is a complex disease marked by the inflammation of the respiratory tract
leading to breathing difficulty. The condition is heterogeneous in its clinical
course and in its response to treatment.
Inhaled glucocorticoids is the standard mode of treatment for asthma.
Glucocorticoids inhibit the production of
Interleukin-13, a pleiotropic cytokine of type 2 helper T cells (Th2),
which is thought to play a role in the onset of asthma.
Nevertheless the disease
remains uncontrolled in many patients.
It has been noticed that patients with uncontrolled asthma continue to have
increased levels of interleukin-13 in
the sputum, despite inhaling
Glucocorticoids. This is in accordance to the hypothesis that interleukin-13
can contribute to Glucocorticoids resistance. Interleukin-13 induces
bronchial epithelial cells to secrete periostin a protein molecule that
has a role in remodeling the airway in asthma patients.
Lebrikizumab is an IgG4 humanized
monoclonal antibody that specifically targets and binds to interleukin-13 and
prevents its function.
A randomized, double-blind, placebo-
controlled, parallel-group, multi-center study was carried out in 219 adults who had uncontrolled asthma despite
being administered with medium-dose to
high-dose inhaled glucocorticoids inhaled glucocorticoid therapy.
The patients were categorized according to baseline
serum periostin level.
Lebrikizumab (at a dose of 250 mg), or a placebo, was administered subcutaneously once a month for a total
of 6 months to the patients. The
placebo comprised of sterile water and
the same excipients as the lebrikizumab formulation.
The results of the study showed
that Lebrikizumab treatment was linked to better lung function. Patients with
greater pre-treatment levels of serum periostin had better improvement in lung
function with the administration of lebrikizumab in comparison to patients with
low periostin levels.
These results further support the evidence of
heterogenous pathogenesis in patients with moderate-to-severe asthma.
The study also reinforces the importance of using
biomarkers to analyze treatment response in patients.
"Lebrikizumab Treatment in Adults with Asthma" Jonathan Corren, M.D., et al NEJM; August 3, 2011