Current and emerging pharmacotherapy for chronic spontaneous Urticaria: a focus on non-biological therapeutics

ABSTRACT

Introduction

Chronic spontaneous urticaria (CSU) refers to urticaria (wheals) or angioedema, which occur for a period of six weeks or longer without an apparent cause. The condition may impair the patient’s quality of life.

Areas covered

Treatment for CSU is mainly symptomatic. Both AAAAI/ACAAI practice parameters and EAACI/GA2LEN/EDF/WAO guidelines suggest CSU management in a stepwise manner. First-line therapy is with second-generation H₁-antihistamines. Treatment should be stepped up along the algorithm if symptoms are not adequately controlled. Increasing the dosage of second-generation H₁-antihistamines, with the addition of first-generation H₁-antihistamines, H₂ antagonist, omalizumab, ciclosporin A, or short-term corticosteroid may be necessary. New medications are being developed to treat refractory CSU. They include spleen tyrosine kinase inhibitor, Bruton tyrosine kinase inhibitor, prostaglandin D₂ receptor inhibitor, H₄-antihistamine, and other agents. The authors discuss these treatments and provide expert perspectives on the management of CSU.

Expert opinion

Second-generation H₁-antihistamines remain the first-line therapeutic options for the management of CSU. For patients not responding to higher-dose H₁-antihistamines, international guidelines recommend the addition of omalizumab. Efficacy and safety data for newer agents are still pending. Large-scale, well-designed, randomized, double-blind, placebo-controlled trials will further provide evidence on the safety profile and efficacy of these agents in patients with CSU.

KEYWORDS:

• Antihistamines
• angioedema
• hives
• idiopathic
• omalizumab
• wheals
• pruritus

Article highlights

• Guidelines recommend a stepwise approach in treating CSU. Treatment aims at symptomatic relief, which means stepping-up or stepping-down according to the disease course.

• Second-generation H₁-antihistamines are the first-line therapy for CSU. Other agents are used as add-ons to it.

• Omalizumab has demonstrated good efficacy and safety profile in multiple RCTs. It is recommended by guidelines for use in CSU patients not achieving adequate response to antihistamines.

• Spleen tyrosine kinase inhibitor, Bruton tyrosine kinase inhibitor, and CRTh2 inhibitor are new agents targeting inflammatory pathways that may be effective in CSU.

• New studies focus on identifying receptor targets or pathways that are involved in CSU pathogenesis.

This box summarizes the key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One referee is a Medical Advisor for Uriach Pharma, Genentech, Novartis, FAES, GlaxoSmithKline and Sanofi. They have also received research grants from Uriach Pharma and Novartis as well as grants from the Instituto Carlos III-FEDER. The same referee has also undertaken Educational activities supported by Uriach Pharma, Novartis, Genentech, Menarini, LEO Pharma, GlaxoSmithKline, Merck Sharp and Dohme, Almirall and Sanofi. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.