## 3 Therapeutic Management of EGPA  
### Standard Therapy  
The cornerstone of therapy for EGPA remission induction is represented by glucocorticoids. Immunosuppressants are usually added to the glucocorticoid regimen, particularly in case of life-threatening organ involvement [12], which may be assessed with the aid of the five factor score (FFS), a prognostic tool proposed in 1996 [13] and revised in 2011 [14] (Table 1). FFS has been shown to be useful for survival prediction in EGPA; however, the original 1996 items have been refined in 2011 based on a better knowledge of the disease outcome [13,14]. Using the original set of items (1996), mortality at 5 years was observed to be 11.9% in the absence of any prognostic factor; with 1 of the 5 factors present, mortality increased to 25.9%, while with 2 or more of the 5 factors present (FFS = 2, see explanation in Table 1), mortality was shown to loom over 45.95% of the patients. In the 2011 update, age \(\geq\) 65 years was also recognized as an independent predictor of poor prognosis, while visceral involvement was retained because it was still found to heavily weigh on the outcome. Conversely, ear, nose, and throat symptoms were associated with a lower relative risk of death. According to the 2011 set of criteria, mortality at 5 years was as follows: 9%, 21%, and 40% with FFS = 0, 1, and 2, respectively. Hence, the FFS may help identify patients requiring more aggressive treatment.  
Figure 2: Literature search strategy (box) and final search outcome.  
Glucocorticoids are administered orally at a dose of 0.5-1.0 mg/kg of prednisone equivalent. EGPA patients with no unfavorable prognostic factors according to the FFS may obtain remission with glucocorticoid therapy only, albeit relapses may still occur [12]. However, in case of impending organ- or life-threatening disease (Table 1), intravenous (i.v.) boluses (e.g., methylprednisolone 500-1000 mg daily for 3-5 days) may be preferred over the oral route as initial therapy, followed by oral administration and progressive tapering, according to clinical response; cyclophosphamide or rituximab are usually added to the i.v. glucorticoid induction regimen [12]. Cyclophosphamide may be administered either orally (1.5-2.0 mg/kg for up to 6 months) or intravenously (15 mg/kg fortnightly for the first 3 infusions, then every three weeks for at least 3 more doses), with the oral route associated with a slightly greater risk of bladder toxicity and the i.v. route associated with a slightly greater risk of relapse. Cardiac involvement or \(\geq\)2 organ involvement may favor the use of cyclophosphamide because of an earlier onset of action with respect to rituximab [12]. Rituximab may be considered in ANCA-positive patients, in case of glomerulonephritis, or unsatisfactory response to cyclophosphamide [12]. Ease of administration with the protocol borrowed from rheumatoid arthritis (1 g, 2 weeks apart) [15] may favor rituximab over cyclophosphamide. Maintenance of remission is then attempted with methotrexate, azathioprine, or mycophenolate mofetil, while glucocorticoids are progressively tapered down [12]. However, many patients experience relapses, particularly during the tapering of glucocorticoids.