Biologics in severe asthma: A pragmatic approach for choosing the right treatment for the right patient

Rogers, Linda; Jesenak, Milos; Bjermer, Leif; Hanania, Nicola A.; Seys, Sven F.; Diamant, Zuzana

doi:10.1016/j.rmed.2023.107414

Cited by 16 publications

(12 citation statements)

References 117 publications

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“…Eosinophils play an important role in the pathogenesis of asthma 1 . Type 2 inflammatory cascade inhibitors such as mepolizumab, benralizumab, and dupilumab are often effective in the treatment of Th2‐severe asthma 1 .…”

Section: Discussionmentioning

confidence: 99%

“…Severe asthma is defined as asthma that remains uncontrolled despite treatment with high‐dose inhaled corticosteroids (ICS) and long‐acting β2‐agonists 1 . Bronchial thermoplasty (BT) can control severe asthma by reducing the amount of smooth muscle in the bronchial wall 2,3 .…”

Section: Introductionmentioning

confidence: 99%

“…Bronchial thermoplasty (BT) can control severe asthma by reducing the amount of smooth muscle in the bronchial wall 2,3 . Furthermore, several clinical studies have shown that biological treatments, such as humanized monoclonal antibody against IL‐5 receptor α (benralizumab), humanized antibody against IL‐4Rα (dupilumab), and humanized monoclonal antibody against interleukin‐5 (IL‐5) (mepolizumab) are effective in severe asthma 1 . Tezepelumab is a human IgG2 monoclonal antibody that inhibits thymic stromal lymphopoietin (TSLP) 4 .…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of tezepelumab against uncontrolled severe non‐type 2 asthma refractory to bronchial thermoplasty, benralizumab, dupilumab and mepolizumab

Kai,

Suzuki,

Kataoka

et al. 2024

Respirology Case Reports

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Severe asthma affects approximately 5%–10% of patients with asthma. Herein, we describe a case of non‐type 2 asthma that progressively worsened over the years. An 80‐year‐old woman was diagnosed with asthma 11 years back. She experienced repeated exacerbations requiring treatment with systemic corticosteroid despite therapy with medications including high‐dose inhaled corticosteroids/long‐acting beta‐agonists plus long‐acting muscarinic antagonist. The patient presented with non‐eosinophilic asthma. Therefore, the patient was initially treated with bronchial thermoplasty, which was effective for 1 year only. Treatment with bronchial thermoplasty, benralizumab, dupilumab, and mepolizumab was ineffective. The fourth treatment, which included tezepelumab, was initiated. The patient's symptoms and quality of life improved significantly. This is the first case of a patient who did not respond to sequential bronchial thermoplasty, benralizumab, dupilumab, and mepolizumab but who presented with good clinical response to tezepelumab. Therefore, tezepelumab may be useful for patients with non‐type 2 asthma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy of tezepelumab against uncontrolled severe non‐type 2 asthma refractory to bronchial thermoplasty, benralizumab, dupilumab and mepolizumab

Kai,

Suzuki,

Kataoka

et al. 2024

Respirology Case Reports

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“…Currently available biologics act on Th2/eosinophilic phenotype molecules, which improve the quality of life of patients with severe asthma, achieving disease control and reducing/stopping oral steroid dependence [ 4 , 5 ]. Type 2 biologics for severe asthma target key points of the type 2 inflammation including immunoglobulin E (IgE) (omalizumab), interleukin 5 (IL-5) (mepolizumab, reslizumab) or its receptor (benralizumab), thymic stromal lymphopoietin (TSLP) (tezepelumab) and interleukin 4 receptor alpha subunit (IL4rα) (dupilumab), which blocks signaling cascades induced by both IL-4 and IL-13 [ 6 , 7 ]. Tezepelumab is a human monoclonal antibody (mAb) to thymic stromal lymphopoietin that was approved for severe uncontrolled asthma in patients aged 12 years and older at the end of 2022 [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Safety of Biological Therapies for Severe Asthma: An Analysis of Suspected Adverse Reactions Reported in the WHO Pharmacovigilance Database

Cutroneo,

Arzenton,

Furci

et al. 2024

BioDrugs

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Background The management of uncontrolled severe asthma has greatly improved since the advent of novel biologic therapies. Up to August 2022, five biologics have been approved for the type 2 asthma phenotype: anti-IgE (omalizumab), anti-IL5 (mepolizumab, reslizumab, benralizumab), and anti-IL4 (dupilumab) monoclonal antibodies. These drugs are usually well tolerated, although long-term safety information is limited, and some adverse events have not yet been fully characterized. Spontaneous reporting systems represent the cornerstone for the detection of potential signals and evaluation of the real-world safety of all marketed drugs. Objective The aim of this study was to provide an overview of safety data of biologics for severe asthma using VigiBase, the World Health Organization global pharmacovigilance database. Methods We selected all de-duplicated individual case safety reports (ICSRs) attributed to five approved biologics for severe asthma in VigiBase, up to 31st August 2022 (omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab). Descriptive frequency analyses of ICSRs were carried out both as a whole class and as individual products. Reporting odds ratios (ROR) with 95% confidence intervals (CIs) were used as the measure of disproportionality for suspected adverse drug reactions (ADRs) associated with the study drugs compared with either all other suspected drugs (Reference Group 1, RG1) or inhaled corticosteroids plus long-acting β-agonists (ICSs/LABAs) (Reference Group 2, RG2) or with oral corticosteroids (OCSs) (Reference Group 3, RG3). Results Overall, 31,724,381 ICSRs were identified in VigiBase and 167,282 (0.5%) were related to study drugs; the remaining reports were considered as RG1. Stratifying all biologic-related ICSRs by therapeutic indication, around 29.4% ( n = 48,440) concerned asthma use; omalizumab was mainly indicated as the suspected drug ( n = 20,501), followed by dupilumab, mepolizumab, benralizumab and reslizumab. Most asthma ICSRs concerned adults (57%) and women (64.1%). Asthma biologics showed a higher frequency of serious suspected ADR reporting than RG1 (41.3% vs 32.3%). The most reported suspected ADRs included asthma, dyspnea, product use issue, drug ineffective, cough, headache, fatigue and wheezing. Asthma biologics were disproportionally associated with several unknown or less documented adverse events, such as malignancies, pulmonary embolism and deep vein thrombosis with omalizumab; alopecia and lichen planus with dupilumab; alopecia and herpes infections with mepolizumab; alopecia, herpes zoster and eosinophilic granulomatosis with polyangiitis related to benralizumab; and alopecia with reslizumab. Conclusions The most frequently reported suspected ADRs of asthma biologics in VigiBase confirmed the presence of well-known adverse effects such as general disorders, injection-sit...

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“…Limited preliminary data, mostly derived from observational studies and case series, suggests this strategy may be safe in selected patients even if combining therapies is not permitted in some countries or by certain payors [19]. Before considering the opportunity to combine biological drugs, a complete reassessment of the patient at the time of treatment failure or partial or deterioration of response can be recommended, which may include pulmonary function tests, airway inflammatory cell count, imaging and/or bronchoscopy for their complicating disorders, and detecting neutralizing drug antibodies, reported in 1-4% of participants in clinical trials [20].…”

Section: Introductionmentioning

confidence: 99%

Combination of Biological Therapy in Severe Asthma: Where We Are?

Carriera,

Fantò,

Martini

et al. 2023

JPM

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Biological drugs have revolutionized the management of severe asthma. However, a variable number of patients remain uncontrolled or only partially controlled even after the appropriate administration of a biologic agent. The combination of two biologics may target different inflammatory pathways, and it has been used in patients suffering from uncontrolled severe asthma with evidence of both allergic and eosinophilic phenotypes or severe asthma and type2 comorbidities. Combination therapy has also been used to handle anti-IL4/13R induced hypereosinophilia. There is insufficient data on combining biologics for the treatment of severe uncontrolled asthma and type 2 comorbidities, also because of the high cost, and currently no guideline recommends dual biologic therapy. A systematic search was performed using the Medline and Scopus databases. Published data on concurrent administration of two biological drugs in severe, uncontrolled asthma patients has been reported in 28 real-world studies and 1 clinical trial. Data extraction was followed by a descriptive and narrative synthesis of the findings. Future studies should be conducted to further assess the safety, efficacy, and cost-effectiveness of this therapeutic strategy.

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Biologics in severe asthma: A pragmatic approach for choosing the right treatment for the right patient

Cited by 16 publications

References 117 publications

Efficacy of tezepelumab against uncontrolled severe non‐type 2 asthma refractory to bronchial thermoplasty, benralizumab, dupilumab and mepolizumab

Efficacy of tezepelumab against uncontrolled severe non‐type 2 asthma refractory to bronchial thermoplasty, benralizumab, dupilumab and mepolizumab

Safety of Biological Therapies for Severe Asthma: An Analysis of Suspected Adverse Reactions Reported in the WHO Pharmacovigilance Database

Combination of Biological Therapy in Severe Asthma: Where We Are?

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