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.