Effect of Reslizumab on small airways in asthma. RESSAPEA

Reslizumab is an approved humanized monoclonal antibody developed to target
interleukin-5 (IL-5). IL-5 is a key cytokine shown to play a crucial role in
the maturation, activation and survival of eosinophils. Increased levels of
eosinophils in the sputum an blood have been shown to positively correlate with
disease severity and increased risk of asthma exacerbations. Reslizumab acts by
binding circulating IL-5 and preventing it from interacting with its receptor.
Clinical studies have shown that Reslizumab significantly reduced the rate of
asthma exacerbations and improved lung function and quality of life in a
specific group of patients with elevated eosinophil levels. However, the
mechanism of Reslizumab action in asthma has not been definitively established.
We hypothesized that the beneficial effect of Reslizumab in patients with
severe eosinophilic asthma is primarily explained by improvement in small
airways function and associated air trapping.

To investigate the effect the effect of a 3-months treatment with Reslizumab on
small airways function in patients with severe eosinophilic asthma, and to
relate the changes in small airway function to changes in asthma symptoms and
quality of life.

This is a double-blind, randomized, placebo-controlled single centre
intervention study in patients with severe eosinophilic asthma . Patients will
be randomized according to a 2:1 schedule. The total number of participants
will be 33. (11 patients in the placebo arm and 22 patients in the active
arm).

Patients will receive Reslizumab (n=22) or placebo (n=11) administered
intravenously every 4 weeks for 3 consecutive months.

Intravenous administration of Reslizumab has a small risk of hematoma. This
will be reduced by the fact that we will work with trained and capable
healthcare professionals.
To our opinion the burden of all pulmonary function test will be the same
compared with the same tests patients are performing during a standard of care
session.
For this study we consider the patients will be on moderate risk.
HRCT scans will be performed at screening and at the end of the study. Although
this will be an extra burden for the patients, the risks can be compared with
two normal X-rays..
With the information collected during the study it will be possible to
evaluate whether or not small airways dysfunction predicts a positive response
to anti IL-5 treatment, which will contribute to improved therapy in patients
with severe asthma