Self-Administered Mepolizumab in the Management of Severe Asthma: Usability and Patient Acceptance

Figures & data

Figure 1 Medication options for asthma.

Notes: ©2020 Global Initiative for Asthma, reprinted with permission. Available from www.ginasthma.org.8

Abbreviations: ICS, inhaled corticosteroid; SABA, short-acting beta2-agonist; LTRA, leukotriene receptor antagonist; LABA, long-acting beta2-agonist; IgE, immunoglobulin E; IL5, interleukin 5; IL5R, interleukin 5 receptor; IL4R, interleukin 4 receptor; OCS, oral corticosteroid.

Figure 2 Therapeutic targets for biologics in severe asthma.

Notes: Adapted from Fajt ML, Wenzel SE. Development of New Therapies for Severe Asthma. Allergy Asthma Immunol Res. 2017;9(1):3–14.22 Mepolizumab and reslizumab are monoclonal antibodies that antagonize IL-5, whereas benralizumab inhibits the alpha unit of IL-5 receptors. Dupilumab targets the alpha unit of IL4 receptors, and omalizumab targets circulating IgE.

Abbreviations: IL-5, interleukin 5; IL5R, interleukin 5 receptor; IL-4, interleukin 4; IL4R, interleukin 4 receptor; IL-13, interleukin 13; IgE, immunoglobulin E; FcεRI, high-affinity IgE receptor; Th2 cell, T helper type 2 cells.

Figure 3 Overview of Clinical Trials with Mepolizumab in the Treatment of Severe Eosinophilic Asthma.

Abbreviation: OCS, oral corticosteroid.

Table 1 Reported Adverse Events with Asthma Biologics

	Omalizumab	Mepolizumab	Reslizumab	Benralizumab	Dupilumab
Anaphylaxis warning	Yes, 0.1% as early as first dose premarketing and at least 0.2% post- marketing	No, but reported	Yes, 0.3% and as early as the second dose	No, but reported	No, but reported
Epinephrine injectable required	Yes	No, or physician decision	Yes	No, or physician decision	No, or physician decision
Pregnancy category	B	?	?	?	?
Injection site reaction, ie pain, erythema, itching, swelling, burning	45% vs 43% with placebo	8% vs 3% with placebo	Not reported	2.2% vs 1.9% with placebo	18% vs 6% with placebo
Headache	15% and similar to placebo	19% vs 18% with placebo	Not reported	8% vs 6% with placebo	Not reported
Pharyngitis or oropharyngeal pain	11% and similar to placebo	< 3%	2.6% vs 2.2% with placebo	5% vs 3% with placebo	2% vs 1% with placebo
Hypersensitivity reactions^§	Moderate to Severe Persistent	3% vs 3% with placebo	Reported with anaphylaxis	3% vs 3% with placebo	<1% in clinical trials
Fever	See Notes below	Not reported	Not reported	3% vs 2% with placebo	Not reported
Blood eosinophils ≥ 3000 cell/µL	Not reported	Not reported	Not reported	Not reported	2% vs <1% with placebo
Parasites (Helminth) infection*	53% vs 42% with placebo in Brazil	Caution, no cases reported	Caution, no cases reported	Caution, no cases reported	Caution, no cases reported
Other	Malignancy 0.5% vs 0.2% with placebo^¶	2 serious Herpes zoster reactions occurred vs none with placebo. Consider prior vaccination	Malignancy 0.6% vs 0.3% with placebo	Risk of cancer unknown	Risk of cancer unknown
Notes	Churg- Strauss syndrome reported^£ With fever + arthralgia + rash + lymph nodes = ? serum sickness = STOP treatment	Indicated for treatment of Churg-Strauss syndrome at dosage of 300 mg SC every 4 weeks

Notes: Direct comparison of adverse events between biologics is invalid for assessment of safety or medical decision-making. Only comparison to placebo in each biologic is valid. ^§Hypersensitivity reactions may include skin rash, urticaria, angioedema, and/or bronchospasm. For mepolizumab, hypotension and anaphylaxis was included in the Prescribing Information as a hypersensitivity reaction. *Treat patients with pre-existing helminth infections before initiating therapy with a biologic. If patients become infected while receiving treatment with biologic and do not respond to anti-helminth treatment, discontinue treatment with biologic until infection resolves. ^¶In a subsequent observational study of 5007 omalizumab-treated and 2829 non- omalizumab-treated adolescent and adult patients with moderate to severe persistent asthma and a positive skin test reaction or in vitro reactivity to a perennial aeroallergen, patients were followed for up to 5 years. In this study, the incidence rates of primary malignancies (per 1000 patient years) were similar among omalizumab-treated (12.3) and non-omalizumab-treated patients (13.0) [see Adverse Reactions (6)]. However, study limitations preclude definitively ruling out a malignancy risk with omalizumab. Study limitations include: the observational study design, the bias introduced by allowing enrollment of patients previously exposed to omalizumab (88%), enrollment of patients (56%) while a history of cancer or a premalignant condition were study exclusion criteria, and the high study discontinuation rate (44%). ^£In rare cases, patients with asthma on therapy with omalizumab may present with serious systemic eosinophilia sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction of OCS therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between omalizumab and these underlying conditions has not been established. ? indicates unknown. Data from Fajt and Wenzel.22

Abbreviations: SC, subcutaneous: OCS, oral corticosteroid.

Figure 4 Difficult-to-control asthma treatment and referral process at UC Davis Asthma Network.

Abbreviations: PFT, pulmonary function test; ACT, asthma control test; ABPA, allergic bronchopulmonary aspergillosis: GERD, gastroesophageal reflux disease: CHF congestive heart failure.

Table 2 Asthma Phenotypes and Endotypes

Asthma Phenotypes
Allergic asthma
Non-allergic asthma
Asthma with obesity
Asthma with fixed airway disease
Asthma with late onset
Asthma endotypes
T2-high, including IgE-mediated asthma and immunogenesis from IL-4, IL-5, IL-9, IL-13
T2-low, including IL-5, IL-13
Eosinophilic with peripheral blood eosinophils ≥ 150 to 300 cells/µL
Non-eosinophilic, including neutrophilic, mixed, and paucigranulocytic

Notes: Data from Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2020.8

Table 3 Biologics for Uncontrolled Severe Asthma

	Omalizumab	Mepolizumab	Reslizumab	Benralizumab	Dupilumab
Mechanism of Action	Anti-IgE	Anti-IL-5	Anti-IL-5	Anti-IL5Rα	Anti-IL4Rα
Dosing In-Office	75 to 375 mg SC every 2 to 4 weeks	100 mg SC every 4 weeks	3 mg/kg IV every 4 weeks	30 mg SC every 4 weeks then every 8 weeks	200 mg or 300 mg every 2 weeks
Dosing At-Home	N/A	100 mg SC every 4 weeks by autoinjector	N/A	30 mg SC every 8 weeks by autoinjector	300 mg every 2 weeks by pre-filled syringe
Anaphylaxis warning	Yes	No	Yes	No	No
Age (years) Eligibility	Age ≥ 6	Age ≥ 6	Age ≥ 18	Age ≥ 12	Age ≥ 12
Asthma severity (NAEPP 2007)	Moderate to Severe Persistent	Severe Persistent	Severe Persistent	Severe Persistent	Moderate to Severe Persistent
Severe Asthma diagnosis (GINA 2019)	Yes Requiring Step 4 or Step 5	Yes Requiring Step 4 or Step 5	Yes Requiring Step 4 or Step 5	Yes Requiring Step 4 or Step 5	Yes Requiring Step 4 or Step 5
Standard of Care	Medium to High-dose ICS ± other controller	High-dose ICS + LABA or LTRA	Medium to High-dose ICS ± another controller	Medium to High-dose ICS + LABA	Medium to High-dose ICS + LABA
Daily OCS accepted	Yes	Yes	Yes	Yes	No
Exacerbation history past 12 months	N/A	≥ 2	≥ 1	≥ 2	≥ 1
Atopy required	Yes	No	No	No	No
IgE level (IU/mL)	30 to 700 IU/Ml	N/A	N/A	N/A	N/A
Eosinophil count (cells/mm3)	N/A	≥ 150, or ≥ 300 in past year	≥ 400	Any or eosinophilic phenotype	Any or eosinophilic phenotype

Abbreviations: SC, subcutaneous; IV, intravenous; N/A, not available; ICS, inhaled corticosteroids; LABA, long-acting beta2-agonist; LTRA, leukotriene receptor antagonist; OCS, oral corticosteroids; NAEPP, National Asthma Education and Prevention Program; GINA, Global Initiative for Asthma 497.

Table 4 Checklist to Qualify for UCAN at-Home Injection Program

All Questions Must Be Answered YES for a Patient to Qualify for Program
1. Diagnosis of asthma is correct?
2. Phenotype and endotype is correct?
3. Asthma is well-controlled or best control achieved? That is Asthma Control Test (ACT) ≥ 20 or attainment of the best control possible (ACT<20) or at least 3 months on a biologic (exception with dupilumab which is discouraged by insurers from being administered in office) and standard of care treatments, ie ICS + LABA ± additional controller
4. Absence of adverse events or side effects attributable to biologic drug?
5. Patient prefers at-home injection?
6. Absence of hypersensitivity reactions and/or anaphylaxis after 3 months of clinic administration of asthma biologic (exception with dupilumab)?
7. Anticipated medication adherence and compliance with at-home administration is good?
8. Competence confirmed using the patient teach-back method in clinic to assess a patient’s competence in employing the necessary knowledge and technique self- administer biologics at home, including storage, checking for expiration date, selection and rotation of injection sites, and proper disposal after use?

Abbreviations: UCAN, University of California, Asthma Network; ACT, Asthma Control Test; ICS, inhaled corticosteroids; LABA, long-acting beta2-agonist.

Table 5 Indications for Discontinuation of Treatment at UCAN at-Home Injection Program

Discontinuation of at-Home Administration is Indicated if Any of the Following Events or Condition Applies
1. Intolerance to biologic, eg persistent headache, nausea
2. Poor adherence or compliance with treatment that is uncorrectable
3. Poor response to treatment, ie decline in asthma control, increase in symptoms and/or acute exacerbations
4. Hypersensitivity and/or anaphylaxis to the biologic or any excipient of the formulation

Abbreviation: UCAN, University of California, Asthma Network.

Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention; 2020.

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Fajt ML, Wenzel SE. Development of New Therapies for Severe Asthma. Allergy Asthma Immunol Res. 2017;9(1):3–14. doi:10.4168/aair.2017.9.1.3

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