1. Omalizumab is a monoclonal antibody approved for treatment of moderate-to-severe or severe persistent allergic asthma. Studies show it reduces exacerbations, improves asthma control, lung function and quality of life compared to placebo. 2. Treatment with omalizumab is associated with reductions in healthcare utilization and absences from work or school. It also decreases oral corticosteroid use. 3. Omalizumab significantly improves asthma control test scores and asthma quality of life questionnaire scores in the short and long-term in real-world studies.

1. Allergic
asthma
ABEER ALHARBI
Pulmonary and Sleep
Medicine Consultant
KFH

2. Asthma
Asthma is a chronic inflammatory airways disease which affects
about 10% of the world wide population.
The most common asthma phenotype in children is allergic
asthma, making up 80---90% of case and in adults it may exceed
50%.
J Allergy Clin Immunol. 2008;122:741---7.
J Allergy Clin Immunol. 2008;121:548---57.
According to the 2002 Global Initiative for Asthma (GINA)
classification, about 30% of asthmatic subjects are affected by
moderate-to-severe asthma.
Int Arch Allergy Immunol.2010;151:70---9.

3. Asthma pathophysiology
Key components: inflammation, bronchial hyper-
reactivity, airway remodeling
1970’s 1980’s 1990’s present
Bronchospasm Bronchospasm
+ Inflammation
Bronchospasm
+ Inflammation
+ Remodeling
CHEST 2013; 144(3):1026–1032.
T cell Eosinophil
Th-2
IL-5 / IL-13
Th17
Dendritic cells

4. Allergic asthma
IgE plays a central role in the pathogenesis of
allergic asthma

5. Stepwise Approach for Managing
Asthma
5
Short-acting Beta2-agonists
Low-dose Inhaled Corticosteroids (ICS)
Low-dose ICS +
Long-acting Beta2-agonists (LABA)
or Medium-dose ICS
Medium-dose ICS + LABA
High-dose ICS + LABA
and Consider Omalizumab
High-dose ICS + LABA +
Oral Corticosteroids
and Consider Omalizumab
1
2
3
4
5
6
Adapted from National Asthma Education and Prevention Program (NAEPP) Guidelines. Expert Panel Report 3: Guidelines for the Diagnosis and Management of
Asthma. National Heart, Lung, and Blood Institute, NIH Publication No. 07-4051, Revised August 2007.

8. Treatment of severe asthma
Anti-IgE Therapy
Biologic antibody therapy (Omalizumab; Xolair) binds to
the Fc region of the IgE in the circulation and prevents it
from activating mast cells and basophils.
Free IgE level soon drop to less than 5% of initial value
before omalizumab therapy
Ann Intern Med. 2011 3;154(9):573-82
Lancet Respir Med. 2013;1(3):189-90.
Cochrane Database Syst Rev. 2014 13;1

10. It is administered subcutaneously every 2–4 weeks.
Dosing is calculated by the patient’s body weight and the
level of serum IgE.
A minimum of 12 weeks of therapy is required prior to
determining the effectiveness of therapy.
No specific laboratory tests are required to monitor the
patients who are clinically improving on anti-IgE therapy.
In patients showing clinical response, the optimal duration of
therapy has not been established.
Anti-IgE therapy
(Omalizumab)

11. PRE-
TREATMENT
SERUM IGE
BODY WEIGHT
30-60
KG
> 60-
70 KG
> 70-
90 KG
> 90-
150
KG
> 30-100
IU/mL
150 mg 150 mg 150 mg 300 mg
> 100-200
IU/mL
300 mg 300 mg 300 mg
> 200-300
IU/mL
300 mg
> 300-400
IU/mL
SEE
TABLE
2
> 400-500
IU/mL
> 500-600
IU/mL
PRE-TREATMENT
SERUM IGE
BODY WEIGHT
30-60 KG
> 60-70
KG
> 70-90
KG
> 90-150
KG
> 30-100 IU/mL
SEE
TABLE 1
> 100-200 IU/mL 225 mg
> 200-300 IU/mL 225 mg 225 mg 300 mg
> 300-400 IU/mL 225 mg 225 mg 300 mg
> 400-500 IU/mL 300 mg 300 mg 375mg
> 500-600 IU/mL 300 mg 375 mg
DO NOT
DOSE
> 600-700 IU/mL 375 mg
Table 1: Subcutaneous Xolair Doses Every 4 Weeks for
Patients 12 Years of Age and Older with Asthma
Table 2: Subcutaneous Xolair Doses Every 2 Weeks for Patients
12 Years of Age and Older with Asthma

12. Omalizumab Criteria for Use in
Asthma

13. Side effect
Anaphylaxis has been reported in at least 0.2% of cases
(compared to less than 0.1% initial incidence during
clinical trials), requiring administration in health care
setting
Malignant neoplasm: 0.5% risk compared with 0.1% of
control population within 1 year follow up
Increased risk of helminthic infections

14. Churg--Strauss syndrome iin
patients treated with omalizumab
Omalizumab treatment may unmask CSS
in patients who have an underlying
eosinophilic disorder due to withdrawal
of corticosteroids or delay corticosteroiid treatment
allowiing for CSS to manifest..
Chest 2009;136;507-18

15. Monitoring
Effectiveness of therapy should be evaluated within 3-6
months and discontinued if not useful.
markers of asthma control:
symptoms severity
frequency of rescue treatments
oral steroid requirements
frequency of urgent outpatient visits and/or
hospitalization.

16. Asthma symptom re--emergence
after omalizumab withdrawal
The reason for omalizumab being ineffective in
some patients is unknown,, but it is reasonable to
ask whether the ‘‘‘‘failures’’’’ result from ineffective
reductions in IgE levels..
• Questions are being asked about whether the dose can be
reduced after months of treatment Reducing omalizumab
doses may result in increase in free IgE causing
deterioration in asthma control
Sallviin RG,, et all.. J Allllergy Clliin IImmunoll 2009;;123(1)::107-13..
MacGllashan D.. J Allllergy Clliin IImmunoll 2009;;123(1)::114-5..

17. Treatment of allergic asthma with monoclonal anti--IgE
antibody:: rhuMAb--E25 Study Group..
Serum concentrations off total and free IgE in subjjects given a
llow dose of rhuMAb--E25 ffor 20 weeks
Milgrom H, et al. N Engl J Med. 1999 Dec 23;341(26):1966-73.

18. Immunohistochemicall
staining of bronchial biopsy
specimens before ((left)) and
after ((right)) 16 weeks off
omalizumab treatment..
Representative sections
show staining with
antibody against::
ECP ((A and B))
Cell--surface IgE ((C and D))
High--affinity IgE R ((E and F))
IIL--4 ((G and H))
Djukanović R, et al. Am J Respir Crit
Care Med 2004;170:583-93.

19. FEV1
FEV1
as a
percentage off
baseline in the
placebo ((A)) and
omalizumab ((B))
groups..
van Rensen E, et al. Allergy 2009;64:72–80.

20. Effect of add--on therapy with omalizumab in
patients with severe persistent asthma whose
asthma was inadequately controlled by therapy with
high--dose ICSs plus a LABA
Humbert M, et al. Allergy 2005; 60:309–16

21. Healthcare Resource Utilization in Patients Receiving
Omalizumab for Allergic Asthma in a Real-World Setting
2-year, multinational, non-Asthma-related healthcare resource
utilization (hospitalizations, emergency room visits or unscheduled-
asthma-related doctor visits or interventions) and absences from
work or school were assessed pre-treatment (12-24 month
Biol Ther (2014) 4:57–67

24. Effectiveness of Omalizumab in Severe Allergic
Asthma: A Retrospective UK Real-World Study
data were collected between February 2010 and January
2011.
documented exacerbations (defined as an increase in
symptoms requiring treatment with systemic
corticosteroids), and hospital visits and admissions and
lung function test results, FEV1% for the 12 months pre-
and post-OMB initiation.

25. Effectiveness of Omalizumab in Severe Allergic
Asthma: A Retrospective UK Real-World Study
the Asthma Control Test (ACT) and Asthma Quality of
Life Questionnaire (AQLQ) at baseline (immediately
pre-OMB initiation), 16 weeks, and most recently up
to 12 months post-OMB initiation
Journal of Asthma, 2013; 50(5): 529–536

27. ACT
An overall ACT score ≤19was found to identify
patients with inadequately controlled
asthma and a score ≤15 predicts uncontrolled
asthma.
25 (well-controlled asthma).

28. Quality of life and asthma control
questionnaires
ALQ addresses six domains of the impact of asthma on patients’
lives: activities and sleep, symptoms, triggers, unscheduled health
care use, medication and psychological state.
A total ALQ score is calculated as the sum of all positive
(yes) responses, ranging from 0 to 20.
Lower scores reflect greater QoL impairment

29. Median ACT score. An ACT score below 19/25 indicates
poorly controlled asthma
Journal of Asthma, 2013; 50(5): 529–536

30. Median AQLQ score. The AQLQ works on a
maximum possible score 7, where lower scores
indicate a poorer quality of life.

31. Short and long-term quality of life and asthma control
withomalizumab therapy in a real life setting in Portugal
Prospective and open-label study in 15 adult patients
with uncontrolled severe persistent allergic asthma on
omalizumab treatment ≥16 weeks.
The short (at 16w) and long-term (at 1 and 2 years) (y)
effects of omalizumab were assessed through the
Asthma Life Questionnaire (ALQ) and the Asthma
Control Test (ACT).
Allergol Immunopathol (Madr). 2014;42(1):3---10

32. The greatest improvement was thus
observed in the ‘non-scheduled medical
visits’ and ‘medication use’ domains

34. Secondary outcomes
1-after one year of treatment, there was a marked
reduction of asthma exacerbations and unscheduled
health care visits by 70.1% (7.5 ± 4.6 to 2.2 ± 1.5
exacerbations, p = 0.002) and 86.1% (6.1 ± 4.4 to 0.9 ±
1.3 visits, p = 0.002), respectively.
After 2 years, reductions in both parameters remained:
75.9% (p = 0.05) in exacerbations and 69.0% (p = 0.12)
in medical visits

35. Secondary outcomes
2- A significant decrease in the mean daily IS dose ( g
budesonide) was also verified (1653.3 ± 571.2 to 1306.7 ±
600.7 at 16 weeks, p = 0.018; 1277.0 ± 604.5 at 1 year, p
= 0.011 and 1111.1 ± 523.4 at 2 years, p =
0.028)
.
3- there was a significant rise in FEV1 (51.7 ± 12.3 to 57.4
± 18.2% at 16 weeks, p = 0.041; 55.6 ± 15.7% at 1 year, p
= 0.007 and 65.0 ± 12.0% at 2 years, p = 0.007

36. Reduction in oral corticosteroid use in patients
receiving omalizumab for allergic asthma in the
real-world setting
2-year, multinational, non-interventional, observational
study
.
Braunstahl et al. Allergy, Asthma & Clinical
Immunology 2013, 9:47

37. n=Number of evaluable patients at each time point.
OCS, oral corticosteroids.

38. n = number of evaluable patients at each time-
point. OCS, oral corticosteroids; SD,

40. Summary
Omalizumab is antimmunoglobulinE (IgE) monoclonal antibody that is
approved for the treatment of patients with uncontrolled moderate-to-
severe) or severe persistent allergic asthma.
The studies have shown that adjunctive therapy with omalizumab
significantly reduces asthma exacerbations and improves asthma
control, lung function and asthma-related quality of life, compared with
placebo .
treatment with omalizumab is associated with reductions in healthcare
resource utilization and absence from work or school

41. New and Emerging Therapies Being
Evaluated for Asthma.
Wechsler ME. N Engl J Med 2013;368:2511-2513

42. THANK
YOU
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