Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma

Massanari, Marc; Nelson, Harold S.; Casale, Thomas B.; Busse, William W.; Kianifard, Farid; Geba, Gregory P.; Zeldin, Robert K.

doi:10.1016/j.jaci.2009.11.022

Cited by 199 publications

(160 citation statements)

References 18 publications

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“…In conjunction with s.c. injection using aeroallergens, omalizumab improved the tolerability of dose escalation while retaining and perhaps improving the long-lasting benefits of immunotherapy (83)(84)(85)(86)(87). Two small, uncontrolled studies of omalizumab combined with rush food oral immunotherapy, where dose escalation was performed at a more rapid pace than usual using either peanut or milk, have recently been published.…”

Section: Pathophysiology Of Food Allergymentioning

confidence: 99%

Emerging therapies for food allergy

Keet¹,

Wood²

2014

J. Clin. Invest.

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Food allergy is a common condition for which there are currently no approved treatments except avoidance of the allergenic food and treatment of accidental reactions. There are several potential treatments that are under active investigation in animal and human studies, but it is not yet clear what the best approach may be. Here, we review approaches that are currently in clinical trials, including oral, sublingual, and epicutaneous immunotherapy, immunotherapy combined with anti-IgE, and Chinese herbal medicine as well as approaches that are in preclinical or early clinical investigation, including modified protein immunotherapy, adjuvants, DNA vaccines, and helminth administration. We discuss the importance of fully exploring the risks and benefits of any treatment before it is taken to general clinical practice and the need for clarity about the goals of treatment.

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Section: Pathophysiology Of Food Allergymentioning

confidence: 99%

Emerging therapies for food allergy

Keet¹,

Wood²

2014

J. Clin. Invest.

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“…A good safety profile, significant decrease in the risk of anaphylaxis and improved rescue medication scores were reported [29,30,51].…”

Section: Combination With Immune Response Modifiersmentioning

confidence: 94%

“…Allergen-SIT vaccines are administered directly into inguinal lymph nodes with the aim of delivering high amounts of allergens into secondary lymphatic organs [22,23]. Significantly fewer systemic allergic reactions were observed, more patients were able to reach the target maintenance immunotherapy dose [29,30] strategy that has been tested is the fusion of FcgRIIb to allergens to down-regulate downstream allergenspecific immune responses. In a similar approach, the fusion of allergens to human Fcg suppressed allergen-induced degranulation of basophils and mast cells by cross-linking Fcg and FcgRI receptors [25,26].…”

Section: Key Pointsmentioning

confidence: 99%

Novel immunotherapy vaccine development

Jutel

Akdiş

2014

Current Opinion in Allergy &Amp; Clinical Immunology

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PURPOSE OF REVIEW: Allergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-of-concept -as well as large, multicenter clinical studies. RECENT FINDINGS: The most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration. SUMMARY: The cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients. Purpose of reviewAllergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-ofconcept -as well as large, multicenter clinical studies. Recent findingsThe most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration. SummaryThe cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients.

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“…More subjects taking omalizumab were able to achieve the target maintenance dose than placebo (87.3% vs 72.1%, P 5 .004). 85 In another study with ragweed SIT, the combination of SIT and omalizumab improved severity scores associated with treatment and offered signifi cant protection from severe IgE-mediated reactions during the impacted season. 86 Similar results have been shown for pediatric patients with SAR and asthma receiving SIT for birch and grass.…”

Section: The Effect Of Slit In Armentioning

confidence: 99%

Allergen Immunotherapy in Allergic Respiratory Diseases

Viswanathan

Busse

2012

Chest

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Over the past 2 decades, the prevalence of allergic respiratory diseases has increased, in part refl ecting changes in lifestyle and environment that promote a T-helper (Th) 2 cell phenotype. 1 It has been estimated that up to 20% of the US and Western Europe populations may be affl icted by allergic respiratory diseases. 2,3 A recent estimate of the total national medical expenditure attributable to adult asthma was reported as $18 billion, with the largest contributors being prescription drugs and inpatient hospitalizations. 4,5 Although allergen avoidance is an integral component and step of therapy, it is often impractical and insuffi cient. As a consequence, the mainstay of allergic disease management has been pharmacotherapy, especially antihistamines, bronchodilators, and inhaled/intranasal corticosteroids, which are targeted to regulate infl ammation of the upper and lower airways. Although these treatments are effective and, in most cases, safe, they offer no lasting benefi t once treatment is stopped and have limited intrinsic disease-modifying effects. Moreover, it has become apparent that allergic diseases are the result of immune dysregulation and refl ect an impairment in the natural tolerance that develops to allergens. 6,7 Immunotherapy has the potential to modify fundamental, underlying disease mechanisms and to have, Allergen-specifi c immunotherapy (SIT) involves the repeated administration of allergenic extracts to atopic individuals over a period of 3 to 5 years either subcutaneously (SCIT) or sublingually (SLIT) for the treatment of allergic respiratory diseases, including asthma and allergic rhinitis (AR). In studies, SCIT and SLIT have been shown to improve existing symptoms of asthma and AR and to also have the capability to cause disease-modifying changes of the underlying atopic condition so as to prevent new allergic sensitization as well as arrest progression of AR to asthma. Recent evidence suggests that immunotherapy brings about these effects through actions that use T-regulatory cells and blocking antibodies such as IgG 4 and IgA 2, which can then result in an "immune deviation" from a T-helper (Th) 2 cell pattern to a Th1 cell pattern. Numerous meta-analyses and studies have been performed to evaluate the existing data among these studies, with the consensus recommendation favoring the use of immunotherapy because of its potential to modify existing diseases. Signifi cant adverse reactions can occur with immunotherapy, including anaphylaxis and, very rarely, death. A primary factor in considering SIT is its potential to provide longlasting effects that are able to be sustained well after its discontinuation. Given the signifi cant burden these allergic diseases impose on the health-care system, SIT appears to be a cost-effective adjunctive treatment in modifying the existing disease state. CHEST 2012; 141(5):1303-1314Abbreviations: AR 5 allergic rhinitis; BHR 5 bronchial hyperresponsiveness; PEF 5 peak expiratory fl ow; SCIT 5 subcutaneous immunotherapy; SIT 5 allergen-specifi c...

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Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma

Cited by 199 publications

References 18 publications

Emerging therapies for food allergy

Emerging therapies for food allergy

Novel immunotherapy vaccine development

Allergen Immunotherapy in Allergic Respiratory Diseases

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