Background/Purpose: Eosinophilic granulomatosis with polyangiitis (EGPA) patients frequently develop glucocorticoid (GC)-dependent asthma and/or ENT manifestations, leading to long-term GC requirement and side effects. Mepolizumab, an anti-IL5 monoclonal antibody, has shown efficacy in severe asthma at a dose of 100 mg/month. The MIRRA study demonstrated that 300 mg/month of mepolizumab was effective in EGPA. Following these studies, EGPA patients could have received mepolizumab at the dose of 100 mg/month or 300 mg/month, depending on the EGPA dose access. In case of inadequate response to 100 mg/month, the question of increasing the dose of mepolizumab to 300 mg/month or switching to another drug is often raised by clinicians. We aimed to evaluate the efficacy of increasing the dose of mepolizumab in EGPA patients with an inadequate response to mepolizumab 100 mg/month.

Methods: We conducted a national multicenter, retrospective study of patients diagnosed with EGPA meeting ACR/EULAR 2022 criteria who were initially treated with mepolizumab 100 mg/month and required mepolizumab dose escalation for inadequate response. Complete response was defined as a BVAS of 0 and a prednisone dose ≤4 mg/day. Partial response was defined as a BVAS of 0 and prednisone dose >4 mg/day.

Results: Twenty-six EGPA patients (median age of 51 years [IQR 38-57] and 30% female) were enrolled. At EGPA diagnosis, 24 (92%) had asthma, 23 (88%) sinonasal abnormalities, 9 (35%) pulmonary infiltrates, 3 (11%) eosinophilic pneumoniae, 2 (7%) pleuritis, 2 (7%) alveolar hemorrhage, 8 skin lesions (31%), 7 (27%) cardiac involvement and 5 (19%) peripheral neuropathy. The median blood eosinophil count was 4500/mm3 [IQR 2250-7750] and MPO-ANCA was positive in 7 (27%) cases. Mepolizumab at the dose of 100 mg/month was initiated after a median time from EGPA diagnosis of 41 [IQR 9.7-98.9] months for uncontrolled asthma in 22 (84.6%) patients, ENT manifestations in 16 (61.5%) and/or vasculitis manifestations in 3 (11.5%). Mepolizumab 100 mg/month failed to control disease after a median of 31 months [IQR 9.25-53.25] due to uncontrolled asthma in 22 (84.6%), disabling ENT manifestations in 11 (42.3%), vasculitis flares in 4 (15.3%), and/or inability to reduce prednisone dose below 5 mg/day in 22 (84.6%). The mepolizumab dose was increased to 300 mg/month in 25 patients and to 200 mg/month in one patient. The median prednisone dose at the time of mepolizumab dose escalation was 10 mg/day (IQR 5-17.5]). Five patients (19%) achieved a complete response and 6 (23%) a partial response. Dose-escalation failed in 12 patients (46.2%), mainly due to uncontrolled asthma in 10, ENT manifestations in 8, or vasculitis flare in 1 case, and treatment was discontinued after a median of 9.3 months [IQR 6.6-10.8]. Among these 12 patients, 4 patients continued mepolizumab and 8 switched to benralizumab or dupilumab in 4 cases each. Finally, 3 remaining patients had a follow-up of < 3 months and were not evaluated for efficacy.

Conclusion: In EGPA patients with an inadequate response to mepolizumab 100 mg/month, increasing the dose of mepolizumab led to a complete response in only 20% of cases. These data raise the question of the optimal strategy in the event of failure of the 100 mg/monthly dose.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-increasing-the-dose-of-mepolizumab-in-eosinophilic-granulomatosis-with-polyangiitis/