Targeted therapy in severe asthma today: focus on immunoglobulin E

Pelaia, Girolamo; Canonica, Giorgio Walter; Matucci, Andrea; Paolini, Rossella; Triggiani, Massimo; Paggiaro, Pierluigi

doi:10.2147/dddt.s130743

Cited by 42 publications

(27 citation statements)

References 76 publications

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“…Airway smooth muscles also express FcεRI, and via IgE activation type I and III collagen production is increased, as seen in asthma remodeling. 39 …”

Section: Biomarkers That Predict Responsiveness To Omalizumabmentioning

confidence: 99%

Omalizumab for severe asthma: toward personalized treatment based on biomarker profile and clinical history

Tabatabaian¹,

Ledford²

2018

JAA

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Asthma is a heterogeneous syndrome with numerous underlining molecular and inflammatory mechanisms contributing to the wide spectrum of clinical phenotypes. Multiple therapies targeting severe asthma with type 2 (T2) high inflammation are or soon will be available. T2 high inflammation is defined as inflammation associated with atopy or eosinophilia or an increase in cytokines associated with T-helper 2 lymphocytes. Omalizumab is a humanized anti-IgE monoclonal antibody and the first biologic therapy approved for moderate–severe allergic asthma. Despite the specificity of biologic therapies like omalizumab, clinical response is variable, with approximately 50% of treated patients achieving the primary outcome. A prior identification of the ideal candidate for therapy would improve patient outcomes and optimize the use of health care resources. As the number of biologic therapies for asthma increases, the goal is identification of biomarkers or clinical phenotypes likely to respond to a specific therapy. This review focuses on potential biomarkers and clinical history that may identify responders to omalizumab therapy for asthma.

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“…Airway smooth muscles also express FcεRI, and via IgE activation type I and III collagen production is increased, as seen in asthma remodeling. 39 …”

Section: Biomarkers That Predict Responsiveness To Omalizumabmentioning

confidence: 99%

Omalizumab for severe asthma: toward personalized treatment based on biomarker profile and clinical history

Tabatabaian¹,

Ledford²

2018

JAA

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“…Sensitization to perennial allergens such as house-dust mite, pet allergens and fungus, and seasonal allergens such as pollen imposes a high risk of developing asthma [ 12 ]. Exposure to aeroallergens triggers Th2 cell-mediated immune response resulting in increased levels of IgE antibodies [ 13 – 15 ], which then bind to the high-affinity IgE receptors (FcεRI) on the effector cells such as mast cells and basophils. Subsequently, this results in the release of various chemical mediators leading to asthma-related symptoms such as wheezing, coughing, chest tightness and shortness of breath [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Improvement of patient-reported outcomes in severe allergic asthma by omalizumab treatment: the real life observational PROXIMA study

Canonica

Rottoli

Bucca

et al. 2018

World Allergy Organization Journal

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BackgroundData on the prevalence of perennial versus seasonal allergic asthma in Italy are lacking; moreover, there is limited evidence on the effect of omalizumab on patient-reported outcomes in Italian patients with severe allergic asthma. PROXIMA, an observational, multicenter study, was designed to assess the prevalence of perennial versus seasonal allergic asthma (cross-sectional phase) and the effect of omalizumab on improving illness perception, quality of life (QoL) and asthma control of Italian patients with severe allergic asthma (longitudinal phase).MethodsThe study included a cross-sectional phase (n = 357) and a longitudinal phase (n = 123): during the longitudinal phase, patients received omalizumab (75–600 mg subcutaneously every month) and were followed-up for 12 months. The primary parameter of cross-sectional phase was prevalence of perennial allergic asthma and that of longitudinal phase was proportion of patients with asthma control (assessed using asthma control questionnaire [ACQ]). Secondary parameters assessed were patients’ disease perception, level of asthma control, exacerbation rate during both cross-sectional and longitudinal phases, and patients' compliance to and persistence with omalizumab, and patients' QoL during the longitudinal phase.ResultsMost patients (95.8%) had perennial allergies; 81% had polysensitization. Of 99 patients in the per-protocol set, 95 (95.96% [95% CI: 89.98–98.89%]) achieved asthma control (ACQ < 4) at both 6 and 12 months of omalizumab treatment; ACQ score decreased after 6 and 12 months (P < 0.0001). Omalizumab treatment resulted in a significant improvement in QoL and patients’ illness perception and 87% decrease in exacerbation rate. The compliance rate with omalizumab was high (73.2%). No new safety signals were identified during treatment.ConclusionThis study demonstrated that in severe allergic asthma, omalizumab improves patient-reported outcomes such as patients’ illness perception and QoL, while confirming improvement of asthma control and exacerbation rate reduction in Italian patients.

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“…Although novel therapeutic approaches (mainly the use of monoclonal antibody to IgE and Th2 cytokines, such as IL5 and IL13) have improved the control of the disease, they do not result in disease modification, or it seems that they can be applied only to a subgroup of patients. 106 – 108 In fact, we are able to reduce exacerbations by targeting eosinophilic inflammation, but novel approaches and targets are required to impact on lung function. 109 On the other hand, PARPs sustain the expression of cytokines, chemokines, and inflammatory mediators, such as TNFα, IL1, IL6, and iNOS.…”

Section: Discussionmentioning

confidence: 99%

Asthma and poly(ADP-ribose) polymerase inhibition: a new therapeutic approach

Zaffini¹,

Gotte²,

Menegazzi³

2018

DDDT

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Asthma is a chronic lung disease affecting people of all ages worldwide, and it frequently begins in childhood. Because of its chronic nature, it is characterized by pathological manifestations, including airway inflammation, remodeling, and goblet cell hyperplasia. Current therapies for asthma, including corticosteroids and beta-2 adrenergic agonists, are directed toward relieving the symptoms of the asthmatic response, with poor effectiveness against the underlying causes of the disease. Asthma initiation and progression depends on the T helper (Th) 2 type immune response carried out by a complex interplay of cytokines, such as interleukin (IL) 4, IL5, and IL13, and the signal transducer and activator of transcription 6. Much of the data resulting from different laboratories support the role of poly(ADP-ribose) polymerase (PARP) 1 and PARP14 activation in asthma. Indeed, PARP enzymes play key roles in the regulation and progression of the inflammatory asthma process because they affect the expression of genes and chemokines involved in the immune response. Consistently, PARP inhibition achievable either upon genetic ablation or by using pharmacological agents has shown a range of therapeutic effects against the disease. Indeed, in the last two decades, several preclinical studies highlighted the protective effects of PARP inhibition in various animal models of asthma. PARP inhibitors showed the ability to reduce the overall lung inflammation acting with a specific effect on immune cell recruitment and through the modulation of asthma-associated cytokines production. PARP inhibition has been shown to affect the Th1–Th2 balance and, at least in some aspects, the airway remodeling. In this review, we summarize and discuss the steps that led PARP inhibition to become a possible future therapeutic strategy against allergic asthma.

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Targeted therapy in severe asthma today: focus on immunoglobulin E

Cited by 42 publications

References 76 publications

Omalizumab for severe asthma: toward personalized treatment based on biomarker profile and clinical history

Omalizumab for severe asthma: toward personalized treatment based on biomarker profile and clinical history

Improvement of patient-reported outcomes in severe allergic asthma by omalizumab treatment: the real life observational PROXIMA study

Asthma and poly(ADP-ribose) polymerase inhibition: a new therapeutic approach

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