Biologics for chronic spontaneous urticaria: toward a personalized treatment

ABSTRACT

Introduction

Chronic spontaneous urticaria (CSU) is characterized by the recurrent occurrence of short-lived wheals with or without angioedema for more than 6 weeks. Although its pathogenesis is not completely defined, several mechanisms seem involved, including autoimmunity and autoallergy with complement and coagulation activation. Various biologics are currently available or under investigation to counteract different CSU pathomechanisms.

Areas covered

The recent literature dealing with biologics in the treatment of CSU was screened and analyzed; the different treatments were divided into anti-IgE and other than anti-IgE biologics. The latter were subdivided according to their target mechanisms.

Expert opinion

Biologic drugs exert their effects in a very precise and specific manner. A majority of patients (arguably those with type I disease) respond to anti-IgE treatment. Others, possibly with type IIa disease, show a slow response to anti-IgE drugs. Things are much more complicated in anti-IgE-refractory patients. Some respond well to nonspecific immune suppressors, such as corticosteroids and cyclosporin suggesting that an immune-mediated pathogenic mechanism, not involving the high-affinity IgE receptor, is probably active. Several ongoing studies are evaluating biologics and small molecules counteracting other pathomechanisms, including anti-receptor biologics, Bruton tyrosine kinase (BTK) inhibitors, mast cell targets, and specific cytokines.

KEYWORDS:

• Autoallergy
• autoimmunity
• biologics
• chronic urticaria
• biologics
• omalizumab

Article highlights

• In the last decade, several pathogenetic mechanisms of chronic spontaneous urticaria (CSU) have been clarified

• Several biologics are currently under investigation to primarily counteract two CSU mechanisms: autoallergy (type I hypersensitivity) and autoimmunity (type IIb hypersensitivity).

• In CSU control, the only biological treatment licensed so far is the anti-IgE mAb omalizumab.

• Other biologics might be potentially effective in CSU by interfering with other pathomecanisms, particularly in patients refractory to anti-IgE treatment.

Declaration of interest

S Ferrucci is Principal Investigator in clinical trials for AbbVie, Sanofi Genzyme, Amgen, and Lilly. R Asero has been a consultant and speaker for Novartis and Sanofi Genzyme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One peer reviewer has received lecture and/or consultation fees from Taiho Pharmaceutical Co., Novartis, Mitsubishi Tanabe Pharma Co., Kaken Pharmaceutical Co., Sanofi, and Kyowa Hakko-Kirin Co. and received funds for sponsored/joint research from Novartis and Taiho Pharmaceutical Co. Peer reviewers in this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.