Identifying Predictors Of Response To Mepolizumab In CRSwNP
Status:
Not yet recruiting
Trial end date:
2026-12-31
Target enrollment:
Participant gender:
Summary
The investigators propose a real-world study to assess the mechanism of action of
long-lasting response to mepolizumab in patients with chronic rhinosinusitis with nasal
polyposis (CRSwNP) and identify clinically useful predictors of response.
Mepolizumab is a monoclonal antibody targeting IL-5 and is approved for use in asthma and
CRSwNP. In clinical studies, 12 months of treatment with mepolizumab improved signs and
symptoms of CRSwNP and reduced the need for surgery. While several biologic medications
targeting facets of the Type 2 mechanism are currently indicated for chronic rhinosinusitis
with nasal polyps mepolizumab alone appears capable of modifying the disease's biological
behaviour and producing long-standing improvements after the cessation of treatment. In the
mepolizumab for CRSwNP regulatory trial (SYNAPSE), a subset of patients experienced dramatic
and long-lasting, which is over 48 months after cessation of administration of the
investigational medicinal product (IMP) in our experience. This has been partially captured
in a follow-on study to the registration trail, which showed that a subset of patients
followed for 24 weeks after cessation of biologic therapy (with continued use of mometasone
furoate) demonstrated persistent improvements over baseline.
However, the mechanism of the long-lasting effect in a subset of patients is not well
understood, and it is impossible currently to identify patients who will derive this maximal
benefit. The mechanism for the prolonged improvements in CRSwNP seen in certain patients with
mepolizumab remains to be established but suggests that effects beyond eosinophil trafficking
are implicated.
The investigators believe that mepolizumab has IL-5-mediated pleiotropic effects which
contribute to disease modification with effects extending beyond eosinophil activation and
trafficking. This may include the following primary or secondary effects:
i) Improving epithelial barrier function ii) Altering mast cell dynamics iii) Reversing
epigenetic modifications iv) Altering the immune response to better clear pathogenic bacteria
or viruses.