Professional Documents
Culture Documents
1
• Approximately two-thirds of asthma is estimated to be allergic
• A correlation between ‘total’ IgE levels and the risk of developing asthma
2
in adults has been reported
• A recent publication challenged the view that the prevalence of atopy
3
declines with age
– atopy has increased over the last 30 years
– atopy does not decline with increasing age
– more recent birth cohorts are more likely to express atopy
4
• More than 50% of patients with severe asthma have allergic asthma
– skin-prick positive ≥1 common aeroallergen
1. Novak N, Bieber T. J Allergy Clin Immunol 2003; 2. Burrows B, et al. N Engl J Med 1989
3. Law M, et al. BMJ 2005; 4. ENFUMOSA. Eur Respir J 2003
Asthma Control ?
38% patients remain inadequately controlled despite optimised treatment with ICS and LABA*.
*GOAL Study
Summary of the allergic inflammatory
cascade in patients with IgE-mediated
asthma
B lymphocyte Allergic
inflammation:
Allergic eosinophils and
ε -switch mediators lymphocytes
Plasma cell
Release Allergens
of IgE Asthma exacerbation
Mast cells
Basophils
Humanized
monoclonal anti-IgE antibody: Xolair®
IgE
Xolair®
Cε 3
Effects of Omalizumab on IgE
Omalizumab
IgE
Fcε RI
omalizumab
Plasma cell
Perennial
Release Omalizumab aeroallergens
of IgE Asthma exacerbation
Reduces
Binds to free high-
IgE, reducing affinity
receptors Reduces asthma
cell-bound IgE
Mast cells exacerbations
Basophils and
symptoms
Proposed mechanisms of action of
Omalizumab
INNOVATE: anti-IgE as a treatment for
inadequately controlled severe allergic
asthma
INNOVATE: INvestigatioN of Omalizumab
in seVere Asthma TrEatment
28 weeks
Randomization
Humbert M, et al. Allergy 2005
Efficacy variables
0.4
0.2
0
Omalizumab Placebo
(n=209) (n=210)
*Adjustment due to a pre-study imbalance in
exacerbation rate; –19.2% (p=0.156) reduction unadjusted Humbert M, et al. Allergy 2005
Omalizumab significantly reduces severe
exacerbations and emergency visits
0.3 •0.3
Previous exacerbations are the
0.24 single most
0.24important predictive
0.2 factor of future events
0.2
0.1 0.1
0 0
Omalizumab Placebo Omalizumab Placebo
(n=209) (n=210) (n=209) (n=210)
Humbert M, et al. Allergy 2005
INNOVATE: conclusions
93% of patients met GINA 2002 criteria for severe persistent asthma
1. Humbert M, et al. Allergy 2005; 2. Ayres JG, et al. Allergy 2004; 3. Vignola AM, et al. Allergy 2004
4. Busse W, et al. J Allergy Clin Immunol 2001; 5. Solèr M, et al. Eur Respir J 2001
6. Holgate ST, et al. Clin Exp Allergy 2004
Efficacy variables
Annualized ∆ –38.3%
exacerbation rate p<0.0001
1.5 1.47
1.0
0.91
0.5
0
Omalizumab Control
(n=2,476) (n=1,797)
Bousquet J, et al. Allergy 2005
Efficacy of Omalizumab
Summary of phase III studies in allergic asthma
93% of patients met GINA 2002 criteria for severe persistent asthma
1. Humbert M, et al. Allergy 2005; 2. Ayres JG, et al. Allergy 2004; 3. Vignola AM, et al. Allergy 2004
4. Busse W, et al. J Allergy Clin Immunol 2001; 5. Solèr M, et al. Eur Respir J 2001
6. Holgate ST, et al. Clin Exp Allergy 2004;7. Bousquet J, et al. Allergy 2005
Omalizumab significantly reduces
emergency visits for asthma: pooled data
80 Omalizumab
68.5*
Marked improvement or complete
Control 66.2**
60.5** 60.2**
60
control† (% patients)
53.1**
20
0
INNOVATE1 SOLAR2 Busse3 Solèr4 Holgate5
• Allergic reactions :
• In clinical trials , anaphylaxis was reported in 3 out of 3507 (0.1%)
patients .
• Based on Post marketing reports , reported incidence from June’03
to Dec’06 has been 0.2% (124 out of 57,300 patients) .
Approximately 1/4th of these patients had a prior history of
anaphylaxis.
• Malignancies :
• Malignant neoplasms were reported in 20 of 5015 patients (0.5%)
omalizumab treated patients and 5 of 2854 (0.2%) control
patients .
• No cases of malignant neoplasia were considered drug related
when carefully assessed by a panel of independent oncologists ,
blinded to treatment assignments.
GINA 2007 guidelines* includes
anti-IgE therapy at step 5
Step 1 Step 2 Step 3 Step 4 Step 5
Asthma education
Environmental control
As needed rapid- As needed rapid-acting β2-agonist
acting β2-agonist
Controller options Select one Select one Add one or more Add one or more
Low-dose ICS Low-dose ICS plus Medium- or Oral corticosteroid
LABA (lowest dose)
high-dose ICS
plus LABA
IgE-mediated asthma
perennial allergy (skin test or RAST)
Severe asthma? No
Yes
Patient ≥ 6 years? No
Yes
Symptomatic with ICS plus LABA? No
Yes
Multiple documented severe exacerbations? No
Yes
Frequent daytime and nocturnal symptoms? No
Yes
FEV1 <80% predicted No
Yes
Yes
Baseline IgE >20-25 >25-30 >30-40 >40-50 >50-60 >60-70 >70-80 >80-90 >90- >125-
(IU/mL) 125 150
>600–700 300
Baseline IgE (IU/mL) >20‑ 25 >25‑30 >30‑40 >40‑ 50 >50‑ 60 >60‑ 70 >70‑ 80 >80‑ 90 >90-125 >125-150 >150-200
> 400-500 225 225 300 300 375 375 525 600
> 700-800 225 225 300 375 450 450 525 600
> 1000-1100 225 300 375 450 600 DO NOT ADMINISTER – data is unavailable for dose recommendation