Anti‐IgE for chronic urticaria – are children little adults after all?

Abstract

Omalizumab is a recombinant monoclonal antibody, targeting the epsilon 3 domain of free serum IgE antibodies, and thus preventing their attachment to the cognate high-affinity receptor on mast cells and reducing the number of cell-bound receptors. It represents the first ‘biological’ that has been studied in allergy and was registered several years ago for the treatment of severe allergic asthma in adults and children by the FDA and the EMA. About one year ago, omalizumab was registered for adult patients with chronic spontaneous urticaria – with or without angioedema – which is insufficiently controlled by standard treatment, including high-dose antihistamines. During the last years, international guidelines have profoundly changed our therapeutic approaches to chronic urticarial patients in which, instead of a previously recommended combination treatment with different histamine receptor antagonists, an increase of non-sedating H-1 receptor antagonists of the second generation up to a quadruple dose of the standard recommended regimen is now the general rule (1,2,3,4). These new recommendations have led to a remarkable improvement of response rates seen in urticarial patients; however, by far not all adult patients with chronic spontaneous urticaria are sufficiently controlled even by high doses of antihistamines. The application of omalizumab as a third-line option has demonstrated an unexpected additional benefit and leads to a complete relief of symptom in almost all treated patients. All three of the pivotal phase III studies in adults have led to a recommended dose of 300 mg omalizumab in 4 weeks, which differs from dose regimens for allergic asthma, where the patient's body weight and the total serum IgE levels determine the omalizumab dose. It seems that with the novel treatment option the vast majority of all adult patients with chronic spontaneous urticaria are adequately controlled without major safety problems, which is a remarkable step forward in the long-term treatment of urticaria. The problems of chronic urticaria in childhood seem to be inadequately perceived, which may be due to its low prevalence compared to adults. Until recently, the natural course of CU has not really been studied in large cohorts of children. A recent prospective study from Thailand suggests that chronic urticaria in children has a more favorable outcome than in adults, with a remission rate of 18.5% after one year and 54% after 3 years 5. Like adults, more than 30% of the children with a chronic spontaneous urticaria were found to have autoantibodies to the alpha subunit of the high-affinity IgE receptor (Fc-epsilon-R 1) and/or anti-IgE antibodies. The presence of these autoantibodies may be screened for by performing the autologous serum skin test (ASST). Up to now, the intervention with the recombinant monoclonal antibody omalizumab has been studied in childhood only for severe asthma as well as in rhinitis. In most parts of the world, it is registered for the treatment of uncontrolled severe asthma after the age of six. A systematic review on the use of omalizumab in children, which appears in this issue, indicates that the addition of omalizumab in patients with uncontrolled allergic asthma can be considered as effective and safe 6. Up to now, there is not a single randomized controlled trial in children with urticaria. Therefore, the different case reports presented in this issue reporting a beneficial effect in refractory solar urticaria, and in spontaneous and physical urticaria are very encouraging and of high interest (7,8,9). Although very severe clinical cases of uncontrollable chronic urticaria compared to adults seem to be rare and the outcome may be more favorable in childhood, the information presented here strongly suggests that the pathophysiologic mechanism leading to chronic urticaria in childhood may be similar. It appears that the time has come to ask for randomized controlled trials with omalizumab and possibly other biologics for an apparently forgotten disorder in childhood which may deserve more attention and consideration than given in the past.