Reflections on Asthma Treatment with Omalizumab

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Reflections on Asthma Treatment with Omalizumab

• Mary C. Tobin MD
• Director, Clinical Services
• University Consultants in Allergy/Immunology

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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
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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

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Treatment of moderate to severe persistent
Asthma Anti-IgE
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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 ICSLABA
  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.

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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 ICSLABA
• Results Primary outcome Asthma exacerbations
  such as ED/hospitalizations, oral steroid use
  during the 48 week study period

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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.

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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

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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 Hashimotos thyroiditis

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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

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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

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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?

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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 dont need it anymore

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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

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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?