A unique solution for severe asthma dr talker olga pulmonary department
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A unique solution for severe asthma. Dr Talker Olga Pulmonary department. C ase Presentation, 10.2009: . 48 year old lady, teacher at school Married +7 s/p op. d/t scoliosis at age 17 No smoking history Family history of severe asthma Allergy to dust mites

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A unique solution for severe asthma dr talker olga pulmonary department

A unique solution for severe asthma.Dr Talker OlgaPulmonary department


C ase presentation 10 2009

Case Presentation, 10.2009:

48 year old lady, teacher at school

Married +7

s/p op. d/t scoliosis at age 17

No smoking history

Family history of severe asthma

Allergy to dust mites

Severe asthma with recurrent exacerbations, recurrent prolonged courses of oral steroids, prednisone 30-40 mg.


A case 10 2009

A case, 10.2009:

BMI- 23

Normal CXR, normal ECHO, p-ANCA, c-ANCA- normal

High eosinophil count-1100

Stool examination- no parasites

PFT- obstructive pattern with FEV1- 60%

Treatment- Prednisone, Seretide 500, Foradil, Flixonase, Omepradex.


A unique solution for severe asthma dr talker olga pulmonary department

What is to be done?


Severe asthma definition

Severe asthma, definition:

Severe asthma- disease that requires high dose inhaled or near continuous oral glucocorticoid treatment to maintain asthma control.


To be excluded

To be excluded:

Ongoing exposure to triggers

Nonadherence

Alternative disorder that mimics asthma

Comorbidities


To be excluded1

To be excluded:

Ongoing exposure to triggers:

allergens, irritants at patient’s home, school, work-laboratory animals, latex, glutaraldehide, toluene diisocyanate, flour, NSAID’s, beta-blockers.

Adherence


To be excluded2

To be excluded:

Conditions that mimic asthma:

Vocal cord dysfunction( combination of inspiratory flow volume loop and laryngoscopy during symptoms), vocal cord paralysis, vocal cord lesions.

Central airway obstruction- tracheal strictures, tracheal copmpression by goiter, thracheal and proximal bronchial tumors, vascular rings( CT, bronchoscopy)

COPD- greater than 20 p.y. smoking history, family history of emphysema or alpha-1 antitrypsin deficiency, irreversible airflow obstruction and low diffusing capacity.


To be excluded3

To be excluded:

Bronchiectasis- copious productive cough, refractory to bronchodilator therapy, HRCT.

ABPA may develop patients with asthma d/t colonization of the airways with aspergillus and typically present with recurrent mucoid impaction and atelectasis, proximal bronchiectasis, skin test positive to aspergillus, elevated IgE (>1000 ng/ml).

Hypersensitivity pneumonitis- exposure to allergens- birds, barns, humidifiers, PFT- mixed obstructive and restrictive pattern, reduced DLCO, fleeting infiltrates.


To be excluded4

To be excluded:

Eosinophilia and respiratory sypmtoms: filariasis, trichinellosis, strongiloides infection- patients from endemic area, blood eosinophilia, elevated IgE, specific IgG to parasites, improvement with specific treatment.

Paranasal sinus disease, skin lesions, peripheral neuropathy, eosynophilia > 10% is common in Churg-Strauss s-me, p-ANCA positive.

Chronic eosinophilic pneumonia- fever, weight loss, night sweats, pulmonary infiltrates.

Endobronchialsarcoidosis- hylaradenopathy and interstitial opacities.

Cardiac disease- echocardiography.


To be excluded5

To be excluded:

Comorbidities:

Chronic rhinosinusitis, allergic rhinitis

GERD

Ongoing smoking

Obesity

OSA

Anxiety , depression.


A case 01 2010

A case, 01.2010:

IgE- 80 u/ml

Started Xolair- monoclonal anti-IgE antibody, 225 mg every two weeks

Prednisone tapering down


A case 11 2010

A case, 11.2010:

Receiving Xolair 225 mg every two weeks

Stopped Seretide

No prednisone

PFT- FEV1- 75%


The ige mediated inflammatory response type i hypersensitivity reaction

The IgE-mediated inflammatory response:type I hypersensitivity reaction

IgE

FceRI

B-cell

Allergen

Mast cell

Histamine

Leukotrienes

Prostaglandins

Cytokines

Atopic

disease

IL-4

IL-13

Th2-cell

IL-5

Antigen-presenting

cell

Eosinophil

Holgate ST. QJM 1998


Xolair omalizumab prevents ige interacting with fc e ri on all cell types

Xolair® (omalizumab)prevents IgE interacting with FceRI on all cell types

IgE

Eosinophil

Macrophage/monocyte

Mast cell

Basophil

Dendritic cell


Omalizumab ige complexes

Omalizumab:IgE Complexes

  • Omalizumab:IgE complexes are either trimers or hexamers, based on Xolair IgE ratio

  • The complexes are of limited size and are eliminated via the reticuloendothelial system

  • No specific organ accumulation, no bigger complexes

Omalizumab (~150 kD)

IgE (~190 kD)

Hexamer

(~1000 kD)

Trimers

(~490 kD- 530 kD)


Reduction in serum free ige following s c administration of xolair

Reduction in serum free IgE following s.c. administration of Xolair®

Median free IgE (ng/mL)

300

  • 300mg administered once monthly for 48 weeks topatients with moderate-to-severe asthma

200

Day 1 post-dose

100

0

0

1

3

7

14

112

168

252

336

Days (not to scale)

Day 0 = screening (n=93)

Source: Extension Study Report 8C


Innovate in vestigatio n of o malizumab in se v ere a sthma t r e atment

INNOVATEINvestigatioN of Omalizumab in seVereAsthma TrEatment

Humbert M, et al. Allergy 2005

  • Patients (aged 12–75 years) with allergic asthma

    • FEV1 40–<80% at randomization

    • Asthma symptoms in the 4 weeks prior to randomization despite high-dose ICS and LABA

    • Clinically meaningful exacerbations in the previous year:

      • Either 2 exacerbations requiring systemic steroids

      • Or a severe exacerbation (PEF or FEV1 <60% personal best) requiring systemic steroids and ER treatment

      • Or hospitalization


Innovate results

Omalizumab

Placebo

* P = 0.04, ** P = 0.002, *** P = 0.038

INNOVATE Results

26 %

50 %

44.2 %


Qol significantly improved overall and across all domains compared with placebo

QoL significantly improved overall and across all domains compared with placebo

Omalizumab

AQLQ score†

Placebo

0.95

**

0.91

***

0.90

***

0.91

***

1.0

0.8

0.6

0.4

0.2

0

0.89

***

ActivitiesEmotionsSymptomsEnvironmentOverall

**p<0.01; ***p<0.001

†Change from baseline (least squares mean)

AQLQ = Asthma Quality of Life Questionnaire


Omalizumab was well tolerated

Omalizumab was well tolerated

  • The percentage of patients who experienced adverse events (AEs) was similar in both treatment groups

    • omalizumab, 72.2%; placebo, 75.5%

  • Fewer serious AEs in the omalizumab group

    • omalizumab, 11.8%; placebo, 15.6%

  • AEs were generally mild or moderate in nature and of short duration

Humbert M, et al. Allergy 2005


Gina 2007 guidelines anti ige therapy at step 5

GINA 2007 guidelines* anti-IgE therapy at step 5

*For children older than 5 years, adolescents and adults†Receptor antagonist or synthesis inhibitor

ICS = inhaled corticosteroid; LABA = long-acting β2-agonist

GINA Workshop Report 2007


Summary of dosing strategy for xolair

Summary of dosing strategy for Xolair®

  • Free IgE target ~25ng/mL(10.4 IU/mL)

  • At least 0.016 mg / kg / IU IgE / month

  • Target Xolair®:IgE ratio greater than 15:1

  • Dose to be adjusted for individual’s baseline IgE and body weight

  • Dosing strategy accommodates a wide range of baseline IgE and body weights


Updated dosing table

Updated Dosing Table


Pulmonary outpatients clinic

Pulmonary outpatients clinic


Omalizumab in severe allergic asthma real life experience meir medical center

Omalizumab in Severe Allergic Asthma: Real Life Experience Meir Medical Center

  • 54 patients

  • 47 patients fulfilled the selection criteria (at least 3 months of treatment)

  • Age: 61± 12 years (26-85)

  • Mean Ig E total levels: 281 ± 236 IU/ml


Omalizumab in severe allergic asthma real life experience meir medical center1

Omalizumab in Severe Allergic Asthma: Real Life ExperienceMeir medical center

  • Duration of disease: 25 ±17 years (2-60)

  • Mean monthly Xolair dosage:

    401± 241mg(150-1200).

  • Mean time on Xolair: 28± 18 months


Real life experience meir medical center sex

Real Life Experience: Meir Medical Center: Sex


Baseline treatment

Baseline treatment


Asthma exacerbation rate one year

Asthma exacerbation rate(one year)

P=0.007


Lung functions

Lung functions

P=0.002

58.1±13.9


Steroids dosages

Steroids dosages

P=0.027


Steroids reduction

Steroids reduction

  • 4 (8.5%) stopped steroids.

  • 10 (21%) reduced the dosage.


Hospitalizations during xolair tx

Hospitalizations during xolair Tx


Side effects

Side effects

  • Only 1 patient withdrawn

  • 5 patients with musculoskeletal pains.

  • No cardiovascular side effects.

  • No anaphylaxis.

  • No malignancies.


Conclusions

CONCLUSIONS

Omalizumab is effective add-on treatment in patients with moderate to severe allergic asthma and accompany by an acceptable safety profile.


Future

Future?


Potential targets for selected novel therapies for treatment resistant asthma

Potential targets for selected novel therapies for treatment resistant asthma


Mepolizumab a humanized anti il 5 mab as a option for severe asthma

Mepolizumab, a humanized anti-IL-5 mAb, as a option for severe asthma


Thank you

Thank You


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