevere granulomatosis with polyangiitis (GPA).[14] Alternative options for these patients include azathioprine or mycophenolate with a corticosteroid.[14] 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.[14]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.[9] There are no trials comparing use of rituximab with other agents in nonorgan threatening GPA or MPA, but trials of rituximab for induction therapy have included this patient group, and their safety and efficacy outcomes were noninferior compared with patients who had more severe baseline disease.[9]Immunosuppressants can lead to myelosuppression, and warrant routine monitoring of complete blood count.Should only be used by an experienced provider in the appropriate clinical setting.Methotrexate must be co-administered with folate to prevent toxicity. Patients taking methotrexate should avoid alcohol. Not recommended for women of childbearing potential unless risks outweigh benefits and also contraindicated in the presence of renal insufficiency.Patients who are deficient in thiopurine methyltransferase are unable to tolerate azathioprine. All patients should be tested for thiopurine methyltransferase activity or genotype before starting azathioprine.Rituximab is associated with infusion-related reactions. Patients should be premedicated with acetaminophen, a corticosteroid, and an antihistamine 30 minutes prior to each infusion. Pneumocystis jiroveci prophylaxis is recommended during rituximab treatment and for at least 6 months after treatment. PCP prophylaxis should also be considered for patients treated with cyclophosphamide. Patients treated with rituximab should not have live virus vaccines prior to, or during treatment.

Primary options

methotrexate: 7.5 to 25 mg orally/subcutaneously once weekly on the same day each week

OR

azathioprine: 1-2 mg/kg/day orally

OR

mycophenolate mofetil: 1 to 1.5 g orally twice daily

OR

rituximab: 375 mg/square meter of body surface area intravenously once weekly for 4 weeks; or 1000 mg intravenously on days 1 and 15

Plus – immunosuppressant maintenance therapy

Back
ACUTE
|
non-life-threatening, non-organ-threatening granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
Plus – 

immunosuppressant maintenance therapy

Treatment recommended for ALL patients in selected patient group

For patients with nonsevere GPA whose disease has entered remission, the American College of Rheumatology recommends methotrexate or azathioprine for remission maintenance.[14]​The European League Against Rheumatism recommends rituximab for remission maintenance. Azathioprine or methotrexate can be used if rituximab is contraindicated.[9]

Primary options

methotrexate: 7.5 to 25 mg orally/subcutaneously once weekly on the same day each week

OR

azathioprine: 1-2 mg/kg/day orally

OR

rituximab: 500 mg intravenously every 6 months; or 1000 mg intravenously every 4 months

Consider – avacopan

Back
ACUTE
|
non-life-threatening, non-organ-threatening granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
Consider – 

avacopan

Treatment recommended for SOME patients in selected patient group

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, for induction of remission.[9]

Primary options

avacopan: 30 mg orally twice daily

ONGOING

resistant to treatment at any stage of therapy

1st line – further investigations and specialist management

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ONGOING
|
resistant to treatment at any stage of therapy
1st line – 

further investigations and specialist management

The possibility that the patient is not having a disease flare should be considered. Infectious complications are common among patients who are chronically immunosuppressed, and can mimic many of the manifestations of vasculitis. Rebiopsy 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 specialist at this stage.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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