Benralizumab for eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Benralizumab is effective in the treatment of eosinophilic asthma and is being investigated for the treatment of other eosinophil-associated diseases. Reports on the use of benralizumab for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) are limited to case reports and small case series. METHODS: We conducted a multicentre, retrospective study including EGPA patients treated with off-label benralizumab. The primary endpoint was the rate of complete response defined as no disease activity (Birmingham Vasculitis Activity Score=0) and a prednisone dose ≤4 mg/day. Partial response was defined as no disease activity and a prednisone dose ≥4 mg/day. RESULTS: Sixty-eight patients were included, including 31 (46%) who had previously received mepolizumab. The use of benralizumab was warranted by uncontrolled asthma in 54 (81%), persistent ear, nose and throat (ENT) manifestations in 27 (40%) and persistent glucocorticoids (GCs) use in 48 (74%) patients. Median (IQR) follow-up after starting benralizumab was 23 (9-34) months. Thirty-three patients (49%) achieved a complete response, 24 (36%) achieved a partial response and 10 (15%) did not respond. Among the 57 patients who initially responded, 10 (18%) eventually required further line treatments. GCs were discontinued in 23 patients (38%). Prior mepolizumab use was associated with a higher rate of primary failure (26.7% vs 5.4%, p=0.034) and less frequent GCs discontinuation (14.8% vs 55.9%, p=0.001). Vasculitis flares occurred in 7 patients (11%) and were associated with histological evidence of vasculitis and/or antineutrophil cytoplasmic antibodies positivity at benralizumab initiation (p=0.004). CONCLUSIONS: Benralizumab appears to be an effective treatment for refractory asthma or ENT manifestations in EGPA and allows GC-sparing. However, its efficacy was lower after prior failure of mepolizumab.

Mepolizumab and benralizumab in patients with severe asthma and a history of eosinophilic granulomatosis with polyangiitis.

Introduction: Asthma associated with eosinophilic granulomatosis with polyangiitis (EGPA) is often severe and corticosteroid-dependent, leading to significant morbidity. Mepolizumab and benralizumab are humanized monoclonal antibodies targeting interleukin 5 (IL-5) and its receptor, respectively. They have been shown to be effective in steroid-sparing in patients with severe eosinophilic asthma. Objective: Our aim was to evaluate the efficacy and safety of mepolizumab and benralizumab prescribed for severe asthma in patients with EGPA under "real-world" conditions. Methods: This was a retrospective analysis of patients with EGPA and persistent asthma who received either mepolizumab 100 or 300 mg administered every 4 weeks, or benralizumab 30 mg administered every 4 weeks for the initial 3 injections and followed by an injection every 8 weeks thereafter, whilst combined with oral glucocorticoids. The follow-up every 6 ± 3 months included an assessment of clinical manifestations, pulmonary function tests and eosinophil cell count. The primary outcome was the proportion of patients at 12 months receiving a daily oral dose of prednisone or equivalent of 4 mg or less with a BVAS of 0. Results: Twenty-six patients were included. After 12 months of treatment with mepolizumab or benralizumab, 32% of patients met the primary outcome and were receiving less than 4 mg of prednisone per day with a BVAS of 0. The median dose of prednisone was 10 mg per day at baseline, 9 mg at 6 months, and 5 mg at 12 months (p ≤ 0.01). At 12 months, 23% of patients were weaned off corticosteroids, while an increase or no change in dose was observed in 27% of patients. The median eosinophil count was significantly reduced from 365 cells/mm3 to 55 cells/mm3 at 6 months and 70 cells/mm3 at 12 months, respectively. No significant change was observed in FEV1. After 12 months of treatment, 14% of patients had had an average of 1 exacerbation of asthma, compared with 52% of patients before baseline. The tolerability profile was favorable. Conclusion: In this real-world study in patients with severe asthma and a history of EGPA asthma, mepolizumab and benralizumab had a significant steroid-sparing effect and reduced asthma exacerbation, but no significant effect on lung function.

Benralizumab for eosinophilic granulomatosis with polyangiitis: a retrospective, multicentre, cohort study.

BACKGROUND: Interleukin-5 (IL-5) inhibitors represent novel therapies for eosinophilic granulomatosis with polyangiitis (EGPA). This study assessed the effectiveness and safety of the IL-5 receptor inhibitor benralizumab in a European cohort of patients with EGPA. METHODS: This retrospective cohort study included patients with EGPA from 28 European referral centres of the European EGPA Study Group across six countries (Italy, France, UK, Russia, Spain, and Switzerland) who received benralizumab as any line of treatment between Jan 1, 2019, and Sep 30, 2022. We assessed the rates of complete response, defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] of 0) and a prednisone dose of up to 4 mg/day, in contrast to partial response, defined as a BVAS of 0 and a prednisone dose greater than 4 mg/day. Active disease manifestations, pulmonary function, variation in glucocorticoid dose, and safety outcomes were also assessed over a 12-month follow-up. FINDINGS: 121 patients with relapsing-refractory EGPA treated with benralizumab at the dose approved for eosinophilic asthma were included (64 [53%] women and 57 [47%] men; median age at the time of beginning benralizumab treatment 54·1 years [IQR 44·2-62·2]). Complete response was reported in 15 (12·4%, 95% CI 7·1-19·6) of 121 patients at month 3, 25 (28·7%, 19·5-39·4) of 87 patients at month 6, and 32 (46·4%, 34·3-58·8) of 69 patients at month 12; partial response was observed in an additional 43 (35·5%, 27·0-44·8) patients at month 3, 23 (26·4%, 17·6-37·0) at month 6, and 13 (18·8%, 10·4-30·1) at month 12. BVAS dropped from 3·0 (IQR 2·0-8·0) at baseline to 0·0 (0·0-2·0) at months 3 and 6, and to 0·0 (0·0-1·0) at month 12. The proportion of patients with systemic manifestations, active peripheral neurological disease, ear, nose, and throat involvement, and pulmonary involvement decreased, with an improvement in lung function tests. Six patients relapsed after having a complete response. The oral prednisone (or equivalent) dose decreased from 10·0 mg/day (5·0-12·5) at baseline to 5·0 mg/day (3·6-8·5) at month 3 (p<0·01), to 5·0 mg/day (2·5-6·3) at month 6, and to 2·5 mg/day (0·0-5·0) at month 12 (p<0·0001). 19 (16%) of 121 patients had adverse events and 16 (13%) discontinued benralizumab. INTERPRETATION: These data suggest that benralizumab could be an effective treatment for EGPA in real-life clinical practice. Further clinical trials are required to confirm the efficacy of benralizumab in patients with a higher baseline disease activity. FUNDING: None.