anti-IgE Antibody Research Articles

Effect of anti-IgE in occupational asthma caused by exposure to low molecular weight agents.

The role of immunoglobulin (Ig)-E in occupational asthma (OA) due to low molecular weight (LMW) agents is not well established compared to classical atopic asthma. In this study, we evaluate whether anti-IgE monoclonal antibody (mAb) has an effect in a mouse model of OA, using persulfate salts. On days 1 and 8, BALB/C mice were dermally sensitized with 5% ammonium persulfate (AP) or dimethyl sulfoxide (DMSO). On days 15, 18, and 21, animals were injected intraperitoneally with anti-IgE mAb or PBS 6 hours before challenge with AP or saline. Airway hyper-responsiveness (AHR) using a methacholine test, airway inflammation in bronchoalveolar lavage (BAL) and lung tissue, and total free IgE in serum samples were analyzed 24, 48, and 96 hours after the last challenge. Anti-IgE mAb treatment almost completely neutralized free serum IgE. In AP-sensitized and challenged mice, anti-IgE mAb treatment abolished AHR 24 hour and 48 hour after the last challenge and significantly reduced the total number of eosinophils and neutrophils 48 hour and 96 hour after the last AP challenge compared with nontreated mice. Levels of interleukin (IL)-13 in BAL were also significantly decreased after anti-IgE administration 24 hour and 48 hour after the last AP challenge. Histological analysis of the lung sections from anti-IgE-treated mice revealed normal inflammatory patterns similar to control groups 48 hour after the last challenge. Anti-IgE-treated mice showed a significant improvement in asthma features related to the AHR and airway inflammation. Anti-IgE mAb has positive effects in OA induced by persulfate salts.

Functional and phenotypic analysis of basophils allows determining distinct subtypes in patients with chronic urticaria.

Chronic urticaria (CU) is a frequent skin disease characterized by relapsing appearance of pruritic hives. While clinical symptoms are due to the release of histamine by cutaneous mast cells, the underlying pathophysiology is still unknown. However, previous studies indicate that basophils might be of relevance. Besides, the occurrence of autoantibodies against IgE or its receptor, FcεRI, and the therapeutic efficacy of anti-IgE antibodies imply that IgE-mediated mechanisms also play an important role in CU. Reactivity of CU patients' peripheral blood basophils (n=60) to specific anti-FcεRI and IgE-independent fMLP stimulation was determined by basophil activation test in comparison with patients suffering from IgE-mediated allergic rhinitis (n=10) and healthy controls (n=10). In addition, immunoglobulin receptor (FcεRI, FcγRII) expression and surface bound antibodies (IgE, IgG) were quantified on basophils. Furthermore, the autoreactive capacity of CU sera was evaluated and urticaria-related symptoms were assessed by both UCT and CU-Q2 oL. Stimulating CU patients' basophils via FcεRI, we identified three distinct immunologic phenotypes. One subgroup of patients' basophils reacted to FcεRI stimulation, whereas the others had anti-FcεRI nonreactive basophils. Among the latter, a subgroup with pronounced basopenia was identified. Of note, this group was characterized by augmented serum-induced basophil activation, increased levels of autoantibodies against thyroid peroxidase, and also exhibited the strongest disease impact on their quality of life. Patients with CU can be categorized into three immunologic subgroups based on their basophil reactivity and frequency. These phenotypes are associated with different clinical characteristics, pointing to basophils as important players in CU pathophysiology.

Justification for IgE as a therapeutic target in chronic spontaneous urticaria.

Monoclonal anti-IgE antibodies (omalizumab) are able to induce clinically significant benefits in patients with severe chronic spontaneous urticaria (CS). Those results led clinicians and investigators to reconsider a possible pathogenic role not previously supported for IgE and its receptors in this disease, and to investigate additional approaches for understanding its pathogenesis. IgE antibodies to unknown environmental allergens able to trigger chronic urticaria are not generally regarded as the etiologic factor for the disease. Other proposed mechanisms for the production of wheals and angioedema in CSU include IgG autoantibodies and CD4-positive T cells directed to the high-affinity IgE receptor, autoantibodies to IgE itself, IgE autoantibodies directed to thyroid and nuclear autoantigens, highly cytokinergic IgE, and histamine-releasing factors able to bind to IgE and cause mast cell activation. It is expected that a better knowledge on the mechanisms leading to CSU and the clarification of the immunological effects of anti-IgE will provide novel therapies for this frequent condition.

Lung function parameters in omalizumab responder patients: An interesting tool?

Omalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and nonresponder patients remain inconclusive. The objective of this real-life study was to compare the changes in forced expiratory volume in 1second (FEV1) of omalizumab responders and nonresponders at 6months. A multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity (FVC), pre- and postbronchodilator FEV1, residual volume (RV), and total lung capacity (TLC) were determined at baseline and at 6months. Omalizumab response was assessed at the 6-month visit. In the omalizumab responder patients, lung function parameters were also obtained at 12, 18, and 24months. Mean prebronchodilator FEV1 showed improvement in responders at 6months, while a decrease was observed in nonresponders (+0.2±0.4L and -0.1±0.4L, respectively, P<.01). After an improvement at 6months, pre- and postbronchodilator FEV1 remained stable at 12, 18, and 24months. The FEV1/FVC remained unchanged over time, but the proportion of patients with an FEV1/FVC ratio <0.7 decreased at 6, 12, 18, and 24months (55.2%, 54.0%, 54.0%, and 44.8%, respectively, P<.05). Mean RV values decreased at 6months but increased at 12months and 24months (P<.05). Residual volume/total lung capacity (RV/TLC) ratio decreased at 6months and remained unchanged at 24months. After omalizumab initiation, FEV1 improved at 6months in responder patients and then remained stable for 2years. RV and RV/TLC improved at 6months.

Immunoadsorption for treatment of severe atopic dermatitis

Atopic dermatitis (AD) is a common disease affecting up to 10–20% of the population with the largest disease burden in childhood. Treatment options include basic emollient treatment, topical as well as systemic immunosuppressants. The pathogenesis is complex and among various triggers, genetic predisposition and immunological alterations contribute to development of disease. Atopy is common in patients with AD and many patients have high levels of Immunoglobulin E (IgE), some of which recognizes exogenous or auto/self-allergens. Treatment options targeting IgE such as specific immunotherapy against e.g. house dust mites or using anti-IgE antibodies (omalizumab) showed variable results that were not convincing. We now review recent data on the application of unspecific and IgE-selective immunoadsorption (IA) in AD. All in all, 53 patients have been treated with non-specific pan Ig IA and 28 patients with IgE-selective IA. Side effects were rarely seen. The efficacy of IgE depletion was generally high (<∼80%) for each IA cycle, but transient and lasted only a few days/weeks. Of note, disease activity appeared to improve in almost all cases and lasted for several weeks. Although the evidence is still weak, these case studies suggest that IgE depletion in AD is effective and helped control the disease. The mechanism of action is not understood yet. Future controlled trials are needed to validate this observation.

IgE und Anti-IgE bei Asthma: eine wechselvolle Geschichte

A long and winding road led to the discovery of immunoglobulin E (IgE) in 1966 and 1967. We are currently on a long and winding road to understand the immunologic basis of the clinical effects of the anti-IgE antibody omalizumab in asthma. It is possible that patients with asthma (as patients with chronic spontaneous urticaria) benefit in different immunologic ways from omalizumab treatment. This article reviews the history of IgE discovery and current concepts of anti-IgE therapy in asthma.

Allosteric mechanism of action of the therapeutic anti-IgE antibody omalizumab

Immunoglobulin E and its interactions with receptors FcϵRI and CD23 play a central role in allergic disease. Omalizumab, a clinically approved therapeutic antibody, inhibits the interaction between IgE and FcϵRI, preventing mast cell and basophil activation, and blocks IgE binding to CD23 on B cells and antigen-presenting cells. We solved the crystal structure of the complex between an omalizumab-derived Fab and IgE-Fc, with one Fab bound to each Cϵ3 domain. Free IgE-Fc adopts an acutely bent structure, but in the complex it is only partially bent, with large-scale conformational changes in the Cϵ3 domains that inhibit the interaction with FcϵRI. CD23 binding is inhibited sterically due to overlapping binding sites on each Cϵ3 domain. Studies of omalizumab Fab binding in solution demonstrate the allosteric basis for FcϵRI inhibition and, together with the structure, reveal how omalizumab may accelerate dissociation of receptor-bound IgE from FcϵRI, exploiting the intrinsic flexibility and allosteric potential of IgE.

Blocking Allergic Reaction through Targeting Surface-Bound IgE with Low-Affinity Anti-IgE Antibodies.

Allergic disorders have now become a major worldwide public health issue, but the effective treatment options remain limited. We report a novel approach to block allergic reactivity by targeting the surface-bound IgE of the allergic effector cells via low-affinity anti-human IgE Abs with dissociation constants in the 10-6 to 10-8 M range. We demonstrated that these low-affinity anti-IgE mAbs bind to the cell surface-bound IgE without triggering anaphylactic degranulation even at high concentration, albeit they would weakly upregulate CD203c expression on basophils. This is in contrast to the high-affinity anti-IgE mAbs that trigger anaphylactic degranulation at low concentration. Instead, the low-affinity anti-IgE mAbs profoundly block human peanut- and cat-allergic IgE-mediated basophil CD63 induction indicative of anaphylactic degranulation; suppress peanut-, cat-, and dansyl-specific IgE-mediated passive cutaneous anaphylaxis; and attenuate dansyl IgE-mediated systemic anaphylaxis in human FcεRIα transgenic mouse model. Mechanistic studies reveal that the ability of allergic reaction blockade by the low-affinity anti-IgE mAbs was correlated with their capacity to downregulate the surface IgE and FcεRI level on human basophils and the human FcεRIα transgenic mouse bone marrow-derived mast cells via driving internalization of the IgE/FcεRI complex. Our studies demonstrate that targeting surface-bound IgE with low-affinity anti-IgE Abs is capable of suppressing allergic reactivity while displaying an excellent safety profile, indicating that use of low-affinity anti-IgE mAbs holds promise as a novel therapeutic approach for IgE-mediated allergic diseases.

United Airway Disease in Occupational Allergy

The term “united airway disease” has been used since 2000 to describe the strong association between asthma and rhinitis. Although this term is not extensively used, it refers to the fact that asthma and rhinitis are frequently associated and share common risk factors, causal agents and mechanisms. Similarly, since 2010 the term occupational united airway disease has been used to describe the strong association between occupational asthma and rhinitis. Rhinitis and occupational rhinitis are less severe diseases but more frequent than asthma and occupational asthma, respectively. Every year several case reports and epidemiological studies enhance the long list of agents responsible for occupational asthma and rhinitis with new agents or occupations. Primary, secondary and tertiary prevention strategies are aimed at reduction of the onset and severity of work-related respiratory diseases. Primary prevention mainly includes avoiding/reducing exposure to known sensitizing/irritant agents. Secondary prevention or early detection should focus on medical surveillance of individuals at risk, health and safety education and training of workers, and recognition of early bronchial/nasal symptoms. Tertiary prevention includes early recognition and diagnosis, appropriate removal from further exposure and pharmacologic treatment. Unfortunately, pharmacologic treatment has seldom been studied in occupational asthma and rhinitis, and it usually refers to the international guidelines of management of asthma and rhinitis aimed to achieve control of the two diseases. For simultaneous treatment of asthma and rhinitis, the anti-IgE monoclonal antibody omalizumab, effective in occupational asthma and rhinitis, is available. Immunotherapy has been shown to be effective in health care workers with occupational asthma due to natural rubber latex, in workers with occupational asthma due to laboratory animals and in baker’s asthma. A limitation of immunotherapy, however, can be systemic reactions after subcutaneous injections of sometimes non-standardized and non-purified extracts.

In vitro impact of anti-immunoglobulin E monoclonal antibodies, including omalizumab on whole blood basophil histamine release: Assessment of direct induction of basophil histamine release and evaluation of modulation of allergen-induced basophil histamine release.

The aim of this study was to evaluate the potential of anti-immunoglobulin E (IgE) and/or anti-IgE-IgE immune complexes to release histamine from peripheral blood basophils. In addition, a potential modulating effect of anti-IgE-IgE complexes on allergen-induced peripheral blood basophil histamine release was evaluated. Whole blood basophil histamine release (WBB-HR) tests done by using glass-fiber-based microtiter plates were performed in 62 patients with allergic rhinitis and/or asthma sensitized to perennial allergens. Evaluation of the direct effects of monoclonal anti-IgEs, including E25, E27, and QGE031, on WBB-HR, and the indirect effects of anti-IgE-serum IgE complexes on spontaneous and allergen-induced WBB-HR were conducted. The tests were performed with and without pretreatment of the basophils with interleukin 3, and the results were expressed as the fraction of total histamine content released. There was no difference between WBB-HR induced by any of the studied anti-IgE antibodies and that induced by isotype antibodies for all blood samples assessed, which, for each patient, was significantly less than that induced by positive anti-IgE control antibodies. Similarly, no effect of any of the studied anti-IgE-IgE complexes on spontaneous or allergen-induced WBB-HR could be demonstrated. There was no evidence that humanized, monoclonal anti-IgE antibodies E25 (omalizumab), E27, or QGE031 directly or indirectly induced histamine release from peripheral blood basophils.

Predictors of response to therapy with omalizumab in patients with severe allergic asthma – a real life study

ABSTRACTObjectives: Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients with IgE levels within the limits of administration, respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab.Methods: We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center. Demographic and functional characteristics, level of asthma control, fractional exhaled nitric oxide, blood and eosinophils and IgE level, induced sputum cell count, eosinophil cationic protein and Interleukin-13 in sputum supernatant were recorded. All measurements were performed before starting treatment with omalizumab. Response to treatment was evaluated according to the physician’s global evaluation of treatment effectiveness. Patients were characterized as early responders when improvement was achieved within 16 weeks and as late responders when improvement was achieved between 16 and 32 weeks. Patients who did not show any improvement after 32 weeks of therapy were considered as non-responders.Results: Forty-one patients treated with omalizumab were included in the study. 28 (68.3%) patients were characterized as responders while 13 patients (31.7%) were considered as non-responders. Among responders, 25 (89%) were early responders and 3 (n = 11%) were late responders. Responders were characterized by lower baseline FEV1 and FEV1/FVC and higher IL-13 levels in induced sputum supernatant compared to non-responders. Late responders had higher serum IgE levels, shorter disease duration and higher number of blood eosinophils. Finally, using ROC curve analysis, the best predictors of response to omalizumab were FEV1 (AUC = 0.718) and IL-13 in sputum supernatant (AUC = 0.709).Conclusion: Lower baseline FEV1 and higher IL-13 levels in induced sputum supernatant were predictors of response to omalizumab. Patients with higher baseline serum IgE levels, shorter disease duration and higher blood eosinophils may experience a late response and might benefit from a more prolonged treatment before being characterized as non-responders.

Detection of IgE autoantibodies to BP180 and BP230 and their relationship to clinical features in bullous pemphigoid

IgE autoantibodies are considered to be involved in the pathogenesis of bullous pemphigoid (BP), particularly inflammatory and erythematous phenotypes. To develop reliable enzyme-linked immunosorbent assays (ELISAs) for the detection of IgE autoantibodies to both BP180 and BP230 in BP sera, and to compare the ELISA results with clinical features. We used commercially available IgG ELISAs to develop IgE ELISAs for both BP180 and BP230. To determine the influence of excess amounts of IgG autoantibodies, all normal and BP sera were tested before and after IgG adsorption. The results of the IgE ELISAs were statistically compared with various ELISAs and various clinical parameters, including our own severity scores and BP phenotypes. IgG adsorption generally showed no changes in sensitivity and specificity for IgE ELISAs, although slight cross-reactivity of anti-IgE secondary antibody to IgG and interference of excess amounts of IgG autoantibodies to IgE reactivity were suggested. IgE autoantibodies to BP180 were found in 21 of 36 BP sera and IgE autoantibodies to BP230 were found in 18 of 36 BP sera. The results of IgG and IgE ELISAs for both BP180 and BP230 were well correlated. IgG and IgE anti-BP180 antibodies correlated with disease activity but IgG and IgE anti-BP230 autoantibodies did not. IgE anti-BP230 autoantibodies correlated with nodular phenotype but not erythematous phenotype. The results of this study indicated that IgE autoantibodies to both BP180 and BP230 are frequently detected in BP sera. IgE anti-BP180 autoantibodies seemed to be pathogenic, while an association between IgE autoantibodies and inflammatory BP phenotype was not indicated.

Reliability of histamine release test in dust mite allergy: Influence of the degree of sensitization

The histamine release test has been proven to be a very useful method for in vitro diagnosis of IgE-mediated allergy to inhalant and food allergens, as well as for the immunotherapy follow-up of the allergic patient. The aim of the present study was to assess the influence of the degree of sensitization in allergic patients sensitive to Dermatophagoides pteronyssinus on their dose-response curves in histamine release tests. To achieve this aim, we studied 109 D. pteronyssinus allergic patients and 25 healthy control subjects. Intracutaneous skin test, D. pteronyssinus-specific and total IgE quantitations, and histamine release tests were carried out in all the patients. In the case of the histamine release test, five D. pteronyssinus extract concentrations were used (2822.5, 282.25, 28.22, 2.82 and 0.28 UBE/ml), and two patterns of histamine release in sensitive patients were found: one with maximal histamine release at the highest antigen concentration (group I) and the other with maximal release attained at lower concentrations (group II). A sensitization score was designed, after the results from specific IgE and intracutaneous skin tests. There were significant differences (p < 0.05) in antigen-specific and total IgE levels, and in papule diameters and sensitization scores, between the control group and groups I and II. Both groups showed significantly higher (p < 0.05) histamine releases than the control group in response to anti-IgE antibodies. When stimulating the cells with anti-IgE antibodies, histamine release in group II was higher than in group I, although this difference was not significant. Finally, the best correlation between sensitization score and antigen-specific histamine release was found at the 2.82 UBE/ml concentration (r = 0.84, p < 0.001).

Biological agents in the treatment of chronic urticaria

Chronic urticaria is a common and recurrent allergic disease in dermatology. Antihistamines are the first-line treatment of chronic urticaria, but nearly half of patients show poor responses to antihistamines. Complicated pathogenesis of chronic urticaria, including imbalance of Th1/Th2 cell subsets and abnormality of inflammatory mediators, IgE and anti-FceRⅠ antibody, may be one of the important reasons why chronic urticaria is hard to cure. Biological agents can selectively regulate or inhibit immune abnormality, and have become a new approach to the treatment of chronic urticaria and other urticaria-related skin diseases. Related biological agents mainly include BCG-polysaccharide nucleic acid, gamma globulins, tumor necrosis factor (TNF) -α inhibitors, interleukin (IL) -1 blockers, rituximab, omalizumab, and so on, and play important roles in the treatment of chronic urticaria. Omalizumab, a kind of anti-IgE monoclonal antibody, has a favorable benefit/risk ratio and good tolerability, and is considered to be one of the ideal biological agents for the treatment of chronic urticaria. Key words: Urticaria; Biological agents; Antibodies, monoclonal; Rituximab; Omalizumab

Effectiveness of omalizumab in a case of urticarial vasculitis.

Urticarial vasculitis (UV) is a mainly leucocytoclastic vasculitis with urticarial plaques. Treating these patients is challenging as the available treatments have poor efficacy. Oral corticosteroids are considered the first-line treatment, but H1 antihistamines, dapsone, colchicine, antimalarials, ciclosporin and antileucotrienes have all been tried also. However, because of their adverse effects and/or lack of efficacy, new agents are still needed. Omalizumab, an anti-IgE antibody, shows efficacy in chronic spontaneous urticaria, and might also be a good treatment for angio-oedema and urticarial vasculitis. To our knowledge, there have been only seven relevant case reports published in the English literature. We add a new case of severe chronic recurrent urticarial vasculitis refractory to all of the drugs mentioned above. We started the patient on subcutaneous omalizumab 300 mg every 4 weeks, which produced clinical improvement within the first month and total remission in the fifth month. The patient has remained stable for 23 months, and follow-up is ongoing.

Immunotherapy for Food Allergy: Are We There Yet?

Current clinical research focuses on food allergen-specific immunotherapy through oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. Immunotherapy relies on the delivery of gradually increasing doses of specific allergens to induce desensitization (defined as temporary antigen hyporesponsiveness that depends on regular food ingestion) and, ultimately, tolerance (defined as the ability to ingest food without symptoms despite prolonged periods of avoidance or irregular intake). Although the majority of the patients treated with OIT achieve desensitization, only a minority achieves tolerance. OIT involves higher maintenance doses of food protein (300 mg-4g) compared with SLIT (2.5-7.5 mg) and EPIT (250-500 mcg). OIT efficacy is higher compared with SLIT, but OIT is associated with higher rate of systemic adverse events compared with SLIT and EPIT. OIT is also associated with a minor risk of eosinophilic esophagitis. Combined treatment of OIT and anti-IgE monoclonal antibody has improved safety but not efficacy compared with OIT alone. Early initiation of peanut OIT in peanut-allergic infants and young children may afford superior efficacy and safety. In this review, we discuss the allergen-specific strategies currently explored for the treatment of food allergy, including immunotherapy with native and heat-modified food proteins. Additional research employs strategies to improve the safety and efficacy of allergen immunotherapy through modifications of allergen structure and addition of immunomodulatory adjuvants.

An Update on Anti-IgE Therapy in Pediatric Respiratory Diseases.

Anti-IgE treatment represents a major breakthrough in the therapeutic management of severe allergic asthma. Omalizumab is the unique biologic treatment registered for asthma therapy in children. The clinical efficacy and safety of omalizumab treatment in the pediatric population has been extensively documented in specific trials and consistently expanded from real-life studies. In addition, new experimental evidence suggests that omalizumab may also interfere with the cellular and molecular mechanisms underlying airway remodeling. Novel investigational anti-IgE monoclonal antibodies with improved pharmacodynamic properties are in the pipeline, potentially offering alternative mechanisms of modulating IgE pathway.The aim of this review is to update current knowledge on anti-IgE therapy in pediatric respiratory diseases.

Omalizumab for treating chronic spontaneous urticaria: an expert review on efficacy and safety

ABSTRACTIntroduction: Chronic spontaneous urticaria (CSU) is characterized by the recurrence of itchy hives and/or angioedema for greater than six weeks, with no known external trigger. Omalizumab, a humanized, recombinant, monoclonal anti-IgE antibody, is the only approved add-on therapy for H1-antihistamine refractory CSU patients.Areas covered: The objective of this article is to discuss the mechanism of action, pharmacokinetics and pharmacodynamics of omalizumab for the treatment of CSU. The review also summarizes efficacy and safety data from proof-of-concept, phase II (X-CUISITE, MYSTIQUE), and pivotal phase III omalizumab studies (ASTERIA I, ASTERIA II, and GLACIAL).Expert opinion: Omalizumab is a clinically effective and safe biological therapy for treating H1-antihistamine refractory CSU patients. It significantly reduces CSU symptoms (hives, itch and angioedema), and improves patient health-related quality of life. While omalizumab is already integral to the treatment of antihistamine refractory CSU, widespread use will depend on legal and economic factors, as well as improvements in the early and accurate diagnosis of CSU patients who would benefit from treatment.

Sensitization to the storage mites Lepidoglyphus destructor and Tyrophagus putrescentiae (Acari, Sarcoptiformes, Astigmatina) in a suburban population in Southern Poland

Mite infestation of stored products is a serious threat to food safety and public health. These stored product mites are not only serious pests of stored food but also cause allergies in humans. Thirty serum samples from patients living in suburban areas of Upper Silesia (South Poland) were tested for sensitization to two species of storage mites: Lepidoglyphus destructor [LD] and Tyrophagus putrescentiae [TP]. Patient antibodies against particular antigens were identified using anti-human anti-IgE monoclonal antibodies. Fifteen protein fractions from LD gave positive reactions with IgE antibodies and 18 from TP. Seven of the 30 samples showed positive reactions to a protein fraction measuring about 29 kDa from LD and six reacted with a fraction measuring about 25 kDa from TP. These findings may imply the existence of many protein fractions with allergenic properties besides the characterized allergens in the two tested species.

IgE and eosinophils as therapeutic targets in asthma.

Asthma is a chronic inflammatory disorder characterized by reversible airflow obstruction, which is being more widely recognized as a broad-spectrum disease that encompasses multiple patient characteristics and pathophysiologic mechanisms. Suboptimal asthma control leads to increasing burden of healthcare costs and loss of productivity to society. Biologic therapies targeted at IgE and eosinophils can be used in poorly controlled allergic and eosinophilic asthma, respectively. The purpose of this review is to analyze the advancements in currently available biologic therapies targeted at IgE and eosinophils in asthma and to identify how these therapies may impact overall healthcare costs. Omalizumab is an anti-IgE antibody that is approved for use of poorly controlled moderate-to-severe asthma. Many studies have confirmed that omalizumab not only improves quality of life and symptom scores, but also decreases urgent care and emergency department visits and hospitalizations. Dupilumab is a biologic agent targeted at TH2 cytokines, but indirectly impacts IgE and is an important biologic agent for atopic disease. Mepolizumab, reslizumab, and benralizumab target IL-5, a key cytokine for eosinophils. For patients with poorly controlled eosinophilic asthma, these biologic agents improve asthma symptoms, reduce exacerbations, and reduce emergency visits and hospitalizations. Poorly controlled severe asthma affects a small portion of patients with asthma in the United States and yet it accounts for large portion of healthcare utilization. Biological therapies in poorly controlled severe persistent asthma have been identified to reduce healthcare utilization, including emergency visits and hospitalizations. Biologic agents have a clear beneficial role in the management of severe asthma, and further evaluations should be continued in identifying optimal patient characteristics for the various agents and overall benefit toward healthcare utilization and cost.