Disease-Modifikation und Dauer einer Omalizumab-Therapie bei Patienten mit schwerem allergischen Asthma

Zusammenfassung

Hintergrund und Methodik: Omalizumab ist ein monoklonaler Anti-IgE-Antikörper zur Behandlung des schweren allergischen Asthma bronchiale. Ziel dieser Arbeit war die Bewertung der vorhandenen Evidenz durch ein Expertengremium und die Formulierung daraus resultierender Empfehlungen zu möglichen krankheitsmodifizierenden Effekten und der Dauer der Behandlung mit Omalizumab.

Ergebnisse: Eine direkte oder indirekte Interaktion zwischen Omalizumab und der IgE-Produktion ist wahrscheinlich. Die aufgrund eines pharmakokinetisch-pharmakodynamischen Modells erwarteten IgE-modulierenden Eigenschaften von Omalizumab werden derzeit in der klinischen Anwendung überprüft. Therapieentscheidungen auf Grundlage dieses Modells zu treffen kann allerdings nicht empfohlen werden. Anhand der verfügbaren Evidenz wird ein abschwächender Einfluss von Omalizumab auf Faktoren der strukturellen Veränderungen in den Atemwegen (Airway Remodeling) angenommen. Daten, um eine Empfehlung zur Dosisreduktion oder zum Absetzen von Omalizumab nach Langzeittherapie auszusprechen, fehlen derzeit.

Schlussfolgerungen: Aktuell kann bei Patienten mit schwergradigem allergischen Asthma unter langfristiger Omalizumab-Behandlung aufgrund der vorliegenden klinischen Daten weder eine Dosisreduktion noch ein Absetzen der Therapie empfohlen werden. Für eine klare Beurteilung müssen die Ergebnisse laufender klinischer Studien abgewartet werden.

Abstract

Background and methods: Omalizumab is a monoclonal anti-IgE-antibody that is used to treat severe allergic asthma. The aim of this review was to evaluate the available evidence in a panel of experts and to provide recommendations on therapy duration with omalizumab.

Results: A direct or indirect interaction between omalizumab and IgE production seems likely. Pharmacokinetic-pharmakodynamic models suggest that omalizumab modulates IgE production. This hypothesis is currently investigated in clinical studies. In addition, available evidence suggests that omalizumab mitigates different factors of airway remodeling. However, based on the currently available data, no recommendations can be given in regard to reduction of dosage or discontinuation of omalizumab in long term treated patients.

Conclusions: Currently, neither dose reductions nor treatment withdrawal can be recommended in patients with severe allergic asthma and long term treatment with omalizumab. Clinical studies addressing these issues are being conducted.

^* alle Autoren waren maßgeblich beteiligt

• Literatur

• 1 Bousquet J, Cabrera P, Berkman N et al. The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma. Allergy 2005; 60: 302-308
• 2 Humbert M, Beasley R, Ayres J et al. 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: 309-316
• 3 Holgate S, Buhl R, Bousquet J et al. The use of omalizumab in the treatment of severe allergic asthma: A clinical experience update. Respir Med 2009 103: 1098-1113
• 4 Novartis Pharma. Fachinformation Xolair. 2012 Ref Type: Generic
• 5 Murphy MK, Black NA, Lamping DL et al. Consensus development methods, and their use in clinical guideline development. Health Technol Assess 1998; 2: i-88
• 6 Lowe PJ, Renard D. Omalizumab decreases IgE production in patients with allergic (IgE-mediated) asthma; PKPD analysis of a biomarker, total IgE. Br J Clin Pharmacol 2011; 72: 306-320
• 7 Hanf G, Brachmann I, Kleine-Tebbe J et al. Omalizumab decreased IgE-release and induced changes in cellular immunity in patients with allergic asthma. Allergy 2006; 61: 1141-1144
• 8 van Rensen EL, Evertse CE, van Schadewijk WA et al. Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment. Allergy 2009; 64: 72-80
• 9 Shields RL, Whether WR, Zioncheck K et al. Inhibition of allergic reactions with antibodies to IgE. Int Arch Allergy Immunol 1995; 107: 308-312
• 10 Prussin C, Griffith DT, Boesel KM et al. Omalizumab treatment downregulates dendritic cell FcepsilonRI expression. J Allergy Clin Immunol 2003; 112: 1147-1154
• 11 MacGlashan Jr DW, Bochner BS, Adelman DC et al. Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol 1997; 158: 1438-1445
• 12 Massanari M, Holgate ST, Busse WW et al. Effect of omalizumab on peripheral blood eosinophilia in allergic asthma. Respir Med 2010; 104: 188-196
• 13 Oliver JM, Tarleton CA, Gilmartin L et al. Reduced FcepsilonRI-mediated release of asthma-promoting cytokines and chemokines from human basophils during omalizumab therapy. Int Arch Allergy Immunol 2010; 151: 275-284
• 14 Strohner P, Korn S, Buhl R et al. The recovery-ELISA -- a novel assay technique to monitor therapy with humanized antibodies: the example of omalizumab. J Immunoassay Immunochem 2013; 34: 83-93
• 15 Korn S, Haasler I, Fliedner F et al. Monitoring free serum IgE in severe asthma patients treated with omalizumab. Respir Med 2012; 106: 1494-1500
• 16 Garcia G, Magnan A, Chiron R et al. A proof-of-concept randomized-controlled trial of omalizumab in patients with severe difficult to control nonatopic asthma. Chest 2013; In press
• 17 Maurer M, Rosen K, Hsieh HJ et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med 2013; 368: 924-35
• 18 Shifren A, Witt C, Christie C et al. Mechanisms of remodeling in asthmatic airways. J Allergy (Cairo) 2012; 2012: 316049
• 19 Rabe KF, Calhoun WJ, Smith N et al. Can anti-IgE therapy prevent airway remodeling in allergic asthma?. Allergy 2011; 66: 1142-1151
• 20 Noga O, Hanf G, Brachmann I et al. Effect of omalizumab treatment on peripheral eosinophil and T-lymphocyte function in patients with allergic asthma. J Allergy Clin Immunol 2006; 117: 1493-1499
• 21 Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med 2012; 18: 693-704
• 22 Noga O, Hanf G, Kunkel G. Immunological and clinical changes in allergic asthmatics following treatment with omalizumab. Int Arch Allergy Immunol 2003; 131: 46-52
• 23 Zietkowski Z, Skiepko R, Tomasiak-Lozowska MM et al. Anti-IgE therapy with omalizumab decreases endothelin-1 in exhaled breath condensate of patients with severe persistent allergic asthma. Respiration 2010; 80: 534-542
• 24 Hoshino M, Ohtawa J. Effects of adding omalizumab, an anti-immunoglobulin E antibody, on airway wall thickening in asthma. Respiration 2012; 83: 520-528
• 25 Riccio AM, Dal Negro RW, Micheletto C et al. Omalizumab modulates bronchial reticular basement membrane thickness and eosinophil infiltration in severe persistent allergic asthma patients. Int J Immunopathol Pharmacol 2012; 25: 475-84
• 26 Pace E, Ferraro M, Bruno A et al. Clinical benefits of 7 years of treatment with omalizumab in severe uncontrolled asthmatics. J Asthma 2011; 48: 387-392
• 27 Eisner MD, Zazzali JL, Miller MK et al. Longitudinal changes in asthma control with omalizumab: 2-year interim data from the EXCELS Study. J Asthma 2012; 49: 642-648
• 28 Molimard M, LeGros V, Bourdeix I. Observational study in severe asthmatic patients after discontinuation of omalizumab for good asthma control. Eur Respir J 2012; 40 (Suppl. 56) 856
• 29 Nopp A, Johansson SG, Ankerst J et al. CD-sens and clinical changes during withdrawal of Xolair after 6 years of treatment. Allergy 2007; 62: 1175-1181
• 30 Nopp A, Johansson SG, Adedoyin J et al. After 6 years with Xolair; a 3-year withdrawal follow-up. Allergy 2010; 65: 56-60
• 31 Kelly HW, Sternberg AL, Lescher R et al. Effect of Inhaled Glucocorticoids in Childhood on Adult Height. N Engl J Med 2012; 367: 904-912
• 32 Slavin RG, Ferioli C, Tannenbaum SJ et al. Asthma symptom re-emergence after omalizumab withdrawal correlates well with increasing IgE and decreasing pharmacokinetic concentrations. J Allergy Clin Immunol 2009; 123: 107-113
• 33 Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention 2011. www ginasthma.org [cited 2012 Sep 20]