## 3 Therapeutic Management of EGPA
### Anti-IL-5-Targeted Therapies
#### 3.2.1. Mepolizumab
Treatment was \(\geq\)6 months and both groups of patients were also administered high-dose steroids at the initiation of therapy. Even considering the critical issues of the study, mainly related to the small groups evaluated (7 patients in the mepolizumab group and 13 patients in the cyclophosphamide group), the results were promising: the retention rate for mepolizumab was again complete (100%), while only 61.5% of patients completed the pulse therapy (6 pulses total); adverse events were nearly twice as frequent in the cyclophosphamide group (53.8% vs. 28.6%, cyclophosphamide vs. mepolizumab, respectively). With regard to efficacy, there were no significant differences in BVAS and eosinophil count reductions between the two groups, however, mepolizumab-treated patients benefitted from a greater steroid dose reduction compared with cyclophosphamide-treated patients. Regarding lung involvement, chest manifestations decreased from 71.4% to 0% and from 58.3% to 8.3% at 6 months, mepolizumab vs. i.v. cyclophosphamide, respectively. Thus, mepolizumab for remission induction therapy in severe EGPA appeared to allow control of disease activity as effectively as cyclophosphamide, but with a greater reduction in concomitant steroid doses and fewer adverse events [28]. Finally, a small series (11 EGPA patients, 3 with uncontrolled asthma), characterized by steroid dependence and unsatisfactory disease control, also achieved improvement of disease activity (no evidence of asthma and vasculitis manifestations at the last study follow-up) following treatment with mepolizumab [29]. Again, the improvement in disease activity allowed notable glucocorticoid tapering. Interestingly, mepolizumab efficacy was also investigated at a lower dose (100 mg every 4 weeks) in real-life EGPA patients. [PERSON] et al. [30] evaluated whether mepolizumab100 mg/month could allow control of asthma symptoms, tapering of glucocorticoids and/or immunosuppressants, maintenance of remission, and prevention of relapses in 18 EGPA patients over a 12-month study period. At the final assessment, more than two thirds of the patients were shown to have been free from asthma exacerbations during treatment, the daily glucocorticoid dose could be at least halved in 77.7% of the subjects, and immunosuppressants could be discontinued in 4 patients. Nearly all patients obtained clinical remission (94.3%) and no relapses were recorded during the study time frame [30]. Further data on the effectiveness of the 100 mg dose were subsequently published. A retrospective European collaborative study compared different biologics, including rituximab, omalizumab, and mepolizumab, for treatment of relapsing or refractory EGPA [31]. While rituximab was primarily chosen to address the treatment of prominent vasculitis features, mepolizumab and omalizumab were administered for the control of steroid-dependent asthma. Mepolizumab was administered to 51 patients and was shown to be highly effective with a good safety profile in patients with steroid-dependent asthma, with a clear advantage over omalizumab in this category of patients (rates of remission and partial responses: 78% and 10% vs. 15% and 33%, mepolizumab vs. omalizumab, respectively). In addition, mepolizumab was administered at the reduced dose of 100 mg monthly in 57% of patients, while the remaining participants received the approved 300 mg dose. Overall, remission rates at 12 months were 76% and 82% among patients receiving mepolizumab at a dose of 100 mg and 300 mg, respectively, with no significant difference [31]. [PERSON] et al. [32] showed that in 16 EGPA patients in remission phase but persisting severe steroid-dependent asthma, not only did mepolizumab 100 mg every 4 weeks prevent vasculitis relapse, but it also achieved asthma control during the 6 months of the study duration. Specifically, both at the 3- and 6-month time points, a significant improvement in Asthma Control Test (ACT) scores, forced expiratory volume in one second (FEV1) %, and exacerbations was observed.