Mepolizumab in patients with eosinophilic granulomatosis with polyangiitis

Moiseev, Sergey; Zagvozdkina, Eugenia; Казарина, В. Э.; Bulanov, Nikolai; Novikov, Pavel

doi:10.1016/j.jaci.2019.03.030

Cited by 4 publications

(3 citation statements)

References 4 publications

(6 reference statements)

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“…In the MIRRA trial, the dose choice was based on the phase IIb/III dose range–finding study of mepolizumab in severe eosinophilic asthma ( 7 ), and in a trial of HES ( 20 , 21 ). This choice was also supported by the concept that EGPA, similarly to HES, is a more aggressive condition compared to eosinophilic asthma ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study

Bettiol¹,

Urban²,

Dagna³

et al. 2021

Arthritis & Rheumatology

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Objective Mepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real‐life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) were observed. We undertook this study to assess the effectiveness and safety of mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks in a large European EGPA cohort. Methods We included all patients with EGPA treated with mepolizumab at the recruiting centers in 2015–2020. Treatment response was evaluated from 3 months to 24 months after initiation of mepolizumab. Complete response to treatment was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg/day. Respiratory outcomes included asthma and ear, nose, and throat (ENT) exacerbations. Results Two hundred three patients, of whom 191 received a stable dose of mepolizumab (158 received 100 mg every 4 weeks and 33 received 300 mg every 4 weeks) were included. Twenty‐five patients (12.3%) had a complete response to treatment at 3 months. Complete response rates increased to 30.4% and 35.7% at 12 months and 24 months, respectively, and rates were comparable between mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks. Mepolizumab led to a significant reduction in BVAS score, prednisone dose, and eosinophil counts from 3 months to 24 months, with no significant differences observed between 100 mg every 4 weeks and 300 mg every 4 weeks. Eighty‐two patients (40.4%) experienced asthma exacerbations (57 of 158 [36%] who received 100 mg every 4 weeks; 17 of 33 [52%] who received 300 mg every 4 weeks), and 31 patients (15.3%) experienced ENT exacerbations. Forty‐four patients (21.7%) experienced adverse events (AEs), most of which were nonserious AEs (38 of 44). Conclusion Mepolizumab at both 100 mg every 4 weeks and 300 mg every 4 weeks is effective for the treatment of EGPA. The 2 doses should be compared in the setting of a controlled trial.

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Section: Discussionmentioning

confidence: 99%

Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study

Bettiol¹,

Urban²,

Dagna³

et al. 2021

Arthritis & Rheumatology

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“…All mentioned extensions were intended to monitor the safety profile and efficacy of mepolizumab over a more extended period of time. In contrast to other antieosinophilic biologics, mepolizumab is approved for use in other conditions, namely chronic rhinosinusitis with nasal polyps (CRSwNP) [ 100 ], eosinophilic granulomatosis with polyangiitis (EGPA) [ 101 , 102 ], and FIP1L1-PDGFRA-negative hypereosinophilic syndrome (HES) [ 103 ].…”

Section: Anti-eosinophil Targeted Therapy In Asthmamentioning

confidence: 99%

Subsets of Eosinophils in Asthma, a Challenge for Precise Treatment

Novosad

Krčmová

Souček

et al. 2023

IJMS

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The existence of eosinophils was documented histopathologically in the first half of the 19th century. However, the term “eosinophils” was first used by Paul Ehrlich in 1878. Since their discovery and description, their existence has been associated with asthma, allergies, and antihelminthic immunity. Eosinophils may also be responsible for various possible tissue pathologies in many eosinophil-associated diseases. Since the beginning of the 21st century, the understanding of the nature of this cell population has undergone a fundamental reassessment, and in 2010, J. J. Lee proposed the concept of “LIAR” (Local Immunity And/or Remodeling/Repair), underlining the extensive immunoregulatory functions of eosinophils in the context of health and disease. It soon became apparent that mature eosinophils (in line with previous morphological studies) are not structurally, functionally, or immunologically homogeneous cell populations. On the contrary, these cells form subtypes characterized by their further development, immunophenotype, sensitivity to growth factors, localization, role and fate in tissues, and contribution to the pathogenesis of various diseases, including asthma. The eosinophil subsets were recently characterized as resident (rEos) and inflammatory (iEos) eosinophils. During the last 20 years, the biological therapy of eosinophil diseases, including asthma, has been significantly revolutionized. Treatment management has been improved through the enhancement of treatment effectiveness and a decrease in the adverse events associated with the formerly ultimately used systemic corticosteroids. However, as we observed from real-life data, the global treatment efficacy is still far from optimal. A fundamental condition, “sine qua non”, for correct treatment management is a thorough evaluation of the inflammatory phenotype of the disease. We believe that a better understanding of eosinophils would lead to more precise diagnostics and classification of asthma subtypes, which could further improve treatment outcomes. The currently validated asthma biomarkers (eosinophil count, production of NO in exhaled breath, and IgE synthesis) are insufficient to unveil super-responders among all severe asthma patients and thus give only a blurred picture of the adepts for treatment. We propose an emerging approach consisting of a more precise characterization of pathogenic eosinophils in terms of the definition of their functional status or subset affiliation by flow cytometry. We believe that the effort to find new eosinophil-associated biomarkers and their rational use in treatment algorithms may ameliorate the response rate to biological therapy in patients with severe asthma.

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“…To the Editor: A recent article by Dr MacGlashan 1 concludes that the ''true'' incidence of IgE receptor antibody in patients with chronic spontaneous urticaria is less than 10%. 1 Although most studies report an incidence of 25% to 45% positive basophil histamine release, constraints were added to the analysis, including dependence of basophil histamine release of SYK, Bruton tyrosine kinase, and phosphoinositide 3-kinase, which are linked to IgE receptor activation, plus successful desensitization using aggregated IgE. The initial histamine release value of 41% was then decreased to 7%.…”

Section: Basophil Histamine Release In Patients With Chronic Spontanementioning

confidence: 99%