Background Chronic urticaria is a frequent and debilitating skin disease. Its symptoms commonly fluctuate considerably from day to day. As of yet, the only reliable tool to assess disease activity is ...the Urticaria Activity Score, which prospectively documents the signs and symptoms of urticaria for several days. Objective We sought to develop and validate a novel patient-reported outcome instrument to retrospectively assess urticaria control, the Urticaria Control Test (UCT). Methods Potential UCT items were developed by using established methods (literature research and expert and patient involvement). Subsequently, item reduction was performed by using a combined approach, applying impact and regression analysis. The resulting UCT instrument was then tested for its validity, reliability, and screening accuracy. Results A 4-item UCT with a recall period of 4 weeks was developed based on 25 potential UCT items tested in 508 patients with chronic urticaria. A subsequent validation study with the 4-item UCT in 120 patients with chronic urticaria demonstrated that this new tool exhibits good convergent and known-groups validity, as well as excellent test-retest reliability. In addition, the screening accuracy to identify patients with urticaria with insufficiently controlled disease was found to be high. Conclusions The UCT is the first valid and reliable tool to assess disease control in patients with chronic urticaria (spontaneous and inducible). Its retrospective approach and simple scoring system make it an ideal instrument for the management of patients with chronic urticaria in clinical practice.
Cold urticaria is a potentially life-threatening disease and placebo treatment of patients does not provide protection from cold-induced systemic reactions including anaphylactic shock. Because the ...interim analysis showed marked clinical and statistical superiority of omalizumab compared with placebo, the study was terminated. ...omalizumab in doses of 150 mg and 300 mg resulted in a high rate of complete and partial responders in patients with cold urticaria and a pronounced overall reduction in disease activity. There were no visible differences between omalizumab and placebo; however, the viscosity of the 2 differed. ...a separate and independent unblinded study team, which did not engage in study-specific communication with the blinded study team, was responsible for the preparation and injection of the study drug. ...a sample size calculation based on previous data was not possible.
Background Patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) often continue to experience symptoms despite receiving standard-of-care therapy with H1 -antihistamines ...along with 1 or more add-on therapies. Objectives We sought to evaluate the safety and efficacy of 24 weeks of treatment with omalizumab in patients with persistent CIU/CSU despite treatment with H1 -antihistamines at up to 4 times the approved dose plus H2 -antihistamines, leukotriene receptor antagonists, or both. Methods In this phase III study patients were randomized to receive 6 subcutaneous injections at 4-week intervals of either 300 mg of omalizumab or placebo, followed by a 16-week observation period. The primary objective of the study was to evaluate the overall safety of omalizumab compared with placebo. Efficacy (itch severity, hive, and urticaria activity scores) was evaluated at weeks 12 and 24. Results The overall incidence and severity of adverse events and serious adverse events were similar between omalizumab and placebo recipients; the safety profile was consistent with omalizumab in patients with allergic asthma. At week 12, the mean change from baseline in weekly itch severity score was −8.6 (95% CI, −9.3 to −7.8) in the omalizumab group compared with −4.0 (95% CI, −5.3 to −2.7) in the placebo group ( P < .001). Significant improvements were seen for additional efficacy end points at week 12; these benefits were sustained to week 24. Conclusion Omalizumab was well tolerated and reduced the signs and symptoms of CIU/CSU in patients who remained symptomatic despite the use of H1 -antihistamines (up to 4 times the approved dose) plus H2 -antihistamines, leukotriene receptor antagonists, or both.
Short Summary This study demonstrates the responsiveness of the Urticaria Control Test (UCT). Changes of its score by 3 points or more reflect a clinically relevant change of disease control (minimal ...important difference).
Background A subgroup of patients with chronic spontaneous urticaria (CU) exhibits IgE antibodies directed against autoantigens, such as thyroperoxidase (TPO). We conducted this study to investigate ...whether such patients with CU with IgE against TPO benefit from treatment with omalizumab, a humanized anti-IgE mAb licensed for the treatment of severe persistent allergic (IgE-mediated) asthma. Objectives We sought to assess the efficacy of omalizumab treatment in patients with CU with IgE autoantibodies against TPO. Methods In this multicenter, randomized, double-blind, placebo-controlled study patients with CU (male/female, 18-70 years of age) with IgE autoantibodies against TPO who had persistent symptoms (wheals and pruritus) despite standard antihistamine therapy were randomized to receive either omalizumab (75-375 mg, dose determined by using the approved asthma dosing table) or placebo subcutaneously once every 2 or 4 weeks for 24 weeks. The primary end point was the change from baseline in mean weekly urticaria activity score after 24 weeks of treatment, as calculated from patients’ diaries. The safety and tolerability of omalizumab were also assessed. Results Of the 49 randomized patients (omalizumab, n = 27; placebo, n = 22), 42 completed the study. At week 24, patients demonstrated a mean reduction in the weekly urticaria activity score from baseline of 17.8 with omalizumab and 7.9 with placebo ( P = .0089). Complete protection from wheal development was observed in 19 (70.4%) patients in the omalizumab group compared with only 1 (4.5%) patient in the placebo group. The rate of adverse events was similar in both groups. Conclusions The results of this study indicate that omalizumab is an effective treatment option for patients with CU with IgE autoantibodies against TPO who are refractory to conventional treatment.
To the Editor: Chronic spontaneous urticaria (CSU) presents as recurrent itchy wheals, angioedema, or both for at least 6 weeks without a specific trigger.1 Roughly half of the patients with CSU ...achieve symptomatic control with H1-antihistamine therapy at approved doses, increased doses, or with additional therapies such as leukotriene receptor antagonists.1 CSU can be unpredictable and debilitating for patients because of a lack of clinical response.2 Recently, omalizumab, a neutralizing anti-IgE mAb, has gained approval for treatment of patients with CSU on the basis of evidence of substantial efficacy.3 However, the treatment benefit with omalizumab is usually lost when treatment is stopped. Specific IgE may target an endogenous antigen, a hypothesis supported by evidence that approximately 50% of patients with CSU have elevated levels of antithyroperoxidase IgE.5 Quilizumab, a humanized, afucosylated, monoclonal IgG1 antibody, binds membrane IgE at the M1-prime segment, which is absent in soluble IgE.6 In animal studies, quilizumab bound membrane IgE on IgE-switched B cells and plasmablasts and depleted them through apoptosis and antibody-dependent cell-mediated cytotoxicity.6 In clinical trials, quilizumab reduced serum total and specific IgE levels in healthy volunteers and in patients with allergic rhinitis or mild asthma.7,8 These reductions were sustained for at least 6 months after the last dose, suggesting that quilizumab affected long-term IgE memory.
Background Hereditary angioedema caused by mutations in the factor XII gene is a recently described disease entity that occurs mainly in women. It differs from hereditary angioedema caused by C1 ...inhibitor deficiency. Objective To assess the clinical symptoms, factors triggering acute attacks, and treatments of this disease. Methods Thirty-five female patients with hereditary angioedema and the factor XII mutations p.Thr309Lys and p.Thr309Arg who came from 13 unrelated families were studied. The observation period was 8.4 years on average (range, 2-26 years). Results Patients had on average 12.7 ± 7.9 angioedema attacks per year. Recurrent facial swellings occurred in all patients; skin swellings other than facial, abdominal pain attacks, tongue swellings, and laryngeal edema occurred less frequently. Some factors that triggered angioedema attacks were trauma, physical pressure, and emotional stress. Clinical symptoms started mainly after intake of oral contraceptives (17 women) or pregnancy (3 women). Exacerbation of the symptoms occurred after oral contraceptive use (8 women), pregnancy (7 women), hormone replacement therapy (3 women), intake of angiotensin-converting enzyme inhibitors (2 women), and an angiotensin 1 receptor blocker (1 woman). Effective treatments included C1 inhibitor concentrate for angioedema attacks (6 women) and, for prophylaxis, progesterone (8 women), danazol (2 women), and tranexamic acid (1 woman). No difference between mutation p.Thr309Arg and p.Thr309Lys was found. Conclusions Facial swelling is a cardinal symptom of this condition. Estrogens may have a great influence, but this influence is highly variable. Various treatment options are available.
To the Editor: Chronic urticaria is a severe skin disease characterized by itchy wheals and/or angioedema1,2 with an estimated lifetime prevalence of 3% to 5% in the general population.3,4 The ...current European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Network (GA2LEN)/European Dermatology Forum (EDF)/World Allergy Organization (WAO) treatment guidelines recommend nonsedating H1-antihistamines as first-line treatment, increasing their dosage as second-line treatment, and switching to another such antihistamine or adding a leukotriene antagonist as the third-line treatment.5 Thereafter, among several other fourth-line options including cyclosporine A,6 the guidelines suggest the possibility of using omalizumab, a humanized mAb that blocks the IgE receptor.7 Since September 2008, our specialized university clinic has used omalizumab (Xolair; Genentech & Novartis, San Francisco & Basel) to treat 8 patients with chronic spontaneous urticaria patients (Table I) who had not benefited from the recommended first-line, second-line, and third-line treatments.
Objective Tooth extractions may trigger clinical symptoms of hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH). The aim of this study was to determine how many tooth extractions were ...followed by symptoms of HAE-C1-INH in patients with and without preoperative short-term prophylaxis with C1 inhibitor concentrate. Study design Tooth extractions and clinical symptoms of HAE-C1-INH were determined from clinical record files of 171 patients with HAE-C1-INH. Results Facial swelling or potentially life-threatening laryngeal edema, or both, occurred in 124/577 tooth extractions (21.5%) without prophylaxis. Similar symptoms occurred in a fewer proportion of patients undergoing extractions (16/128; 12.5%) after short-term prophylaxis with C1 inhibitor concentrate. The graded dose-response relationship was significant at P < .05. Conclusions Short-term prophylaxis with C1 inhibitor concentrate significantly reduces the risk of HAE-C1-INH symptoms after tooth extraction. In some patients, however, facial swellings and laryngeal edema symptoms may occur despite prophylaxis.
Chronic spontaneous urticaria (CSU) lasting more than 6 weeks is one of the most disabling types of urticaria and often results in severely impaired quality of life. Patients with CSU are often ...unsatisfied with the standard treatment. Another treatment option recommended for patients with so-called nonresponding CSU according to the newest guidelines is intravenous immunoglobulin (IVIG).
To assess the efficacy and safety of high-dose IVIG as a treatment option in patients with therapy-resistant CSU.
Six patients with severe CSU unresponsive to other treatment options according to the newest guidelines for several weeks were treated with high-dose IVIG (2 g/kg every 4-6 weeks). The response to treatment was observed on the basis of clinical signs and reduction of co-medications using a special treatment score. Patients were studied during the treatment period and were followed up for an average of 16 months. Adverse events were assessed.
Patients showed an improvement in symptoms and a reduction in co-medication use just after the first cycle. Symptoms such as itching, wheals, and edema were reduced after the first or second cycle of IVIG treatment. Four of 6 patients had complete remission after 2 to 4 cycles. One patient needed a longer continuation of treatment to reach a stable state of improvement, and another patient had a slight relapse after the seventh cycle. Adverse effects, such as headache and increased blood pressure, were observed only at the beginning of treatment.
High-dose IVIG represents an important therapeutic option in patients with severe CSU.
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