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

    Desaintjean, Charlene / Ahmad, Kaïs / Traclet, Julie / Gerfaud-Valentin, Mathieu / Durel, Cecile-Audrey / Glerant, Jean-Charles / Hot, Arnaud / Lestelle, François / Mainbourg, Sabine / Nasser, Mouhamad / Seve, Pascal / Turquier, Ségolène / Devouassoux, Gilles / Cottin, Vincent

    Frontiers in medicine

    2024  Volume 11, Page(s) 1341310

    Abstract: 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 ... ...

    Abstract 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 (
    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.
    Language English
    Publishing date 2024-03-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2024.1341310
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Benralizumab for eosinophilic granulomatosis with polyangiitis.

    Cottu, Adrien / Groh, Matthieu / Desaintjean, Charlene / Marchand-Adam, Sylvain / Guillevin, Loïc / Puechal, Xavier / Beaumesnil, Stacy / Lazaro, Estibaliz / Samson, Maxime / Taille, Camille / Durel, Cécile-Audrey / Diot, Elizabeth / Nicolas, Sarah / Guilleminault, Laurent / Ebbo, Mikael / Cathebras, Pascal / Dupin, Clairelyne / Yildiz, Halil / Belfeki, Nabil /
    Pugnet, Grégory / Chauvin, Pierre / Jouneau, Stephane / Lifermann, Francois / Martellosio, Jean-Philippe / Cottin, Vincent / Terrier, Benjamin

    Annals of the rheumatic diseases

    2023  Volume 82, Issue 12, Page(s) 1580–1586

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Humans ; Granulomatosis with Polyangiitis/drug therapy ; Granulomatosis with Polyangiitis/complications ; Churg-Strauss Syndrome/drug therapy ; Prednisone/therapeutic use ; Retrospective Studies ; Glucocorticoids/therapeutic use ; Asthma/drug therapy ; Asthma/complications
    Chemical Substances benralizumab (71492GE1FX) ; Prednisone (VB0R961HZT) ; Glucocorticoids
    Language English
    Publishing date 2023-08-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 7090-7
    ISSN 1468-2060 ; 0003-4967
    ISSN (online) 1468-2060
    ISSN 0003-4967
    DOI 10.1136/ard-2023-224624
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Benralizumab for eosinophilic granulomatosis with polyangiitis: a retrospective, multicentre, cohort study.

    Bettiol, Alessandra / Urban, Maria Letizia / Padoan, Roberto / Groh, Matthieu / Lopalco, Giuseppe / Egan, Allyson / Cottin, Vincent / Fraticelli, Paolo / Crimi, Claudia / Del Giacco, Stefano / Losappio, Laura / Moi, Laura / Cinetto, Francesco / Caminati, Marco / Novikov, Pavel / Berti, Alvise / Cameli, Paolo / Cathébras, Pascal / Coppola, Angelo /
    Durel, Cécile-Audrey / Folci, Marco / Gullo, Alberto Lo / Lombardi, Carlo / Monti, Sara / Parronchi, Paola / Rivera, Carlos Martinez / Solans, Roser / Vacca, Angelo / Espígol-Frigolé, Georgina / Guarnieri, Gabriella / Bianchi, Fulvia Chieco / Marchi, Maria Rita / Tcherakian, Colas / Kahn, Jean-Emmanuel / Iannone, Florenzo / Venerito, Vincenzo / Desaintjean, Charlene / Moroncini, Gianluca / Nolasco, Santi / Costanzo, Giulia Anna Maria Luigia / Schroeder, Jan Walter / Ribi, Camillo / Tesi, Michelangelo / Gelain, Elena / Mattioli, Irene / Bello, Federica / Jayne, David / Prisco, Domenico / Vaglio, Augusto / Emmi, Giacomo

    The Lancet. Rheumatology

    2023  Volume 5, Issue 12, Page(s) e707–e715

    Abstract: 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 ...

    Abstract 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.
    MeSH term(s) Male ; Humans ; Female ; Adult ; Middle Aged ; Retrospective Studies ; Cohort Studies ; Churg-Strauss Syndrome/diagnosis ; Prednisone ; Granulomatosis with Polyangiitis/drug therapy ; Interleukin Inhibitors ; Leukocyte Disorders ; Pathologic Complete Response ; Antibodies, Monoclonal, Humanized
    Chemical Substances benralizumab (71492GE1FX) ; Prednisone (VB0R961HZT) ; Interleukin Inhibitors ; Antibodies, Monoclonal, Humanized
    Language English
    Publishing date 2023-11-06
    Publishing country England
    Document type Multicenter Study ; Journal Article
    ISSN 2665-9913
    ISSN (online) 2665-9913
    DOI 10.1016/S2665-9913(23)00243-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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