Treatment optimisation in chronic urticaria and angioedema

Abstract

This thesis offers new insights into the pathogenesis and management of chronic urticaria (CU), including angioedema, and suggests possibilities for a more personalized treatment approach. Using drug-survival analysis, we found that omalizumab treatment in adults and children was mainly discontinued due to well-controlled disease. Ineffectiveness or side effects are rare reasons for discontinuation, demonstrating the high effectiveness and safety of omalizumab in the treatment of CU in daily practice. In patients with a good or complete response, omalizumab treatment intervals can be extended from the standard of 4 weeks to 7 weeks (median) or longer. In patients with an insufficient treatment response to omalizumab with the standard dose of 300 mg, an increase in the dose up to 600 mg led to a significant improvement in 61% of patients. The exact pathomechanism of CU and the exact mechanism of action of omalizumab remain unknown. We found that FcεRI expression on basophils decreased significantly after omalizumab administration, while anti-IgE-induced degranulation increased significantly. Additionally, we demonstrated complement component C4d deposition in affected skin and elevated blood levels of C5a in CU patients. None of the findings regarding the complement system or FcεRI expression, however, could be related to omalizumab treatment response. Angioedema might occur, with or without wheals, and is highly manageable in the majority of patients without prophylactic therapy or with antihistamine monotherapy. Fourteen percent required add-on treatment with omalizumab or other drugs. In patients with angioedema without wheals, recombinant human C1 esterase inhibitor treatment might be a treatment option when omalizumab has failed.