Andy Nish, MD is Fellow of American Academy of Allergy, Asthma & Immunology (FAAAAI) and the President of Northeast Georgia Physicians Group (NGPG) — Allergy and Asthma, GA. Dr Nish talks about the impact of biologics therapy in asthma, as well as the other advances in better defining and managing the chronic airway inflammatory disease. Edited excerpts:
Nearly half a dozen biologics are now approved to treat asthma. And many more are under development. Can biologics eventually replace the current line of steroid-centred management of the symptoms and offer a lasting solution, if not a permanent cure, for the disease?
Biologics have made a tremendous difference in the lives of many asthmatics.
However, it is unlikely that the biologics will be able to completely replace current asthma therapies. For one, the biologics target a specific pathway which provides a narrower therapeutic efficacy than current standard therapies. And asthmatics in the intermittent, mild persistent and moderate persistent categories can typically be controlled with currently available therapies with a very acceptable risk to benefit ratio. In addition, the current costs of manufacturing the biologics make them cost-prohibitive to be used broadly.
Unfortunately, the currently available biologics have not been shown to have disease-modifying properties for asthma. Studies have shown that asthma returns to its previous state of inflammation and pathology over time once the biologics are stopped.
So, it’s unlikely that biologics, as we currently know them, can function as monotherapy for asthma or produce a cure, but then twenty years ago who could have known of the advances we have available today.
Apart from monoclonals, what are the other approaches using biologics, currently being explored to address asthma?
Despite the advances and benefits of currently available biologics, which are genetically engineered proteins, continued improvement is welcomed and there are definitely holes in our treatment choices. For the Th17 (non T2) type asthmatic, there are currently no highly effective biologics. Whereas currently 98% of all asthma treatment is small particle, the research pipeline contains 12% monoclonal and 17% non-monoclonal antibodies.
The incidence of asthma is on the rise the world over despite wider availability of effective and comparatively less costly medicines to control the attacks. Why?
It is estimated that asthma may have increased as much as 12% over the past decade. There are a number of theories as to why the incidence of asthma is on the rise. In reality, it is probable that a number of these are contributing.
First, it is suggested that asthma is more recognized and coded as such.
Allergic disease, in general, has been increasing, not only asthma but also allergic rhinitis, food allergy, and atopic dermatitis. One theory is called the hygiene hypothesis, that our lymphocytes no longer have to fight infection as much as in the past, so they are becoming more Th2 cells and producing allergic disease.
Air pollution has been linked to increased incidence of asthma in children, as has exposure to cigarette smoke, particularly if the mother smokes while pregnant. In addition, if a child’s diet is leading to obesity and overweight, it can be associated with an increased risk of asthma. Birth by c-section changes the gut flora and increases the risk of asthma also.
So, the rise in asthma is likely multifactorial, but the good news is that we do have more and better asthma medicines to use over time.
Some of the experts in the field argue that the term “asthma” needs to be redefined, giving more emphasis on the heterogeneity of the disease. What is your comment?
I definitely agree with this concept. As we have learned particularly in recent years, there is so much heterogeneity in the pathology of asthma and the inflammation thereof and response to treatment.
The more medicines that have been developed, the more we learn about which patients do or don’t respond to particular of those medicines, and then research helps to delineate why that is.
Some patients are primarily T2 driven and some primarily Th17 driven. Some are primarily eosinophil driven and some primarily neutrophils. Some asthmatics respond dramatically to very small doses of inhaled corticosteroids and some respond minimally to very high doses of inhaled or even systemic steroids. It’s important that we recognize that asthma treatment is not “one size fits all”.
Are corticosteroids being overprescribed for managing asthma?
If the question is in regard to inhaled steroids, I would suggest that the answer is no. It may even be that inhaled steroids are not being prescribed often enough, partly because of steroid phobia, particularly on the part of parents. Other studies have suggested that asthma is underdiagnosed in general and the severity is underappreciated.
It is recommended by experts that the drug of choice for the first-line treatment of mild, moderate and severe persistent asthma is inhaled steroids, of course with other medicines as needed as severity increases.
We have good evidence from longitudinal studies that, if inhaled steroids affect children’s final adult height, it is a minimal effect and that other potential side effects, in general, present a favourable risk to benefit ratio. It is worth pointing out that inhaled steroids are in microgram doses and systemic steroids, if needed for an asthma flare, are in milligram doses, or 1000 times stronger.
It is important to note that objective measures, such as pulmonary function tests, should be used to make sure that treatment is effective, and at the lowest possible dose for the fewest side effects.