xolair and cinqair for allergic asthma
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Severe Allergic Asthma Treatment
Options By: Joseph DiMasso
Overview of Presentation
• Background of severe allergic asthma
• Therapies to manage severe allergic asthma
• Therapeutic efficacy of the treatment agents
• Cost effectiveness of the treatment agents
What is severe allergic asthma?
• A hypersensitive immune reaction that leads to:
• Airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness (more sensitive to airway narrowing stimuli)
• Cytokines play a critical role in amplifying inflammatory response
• Those specific to allergic inflammation: IL-4,5,9, & 13
• These are derived from Th2
How is severe allergic asthma controlled?
High Dose ICS + LABA
• Step 5 & 6 recommendation:
• Control symptoms & exacerbations for most pts
• Works by treating & reducing the inflammation
Addition of a biologic• Xolair, Cinqair or Nucala:
• Provides eosinophil suppression unlike ICS + LABA
• Works by keeping the inflammation from developing in the first place
VS.
Ensure to rule out other contributing factors
The biologic treatment targets
IgE: Xolair• MOA:
• Inhibits the binding of IgE to the IgE receptor on the surface of mast cells and basophils
• This limits the degree of release of mediators of the allergic response & reduces the number of receptors on basophils in atopic patients
IL-5: Cinqair & Nucala• MOA:
• Interleukin-5 (IL-5) antagonist that reduces the production and survival of eosinophils
• This is done by blocking the binding of IL-5 to the alpha chain of the receptor complex on the eosinophil cell surface
-Blocking IL-5: Specific for reducing eosinophilic inflammation
-Blocking IgE: Helps prevent allergic reactions
*Both aim to fix the balance between Th1 & Th2
Proposed benefits of biologic agent addition• Targets the 5-10% of pts with severe asthma; costing the
healthcare system $25 billion dollars a year• Prevents the inflammation as opposed to reducing and treating
the inflammation
• Reduce the risk of long term use of oral corticosteroids such as: • Drug induced hyperglycemia • Immunosuppression; increased risk of infection• Osteoporosis; thinning of the bones• Muscle wasting & weakness• Cataracts & Glaucoma
Potential issues of biologic agent addition• Antibody formation against the drug itself (appeared to be
transient in trials) • Unknown cancer risk• No clinical studies were conducted to assess the effect of
hepatic or renal impairment on the PK of the medications • Cannot be used in pregnancy or lactation • Not studied adequately in ages over 65yrs• Long term effects are unknown • May be very costly yet ineffective for some pts
Clinical trial result measurements
• Symptom improvement: Subjectively measured by questionnaires including the SGRQ (breathlessness attacks), AQLQ (triggers & symptoms) & the ACQ-7
• Changes in FEV1: Measured in mL at the end of each trial
• Avg decrease of OCS dose: Dose reduction after 12 weeks of therapy vs. placebo
• Total exacerbation rate: Included pts that needed to double the dose of ICS to gain better control, initiate 3+ days of OCS as well as ER visits and hospitalizations
• Hospitalization rate: Included only those who had to stay in the hospital; this averaged 3.8 days
Clinical Trial Results Result (N=850) Xolair Placebo Symptom improvement
67.8% 61.0%
Change in FEV1 N/A N/AAvg decrease of OCS dose
44% decrease in need
-
Total exacerbation rate
35.6% 42.6%
Hospitalization rate 3.7% 4.0%Result (N=1,192)
Nucala Placebo
Symptom improvement
53.1% 42.2%
Change in FEV1 140mL 138mLAvg decrease of OCS dose
50% decrease in need
-Total exacerbation rate
7.2% 13.1%
Hospitalization rate N/A N/A
Result (N=963) Cinqair Placebo Symptom improvement
66.67% 57.0%
Change in FEV1 137mL 98mLAvg decrease of OCS dose
54% decrease in need
-
Total exacerbation rate
31.5% 49.5%
Hospitalization rate 3% 5%
Overview of Xolair (Omalizumab)
• Dosing is based on weight and baseline IgE level • Drawn up in a 18gauge syringe and injected with a 25
gauge syringe• No more than 150mg (1.2mL) injection at one site • Used in ages 12+
PK Parameter Value Bioavailabilty 62% Tmax 8days Clearance Via liver & bile T1/2 25days
Xolair Dosing
Xolair (Omalizumab)
The good • Minimal significant drug
interactions • Lowers the incidence of
asthma exacerbations if uncontrolled on high dose ICS + LABA • Lowers need of OCS usage • Cheapest option
The not so good• 45% pts get injection site rxns• Over 50% of at risk pts for
Helminthic infection (parasite) are affected • Worsening pulmonary
symptoms may occurs during OCS taper • Q2-4week SQ injection in
office
Overview of Nucala (Mepolizumab)
• 100mg SQ dose found to be equally effective to higher doses • Mechanically reconstituted then drawn up and injected in
one site• Much less injection site reactions when compared to Xolair • Must have baseline eosinophils >150 cells/uL• Used in ages 12+ PK Parameter Value
Bioavailabilty 80% Tmax 6days T1/2 20days Metabolism Enzymatic proteolysis
Nucala (Mepolizumab)
The good • Fixed dose of 100mg SQ q4wk• No dose adjustments needed• For pts with eosinophilic
asthma that may be insensitive to steroids
• Lowers the incidence of asthma exacerbations if uncontrolled on high dose ICS + LABA
• Lowers need of OCS usage
The not so good• Severe headaches occur in
20% of pts • Antibody development
occurred in 6% of pts; rendering it ineffective• Not included in guidelines• Q4wk SQ injection in office
Overview of Cinqair (Reslizumab)
• 3mg/kg IV infusion of 20-50min• May require multiple vials • Much less injection site reactions when compared to Xolair • Must have baseline eosinophils >400cells/uL• Used in ages 18+
PK Parameter Value Bioavailabilty N/A Tmax N/A T1/2 24days Metabolism Enzymatic proteolysis
Cinqair (Reslizumab)
The good• Minimal significant drug
interactions• For pts with eosinophilic
asthma that may be insensitive to steroids • Lowers the incidence of
asthma exacerbations if uncontrolled on high dose ICS + LABA • Lowers need of OCS usage
The not so good• 1-20% pts had elevated
creatine kinase levels • Associated with heart attack,
skeletal muscle & brain damage
• Not included in guidelines• Infusion Q4wk in office• Most expensive option
Are these cost effective treatments?
Xolair Avg Dose: 300mg IVAvg cost per year: $23,400QALY: $492,000 to 633,500Anticipated savings: Indirect costs due to less hospitalizations & OCS use
Nucala Avg Dose: 100mg SQ Avg cost per year: $32,500QALY: $386,000Anticipated savings: Indirect costs due to less hospitalizations & OCS use
CinqairAvg Dose: 240mg IV Avg cost per year: $55,000QALY: $322,000 to $491,000Anticipated savings: Indirect costs due to less hospitalizations & OCS use
How to apply QALY’s to a patient centered care approach
Medication QALY High Dose ICS + LABA $4,100Xolair $492,000 to 633,500Nucala $386,000Cinqair $322,000 to $491,000
*Anticipate a significant cost barrier with both the patient and insurance
Conclusion
• The biologic agents do lower the rate of exacerbations & the use of oral corticosteroids • While inhaled steroids work by treating and reducing the inflammation, anti-
IgE & IL-5 therapies works by keeping inflammation from developing in the first place.
• These agents are most effective in a certain subgroup of patients• More significant therapeutic outcomes in those with more severe asthma• Adherence of pts to inhalers was not addressed in any study prior to
enrollment
• But; extremely expensive & long term side effects as well as effectiveness are unknown
References
• http://www.aafa.org/page/asthma.aspx• http://www.ncbi.nlm.nih.gov/pubmed/21536936• https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescri
bing_Information/Nucala/pdf/NUCALA-PI-PIL.PDF• http://www.fda.gov/Drugs/InformationOnDrugs/ucm493518.htm• http://www.ispor.org/ValueInHealth/ShowValueInHealth.aspx?issue=5D62980A-5
2D1-42F8-8BB6-D0D18B58EE8D• http://icer-review.org/wp-content/uploads/2016/03/
ICER_Mepolizumab_AAG_031416.pdf
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