Omalizumab-induced decrease of FcɛRI expression in patients with severe allergic asthma

Chanez, Pascal; Contin‐Bordes, Cécile; Garcia, Gilles; Verkindre, C.; Didier, A.; Blay, F. De; Lara, Manuel Tuñón de; Blanco, Patrick; Moreau, Jean-François; Robinson, Philip; Bourdeix, I.; Trunet, P; Gros, V. Le; Humbert, Marc; Molimard, Mathiéu

doi:10.1016/j.rmed.2010.07.011

Cited by 81 publications

(61 citation statements)

References 25 publications

(26 reference statements)

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“…The decrease in the FceRI expression on dendritic cells correlated with the decrease in its expression on basophils. Chanez et al [15], who conducted similar studies on precursor of plasmacytoid dendritic cells, made similar conclusions. However, he did not find a correlation between decreased FceRI expression and clinical parameters [15].…”

Section: Pharmacodynamic Properties Of Omalizumabmentioning

confidence: 62%

“…Chanez et al [15], who conducted similar studies on precursor of plasmacytoid dendritic cells, made similar conclusions. However, he did not find a correlation between decreased FceRI expression and clinical parameters [15]. Feuchtinger et al [23] observed normalization of the number of dendritic cells in grass pollen season in patients with pollinosis allergic to grass, who underwent specific immunotherapy and were also administered omalizumab.…”

Section: Pharmacodynamic Properties Of Omalizumabmentioning

confidence: 62%

“…As noted by Lin et al [13], this inhibition of FceRI expression on basophils can be seen after seven days from omalizumab administration, and as MacGlashan et al [14] demonstrated, three months following the commencement of treatment, the inhibition effect is 96%. Chanez et al [15] made a similar observation; the FceRI expression on basophils after 16 week-therapy with omalizumab decreased by 83%. A study conducted by Saini et al [16] revealed that discontinuation of omalizumab therapy results in a gradual increase of FceRI density on basophils simultaneously to the free IgE in serum, which confirms the active role of omalizumab in the inhibition of this receptor on basophils.…”

Section: Pharmacodynamic Properties Of Omalizumabmentioning

confidence: 64%

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The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

Kupryś‐Lipińska¹,

Molińska²,

Kuna³

2016

Advances in Respiratory Medicine

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Bronchial asthma is characterised by high levels of immunoglobulin E (IgE) and overproduction of pro-inflammatory cytokines, including interleukins IL-4, IL-13 and IL-5 needed for, amongst other things, the production of IgE and the differentiation, maturation, migration and survival of eosinophils. Eosinophils are one of the most important cells in allergic inflammation. Their presence in tissue is linked to the persistence of inflammatory infiltrate, tissue damage and remodelling. Although these cells are very sensitive to corticosteroids, some asthmatic patients do not respond to high doses of these drugs, even when administered systemically. Transbronchial biopsies and bronchoalveolar lavage performed in patients with steroid-resistant asthma have demonstrated higher levels of eosinophils and Th2-type cytokines (IL-4 and IL-5) compared to steroid-sensitive patients. Clinical studies have confirmed that the very effective treatment in these cases is therapy with omalizumab -an anti-IgE monoclonal antibody. The paper discusses the efficacy of omalizumab in reducing eosinophil number in peripheral blood and in the airways of asthmatic patients based on basic, clinical, observational studies and case reports. The significance of omalizumab therapy in asthma control and mechanisms that regulate the effects of omalizumab on eosinophils are evaluated.

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Section: Pharmacodynamic Properties Of Omalizumabmentioning

confidence: 62%

Section: Pharmacodynamic Properties Of Omalizumabmentioning

confidence: 62%

Section: Pharmacodynamic Properties Of Omalizumabmentioning

confidence: 64%

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The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

Kupryś‐Lipińska¹,

Molińska²,

Kuna³

2016

Advances in Respiratory Medicine

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“…The studies had a broad global representation, with 10 multi-national RCTs included [13][14][15][16][17][18][19][20][21][22] . The majority of included analyses evaluated patients aged 12 years and older (15 of 26 studies) [13][14][15][16][17][18]20,[22][23][24][25][26][27] ; five trials included adults, aged 18 years and older, only 21,[28][29][30][31] , and two trials included children aged 6 to <12 years 19,32 . The majority of RCTs were large (69% had n > 300 patients).…”

Section: Summary Of Studies Includedmentioning

confidence: 99%

Patient-reported outcomes in moderate-to-severe allergic asthmatics treated with omalizumab: a systematic literature review of randomized controlled trials

Corren

Kavati

Ortiz

et al. 2017

Current Medical Research and Opinion

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Objective: Randomized controlled trials (RCTs) have established the safety and efficacy of omalizumab on clinical parameters, and have also evaluated its impact on patient-reported outcomes (PROs). The purpose of this systematic literature review was to review published data based on PRO endpoints in order to determine the benefit of omalizumab as add-on therapy to inhaled corticosteroids in patients with moderate-to-severe persistent allergic asthma. Methods: A systematic literature review was conducted of reference databases and recent conferences. RCTs of add-on omalizumab therapy in adults, adolescents, and children with moderate-to-severe persistent asthma were included. Two researchers independently screened and reviewed articles with regards to inclusion and exclusion criteria for relevant studies. Results: Twenty-six trials met the criteria for inclusion. Of these, PRO measures were included in 19 trials to capture the impact of omalizumab on symptoms, 11 assessed patients for health-related quality-of-life (HRQoL), and four evaluated asthma control. Other PROs related to global evaluation of treatment effectiveness and work productivity. Overall, results demonstrated a significant difference across most PROs in favor of omalizumab add-on therapy vs placebo or comparators. Conclusions: PROs are an integral part of outcome assessment in clinical trials related to asthma. The RCTs reviewed demonstrate that omalizumab treatment improves PROs in patients with moderate-tosevere persistent allergic asthma, particularly symptom control and HRQoL.ARTICLE HISTORY

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“…5, 6, 7 As the binding site of omalizumab overlaps with the binding site of IgE to FcεRI, omalizumab does not induce mast cell and basophil activation or anaphylactic reactions and inhibits binding of circulating IgE to its receptor on effector cells. Administration of omalizumab therefore reduces mediator release after approximately 16 weeks of therapy, which is associated with a downregulation of FcεRI expression on basophils, mast cells and antigen‐presenting cells 8, 9, 10, 11. More recently, it has been shown that omalizumab is also effective for the treatment of chronic spontaneous urticaria 12…”

Section: Introductionmentioning

confidence: 99%

Intranasal administration of allergen increases specific IgE whereas intranasal omalizumab does not increase serum IgE levels—A pilot study

Eckl‐Dorna

Fröschl

Lupinek

et al. 2017

Allergy

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BackgroundAdministration of the therapeutic anti‐IgE antibody omalizumab to patients induces strong increases in IgE antibody levels.ObjectiveTo investigate the effect of intranasal administration of major birch pollen allergen Bet v 1, omalizumab or placebo on the levels of total and allergen‐specific IgE in patients with birch pollen allergy.MethodsBased on the fact that intranasal allergen application induces rises of systemic allergen‐specific IgE, we performed a double‐blind placebo‐controlled pilot trial in which birch pollen allergic subjects were challenged intranasally with omalizumab, placebo or birch pollen allergen Bet v 1. Total and allergen‐specific IgE, IgG and basophil sensitivity were measured before and 8 weeks after challenge. For control purposes, total, allergen‐specific IgE levels and omalizumab‐IgE complexes as well as specific IgG levels were studied in subjects treated subcutaneously with either omalizumab or placebo. Effects of omalizumab on IgE production by IL‐4/anti‐CD40‐treated PBMCs from allergic patients were studied in vitro.ResultsIntranasal challenge with Bet v 1 induced increases in Bet v 1‐specific IgE levels by a median of 59.2%, and this change differed significantly from the other treatment groups (P = .016). No relevant change in allergen‐specific and total IgE levels was observed in subjects challenged with omalizumab. Addition of omalizumab did not enhance IL‐4/anti‐CD40‐induced IgE production in vitro. Significant rises in total IgE (mean IgE before: 131.83 kU/L to mean IgE after: 505.23 kU/L) and the presence of IgE‐omalizumab complexes were observed after subcutaneous administration of omalizumab.ConclusionIntranasal administration of allergen induced rises of allergen‐specific IgE levels, whereas intranasal administration of omalizumab did not enhance systemic total or allergen‐specific IgE levels.

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Omalizumab-induced decrease of FcɛRI expression in patients with severe allergic asthma

Abstract: The study was registered with ClinicalTrials.gov (identifier: NCT00454051) and the European Clinical Trials Database, EudraCT (identifier: 2006-003591-35).

Cited by 81 publications

References 25 publications

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

Patient-reported outcomes in moderate-to-severe allergic asthmatics treated with omalizumab: a systematic literature review of randomized controlled trials

Intranasal administration of allergen increases specific IgE whereas intranasal omalizumab does not increase serum IgE levels—A pilot study

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