Mepolizumab for Treatment of Asthma: Post-Approval Academic Practice Experience

Benjamin, Mariel R.; Bochner, Bruce S.; Peters, Anju T.

doi:10.1016/j.jaci.2017.12.034

Cited by 7 publications

(5 citation statements)

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“…Herpes zoster has been reported post approval [136]. Cases of Herpes zoster have also been reported with mepolizumab, including during the initial clinical trials and post approval [137,138]. Patients with known helminth infections were excluded from participation in registration clinical trials for benralizumab, mepolizumab, and reslizumab, and such infections are uncommon in countries where IL-5-targeted therapies have generally been trialed.…”

Section: Discussionmentioning

confidence: 99%

Safety of Eosinophil-Depleting Therapy for Severe, Eosinophilic Asthma: Focus on Benralizumab

Jackson

Korn²,

Mathur

et al. 2020

Drug Saf

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Eosinophils play a pivotal role in the inflammatory pathology of asthma and have been the target of new biologic treatments for patients with eosinophilic asthma. Given the central role of interleukin (IL)-5 in the eosinophil lifecycle, several therapies directed against the IL-5 pathway have been developed, including the anti-IL-5 antibodies mepolizumab and reslizumab and the IL-5 receptor α (IL-5Rα)-directed cytolytic antibody benralizumab. Eosinophil-depleting therapies represent a relatively new class of asthma treatment, and it is important to understand their long-term efficacy and safety. Eosinophils have been associated with host protection and tumor growth, raising potential concerns about the consequences of long-term therapies that deplete eosinophils. However, evidence for these associations in humans is conflicting and largely indirect or based on mouse models. Substantial prospective clinical trial and postmarketing data have accrued, providing insight into the potential risks associated with eosinophil depletion. In this review, we explore the current safety profile of eosinophil-reducing therapies, with particular attention to the potential risks of malignancies and severe infections and a focus on benralizumab. Benralizumab is an IL-5Rα-directed cytolytic monoclonal antibody that targets and efficiently depletes blood and tissue eosinophils through antibody-dependent cell-mediated cytotoxicity. Benralizumab is intended to treat patients with severe, uncontrolled asthma with eosinophilic inflammation.

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Section: Discussionmentioning

confidence: 99%

Safety of Eosinophil-Depleting Therapy for Severe, Eosinophilic Asthma: Focus on Benralizumab

Jackson

Korn²,

Mathur

et al. 2020

Drug Saf

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“…Previous studies have shown that monoclonal antibodies targeting type 2 inflammation are beneficial in treating symptoms in CRS and reducing polyp size in patients with CRSwNP. [26][27][28][29][30] Dupilumab recently showed a reduction in polyp size, sinus opacification, and severity of symptoms in patients with inadequately controlled CRSwNP in phase III trials, and this has led to a recent US Food and Drug Administration indication as an add-on maintenance therapy in these patients. 30 However, the question as to whether biologic agents treating type 2 inflammation would have an effect on reducing exacerbation frequency or antibiotic and/or systemic corticosteroid use still remains.…”

Section: Discussionmentioning

confidence: 99%

Clinical factors associated with acute exacerbations of chronic rhinosinusitis

Kwah

Somani

Stevens

et al. 2020

Journal of Allergy and Clinical Immunology

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Background: Chronic rhinosinusitis (CRS) is complicated by frequent acute exacerbations leading to significant health care burden and impaired quality of life. Objective: The objective of this study was to identify clinical factors associated with frequent acute exacerbation of CRS (AECRS). Methods: This is a retrospective cohort study of patients with CRS from January 1, 2014, to May 31, 2016. Frequent AECRS was defined as at least 4 episodes over a 12-month period in which an antibiotic was prescribed for worsening sinus symptoms, and infrequent AECRS was defined as 0 to 3 episodes. Clinical factors, including asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, and autoimmune disease, were evaluated for associations between the 2 groups. Results: Of the 3109 patients with CRS who were identified, 600 (19.3%) were classified as having frequent exacerbation. Asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, and autoimmune disease were associated with frequent AECRS with statistically significant adjusted odds ratios (aORs) after controlling for age, race, and sex in multivariate analysis (asthma aOR 5 2.61 [95% CI 5 2.14-3.18]; allergic rhinitis aOR 5 1.96 [95% CI 5 1.58-2.42]; eosinophil count of at least 150 cells per microliter aOR 5 1.54 [95% CI 5 1.21-1.97]; and autoimmune disease aOR 5 1.68 [95% CI 5 1.36-2.07]). Antibody deficiency, antibiotic allergy,

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“…It is worth mentioning, that although there is no evidence of increased risk of opportunistic infections in asthmatic patients receiving biologics, cases of herpes zoster have been reported in patients treated with mepolizumab, 31,32 and benralizumab 33,34 indicating that anti‐IL‐5/anti‐IL‐5R treatment might increase the risk of shingles and revealing a possible need of switching to a different class (when possible) when this kind of infection occurs. Furthermore, although considerations were reported regarding the long‐term eosinophil depletion and the incidence of opportunistic infections, neither benralizumab nor reslizumab has been proven to increase this risk 35,36 .…”

Section: When Should Switching Been Considered?mentioning

confidence: 99%

Section: When S Hould Switching B Een Cons Idered?mentioning

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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Mepolizumab for Treatment of Asthma: Post-Approval Academic Practice Experience

Cited by 7 publications

References 0 publications

Safety of Eosinophil-Depleting Therapy for Severe, Eosinophilic Asthma: Focus on Benralizumab

Safety of Eosinophil-Depleting Therapy for Severe, Eosinophilic Asthma: Focus on Benralizumab

Clinical factors associated with acute exacerbations of chronic rhinosinusitis

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

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