Asthma Management Handbook

Monoclonal antibody therapy

Recommendations

When administering maintenance doses of monoclonal antibody therapy, instructions for storing, preparing and administering doses should be followed carefully. The patient must be monitored under direct observation by a health professional (e.g. registered nurse or GP) for at least 30 minutes after each injection.

  • Resuscitation facilities should be available

Note: Monoclonal antibody therapies for asthma are prescribed by specialists. The first few (typically 3) doses are administered in a specialist clinic. Subsequent maintenance doses can be given in the GP’s office or at home for patients participating in a home support program.

Ensure that dispensing arrangements are agreed between the patient, specialist and pharmacist and that the patient clearly understands the process for ordering injections.

 

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available), with particular reference to named source(s):

  • Centre of Excellence in Severe Asthma 20171, 2

Last reviewed version 2.0

Ensure that patients understand that they must attend all scheduled specialist visits in order to remain eligible for access to monoclonal antibody therapy through the PBS.

Note: The specialist prescriber must reapply for PBS application at prescribed intervals, which depend on the agent. Advise patients to make sure they receive advice on timing of required consultations and that they have booked a specialist appointment well before using their last injection.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Advise patients who have been prescribed a monoclonal antibody therapy to keep taking their inhaled corticosteroid preventer. Continue to check adherence and inhaler technique regularly.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Ensure that each patient has an up-to-date written asthma action plan: review it at least yearly or whenever the medication regimen is changed. Remind patients taking monoclonal antibody therapy to follow their written asthma action plan when symptoms worsen.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

More information

Monoclonal antibody therapy for severe asthma

Three monoclonal antibody therapies (omalizumab, mepolizumab and benralizumab) are available in Australia for the treatment of patients with severe asthma whose asthma is uncontrolled despite optimised standard treatment including high-dose inhaled corticosteroids and long-acting beta2 agonists.

Table. Monoclonal antibody therapies currently available in Australia for severe asthma

Name Description Indication*

Dosage & route of

administration

Benralizumab (Fasenra)

Anti-IL-5 receptor

Humanised monoclonal antibody directed against IL-5 receptor Rα on surface of eosinophils and basophils

Add-on treatment for uncontrolled severe eosinophilic asthma in adults and adolescents aged ≥ 12 years

Prefilled syringe for SC injection

30 mg SC every 4 weeks for three injections then every 8 weeks
Mepolizumab (Nucala)

Anti-IL-5

Humanised monoclonal antibody directed against IL-5
Add-on treatment for uncontrolled severe eosinophilic asthma in adults and adolescents ≥12 years

Powder for SC injection in a single-use vial

100 mg SC every 4 weeks
Omalizumab (Xolair)

Anti-IgE

Humanised monoclonal antibody directed against IgE

Add-on treatment for uncontrolled severe allergic asthma in adults, adolescents and children aged ≥6 years

Prefilled syringe for SC injection

Dose calculated according to baseline IgE and body weight. Usual dose every 2–4 weeks (larger doses divided in 2 and administered every 2 weeks)

SC: subcutaneous

*Refer to TGA-approved indications and PBS criteria

Last reviewed version 2.0

Asset ID: 118

Close

Monoclonal antibody therapy reduces the rate of severe flare-ups requiring systemic corticosteroids.[REFERENCE226], 45, 6, 7, 8, 9, 1011, 12, 13 Many patients also experience improvement in asthma symptoms3, 4, 6, 7, 810, 13, 14, 15 and quality of life.3, 8, 9, 16 Some studies have also shown a reduction in oral corticosteroid in patients with severe asthma.3, 4, 17, 8, 12, 13

These therapies are generally well tolerated.3, 6, 7, 11, 18 Injection site reactions are among the most common adverse events. Systemic reactions, including anaphylaxis, are rare but can occur.19

Monoclonal antibody therapies are funded by PBS only when prescribed by specialists (respiratory physician, clinical immunologist, allergist or general physician or paediatrician experienced in severe asthma management), for patients attending a public or private hospital, and when patients meet certain general and product-specific criteria. After treatment is initiated by a specialist, ongoing maintenance doses can be administered in primary care, but regular review for continuing PBS-funded treatment must be carried out by the specialist.

Last reviewed version 2.0

Close
Investigations for severe asthma

Allergy tests

Allergy tests (skin prick testing or specific IgE test) are used to identify sensitisation to potentially avoidable allergens that may be contributing to symptoms. Allergy tests should always be interpreted with consideration of the clinical history.

Specialist investigations before starting monoclonal antibody therapies

The following are required for PBS subsidy for monoclonal antibody therapies:

  • blood eosinophil count within the previous 12 months  – required for benralizumab and mepolizumab
  • total serum IgE level within the previous 12 months – required for omalizumab
  • allergy tests skin prick testing or specific IgE test – required for omalizumab.

Eosinophil count and serum IgE level are arranged by the prescribing specialist. Eosinophil counts may be normal in patients taking oral corticosteroids. The dose is sometimes reduced before repeating the test.20

Other specialist investigations to identify severe asthma phenotype

Sputum eosinophil count may help predict response to benralizumab and mepolizumab therapy, but the optimal cut-off value for this purpose has not been identified.20

Fractional FeNO may help predict response to monoclonal antibody therapies, but the evidence is inconclusive.20

Specialist investigations to investigate severe asthma or rule out other conditions

High-resolution computed tomography of the chest is the most common imaging modality used in the investigation of severe asthma.21 Its main purpose is to exclude alternative diagnoses or comorbid conditions (e.g. bronchiectasis, emphysema, mucus plugging, fibrosis, paralysed hemidiaphragm, idiopathic interstitial pneumonia including eosinophilic pneumonia, allergic bronchopulmonary aspergillosis).

Bronchoscopy may be used to evaluate tissue inflammation and structural abnormalities.22 Its main purpose is to rule out other causes of symptoms.21

Transbronchial biopsy of peripheral airways might help identify specific lesions or diseases (e.g. malignancy, sarcoidosis).21

Last reviewed version 2.0

Close
Written asthma action plans for adults

Every person with asthma should have their own written asthma action plan.

When provided with appropriate self-management education, self-monitoring and medical review, individualised written action plans consistently improve asthma health outcomes if they include two to four action points, and provide instructions for use of both inhaled corticosteroid and oral corticosteroids for treatment of flare-ups.23 Written asthma action plans are effective if based on symptoms24 or personal best peak expiratory flow (not on percentage predicted).23

How to develop and review a written asthma action plan

A written asthma action plan should include all the following:

  • a list of the person’s usual medicines (names of medicines, doses, when to take each dose) – including treatment for related conditions such as allergic rhinitis
  • clear instructions on how to change medication (including when and how to start a course of oral corticosteroids) in all the following situations:
    • when asthma is getting worse (e.g. when needing more reliever than usual, waking up with asthma, more symptoms than usual, asthma is interfering with usual activities)
    • when asthma symptoms get substantially worse (e.g. when needing reliever again within 3 hours, experiencing increasing difficulty breathing, waking often at night with asthma symptoms)
    • when peak flow falls below an agreed rate (for those monitoring peak flow each day)
    • during an asthma emergency.
  • instructions on when and how to get medical care (including contact telephone numbers)
  • the name of the person writing the action plan, and the date it was issued.

Table. Options for adjusting medicines in a written asthma action plan for adults Opens in a new window Please view and print this figure separately: http://www.asthmahandbook.org.au/table/show/42

Table. Checklist for reviewing a written asthma action plan

  • Ask if the person (or parent) knows where their written asthma action plan is.
  • Ask if they have used their written asthma action plan because of worsening asthma.
  • Ask if the person (or parent) has had any problems using their written asthma action plan, or has any comments about whether they find it suitable and effective.
  • Check that the medication recommendations are appropriate to the person’s current treatment.
  • Check that all action points are appropriate to the person’s level of recent asthma symptom control.
  • Check that the person (or parent) understands and is satisfied with the action points.
  • If the written asthma action plan has been used because of worsening asthma more than once in the past 12 months: review the person's usual asthma treatment, adherence, inhaler technique, and exposure to avoidable trigger factors.
  • Check that the contact details for medical care and acute care are up to date.

Asset ID: 43

Close

Templates for written asthma action plans

Templates are available from National Asthma Council Australia:

  • National Asthma Council Australia colour-coded plan, available as a printed handout that folds to wallet size and as the Asthma Buddy mobile site
  • Asthma Cycle of Care asthma action plan
  • A plan designed for patients using budesonide/formoterol combination as maintenance and reliever therapy
  • Remote Indigenous Australian Asthma Action Plan
  • Every Day Asthma Action Plan (designed for remote Indigenous Australians who do not use written English – may also be useful for others for whom written English is inappropriate).

Some written asthma action plans are available in community languages.

Software for developing electronic pictorial asthma action plans2526 is available online.

Close

References

  1. Centre of Excellence in Severe Asthma,. Clinical recommendations for the use of mepolizumab in severe asthma. Version 4. Centre of Excellence in Severe Asthma, Newcastle NSW, 2017.
  2. Centre of Excellence in Severe Asthma,. Clinical recommendations for the use of omalizumab in severe asthma in adults. Version 2. Centre of Excellence in Severe Asthma, Newcastle NSW, 2017.
  3. Nair, P., Wenzel, S., Rabe, K. F., et al. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med. 2017; 376: 2448-2458. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1703501
  4. Bel, E. H., Wenzel, S. E., Thompson, P. J., et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014; 371: 1189-97. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1403291
  5. Yancey, S. W., Ortega, H. G., Keene, O. N., et al. Meta-analysis of asthma-related hospitalization in mepolizumab studies of severe eosinophilic asthma. J Allergy Clin Immunol. 2017; 139: 1167-1175.e2. Available from: http://www.jacionline.org/article/S0091-6749(16)30891-0/fulltext
  6. Bleecker, E. R., FitzGerald, J. M., Chanez, P., et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016; 388: 2115-2127. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27609408
  7. FitzGerald, J. M., Bleecker, E. R., Nair, P., et al. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016; 388: 2128-2141. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27609406
  8. Abraham, I., Alhossan, A., Lee, C. S., et al. 'Real-life' effectiveness studies of omalizumab in adult patients with severe allergic asthma: systematic review. Allergy. 2016; 71: 593-610. Available from: https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.12815
  9. Wang, F. P., Liu, T., Lan, Z., et al. Efficacy and safety of anti-interleukin-5 therapy in patients with asthma: a systematic review and meta-analysis. PloS One. 2016; 11: e0166833. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119789
  10. Ortega, H. G., Liu, M. C., Pavord, I. D., et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014; 371: 1198-207. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1403290
  11. Normansell, R, Walker, S, Milan, S J, et al. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014; Issue 1: Art. No.: CD003559. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24414989
  12. Norman, G., Faria, R., Paton, F., et al. Omalizumab for the treatment of severe persistent allergic asthma: a systematic review and economic evaluation. Health Technol Assess. 2013; 17: 1-342. Available from: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0083500/
  13. Braunstahl, G. J., Chen, C. W., Maykut, R., et al. The eXpeRience registry: the 'real-world' effectiveness of omalizumab in allergic asthma. Respir Med. 2013; 107: 1141-51. Available from: http://www.resmedjournal.com/article/S0954-6111(13)00167-4/fulltext
  14. Humbert, M., Taille, C., Mala, L., et al. Omalizumab effectiveness in patients with severe allergic asthma according to blood eosinophil count: the STELLAIR study. Eur Respir J. 2018; 51: . Available from: http://erj.ersjournals.com/content/51/5/1702523.long
  15. Gibson, P. G., Reddel, H., McDonald, V. M., et al. Effectiveness and response predictors of omalizumab in a severe allergic asthma population with a high prevalence of comorbidities: the Australian Xolair Registry. Intern Med J. 2016; 46: 1054-62. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27350385
  16. Lai, T., Wang, S., Xu, Z., et al. Long-term efficacy and safety of omalizumab in patients with persistent uncontrolled allergic asthma: a systematic review and meta-analysis. Sci Rep. 2015; 5: 8191. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314644/
  17. Brusselle, G. G., Vanderstichele, C., Jordens, P., et al. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax. 2013; 68: 322-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23291349
  18. Farne, H. A., Wilson, A., Powell, C., et al. Anti-IL5 therapies for asthma. Cochrane Database Syst Rev. 2017; Issue 9: CD010834. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010834.pub3/full
  19. Loprete, J N, Katelaris, C H. Hypersensitivity reactions to monoclonal antibody treatments for immune disorders. Medicine Today. 2018; 19: 55-60. Available from: https://medicinetoday.com.au/2018/january/regular-series/hypersensitivity-reactions-monoclonal-antibody-treatments-immune
  20. FitzGerald, JM, Lemiere, C, Lougheed, M D, et al. Recognition and management of severe asthma: a Canadian Thoracic Society position statement. Can J Respir Crit Care Med. 2017; 1: 199-221. Available from: https://www.tandfonline.com/doi/full/10.1080/24745332.2017.1395250
  21. Centre of Excellence in Severe Asthma,, Severe asthma toolkit. **, Centre of Excellence in Severe Asthma 2018. Available from: https://toolkit.severeasthma.org.au
  22. Israel E, Reddel HK. Severe and difficult-to-treat asthma in adults. N Engl J Med. 2017; 377: 965-976. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28877019
  23. Gibson PG, Powell H. Written action plans for asthma: an evidence-based review of the key components. Thorax. 2004; 59: 94-99. Available from: http://thorax.bmj.com/content/59/2/94.full
  24. Powell H, Gibson PG. Options for self-management education for adults with asthma. Cochrane Database Syst Rev. 2002; Issue 3: CD004107. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004107/full
  25. Roberts NJ, Mohamed Z, Wong PS, et al. The development and comprehensibility of a pictorial asthma action plan. Patient Educ Couns. 2009; 74: 12-18. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18789626
  26. Roberts NJ, Evans G, Blenkhorn P, Partridge M. Development of an electronic pictorial asthma action plan and its use in primary care. Patient Educ Couns. 2010; 80: 141-146. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19879092