Omalizumab is a humanized monoclonal antibody that binds to IgE and is used as an add-on treatment for moderate-to-severe allergic asthma. Studies have shown that adding omalizumab to standard asthma treatment can reduce systemic corticosteroid use and exacerbations while maintaining or improving asthma control. Larger pooled analyses found that omalizumab reduced asthma exacerbations by 38% and emergency visits by 42% compared to placebo or standard treatment alone in patients with severe persistent asthma. Omalizumab is generally well tolerated with a safety profile similar to placebo.

1. Omalizumab in practical use
Sadudee Boonmee, MD

2. Topic outline
• Introduction of anti IgE
• Clinical application for
- Asthma
- Allergic rhinitis
- Immunotherapy
- Chronic urticaria
• Dosage
• Safety

3. • Omalizumab is a humanized monoclonal anti-
IgE antibody (IgG1), molecular weight 150 kD
• binds to Fc portion of IgE molecule at Cε3
same site where IgE binds to FcεRI

4. Mechanism o action
• primary mechanism of action of omalizumab is the binding of
free IgE in the circulation
• secondary mechanism of action  down regulation of FcεRI
expression (on Mast cell, Basophil, DC, monocyte) and Low
affinity FcεRII (CD23) (B cell )
Journal of Asthma and Allergy 2011:4

5. • Form trimer of two omalizumab molecule per
IgE antibody or form other complex
biologically inert complex do not activate complement
and are cleared by the reticular endothelial system
Half life = 26 day
Anti-IgE therapyImmunol Allergy Clin N Am ( ) –

6. • omalizumab does not bind to receptor-bound
IgE  does not trigger degranulation by cross-
linking IgE located on FceRI receptors of mast
cells or basophils

7. Omalizumab and asthma

8. Expert Panel Report 3:
Guidelines for the Diagnosis and and management of asthma
Omalizumab may be considered at this step for patients who have sensitivity to
relevant perennial allergens (e.g., dust mites, cockroach, cat, or dog) (Evidence B)

9. GINA Guideline 2011

10. Effectiveness of omalizumab in reducing
corticosteroid burden in patients with moderate
to severe persistent allergic asthma
• pooled analysis (N 1,071) of 2 similarly
designed, randomized, double-blind, placebo-
controlled omalizumab trials and their
extension phases
• Pt. aged 12 to 75 years with moderate to
severe, persistent, allergic asthma and
inadequately controlled with ICSs

11. J ALLERGY CLIN IMMUNOL AUGUST 2001
Eur Respir J 2001; 18: 254–261

12. Ann Allergy Asthma Immunol. 2003;91:154–159.
Eur Respir J 2002; 20: 73–78

14. • Inclusion criteria
1. positive skin prick test result in response to at least 1
perennial allergen (including Dermatophagoides
farinae, Dermatophagoides pteronyssinus, cockroach, dog, or
cat)
2. total serum IgE level of 30 IU/mL through 700 IU/mL
3. body weight of 150 kg or less
4. 12% or greater increase in forced expiratory volume in 1
second (FEV1) over baseline value within 30 minutes of taking
1 to 2 puffs of albuterol (90 g per puff)
5. baseline FEV1 of 40% through 80% of the predicted normal
value for the patient
6. mean daily total symptom score of 3.0 or higher (range, 0-
9) during the 14 days before randomization
7. ICS doses equivalent to beclomethasone dipropionate of
420 through 840 g/d (study 1 ) and 500 through 1,200 g/d

16. Outcome Measures
• Corticosteroid burden Median change in ICS from
baseline to the end of
steroid – reduction phase
and steroid extension phase
P < 0.001 for
each phase
Phase Dose of BDP Dose of BDP
equivalent in equivalent in
Omalizumab group Placebo group
Steroid stable 669.7 680
Steroid reduction 210.5 338
Extension 263 394

17. Outcome
• Number of OCS bursts significantly lower for the omalizumab group

18. Outcome
• Clinical outcome (28 wk core study and 24 wk
extension phase)

19. Adverse events

21. • Summary
• Pt. persistent asthma symptoms at baseline who received
adjunctive omalizumab
- able to reduce systemic corticosteroid burden
- Maintaining or improving asthma control and
lung function
- improved clinical outcomes (reduced asthma
impairment and a decreased risk of exacerbations)
- Omalizumab  effective option for treating
moderate to severe persistent allergic asthma, which
can minimize the burden of systemic corticosteroids

22. Efficacy and tolerability of anti-immunoglobulin E
therapy with omalizumab in patients with poorly
controlled (moderate-to-severe) allergic asthma: ETOPA
• randomized, open-label, multicentre, parallel-group
Study
• 312 pt ( 12 – 75 yr) with poorly control (moderate to
severe ) allergic asthma , treat step 3 and 4 of the NHLBI
receiving ≥ 400 mcg/day (adolescent) or ≥ 800 mcg/day
(adult) inhaled BDP or equivalent were included
• patients were randomized (2 : 1) to receive BSC (best
starndard care ) with or without subcutaneous omalizumab
for 12 months
Allergy 2004: 59: 701–708

23. • dose of omalizumab at least 0.016 mg/kg for
every IU/ml of total IgE every 4 weeks
according to patient body weight and serum
total IgE at screening
Allergy 2004: 59: 701–708

24. • primary efficacy variable : annualized number of
asthma deterioration-related incidents (ADRIs)
- those treated with omalizumab experienced 4.84
fewer ADRIs per patient-year compared with BSC
alone, a reduction of 49.6% [95%CI : 27.8–64.8%]
- omalizumab-treated patients remained ADRI-free
during the study compared with BSC alone [36.1% vs
20.2%
- prolongation of the time to first ADRI with
omalizumab vs. BSC (median time to first ADRI of
126 vs 75 days )
Allergy 2004: 59: 701–708

25. • Secondary efficacy variables annualized mean number of
exacerbations
- lower with omalizumab than BSC (1.12 and 2.86 per patient-
year ; P < 0.001) = a reduction of 60.8% (95% CI: 46.9–71.0%)
- omalizumab remained exacerbation-free during the study
compared with BSC alone ( 49.5% and 26.4%;
P = 0.001)
• median rescue bronchodilator use
0.60 puffs / day for omalizumab vs 3 puffs per/day for BSC
(P < 0.001)
• Patients treated with omalizumab showed a significant
improvement in morning FEV1 , difference in absolute
FEV1 of 0.2 L (2.48 and 2.28 L ; P = 0.02 )
Allergy 2004: 59: 701–708

26. • In conclusion : therapy with
omalizumab, combined with BSC, is well
tolerated and offers the potential to improve
disease control and symptoms in patients with
poorly controlled (moderate-to-severe)
allergic asthma
Allergy 2004: 59: 701–708

27. 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
• 28 weeks in a double-blind, parallel-group, multicentre study
• 419 pt (12–75 yr ) inadequately controlled with high-dose ICS
and LABA with reduced lung function were randomized to
receive either omalizumab ( 209 pt) vs placebo ( 210 pt )
• Omalizumab dose of at least 0.016 mg/kg per IU/ml of IgE
subcutaneously (based on the patient’s bodyweight and total
serum IgE level ) was administered every 2 or 4 weeks
Allergy 2005: 60: 309–316

28. - In omalizumab treated group ,clinically significant asthma
exacerbation (adjustment for baseline exacerbation rate )
was reduced by 26% as compared with placebo (0.68 vs 0.91,
P = 0.042)
- Severe exacerbation rate (PEF or FEV1 <60% of personal
best, requiring treatment with systemic corticosteroids) was
halved in the omalizumab group (0.24 vs 0.48, P = 0.002 )
Allergy 2005: 60: 309–316

29. • Total emergency visits in the treated-group were reduced
by 44% ( 0.24 vs 0.43, P = 0.038 )
• Clinically meaningful improvement asthma quality of life
questionnaire (AQLQ) ( > 0.5-point from baseline) was
observed in the treated-group as compared to placebo
(60.8% vs 47.8%, p =0.008)
• Mean morning PEF sinificant greater for omalizumab
than placebo ( P= 0.042)
• FEV1 (% predicted) difference = 2.8% ( P=0.0043 )
Allergy 2005: 60: 309–316

30. Safety and tolerability : similar in Omalizumab and
Placebo
Allergy 2005: 60: 309–316

31. • conclusion, omalizumab significantly
- decreased asthma exacerbation rates in these difficult-to-
treat pt with severe persistent asthma who were
inadequately controlled despite high-dose ICS and
concomitant LABA therapy as recommended according to
GINA step 4.
- Omalizumab also significantly reduced the severe asthma
exacerbation rate and the need for
emergency medical interventions
- Patients QoL was improved,
Allergy 2005: 60: 309–316

32. The effect of treatment with omalizumab, an anti-IgE
antibody, on asthma exacerbations and emergency
medical visits in patients with severe persistent asthma
• pooled data from 7 studies ,omalizumab was
added to current asthma therapy and
compared with placebo (in five double-blind
studies) or with current asthma therapy alone
(in two open-label studies)
• included 4308 patients (2511 treated with
omalizumab and 1797 were control ), 93%
severe persistent asthma
Allergy 2005: 60: 302–308

33. Study 1 : INNOVATE
Study 2 : ETOPA
Study 3 : SOLAR
Study 4,5 : 2
Study 6 :
Study 7 : ALTO unpublished
Allergy 2005: 60: 302–308

34. • Asthma exacerbations
←
←
←
←
←
Reduced asthma
← exacerbation 38% in
omalizumab group
Allergy 2005: 60: 302–308

35. • Emergency visits
Reduced ER visit 47 % in
omalizumab group
Allergy 2005: 60: 302–308

36. Improvement with omalizumab was seen
regardless of age, sex, baseline FEV1, baseline
serum IgE, dosind schedule
Allergy 2005: 60: 302–308

37. • Conclusion :
Omalizumab should be considered as
add-on treatment for patients with severe
persistent asthma who continue to suffer with
inadequately controlled asthma despite best
available therapy.
Allergy 2005: 60: 302–308

38. Omalizumab for the treatment of exacerbations
in children with inadequately controlled allergic
(IgE-mediated) asthma
• International, multicenter
randomized, double-blind, placebo-controlled
trial
• Children age 6 to <12 years with moderate to
severe allergic asthma
• BW 20 -150 kg , SPT + at least 1 perrennial
allergen, serum total Ig E 30 -1300 IU/ml
Bob Lanier (J Allergy Clin Immunol
-

39. • 1 week of screening phase
• 8 week of run-in phase ( adjust ICS dose to
optimized asthma control for first 4 wk )
• Pt. were randomized to receive omalizumab or
placebo
• In study group Omalizumab 75 -300 mg 1-2 time q
month ( every 2-4 wk )
• Double-blind treatment period
- 24-week fixed-steroid phase (constant ICS dose
unless adjustment was required for an exacerbation)
- 28-week adjustable-steroid phase
Bob Lanier (J Allergy Clin Immunol
-

40. Bob Lanier (J Allergy Clin Immunol
-

42. Primary efficacy end point :
rate of clinically significant
asthma exacerbation over 24
wk period
Secondary efficacy end point
: rate of clinically significant
asthma exacerbation over 52
wk period
Bob Lanier (J Allergy Clin Immunol
-

43. • Rate of clinically severe exacerbations reduced 44% over a
period of 24 weeks (0.10 vs 0.18; RR [95% CI], 0.55 [0.32-
0.95]; P=0.031)
• Sustained over a period of 52 weeks (rate, 0.12 vs 0.24)
 50% reduction (RR [95% CI], 0.49 [0.30-0.80]; P 0.004)
• Investigator and patient global evaluation of treatment
effectiveness (GETE) at 52 weeks favored omalizumab
with rate of excellent or good by 79 % and 80% ( physicial
and patient respectively )
by 56% and 72% respectively in placebo group
( both P < 0.001 )
Bob Lanier (J Allergy Clin Immunol
-

44. • Other secondary end point
- nocturnal asthma symptom Numerically greater
change in omalizumab
- daily puff of rescue medication group but no statistically
- QoL significant
Clinical implications: Many children with moderate-to-severe
allergic (IgE-mediated) asthma remain inadequately controlled
• Safety
despite treatment with ICSs. Add-on omalizumab reduces
exacerbations in this population and may provide an additional
therapeutic option At least 1 AE; mild or
moderate in severity.
no statistically significant of
AEs in the omalizumab
group compared with
placebo

45. Randomized Trial of Omalizumab (Anti-IgE)
for Asthma in Inner-City Children
• randomized, double-blind, placebo-
controlled, parallel-group trial at multiple centers
• 419 inner-city children, adolescents, and young
adults (6 to 20 years of age) with persistent allergic
asthma
• at least 1 + SPT to perennial allergen, BW 20 – 150
kg, tatol serum IgE 30-1300 IU/mL
William W. Busse, N ENGL J MED 364;11

46. 4 wk run - in Wk 0 Wk 36 Wk 60
Randomized Wk 12 wash -in
Omalizumab vs placebo sc injection
Omalizumab 75-375 mg every 2-4 wk
Additional visit for evalute and management of care every 3 mo
- Adjusted Rx based on symptom that occured during previous 2 wk
-adherence to the study regimen
- other asthma treatments
- FEV1
William W. Busse, N ENGL J MED 364;11

47. • Allergen skin testing of a panel of 14 extracts: mouse and rat
epithelia, dog epithelium, dust mites (Der f and Der p), cat
hair, an American–German cockroach mix, German
cockroach, molds (Penicillium notatum, aspergillus
species, Alternaria tenuis, and Cladosporium
herbarum),timothy grass, and a ragweed mix (Greer
Laboratories)
• Total serum levels of IgE and allergen-specific IgE levels
for dust mites, German cockroach, and A. tenuis were
measured
• Dust from the participant’s bed and bedroom floor was
collected with validated self-collection procedure and
assayed for dust mite (Der p 1 and Der f 1), German
cockroach (Bla g 1), cat (Fel d 1), dog (Can f 1), and
mouse (Mus m 1)
William W. Busse, N ENGL J MED 364;11

48. • Nasal-secretion samples collected at 4/8
research sites at week 48 and within 7 days
after the onset of an asthma exacerbation.
Total RNA was extracted and analyzed (PCR)
William W. Busse, N ENGL J MED 364;11

49. William W. Busse, N ENGL J
MED 364;11

50. Primary outcome : days with symptom (No./2wk )
Reduced 24.5%
William W. Busse, N ENGL J MED 364;11

51. Primary outcome : Exacerbation (%)

52. Primary outcome : Lower dose of ICS
William W. Busse, N ENGL J MED 364;11

53. Other outcome
←
←
←
←
←

54. Subgroup analysis
• omalizumab’s benefit was greatest in participants
who were both sensitized and exposed to cockroach
allergen and in those sensitized to dust mites, two
major relevant indoor allergens
- reduced day of symptom per 2 week interval 48.5%
- reduced dose of ICS 32.9%
- reduced asthma exacerbation 38.4% , OR 3.7
William W. Busse, N ENGL J MED 364;11

55. post hoc analysis of Omalizumab on Seasonal
Exacerbations
nearly doubled in the placebo group seasonal spike exacerbations was not
during the fall and spring as compared observed in the omalizumab group
with summer (4.3% in fall and 4.2% in spring vs. 3.3% in
(9.0% and 8.1%, respectively, vs. 4.6%; summer), and the difference between the
P<0.001). placebo and omalizumab groups was
significant (P<0.001 )
William W. Busse, N ENGL J MED 364;11

56. post hoc analysis of Omalizumab on Seasonal
Exacerbations
daily dose of ICS varied little during the year in the omalizumab
group whereas in the placebo group, dose adjustments
were required to achieve asthma control
William W. Busse, N ENGL J MED 364;11

57. One or more adverse events were reported in 47.4% of
Safety participants in the placebo group and 39.4% of those in
the omalizumab group (P = 0.06)
- Omalizumab group had significantly more GI disorders but significantly fewer hematologic
disorders compared with placebo gr.
- Seven participants had anaphylaxis: 6 in placebo gr. and 1 in omalizumab gr.
William W. Busse, N ENGL J MED 364;11

58. Randomized Trial of Omalizumab (Anti-IgE)
for Asthma in Inner-City Children
• In summary omalizumab reduces symptoms
and exacerbations in children, adolescents, and
young adults with persistent allergic asthma,
providing protection beyond that conferred with
guidelines-directed care. Our findings may also
help identify those patients most likely to have a
response to omalizumab and provide insight
into novel mechanisms of asthma exacerbations
that could lead to improved treatment
William W. Busse, N ENGL J MED 364;11

59. Omalizumab and AR

60. Effect of Omalizumab on Symptoms
of Seasonal Allergic Rhinitis
A Randomized Controlled Trial
• Randomized, double-blind, dose-ranging, placebo-
controlled trial ,25 OPD center in USA
• 536 patients (12 to 75 years) with at least a 2-year Hx of
moderate to severe ragweed-induced seasonal allergic
rhinitis and a baseline IgE level between 30 and 700
IU/mL.
• randomly assigned to receive omalizumab, 50 m, 150
mg, 300 mg or placebo sc 2 wk prior to ragweed season
and repeated during the pollen season every 3-4 wk
JAMA, December 19, 2001—Vol 286, No. 23

61. JAMA, December 19, 2001—
Vol 286, No. 23

62. Rhinitis-specific quality of
life scores were consistently
better in pt. who received
300 mg of omalizumab
than in those who received
lower dosages or placebo
and did not decline during
peak season

63. Efficacy and tolerability of anti-immunoglobulin E
therapy with omalizumab in patients with
concomitant allergic asthma and persistent allergic
rhinitis: SOLAR
• aim : to evaluate the efficacy and safety of
omalizumab in patients with moderate-to-severe
asthma and persistent AR
• multicentre, randomized, double-blind, parallel-
group, placebo controlled trial
• 405 patients (12–74 years) with a stable asthma
treatment
• Omalizumab (≥ 0.016 mg/kg/IgE [IU/ml] per 4
weeks) or placebo for 28 weeks
Allergy 2004: 59: 709–717

64. • patients treated with omalizumab fewer experienced
asthma exacerbations (20.6% vs 30.1%, P = 0.02 )
• Clinically significant (≥ 1.0 point) improvement in AQLQ
and RQLQ occurred in 57.7% of omalizumab pt vs 40.6%
placebo pt . (P < 0.001)
Allergy 2004: 59: 709–717

65. P < 0.05
In conclusion, thisasthma symptom score
Change from baseline in total
study of patients with concomitant asthma and
P< 0.001
PAR found that omalizumab is significantly more efficacious than
placebo in preventing asthma exacerbations and in improving
disease-related QoL when added to standard asthma and rhinitis
therapies.
P< 0.001
Change from baseline in total combined symptom score
Change from baseline in total rhinitis symptom score Allergy 2004: 59: 709–717

66. Omalizumab and IT

67. Omalizumab pretreatment decreases acute
reactions after rush immunotherapy for
ragweed-induced seasonal allergic rhinitis
• randomized, double-blind, placebo-controlled study
• 159 pt. were randomized to the 4 treatment arms
• Pretreatment with omalizumab vs placebo
• One-day RIT completed at least 3 weeks before the start of
ragweed season
• After RIT, pt. had 12 weekly visits to receive IT and
omalizumab injections (weeks 0-12) ,
3 additional follow-up visits (weeks 13, 19, and 31)
(J Allergy Clin Immunol 2006;117:134-40.)

68. (J Allergy Clin Immunol 2006;117:134-40.)

69. (J Allergy Clin Immunol 2006;117:134-40.)

70. • primary efficacy endpoint : comparison of the
average daily allergy severity scores between
Pt. receiving omalizumab + IT vs IT alone
statistically significant
improvement in severity scores
for patients treated with
omalizumab and IT vs IT alone
(P = 0.02)
intent-to-treat basis, the benefit of
omalizumab + IT was significant
Improve in severity scores 0.69 vs 0.86
(P < 0 .044).
Casale et al JACI 2006;117:134-40

71. • secondary endpoint : comparison of the
incidence of AE (examine of omalizumab on
the safety of IT)
Casale et al JACI 2006;117:134-40

72. Omalizumab + immunotherapy vs immunotherapy only demonstrated
that the addition of omalizumab
resulted in a significant, 5-fold decrease in risk of
anaphylaxis caused by RIT (OR, 0.17; P = 0.026 )
Casale et al JACI 2006;117:134-40

73. • Summary :
- Omalizumab pretreatment enhances the
safety of RIT for ragweed allergic rhinitis
- combined therapy (omalizumab + IT)
: effective strategy to permit more rapid and
higher doses of allergen IT
: given more safely and greater efficacy to
patients with allergic diseases
Casale et al JACI 2006;117:134-40

74. • Randomized, double-blind, parallel-group, 26 wk
study
• 275 adult pt. with at least moderate persistent
allergic asthma inadequately controlled with ICS
• SPT positive to at least 1 of 3 perennial aeroallergens
• Specific immunotherapy (SIT) began after 12 wk of
omalizumab or placebo
• Antihistamine could also be administered prior to
each SIT dose
• Systemic allegic reaction were evaluated
J Allergy Clin Immunol
-

75. 3 wk overlap
omalizumab/placebo +SIT
SIT to HDM and cat 4 wk, 18
injection cluster regimen
followed by 7 wk of weekly
maintenance therapy
Randomized Efficacy population
N=275 n=248
J Allergy Clin Immunol
-

76. • primary efficacy variable was a SAR within 1
hr after injection of SIT
• SAR within 1st hr occurred in 49 pt. (19.8%)
• 32 (26.2%) in placebo gr. vs 17 (13.5%) in
omalizumab gr , the difference was significant
(P < 0.006)
J Allergy Clin Immunol
-

77. Day 98
Placebo = 13 pt
Omalizumab =3 pt
less proportion of pt. who had their 1st
SAR after injection in omalizumab
group than placebo
J Allergy Clin Immunol
-

78. Secondary efficacy variables
1. Severity of the first SAR to SIT
P = 0.192
J Allergy Clin Immunol
-

79. Secondary efficacy variables
2. Decreased in propotion of pt. receiving recue medication
during SIT
Treatment with omalizumab decreased the proportion of
patients receiving at least 1 rescue medication during SIT
(10.3% for omalizumab vs 24.6% for placebo).
J Allergy Clin Immunol
-

80. Secondary efficacy variables
3. More pt. achieved target maintenance SIT
dose in the omalizumab treatment group
87.3%
72.1%,
Placebo Omalizumab
J Allergy Clin Immunol
-

81. Post hoc : subgroup analysis was conducted to determine
whether antihistamine pretreatment to SIT affected the rate of SARs
27.1%
Antihistamine pre Rx
Nonantihistamine preRx
24.3%
14.5%
12%
Loacal reaction
Omalizumab = 53.2%
Placebo :49.2%
P = 0.52
J Allergy Clin Immunol
-

82. Total Asthma Symptom Daily puffs of rescue
0.72
Score (mean) beta agonist(mean)
0.69
0.45
0.46 Asthma No. of puff of
symptom rescue beta
score agonist
Placebo Omalizumab
placebo Omalizumab
Post hoc : Lower total asthma
symptom scores and lower daily
puffs of rescue beta agonist – 1
week prior to cluster SIT
J Allergy Clin Immunol
-

83. Total asthma Daily puffs of rescue β agonist
symptom score (mean )
(mean)
23%
23.9%
% of Pt. developed grade 3 SAR
% of Pt. developed grade 3 SAR
9%
12.5%
6%
7.4%
3.5% 2%
No. of No.
puff > of puff
Score > Score =
placebo Omalizumab
Post hoc: Level of asthma control on
the rate of respiratory (grade 3) SAR
J Allergy Clin Immunol
-

84. • In summary : omalizumab pre treatment + SIT
- Improved asthma symptom
- Reduced recue use of β- agonist
- Significant reducing the proportion of pt.
who experienced SAR to SIT
- Enable more pt. to achieve the target
maintenance dose of immunotherapy.
J Allergy Clin Immunol
-

85. Omalizumab and urticaria

86. • evaluate the efficacy and safety of omalizumab in patients with CIU
who remain symptomatic despite H1-antihistamine therapy
• phase II, prospective, double-blind, placebo controlled, dose-
ranging study investigated omalizumab in
- pt. 12 to 75 years in USA
- pt. 18 to 75 years in Germany 90 patients
(UAS over 7 days (UAS7) of 12 or greater despite antihistamine Rx)
• randomized to receive a single SC dose of 75, 300, or 600 mg of
omalizumab or placebo added to a stable dose of H1-antihistamine
(J Allergy Clin Immunol 2011;128:567-73.)

87. • 300 mg omalizumab group (-19.9 vs- 6.9, P < .001)
600-mg omalizumab group (- 14.6 vs - 6.9, P < 0.047)
greater improvement versus the placebo in UAS
• Summary : fixed dose of 300 or 600 mg of
omalizumab provides rapid and effective treatment
of CIU in patients who are symptomatic despite
treatment with H1-antihistamines
(J Allergy Clin Immunol 2011;128:567-73.)

88. Indication for omalizumab in asthma
• FDA approved omalizumab (Xolair )
- adults and adolescents ( ≥ 12 years )
- moderate to severe persistent asthma
- test positive for reactivity to a perennial aero
allergen
- whose symptoms are inadequately
controlled with inhaled corticosteroids
http://www.xolairhcp.com/xolairhcp/dosing-and-administration.html

89. The 2007 NHLBI Guidelines state that signs of
lack of control
• >2 exacerbations per year requiring oral corticosteroid
bursts
• Symptoms >2 days per week
• Reliever medication required >2 days per week
• Nighttime awakenings 1 to 3 times per week
• FEV1 or peak flow at 60% to 80% predicted/personal
best
• Limited participation in normal activities
• Needing urgent medical care, including hospitalization
http://www.xolairhcp.com/xolairhcp/dosing-and-administration.html

90. Recommendation by TAC
• Omalizumzb (Anti-IgE)
•
•
•
• Total lgE - IU/mL
• skin prick
test specific IgE aero-
allergen)
•
Uncontrolled

91. Recommendation by TAC
• Exacerbation)
systemic corticosteroids
Prednisolone)

92. GINA ( ≥ 5 years) and TAC
- Pt. age > 6 yr. with moderate to severe
asthma with uncontrolled by GINA step 4
- Sensitization to aeroallergen
- High Ig E level

94. Recommended dose
• Dosing base on body weight and total serum
IgE level
• Recommended dose 0.016 mg/kg//IU of IgE
/4 wk, administered SC every 2-4 wk interval
(150 to 375 mg)
• 150 mg lyophilized powder+sterile water = 5
ml/vial

95. After recommended dose serum free IgE declines rapidly and
reach < 50 ng/ml
Slowly absorb peak level 7-8 days
Half-life 26 days
Omalizumab 150 mg >> 18100
Asian Pac J Allergy Immunol 2011;29:209-19

96. Predicting response to omalizumab
• patients who had a response to omalizumab
- ratio of observed to expected forced expiratory
volume in one second (FEV1) < 65 %
- taking doses of inhaled corticosteroids equivalent to
more than 800 μg of beclomethasone dipropionate per
day
- at least one visit to the emergency department in the
past year
• Patients requiring daily oral corticosteroids to control
their asthma less likely to have a response to
omalizumab
Chest 2004;125;1378-1386

97. • Omalizamab
Omalizamab
controlled GINA
PEF variability <
15%
controlled

98. Side effect of omalizumab
• most common adverse • adverse events needed clinical
reactions (>1% more frequent intervention
in XOLAIR-treated patients) - injection site reaction (45%)
- arthralgia (8%) - viral infections (23%)
- pain (general) (7%) - URI (20%)
- leg pain (4%) - sinusitis (16%)
- fatigue (3%) - headache (15%)
- dizziness (3%) - pharyngitis (11%)
- fracture (2%)
- arm pain (2%) (Omalizumab = control)
- pruritus (2%)
- dermatitis (2%)
- earache (2%)

99. Omalizumab safety
• In 2007 Omalizumab Joint Task Force (OJTF)
report anaphlaxis rate 0.1% of 39,510 pt.
(incidence approximately 0.2% )
• five-step recommendations
1.obtaining informed consent
2.delivery of anaphylaxis education
3.availability epinephrine autoinjector
4. pre-injection health assessment
5. waiting period of 30 minutes after each
injection (with an extended waiting period after
the first 3 injections to 2 hours)
J Allergy Clin Immunol
-

100. Anaphylaxis to omalizumab
• It lacks complement fixing activity
• the molecule is so extensively humanized that
antibodies to the remaining mouse epitopes
are unlikely but merit further study
• Polysorbate, an additive used to promote the
rapid solubilization of pharmaceuticals in
aqueous solutions, has been reported to
cause hypersensitivity reactions
J Allergy Clin Immunol
-

101. • Possible mechanisms
- antiallotypic or anti-idiotypic antibodies (IgE
or IgG) against this reagent that were either
pre-existing before drug administration or had
developed after initial exposures or a
response to the aggregated preparations of
omalizumab
• Another possible mechanism is that an
unrelated event happened to occur near the
time of omalizumab administration
(eg, accidental food allergen ingestion
J Allergy Clin Immunol
-

102. • Previous pooled data (2003) malignancies arising in
omalizumab recipients (0.5%) compared with control
subjects (0.2%) warranting further investigation
• This pooled analysis primary assessed the incidence of
primary malignancy in 32
randomized, doubleblind, placebo-controlled (RDBPC)
trials
• 11,459 unique patients in all clinical trials
• The primary analysis identified malignancies in 25
patients (RDBPC trials):
- 14 in 4,254 omalizumab-treated patients
- 11 in 3,178 placebo-treated patients
J Allergy Clin Immunol 2012;129:983-9.)

103. • Incidence rates per 1,000 patient-years of
observation time for omalizumab- and
placebo-treated patients were 4.14 and
4.45, respectively
• no association was observed between
omalizumab treatment and risk of malignancy
in RDBPC trials
• The data suggest that a causal relationship
between omalizumab therapy and malignancy
is unlikely
J Allergy Clin Immunol 2012;129:983-9.)

104. Evaluating the Clinical Effectiveness and Long-
Term Safety in Patients with Moderate to Severe
Asthma (EXCELS)
• observational study
• 5000 Xolair treated patients and 2500 non-Xolair
treated patients(control group)
• primary objective
- to assess the long-term safety profile of Xolair in
patients followed for 5 years
• Interim data may suggest a risk of cardiovascular
and cerebrovascular adverse event
• EXCELS study is ongoing and final results are not
expected until 2013
Early Communication about an Ongoing Safety Review of Omalizumab ,FDA , 7/16/2009

105. IgE level mornitoring
• Monitoring of total serum IgE levels during
the course of therapy with omalizumab is not
indicated,
(these levels will be elevated as a result of the
presence of circulating IgE–anti-IgE
complexes)
Nat Biotechnol 2000; -

106. Omalizumab mechanism of action
• Decreased free serum IgE
• Decreased expression of FcεRI (on mast
cell, basophil, dendritic cell, and monocyte)
• Decreased FeNO
• Decreased eosinophil (serum, sputum, bronchial
biopsy)
• Decreased circulating IL 13
• Decreased B lymphocyte
• Decreased Ag-induced mediator release from
basophil and mast cells
• Decreased airway inflamation

107. Omalizumab effects on asthma
• Decreased exacerbation
• Decreased ICS dose
• Decreased asthma symptoms
• Decreased recue medication use
• Increased quality of life
• Deceased ER visit
• Decreased hospitalization
• Improved pulmonary function (small effect)

108. Omalizumab on AR
• Decreased daily symptom
• Decreased recue medication usage
• Improved quality of life
• Decreased nasal allergen challenge response
• Decreased missed school and work days

109. Thank you

110. Pharmacoeconomis
• Cost-effectiveness
• QALY = Quality Adjusted Life Year
• Best day in your life = 100
• What is your score today?
• If your score today = 80
• And this condition continues for 5 years
• So you lost 1 QALY

116. From Xolair website