Efficacy of benralizumab for patients with severe eosinophilic asthma: a retrospective, real-life study

Numata, Takanori; Miyagawa, Hanae; Nishioka, Saiko; Okuda, Kunio; Utsumi, Hirofumi; Hashimoto, Mitsuo; Minagawa, Shunsuke; Ishikawa, Takeo; Hara, Hiromichi; Araya, Jun; Kuwano, Kazuyoshi

doi:10.1186/s12890-020-01248-x

Cited by 30 publications

(31 citation statements)

References 32 publications

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“…Several reports have focused on simple switching from omalizumab to mepolizumab 29–31 and from mepolizumab to benralizumab 17 , 32 among the three anti-IL-5/IL-5 receptor antibodies 33 and from a biologic to dupilumab. 34 Most of those reports showed the efficacy of switching biologics.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Switching Biologics for Severe Asthma Patients in Japan: A Single-Center Retrospective Study

Numata¹,

Araya²,

Miyagawa³

et al. 2021

JAA

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Background In Japan, biologic therapy was initiated for patients with severe asthma in 2009. In recent years, four biologics with different mechanisms of action have become available in the clinical setting. However, the efficacy of switching between biologics remains uncertain. Methods To elucidate the efficacy of switching between biologics, 97 patients were enrolled who had received any biologic therapy for severe asthma at Jikei University Hospital, Tokyo, Japan, from July 2009 to December 2020. We retrospectively examined the patient characteristics, biomarkers, pulmonary function test results, selected biologics, and efficacy. Results Thirty-one males and 66 females received any biologics. The mean age was 53.3 years at the initiation of biologic therapy. Initially, 33, 41, 15 and eight patients received omalizumab, mepolizumab, benralizumab, and dupilumab, respectively. Among three representative indicators for biologics administration, the peripheral blood eosinophil count, serum IgE levels and fractional exhaled nitric oxide, 64% of the patients had two indicators, and 28% had three indicators. Thirty-four patients (35%) switched from the initial biologic to another, and the reasons for switching included persistent asthmatic symptoms (n=22), schedule of hospital visits (n=5), and other reasons. Thus, the treatment was effective in 11 patients after switching. In addition, two patients received combination therapy with different biologics. Eighteen patients (19%) interrupted treatment for various reasons. Regardless of whether the biologic was the initial therapy, the overall efficacy of the four biologics was 60% based on the global evaluation of treatment effectiveness. Conclusion Switching between biologics can be a promising option for severe asthma patients in whom treatment with an initial biologic is ineffective.

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Section: Discussionmentioning

confidence: 99%

Effectiveness of Switching Biologics for Severe Asthma Patients in Japan: A Single-Center Retrospective Study

Numata¹,

Araya²,

Miyagawa³

et al. 2021

JAA

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“…Hill et al 144 reported that omalizumab therapy to asthmatic children reduces blood basophil frequencies. Furthermore, treatment with benralizumab, a human antibody against IL-5Rα, reduced the number of basophils as well as eosinophils, [145][146][147] suggesting that the beneficial effect of benralizumab on severe asthma might be attributed to the depletion of not only eosinophils but also basophils. In addition, several mouse studies indicated the involvement of basophils in the development of asthma pathology.…”

Section: Lung Allergic Inflammationmentioning

confidence: 99%

Basophils and their effector molecules in allergic disorders

Miyake

Shibata

Yoshikawa

et al. 2020

Allergy

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Basophils are the least common granulocytes which possess basophilic granules in their cytoplasm. Although they were first documented by Paul Ehrlich more than 140 years ago, their functional significance had long been an enigma, partly because of their rarity and the lack of analytical tools for basophils. In addition, basophils had been erroneously regarded as "blood-circulating mast cells," due to their similarities to tissue-resident mast cells, such as the expression of high-affinity IgE receptor (FcεRI) on their cell surface and the release of histamine upon their activation. Nevertheless, basophils and mast cells differ in a number of aspects. Basophils circulate in the peripheral blood under homeostatic conditions while mast cells typically reside in peripheral tissues and are hardly detected in the peripheral blood. Transcriptomic analyses revealed that basophils display distinct transcriptomic profiles from mast cells in both mice and humans. [1][2][3] Recent development of analytical tools for basophils has enabled us to identify nonredundant functions of basophils in multiple immune reactions, including allergic inflammation, and protective immunity against parasites. [4][5][6][7][8] In addition, the involvement of basophils is also demonstrated in several nonallergic disorders, such as lupus nephritis, 9-11 chronic obstructive pulmonary disease, 12 allograft rejection, 13,14 and carcinogenesis. 15,16 In this review, we summarize recent advances in our understanding of basophil biology, especially focusing on the roles of basophils in the context of allergic inflammation (Boxes 1 and 2). | ONTOG ENY OF BA SOPHIL SAlthough it is widely accepted that basophils differentiate from hematopoietic stem cells (HSCs), 17,18 the pathway of their differentiation

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“…56 In another small study from a cohort of patients with eosinophilic asthma, a subgroup was directly switched from mepolizumab to benralizumab without a wash-out period and experienced significant improvement in all study outcomes. 57 Finally, in a small study, ten prednisonedependent patients with blood (>300 cells/μL) and sputum (>3%) eosinophilia and poor response to mepolizumab (100 mg SC, every 4 weeks), improved lung function and asthma control F I G U R E 1 A proposed algorithm for switching between biologics based on biomarkers and some patients' characteristics.…”

Section: Switching B E T Ween Ag Ents Targ E Ting the Same Pathwaymentioning

confidence: 99%

“…One publication described a case report of one patient with inadequate response to mepolizumab, who experienced clinical and functional improvement after switching to benralizumab, 43 while in a small case series of 3 patients with eosinophilic asthma and suboptimal response to mepolizumab, significant clinical improvement was also achieved after switching to benralizumab 56 . In another small study from a cohort of patients with eosinophilic asthma, a subgroup was directly switched from mepolizumab to benralizumab without a wash‐out period and experienced significant improvement in all study outcomes 57 . Finally, in a small study, ten prednisone‐dependent patients with blood (>300 cells/μL) and sputum (>3%) eosinophilia and poor response to mepolizumab (100 mg SC, every 4 weeks), improved lung function and asthma control when they were switched to weight‐adjusted intravenous reslizumab 55 .…”

Section: Switching Between Agents Targeting the Same Pathwaymentioning

confidence: 99%

Switching between biologics in severe asthma patients. When the first choice is not proven to be the best

Papaioannou

Fouka

Papakosta

et al. 2020

Clin Experimental Allergy

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During the last decades, new treatments targeting disease mechanisms referred as biologics have been introduced in the therapy of asthma, resulting in a revolution in disease control and medical history. These treatments include monoclonal antibodies, recombinant cytokines and fusion proteins, with the former to be, at the moment, the only approved biological therapy for severe refractory asthma, also included in the disease recommendations. 1 To date, five monoclonal antibodies have been approved for the treatment of asthma. Omalizumab, the first biologic drug approved for the treatment of severe allergic asthma, is a recombinant humanized monoclonal antibody that selectively targets circulating IgE and blocks it from binding to its receptor found on mast cells and basophils. Omalizumab interrupts the IgE mediated asthma inflammatory cascade at an early stage 2 and thus, interrupts both early and late asthmatic responses. 3,4 Mepolizumab and reslizumab both target IL-5, which is a key component in eosinophil proliferation, activation and recruitment, preventing consequently its binding to the α-chain of the IL-5 receptor (IL-5α) on eosinophils. 5,6 Benralizumab targets directly IL-5Rα in all cells that express the receptor, such as eosinophils, basophils and mast cells, resulting not only in the blockade of IL-5 mediated survival of these cells but also in a direct eosinophil apoptosis augmentation, via antibody-dependant cell-mediated cytotoxity (ADCC) induced by the enhanced activation of the FcγRIIIa part of the IL-5Rα receptor of mature natural-killer (NK) cells and macrophages, leading in a near depletion of peripheral eosinophils. 7,8 All three

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Efficacy of benralizumab for patients with severe eosinophilic asthma: a retrospective, real-life study

Cited by 30 publications

References 32 publications

Effectiveness of Switching Biologics for Severe Asthma Patients in Japan: A Single-Center Retrospective Study

Effectiveness of Switching Biologics for Severe Asthma Patients in Japan: A Single-Center Retrospective Study

Basophils and their effector molecules in allergic disorders

Switching between biologics in severe asthma patients. When the first choice is not proven to be the best

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