Predicting individual effectiveness of biologics in severe asthma

Choosing a biological treatment for asthma requires the presence of exacerbations or necessity of daily oral corticosteroids (OCS). The use of special predictors of the efficaciousness of different modes of action can help to tailor treatment [1].

“To diagnose severe asthma is actually the most challenging part of identifying patients for biological treatments,” said Prof. Celeste Michala Porsbjerg (Bispebjerg-Frederiksberg University Hospital, Denmark) [1]. As a first step, it is essential to distinguish difficult-to-treat asthma from severe asthma by systematically evaluating all factors that may contribute to poor asthma control like deficient adherence or untreated comorbidities [2-4]. A very recent study found that the systematic assessment of patients within a group of high-dose treated asthma revealed only 12% with severe asthma and 88% difficult-to-treat asthma, with a possibly substantial rate of overlap of patients suffering from severe asthma but having contributing causes on top [5]. Thus, before choosing a biological, it is important to treat the comorbidities that can be found in most patients with severe asthma, as this might already increase symptom control [4]. “We don’t know how well the biological will work in a patient with untreated comorbidities, but possibly not as well as if they are managed,” stated Prof. Porsbjerg.

Regardless of the specific choice of biologic treatment, the agents will exert their clinical effects mainly in the form of decreased exacerbations and lowering the use of OCS. “For all biologics we can, certainly in individual patients, see very good effects on lung function and symptom control, but we cannot promise our patients that we will see an effect,” stressed Prof. Porsbjerg.

An anti-IgE therapy is indicated in the case of perennial allergy on top of the prerequisite for all forms of biologic treatment in patients with severe asthma, i.e. exacerbations or daily use of OCS [6]. Highly symptomatic patients exhibiting low lung function without exacerbations or daily OCS do not constitute an indication for biologicals [1]. Predictors of efficacy of anti-IgE treatment are high levels of eosinophils and fractioned exhaled nitric oxide (FeNO) as well as allergic rhinitis and childhood onset of asthma [6]. To receive anti-IL-5 therapy, a patient should have elevated levels of eosinophils together with the abovementioned prerequisites. A reduction in eosinophils can be seen as a biomarker of effectiveness of anti-IL-5 that may be predicted prior to treatment by adult onset of asthma, high rates of exacerbation, and levels of eosinophils, along with nasal polyposis [6]. Finally, anti-IL-4 receptor (IL-4R) therapy reduces IgE and FeNO, as anti-IL-4R affect the IL-13 pathway [6]. Thus, FeNO and eosinophil levels can also serve as prognosticators of effective treatment.

Prof. Porsbjerg concluded that knowledge and inclusion of the specific predictors of clinical effects should play a key role pre-biologic therapy assessment [1].

 

1. 
   
   1. Porsbjerg C. Identifying patients with severe asthma that will be benefit from biological therapy. Abstract 4202, ERS International Virtual Congress 2020, 7-9 Sept.
   2. Chung KF, et al. Eur Respir J. 2014;43:343-73.
   3. Hew M, et al. J Allergy Clin Immunol Pract. 2020;8:2222-2233.
   4. Porsbjerg C, et al. Respirology. 2017;22:651-661.
   5. Von Bülow A, et al. Respir Med. 2018;145:41-47.
   6. Holguin F,et al. Eur Respir J. 2020;55:1900588.

Posted on 29 October 2020