Chronic spontaneous urticaria
The efficacy of OMZ has been shown in many clinical trials and
summarized in a recent systematic review, which identified 10 randomized
controlled trials (RCTs) with a total of 1620 CSU
patients152. Although most CSU patients respond well
to OMZ, their response to treatment in the clinical setting defined two
endotypes: early responders (usually before week 4), with autoallergic
CSU and IgE AAb , and late responders (after week 4 up to week 24) with
type IIb autoimmune CSU and anti-FcεRI or anti-IgE IgG AAb153. Rapid reduction of free IgE by OMZ in patients
with autoallergic CSU leads to a rapid depletion of IgE AAb and thus a
rapid response to treatment153, whereas a slow
response could be explained by FcεRI downregulation by skin mast cells,
which may take months154, and the action of anti-IgE
IgG AAb on remaining occupied FcεRI 155. Complete
non-response, seen in up to 20% of CSU patients156,
suggests the existence of other endotype(s), with a pathogenesis not
involving IgE or FcεRI152.
LGZ was found to outperform OMZ efficacy, in terms of rate of complete
responders and longer lasting effects, in a multicenter randomized,
controlled, phase IIb study including 382 patients with inadequately
controlled CSU157,158. However, LGZ was not found
superior to OMZ in phase III CSU trials, and the development for CSU was
stopped. LGZ has the same drawbacks as OMZ for the treatment of type IIb
autoimmune CSU and non-autoallergic endotypes. In a phase I clinical
trial with 15 CSU patients, a single dose of UB-221 led to a decrease in
total serum IgE levels and improved disease
symptoms151. Of note, quilizumab, an anti-IgE mAb that
binds only to membrane IgE on B cells (BCR) and not soluble IgE, was
tested in CSU and reduced median serum total IgE levels by 30% at week
20. However, the treatment did not result in meaningful improvements in
disease activity159.