A drug that restrains eosinophils, the killer of asthma

Key words: asthma, eosinophils, IL-5

Clinical scientific research is a kind of medical scientific research with patients as the main research object. The basic starting point is to clarify the important issues in etiology, treatment and prognosis of diseases, so as to achieve the purpose of safeguarding human health.
Therefore, clinical and scientific research have always been complementary to each other.

In China, the incidence of asthma among people over the age of 20 is 4.2 percent, and the number of cases has increased to 45.7 million.
Research into an effective treatment for asthma is urgent.
Next, an example of the literature on eosinophil biomarkers by benralizumab in patients with asthma is presented. Learn, with the author, how he has perfected the synthesis of clinical asthma treatment and research, and how he has published an article quickly and easily.

preface

Airway eosinophilic inflammation is a marker of disease severity in individuals with severe asthma, and eosinophilic driven inflammation is associated with mucus hypersecretion, bronchial hyperresponsiveness, and subepithelial fibrosis in asthma patients.
Current studies have shown that treatments that reduce eosinophilic activity can help relieve symptoms in asthmatic patients with persistent eosinophilic increase.

Among various soluble mediators that regulate airway inflammation in asthma, interleukin 5 (IL-5) mediates eosinophil differentiation, proliferation, activation, and survival.
Benralizumab is a humanized, phosphorylated, anti-IL-5RA monoclonal antibody that selectively reduces eosinophils and basophils by enhancing antibody-dependent cell-mediated cytotoxicity.
So, what about Benralizumab in the clinic?

The results of

  1. Baseline characteristics of patients

The phase I study (MI-CP166) included 14 patients with moderate asthma and the phase IIa study (MI-CP197) included 24 patients with mild to moderate asthma.
Three doses of placebo or Benralizumab were given subcutaneously every 4 weeks.
In both studies, baseline FEV1 and total IgE results were not significantly different between the placebo and Benralizumab treatment groups.
However, baseline FeNO was higher in the Benralizumab group compared to the placebo group.

  1. Markers of eosinophilic inflammation increased in asthmatic patients

Serum EDN concentrations were increased in asthmatic patients in the MI-CP166 and MI-CP197 studies compared with healthy volunteers.
There was a linear correlation between serum baseline EDN concentration and blood eosinophils.

Figure 2 Baseline serum EDN concentrations in asthmatic patients and healthy volunteers in the MI-CP166 and MI-CP197 studies (A,B);
Percentage association between serum EDN concentration and FEV1 predicted by MI-CP166 in asthmatic patients (C);
Eosinophil count (D, F)

  1. Eosinophil granulosin decreased after Benralizumab administration

In the MI-CP166 and MI-CP197 studies, blood eosinophil, serum EDN, and serum ECP concentrations were significantly reduced at all time points, regardless of dose, after Benralizumab treatment (25, 100, or 200 mg) compared to baseline.

Figure 3 Serum eosinophils (A, B), EDN(C, D), and ECP concentrations (E, F) of asthmatic patients in the MI-CP166 and MI-CP197 studies.

  1. Increased IL-5, eotaxin, and eotaxin-2 after Benralizumab administration

Serum IL-5 levels increased in both studies compared to baseline in the Benralizumab group compared to the placebo group.
Serum concentrations of eotaxin-2 / CCL24 were significantly increased in asthmatic patients on day 84 after Benralizumab (200 mg) treatment compared to baseline.
In the placebo group, serum chemokine proteins were not significantly regulated at any time point.

Figure 4 Serum concentrations of IL-5(A, B), eotaxin/CCL11(C, D), and eotaxin-2/CCL24(E, F) in asthmatic patients in two studies.

  1. Benralizumab did not regulate other inflammatory proteins

In the MI-CP166 and MI-CP197 studies, serum concentrations of inflammation-related markers IFN-G, IL-17A, TNF, IL-10, IgE, and CTACK/CCL27 remained unchanged or lower than baseline serum concentrations.

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