Definition of terms:
Ig = immunoglobulin
FcRI = high-affinity IgE receptor
FEV1 = forced expiratory volume in one second
PEF = peak expiratory flow

[INFORMATIONAL NOTE: The FDA-approved Xolair (omalizumab) package insert has the following black box warning:
Anaphylaxis, presenting as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue, has been reported to occur after administration of Xolair. Anaphylaxis has occurred as early as after the first dose of Xolair, but also has occurred beyond 1 year after beginning regularly administered treatment. Because of the risk of anaphylaxis, patients should be closely observed for an appropriate period of time after Xolair administration, and health care providers administering Xolair should be prepared to manage anaphylaxis that can be life-threatening. Patients should also be informed of the signs and symptoms of anaphylaxis and instructed to seek immediate medical care should symptoms occur.

In July 2010, a warning was added for patients to stop Xolair if patients develop signs and symptoms similar to serum sickness. According to postmarketing surveillance, a constellation of signs and symptoms including arthritis/arthralgia, rash (urticarial or other forms), fever and lymphadenopathy similar to serum sickness have been reported in postapproval use of Xolair

In September 2014, a warning regarding potential malignancies was added to the prescribers’ information in the FDA approved package insert, after clinical trials observed malignant neoplasms in 0.5% of Xolair-treated patients compared with 0.2% of control patients. The observed malignancies included breast, non-melanoma skin, prostate, melanoma, and parotid occurring more than once, and five other types occurring once each.]

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)

The requirements of the Horizon BCBSNJ Omalizumab (Xolair) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).


1. Please refer to a separate policy on Site of Administration for Infusion and Injectable Prescription Medications (Policy #142) under the Drug Section.

• Member has the diagnosis of moderate to severe persistent allergic asthma; (see Appendix C and D)
  [INFORMATIONAL NOTE: Based on the National Asthma Education and Prevention Program, moderate persistent asthma is classified as daily daytime symptoms, night time awakenings of greater than once per week but not nightly, daily use of short-acting beta₂-agonist for symptom control, some limitation of normal activity, FEV₁ >60% but <80% of predicted value and FEV1/FVC reduced up to 5%. Severe persistent asthma is classified as symptoms throughout the day, nighttime awakenings often 7 times per week, use of short-acting beta₂-agonist for symptom control, extreme limitation of daily activity, FEV₁ <60% of predicted, and FEV₁/FVC reduced >5%.]
• Member is at least 6 years of age;
  [INFORMATIONAL NOTE: A 2010 labeling revision included the results of 2 studies in 926 asthma patients 6 to 12 years of age. One trial showed a statistically significant reduction in exacerbation rate, however, it did not demonstrate changes in nocturnal symptom scores, beta-agonist use, or measures of airflow.]
• Member has a weight between 20 kg (44 lbs) and 150 kg (330 lbs)
• Evidence of reversibility; (This requirement is necessary to document that the condition being treated is asthma and not a restrictive or other chronic lung disease. Ideally, there should be demonstration of at least a >12% improvement in FEV₁ or >20% improvement in PEF after using a short acting inhaled beta-2 agonist. However, it would also be acceptable if evidence of reversibility is demonstrated through spirometry measurements over time with the latest measurement being taken in reasonably close timeframe to the request for Xolair.)
• Baseline IgE level ≥ 30 IU/ml and ≤700 IU/ml (≤1300 IU/mL if ages between 6 and 12);
  [INFORMATIONAL NOTE: Limited clinical information is available regarding Xolair use for patients over the age of 12 with IgE levels >700 IU/mL.
  Limited clinical information is available regarding Xolair use for pediatric patients between the ages of 6- 12 years old with IgE levels of > 1300 IU/mL. ]
• Evidence of specific allergic sensitivity, i.e., positive skin test or in vitro reactivity to a perennial aeroallergen (e.g. prick/puncture test, intracutaneous test, RAST);
• Member is symptomatic (or inadequately controlled) despite continued use for trial of at least 3 months of previous combination therapy including medium- or high-dose inhaled corticosteroids PLUS another controller medication (e.g. long-acting beta-2 agonist, leukotriene receptor antagonist, theophylline, etc.). (see Steps 5 and 6 in Appendix A).
• Member is not currently smoking.
  [INFORMATIONAL NOTE: Since in the pivotal trials the population studied did not include smokers, the safety and efficacy of the drug for a person who smokes is not known.]
· Omalizumab (Xolair) is not used in combination with benralizumab (Fasenra), mepolizumab (Nucala), or reslizumab (Cinqair)
• The prescriber is a specialist in the area of the patient’s diagnosis (e.g., allergist, pulmonologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis
• The requested drug will be administered in an office/outpatient setting by a healthcare professional
B. Chronic idiopathic urticarial, when ALL of the following criteria are met:
• Member has the diagnosis of chronic idiopathic urticaria;
  [INFORMATIONAL NOTE: Xolair is not indicated for other allergic conditions or other forms of urticaria.]
• Member is at least 12 years of age;
• Member is refractory or symptomatic to at least 1 month trial of a second-generation H1-antihistamine AND refractory or symptomatic to at least 1 month trial of updosing/dose advancement (up to 4-fold) of a second generation H1-antihistamine or add-on therapy with a leukotriene antagonist, another H1-antihistamine, a H2-antagonist, or cyclosporin A;
• Completion and documentation of baseline evaluation of quality-of-life instruments (will be used to determine if member is achieving efficacy for continuation of therapy: Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), Chronic Urticaria Quality-of-Life Questionnaire (CU-Q2oL), angioedema activity score (AAS), or Angioedema Quality of Life (AE-QoL) score.
• Omalizumab (Xolair) is not used in combination with benralizumab (Fasenra), mepolizumab (Nucala), or reslizumab (Cinqair)
• The prescriber is a specialist in the area of the patient’s diagnosis (e.g., allergist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis
• The requested drug will be administered in an office/outpatient setting by a healthcare professional

A. For allergic asthma:

	30-60	>60-70	>70-90	>90-150
> 30-100	150	150	150	300
>100-200	300	300	300
>200-300	300
>300-400			See Table 2
>400-500			Below
>500-600

	30-60	>60-70	>70-90	>90-150
> 30-100		See Table 1
>100-200		Above		225
>200-300		225	225	300
>300-400	225	225	300
>400-500	300	300	375
>500-600	300	375
>600-700	375		Do Not Dose

Table 3. Omalizumab Doses (mg) Administered by Subcutaneous Injection Every 2 or 4 Weeks* for Pediatric Patients with Asthma Who Begin Xolair Between the Ages of 6 to <12 years old

		20-25	>25-30	>30-40	>40-50	>50-60	>60-70	>70-80	>80-90	>90-125	>125-150
30-100	4	75	75	75	150	150	150	150	150	300	300
>100-200		150	150	150	300	300	300	300	300	225	300
>200-300		150	150	225	300	300	225	225	225	300	375
>300-400		225	225	300	225	225	225	300	300
>400-500		225	300	225	225	300	300	375	375
>500-600		300	300	225	300	300	375
>600-700		300	225	225	300	375
>700-800		225	225	300	375
>800-900		225	225	300	375		Do Not Dose
>900-1000		225	300	375
>1000-1100	2	225	300	375
>1100-1200		300	300
>1200-1300		300	375

[INFORMATIONAL NOTE: Omalizumab (Xolair) is administered subcutaneously over 5-10 seconds because of the viscosity of the information. There have been documented anaphylactic reactions (including urticaria, throat and/or tongue edema) within two hours of the first or subsequent administration of omalizumab; hence, patients should be observed after injection.]

B. For chronic idiopathic urticaria
· Xolair 150 or 300 mg by subcutaneous injection every 4 weeks.

[INFORMATIONAL NOTE: Dosing of Xolair in CIU patients is not dependent on serum IgE (free or total) level or body weight. Clinical trials studied omalizumab (Xolair) doses ranging from 75mg – 600mg every 4 weeks. In all trials, the 75mg dose did not meet the primary endpoint of improving itch severity scores (ISS). The 600mg dose used in a Phase II study did not show added benefit when compared to the 300mg dose.]

• Member has not experienced anaphylactic reaction to previous administration of omalizumab; AND
• Member has any of the following:
  • reduced number of asthma exacerbations;
  • reduced duration of asthma exacerbations;
  • reduced corticosteroid usage;
  • reduced utilization of rescue medications;
  • improvements in pulmonary function tests;
  • reduced number of hospitalizations or emergency room visits; OR
  • reduced reported symptoms, as evidenced by decreases in frequency or magnitude of one or more of the following symptoms:
    • asthma attacks OR
    • chest tightness or heaviness OR
    • coughing or clearing throat OR
    • difficulty taking deep breath or difficulty breathing out OR
    • shortness of breath OR
    • sleep disturbances, night wakening, or symptoms upon awakening OR
    • tiredness OR
    • wheezing/heavy breathing/fighting for air; AND
• The requested drug will be administered in an office setting by a healthcare professional

• Member has maintained stable chronic urticarial symptoms based on one of the following quality-of-life measurement tools use from baseline:
  • Urticaria Activity Score (UAS7)
  • Dermatology Life Quality Index (DLQI)
  • Chronic Urticaria Quality-of-Life Questionnaire (CU-Q2oL)
  • Angioedema activity score (AAS)
  • Angioedema Quality of Life (AE-QoL) score; AND
• The requested drug will be administered in an office/outpatient setting by a healthcare professional

APPENDIX A: Stepwise Approach for Managing Asthma in Youths >12 Years of Age and Adults.



	Daily Medications Assess control: Step up if needed (first, check adherence, environmental control, and comorbid conditions) Step down if possible (and asthma is well controlled at least 3 months) For persistent asthma, consult with asthma specialists if step 4 care or higher is required. Consider consultation at step 3.
Step 6 Persistent	Preferred Treatment high-dose ICS and LABA and oral corticosteroid; AND consider omalizumab for patients who have allergies
Step 5 Persistent	Preferred Treatment high-dose ICS and LABA; AND consider omalizumab for patients who have allergies
Step 4 Persistent	Preferred Treatment medium-dose ICS AND LABA Alternative Treatment: Medium-dose ICS AND either LTRA, theophylline, or zileuton
Step 3 Persistent	Preferred Treatment low-dose ICS AND LABA, OR medium-dose ICS Alternative treatment: low-dose ICS AND either LTRA, theophylline, or zileuton
Step 2 Persistent	Preferred Treatment low-dose ICS Alternative treatment: cromolyn OR LTRA OR nedocromil OR theophylline.
Step 1 Intermittent	Preferred: SABA PRN
Quick Relief Medication for All Patients	SABA as needed for symptoms. Intensity of treatment will depend on severity of exacerbation; up to 3 treatments at 20-minute intervals as needed. Short course of oral systemic corticosteroids may be needed. Use of short-acting inhaled beta2-agonists greater than 2 days a week for symptom relief (not prevention of exercise-induced bronchospasm) generally indicates inadequate control and the need to step up treatment.
Key: Alphabetic order is used when more than one treatment option is listed within either preferred or alternative therapy. EIB - exercise-induced bronchospams; ICS - inhaled corticosteroids; LABA - long-acting inhaled beta2-agonist; LTRA - leukotriene receptor antagonist; SABA - inhaled short-acting beta2-agonist.
NOTES: The stepwise approach is meant to assist, not replace the clinical decision-making required to meet individual patient needs. If alternative treatment is used and response is inadequate, discontinue it and use the preferred treatment before stepping up. Zileuton is a less desirable alternative due to limited studies as adjunctive therapy and the need to monitor liver function. Theophylline requires monitoring of serum concentration levels. In step 6, before oral systemic corticosteroids are introduced, a trial of high-dose inhaled corticosteroid(s) and long-acting beta2 agonist(s) and either LTRA, theophylline, or zileutron may be considered, although this approach has not been studied in clinical trials. Steps 1, 2, and 3 preferred therapies are based on Evidence A; step 3 alternative therapy is based on Evidence A for LTRA, Evidence B for theophylline, and Evidence D for zileuton. Step 5 preferred therapy is based on Evidence B. Step 6 preferred therapy is based on (EPR--2 1997) and Evidence B for omalizumab. Immunotherapy for steps 2-4 is based on Evidence B for house-dust mites, animal danders, and pollens; evidence is weak or lacking for molds and cockroaches. Evidence is strongest for immunotherapy with single allergens. The role of allergy in asthma is greater in children than in adults. Clinicians who administer immunotherapy or omalizumab should be prepared and equipped to identify and treat anaphylaxis that may occur.

Adopted from the National Asthma Education and Prevention Program: Expert Panel Report 3: Guidelines for the Diagnosis and
Management of Asthma. 2007.

APPENDIX B: Stepwise Approach for Managing Asthma in Children 5-11 Years of Age



	Assess Control: Step up if needed (first, check adherence, inhaler technique, environmental control, and comorbid conditions) Step down if possible (and asthma is well controlled at least 3 months) Persistent Asthma: Daily Medication Consult with asthma specialist if step 4 care or higher is required. Consider consultation at step 3.
Step 6 Persistent	Preferred treatment: High-dose ICS AND LABA AND oral systemic corticosteroid Alternative treatment: High-dose ICS AND either LTRA or theophylline AND oral systemic corticosteroid
Step 5 Persistent	Preferred treatment: High-dose ICS AND LABA Alternative treatment: High-dose ICS AND either LTRA or theophylline
Step 4 Persistent	Preferred treatment: Medium-dose ICS AND LABA Alternative treatment: Medium-dose ICS AND either LTRA or theophylline
Step 3 Persistent	Preferred treatment: Either low-dose ICS AND either LABA, LTRA, or theophylline OR Medium-dose ICS
Step 2 Persistent	Preferred treatment: Low-dose ICS Alternative treatment: Cromolyn, LTRA, nedocromil, or theophylline
Step 1 Intermittent	Preferred treatment: SABA PRN
Each step: Patient education, environmental control, and management of comorbidities. Step 2-4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma (see notes).
Quick-Relief Medication for All Patients SABA as needed for symptoms, intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals as needed. Short course of oral systemic corticosteroids may be needed. Caution: increasing use of SABA or use >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to step up treatment.
Key: Alphabetical order is used when more than one treatment option is listed within either preferred or alternative therapy. ICS-inhaled corticosteroid LABA-inhaled long-acting beta2-agonist LTRA-leukotriene receptor antagonist SABA-inhaled short-acting beta2-agonist
Notes: The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs. If alternative treatment is used and response is inadequate, discontinue it and use the preferred treatment before stepping up. Theophylline is a less desirable alternative due to the need to monitor serum concentration levels. Step 1 and step 2 medications are based on Evidence A. Step 3 ICS+adjunctive therapy and ICS are based on Evidence B for efficacy for each treatment and extrapolation from comparator trials in older children and adults-comparator trials are not available for this age group; steps 4-6 are based on expert opinion and extrapolation from studies in older children and adults. Immunotherapy for steps 2-4 is based on Evidence B for house-dust mites, animal danders, and pollens; evidence is weak or lacking for molds and cockroaches. Evidence is strongest for immunotherapy with single allergens. The role of allergy in asthma is greater in children than in adults. Clinicians who administer immunotherapy should be prepared and equipped to identify and treat anaphylaxis that may occur.

Adopted from the National Asthma Education and Prevention Program: Expert Panel Report 3: Guidelines for the Diagnosis and
Management of Asthma. 2007.

APPENDIX C: Classifying Asthma Severity and Initiating Treatment in Youths ≥12 Years of Age and Adults.
Assessing severity and initiating treatment for patients who are not currently taking long-term control medications.



Components of Severity	Classification of Asthma Severity (≥12 years of age)
	Intermittent	Persistent
		Mild	Moderate	Severe
Impairment:
Symptoms	≤2 days/week	>2 days/week but not daily	Daily	Throughout the day
Nighttime awakenings	≤2x/month	3-4 4x/month	>1x/week but not nightly	Often 7x/week
Short-acting beta2-agonist use for symptom control (not for prevention of EIB)	≤2 days/week	>2 days/week but not daily, and not more than 1x on any day	Daily	Several times per day
Interference with normal activity	None	Minor limitation	Some limitation	Extremely limited
Lung function	Normal FEV1 between exacerbations FEV1 >80% predicted FEV1/FVC normal	FEV1>80% predicted FEV1/FVC normal	FEV1>60% but <80% predicted FEV1/FVC reduced 5%	FEV1<60% predicted FEV1/FVC reduced >5%
Risk:
Exacerbations requiring oral systemic corticosteroids	0-1/year (see note)	≥2/year (see note)
	Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time for patients in any severity category. Relative annual risk of exacerbations may be related to FEV1.
Recommended Step for Initiating Treatment (See Appendix A for treatment steps)	Step 1	Step 2	Step 3	Step 4 or 5
			and consider short course of oral systemic corticosteroids
	In 2-6 weeks, evaluate level of asthma control that is achieved and adjust therapy accordingly.
Key: FEV1 - forced expiratory volume in 1 second; FVC - forced vital capacity; ICU - intensive care unit Normal FEV1/FVC: 8-19 yr = 85%; 20-39 yr = 80%; 40-59 yr = 75%; 60-80 y r= 70% Notes: The stepwise approach is meant to assist, not replace the clinical decision-making required to meet individual patient needs. Level of severity is determined by assessment of both impairment and risk. Assess impairment domain by patient's/caregiver's recall of previous 2-4 weeks and spirometry. Assign severity to the most severe category in which any feature occurs. At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma control. In general, more frequent and intense exacerbations (e.g., requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate poorer disease control. For treatment purposes, patients who had >2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as patients who have not-well-controlled asthma, even in the absence of impairment levels consistent with not-well-controlled asthma.

Adopted from the National Asthma Education and Prevention Program: Expert Panel Report 3: Guidelines for the Diagnosis and
Management of Asthma. 2007.

Assessing severity and initiating treatment for patients who are not currently taking long-term control medications.



Components of Severity	Classification of Asthma Severity (5-11 years of age)
	Intermittent	Persistent
		Mild	Moderate	Severe
Impairment:
Symptoms	≤2 days/week	>2 days/week but not daily	Daily	Throughout the day
Nighttime awakenings	≤2x/month	3-4x/month	>1x/week but not nightly	Often 7x/week
Short-acting beta2-agonist use for symptom control (not for prevention of EIB)	≤2 days/week	>2 days/week but not daily	Daily	Several times per day
Interference with normal activity	None	Minor limitation	Some limitation	Extremely limited
Lung function	Normal FEV1 between exacerbations FEV1 >80% predicted FEV1/FVC >85%	FEV1≥80% predicted FEV1/FVC >80%	FEV1≥60% but <80% predicted FEV1/FVC = 75-80%	FEV1<60% predicted FEV1/FVC <75%
Risk:
Exacerbations requiring oral systemic corticosteroids	0-1/year (see note)	≥2/year (see note)
	Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time for patients in any severity category. Relative annual risk of exacerbations may be related to FEV1.
Recommended Step for Initiating Treatment (See Appendix Bfor treatment steps)	Step 1	Step 2	Step 3, medium-dose ICS option	Step 3, medium-dose ICS option, or step 4
			and consider short course of oral systemic corticosteroids
	In 2-6 weeks, evaluate level of asthma control that is achieved and adjust therapy accordingly.
Key: EIB - exercise-induced bronchospasm; FEV1 - forced expiratory volume in 1 second; FVC - forced vital capacity; ICS – inhaled corticosteroids Notes: · The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs. · Level of severity is determined by assessment of both impairment and risk. Assess impairment domain by patient's/caregiver's recall of previous 2-4 weeks and spirometry. Assign severity to the most severe category in which any feature occurs. · At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma control. In general, more frequent and intense exacerbations (e.g., requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate greater underlying disease severity. For treatment purposes, patients who had ≥2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma.


Adopted from the National Asthma Education and Prevention Program: Expert Panel Report 3: Guidelines for the Diagnosis and
Management of Asthma. 2007.

APPENDIX E: Assessing Asthma Control and Adjusting Therapy in Youths >12 Years of Age and Adults.

Components of Control	Classification of Asthma Control (>12 years of age)
	Well Controlled	Not Well Controlled	Very Poorly Controlled
Impairment:
Symptoms	≤2 days/week	>2 days/week	Throughout the day
Nighttime awakenings	≤2x/month	1-3x/week	≥4x/week
Interference with normal activity	None	Some limitation	Extremely limited
Short-acting beta2-agonist use for symptom control (not prevention of EIB)	≤2 days/week	>2 days/week	Several times per day
FEV1 or peak flow	>80% predicted/ personal best	60-80% predicted/ personal best	<60% predicted/ personal best
Validated questionnaires: ATAQ ACQ ACT	0 ≤0.75* >20	1-2 >1.5 16-19	3-4 N/A ≤15
Risk:
Exacerbations requiring oral systemic corticosteroids	0-1/year	>2/year (see note)
	Consider severity and interval since last exacerbation
Progressive loss of lung function	Evaluation requires long-term follow-up
Treatment-related adverse effects	Medication side effects can vary in intensity from none to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in the overall assessment.
Recommended Action for Treatment (see Appendix A for treatment steps)	Maintain current step, Regular follow-ups every 1-6 months to maintain control Consider step down if well controlled for at least 3 months.	Step up 1 step and Re-evaluate in 2-6 weeks. For side effects, consider alternative treatment options.	Consider short course of oral systemic corticosteroids Step up 1-2 steps, and Re-evaluate in 2 weeks. For side effects, consider alternative treatment options.
*ACQ values of 0.76-1.4 are indeterminate regarding well-controlled asthma. Key: EIB - exercise-induced bronchospams; ICU - intensive care unit Notes: The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs. The level of control is based on the most severe impairment or risk category. Assess impairment domain by patient's recall of previous 2-4 weeks and by spirometry peak flow measures. Symptom assessment for longer periods should reflect a global assessment, such as inquiring whether the patient's asthma is better or worse since the last visit. At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma control. In general, more frequent and intense exacerbations (e.g., requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate poorer disease control. For treatment purposes, patients who had >2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as patients who have not-well-controlled asthma, even in the absence of impairment levels consistent with not-well-controlled asthma. Validated Questionnaires for the impairment domain (the questionnaires do not assess lung function or the risk domain): ATAQ = Asthma Therapy Assessment Questionnaires ACQ = Asthma Control Questionnaires ACT = Asthma Control Test Before step up in therapy: -- Review adherence to medication, inhaler technique, environmental control, and co-morbid conditions. -- If an alternative treatment option was used in a step, discontinue and use the preferred treatment for that step.

Adopted from the National Asthma Education and Prevention Program: Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. 2007.

APPENDIX F: Assessing Asthma Control and Adjusting Therapy in Children 5-11 Years of Age

Components of Control	Classification of Asthma Control (5-11 years of age)
	Well Controlled	Not Well Controlled	Very Poorly Controlled
Impairment:
Symptoms	≤2 days/week but not more than once on each day	>2 days/week or multiple times on ≤2 days/week	Throughout the day
Nighttime awakenings	≤1x/month	≥2x/month	≥2x/week
Interference with normal activity	None	Some limitation	Extremely limited
Short-acting beta2-agonist use for symptom control (not prevention of EIB)	≤2 days/week	>2 days/week	Several times per day
Lung Function · FEV1 or peak flow · FEV1/FVC	>80% predicted/ personal best >80%	60-80% predicted/ personal best 75-80%	<60% predicted/ personal best <75%
Risk:
Exacerbations requiring oral systemic cortiosteroids	0-1/year	≥2/year (see note)
	Consider severity and interval since last exacerbation
Reduction in lung growth	Evaluation requires long-term follow-up
Treatment-related adverse effects	Medication side effects can vary in intensity from none to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in the overall assessment.
Recommended Action for Treatment (see Appendix B for treatment steps)	Maintain current step, Regular follow-ups every 1-6 months to maintain control Consider step down if well controlled for at least 3 months.	Step up at least 1 step and Re-evaluate in 2-6 weeks. For side effects, consider alternative treatment options.	Consider short course of oral systemic corticosteroids Step up 1-2 steps, and Re-evaluate in 2 weeks. For side effects, consider alternative treatment options.
Key: EIB - exercise-induced bronchospasm; FEV1-forced expiratory volume in 1 second; FVC-forced vital capacity Notes: The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs. The level of control is based on the most severe impairment or risk category. Assess impairment domain by patient's recall of previous 2-4 weeks and by spirometry/or peak flow measures. Symptom assessment for longer periods should reflect a global assessment, such as inquiring whether the patient's asthma is better or worse since the last visit. At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma control. In general, more frequent and intense exacerbations (e.g., requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate poorer disease control. For treatment purposes, patients who had ≥2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as patients who have not-well-controlled asthma, even in the absence of impairment levels consistent with persistent asthma Before step up in therapy: Review adherence to medication, inhaler technique, environmental control, and co-morbid conditions. If an alternative treatment option was used in a step, discontinue and use the preferred treatment for that step.

APPENDIX G: Estimated Comparative Daily Dosages for Inhaled Corticosteroids for Youths ≥12 Years of Age and Adults

Drug	Low Daily Dose Adult	Medium Daily Dose Adult	High Daily Dose Adult
Beclamethasone HFA 40 or 80 mcg/puff	80-240 mcg	>240-480 mcg	>480 mcg
Budesonide DPI 90, 180, or 200 mcg/inhalation	180-600 mcg	>600-1,200 mcg	>1,200 mcg
Flunisolide 250 mcg/puff	500-1,000 mcg	>1,000-2,000 mcg	>2,000 mcg
Flunisolide FHA 80 mcg/puff	320 mcg	>320-640 mcg	>640 mcg
Fluticasone HFA/MDI: 44, 110, ir 220 mcg/inhalation DPI: 50, 100, or 250 mcg/inhalation	88-264 mcg 100-300 mcg	>264-440 mcg >300-500 mcg	>440 mcg >500 mcg
Mometasone DPI 200 mcg/inhalation	200 mcg	400 mcg	>400 mcg
Mometasone/Formoterol DPI 100 mcg/5mcg and 200 mcg/5 mcg inhalation	200 mcg	400 mcg	> 400 mcg
Triamcinolone acetonide 75 mcg/puff	300-750 mcg	>750-1,500 mcg	>400 mcg
Key: DPI - dry powder inhaler; HFA - hydrofluoroalkane; MDI: metered-dose inhaler Note: The most important determinant of appropriate dosing is the clinician's judgement of the patient's response to therapy. The clinician must monitor the patient's response on several clinical parameters and adjust the dose accordingly. The stepwise approach to therapy emphasized that once control of asthma is achieved, the dose of medication should be carefully titrated to the minimum dose required to maintain control, thus reducing the potential for adverse effect.

Adopted from the National Asthma Education and Prevention Program: Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. 2007.

APPENDIX H: Estimated Comparative Daily Dosages for Inhaled Corticosteroids in Children 5-11 Years of Age



Drug	Low Daily Dose	Medium Daily Dose	High Daily Dose
Beclamethasone HFA 40 or 80 mcg/puff	80-160mcg	>160-320 mcg	>320 mcg
Budesonide DPI 90, 180, or 200 mcg/inhalation	180-400 mcg	>400-800 mcg	>800 mcg
Budesonide inhaled Inhaled suspension for nebulization (child dose)	0.5 mg	1.0 mg	2.0 mg
Flunisolide 250 mcg/puff	500-750 mcg	>1,000-1,250 mcg	>1,250 mcg
Flunisolide FHA 80 mcg/puff	160 mcg	320 mcg	≥640 mcg
Fluticasone HFA/MDI: 44, 110, or 220 mcg/inhalation DPI: 50, 100, or 250 mcg/inhalation	88-176 mcg 100-200 mcg	>176-352 mcg >200-400 mcg	>352 mcg >400 mcg
Mometasone DPI 200 mcg/inhalation	NA	NA	NA
Triamcinolone acetonide 75 mcg/puff	300-600 mcg	>600-900 mcg	>900 mcg
Key: HFA-hydrofluoroalkane; NA-not approved and no data available for this age group Note: · The most important determinant of appropriate dosing is the clinician's judgment of the patient's response to therapy. The clinician must monitor the patient's response on several clinical parameters and adjust the dose accordingly. The stepwise approach to therapy emphasized that once control of asthma is achieved, the dose of medication should be carefully titrated to the minimum dose required to maintain control, thus reducing the potential for adverse effect.


Adopted from the National Asthma Education and Prevention Program: Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. 2007.

Medicare Coverage

There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for Omalizumab (Xolair). Therefore, Medicare Advantage will follow the Horizon Policy.

**Note: Bullet 1 of the policy section referring to Site of Administration for Infusion and Injectable Prescription Medications (Policy #142) does not apply for Medicare Advantage Products.

Per Local Coverage Article A53127 Self-Administered Drug Exclusion List, Medicare covers drugs that are furnished “incident to” a physician’s service provided that the drugs are medically reasonable and necessary, approved by the Food and Drug Administration (FDA) and are not usually administered by the patients who take them. Therefore, Medicare Advantage Products will cover Omalizumab (Xolair) when administered by a licensed medical provider as part of a physician service when the Horizon BCBSNJ Medical policy criteria is met.

Local Coverage Article:Self-Administered Drug Exclusion List: (A53127). Available to be accessed at Novitas Solutions, Inc., Medical Policy Search page: https://www.novitas-solutions.com/webcenter/portal/MedicareJL/pagebyid?contentId=00024370.

Medicaid Coverage

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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Omalizumab (Xolair)
Xolair (Omalizumab)

References:
1. Xolair. Prescribing Information. Genentech, Inc. South San Francisco, CA. May 2019.

2. National Heart, Lung and Blood Institute and the National Asthma Education and Prevention Program. Guidelines for the diagnosis and management of asthma. Expert Panel Report 2, Pub. No. 97-4051. Bethesda, MD: U.S. Department of Health and Human Services; 1997.

3. Boushey HA. Experiences with monoclonal antibody therapy for allergic asthma. J Allergy Clin Immunol 2001;108:S77-S83.

4. Rosenwasser L, et al. Incorporating Omalizumab into Asthma Treatment Guidelines: Consensus Panel Recommendations. P & T June 2003. Vol. 28 No. 6.

5. Busse W, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol 2001;180:184-90.

6. Soler M, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. European Respir J 2001;18:254-61.

7. Milgrom H, et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (Omalizumab). Pediatrics 2001;108-18.

8. Corren J, et al. Omalizumab, a recombinant humanized anti-IgE antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma. J Allergy Clin Immunol 2003;111(1):87-90.

9. Finn A, et al. Omalizumab improves asthma-related quality of life in patients with severe allergic asthma. J Allergy Clin Immunol 2003;111(2):278-84.

10. Casale T, et al. Effect of Omalizumab on symptoms of seasonal allergic rhinitis. JAMA 2001;286:2956-67.

11. Chervinsky P, et al. Xolair in the treatment of perennial allergic rhinitis. J Allergy Clin Immunol 2001;107:S156.

12. Adelroth E, et al. Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis. J Allergy Clin Immunol 2000;106:253-9.

13. Kuehr J, et al. Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis. J Allergy Clin Immunol 2002;109:274-80.

14. National Asthma Education and Prevention Program Expert Panel Report. Guidelines for the Diagnosis and Management of Asthma. J Allergy Clin Immunol 2002;110(5):S141-219.

15. Leung DYM, et al. Effect of anti-IgE therapy in patients with peanut allergy. N Eng J Med 2003;348:986-93.

16. Milgrom H, Berger H, Nayak A, et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics 2001;108(2):E36.

17. Berger W, Gupta N, McAlary M, et al. Evaluation of long-term safety of the anti-IgE antibody, omalizumab, in children with allergic asthma. Annals of Allergy, Asthma, & Immunology 2003;91(2):182-188.

18. Bousquet J, Wenzel S, Holgate S, et al. Predicting Response to Omalizumab, an Anti-IgE Antibody, in Patients With Allergic Asthma. Chest 2004;125:1378-1386.

19. Humbert M, Beasley R, Ayres J, et al. 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. Allergy 2005;60:309-316.

20. National Heart, Lung and Blood Institute and the National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. U.S. Department of Health and Human Services; 2007. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf. Accessed February 2019.

21. Hirdt A. Effectiveness of Omalizumab in Patients with IgE Greater than 700. J Allergy Clin Immunol 2008;121(2): S219 (Abstract).

22. Wolff K, Goldsmith L, Katz S, et al. Fitzpatrick's Dermatology in General Medicine, 7th Edition. The McGraw-Hill Companies, 2008.

23. Gober L, Sterba P, Eckman J, et al. The effect of Anti-IgE in Chronic Idiopathic Urticaria Patients. J Allergy Clin Immunol 2008;121(2):S147 (Abstract).

24. Mark S, Chesnutt M, James A, et al. Current Medical Diagnosis & Treatment 2008, Forty-Seventh Edition- Pulmonology. The McGraw-Hill Companies, July 2008.

25. Zirbes J, Milla C. Steroid-Sparing Effect of Omalizumab for Bronchopulmonary Aspergillosis and Cystic Fibrosis. Pediatric Pulmonology 2008;43:607-610.

26. Xolair (Omalizumab). Wolters Kluwer Health, Inc. Facts and Comparisons. 2009.

27. Casale TB, Busse WW, Kline JN, et al; Immune Tolerance Network Group. Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol 2006;117(1):134-140.

28. Okubo K, Ogino S, Nagakura T, Ishikawa T. Omalizumab is effective and safe in the treatment of Japanese cedar pollen-induced seasonal allergic rhinitis. Allergol Int 2006;55(4):379-386..

29. Vennera M, Picado C, Mullol J, et al. Efficacy of omalizumab in the treatment of nasal polyps. Thorax. 2010 Nov 25. [Epub ahead of print]

30. Caruso C, Gaeta F, Valluzzi R, et al. Omalizumab efficacy in a girl with atopic eczema. Allergy. 2010 Feb;65(2):278-9. Epub 2009 Oct 1

31. A randomized, double-blind, placebo-controlled study of omalizumab for idiopathic anaphylaxis. Clinicaltrial.gov at: http://clinicaltrial.gov/ct2/show/NCT00890162?term=omalizumab&rank=12 [Accessed Jan 14, 2011]

32. Dulera (mometasone furoate and formoterol fumarate dehydrate) prescribing information. Merck & Co, Inc. Whitehouse Station, NJ. December 2011.

33. Zuberbier T, Asero R, Bindslev-Jensen et.al; Dermatology Section of the European Academy of Allergology and Clinical Immunology; Global Allergy and Asthma European Network; European Dermatology Forum; World Allergy Organization. EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria. Allergy. 2009 Oct;64(10):1427-43. Accessed February 2019.

34. Kanani A, Schellenberg R, Warrington R. Urticaria and angioedema. Allergy Asthma Clin Immunol. 2011 Nov 10;7 Suppl 1:S9.

35. Saini S, Rosen KE, Hsieh HJ, et.al. A randomized, placebo-controlled, dose-ranging study of single-dose omalizumab in patients with H1-antihistamine-refractory chronic idiopathic urticaria. J Allergy Clin Immunol. 2011 Sep;128(3):567-73.e1.

36. Muller BA. Urticaria and angioedema: a practical approach. Am Fam Physician.2004 Mar 1;69(5):1123-8.

37. Maurer M, Rosén K, Hsieh HJ, Saini S, Grattan C, Gimenéz-Arnau A, Agarwal S, Doyle R, Canvin J, Kaplan A, Casale T. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013 Mar 7;368(10):924-35. doi: 10.1056/NEJMoa1215372

38. Kaplan A, Ledford D, Ashby M, et al. Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticarial despite standard combination therapy. J Allergy Clin Immunol. 2013 Jul;132(1):101-109.

39. Zuberbier T, Asero R, Bindslev-Jensen C, et al. EAACI/GA(2)LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy. 2009;64:1427–1443.

40. Baiardini I, Braido F, Bindslev-Jensen C, et al. Recommendations for assessing patient-reported outcomes and health-related quality of life in patients with urticarial: a GA²LEN taskforce position paper. Allergy. 2011; 66: 840-844.

41. Lanier B, Bridges T, Kulus M, et al. Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol. 2009 Dec;124(6):1210-6.

42. National Comprehensive Cancer Network. NCCN Drugs & Biologics Compendium: Omalizumab. Accessed March 1, 2020.

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

HCPCS

J2357