Anti-IgE for the Treatment of Chronic Urticaria

Abstract

Urticaria and angioedema are very common. Management of chronic urticaria subtypes, which usually persist for many years, is challenging. Recent years have demonstrated that targeting IgE with antibodies provides a safe and efficient treatment approach. Whilst several anti-IgE antibodies have been developed, omalizumab is currently the only one approved for use. International and national guidelines recommend its use after failure of antihistamines at standard and increased dose. Whilst not yet approved, many new anti-IgE approaches are currently being investigated in pre-clinical studies or clinical trials. This non-systematic focused review summarizes current knowledge of omalizumab and other anti-IgE biologics in chronic urticaria using data extracted from PubMed, Google Scholar and clinical trial databases, clinicaltrials.gov and clinicaltrials.eu. For adults, there is good evidence from randomized clinical trials and real-world data that symptomatic treatment with omalizumab is efficacious and safe in chronic spontaneous urticaria (CSU), whereas evidence in chronic inducible urticaria (CINDU) and special populations is limited. Easy-to-use tools to identify non-responders and predict the required duration of treatment have not been established yet. Phase 2 b results of ligelizumab have not only demonstrated efficacy and safety but also superiority to omalizumab. Indeed, there is preliminary evidence that omalizumab non- or partial responders benefit from ligelizumab. Whereas further development of quilizumab was discontinued, other approaches, eg UB-221 or DARPins are under investigation. Anti-IgE treatment with omalizumab represents a landmark in the treatment of chronic urticaria, with and without angioedema, and there is light on the horizon suggesting success may come with various next-generation anti-IgE approaches.

IgE and high‐affinity IgE receptor in chronic inducible urticaria, pathogenic, and management relevance

“…For adults, there is good evidence that omalizumab is efficacious in CSU, with it having a notable effect on basophil FcεRI receptor density 9–11,31 . Clinical evidence in CIndU is not as extensive, and based on small samples, but it is increasing 32–34 . The current literature is slightly contradictory, with some articles postulating that omalizumab shows less efficacy in CIndU compared to CSU, but this has not yet been addressed systematically, 34 while others support the use of omalizumab in the treatment of patients with antihistamine treatment‐resistant CIndU 33 .…”

“…Clinical evidence in CIndU is not as extensive, and based on small samples, but it is increasing 32–34 . The current literature is slightly contradictory, with some articles postulating that omalizumab shows less efficacy in CIndU compared to CSU, but this has not yet been addressed systematically, 34 while others support the use of omalizumab in the treatment of patients with antihistamine treatment‐resistant CIndU 33 . Contrary to what was observed when differentiating patients according to the antihistaminic response, total IgE serum levels and disease severity did not show significant differences according to the response to omalizumab in patients with CIndU, though higher baseline FcεRI levels in responders to omalizumab versus non‐responders was observed.…”

“…[9][10][11]31 Clinical evidence in CIndU is not as extensive, and based on small samples, but it is increasing. [32][33][34] The current literature is slightly contradictory, with some articles postulating that omalizumab shows less efficacy in CIndU compared to CSU, but this…”

Contemporary Grand Challenges and Opportunities in Skin Allergies

“…The ligelizumab phase III trial program ( Table 1 ) will have to confirm the promising results of the phase II trial ( 3 ) demonstrating superiority compared to omalizumab. Prospective clinical trials including CINDU subtypes and angioedema without wheals, but also including special populations, i.e., children and adolescents, elderly, obese patients, and patients with concomitant immunosuppressive or biological treatment or with cancer are required to approve efficacy and safety of omalizumab and other anti-IgE therapies ( 4 ). In addition, as of now, easy-to-use tools to identify non-responders, to predict the required duration of treatment and consented strategies on how to wean anti-IgE therapy are lacking.…”

“…In addition, as of now, easy-to-use tools to identify non-responders, to predict the required duration of treatment and consented strategies on how to wean anti-IgE therapy are lacking. Additional anti-IgE approaches such as UB-221 and DARPins are under investigation ( 4 , 5 ). DARPins are able to neutralize free IgE and actively dissociate pre-formed IgE:FcεRI complexes.…”