Stepping Down Treatment in Chronic Spontaneous Urticaria: What We Know and What We Don’t Know

Abstract

In chronic spontaneous urticaria (CSU), wheals, angioedema, or both appear spontaneously for > 6 weeks. Current recommended treatment options for urticaria target mast cell mediators such as histamine, or activators, such as autoantibodies. The goal of CSU treatment is to treat the disease until it is gone as effectively and safely as possible. As no cure is available for CSU as of now, the treatment is aimed at continuously suppressing disease activity, with complete control of the disease and a normalization of quality of life. To achieve this, pharmacological treatment should be continued until no longer needed. Treatment of CSU should follow the basic principles of treating as much as needed and as little as possible taking into consideration that the activity of the disease may vary. Since CSU is a disease with spontaneous remission, it is hard to tell, in patients with complete control and no signs or symptoms, when medication is no longer needed. The current international guideline for urticaria suggests that the treatment can be stepped down once a patient is free of signs and symptoms. Other reasons for stepping down the treatment of CSU patients include safety concerns or issues, pregnancy or wanting to become pregnant, and economic factors. As of now, it is unclear over which period, with what intervals and with which dosages CSU treatment should be stepped down. Guidance on this is needed for all recommended therapies: (i) standard-dosed secondgeneration H1-antihistamine (sgAH), (ii) higher than standard-dosed sgAH, (iii) standard-dosed omalizumab, (iv) higher than standard-dosed omalizumab, and (v) cyclosporine. However, there is a lack of controlled trials on the step down and discontinuation of these treatments. Here, we aim to provide a summary of what is known and what needs to be investigated in further studies, based on our own experience and real-world evidence.

A global perspective on stepping down chronic spontaneous urticaria treatment: Results of the Urticaria Centers of Reference and Excellence SDown‐CSU study

“…In patients with a complete response to high dose antihistamine therapy for 3 months, nearly all UCAREs prefer a gradual AH dose reduction. Previous expert reports support this and recommend reducing the daily dose by one tablet every month, with regular monitoring of signs and symptoms 9,10 . Omalizumab is an add‐on treatment to AHs and both treatments should be used together during stepping up.…”

“…The reappearance of symptoms within less than 6 months should be regarded as relapse, whereas it is reasonable to define the onset of urticaria after more than 6 months, especially after 1 year, as a new urticaria episode. In case of disease relapse after discontinuation of the ongoing treatment, retreatment with the same drug is advised by previous studies 9–11,18,19 …”

“…and previous reports recommend stepping down attempts only in patients with completely controlled disease (UCT = 16). 10,19,20 In case of well-controlled disease (UCT≥12), the international urticaria guideline recommends continuing and optimizing the treatment in these patients. 1 However, one third of physicians (35%) reported that they step down omalizumab in patients who did not achieve complete control.…”

“…8,9 Apart from the need to check for spontaneous remission of the disease, other issues such as safety concerns, treatment burden, economic factors, pregnancy, onset of another disease, or intake of a new treatment may necessitate stepping down the treatment of CSU. 10 Over the past decades, there have been significant advancements in the treatment of urticaria. 11 As our knowledge of the pathogenesis of the disease increases, new targeted treatment options are being developed, and the near future of CSU treatment is promising.…”

“…Currently, there is no established biomarker to discriminate between the two 8,9 . Apart from the need to check for spontaneous remission of the disease, other issues such as safety concerns, treatment burden, economic factors, pregnancy, onset of another disease, or intake of a new treatment may necessitate stepping down the treatment of CSU 10 …”