- Section I 1800–1899
- Section II 1900–1949
- Section III 1950–1999
- Chapter 23 In praise of famous men: early cortisone studies
- Chapter 24 The relationship between mast cells and histamine
- Chapter 25 What goes round comes around: developing allergen immunotherapy
- Chapter 26 Burnet, clonal selection theory, and acquired immunological tolerance
- Chapter 27 Slow-reacting substance of anaphylaxis
- Chapter 28 Loveless and wasp-venom immunotherapy
- Chapter 29 Developing an understanding of mast cell biology
- Chapter 30 Disodium cromoglycate for allergic asthma
- Chapter 31 Ancient Egyptian soup for treating asthma: Cox and Intal
- Chapter 32 RAST: Iconic test for allergic sensitization
- Chapter 33 The discovery of IgE
- Chapter 34 Penicillin allergy: a model for practical clinical translational science
- Chapter 35 Unravelling the relationship between <i>Dermatophagoides pteronyssinus</i> and asthma
- Chapter 36 The Gell–Coombs classification
- Chapter 37 The dawn of molecular allergology
- Chapter 38 Immunotherapy can change the natural history of respiratory allergy
- Chapter 39 Anatomy of the asthmatic bronchi
- Chapter 40 Identifying a novel cause of occupational allergy
- Chapter 41 Delayed hypersensitivity to pollen allergens
- Chapter 42 Inhaled beclomethasone dipropionate: stepping-up asthma care
- Chapter 43 Challenging notions of the ‘atopic personality’
- Chapter 44 Establishing and investigating the relationship between food allergy and asthma
- Chapter 45 The histamine-inhalational test
- Chapter 46 Allergic reactions to colloid infusions—another chapter in the colloid debate
- Chapter 47 Total and specific IgE and allergic bronchopulmonary aspergillosis
- Chapter 48 Immunotherapy for venom allergy comes of age
- Chapter 49 Extending the evidence for immunotherapy to the management of children with house-dust-mite-triggered asthma
- Chapter 50 Insights from Xhosa children into environmental risk factors for the development of asthma
- Chapter 51 Viral infection, allergic sensitization, and asthma
- Chapter 52 Immune responses in atopic eczema
- Chapter 53 Understanding the relationship between atopic sensitization and airway hyper-responsiveness in asthma
- Chapter 54 Key insights into the relationship between food allergy and atopic dermatitis
- Chapter 55 From slow-reacting substance of anaphylaxis to anti-leukotrienes
- Chapter 56 Once more unto the breach: the role of the damaged bronchial epithelium in asthma
- Chapter 57 Management of anaphylactic shock
- Chapter 58 The hygiene hypothesis
- Chapter 59 In search of the elixir for childhood allergy and asthma prevention
- Chapter 60 A new way of considering ‘quality of life’
- Chapter 61 Food allergy and anaphylaxis
- Chapter 62 Allergen avoidance: the Isle of Wight study
- Chapter 63 Introducing sputum counts
- Chapter 64 Atopic asthma is a TH2-cell-mediated disease
- Chapter 65 Investigating the impact of hay fever on educational performance
- Chapter 66 Findings from an early peanut immunotherapy trial
- Chapter 67 Auto-immune mechanisms in chronic urticaria
- Chapter 68 Air pollution, mortality, and the need for public health policy
- Chapter 69 The geography of asthma and atopy: after the Berlin wall came down
- Chapter 70 The role of animal allergens in allergic disease
- Chapter 71 The natural history of wheezing: the Tucson cohort
- Chapter 72 Measuring food-specific IgE values
- Chapter 73 Tuberculosis exposure and atopy
- Chapter 74 The inner-city home environment and asthma
- Chapter 75 Mapping the burden of allergic disease in childhood: ISAAC
- Chapter 76 The relationship between obesity and asthma
- Chapter 77 The emergence of monoclonal antibodies
- Chapter 78 The renaissance in allergen immunotherapy
- Chapter 79 Pet exposure in early life and the development of allergy and asthma
- Section IV 2000–2012
- Section V Conclusions
(p. 251) The emergence of monoclonal antibodies
- Chapter:
- (p. 251) The emergence of monoclonal antibodies
- Author(s):
Michael Daines
and Wayne Morgan
- DOI:
- 10.1093/med/9780199651559.003.0077
Background: Immune responses mediated by IgE are important in the pathogenesis of allergic asthma. A recombinant humanized monoclonal antibody (rhuMAb-E25) forms complexes with free IgE and blocks its interaction with mast cells and basophils. We studied the efficacy of rhuMab-E25 as a treatment for moderate-to-severe allergic asthma. Methods: After a 4-week run-in period, we randomly assigned 317 subjects (age range, 11 to 50 years) who required inhaled or oral corticosteroids (or both) to receive either placebo or one of two regimens of rhuMAB-E25: high-dose rhuMAb-E25 (5.8 microg per kilogram of body weight per nanogram of IgE per milliliter or low-dose rhuMAb-E25 (2.5 microg per kilogram per nanogram of IgE per milliliter) intravenously on days 0 (half a dose), 4 (half a dose), and 7 (full dose) and then once every 2 weeks thereafter for 20 weeks. For the first 12 weeks of the study, the subjects continued the regimen of corticosteroids they had received before enrollment. During the following eight weeks, the doses of corticosteroids were tapered in an effort to discontinue this therapy. The primary outcome measure was an improvement in the asthma symptom score at 12 weeks, according to a 7-point scale, in which a score of 1 indicated no symptoms and a score of 7 the most severe symptoms. Results: A total of 106 subjects were assigned to receive a high dose of rhuMAb-E25, 106 were assigned to receive a low dose, and 105 were assigned to receive placebo. At base line, the mean asthma symptom score was 4.0. After 12 weeks of therapy, the mean (+/-SE) scores were 2.8+/-0.1 in the high-dose group (P = 0.008) and 2.8+/-0.1 in the low-dose group (P = 0.005), as compared with 3.8+/-0.1 in the placebo group. At 20 weeks, the mean scores were 2.7+/-0.1 in both the high-dose group (P = 0.048) and the low-dose group (P = 0.14), as compared with 2.9+/-0.1 in the placebo group. More subjects in the two rhuMAb-E25 groups were able to decrease or discontinue their use of corticosteroids than in the placebo group, but only some of the differences were significant. After 20 weeks, serum free IgE concentrations decreased by a mean of more than 95 percent in both rhuMAb-E25 groups. The therapy was well tolerated. After 20 weeks, none of the subjects had antibodies against rhuMAb-E25. Conclusions: A recombinant humanized monoclonal antibody directed against IgE has potential as a treatment for subjects with moderate or severe allergic asthma.
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- Section I 1800–1899
- Section II 1900–1949
- Section III 1950–1999
- Chapter 23 In praise of famous men: early cortisone studies
- Chapter 24 The relationship between mast cells and histamine
- Chapter 25 What goes round comes around: developing allergen immunotherapy
- Chapter 26 Burnet, clonal selection theory, and acquired immunological tolerance
- Chapter 27 Slow-reacting substance of anaphylaxis
- Chapter 28 Loveless and wasp-venom immunotherapy
- Chapter 29 Developing an understanding of mast cell biology
- Chapter 30 Disodium cromoglycate for allergic asthma
- Chapter 31 Ancient Egyptian soup for treating asthma: Cox and Intal
- Chapter 32 RAST: Iconic test for allergic sensitization
- Chapter 33 The discovery of IgE
- Chapter 34 Penicillin allergy: a model for practical clinical translational science
- Chapter 35 Unravelling the relationship between <i>Dermatophagoides pteronyssinus</i> and asthma
- Chapter 36 The Gell–Coombs classification
- Chapter 37 The dawn of molecular allergology
- Chapter 38 Immunotherapy can change the natural history of respiratory allergy
- Chapter 39 Anatomy of the asthmatic bronchi
- Chapter 40 Identifying a novel cause of occupational allergy
- Chapter 41 Delayed hypersensitivity to pollen allergens
- Chapter 42 Inhaled beclomethasone dipropionate: stepping-up asthma care
- Chapter 43 Challenging notions of the ‘atopic personality’
- Chapter 44 Establishing and investigating the relationship between food allergy and asthma
- Chapter 45 The histamine-inhalational test
- Chapter 46 Allergic reactions to colloid infusions—another chapter in the colloid debate
- Chapter 47 Total and specific IgE and allergic bronchopulmonary aspergillosis
- Chapter 48 Immunotherapy for venom allergy comes of age
- Chapter 49 Extending the evidence for immunotherapy to the management of children with house-dust-mite-triggered asthma
- Chapter 50 Insights from Xhosa children into environmental risk factors for the development of asthma
- Chapter 51 Viral infection, allergic sensitization, and asthma
- Chapter 52 Immune responses in atopic eczema
- Chapter 53 Understanding the relationship between atopic sensitization and airway hyper-responsiveness in asthma
- Chapter 54 Key insights into the relationship between food allergy and atopic dermatitis
- Chapter 55 From slow-reacting substance of anaphylaxis to anti-leukotrienes
- Chapter 56 Once more unto the breach: the role of the damaged bronchial epithelium in asthma
- Chapter 57 Management of anaphylactic shock
- Chapter 58 The hygiene hypothesis
- Chapter 59 In search of the elixir for childhood allergy and asthma prevention
- Chapter 60 A new way of considering ‘quality of life’
- Chapter 61 Food allergy and anaphylaxis
- Chapter 62 Allergen avoidance: the Isle of Wight study
- Chapter 63 Introducing sputum counts
- Chapter 64 Atopic asthma is a TH2-cell-mediated disease
- Chapter 65 Investigating the impact of hay fever on educational performance
- Chapter 66 Findings from an early peanut immunotherapy trial
- Chapter 67 Auto-immune mechanisms in chronic urticaria
- Chapter 68 Air pollution, mortality, and the need for public health policy
- Chapter 69 The geography of asthma and atopy: after the Berlin wall came down
- Chapter 70 The role of animal allergens in allergic disease
- Chapter 71 The natural history of wheezing: the Tucson cohort
- Chapter 72 Measuring food-specific IgE values
- Chapter 73 Tuberculosis exposure and atopy
- Chapter 74 The inner-city home environment and asthma
- Chapter 75 Mapping the burden of allergic disease in childhood: ISAAC
- Chapter 76 The relationship between obesity and asthma
- Chapter 77 The emergence of monoclonal antibodies
- Chapter 78 The renaissance in allergen immunotherapy
- Chapter 79 Pet exposure in early life and the development of allergy and asthma
- Section IV 2000–2012
- Section V Conclusions