Pharmacokinetics and immunological aspects in nasal polyp patients treated with biologics: a pilot study

Chronic rhinosinusitis with nasal polyps is an inflammatory disease of the
upper airways. Common complaints are nasal congestion, rhinorrhea, postnasal
drip, a loss of smell, headaches and involvement of the lower airways. Until
recently, treatment options were limited to local and oral steroids, and
surgery when medical treatment was insufficient. Due to the chronic and
sometimes recalcitrant nature of the disease, result outcomes can be very
disappointing. Since 2020, we are able to prescribe biologics for this disease,
with excellent results. At the moment these biologics include dupilumab,
omalizumab and mepolizumab, which respectively suppress IL4R signalling, IgE
mediated allergy and IL-5 function. Resulting modulation of type 2 helper T
cell driven immune response, allergic response and eosinophilic granulocyte
function may contribute to efficacy of treatment. In most patients, polyps
shrink fast and even smell can return already a few days after the first
injection. The outcome is far better than we could achieve in the past.
Downside is the high costs of the treatment, which has led to defining
inclusion criteria for the initiation of biologics. These include age >= 18, a
history of previous (extensive) sinus surgery, and 3 out of 5 of the following
criteria: signs of eosinophily, anosmia, SNOT22 questionnaire >= 40 (symptom
score, part of the attachments), a chronic need for oral steroids, and the use
of inhalation corticosteroids.
As this is a relatively new treatment within patients with chronic
rhinosinusitis with nasal polyps, there is no extensive knowledge of its
underlying immunological mechanisms and their potential contribution to
efficacy of treatment as indicated above. In this pilot study, we aim to
investigate the effects of biologics on the immunologic and allergic response
associated with CRSwNP and correlate them with subjective patients outcome. We
also plan to investigate dose-response relationship between serum levels of
biologics and efficacy of treatment in order to determine an optimal
therapeutic window of biologic treatment.

Primary objective:
To investigate the dose - (clinical) response relationship and therapeutic
window of biologics in the treatment of CRSwNP.

Secondary objectives:
- To investigate the effect of biologics on the sensibilisation pattern of
specific IgE and its relationship with (clinical) treatment outcome.
- To investigate the effect of biologics on type 2 T helper and regulatory T
cells, and its relationship with (clinical) treatment outcome.

This pilot study will take approximately 3 years to complete: 2 years of
inclusion, last blood withdrawal is 12 months after final inclusion. It will be
an observational cohort study, in which the following data will be gathered:
- the completion of the SNOT22 questionnaire(5) and Asthma Control Test(6) (in
case of asthma or the use of inhalation corticosteroids)
- smelling test
- fiberendoscopic evaluations of the nose
- blood test: eosinophils and total IgE
All of the above procedures are currently part of the standard diagnostic
procedures in the treatment of CRSwNP patient. For study purposes, during the
regular blood testing (time points: before treatment, and at 1, 3, 6 and 12
months after initiation of treatment; extra blood sampling will be done when
clinically required, i.e. when eosinophils are increased), we will take an
extra 3 tubes of blood.

The results of this study are not directly beneficial to the subject, although
this may be so in the future, depending results. The risks associated with
participation can be considered negligible and the burden minimal, as patients
are not subjected to any additional activities outside the regular standard of
care.