Treatment of adults with organ- or life-threatening eosinophilic granulomatosis with polyangiitis (EGPA)

ANCA: anti-neutrophil cytoplasmic antibodies; ECG: electrocardiogram; EGPA: eosinophilic granulomatosis with polyangiitis; ENT: ears, nose, and throat; GI: gastrointestinal; ICU: intensive care unit; IL: interleukin; IV: intravenous; IVIG: intravenous immunoglobulin.

* Typically, a prednisone equivalent of 80 to 120 mg per day is the maximal dose given, regardless of patient weight. Occasionally, higher doses may be used in severe disease or if initial response to pulse-dose glucocorticoids is suboptimal. Dosing should be quickly decreased toward the typical range once a significant clinical response has been achieved.

¶ Typical dosing of cyclophoshamide is 15 mg/kg (maximum 1200 mg) IV every two weeks for three doses and then every three weeks for at least three doses, with dose reductions for kidney function and age ≥60 years. For less severe disease or after initial dosing, cyclophosphamide may be given orally 1.5 to 2 mg/kg daily (maximum 200 mg/day), typically for three to six months, with additional dose reduction for kidney insufficiency or older age. Cyclophosphamide may be favored in those with rapid disease, life-threatening cardiac involvement, severe pulmonary hemorrhage, ANCA-negative disease, and those with neurologic or GI manifestations.

Δ Typical induction dosing for rituximab is 375 mg/m² IV once weekly for four doses or (in adults) 1000 mg IV on days 1 and 15; rituximab may be favored for those with concern for gonadal toxicity, prior treatment with cyclophosphamide, active glomerulonephritis, and those with positive ANCA. Rituximab is not typically redosed after induction unless needed for relapse or maintenance. When needed, additional dosing is 500 to 1000 mg IV every four to six months.

◊ Anti-IL-5/5R therapies used for the treatment of EGPA include mepolizumab 300 mg subcutaneously every four weeks or benralizumab 30 mg subcutaneously every four weeks.

§ The pace of the taper requires adjustment based on individual patient response to therapy. Eosinophil counts and symptoms should be assessed carefully during the taper to avoid severe relapses. Patients who have had relapses may require a slower taper or a halt to the taper prior to completion.

¥ In this context, remission means absence of clinical signs and symptoms attributable to active disease, with the exception of asthma and ENT symptoms, which must be greatly improved. Evaluation includes monitoring of eosinophilia and any organ system previously involved (eg, creatinine clearance and microscopic urinalysis; pulmonary function testing; chest imaging; ECG or echocardiogram; skin, eye, or ENT examination). Please see UpToDate content on the treatment of EGPA for additional details.

‡ Alternative immunosuppressants other than IL-5-targeted therapies and glucocorticoids (eg, methotrexate or mycophenolate mofetil) should be held prior to repeat induction therapy with cyclophosphamide or rituximab.

† Comparative efficacy of add-on therapies has not been well-studied, particularly in the context of background anti-IL-5/5R therapy. Our authors typically choose methotrexate or mycophenolate. Rituximab is typically reserved for those with recurrent organ-threatening disease and/or recurrence despite a trial of another agent. Please see UpToDate content on treatment of EGPA for dosing information, including timing of initiation after induction therapy and additional less commonly used alternatives.

** Timing of trials off steroid-sparing agents is uncertain. Our authors typically stop immunosuppressant agents (eg, methotrexate, mycophenolate, rituximab) before trying to stop anti-IL-5/5R therapy because the immunosuppressant therapies have greater adverse effects/toxicities. Anti-IL-5/5R therapies should be maintained for at least 18 months in all patients with severe initial disease and even longer in those with difficult-to-achieve remission. Patients who have had multiple relapses may require lifelong therapy. Please refer to UpToDate topics on EGPA treatment for additional details regarding tapering glucocorticoid-sparing therapies.