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Monoclonal antibody therapies for severe asthma can reduce risky corticosteroid loads, but are still underutilised, writes clinical associate professor Debbie Rigby.
Monoclonal antibody therapies are an effective add-on treatment for patients with severe allergic or eosinophilic asthma that does not respond adequately to treatment with high-dose inhaled corticosteroids (ICS) in combination with long-acting beta2 agonists (LABAs). Monoclonal antibody therapies work by blocking inflammatory pathways that cause airway inflammation.
These medicines can greatly reduce the rate of severe asthma exacerbations, improve symptom control, and reduce the use of systemic corticosteroids — sometimes so dramatically that it has prompted a new focus on the possibility of asthma “remission”.
Four monoclonal antibodies are approved by the Therapeutic Goods Administration for the treatment of severe asthma: benralizumab, dupilumab, mepolizumab and omalizumab. All are subsidised by the Pharmaceutical Benefits Scheme (PBS) for patients who meet specific criteria for severe allergic or eosinophilic asthma. They are prescribed by specialists and can be administered in primary care or by the patient or carer.
Although this class was introduced more than 20 years ago, some patients may be missing out on potential benefit while relying on outdated and risky treatments.
Oral corticosteroid treatment is a last resort, not a treatment
Maintenance treatment of asthma with oral corticosteroids (OCS) is very rarely necessary — it is considered only when no other option is available to prevent severe and potentially life-threatening exacerbations, and under specialist supervision. International guidelines like the Global Strategy for Asthma Management and Prevention describe it as a last resort. However, Australian patients are heavily reliant on oral corticosteroids to manage asthma.
Short courses of oral corticosteroids remain necessary to manage asthma exacerbations, but we now know that each course adds to a person’s lifetime risk of osteoporosis, pneumonia, cardiovascular or cerebrovascular diseases, cataract, sleep apnoea, renal impairment, depression/anxiety, type 2 diabetes, and weight gain. A large long term observational study in the UK reported that a cumulative dose of more than 1000 mg prednisolone significantly increases the risk of type 2 diabetes, cerebrovascular accidents, heart failure, and cardiovascular or cerebrovascular disease, compared with cumulative doses below 500 mg. Even a cumulative dose of only 500 mg to < 1000 mg increases the risk of type 2 diabetes, compared with lower use.
More than a quarter of Australians aged 12 years and older who use preventers for asthma have been prescribed potentially toxic amounts of oral corticosteroids. In a retrospective cohort study analysing a 10% random sample of PBS dispensing data, about half of the cohort had at least one OCS script and just over 25% were dispensed more than 1000 mg of prednisolone or prednisone. Dispensing of diabetes and osteoporosis medications was more common for people cumulatively dispensed 1000 mg prednisolone or more.
When added to currently recommended ICS–LABA treatment, monoclonal antibody therapies reduce the need for short courses of systemic corticosteroids, and may allow patients to reduce or stop oral corticosteroid treatment, according to a review completed by the European Academy of Allergy and Clinical Immunology.
Long term treatment with high doses of ICS is not normal
For most adults and adolescents, asthma can be effectively treated with regimens based on low doses of inhaled corticosteroids, such as low-dose budesonide–formoterol taken as needed for symptom relief, or maintenance-and-reliever therapy with a low dose of budesonide–formoterol or beclometasone–formoterol. But for a small proportion of patients, recommended doses of ICS-based medicines fail to control asthma despite good adherence and correct inhaler technique.
Very few patients should need high doses of ICS for the long term. The National Asthma Council Australia (NAC) emphasises that asthma that fails to respond to medium doses of ICS should be investigated by a specialist as soon as possible, to avoid futile dose escalation and delays to effective treatment.
Early referral could save patients years of uncontrolled asthma
The NAC new information paper on monoclonal antibody therapy for severe asthma urges primary care clinicians to refer patients with suspected severe asthma immediately, so that those found to be eligible for monoclonal antibody therapy can access it as soon as possible. It emphasises not to wait until the patient needs maintenance treatment with oral corticosteroids or frequent short courses of oral corticosteroids.
The NAC warns that severe asthma should be suspected when someone has uncontrolled asthma (persistent symptoms, recurrent exacerbations or both) despite treatment with medium-dose ICS in combination with a long-acting beta2-agonist bronchodilator. In this situation, the NAC Australian Asthma Handbook recommends first systematically checking common reasons for poor asthma control, which include incorrect inhaler technique, poor adherence, continued exposure to smoking or relevant allergens, the symptoms not being due to asthma, or complicating factors like chronic rhinosinusitis.
Primary care clinicians can also arrange investigations to identify the type of asthma and assess which of these targeted treatments may work best for the individual: fractional exhaled nitric oxide (FeNO) test, blood eosinophil count, and total serum immunoglobulin E.
Working through the NAC step-by-step advice could save patients from enduring years of intensive conventional treatment when it is failing to treat their severe asthma exacerbations or troublesome ongoing symptoms.
It could also spare them risky courses of oral corticosteroids, which could compromise their future health.
The NAC has a helpful series of how-to videos for patients on Using your monoclonal antibody therapy that can assist them to use the right technique.
Clinical associate professor Debbie Rigby is clinical executive lead at the National Asthma Council Australia, and adjunct associate professor in the School of Pharmacy and Pharmaceutical Sciences at The University of Queensland.
The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.
The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.
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