Subject: Xolair (Omalizumab) for Chronic Idiopathic Urticaria Original Effective Date: 6/23/2014

Policy Number: 178 Revision Date(s):

Review Date(s): 12/16/15; 9/15/2016; 6/22/2017

DISCLAIMER

This Medical Policy is intended to facilitate the Utilization Management process. It expresses Molina's determination as

to whether certain services or supplies are medically necessary, experimental, investigational, or cosmetic for purposes of

determining appropriateness of payment. The conclusion that a particular service or supply is medically necessary does

not constitute a representation or warranty that this service or supply is covered (i.e., will be paid for by Molina) for a

particular member. The member's benefit plan determines coverage. Each benefit plan defines which services are

covered, which are excluded, and which are subject to dollar caps or other limits. Members and their providers will need

to consult the member's benefit plan to determine if there are any exclusion(s) or other benefit limitations applicable to

this service or supply. If there is a discrepancy between this policy and a member's plan of benefits, the benefits plan will

govern. In addition, coverage may be mandated by applicable legal requirements of a State, the Federal government or

CMS for Medicare and Medicaid members. CMS's Coverage Database can be found on the CMS website. The coverage

directive(s) and criteria from an existing National Coverage Determination (NCD) or Local Coverage Determination

(LCD) will supersede the contents of this Molina medical coverage policy (MCP) document and provide the directive for

all Medicare members.

SUMMARY OF EVIDENCE/POSITION STATEMENTS

This policy addresses the coverage of Xolair® (Omalizumab) for the treatment of chronic idiopathic urticaria in adults

and adolescents 12 years and older who remain symptomatic despite H1 antihistamine treatment.

Other FDA-approved indications are not addressed in this document.

The intent of the Xolair® (omalizumab) medical coverage policy is to ensure appropriate selection of patients for therapy

based on product labeling, clinical guidelines, and clinical studies.

∑ Omalizumab is currently classified as fourth-line therapy in the 2009 EAACI/GA(2)LEN/EDF/WAO* guidelines.

Consensus guidelines on chronic urticaria from leading allergy and immunology organizations classify omalizumab as

fourth-line therapy for the treatment of chronic urticaria; it should only be considered for the treatment of patients

who have failed or who are unable to use the recommended first-, second-, and third-line treatments (high-dose

antihistamines, LTRAs, H2-antagonists, anti-inflammatory agents, and immunosuppressants). *European Academy of Allergy and Clinical Immunology (EAACI), Global Allergy and Asthma European Network

(GA2LEN), European Dermatology Forum (EDF) and World Allergy Organization (WAO)

∑ Omalizumab may reduce urticaria severity, as measured by itch-severity score, in patients with chronic idiopathic

urticaria who remained symptomatic despite use of H1-antihistamine therapy. However, omalizumab has not been

proven to eliminate itching or improve functional impairment due to urticaria symptoms.2,3,B

Page 1 of 13

FDA INDICATIONS�

Chronic idiopathic urticaria: Treatment of chronic idiopathic urticaria in adults and adolescents 12 years and older who

remain symptomatic despite H1 antihistamine treatment.

The updated FDA prescribing information included the following limitations of use:

• Xolair is not indicated for treatment of other allergic conditions or other forms of urticaria;

• Xolair is not indicated for the relief of acute bronchospasm or status asthmaticus;

• Xolair is not indicated for use in pediatric patients less than 12 years of age (FDA, 2014).

Available as: 150mg Powder for Injection

Approved by the FDA: March 2014

RECOMMENDATIONS/COVERAGE CRITERIA

Initiation of therapy with Xolair® (Omalizumab) may be authorized for members who meet ALL of the following criteria

[ALL]

1. � Prescriber specialty [ONE]

ß Board-certified allergy/immunology, dermatology, or pulmonary medicine specialist

2. � Diagnosis/Indication [ALL]

¶ Diagnosis of chronic idiopathic urticaria (CIU) for at least 6 months on most days of the week.C

¶ Other specific causes have been considered and ruled out, and if applicable, possible conditions or triggers for

urticaria are being maximally managed without improvement ‹ Urticaria may be caused or exacerbated by allergen, physical event, or drugs. Among the more common drug

triggers are aspirin and other NSAIDs, opioids, angiotensin-converting enzyme (ACE) inhibitors, and alcohol.

¶ An urticaria activity score (UAS) during a 7-day period (UAS7) of 16 or more (on a scale ranging from 0 to

42, with higher scores indicating greater) ‹ Urticaria Activity Score (UAS): A patient reported CIU measure which captures intensity of pruritus and

number of hives. Daily intensity of pruritus (range: 0 = none to 3 = severe) and number of hives ratings (range:

0 = none to 3 = more than 12 hives) are summed over a week to create the UAS7 (range: 0–42) score.

3. � Age/Gender/Other restrictions [ALL]

ß 12 years of age or oldera-f

‹ Safety and effectiveness have not been established for patients younger than 12 years of age.

ß Clinical documentation of functional impairment due to poor urticaria control or exacerbations

Page 2 of 13

4. � Step/Conservative Therapy/Other condition Requirements [ALL]

NOTE: A step-wise approach to treatment is currently advocated in the EAACI/GA2LEN/EDF/WAO 2009 treatment

guidelines.B Omalizumab is classified as fourth-line therapy for the treatment of chronic urticaria;B it should

only be considered for the treatment of patients who have failed or who are unable to use the recommended first-,

second-, and third-line treatments (high-dose antihistamines, leukotriene receptor antagonist (LTRA), H2-antagonists,

anti-inflammatory agents, and immunosuppressants).

¶ Member continues to experience hives associated with itching despite adequate trials, minimum 4 weeks, of

ALL of the following treatments. Intolerance, FDA labeled contraindication, or hypersensitivity to the

following treatment must be clearly documented and submitted for review. Prescriber to submit

documentation of trial/failure with dates to drug therapy: [ALL]

û Two (2) different H1-antihistamines at the maximally tolerated doses (up to 4 times normal dose daily

dose], unless medically contraindicated ‹ Doses of non-sedating H1-antihistamines should be increased if necessary, up to 4-foldB

‹ First Generation (non-selective, “sedating”) H1-Antihistamines: brompheniramine chlorpheniramine

(Chlor-Trimeton), clemastine (Tavist), cyproheptadine (Periactin), dexbrompheniramine,

dexchlorpheniramine, diphenhydramine (Benadryl), hydroxyzine (Vistaril)

‹ Second Generation (peripherally-selective, “non-sedating”) H1-Antihistamines: cetirizine (Zyrtec),

desloratadine (Clarinex), fexofenadine (Allegra), levocetirizine (Xyzal) loratadine (Claritin)

û A H1-antihistamine in combination with leukotriene receptor antagonist (LTRA) at the maximally

tolerated doses (up to 4 times normal dose daily dose), unless medically contraindicated ‹ LTRA: montelukast (Singulair), zafirlukast (Accolate), zileuton (Zyflo)

‹ The use of LTRA as monotherapy cannot be recommended. LTRA are effective add-on therapy to anti-

histamines, and their use in patients responding poorly to antihistamines is justifiable. Further well

designed randomized controlled trials with clear and standardized outcome measures are needed to

determine the role of LTRA in chronic urticaria.

û A H1-antihistamine at the maximally tolerated doses (up to 4 times normal dose daily dose) in

combination with: [ONE]

o H2-Antihistamines [e.g. cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid),

ranitidine (Zantac)]

o an anti-inflammatory agent (e.g. dapsone, hydroxychloroquine, sulfasalazine)

o an immunosuppressant agent (e.g. cyclosporine, mycophenolate)

5. � Contraindications/Exclusions/Discontinuations to Xolair® (Omalizumab) therapy

Authorization will not be granted if ANY of the following conditions apply [ANY]

¶ Non-FDA approved indications

¶ Severe hypersensitivity reaction to omalizumab or any component of the formulation

6. � Labs/Reports/Documentation required [ALL]

Prescriber has submitted ALL documentation (lab reports, medical records, chart notes) demonstrating above criteria

are met. NO EXCEPTIONS [ALL]

¶ Documented diagnosis of chronic idiopathic urticaria (CIU) for at least 6 months on most days of the week.C

¶ Documentation that other specific causes have been considered and ruled out, and if applicable, possible

conditions or triggers for urticaria are being maximally managed without improvement

Page 3 of 13

¶ Documentation of an urticaria activity score (UAS) during a 7-day period (UAS7) of 16 or more (on a scale

ranging from 0 to 42, with higher scores indicating greater)

ß Clinical documentation of functional impairment due to poor urticaria control or exacerbations

¶ Documentation that member continues to experience hives associated with itching despite adequate trials,

minimum 4 weeks, of ALL of the following treatments. Prescriber to submit documentation of trial/failure

with dates to drug therapy: [ALL]

NOTE: Intolerance, FDA labeled contraindication, or hypersensitivity to any the following treatments must

be clearly documented and submitted for review.

û Two (2) different H1-antihistamines at the maximally tolerated doses (up to 4 times normal dose daily

dose], unless medically contraindicated ‹ Doses of non-sedating H1-antihistamines should be increased if necessary, up to 4-foldB

‹ First Generation (non-selective, “sedating”) H1-Antihistamines: brompheniramine chlorpheniramine

(Chlor-Trimeton), clemastine (Tavist), cyproheptadine (Periactin), dexbrompheniramine,

dexchlorpheniramine, diphenhydramine (Benadryl), hydroxyzine (Vistaril)

‹ Second Generation (peripherally-selective, “non-sedating”) H1-Antihistamines: cetirizine (Zyrtec),

desloratadine (Clarinex), fexofenadine (Allegra), levocetirizine (Xyzal) loratadine (Claritin)

û A H1-antihistamine in combination with leukotriene receptor antagonist (LTRA) at the maximally

tolerated doses (up to 4 times normal dose daily dose), unless medically contraindicated ‹ LTRA: montelukast (Singulair), zafirlukast (Accolate), zileuton (Zyflo)

‹ The use of LTRA as monotherapy cannot be recommended. LTRA are effective add-on therapy to anti-

histamines, and their use in patients responding poorly to antihistamines is justifiable. Further well

designed randomized controlled trials with clear and standardized outcome measures are needed to

determine the role of LTRA in chronic urticaria.

û A H1-antihistamine at the maximally tolerated doses (up to 4 times normal dose daily dose) in

combination with: [ONE]

o H2-Antihistamines [e.g. cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid),

ranitidine (Zantac)]

o an anti-inflammatory agent (e.g. dapsone, hydroxychloroquine, sulfasalazine)

o an immunosuppressant agent (e.g. cyclosporine, mycophenolate)

Page 4 of 13

ADMINISTRATION, QUANTITY LIMITATIONS, AND AUTHORIZATION PERIOD

7. � Recommended Dosing Regimen [AS APPLICABLE]

¶ Chronic Idiopathic Urticaria (CIU): Omalizumab 150 or 300 mg SC every 4 weeks. Dosing in CIU is not

dependent on serum IgE level or body weight. ‹ IgE levels are not measured nor used as a marker for omalizumab therapy with urticaria.

‹ Dosing in chronic idiopathic urticaria is not dependent on serum IgE (free or total) level or body weight.a-e

Dosing for allergic asthma is based on body weight and pretreatment total IgE serum levels. IgE levels remain

elevated up to 1 year following treatment; therefore, levels taken during treatment cannot and should not be

used as a dosage guide.

‹ 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.

8. � Authorization Limit [ALL]

¶ Initial authorization may be authorized of 150mg or 300mg SQ every 4 weeks for 3 doses (for a 3 month

approval).

¶ Quantity and dispensing limit: 3 doses (per a 3-month approval)

¶ Re-authorization for continuation of treatment is required every 3 months to determine continued need based

on documented positive clinical response [defined as sustained clinical improvement from reduced

asthma/urticaria symptoms (such as reduced missed days from work or school) or stable asthma control]

ß TOTAL DURATION OF TREATMENT: The appropriate duration of therapy for CIU has not been

evaluated. Periodically reassess the need for continued therapy.

9. � Route of Administration [ALL]

ß Xolair® (Omalizumab) is considered to be provider-administered by subcutaneous injection in the

Prescriber’s office ‹ 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.

ß If member meets all criteria and approval for therapy is granted, medication will be dispensed by a specialty

pharmacy vendor at the discretion of Molina Healthcare.

Page 5 of 13

CONTINUATION OF THERAPY

Continuation of therapy with Xolair® (Omalizumab) may be authorized for members who meet ALL of the following

criteria [ALL]

1. � Initial Coverage Criteria

ß Member currently meets ALL initial coverage criteria

2. Compliance

ß Adherence to therapy at least 85% of the time as verified by Prescriber and member’s medication fill history

(review Rx history for compliance), including: [ALL]

û Member is compliant in taking the medication as scheduled

û Member tolerated the medication

û Member did not experience any severe adverse reactions while taking the medication

û Member had at least a 20% reduction in parenteral support volume

NOTE: Therapy may be discontinued due to poor adherence upon recommendation of the Molina Medical

Director when adherence < 85% has been demonstrated in at least two months during the course of therapy

ß Documentation by Molina Internal Staff: History of non-compliance or non-adherence as verified by

member’s medication fill history or prescription drug profile [MOLINA MEDICAL/PHARMACY

REVIEWER TO VERIFY]

3. � Labs/Reports/Documentation required [ALL APPLICABLE]

Xolair® (Omalizumab) maintenance therapy may be authorized when therapy has demonstrated efficacy as evidenced

by an improvement in disease activity after initial therapy. Documentation of disease stabilization or improvement

is required for continuation of therapy.

ß Positive response or demonstrated efficacy to therapy clinically documented by an improvement as

measured by a standardized disease activity tool, such as The Dermatology Life Quality Index (DLQI) ‹ Dermatology Life Quality Index (DLQI): A self-administered 10-item questionnaire that rates the impact of skin

disease on symptoms and feelings, daily activities, leisure, work and school, personal relationships and

treatment. The average completion time of 2 minutes. The DLQI may be used for routine clinical use by

clinicians in order to assist the clinical consultation, patient evaluation and monitoring and to help with clinical

decision making process.

¶ Documentation of a minimum 9.5 point improvement in UAS7 score with initial treatment course1

‹ Urticaria Activity Score (UAS): A patient reported CIU measure which captures intensity of pruritus and

number of hives. Daily intensity of pruritus (range: 0 = none to 3 = severe) and number of hives ratings (range:

0 = none to 3 = more than 12 hives) are summed over a week to create the UAS7 (range: 0–42) score.

‹ Clinical studies have demonstrated improved disease control, as reflected by a decrease in the urticaria activity

score over 7 days (UAS7), in patients with moderate to severe chronic urticaria treated with omalizumab

compared to placebo. The minimal important difference (MID) ranged from 9.5 to 10.5 for the UAS7.

4. � Discontinuation of Treatment [ANY]

ß Poor response to treatment as evidenced by physical findings and/or clinical symptoms

ß Intolerable adverse effects or drug toxicity

ß Persistent and uncorrectable problems with adherence to treatment

ß Contraindications/Exclusions to therapy�Authorization will not be granted if ANY of the following conditions applya,b [ANY]�û Non-FDA approved indications

û Severe hypersensitivity reaction to omalizumab or any component of the formulation

Page 6 of 13

ADMINISTRATION, QUANTITY LIMITATIONS, AND AUTHORIZATION PERIOD

5. � Recommended Dosing Regimen [AS APPLICABLE]

¶ Chronic Idiopathic Urticaria (CIU): Omalizumab 150 or 300 mg SC every 4 weeks. Dosing in CIU is not

dependent on serum IgE level or body weight. ‹ IgE levels are not measured nor used as a marker for omalizumab therapy with urticaria.

‹ Dosing in chronic idiopathic urticaria is not dependent on serum IgE (free or total) level or body weight.a-e

Dosing for allergic asthma is based on body weight and pretreatment total IgE serum levels. IgE levels remain

elevated up to 1 year following treatment; therefore, levels taken during treatment cannot and should not be

used as a dosage guide.

‹ 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.

6. � Authorization Limit [ALL]

¶ Initial authorization may be authorized of 150mg or 300mg SQ every 4 weeks for 3 doses (for a 3 month

approval).

¶ Quantity and dispensing limit: 3 doses (per a 3-month approval)

¶ Re-authorization for continuation of treatment is required every 3 months to determine continued need based

on documented positive clinical response [defined as sustained clinical improvement from reduced

asthma/urticaria symptoms (such as reduced missed days from work or school) or stable asthma control]

¶ TOTAL DURATION OF TREATMENT: The appropriate duration of therapy for CIU has not been

evaluated. Periodically reassess the need for continued therapy.

7. � Route of Administration [ALL]

ß Xolair® (Omalizumab) is considered to be provider-administered by subcutaneous injection until

information from the manufacturer, scientific literature, practice standards, or governing State or Federal

agency indicates otherwise.

ß Xolair® (Omalizumab) will be covered only if administered in the prescriber’s office. ‹ 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.

ß If member meets all criteria and approval for therapy is granted, medication will be dispensed by a specialty

pharmacy vendor at the discretion of Molina Healthcare.

Page 7 of 13

COVERAGE EXCLUSIONS

All other uses of the mentioned drugs that are not an FDA-approved indication or included in ‘Coverage Criteria’ section

above are considered experimental/investigational and is not a covered benefit. The following list is not all-inclusive

and is subject to change based on research and medical literature:

¶ Allergic broncho-pulmonary aspergillosis

¶ Allergic conditions without asthma

¶ Atopic dermatitis

¶ Allergic rhinitis

¶ Bullous pemphigoid

¶ Eosinophilic esophagitis

¶ Food allergy (including peanut)

¶ Hyperimmunoglobulin E syndrome (including Job’s syndrome)

¶ Initial therapy for allergic asthma

¶ Insulin allergy

¶ Latex allergy

¶ Non-allergic (non-atopic) asthma

¶ Peanut allergy

¶ Subcutaneous immunotherapy, adjunct

¶ Vibratory angioedema

¶ Urticaria, non-idiopathic (e.g. cold-induced)

Page 8 of 13

SUMMARY OF EVIDENCE/POSITION STATEMENTS

Omalizumab (Xolair) is a recombinant humanized monoclonal antibody that binds to immunoglobulin (Ig) E. It is specific

for circulating free IgE and cannot bind to cell-bound IgE or IgG, as it is engineered to bind to the CH3 domain of the e

chain, which is close to the binding site of IgE for high affinity receptors (FcεRI) and CD23.

The FDA approved Xolair for the treatment of chronic idiopathic urticaria (CIU), a form of chronic hives in March 2014.

Xolair® (Omalizumab) is the first biologic medicine and first medicine approved by the FDA for CIU since non-sedating

H1-antihistamines. This indication is for patients 12 years of age and older who remain symptomatic despite treatment

with H1-antihistamine therapy. Xolair® (Omalizumab) is not used to treat other forms of urticaria (hives) and is not for

use in children less than 12 years of age.

Chronic idiopathic urticaria (CIU)

Chronic idiopathic urticaria (CIU), also known as chronic spontaneous urticaria (CSU), is diagnosed when hives occur

without an identifiable cause, spontaneously present and reoccur for more than six weeks.D,E CIU can have burdensome

symptoms including swelling, severe itch, pain and discomfort that may last for many months and even years.F,G Urticaria

(hives) presents as a raised, itchy rash on the skin that can be localized or spread across large areas of the body.H Urticaria

with a non-specific cause characterized by the spontaneous emergence of wheals, angioedema, or both without external

physical stimuli is classified as CSU if symptoms occur daily or almost daily for more than 6 weeks.3

Patients with chronic urticaria often have a severely impaired quality of life, with negative effects on sleep, daily

activities, school or work life, and social interactions.5 CIU may carry a high burden for patients, high direct and indirect

healthcare costs, and large socio-economic implications.C

Approximately 1.5 million people in the U.S. develop CIU at some stage in their life.F,G Women are twice as likely as men

to experience CIU and most develop symptoms between the ages of 20 and 40.F

Clinical Efficacy

The FDA approval is primarily based on positive and consistent results from two landmark phase III studies, ASTERIA I

and II, which involved CIU/CSU patients not responding to approved doses of H1-antihistamines.2,7,8

Two global Phase 3, randomized, double-blinded, placebo-controlled studies that evaluated the safety and efficacy of

omalizumab administered SC at 75, 150, or 300 mg every 4 weeks in patients with CIU who remain symptomatic despite

standard-dose H1 antihistamine treatment. The two studies differed in that the treatment period for ASTERIA I was 24

weeks compared with a treatment period of 12 weeks for ASTERIA II. 2,7,8

Xolair 300mg and 150mg met all primary endpoints across these studies, which also showed Xolair significantly

improved itch and hives, including rapid itch relief, and in many cases completely cleared symptoms.2,7,8 Quality of life

was also significantly improved for patients treated with Xolair 300mg. Negative effects of CIU/CSU on quality of life

may include sleep deprivation and psychological comorbidities such as depression and anxiety.

In all three phase III studies, a significant proportion of patients became either completely free of itch and hives (range 34-

44%; p<0.001 to p<0.0001 at 300 mg) or had their symptoms suppressed to minimal levels (52-66%; p<0.0001 at 300mg).

ASTERIA I7

‹ ASTERIA I trial (n= 318, 12-75 years with chronic spontaneous urticaria who remained symptomatic despite prior

treatment with H1 antihistamine treatment). Patients treated with the highest dose of Xolair had a response as early as

week 1 vs. week 4 in the placebo group.

‹ ASTERIA I trial employed omalizumab as add-on therapy to H1-antihistamines at approved doses. The 318

participants had a baseline mean weekly Itch Severity Scale (ISS) score of 14.3 out of a possible 21 despite being on

H1-antihistamines. Their baseline urticaria activity score over 7 days (UAS7) was 31.1 on a scale of 0-42.

Page 9 of 13

‹ By week 12, all 3 Xolair doses were significantly superior to placebo in improving patients´ weekly Itch Severity

Score (ISS) (primary endpoint) and this benefit was maintained throughout active treatment.

‹ The mean weekly ISS improved by 9.4 in the group receiving the highest dose, 6.7 in the intermediate dose, and 6.5 in

the lowest dose group, vs 3.6 in the placebo arm. QoL scores with in the high dose group showed nearly twice the

improvement seen in the placebo group.

‹ In the ASTERIA I study, Xolair-treated patients experienced a rapid reduction in itch and hives as early as Week 1,

with the therapeutic benefit sustained over 24 weeks of active treatment (p<0.0001). ClinicalTrials.gov. A study of the efficacy and safety of xolair (omalizumab) in patients with chronic idiopathic urticaria

(CIU)/chronic spontaneous urticaria (CSU) who remain symptomatic despite antihistamine treatment (H1).

http://clinicaltrials.gov/ct2/show/NCT01287117

ASTERIA II study2

‹ 323 pts (aged ≥12 years) with chronic idiopathic urticaria (duration of ≥6 months) who remained symptomatic despite

H1-antihistamine therapy were randomized to omalizumab 75mg, 150mg, or 300mg, or placebo (three injections of

each were administered four weeks apart).

‹ The primary endpoint was change from baseline to week 12 in a weekly itch-severity score (ranging from 0 to 21,

with higher scores indicating more severe itching), with evaluation in the modified intention-to-treat population (all

pts who had undergone randomization and who had received at least one dose of a study drug).

‹ At baseline, the score was approximately 14 in all study groups. At week 12, the mean (±SD) reduction in the score

from baseline was 5.1±5.6 in the placebo group, 5.9±6.5 in the 75mg group (P=0.46), 8.1±6.4 in the 150mg group

(P=0.001) and 9.8±6.0 in the 300mg group (P<0.001).

‹ The authors report that most of the prespecified secondary outcomes at week 12 showed similar dose-dependent

effects. In the ASTERIA II study, 44% of patients receiving Xolair 300mg were itch-and hive-free after 12 weeks of

treatment (p<0.0001).

‹ The frequency of adverse events was similar across groups, with at least one event seen in 61% in the placebo group,

59% in the 75mg omalizumab group, 67% in the 150mg group, and 65% in the 300mg group. The frequency of

serious adverse events was low, although the rate was higher in the 300mg group (6%) than in the placebo group (3%)

or in either the 75mg or 150mg group (1% for each) ClinicalTrials.gov. A study to evaluate the efficacy, response duration and safety of xolair (omalizumab) in patients with chronic

idiopathic urticaria (CIU)/chronic spontaneous urticaria (CSU) who remain symptomatic despite antihistamine treatment (H1).

http://clinicaltrials.gov/ct2/show/NCT01292473

GLACIAL Study8

‹ GLACIAL was a 40-week, global, multi-center, randomized double-blind study that evaluated the safety and efficacy

of omalizumab compared to placebo. It involved 335 patients aged between 12 and 75 with moderate-to-severe

refractory CSU despite receiving standard-of-care therapy, consisting of concomitant H1 antihistamine therapy (up to

four times the approved dose) and other background medications including H2 antihistamines and/or leukotriene

receptor antagonists (LTRAs). Patients were randomized to omalizumab 300 mg or placebo (3:1), given

subcutaneously every four weeks for a total period of 24 weeks.

‹ In the GLACIAL study8, more than half of patients had failed multiple therapies including H1-antihistamines (at up to

four times the approved dose) and H2-antihistamines and/or leukotriene receptor antagonists (LTRAs). Patient

response in GLACIAL was similar to that seen in ASTERIA I and II, leading to elimination or suppression of

symptoms to minimal levels within 2 weeks of the start of treatment, and sustained throughout the 24 week treatment

period. 2,3

‹ Efficacy endpoints included weekly itch severity, health-related quality of life, number of angioedema-free days,

weekly hive scores (number, size), reduction or elimination of disease symptoms (itch, hives) and the time it took to

achieve a clinically significant benefit.

‹ The key efficacy endpoint was assessed by the weekly Itch Severity Score (ISS), on a 21-point scale. The study

showed that omalizumab significantly improved the mean weekly ISS from baseline by 8.6 (p<0.001), compared to a

4.0 improvement in patients on placebo.7 Disease control was also assessed by a measure of itch and hives called the

weekly urticaria activity score (UAS7), where any score of 6 or less out of a 42 point score is considered to represent

a well-controlled disease and a score of zero represents a complete resolution of symptoms.

Page 10 of 13

ClinicalTrials.gov. A safety study of Xolair (omalizumab) in patients with chronic idiopathic urticaria (CIU) who remain symptomatic

despite treatment with H1 antihistamines, H2 blockers, and/or leukotriene receptor antagonists.

http://clinicaltrials.gov/ct2/show/study/NCT01264939

APPENDIX

Appendix 1: Dermatology Life Quality Index (DLQI)

DERMATOLOGY LIFE QUALITY INDEX (DLQI)

Prescriber Name:_______________________ Prescriber Phone No.____________________ Date:_______________ Patient/Member Name:__________________________________ Member ID#:________________________________ Diagnosis:_______________________________________________

DLQI SCORE:

The aim of this questionnaire is to measure how much your skin problem has affected your life

OVER THE LAST WEEK. Please tick X one box for each question.

1.­ Over the last week, how itchy, sore, Very much ¶

painful or stinging has your skin A lot ¶

been? A little ¶

Not at all ¶

2.­ Over the last week, how embarrassed Very much ¶

or self conscious have you been because A lot ¶

of your skin? A little ¶

Not at all ¶

3.­ Over the last week, how much has your Very much ¶

skin interfered with you going A lot ¶

shopping or looking after your home or A little ¶

garden? Not at all ¶ Not relevant ¶

4.­ Over the last week, how much has your Very much ¶

skin influenced the clothes A lot ¶

you wear? A little ¶

Not at all ¶ Not relevant ¶

5.­ Over the last week, how much has your Very much ¶

skin affected any social or A lot ¶

leisure activities? A little ¶

Not at all ¶ Not relevant ¶

6.­ Over the last week, how much has your Very much ¶

skin made it difficult for A lot ¶

you to do any sport? A little ¶

Not at all ¶ Not relevant ¶

7.­ Over the last week, has your skin prevented Yes ¶

you from working or studying? No ¶ Not relevant ¶

If "No", over the last week how much has� A lot ¶

Page 11 of 13

your skin been a problem at work or studying?

A little Not at all

¶

¶

8. Over the last week, how much has yourskin created problems with yourpartner or any of your close friendsor relatives?

Very much A lot A little Not at all

¶

¶

¶

¶ Not relevant ¶

9. Over the last week, how much has yourskin caused any sexualdifficulties?

Very much A lot A little Not at all

¶

¶

¶

¶ Not relevant ¶

10. Over the last week, how much of aproblem has the treatment for yourskin been, for example by makingyour home messy, or by taking up time?

Very much A lot A little Not at all

¶

¶

¶

¶ Not relevant ¶

Please check you have answered EVERY question. Thank you. AY Finlay, GK Khan, April 1992 www.dermatology.org.uk

Available at: http://www.dermatology.org.uk/downloads/dlqiquest.pdf

CODING INFORMATION

CPT Description

96372 Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular -

considered to be provider-administered by subcutaneous injection until information from the manufacturer,

scientific literature, practice standards, or governing State or Federal agency indicates otherwise.

HCPCS Description

J2357 Injection, omalizumab, 5 mg

ICD-9 Description[For dates of service prior to 10/01/2015]

708.8 Other specified urticaria; chronic

ICD-10 Description [For dates of service on or after 10/01/2015] L50.8 Chronic urticaria

REFERENCES

Package Insert, FDA, Drug Compendia

a. � Xolair (omalizumab) [prescribing information]. San Francisco, CA: Genentech Inc; March 2014

b. � AHFS Drug Information® with AHFS®. (www.statref.com), American Society Of Health-System Pharmacists®,

Bethesda, MD. Updated periodically.

c. � DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically.

d. � Drug Facts and Comparisons on-line. (www.drugfacts.com), Wolters Kluwer Health, St. Louis, MO. Updated

periodically.

e. � Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2012. URL:

http://www.clinicalpharmacology.com.

Clinical Trials, Definitions, Peer-Reviewed Publications

1. � Mathias SD, Crosby RD, Zazzali JL, Maurer M, Saini SS. Evaluating the minimally important difference of the

urticaria activity score and other measures of disease activity in patients with chronic idiopathic urticaria. Ann Allergy

Asthma Immunol 2012;108:20-24

2. � Maurer M, Rosén K, Hsieh H, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N

Engl J Med 2013 March; 368:924-935.

Page 12 of 13

3.� 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. The Journal of Allergy and Clinical

Immunology 2011;128(3):567-573.e1.

4.� Sánchez-Borges M, Asero R, Ansotegui IJ, et al. Diagnosis and treatment of urticaria and angioedema: a worldwide

perspective (position paper). World Allergy Organization Journal. 2012; 5:125-147.

5.� O'Donnell BF, Lawlor F, Simpson J et al. The impact of chronic urticaria on the quality of life. British Journal of

Dermatology 1997;136(2):197-201.

6.� Sabroe R, Greaves M. What is Urticaria? Anatomical, Physiological, and Histological Considerations and

Classification. In: Kaplan A, Greaves M, editors. Urticaria and Angioedema. New York: Informa Healthcare; 2009. p.

1-14.

7.� Maurer M, Staubach P, Ashby M, et al. The safety and efficacy of omalizumab in chronic idiopathic/spontaneous

urticaria (CIU/CSU): results from a Phase III randomized, double-blind, placebo-controlled study. European

Academy of Allergy and Clinical Immunology-World Allergy Organization (EAACI-WAO) World Allergy and

Asthma Congress annual meeting 2013. Late Breaking Poster. 25 June 2013, 12:00 p.m.

8.� Kaplan A, Ledford D, Ashby M, et al. Omalizumab in patients with symptomatic chronic idiopathic/spontaneous

urticaria despite standard combination therapy. J Allergy Clin Immunol. 2013;132(1):101-9.

9.� Maurer M, Weller K, Bindslev-Jensen C, et al. Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN

task force report. Allergy. 2011;66:317-330.

Government Agencies, Professional Societies, and Other Authoritative Publications

A.� Zuberbier T, et al. A summary of the new International EAACI/GA(2)LEN/EDF/WAO guidelines in urticaria.

World Allergy Organ J. 2012; 5(Suppl 1):S1-5.

B.� Zuberbier T, 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. PubMed

PMID: 19772513.

C.� Zuberbier T, 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: definition, classification and diagnosis of urticaria. Allergy. 2009b;

64(10):1417-1426.

D.� Asthma and Allergy Foundation of America (AAFA) website. Chronic Urticaria (Hives).

http://www.aafa.org/display.cfm?id=9&sub=23&cont=328. Accessed June 2014.

E.� American Academy of Allergy Asthma & Immunology (AAAAI) website. Skin Allergy Overview. Available at:

http://www.aaaai.org/conditions-and-treatments/allergies/skin-allergy.aspx. Accessed June 2014.

F.� Maurer M, Weller K, Bindslev-Jensen C, et al. Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN task force

report. Allergy 2011; 66: 317–330.

G.� Census Bureau Projects U.S. Population of 317.3 Million on New Year's Day. United States Census Bureau. December 30,

2013. Available at: http://www.census.gov/newsroom/releases/archives/population/cb13-tps112.html. Accessed June 2014

H.� NHS Choices. Urticaria (hives). http://www.nhs.uk/conditions/Nettle-rash/Pages/Introduction.aspx Accessed 26 July

2012. Accessed June 2014

I.� de Silva et al. Leukotriene receptor antagonists for chronic urticaria: a systematic review. Allergy, Asthma & Clinical

Immunology 2014, 10:24 Available at: http://www.aacijournal.com/content/10/1/24 Accessed June 2014

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