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SEVERE asthmatics treated with a new monoclonal antibody drug showed improved lung function after 12 weeks, in research which adds to the growing understanding of asthma as a heterogeneous disease requiring personalised treatments.
The randomised controlled trial, published in the New England Journal of Medicine, allocated 219 people with severe asthma to receive either subcutaneous lebrikizumab (a monoclonal antibody to interleukin-13) or placebo, monthly for 6 months. (1)
All the study participants had poorly controlled asthma at baseline despite treatment with inhaled glucocorticoid therapy. Researchers hypothesised that the role of interleukin-13 could explain variation in treatment response in their subjects, so patients were stratified according to their serum periostin level, which was used as a marker for interleukin-13 activity. Interleukin-13 induces bronchial epithelial cells to secrete periostin.
Slightly more than half the total cohort had elevated periostin levels.
After 12 weeks, the mean increase in forced expiratory volume in 1 second (FEV1) from baseline was 5.5 percentage points higher in the lebrikizumab group than in the placebo group. For patients with the highest levels of periostin, the increase in FEV1 from baseline was 8.8 percentage points higher in those taking lebrikizumab.
“[These results] are consistent with the hypothesis that phenomena driven by interleukin-13 are clinically important in such patients”, the researchers wrote.
The study also found a non-significant trend towards reduced rates of severe asthma exacerbations among patients treated with lebrikizumab; however, the study wasn’t sufficiently powered for this outcome.
Associate Professor Frank Thien, of the National Asthma Council Australia, said the research advanced the understanding that there are distinct phenotypes of asthma requiring individual treatment options.
“It shows that you can improve asthma by treating the mechanism rather than the manifestation of the disease … it’s proof of concept that the mechanism is important in people with asthma.”
Participants treated with lebrikizumab had improvements in lung function after just 1 week. “That’s important and suggests the mechanism can be switched off quite quickly”, Professor Thien said.
Professor Philip Thompson, director of the Lung Institute of WA, agreed that the research highlighted the fact that “asthma isn’t one disease”. “The end product looks the same but the pathways that get you there aren’t.”
Professor Thompson said the research fitted in the context of growing interest in monoclonal antibody treatments for asthma. An anti-IgE treatment (Xolair) had just been listed on the PBS, while an anti-IL5 treatment was undergoing clinical trials in Australia and overseas.
Although lebrikizumab is not currently available in Australia, Professor Thompson believed Australian clinical trials are likely to occur within the next 6 months.
Professor Paul Foster, director of the Priority Research Centre for Asthma and Respiratory Disease at the University of Newcastle, said asthma treatment was no longer “one-size fits all”.
“It’s now recognised that one treatment for all asthmatics is not going to work. The take-home message is that you need to put patients into specific subgroups and then target the treatment to the molecule that’s causing the problem in that group.”
He said the current research on interleukin-13 had developed from basic science studies on the role of the molecule in asthma using mice models more than 10 years ago.
Conjoint Professor Peter Gibson, NHMRC practitioner research fellow at the University of Newcastle, said lebrikizumab was part of the “next wave” of treatments for severe asthma.
He said the research was reassuring for severe asthma patients, who currently had limited treatment options.
“There have been a lot of advances for mild to moderate asthma. The gap is in treatments for severe asthma. We need new approaches, and that’s what’s exciting about this class of drug.”
– Sophie McNamara
1. NEJM 2011; 3 August (online)
Posted 8 August 2011
This does not really come as any surprise. I remember way back in my early GP years having what one might call an epiphany when it comes to the understanding of asthma – why some have it, why most don’t, and why it did not die out of our species if it was all a negative thing – when a colleague, during a discussion about childhood asthma, commented “it is almost like the bronchospastic response is akin to a ‘pulmonary flinch'”. Wham…! Right there I got it. It does have survival value. It is the protective filter the lungs have which gives them the ability to filter out ‘nasty’ stuff in the air, which the body perceives as potentially harmful. That’s why natural selection did not elliminate it, and that’s, of course, why people basically only died of staus asthmaticus AFTER the development of the b-sympathomimetics, (adrenaline analogues), which only removed natures filter, without addressing the underlying allergic inflammation that triggered that response. Suddenly the whole logic of what to use, when, why and in what order, made sense, and as soon as I started teaching this to my patients, they started only ever needing to see me for rpt scripts. The explanation then as to who gets asthma and why lies in the yet to be ellucidated issue of why the body in some cases identies non-assailants (allergens) as potential enemy, and “tries to keep it out”. This is also why steroids, which block the allergic inflammatory pathway, work… and that is why Singulair works also, so this new drug, which is an antibody also acting at an even different place on the pathway should also work – how well is another matter.