title: Targeting key proximal drivers of type 2 inflammation in disease.
abstract: Systemic type 2 inflammation encompassing T helper 2 (TH2)-type responses is emerging as a unifying feature of both classically defined allergic diseases, such as asthma, and a range of other inflammatory diseases. Rather than reducing inflammation with broad-acting immunosuppressants or narrowly targeting downstream products of the TH2 pathway, such as immunoglobulin E (IgE), efforts to target the key proximal type 2 cytokines - interleukin-4 (IL-4), IL-5 and IL-13 - represent a promising strategy to achieve therapeutic benefit across multiple diseases. After several initial disappointing clinical results with therapies targeting IL-4, IL-5 or IL-13 in asthma, applying a personalized approach achieved therapeutic benefit in an asthma subtype exhibiting an 'allergic' phenotype. More recently, efficacy was extended into a broad population of people with asthma. This argues that the Type 2 inflammation is broadly relevant across the severe asthma population if the key upstream drivers are properly blocked. Moreover, the simultaneous inhibition of IL-4 and IL-13 has shown significant clinical activity in diseases that are often co-morbid with asthma - atopic dermatitis and chronic sinusitis with nasal polyps - supporting the hypothesis that targeting a central 'driver pathway' could benefit multiple allergic diseases.
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, New York 10591, USA.
authors.forename: Namita A
authors.initials: NA
authors.lastname: Gandhi
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, New York 10591, USA.
authors.forename: Brandy L
authors.initials: BL
authors.lastname: Bennett
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, New York 10591, USA.
authors.forename: Neil M H
authors.initials: NM
authors.lastname: Graham
authors.affiliation: Research and Development, Sanofi, Bridgewater, New Jersey 08807, USA.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Pirozzi
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, New York 10591, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Stahl
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, New York 10591, USA.
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology*; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000276:immunology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000276:immunology; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000276:immunology; D018448:Models, Immunological; D058990:Molecular Targeted Therapy / Q000379:methods*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018793:Interleukin-13; D015848:Interleukin-5; D015847:Interleukin-4