Jiaci

J Investig Allergol Clin Immunol 2019; Vol. 29(5): 399-400

doi: 10.18176/jiaci.0414

LETTERS TO THE EDITOR

Selection of Biologics for Severe Type-2 Asthma

Yilmaz I

Erciyes University School of Medicine, Department of Chest

Diseases, Division of Immunology and Allergy, Kayseri, Turkey

J Investig Allergol Clin Immunol 2019; Vol. 29(5): 399-400

doi: 10.18176/jiaci.0414

Key words:

Severe asthma. Atopy. Eosinophil. Nasal polyp. Biologics.

Palabras clave:

Asma grave.Atopia. Eosinófilo. Pólipo nasal. Biológicos.

To the Editor:

We read with great interest the report of Sanchez-Jereno

et al [1], who reported the first case of severe uncontrolled

allergic eosinophilic asthma with the failure of 2 biological

therapies (anti-IgE and anti-IL13 monoclonal antibodies

[mAbs]) and marked improvement with anti-IL5 mAb. We

would like to thank Sanchez-Jereno et al for their contribution

to the literature with a case report that suitably addresses the

selection of biologics in severe asthma. We would also like to

share our clinical experience and opinions on this case report.

The authors state that although several biologics have

been approved for uncontrolled severe asthma, no specific

biomarkers have been developed to predict a good response

to these biologics. However, in the GINA severe asthma

guideline published at the end of 2018, suggestions were made

on which biologics should be given for the type-2 high asthma

phenotype, and it was emphasized that factors determining the

response to treatment should be taken into consideration [2].

Therapy should start with anti-IL5/anti-IL5RmAbs in patients

with uncontrolled severe asthma and a blood eosinophils ≥300/

µL. The factors that may predict a good response to anti-IL5/

anti-IL5R biologics are as follows: (

) higher blood eosinophil

counts (strongly predictive), (

) more frequent severe

exacerbations during the previous year (strongly predictive),

(

) adult-onset asthma, and (

) nasal polyposis (treated with

maintenance oral corticosteroids [OCS]). Anti-IgE should be

started in patients with uncontrolled severe asthma who are

sensitized to inhaled allergen(s) in skin prick testing or specific

IgE. The factors that may predict a good response to anti-IgE

mAb are as follows: (

) blood eosinophils ≥260/µL, (

) FeNO

≥20 ppb, (

) allergen-driven symptoms, and (

) childhood-

onset asthma. The issue to be discussed here is the approach

to be adopted if the characteristics that determine the choice

of treatment coincide in some patient groups, as in the case

reported by the authors. The patient, who had a type-2 high

asthma phenotype, was treated with anti-IL5 mAbs because he

had late-onset asthma, nasal polyps, and high eosinophilia. The

patient was also given anti-IgE therapy because of atopy and

blood eosinophils ≥260/µL. However, what is important here

is whether the patient’s atopy status is really appropriate, given

the clinical history (childhood allergic asthma, comorbidities

such as atopic dermatitis/allergic rhinitis, and respiratory

symptoms with exposure to aeroallergens). We think that

starting anti-IgE therapy based only on atopy (determination

of positivity with skin prick testing and/or determination of

specific IgE to common aeroallergens) may not be the ideal

approach and that the clinical history should be taken into

consideration. In this case, the first-choice biological agent

should be an anti-IL5/anti-IL5RmAb owing to the presence of

strong predictive markers suggesting a good response to mAbs,

such as higher blood eosinophil counts and a higher number

of severe exacerbations in the previous year, as well as other

predictors such as nasal polyps, late onset, and dependence

on OCS [2,3].

Unfortunately, strong evidence for the comparative efficacy

and effectiveness of biologics in severe asthma is lacking, since

there are no head-to-head studies comparing anti-IgE and anti-

IL5/anti-IL5R therapy. Data from recent reports on the selection

of biologics for severe asthma screened using biomarkers,

as well as the GINA recommendations [4-7], indicate that if

the main clinical target is to reduce the maintenance dose

of OCS, omalizumab should not be the first-choice biologic

in patients with OCS-dependent severe eosinophilic asthma

[4], because there are no clear data to support reducing OCS

in patients treated with omalizumab. However, decreasing

the total use of OCS has been shown to facilitate complete

weaning from chronic OCS (14%-50%) in patients treated

with anti-IL5/anti-IL5R mAbs [4,8]. In fact, some patients

with eosinophilic asthma require sustained use of OCS to

maintain disease control. In any case, long-term use of OCS is

associated with significant adverse effects. Bel et al [9] showed

that mepolizumab led to a 50% reduction in OCS dosage in

patients with eosinophilic asthma taking chronic OCS. The

effects of reduced exacerbations and improved asthma control

were maintained despite the reduction.

In eosinophilic asthma with chronic nasal polyposis,

the most appropriate biologic would be an anti-IL5/anti-

IL5R mAb, since the main mechanisms are dysregulation

of leukotriene synthesis and chronic epithelial damage and

activation by agents such as superantigens and environmental

pollutants, which release epithelial cell-derived cytokines such

as TSLP, IL-25, and IL-33. These cytokines stimulate type-2

innate lymphoid cell activation, which leads to overproduction

of IL-5[10-12]. In our clinic, we also prefer anti IL5/anti-IL5R

as the first-choice mAb in severe eosinophilic asthma (atopic

or nonatopic) with nasal polyposis [13].

In conclusion, current or future biologics for severe type-

2 high asthma should be chosen wisely following logical

recommendations, which can currently be made based on

the mechanisms of action of the drugs and the underlying

pathophysiology of various asthma phenotypes. Unfortunately,