Markers of Efficacy of Xolair (Omalizumab) in Chronic Spontaneous Urticaria

Omalizumab is effective in the treatment of CSU, but the exact mechanism of
action of omalizumab in CSU patients is not fully elucidated so far. Sera from
patients with CSU can induce degranulation of mast cells and basophils, and
during this process the presence of intact complement is essential. The
efficacy of omalizumab in CSU may be caused by influencing complement mediated
inflammation in the skin. Furthermore, it is known that an effect on mast cells
is seen after 1-2 months of treatment. The clinical effect of omalizumab occurs
much faster: within days or weeks. This may indicate that other cell types such
as basophils have a role in the pathogenesis of CSU.

To relate the reduction of inflammatory characteristics in skin and in
peripheral blood to clinical efficacy in patients with CSU. Major focusses of
this study are the (early) effects on basophils and other Fc*RI-bearing
leukocytes before, during, and after treatment with omalizumab in CSU patients.
Additionally, this study is designed to define complement activation and
complement deposition in venous blood and skin, induced by omalizumab.

Exploratory prospective cohort study. All patients will receive 6 doses of 300
mg omalizumab per 4 weeks, followed by a follow-up period of up to 2 months. At
pre-defined time-points venipunctures and biopsies will be performed to
determine the main study parameters.

omalizumab 6 x 300 mg, per 4 weeks

After screening for eligibility and signing informed consent, participants will
be treated with 6 doses of 300 mg omalizumab per 4 weeks, as proven effective
and safe, and as recommended by recent guidelines. During treatment, a total of
4 biopsies of 3mm and 14 venipunctures, of which 5 may be taken from an
intervenous line, will be performed. The study comprises a flexible amount of
9-11 study visits. During these visits, a physical examination is performed,
safety information is collected, and information about concomitant treatment is
collected.
Possible side effects of treatment are sinusitis, headache, or arthralgia.
Anaphylactic reactions are a known adverse reaction in asthma patients treated
with omalizumab, however it is not reported in CSU patients. Nevertheless, when
omalizumab is administered, a pre-defined observation time is maintained,
during which patients fill in questionnaires regarding quality of life (four
times) and disease control (every 4 weeks). Disease activity is measured daily
throughout the study. A follow-up period of up to two months is maintained.