Current and future therapies for treating chronic spontaneous urticaria

ABSTRACT

Introduction: Chronic spontaneous urticaria (CSU) is a disabling condition that causes deterioration of quality of life.

Areas covered: The international EAACI/GA²LEN/EDF/WAO guidelines have provided a stepwise treatment algorithm for CSU management. Second-generation H₁-antihistamines are the first-line treatment, and the second step is the up-dosing of the same drugs. In refractory patients, the guidelines recommend the addition of omalizumab, ciclosporin A or montelukast. Systemic corticosteroids can be used as a short course during acute exacerbations. A plethora of alternative treatments has been evaluated, although the overall level of evidence for such treatments is low. Future treatment options may include inhibitors of skin mast cells and antagonists to mast cell-activating signals that are relevant for the induction of CSU signs and symptoms.

Expert opinion: The only licensed options included in the guidelines algorithm are standard-dosed second-generation H₁-antihistamines and omalizumab. High-quality evidence has documented a rapid and strong symptomatic effect of omalizumab in CSU, although the optimal long-term regimens should be further investigated. The role of alternative drugs deserves additional studies. The potential of the existing treatments for inducing remission of CSU is unknown, and this is an important area of research, as is the evaluation of predictors of response, prognostic factors, and pathomechanisms.

KEYWORDS:

• Alternative drugs
• antihistamines
• chronic spontaneous urticaria
• ciclosporin
• montelukast
• omalizumab

Article highlights

• The EAACI⁄GA²LEN⁄EDF⁄WAO guidelines recommend sg-AHs as the mainstay of treatment of CSU, and up-dosing of these drugs as second-line treatment.

• In refractory patients, the third-line treatment suggested by the guidelines consists of the addition of one of the following drugs: omalizumab, ciclosporin A, or montelukast.

• Omalizumab is the only drug approved for treatment of CSU in patients with inadequate response to AHs.

• Long-term use of systemic corticosteroids should be avoided, while a short course can be tried to manage acute exacerbations.

• Several alternative therapies have been evaluated in severe recalcitrant cases, but the level of evidence for such approaches is low and their role deserves further studies.

• Novel agents are under investigation and future options may include inhibitors of skin mast cells and antagonists to mast cell-activating signals.

This box summarizes key points contained in the article.

Declaration of interest

M Maurer is or recently was a speaker and/or advisor for FAES Farma, Almirall Hermal, Genentech, GlaxoSmithKline, Merckle Recordati, Novartis, Sanofi Aventis, Schering-Plough, Merck Sharp & Dohme, Merck, Moxie, Takeda, UCB Pharma, and Uriach.

G A. Vena has been a speaker and/or a scientific consultant and/or an advisory board member for Astellas, Abbvie, Janssen-Cilag, Leo Pharma, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, and UCB Pharma.

N Cassano has been a speaker and/or a scientific consultant for Astellas, Abbvie, Leo Pharma, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Rottapharm Madaus, and UCB Pharma.

T Zuberbier is a consultant for the following companies: Ansell, Bayer Schering, DST, FAES Farma, Fujisawa, HAL Allergy, Henkel, Kryolan, Leti, Menarini, Merck, Merck Sharp & Dohme, Novartis, Procter and Gamble, Ranbaxy, Sanofi-Aventis, Schering Plough, Stallergenes, and UCB Pharma. He has the following organizational affiliations: Scientific Advisory Board, German Society for Allergy and Clinical Immunology (DGAKI); Head, European Centre for Allergy Research Foundation (ECARF); Committee member, WHO-Initiative Allergic Rhinitis and its Impact on Asthma (ARIA); Member, World Allergy Organisation Communications Council (WAO); Secretary General, Global Allergy and Asthma European Network (GA²LEN). 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.