irst published 14 November 2016
Approved indication: asthma
Nucala (GlaxoSmithKline)
vials containing 144 mg powder for reconstitution
Australian Medicines Handbook section 19.1.6
Some patients with
asthma have severe disease that is not well controlled by inhaled treatments.
They may require regular oral corticosteroids to control airway inflammation.
In some patients there can be high concentrations of IgE which may respond to
treatment with omalizumab. Other patients have high concentrations of
eosinophils so these cells are potential targets for new drugs such as
mepolizumab.
The life cycle of
eosinophils is controlled by interleukin 5. This cytokine may be overproduced
in patients with eosinophilic asthma. Mepolizumab is a humanised monoclonal
antibody that binds to interleukin 5. This prevents interleukin 5 from binding
to its receptors on the surface of eosinophils. A dose of mepolizumab will
reduce eosinophils by at least 50%.
As mepolizumab is an
immunoglobulin (IgG) it has to be given by injection. When reconstituted with
water for injection, the powder forms a solution with a strength of 100 mg/mL.
The usual dose is 100 mg injected subcutaneously every four weeks. After
injection into the arm the bioavailability is 74–80%. The peak concentration is
reached in 4–8 days and the terminal half-life following metabolism is 16–22
days. There have been no formal studies of hepatic or renal impairment or of
drug interactions.
The Cochrane Airways Group
has reviewed eight trials comparing mepolizumab with placebo in 1707 patients.
Due to the heterogeneity of the studies the role of mepolizumab was uncertain,
but it did reduce exacerbations and improve health-related quality of life in
patients with severe eosinophilic asthma.1
One of the studies in
the review randomised 621 patients with eosinophilic inflammation to
intravenous infusions of placebo or mepolizumab 75 mg, 250 mg or 750 mg.
Thirteen infusions were given at four-week intervals. Mepolizumab significantly
reduced the numbers of eosinophils in the blood. There were 806 asthma
exacerbations which required treatment with oral steroids. Compared to placebo
the number of exacerbations per patient per year was reduced significantly by
all doses of mepolizumab. For example, there was a 48% reduction with the 75 mg
dose.2
A subcutaneous regimen
was included in a trial involving patients with severe eosinophilic asthma who
had experienced at least two exacerbations of asthma in the previous year. Treatment
was given every four weeks for 32 weeks. There were 449 exacerbations. In the
194 patients assigned to receive mepolizumab 100 mg subcutaneously, the annual
exacerbation rate was 0.83 compared with 1.74 in the 191 patients assigned to
placebo.3
Another trial assessed
whether subcutaneous mepolizumab can reduce the amount of oral corticosteroids
consumed by patients with severe eosinophilic asthma. The 135 patients in the
trial had been taking 5–35 mg of prednisone or equivalent for at least six months.
After injecting mepolizumab or a placebo every four weeks for 20 weeks their
use of corticosteroids was reassessed. The median reduction from their baseline
dose was 50% for the patients taking mepolizumab. There was no reduction in the
placebo group. The annual exacerbation rate was 1.44 with mepolizumab and 2.12
with placebo.4
Safety information is
available for 1018 patients who took mepolizumab 100 mg subcutaneously. Common
adverse events were headache and nasopharyngitis. Injecting an antibody can
cause hypersensitivity reactions which may have a delayed onset. Approximately
6% of patients developed antibodies against mepolizumab. Injection site
reactions affected 8% versus 3% of the placebo group. As eosinophils have a
role in the immune response, mepolizumab may alter the response to parasitic
infections. Although there were only a few cases of herpes zoster, two of them
were serious. There is currently no information about the drug’s safety in
pregnancy, lactation or in children younger than 12 years.
The optimum use of
mepolizumab is yet to be determined. Not all patients benefit, for example 36%
were unable to reduce their dose of oral corticosteroid, withdrew from
treatment or had a lack of asthma control.4 Some of the patients suitable for
treatment with mepolizumab may also qualify for treatment with omalizumab so
the treatments should be compared. If a patient with severe refractory
eosinophilic asthma is prescribed mepolizumab, how long should they take it
for? A follow-up of some of the patients in the trials found that after
stopping treatment there was a rise in eosinophil count and an increase in
asthma symptoms and exacerbations.5
