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Severe asthma treatment options

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Treating severe asthma

According to treatment guidelines, severe asthma therapy consists of the same inhaler options as mild/moderate asthma, but at high doses and usually in combination with a LABA. OCS may also be prescribed to help achieve severe asthma control. 1-2 Certain individuals may find therapies such as allergen desensitisation therapy and non-pharmacologic interventions beneficial. Eligible patients may also receive a biologic agent. 1-2

Stepping-up asthma therapy with severity

According to the GINA guidelines, most patients with mild/moderate asthma (Steps 1 and 2) should be treated with low-dose ICS with a SABA taken as needed. As severity increases to Step 3, it may be necessary to increase maintenance therapy by adding a LABA to low-dose ICS, with other controller options including LTRA or theophylline add-on therapy. Low-dose ICS/formoterol reliever therapy may also be required in addition to SABAs. 1

Step 4 patients require medium-high doses of ICS/LABA maintenance therapy. Other controller options are tiotropium, and high-dose ICS with either a LTRA or theophylline. 1

The following table indicates what is considered a ‘high’ dose of ICS in adolescent and adult patients. 2

GINA classification of inhaled steroids, 20171

Low, medium and high daily doses of ICS, as defined in GINA 2017

Inhaled corticosteroid

Daily doses (µg) in adults and adolescents (≥12 years)

Low

Medium

High

Beclometasone dipropionate (CFC)

200–500

>500–1000

>1000

Beclometasone dipropionate (HFA)

100–200

>200–400

>400

Budesonide (DPI)

200–400

>400–800

>800

Ciclesonide (HFA)

80–160

>160–320

>320

Fluticasone furoate (DPI)

100

N/A

200

Fluticasone propionate (DPI)

100–250

>250–500

>500

Fluticasone propionate (HFA)

100–250

>250–500

>500

Mometasone furoate

110–220

>220–440

>440

Triamcinolone acetonide

400–1000

>1000–2000

>2000

ATS, American Respiratory Society; CFC, chloroflurocarbon; DPI, dry powder inhaler; ERS, European Respiratory Society; HFA, hydrofluoroalkane; ICS, inhaled corticosteroids; MDI, metered-dose inhaler. 1

Add-on therapy for severe asthma patients

If high-dose ICS does not offer sufficient asthma control then the patient is classed as Step 5. 2 At this stage they should be referred for add-on treatment. 2 An example of a Step 5 treatment option is anti-IgE therapy with the biologic agent omalizumab. 1 Low-dose OCS is also considered a maintenance treatment option for Step 5 patients, as well as some additional therapies, which may be appropriate in specific severe asthma populations. 1-2

Severe asthma treatment recommendations

Therapeutic option

Comments

OCS

  • OCS are often added as maintenance therapy, but should be accompanied by prudent monitoring of weight, blood pressure, blood glucose, eyesight and bone density

Anti‐IgE agents

  • Suggest a therapeutic trial of omalizumab for severe allergic asthma in adults with a high serum IgE titre

Methotrexate (steroid‐sparing)

  • Not recommended in severe asthma due to probable adverse effects and need for monitoring. Any use of methotrexate should be limited to specialised centres and only in patients who require daily OCS

Macrolides

  • Not recommended for the general treatment of severe asthma. They may be appropriate in certain patients whose asthma is characterised by corticosteroid insensitivity and who show increased sputum neutrophils and/or bacterial infections

Anti‐fungal treatments

  • Recommended in adults with severe asthma and recurrent exacerbations of ABPA. Familiarity with the drugs and relevant side-effect monitoring required
  • Not recommended in severe asthma without ABPA irrespective of sensitisation to fungi

Bronchial thermoplasty

  • Recommend that bronchial thermoplasty is performed in adults with severe asthma only in the context of an approved independent systematic registry or a clinical study
  • May be suitable for patients with chronic airflow obstruction associated with airway wall remodelling
  • Recommend that further studies are conducted

ABPA, allergic bronchopulmonary aspergillosis; IgE, immunoglobulin E; OCS, oral corticosteroids.

Adapted from Chung, et al. 2014. 2  

Limitations of existing severe asthma therapies

Oral corticosteroids

OCS are a mainstay of severe asthma maintenance treatment and often added as a maintenance therapy in GINA Stage 5 patients to improve control and prevent future exacerbations. 1OCS are frequently used in addition to ICS to treat severe asthma. 1

Prescribed maintenance OCS dose should be as low as possible, and should be re-evaluated at regular intervals. However, they are only recommended for adults with severe asthma who have poor symptom control and/or frequent exacerbations, despite good inhaler technique and high treatment adherence. 1

Both patients and physicians have concerns over the long-term use of OCS. Side-effects include: 3-4

  • Osteoporosis and bone fractures
  • Muscle weakness
  • Cataracts
  • Hunger
  • Weight gain, sometimes significant
  • Change in shape of face (moon face)
  • Mood swings/depression
  • Swollen legs
  • Nausea
  • Difficulty sleeping

Even with good adherence to OCS some severe asthma patients remain uncontrolled. Such patients are often referred to as corticosteroid-dependent refractory or corticosteroid insensitive. 2OCS are also used to treat severe asthma exacerbations. 2

Some patients may need to take additional medication to deal with side effects, such as bisphosphonates to counteract osteoporosis, or antidepressants. Furthermore, OCS insensitivity can develop, necessitating higher doses to achieve the same efficacy. 2Adverse event risk is linked to OCS dose. 3

Patients often report being worried about the long-term use of OCS, for reasons that include potential damage to organs, developing resistance and the side effects. 4

Continuous OCS use, and perhaps to a lesser degree high-dose ICS, should be accompanied by prudent monitoring of weight, blood pressure, blood glucose, eyes and bone density.

Chung, et al. 2014. 2

These recommendations are driven by concerns over the safety of the long term use of OCS, especially at high doses. Adverse effects associated with steroid use include fracture, cataract, diabetes, myocardial infarction, peptic ulcer, stroke, sleep disturbances, adrenal suppression and hypertension. 35–7A large body of evidence exists to support these concerns, in particular regarding the impact long term OCS use can have on bone density and fractures. 35–7

In a UK-based study of 367 patients with lung diseases and 734 matched controls, patients receiving OCS were ten times more likely to have a vertebral fracture and six times more likely to have a hip fracture versus controls. They were also over twice as likely to have a cataract than the control group.

Adverse effect incidence was dose-related, but effects were observed even at low maintenance OCS doses.

Walsh, et al. 2001. 3

 

Biologics

Biologics are a growing treatment option for severe asthma, when patients have tested eligible for a particular biomarker. 1-2 Biologic therapies exists for certain patient subpopulations. 1

More information on biologics as a therapeutic class is available here.

To learn more about the specific use of biologics in severe asthma, click here.

References

  1. GINA 2017 © 2017 Global Initiative for Asthma, all rights reserved.  Use is by express license from the owner. www.ginasthma.org (Last accessed December 2016).
  2. Chung KF, Wenzel SE, Brozek JL et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014;43(2):343-73.
  3. Walsh L, Wong C, Oborne J et al. Adverse effects of oral corticosteroids in relation to dose in patients with lung disease. Thorax 2001;56:279–284.
  4. Hyland ME, Whalley B, Jones RC et al. A qualitative study of the impact of severe asthma and its treatment showing that treatment burden is neglected in existing asthma assessment scales. Quality of Life Research 2015;24:631-639.
  5. Sarnes E, Crofford L, Watson M et al. Incidence and US costs of corticosteroid-associated adverse events a systematic literature review. Clinical Therapeutics 2011;33:1413-1432.
  6. Souverein PC, Berard A, Van Staa TP et al. Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular disease in a population based case control study. Heart 2004;90:859-865.
  7. Walsh LJ, Lewis SA, Wong CA et al. The impact of oral corticosteroid use on bone mineral density and vertebral fracture. Am J Crit Care Med American Journal of Respiratory and Critical Care Medicine 2002;166:691-695.