Targeting anti-IL-13 in asthma
Published Online: May 31, 2013
Lebrikizumab, an anti-IL-13 monoclonal antibody, has been reported to significantly improve lung function in asthma patients who are symptomatic despite inhaled corticosteroid (ICS) therapy. However, as ICS inhibits IL-13 there is a need to understand the effect of lebrikizumab without the confounding effects of ICS.
In a study recently published in The Journal of Allergy and Clinical Immunology (JACI), Noonan et al. investigated the effect of lebrikizumab in a population of patients with moderate asthma who were not receiving ICS. Results from the study provide valuable insight into the heterogeneous nature of asthma and the need to target lebrikizumab to patients with asthma that is driven by IL-13 despite ICS treatment. All patients in the study had reduced lung function and β-agonist reversibility of at least 15%, suggesting they had the capacity to show improvements in lung function. Lebrikizumab did not significantly improve lung function compared with placebo. However, a smaller proportion of patients receiving lebrikizumab needed to initiate ICS treatment compared with patients receiving placebo. There were no apparent differences in efficacy between doses of lebrikizumab, indicating that the maximum effect of IL-13 inhibition in this population was achieved with the lowest dose (125 mg). As previously shown, lebrikizumab significantly reduced levels of fractional exhaled nitric oxide (FeNO), suggesting that it substantially inhibited airway inflammation.
These findings show that anti-IL-13 therapy is most effective in symptomatic asthma patients despite ICS therapy who have high serum-periostin levels and that blocking IL-13, a single cytokine, in patients not receiving ICS is insufficient to improve FEV1 compared with existing treatments. These disparate findings in patients receiving vs. not receiving ICS raises questions as to the selection of patients with residual IL-13 activity despite ICS and the interaction between the effects of IL-13 inhibition and steroid treatment, particularly in terms of lung function. In the current study, lebrikizumab provided a notable protection against treatment failure, suggesting that the FEV1 endpoint may reflect a different pathophysiology than worsening symptoms or exacerbations.
Patient selection will be critical to direct lebrikizumab to those who can benefit significantly. The serum-periostin assay was not available for patient stratification at the time of randomization, which may be important given the relatively small FEV1 increase that was seen in this study. These findings provide further evidence that asthma is a complex disease with marked heterogeneity in its clinical course and response to treatment and new interventions will need to be effectively targeted at the population most likely to respond. Understanding the complex and varied pathophysiology of the disease as well as the potential interactions between concomitant treatments is vital for future research and clinical practice.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.