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Reflections on Asthma Treatment with Omalizumab Mary C. Tobin MD Director, Clinical Services University Consultants in Allergy/Immunology Reflections on Asthma Treatment with Omalizumab Disclosure of Conflict of Interest Information I have the following relationships that exist related to this presentation: Co-Investigator/Investigator initiated research: IgE receptors on neutrophils in IgE mediated asthma Speakers’ Bureau Glaxo-SmithKline Novartis Genetech Disclosure information stated above is current as of November 18, 2008 Omalizumab • Clinical trials with omalizumab= 60 – – – – – – – – – Allergic asthma Seasonal allergic rhinitis Food allergy Eosinophilic esophagitis Atopic dermatitis Bullous pemphigoid Urticaria Cystic fibrosis with ABPA Basic science • Allergy cells • Markers of inflammation • Airway hypersensitivity Treatment of moderate to severe persistent Asthma Anti-IgE QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. Phase IIIb, Multi-center, Randomized Double-Blind, Placebo Controlled Study of Omalizumab in Subjects with Moderate to Severe Persistent Asthma Inadequately Controlled with High Dose Inhaled Corticosteroids and Long- Acting Beta -Agonists • EXTRA Background: IgE plays a key role in inflammation. A decrease in free IgE causes a decrease in the initiation of Ag responses in patients with asthma. Objective: To evaluate the efficacy, safety and tolerability of SQ injections of Omalizumab vs.. placebo as add-on therapy to high-dose ICS+LABA for subjects with moderate to severe persistent asthma inadequately controlled as judged by asthma exacerbations requiring treatment with oral steroids during a 48 week treatment period. EXTRA • Methods: 850 subjects 12-75 years of age on high dose ICS and LABA with inadequately controlled asthma. Subjects received 48 weeks of study drug (Omalizumab or placebo) in addition to ICS+LABA • Results: Primary outcome: Asthma exacerbations such as ED/hospitalizations, oral steroid use during the 48 week study period EXTRA • Results: – Secondary outcomes: • Change from baseline to week 48 in overall asthma-related quality of life. • Change from baseline to week 48 in nocturnal and daytime asthma symptom scores • Change in baseline to week 48 in the number of puffs/day of beta-agonist rescue medication • Frequency and severity of treatment-emergent adverse events during the 48-week treatment period. Omalizumab • University Consultants in Allergy/Immunology – Retrospective evaluation • 26 patients who have been on or recently started Omalizumab. – 23 patients for asthma (age 13-76 years) » 7 males and 16 females » 22 patients had severe persistent asthma » 1 patient had mild asthma with severe allergic rhinitis and anaphylaxis to IT Omalizumab • 3 patients started Omalizumab for urticaria resistant to multiple antihistamines, montelukast, cytotoxic agents – 1/3 had resolution of urticaria with 6 months of therapy and has been discontinued for 2 months – One of the patients who did not improve has been diagnosed with Hashimoto’s thyroiditis Omalizumab • Asthma patients – 21 patients have had at least 3 months of therapy • 2/21 patients did not respond and received therapy for 12 months-no decrease in steroid use, no improvement in ACT scores • 19 patients had some improvement with decrease in oral steroids, high dose ICS, decrease in beta-agonist use, decrease in nocturnal awakening and improvement in ACT scores. • 14 patients have had dramatic improvement – – – – Step down to moderate persistent Decrease dose of oral steroids to none or less than 9 mg/day Normalization of ACT scores No ED or hospitalization Omalizumab • 3 patients had asthma with nasal polyps – 2/3 patients had a decrease in the size of the polyps and in the number of sinus infections • 2 patients had a component of COPD and seemed to take longer to respond Omalizumab • Issues of concern – Adverse reactions: • First dose- shortness of breath and urticaria-drug stopped by allergist • Sixth dose- pruritic rash-drug stopped by allergist – When should the drug be stopped or restarted? • If patient is responding what adjustments could be made? • Should skin testing be done with the drug to assess potential mechanism? Omalizumab – Issues of Concern: • Patient compliance: – Responders tend to decrease medication too quickly on their own and then have an exacerbation – Responders tend to stop coming because they are better – Insurance companies deny continuing drug because “they don’t need it anymore” Omalizumab • Final reflections: – Patients with asthma should be evaluated for allergies. Allergies are present in at least 50% of asthmatics age 50 years or younger Patients with moderate to severe persistent IgE mediated asthma should be considered for Omalizumab • If there IgE level is less than 30, repeat when off steroid burst for 4 weeks • Risk of adverse reactions is relatively low and benefit can be life-changing Omalizumab • Nagging Questions for the future: – When to stop Omalizumab??????? • 1 patient just stopped after 4.5 years- She had had severe asthma since childhood with multiple hospitalization. She is only on antihistamine, nasal steroid, and montelukast. • 1 patient stopped after 3 years because of college- no update yet – When she stopped Omalizumab prior to this after 6 months she would return to her pre-Omalizumab status- severe persistent and react to minute amounts of peanut. – Some patients stopped coming on there own. Is there any danger in this? – Some patients have been stopped at 12 months who were benefiting from therapy? Is that long enough?