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

ACUTE

non-severe EGPA

1st line – remission induction: corticosteroid

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ACUTE
|
non-severe EGPA
1st line – 

remission induction: corticosteroid

The American College of Rheumatology and the Vasculitis Foundation guideline on the management of anti-neutrophil cytoplasmic antibody-associated vasculitis define non-severe EGPA as vasculitis without life- or organ-threatening manifestations (e.g., rhinosinusitis, asthma, mild systemic symptoms, uncomplicated cutaneous disease, and mild inflammatory arthritis).[34]

A corticosteroid alone may be appropriate for patients with mild asthma, allergic symptoms, use during pregnancy, or with other individual patient factors.[34]

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).[55]​ See Osteoporosis (Management approach). Patients taking ≥20 mg/day of prednisolone or corticosteroid-sparing agents should consider prophylaxis against Pneumocystis jirovecii.[34][54] See Pneumocystis jirovecii pneumonia.

Primary options

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

Consider – remission induction: mepolizumab or immunosuppressant

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ACUTE
|
non-severe EGPA
Consider – 

remission induction: mepolizumab or immunosuppressant

Additional treatment recommended for SOME patients in selected patient group

Mepolizumab plus an oral corticosteroid is the preferred initial treatment for patients with active non-severe EGPA when a corticosteroid alone are not suitable or if there is an inadequate response to a corticosteroid alone.[34]

The clinical profile of non-severe EGPA includes predominantly asthma, sinus disease, and non-severe vasculitis.[34]

Mepolizumab, an interleukin (IL)-5 receptor antagonist monoclonal antibody, is approved in the US and Europe for the treatment of EGPA. Elevated levels of IL-5 are found in active EGPA.[40][41] Approval was based on a multicentre randomised controlled trial of mepolizumab versus placebo as an add-on agent to corticosteroids with or without other immunosuppressants in patients with relapsing or refractory EGPA. Patients who had had organ or life-threatening manifestations in the previous 3 months were excluded. Its use was associated with more weeks in remission (a combined vasculitis and asthma endpoint) and corticosteroid reduction.[42] Based on the data from this trial, it is reasonable to consider mepolizumab as a corticosteroid-sparing agent in patients without severe active vasculitic manifestations or in whom such manifestations have been brought under control. Its optimal place in therapy is yet to be established.

If mepolizumab is contraindicated, a corticosteroid plus methotrexate, azathioprine, or mycophenolate should be considered.[34] There is significant clinical experience with these treatments, but few data from clinical trials regarding their efficacy.[34] One study has shown that treatment of this group with a corticosteroid and azathioprine, versus a corticosteroid alone, did not lead to superior outcomes and was associated with no significant reduction in relapse rates or any corticosteroid-sparing effect.[43]

Rituximab, an anti-CD20 monoclonal antibody, in addition to a corticosteroid may be considered for patients with active non-severe EGPA if other agents are ineffective.[34] Rituximab is an established treatment for both microscopic polyangiitis and granulomatosis with polyangiitis.[34][47]​​​​​ Standard clinical care is to treat EPGA with severe vasculitic manifestations in the same manner as the other severe anti-neutrophil cytoplasmic antibody-associated vasculitides.[10]​​[47]​​ Evidence from retrospective studies supports the use of rituximab in patients with refractory or relapsed EGPA.[52][53]​​ One RCT, including 105 patients with new onset or relapsing EGPA, of which 42 patients had life-threatening or organ-threatening disease (five-factor score ≥1), demonstrated that rituximab was as effective as standard therapy for remission induction at 180 and 360 days.[48] Results were similar in both newly diagnosed and relapsing disease. However, the superiority design, lack of fully published results, and limited number of patients do not allow for strong conclusions regarding non-inferiority.[47] One phase 3 randomised placebo-controlled trial is ongoing.[49] Rituximab is associated with infusion-related reactions. Patients should be pre-medicated with paracetamol, intravenous methylprednisolone, and an antihistamine 30 minutes prior to each infusion. Patients treated with rituximab should not have live virus vaccines prior to or during treatment.

Primary options

mepolizumab: 300 mg subcutaneously every 4 weeks

Secondary 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

Tertiary options

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

Plus – remission maintenance therapy

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ACUTE
|
non-severe EGPA
Plus – 

remission maintenance therapy

Treatment recommended for ALL patients in selected patient group

For patients who achieve remission with corticosteroids alone, based on symptoms and laboratory markers of inflammation, corticosteroids can be slowly tapered over several months. Patients may need to be maintained on low-dose (≤10 mg/day) prednisolone long term.[44] This may be required to control asthma symptoms.

For patients who achieve remission with mepolizumab, methotrexate, azathioprine, or mycophenolate plus a corticosteroid, continuation of the same treatment is conditionally recommended.[34] Corticosteroid tapering should be guided by the clinical response, as tolerated by the patient.[34]

For patients who achieve remission with rituximab, treatment with methotrexate, azathioprine, or mycophenolate are conditionally recommended for maintenance of remission.[34]

Consider – asthma management

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ACUTE
|
non-severe EGPA
Consider – 

asthma management

Additional treatment recommended for SOME patients in selected patient group

Inhaled corticosteroids may be used to manage airway inflammation and may allow a more successful taper of oral corticosteroids. Patients on leukotriene receptor antagonists at the time of their EGPA diagnosis may be continued on these medications.[20][34] 

Standard asthma therapy may also be needed.

severe EGPA

1st line – remission induction: corticosteroid

Back
ACUTE
|
severe EGPA
1st line – 

remission induction: corticosteroid

The American College of Rheumatology and the Vasculitis Foundation guideline on the management of anti-neutrophil cytoplasmic antibody-associated vasculitis define severe EGPA as vasculitis with life- or organ-threatening manifestations (e.g., alveolar haemorrhage, glomerulonephritis, central nervous system vasculitis, mononeuritis multiplex, cardiac involvement, mesenteric ischaemia, limb/digit ischaemia).[34]

For patients with severe EGPA, either intravenous pulse dose corticosteroid or high-dose oral corticosteroid are recommended as initial treatment.[34]

Corticosteroids are started at a high dose and can be slowly tapered over several months according to clinical response.

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).[55]​ See Osteoporosis (Management approach). Patients taking ≥20 mg/day of prednisolone or corticosteroid-sparing agents should consider prophylaxis against Pneumocystis jirovecii.[34][54] See Pneumocystis jirovecii pneumonia.

Primary options

methylprednisolone sodium succinate: 0.5 to 1 g intravenously every 24 hours for 3-5 days, followed by oral prednisolone

and

prednisolone: 1 mg/kg/day orally following methylprednisolone course, maximum 80 mg/day

OR

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

Plus – remission induction: cyclophosphamide or rituximab

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ACUTE
|
severe EGPA
Plus – 

remission induction: cyclophosphamide or rituximab

Treatment recommended for ALL patients in selected patient group

Either cyclophosphamide or rituximab may be considered for remission induction in patients with active severe EGPA.[34][45]

Treatment should be individualised; for example, cyclophosphamide would be the preferred treatment for patients with cardiac involvement, as cardiomyopathy is the main independent predictor of death in EGPA, and there is more evidence to support this treatment. Cyclophosphamide is also preferred if patients are anti-neutrophil cytoplasmic antibody (ANCA)-negative and have severe neurological or gastrointestinal manifestations.[34] Rituximab may be preferred for patients with positive ANCA results, active glomerulonephritis, prior cyclophosphamide treatment, or those at risk of gonadal toxicity from cyclophosphamide.[34]

Cyclophosphamide can be given intravenously or orally. The CYCLOPS trial (daily oral versus intravenous pulse dose cyclophosphamide for renal vasculitis) in granulomatosis with polyangiitis (GPA) suggested that intravenous pulse dosing is preferable because efficacy seems similar and it may be safer due to lower total cyclophosphamide dose received, although whether this may lead to a higher relapse rate has yet to be determined.[46] While patients with EGPA were excluded from this and other multicentre randomised ANCA vasculitis trials, the recommendation is to treat EGPA with severe manifestations in the same way as GPA and microscopic polyangiitis (MPA).

The choice between daily oral and pulse intravenous cyclophosphamide administration may be influenced by factors including the patient's risk of relapse, compliance with treatment and monitoring schedules, fertility issues, and potential susceptibility to other adverse effects of cyclophosphamide. If intravenous cyclophosphamide is used, the protocol should incorporate intravenous fluids and mesna (a uroprotective agent) to minimise bladder toxicity. To reduce the risk of toxicity from oral cyclophosphamide, it should be taken in the morning and a liberal fluid intake maintained throughout the day. Full blood count and urinalysis should be monitored regularly, in accordance with local protocols.

For patients with severe EGPA who have contraindications to cyclophosphamide, rituximab (an anti-CD20 monoclonal antibody) in combination with a corticosteroid is recommended as an alternative.[47] One RCT, including 105 patients with new onset or relapsing EGPA, of which 42 patients had life-threatening or organ-threatening disease (five-factor score ≥1), demonstrated that rituximab was as effective as standard therapy for remission induction at 180 and 360 days.[48] Results were similar in both newly diagnosed and relapsing disease. However, the superiority design, lack of fully published results, and limited number of patients do not allow for strong conclusions regarding non-inferiority.[47] One phase 3 randomised placebo-controlled trial is ongoing.[49]​ Rituximab is associated with infusion-related reactions. Patients should be pre-medicated with paracetamol, intravenous methylprednisolone, and an antihistamine 30 minutes prior to each infusion. Patients treated with rituximab should not have live virus vaccines prior to or during treatment.

Primary options

cyclophosphamide: 1-2 mg/kg/day orally for 3-6 months; or 15 mg/kg intravenously every 2 weeks for 3 doses, followed by 15 mg/kg every 3 weeks for at least 3 doses

OR

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

Plus – remission maintenance therapy

Back
ACUTE
|
severe EGPA
Plus – 

remission maintenance therapy

Treatment recommended for ALL patients in selected patient group

For patients with severe EGPA who achieve remission with either 3 to 6 months of cyclophosphamide or 4 weeks of rituximab plus a corticosteroid, treatment with methotrexate, azathioprine, or mycophenolate are conditionally recommended for maintenance of remission.[34]

Corticosteroid tapering should be guided by the clinical response, as tolerated by the patient.

Consider – plasma exchange

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ACUTE
|
severe EGPA
Consider – 

plasma exchange

Additional treatment recommended for SOME patients in selected patient group

In circumstances where disease is severe and life-threatening, plasma exchange may be used as an adjunct to corticosteroids and cyclophosphamide.[10]

One subsequent systematic review and meta-analysis demonstrated that adjunctive treatment with plasma exchange reduced 12-month risk of end stage kidney disease, regardless of baseline kidney disease, in patients with ANCA-associated vasculitis, but had no important effect on mortality and increased the risk of serious infections.[50] ​BMJ: plasma exchange and glucocorticoid dosing for patients with ANCA-associated vasculitis: a clinical practice guideline Opens in new window​

Consult a specialist when considering plasma exchange.

Consider – asthma management

Back
ACUTE
|
severe EGPA
Consider – 

asthma management

Additional treatment recommended for SOME patients in selected patient group

Inhaled corticosteroids may be used to manage airway inflammation and may allow a more successful taper of oral corticosteroids. Patients on leukotriene receptor antagonists at the time of their EGPA diagnosis may be continued on these medications.[20][34] 

Standard asthma therapy may also be needed.

ONGOING

relapse following successful remission

1st line – remission re-induction therapy

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ONGOING
|
relapse following successful remission
1st line – 

remission re-induction therapy

Mepolizumab is conditionally recommended for patients who have relapsed disease with non-severe disease manifestations (i.e., asthma and/or sinonasal disease), who are being treated with a low-dose corticosteroid alone; are being treated with methotrexate, azathioprine, or mycophenolate; have high serum immunoglobulin E levels and are being treated with methotrexate, azathioprine, or mycophenolate.[34]

Clinical trials have demonstrated the effectiveness of mepolizumab in patients with relapsing non-severe EGPA who are receiving immunosuppressive therapy and in patients with eosinophilic asthma.[51][42] The addition of mepolizumab is preferred to the addition of systemic immunosuppressants in patients receiving corticosteroids alone, and in preference to switching to an alternative agent in patients being treated with methotrexate, azathioprine, or mycophenolate.[34]

For patients who have experienced relapse with severe disease manifestations after prior successful remission induction, rituximab is preferred for remission re-induction, as re-treatment with cyclophosphamide should be avoided if possible.[34] Evidence from retrospective studies supports the use of rituximab in patients with refractory or relapsed EGPA.[52][53]

Inhaled therapy for active asthma should be optimised before increasing systemic immunosuppressive treatment in patients with non-severe disease relapse.[34]

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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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