Targeted Therapy for Chronıc Spontaneous Urtıcarıa: Ratıonale and Recent Progress

Abstract

Chronic spontaneous urticaria (CSU) is characterized by the presence of wheals, angioedema, or both for at least 6 weeks. It may persist for a long time-up to 50% of the patients have been reported to be symptomatic 5 years after the onset. Some patients can suffer more than one episode of CSU during their lifetime. Considering the recurrences, disabling symptoms, and significant impact on quality of life, proper and effective treatment of CSU is critical. The use of antihistamines (AHs) is still the mainstay of treatment. However, given the low rates of response to AHs (38.6% and 63.2% to standard doses and higher doses, respectively), the complete control of symptoms seems difficult to attain. The use of omalizumab for CSU has been a major breakthrough in the care of patients with CSU. However, the partial response and lack of response to omalizumab in a subgroup of patients, as high as 70% in some studies, make the development of alternative treatments desirable. Ever-increasing knowledge on the pathogenesis is making new target molecules available and enabling drug development for CSU. In addition to drug repurposing as in anti-IL-4/13, IL-5, and IL-17 antibodies, novel targeted therapy options such as ligelizumab and Bruton's tyrosine kinase inhibitors are currently undergoing clinical trials and will be available in the near future. This article reviews the current challenges in the treatment of CSU, the pathogenesis and potential target molecules, and the rationale for novel treatments and their rapidly developing status.

Urticaria

“…Omalizumab is the first in-class anti-IgE monoclonal antibody (mAb) and binds and lowers free IgE, with subsequent downregulation of FcεRI on basophils and mast cells [164][165][166][167] . Lowered FcεRI expression may render the cells less susceptible to activation by IgE and IgG anti-FcεRI and prevent histamine release and inflammation 167 .…”

“…Only some biomarkers of response to treatment are shown 246,259 strategies 176 . Alternative approaches include combination therapy with other systemic immunosuppressives (cyclosporine, dapsone and colchine), although evidence is very limited, or a complete switch to cyclosporine, a third-line treatment of CU 4, 164,177,178 .…”

Chronic urticaria in the real-life clinical practice setting in Portugal: 2-years results from the non-interventional multicenter AWARE study

“…Omalizumab has been a major breakthrough in the care of these patients. 30 The most important factors contributing to the impact of CU in QoL and psychological distress are the severe pruritus and the unpredictability of the disease episodes, 31 as well as the presence of angioedema and concomitant CIndU. Therefore, the impact of CU in the life of patients goes beyond the effects on the skin.…”

Combined treatment with omalizumab and secukinumab in a patient with chronic spontaneous urticaria and psoriasis

“…Many mediators are implicated in CSU pathogenesis and new therapeutic targets are being investigated. 6 The successful results in this case reports suggest that the combined use of biologic therapies can suppress inflammation by targeting different pathways and provide more successful results.…”