For several decades, attenuated androgens were the only oral prophylaxis drugs widely used in HAE despite their androgenic and anabolic effects.8 Managing HAE with safe oral medicines is considered a ...critical unmet need.9 Given the encouraging results of this trial, studies of longer duration are indicated to understand the durability of benefit and long-term tolerability and safety profile of oral avoralstat.
Clinical Measures of Chronic Urticaria Weller, Karsten; Siebenhaar, Frank; Hawro, Tomasz ...
Immunology and allergy clinics of North America,
02/2017, Letnik:
37, Številka:
1
Journal Article
Recenzirano
The use of standardized, valid, and reliable clinical measures is an important element in modern patient management, particularly in diseases that are not objectively assessable and are associated ...with a high disease burden. Chronic urticaria is such a disorder for which several new and well-developed clinical measures became available. These measures comprise tools to assess disease activity, disease control, and health-related quality-of-life impairment. This review provides an overview of the currently available clinical measures for chronic urticaria. In addition, it provides information on their strengths and limitations and how to best use them and evaluate their results.
Physical urticarias and cholinergic urticaria Abajian, Marina; Schoepke, Nicole; Altrichter, Sabine ...
Immunology and allergy clinics of North America,
02/2014, Letnik:
34, Številka:
1
Journal Article
Recenzirano
Physical urticarias are a unique subgroup of chronic urticaria in which urticarial responses can be reproducibly induced by different specific physical stimuli acting on the skin. These conditions ...include urticaria factitia/symptomatic dermographism, delayed pressure urticaria, cold contact urticaria, heat contact urticaria, solar urticaria, and vibratory urticaria/angioedema. Physical urticarias and cholinergic urticarias are diagnosed based on the patients' history and provocation tests including trigger threshold testing where possible. Treatment is mainly symptomatic. Many patients benefit from avoiding eliciting triggers, and desensitization to these triggers can be helpful in some physical urticarias and in cholinergic urticaria.
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.
Angioedema, present in some patients with chronic idiopathic/spontaneous urticaria (CIU/CSU), may have a negative effect on patient quality of life.
To describe patient-reported angioedema and its ...management in the pivotal omalizumab studies (ASTERIA I, ASTERIA II, GLACIAL).
Enrolled patients with CIU/CSU remained symptomatic despite treatment with histamine1 (H1)-antihistamines at licensed doses (ASTERIA I, ASTERIA II) or H1-antihistamines at up to 4 times the approved dose plus H2-antihistamines and/or a leukotriene receptor antagonist (GLACIAL). All studies administered omalizumab (75, 150, or 300 mg in ASTERIA I and ASTERIA II; 300 mg in GLACIAL) or placebo subcutaneously every 4 weeks for at least 12 weeks. Urticaria Patient Daily Diary entries were completed by patients and summarized.
At baseline, angioedema prevalence was higher in GLACIAL (53.1%) than in ASTERIA I (47.5%) or ASTERIA II (40.7%). The mean proportion of angioedema-free days during weeks 4 to 12 was greater for patients treated with 300 mg of omalizumab than placebo in ASTERIA I (96.1% vs 88.2%, P < .001), ASTERIA II (95.5% vs 89.2%, P < .001), and GLACIAL (91.0% vs 88.7%, P = .006). Most patient-reported angioedema was managed by low-intensity interventions (doing nothing or taking medication).
Treatment with 300 mg of omalizumab was efficacious in reducing patient-reported angioedema. Low-intensity interventions were generally used to manage angioedema episodes.
clinicaltrials.gov Identifiers: NCT01287117 (ASTERIA I), NCT01292473 (ASTERIA II), and NCT01264939 (GLACIAL).
Data from the 3 omalizumab pivotal trials in patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) represent the largest database of patients reported to date with ...refractory disease (omalizumab, n = 733; placebo, n = 242).
The objective of this study was to compare results from ASTERIA I and II, which included only approved doses of H1-antihistamine as background therapy based on regulatory authority requirements, to those from GLACIAL, which permitted higher doses of H1-antihistamines as well as other types of background therapy, in a post hoc analysis.
Efficacy data from the placebo, omalizumab 150-mg, and omalizumab 300-mg treatment arms of ASTERIA I and II were pooled and analyzed (n = 162 and n = 160, respectively). The 300-mg treatment arm analyses were compared with the analysis of data from GLACIAL (n = 252) using analysis of covariance models. The key efficacy endpoint was change from baseline to week 12 in mean weekly itch severity score (ISS); other endpoints were also evaluated. Safety data were pooled from all 3 studies.
Mean ISS was significantly reduced from baseline at week 12 in the pooled ASTERIA I and II omalizumab 150- and 300-mg treatment arms and in the GLACIAL omalizumab 300-mg arm. The weekly ISS reduction magnitude at week 12 was similar between the omalizumab 300-mg groups in the ASTERIA I and II pooled and GLACIAL studies. Similar treatment effect sizes were observed across multiple endpoints. Omalizumab was well tolerated and the adverse-event profile was similar regardless of background therapy for CIU/CSU. The overall safety profile was generally consistent with omalizumab therapy in allergic asthma.
Omalizumab 300 mg was safe and effective in reducing CIU/CSU symptoms regardless of background therapy.
The Urticaria Activity Score (UAS) is a widely used patient-reported outcome measure for patients with chronic idiopathic urticaria (CIU) that includes 2 items: intensity of pruritus and number of ...hives. Items are scored individually, and the UAS7 is calculated as the sum of pruritus and number of hives over 1 week. Recently, its instructions were enhanced.
To assess the measurement properties of the enhanced UAS.
Seventy-three subjects with CIU completed the UAS with enhanced instructions, other measures of disease activity including the size of the largest hive, and collateral measures during a multicenter, randomized, double-blind, placebo-controlled study of omalizumab for the treatment of CIU. The minimal important difference (MID) was estimated through distribution- and anchor-based approaches. Test-retest reliability was assessed with the intraclass correlation coefficient (ICC); internal consistency reliability was evaluated with Cronbach's alpha; 3 responsiveness coefficients were calculated; known groups validity was assessed based on physician in-clinic UAS scores; and construct validity was assessed through Spearman correlation coefficients with collateral measures.
The MID ranged from 9.5 to 10.5 for the UAS7, 5.0 to 5.5 for number of hives (weekly average), and 4.5 to 5.0 for pruritus and size of largest hive (weekly average). Internal consistency was supported by alpha coefficients greater than 0.80. The ICC values for test-retest reliability ranged from 0.602 to 0.884. For subjects on active treatment, responsiveness coefficients were greater than 0.80. Known-groups validity was supported for most UAS scores; and construct validity was demonstrated by relationships with collateral measures.
The enhanced UAS has adequate measurement properties to support its use in clinical research.
Following the bite in August, 2001, the reaction developed rapidly, and he immediately lost consciousness and went into cardiac arrest before the ambulance arrived. Because of delayed resuscitation, ...he had hypoxic brain damage to the basal ganglia, resulting in spastic tetraplegia. Despite having only slightly raised serum tryptase of 11·5 ?g/L (normal range <11·4 ?g/L), bone marrow examination showed spindle shaped mast cells expressing CD25, and the typical Kit-mutation (D816V) was detected by PCR of peripheral blood leucocytes.1 From the patient's description of the appearance of the mosquitoes that bit him, and knowledge of the geographic region where the incidents occurred, Culex pipiens was identified by an expert from the Bernhard Nocht Institute, Hamburg, Germany, as the most likely of the 100 known mosquito species in central Europe to be responsible for inducing such reactions.
Treatment strategies in mastocytosis Siebenhaar, Frank; Akin, Cem; Bindslev-Jensen, Carsten ...
Immunology and allergy clinics of North America,
05/2014, Letnik:
34, Številka:
2
Journal Article
Recenzirano
Treatment recommendations for mastocytosis are based mostly on expert opinion rather than evidence obtained from controlled clinical trials. In this article, treatment options for mastocytosis are ...presented, with a focus on the control of mediator-related symptoms in patients with indolent disease.
Background Mast cells (MCs) and nerves can induce cutaneous inflammatory responses, both independently and by interacting with each other. However, little is known about the role of skin nerves and ...neuropeptides in the regulation of MC-mediated skin inflammation, and the contribution of MCs in neurogenic inflammation is still controversial. Objective The aim of this study was to investigate the effects of cutaneous sensory nerves on MC-driven inflammatory responses. Methods Passive cutaneous anaphylaxis, a model for type I allergic skin responses, was studied in the presence or absence of sensory nerves by using a murine model of selective cutaneous denervation. Results Passive cutaneous anaphylaxis was significantly impaired in the absence of sensory nerves. This effect was not a result of an alteration of mast cell numbers in denervated skin. Moreover, IgE-mediated activation of mast cells was markedly decreased in denervated compared with normal skin. Notably, pretreatment of mice with selective antagonists of the neuropeptides substance P and/or calcitonin gene-related peptide also resulted in decreased inflammatory responses after MC activation. Conclusion These data suggest that sensory skin nerves augment MC-driven inflammatory responses by releasing neuropeptides that increase MC degranulation.
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