Anti-IgE – Beyond the Current Indications
William W. Busse
Professor, Department of Medicine
University of Wisconsin - Madison
William W. Busse
Professor, Department of Medicine, University of Wisconsin - Madison, United States
IgE-dependent activation of mast cells is important in many disease states – asthma, allergic rhinitis, anaphylaxis, and urticaria. Given the contribution of IgE to these processes, and its safety and effectiveness in some patients with asthma, it is logical to presume that omalizumab would provide benefit in other IgE-dependent processes as well. Evidence will be presented that treatment with omalizumab reduces systemic reactions, i.e. anaphylaxis, to immunotherapy in patients with persistent asthma, an at-risk situation for systemic reactions to antigen. In addition, omalizumab has been shown to reduce asthma exacerbations, which are most frequently caused by rhinovirus respiratory infections. Serum IgE levels have been found to be risk factors in the severity of a respiratory infection and consequently a virus provoked exacerbation of asthma. Thus, a reduction in IgE may contribute to fewer asthma exacerbations from colds. An in vitro series of experiments with dendritic cells suggests that dendritic cell bound IgE may be a factor in determining the severity of a cold and hence a risk factor for asthma exacerbations.
- Casale TB, Busse WW, Line JN, Ballas ZK, Moss MH, Townley RG, Mokhtarani M, Seyfert-Margolis V, Asare A, Bateman K, Beniz Y; Immune Tolerance Network Group. Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol 2006; 117(1):134-40.
- Busse W, Corren J, Lanier BQ, McAlary M, Fowler-Taylor A, Della Cioppa G, van As A, Gupta N. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol 2001; 108:183-190.
- Humbert M, Beasley R, Ayres J, Slavin R. HJbert J, Bousquet J, Beeh KM, Ramos S, Canonica GW, Hedgecock S, Fox H, Blogg M, Surrey K. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy 2005; 60:309-16.
- Zambrano JC, Carper HT, Rakes GP, Patrie J, Murphy DD, Platts-Mills TA, Hayden FG, Gwaltney JM Jr, Hatley TK, Owens AM, Heymann PW. Experimental rhinovirus challenges in adults with mild asthma: response to infection in relation to IgE. J Allergy Clin Immunol 2003; 111:1008-16.
- Kelly JT, Busse WW. Host immune responses to rhinovirus: mechanisms in asthma. J Allergy Clin Immunol 2008; 122:671-82.of co-morbid conditions and the management strategies need to include pharmacological and non-pharmacological approaches. The role of so-called biologicals is at best very limited, with the exception of anti-IgE for highly selected patients. Finally, clinical trials in the future should be performed in pathologically well phenotyped patients to test the efficacy of novel biological interventions; At present, most of the evidence is lacking.