This large, randomized, placebo-controlled trial showed the efficacy of omalizumab, an injectable anti–IgE humanized monoclonal antibody, in the treatment of chronic idiopathic urticaria.
Chronic ...idiopathic urticaria (also called chronic spontaneous urticaria) is defined as itchy hives that last for at least 6 weeks, with or without angioedema, and that have no apparent external trigger.
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The condition generally has a prolonged duration of 1 to 5 years (persisting for >5 years in 11 to 14% of patients
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) and has a detrimental effect on patients' emotional and physical health-related quality of life.
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The impairment accompanying this disorder has been likened to that seen in patients with ischemic heart disease, with patients feeling a similar lack of energy, social isolation, and emotional upset . . .
Background
It is recommended that patch test readings include a day (D)7 reading. Substitution of the D7 reading with a photo may be a valid option.
Objectives
To compare the sensitivity of digital ...photos at D7 to clinical readings, to assess the number of positive reactions appearing at D7 only (late reactions), and after D7 only (delayed reactions).
Methods
Patients patch tested in six European clinics were instructed to forward photos of the patch test reactions to the respective clinics at D7 (before attending the clinic) and at D21. Only allergens in the baseline series or TRUE Test were included in the data analysis.
Results
Two hundred ninety‐three of 629 patients had a total of 599 positive reactions, with 6.3% occurring at D7 only. When substituting the D7 reading with a photo (90% submitted), 26.3% of late reactions were missed and nine false‐positive reactions were found. Delayed reactions were detected in four patients at D21 (65.3% submitted).
Conclusion
Our data show that if the D7 reading is not performed, 6.3% of positive reactions from the baseline series would be missed, and if substituting the D7 reading by digital photo, 26.3% late reactions would be missed. Delayed reactions seemed rare.
Our data support the importance of a day (D)7 reading, since 6.3% late reactions were present at D7 only.
When the D7 reading was substituted with a photo, 26.3% of late reactions and 1.7% of all reactions were missed.
Forwarding a digital photo at D7 may be an opportunity for patients having difficulties with attending the clinical D7 reading.
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.
Background
Patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) report difficulty with sleep.
Methods
We examined the effect of omalizumab on sleep‐related outcomes during 3–6 months ...omalizumab or placebo treatment and a 16‐week follow‐up period within three Phase III double‐blind randomized placebo‐controlled pivotal trials in CIU/CSU: ASTERIA I, ASTERIA II, and GLACIAL. Sleep quality was assessed in all three studies using sleep‐related questions included in an electronic diary, the Chronic Urticaria Quality of Life Questionnaire, and the Medical Outcomes Study Sleep Scale. Score changes from baseline in the treatment arms were compared with that in the placebo arm and adjusted for baseline score and weight. We also examined correlations of sleep scores at baseline, week 12, and week 24 and the slopes of change between sleep and itch and hive.
Results
Patients treated with omalizumab reported a larger reduction in sleep problems than those in the placebo arm; omalizumab 300 mg demonstrated the greatest improvement on all sleep components among all treatment arms. The largest reduction in sleep problems was reported within the first 4 weeks of therapy. After treatment discontinuation, sleep quality worsened. Sleep scores demonstrated moderate‐to‐strong correlation between them, and the change in sleep scores was associated with changes in itch and hives.
Conclusions
Improvement in sleep was reported after the first dose of omalizumab. Sleep continued to improve throughout the active treatment period. Patients receiving omalizumab 300 mg achieved greater improvement in sleep than those in other treatment arms.
Trial registration ClinicalTrials.gov, NCT01287117 (ASTERIA I), NCT01292473 (ASTERIA II), and NCT01264939 (GLACIAL)
Chronic spontaneous urticaria (CSU) is a debilitating skin disease characterized by intensely itchy wheals, angioedema, or both. Symptoms recur spontaneously, on a near‐daily basis, over >6 weeks; ...many patients experience flare‐ups over several years and, consequently, reduced quality of life. Differences between the inflammatory profiles of the skin of CSU patients (wheals and nonlesional sites) and healthy controls indicate that key drivers such as mast cells, eosinophils, and basophils interact, release vasoactive mediators, and prime the skin, leaving patients predisposed to symptoms. Many cytokines and chemokines involved in these inflammatory networks and their corresponding intracellular signaling cascades have been identified. These insights informed the development of therapies such as omalizumab, dupilumab, and Bruton's tyrosine kinase (BTK) inhibitors, marking a renewed focus on pathogenesis in CSU clinical research. Despite progress, current therapies provide symptomatic control but do not appear to redress the inflammatory balance in the skin permanently. A deeper understanding of CSU pathogenesis will permit a more targeted approach to developing novel treatments with curative intent. Here, we review what is known about the pathogenesis of CSU and consider how this can be used to identify rational targets to improve patient care further.
Immediate and nonimmediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5%‐3% of patients receiving nonionic ICM. The diagnosis ...and management of these patients vary among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and nonimmediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Re‐exposition or drug provocation test should only be done with skin test‐negative ICMs. The decision for performing either re‐exposition or drug provocation test needs to be taken based on a risk‐benefit analysis. The role of in vitro tests for diagnosis and pretreatment for preventing reactions remains controversial.
Chronic spontaneous urticaria (CSU) is defined as the spontaneous development of itchy hives and/or angioedema due to known or unknown causes that last for at least 6 weeks. At any given time, CSU is ...believed to affect 0.5–1% of the global population. Omalizumab (a recombinant, humanized anti-immunoglobulin-E antibody) is the only approved treatment for antihistamine refractory CSU. However, ~ 30% of patients remain symptomatic at licensed doses of omalizumab 150 mg and 300 mg, even after a treatment period of over 6 months. In the recent years, there have been several studies on updosing of the drug, suggesting that the individualized approach for urticaria treatment with omalizumab is useful. In this article, we provide an overview of these studies and the real-world data on omalizumab updosing as it became necessary to obtain complete CSU symptom control in a proportion of patients. Published observational studies (from June 2003 to October 2019) on the updosing of omalizumab in CSU were identified using PubMed and Ovid databases. Reports mainly show that updosing/dose adjustment evaluated with the assessment of disease activity (Urticaria Activity Score) and control (Urticaria Control Test) achieves better clinical response to omalizumab with a good safety profile in a pool of patients with CSU. These real-world data will provide an overview of updosing of omalizumab in CSU and aid in setting informed clinical practice treatment expectations.
Summary
The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact ...dermatitis or other delayed‐type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.
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