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Background: Omalizumab, an anti-IgE monoclonal antibody, is an effective treatment in chronic spontaneous urticaria (CSU). Predictors of fast and good response for omalizumab treatment have not yet been identified and characterized., Objective: To evaluate whether soluble FcεRI (sFcεRI), a marker of IgE-mediated mast cell activation, predicts the time of response to omalizumab in CSU., Methods: Sera of 67 CSU patients were obtained before omalizumab treatment and analysed for sFcεRI levels by ELISA (2 ng/mL was used as cut-off for elevated sFcɛRI). Treatment response during the first 4 weeks was assessed with the urticaria activity score (UAS7), urticaria control test (UCT) and the rolling UAS7 (rUAS7)., Results: Elevated pre-treatment sFcɛRI levels were detected in more than 70% of patients with completely controlled disease (UCT = 16) and well-controlled disease (UCT = 12-15) and were significantly associated with disease control (χ 2  = 4.94, p < 0.05). More than half of the patients (14/25) with low levels had poor disease control (UCT < 12). Of the patients who achieved complete and marked UAS7 response, respectively, 75% and 63% had elevated baseline sFcɛRI levels. Post-treatment UAS7 scores were lower in patients with elevated sFcɛRI levels reaching statistical significance at Week 3 (p < 0.05). Patients with elevated baseline sFcɛRI levels achieved rUAS7 ≤ 6 and = 0 earlier than those with lower levels (Days 9 vs. 13 and Days 12 vs. 14, respectively)., Conclusion: Elevated sFcεRI serum levels predict early and good response to treatment with omalizumab, which may help to better design treatment options for CSU patients., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Although chronic urticaria (CU) is a common and primarily affects females, there is little data on how pregnancy interacts with the disease., Objective: To analyse the treatment use by CU patients before, during and after pregnancy as well as outcomes of pregnancy., Methods: PREG-CU is an international, multicentre study of the Urticaria Centers of Reference and Excellence network. Data were collected via a 47-item-questionnaire completed by CU patients who became pregnant during their disease course., Results: Questionnaires from 288 CU patients from 13 countries were analysed. During pregnancy, most patients (60%) used urticaria medication including standard-dose second generation H1-antihistamines (35.1%), first generation H1-antihistamines (7.6%), high-dose second-generation H1-antihistamines (5.6%) and omalizumab (5.6%). The preterm birth rate was 10.2%; rates were similar between patients who did and did not receive treatment during pregnancy (11.6% vs. 8.7%, respectively). Emergency referrals for CU and twin birth were risk factors for preterm birth. The caesarean delivery rate was 51.3%. More than 90% of new-borns were healthy at birth. There was no link between any patient or disease characteristics or treatments and medical problems at birth., Conclusion: Most CU patients used treatment during pregnancy especially second-generation antihistamines which seem to be safe during pregnancy regardless of the trimester. The rates of preterm births and medical problems of new-borns in CU patients were similar to population norms and not linked to treatment used during pregnancy. Emergency referrals for CU increased the risk of preterm birth and emphasize the importance of sufficient treatment to keep urticaria under control during pregnancy., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: The anti-IgE antibody omalizumab has been approved for the treatment of chronic spontaneous urticaria (CSU) in patients insufficiently responding to antihistamines. However, its mode of action in CSU is not clearly understood., Objectives: The aim of this study was to get a better insight in the immune mechanisms involved in clinical improvement of CSU patients treated with omalizumab., Methods: Chronic spontaneous urticaria patients (n = 15) were followed for 5 months after initiation of omalizumab treatment. Clinical symptoms were assessed by UCT and CU-Q 2 oL. Cell-bound IgE was quantified on both FcεRI- and FcεRII-expressing cell populations in peripheral blood. In addition, IgE and IgG as well as their receptors were measured on basophils, and basophil activation was assessed with different concentrations of anti-FcεRI and fMLP. Furthermore, the frequencies of different T-cell subsets secreting IL-5, IL-10, IL-31 or IFN-γ were analysed by ELISpot assay., Results: Seven patients showed a full, five a partial and three no clinical response to omalizumab. Cell-bound IgE was reduced on FcεRI-bearing cells, but not on FcεRII-expressing cells. Likewise, the expression of FcεRI declined. Basophil activation increased upon FcεRI-stimulation while their sensitivity was not affected. Both basophil and T-cell frequencies remained unchanged. However, when comparing the individual response to omalizumab treatment with distinct T-cell subsets, a significant correlation was found between improved UCT and decreased frequencies of IL-10-, IL-31- and IFN-γ-secreting T cells., Conclusions: We here show that besides addressing IgE-dependent immune mechanisms, omalizumab treatment of CSU patients has effects on distinct T-cell subsets, which correlate with clinical improvement., (© 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Chronic spontaneous urticaria (CSU) is characterized by the repeated occurrence of persistent hives and/or angioedema for ≥6 weeks, without specific external stimuli. H 1 -antihistamines have long been the standard of care of CSU, but many patients remain uncontrolled even at 4× the approved dose. Add-on therapy with omalizumab has proven effective in clinical trials, but little is known about omalizumab treatment in Belgium., Objective: To collect real-world clinical data on omalizumab treatment in adults with CSU in Belgium., Methods: This was an observational, retrospective chart review of adults with CSU, who initiated omalizumab treatment between August 2014 and December 2016 (maximum 28 months follow-up)., Results: In total, 235 patients were included (median time from symptom onset to diagnosis, 5.4 months; median time from diagnosis to commencing omalizumab, 6.7 months). Treatments used before/after commencing omalizumab did not always adhere to guidelines; many patients (26.4%/11.1%) received first-generation H 1 -antihistamines, while 20.4% used omalizumab monotherapy after initiating treatment. The mean interval between omalizumab administrations was 4.8 (SD 1.7) weeks; 67.8% of patients had ≥1 interval prolongation and/or shortening. Mean baseline 7-day Urticaria Activity Score (UAS7) was 32.0 (SD 6.05); this improved to 12.6 (SD 11.2) after 1 month of omalizumab. About 67.2% of patients reached UAS7 ≤ 6 (well controlled) during the study. A total of 87 patients stopped omalizumab and never restarted before the end of the observation period; the most prevalent reason was remission of symptoms (49.4% of patients), followed by lack of effect (12.6%), lost to follow-up (6.9%) and adverse events (3.4%). Headache was the most common adverse event (n = 8/82). No anaphylaxis was reported., Conclusions: This study revealed that patients initiated on omalizumab in Belgium had severe CSU at baseline, and showed substantial improvements after 1 month of treatment. Greater adherence to the prescription of guideline-recommended medications is needed for the treatment of CSU., (© 2019 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Chronic spontaneous urticaria (CSU) is defined as spontaneous occurrence of wheals and/or angioedema for ≥6 weeks. Omalizumab is a monoclonal anti-IgE antibody effective in refractory CSU, but its mechanism of action and markers predictive of response remain not completely defined., Objectives: To correlate baseline levels of two proposed biomarkers, total IgE (bIgE) and d-dimer (bd-dimer), and clinical parameters to omalizumab response and to relapses after drug withdrawal., Methods: In this retrospective Italian multicentre study, clinical data were collected in 470 CSU patients, and bIgE and bd-dimer were measured in 340 and 342 patients, respectively. Disease activity was determined by Urticaria Activity Score 7 (UAS7) at week 1 and 12 after omalizumab starting. Relapses were evaluated during a 2- and 3-month interval after a first and a second course of treatment, respectively., Results: bIgE correlated to a good response to omalizumab since levels were significantly higher in responders than non-responders (P = 0.0002). Conversely, bd-dimer did not correlate to response. There was no correlation between both bIgE and d-dimer and either first or second relapse. Disease duration was significantly longer in patients who experienced either first or second relapse (P < 0.0001 and P = 0.0105, respectively), while baseline UAS7 correlated only to first relapse (P = 0.0023)., Conclusions: Our study confirms bIgE as a reliable biomarker predicting response to omalizumab in CSU, while it does not support the usefulness of bd-dimer unlike previous findings. CSU duration before omalizumab and baseline UAS7 may be clinical markers of relapse risk., (© 2018 European Academy of Dermatology and Venereology.)

Aim: To examine the effectiveness of omalizumab (anti-IgE) on symptoms and disease-related quality of life in chronic spontaneous urticaria (CSU) and to identify possible patient-specific factors associated with response to omalizumab in patients with antihistamine refractory CSU., Methods: Six months prospective trial of omalizumab 300 mg every 4 weeks among patients with CSU from a dermatological university department. The primary outcome was the urticaria activity score in the past week (UAS7) at 3 months., Results: A total of 117 patients (39 men and 78 women) with a mean age of 42 years were included. The mean baseline UAS7 score was 29.3 points (SD = 10.8), which improved to 11.9 points (SD = 12.9) at 3 months follow-up, difference = 17.4 points (95% CI: 14.8-19.9), P < 0.0001. Other patient-reported outcomes (PROs) also improved significantly during 3 months of treatment. No significant further improvement was seen between three and 6 months follow-up. None of the following patient-specific factors: sex, age, age of onset of CSU, symptom duration, presence of chronic inducible urticaria (CINDU), comorbidities, positive urticaria HR test, smoking, ethnicity, angio-oedema, serum total IgE level, CRP, leucocytes, absolute neutrophil count or previous treatment with prednisolone or montelukast were significantly associated with response to omalizumab at 3 months, P > 0.05 for all comparisons. Previous treatment with traditional immunosuppressant drugs (azathioprine, cyclosporine or methotrexate) was associated with poorer treatment response to omalizumab at 3 months, P < 0.001. A strong correlation was seen between different patient-reported outcomes (PROs) at baseline and 3 months follow-up. Fifteen patients (12.8%) reported side-effects of the treatment., Conclusion: Omalizumab is a highly effective therapy for antihistamine refractory CSU with treatment effects similar to those observed in randomized controlled trials. Validated PROs to assess disease activity, disease control and impairment of quality of life are valuable tools in the clinical management of CSU. Identification of patient-specific predictors of effect and safety of omalizumab in CSU is still warranted., (© 2018 European Academy of Dermatology and Venereology.)

Background: Chronic spontaneous/idiopathic urticaria (CSU/CIU) has substantial detrimental effects on health-related quality of life (HRQoL) with an effect comparable to or worse than many other skin diseases., Objective: To assess the effect of omalizumab on CSU patients' HRQoL, measured by the Dermatology Life Quality Index (DLQI) in three phase III studies ASTERIA I, ASTERIA II and GLACIAL., Methods: A post hoc analysis examined changes in DLQI scores, distribution of patients across DLQI bands and the proportion reaching minimal clinically important difference (MCID) following omalizumab vs. placebo., Results: Omalizumab 300 mg significantly improved total DLQI scores vs. placebo, with a mean decrease from baseline to week 12 of -10.3 vs. -6.1 (P < 0.0001) in ASTERIA I, -10.2 vs. -6.1 (P = 0.0004) in ASTERIA II and -9.7 vs. -5.1 (P < 0.0001) in GLACIAL. A significant shift from high disease impact on life at baseline towards less impact at week 12 was seen with omalizumab 300 mg vs. placebo (P < 0.001; all studies). The proportion of patients where change in mean total DLQI score from baseline to week 12 reached an MCID of ≥4 was 74.1%, 76.0% and 77.2% in ASTERIA I, II and GLACIAL, respectively (P < 0.01; all studies)., Limitations: Maximum duration of omalizumab treatment was 24 weeks., Conclusion: This additional analysis assessed the impact of CSU and benefit of treatment with omalizumab by exploring different facets of DLQI data by treatment arm at multiple assessment points. The original aspects of analysis included applying the concept of the recently validated score for the MCID of the DLQI, changes in DLQI domain scores and in the distribution of subjects based on validated total DLQI score bands. It showed consistently that omalizumab provides significant and clinically relevant improvements in many aspects of HRQoL that are important to patients with CSU. These results contribute to a better understanding of the impact of CSU and its treatment on patients and can support clinical decision-making in routine medical practice., (© 2017 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Approximately 50% of patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) report hives and angioedema; some experience hives/angioedema only., Objective: Assess omalizumab's effect on angioedema and quality of life (QoL) in subgroups with refractory CIU/CSU: those with and without angioedema., Methods: Patients received omalizumab (75, 150 or 300 mg) or placebo every 4 weeks for 12/24 weeks. Angioedema and QoL were assessed [Urticaria Patient Daily Diary and Dermatology Quality of Life Index (DLQI)]. Subgroups were based on the presence/absence of baseline angioedema 7 days prior to randomization., Results: Patients with baseline angioedema randomized to omalizumab 300 mg had a greater reduction in mean weekly incidence of angioedema and mean number of days/week with angioedema vs. placebo at 12 and 24 weeks. A 3.3- to 4.5-point greater mean reduction in DLQI score was achieved with omalizumab 300 mg treatment vs. placebo, above the minimal clinically important difference threshold. Results with lower doses vs. placebo were variable., Conclusion: Compared with placebo, omalizumab 300 mg treatment over 12-24 weeks resulted in marked reduction in incidence and number of days/week with angioedema accompanied by clinically relevant improvement in QoL., (© 2016 European Academy of Dermatology and Venereology.)

Background: Bullous pemphigoid (BP) is an autoimmune blistering disease that is characterized by formation of subepidermal bullae due to functional disturbance of the hemidesmosomal proteins on the keratinocytes at the basal membrane zone. In recent years, several studies have emphasized the important role of IgE autoantibodies in the pathogenesis of BP. Consequently, a therapeutic approach using IgE depleting antibodies, such as a humanized monoclonal anti-IgE antibody (e.g. omalizumab) may represent a new option for treatment of this autoimmune disease., Methods: In this paper, we report about the successful treatment of BP with omalizumab in two patients and provide a review of the current literature on the relationship between IgE antibodies and this autoimmune blistering disease., Results: Two patients with therapy-resistant BP were treated with humanized monoclonal anti-IgE antibody omalizumab 300 mg subcutaneously every 3 weeks as corticosteroid-sparing agent. Under this therapy, both patients experienced a significant improvement of skin condition and almost complete resolution of pruritus. The treatment was well tolerated., Conclusion: Until recently IgG autoantibodies against the basal membrane proteins BP180 und BP230 were considered to be causative in the pathogenesis of BP. However, new in vitro studies as well as data from experimental mouse models have indicated that in addition to specific IgG, also IgE antibodies against BP180 and BP230 play a role in the development of this disease. Based on these new findings, new treatment modalities of BP became possible., (© 2016 European Academy of Dermatology and Venereology.)

This supplement reports proceedings of the second international Global Urticaria Forum, which was held in Berlin, Germany in November 2015. Omalizumab is approved for the treatment of chronic spontaneous urticaria (CSU) in adult and adolescent (12 years and above) patients with inadequate response to/who remain symptomatic despite H1 -antihistamine treatment, and has demonstrated good efficacy and safety in the clinical trial setting. Real-life clinical experience with omalizumab can be explored to address important practical questions relating to its use in CSU patients. Some experts have proposed that a consensus algorithm, covering various aspects to consider when using omalizumab in real-life clinical practice for the management of CSU, could answer many of these questions., (© 2016 European Academy of Dermatology and Venereology.)

Background: In March 2014, omalizumab, a monoclonal anti-IgE antibody, was approved for the treatment of chronic spontaneous urticaria (CSU). The primary mode of action of omalizumab is considered to be the reduction in free IgE serum levels and the subsequent down-regulation of FcεRI, the high affinity receptor for IgE, on mast cells and basophils. Recently, it has been suggested that most CSU patients have an autoimmune aetiology which may lead to chronic activation of mast cells and basophils., Objective: To understand more of the mechanisms by which omalizumab may exert its effects in CSU, its efficacy was tested on human mast cells and basophils., Methods: Omalizumab, which was or was not preincubated with serum from healthy donors or CSU patients, was coincubated with isolated healthy donor skin mast cells or peripheral blood-derived monocytes containing 1-2% basophils. Degranulation was induced using anti-human IgE, C5a, or substance P and histamine release determined., Results: Anti-human IgE-induced histamine release from mast cells or basophils was not altered in the presence or absence of omalizumab. In contrast, preincubation of mast cells with DARPin Fc fusion protein, a positive control for negative signalling via FcεRI-FcγRIIb cross activation, significantly diminished histamine release. Moreover, omalizumab, that was preincubated with healthy donor serum, CSU patient serum or auto-reactive CSU serum to allow for the formation of potential immune complexes, did not alter induced histamine release in a coincubation setup with mast cells or basophils as compared to the absence of omalizumab. In vivo, blood basophil numbers and basophil histamine content increase under omalizumab therapy., Conclusion: Our results suggest that the rapid response to omalizumab therapy is more likely to result from the elimination of an activating signal rather than the generation of a negative, inhibitory signal., (© 2014 European Academy of Dermatology and Venereology.)

Developments increasing our understanding of chronic urticaria have resulted in the simplification and improvement of available treatments. Currently, many treatments target mast cell mediators, but we can now disrupt mast cell activation with the anti-IgE antibody omalizumab, which has markedly advanced the treatment landscape for patients with difficult-to-treat urticaria. Current guidelines provide a framework for the management and treatment of patients with CU but, as each patient is different, knowledge and experience of specialist dermatologists and allergists are key to effective pharmacotherapy. This article reviews the different therapeutic options for patients with chronic spontaneous urticaria (also called chronic idiopathic urticaria) or chronic inducible urticaria and discusses management of special populations or special circumstances related to CU., (© 2015 European Academy of Dermatology and Venereology.)