H1-antihistamine Treatment Research Articles

Exploring the Impact of Pre-existing Allergic Conjunctivitis on the Efficacy of Refractory Medications in Chronic Spontaneous Urticaria: A TrinetX Database Analysis

Chronic Spontaneous Urticaria, often characterized by pruritic hives, can significantly impact quality of life [1][4]. Standard treatment involves second-generation antihistamines, but some cases may become refractory, requiring stronger medications such as cyclosporine A [2]. Purpose: To investigate the association of allergic conjunctivitis alongside CSU and use of cyclosporine A compared to those without pre-existing AC in treating CSU, using TrinetX database. Methods: Analysis included ICD-10 codes ‘urticaria, unspecified, ‘idiopathic urticaria,’ or ‘other urticaria’ for patients seen during 2020-2024, with at least two consecutive visits at least 4-6 weeks apart, in addition to receiving a second-generation H1-antihistamine treatment. Compare prevalence of cyclosporine use between two cohorts: AC (+) x urticaria x pretreated with H1 and AC (-) x urticaria x pretreated with H1 and patients with and without AC, requiring the addition of cyclosporine A to H1 for treatment of CSU over an observation period of 5 years. Propensity score matching to pair the two cohorts for age, sex, and race [3]. Results: In AC (+) x urticaria x pretreated with H1 group, there were 38,530 patients, out of which 446 required the addition of cyclosporine treatment, resulting in a risk percentage of 1.158%. In AC (-) x urticaria x pretreated with second-generation antihistamine group, with 415,786 patients, 2,812 required the addition of cyclosporine treatment, resulting in a lower risk percentage of 0.676%. Risk Ratio (RR) is calculated as 1.711, with a 95% confidence interval of (1.55, 1.89). Conclusion: A greater proportion of CSU patients with AC required cyclosporine compared to those without AC.

Benralizumab does not elicit therapeutic effect in patientswith chronic spontaneous urticaria: results from the phase IIb multinational randomized double-blind placebo-controlled ARROYO trial.

Chronic spontaneous urticaria (CSU) is a relatively common skin disease associated with hives and angio-oedema. Eosinophils play a role in CSU pathogenesis. Benralizumab, an anti-interleukin-5 receptor-α monoclonal antibody, has been shown to induce nearly complete depletion of eosinophils. To determine the clinical efficacy and safety of benralizumab in patients with CSU who were symptomatic despite H1 antihistamine treatment. The 24-week, randomized, double-blind, placebo-controlled, phase IIb portion of the ARROYO trial enrolled adult patients with CSU who were currently on H1 antihistamine treatment. Patients were randomized to one of five treatment groups according to benralizumab dose and regimen for a 24-week treatment period. The primary endpoint was change from baseline in Itch Severity Score (ISS)7 at week 12. The key secondary endpoint was change from baseline in Urticaria Activity Score (UAS)7 at week 12. Additional secondary endpoints included other metrics to assess CSU at week 24, blood eosinophil levels, and pharmacokinetics and immunogenicity assessments. Exploratory subgroup analyses were conducted to explore responses according to demographics, clinical features and biomarkers. Safety was assessed in all treatment groups. Of 155 patients, 59 were randomized to benralizumab 30 mg, 56 to benralizumab 60 mg and 40 to placebo. Baseline and disease characteristics were consistent with what was expected for patients with CSU. There were no significant differences in change from baseline in ISS7 score at week 12 between benralizumab and placebo [benralizumab 30 mg vs. placebo, least-squares mean difference -1.01, 95% confidence interval (CI) -3.28 to 1.26; benralizumab 60 mg vs. placebo, least-squares mean difference -1.79, 95% CI -4.09 to 0.50] nor in change from baseline in UAS7 score at week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, P = 0.407; benralizumab 60 mg vs. placebo, P = 0.082). Depletion of blood eosinophil levels was observed at week 24 in patients treated with benralizumab. All other secondary endpoints and exploratory/subgroup analyses indicated no significant differences between benralizumab and placebo. Safety results were consistent with the known profile of benralizumab. Although benralizumab resulted in near-complete depletion of blood eosinophils, there was no clinical benefit over placebo.

DUPILUMAB EFFICACY IN PATIENTS WITH CHRONIC SPONTANEOUS URTICARIA BY IGE LEVEL: LIBERTY-CSU CUPID STUDY A

<h3>Introduction</h3> Chronic spontaneous urticaria (CSU) causes recurrent itchy hives and/or angioedema, significantly impacting quality of life. Many patients experience a substantial disease burden despite treatment with licensed and escalated doses of H1 antihistamines. <h3>Methods</h3> In LIBERTY-CSU CUPID Study A (NCT04180488), a randomized, placebo-controlled, 24-week, phase 3 trial, patients (≥6 years) with CSU who remained symptomatic despite H1 antihistamine treatment received add-on dupilumab (n=70) (adults/adolescents ≥60kg: 300mg; adolescents <60kg/children ≥30kg: 200 mg) or matching placebo (n=68) subcutaneously every 2 weeks. Endpoints included change from baseline at Week-24 over 7 days in Itch Severity Score (ISS7), Hives Severity Score (HSS7), and Urticaria Activity Score (UAS7). <h3>Results</h3> Baseline characteristics were balanced; mean ISS7 and UAS7 (dupilumab/placebo) were 16.1/15.7 and 31.9/30.8, respectively. At Week-24, least squares (LS) mean change from baseline in ISS7 (range: 0–21) was –10.2/–6.0 (dupilumab/placebo, respectively) (LS mean difference –4.2; <i>P</i>=0.0005) and for UAS7 (range: 0–42) was –20.5/–12.0 (difference –8.5; <i>P</i>=0.0003). Baseline median serum total IgE was 101.0IU/mL (overall population). Dupilumab significantly reduced itch (ISS7), hives (HSS7), and urticaria activity (UAS7) at Week-24 regardless of baseline serum total IgE (<100 /≥100IU/mL): ISS7 LS mean difference vs placebo(95% confidence interval) −4.2(−7.86, −0.62)/−4.6(−8.22, −1.04), respectively; HSS7, −4.2(−7.60, −0.70)/−6.1(−9.95, −2.33); UAS7, –8.2(–15.04, –1.29)/–10.6(–17.72, –3.54). Occurrence of treatment-emergent adverse events (TEAEs) for dupilumab/placebo were 35(50.0%)/40(58.8%); injection-site reactions, 8(11.4%)/9(13.2%); conjunctivitis, 0/1(1.5%); serious TEAEs, 2(2.9%)/5(7.4%). <h3>Conclusion</h3> Dupilumab demonstrated clinically meaningful and statistically significant improvements in patients with H1 antihistamine-resistant CSU regardless of baseline IgE level and was well tolerated.

Do Pediatric Emergency Physicians Comply With Guideline Recommendations in Management of Patients With Acute Urticaria?

To determine the level of knowledge and practical preferences of pediatricians regarding acute urticaria (AU) management and to assess the effects of training provided in accordance with the current urticaria guideline recommendations on pediatricians who work in the pediatric emergency department (PED). A theoretical training was provided to pediatricians regarding the diagnosis and treatment of AU in line with current urticaria guideline recommendations. Before the training, pediatricians completed a 10-item questionnaire. This prospective study assesses their treatment approaches in patients admitted to PED because of AU during the 6-month period before and the 1-year period after training. Four hundred seventeen children in the pretraining and 1085 children in the posttraining periods were treated for AU in PED. Forty-eight pediatricians participated in the training. According to their questionnaire responses, 35% of them used only H1 antihistamine (AH) treatment, 50% used second-generation H1 AH (2nd-GAH) as AHs, 75% preferred the oral route of administration, and 85.4% did not administer systemic corticosteroid (sCS) to all patients. Comparing the practice approaches of the pediatricians in the pretraining and posttraining periods, first-generation H1 antihistamine (1st-GAH) preference rate decreased from 68.4% to 30.3% and the sCS preference rate decreased from 58.5% to 25.7%, while the 2nd-GAH preference rate increased from 31.7% to 69.7% (P < 0.001 for all). No treatments were prescribed for 10.8% of patients before the training and 3% after the training during discharge at home (P < 0.05). Comparing the home treatment choices of the pediatricians in the pretraining and posttraining periods, 1st-GAH preference rate decreased from 11.5% to 5%, while the 2nd-GAH preference rate increased from 78.7% to 91.5% (for both parameters, P < 0.001). Practical treatment preferences of pediatricians in the treatment of children with AU differ considerably from both current guideline recommendations and their own theoretical knowledge, and training can enhance pediatricians' compliance with current guideline recommendations.

Practical aspects of treatment with omalizumab in chronic spontaneous urticaria during COVID-19 vaccination campaign

Omalizumab is the first monoclonal antibody approved for use in patients with chronic spontaneous urticaria who remain symptomatic despite H1 antihistamine treatment. Recent data on the dosage of this drug in urticaria and practical aspects of subcutaneous administration of prefilled syringes with omalizumab during the COVID-19 vaccination campaign are presented. In our opinion, doses of omalizumab before and after COVID-19 vaccination should be injected subcutaneously in the thigh or abdomen, avoiding the same arm as the site of intramuscular injection of the vaccine. The recommendations for the time intervals between COVID-19 vaccinations and biological treatments are presented in accordance with the Position Paper of the German Society of Allergology and Clinical Immunology (DGAKI) and the German Society of Applied Allergology (AeDA). COVID-19 vaccination should be given between two administrations of omalizumab, preferably with a time lag of at least one week after the previous biological treatment and at least one week before the next planned biological treatment.

Antihistamines for treating pruritus : The end of an era?

Antihistamines, mostly H1 antihistamines, administered both topically and systemically, are among the most widely used drugs. While systemically applicable antihistamines are usually taken orally or administered intravenously, while local therapy is used on the eye, nose or skin. Systemic antihistamines are most frequently used during the pollen season (hay fever, asthma) or are used all year round, e.g., for house dust and animal hair allergies. Furthermore, urticaria is amajor indication for the use of H1 antihistamines, also as long-term treatment. Although H1 antihistamines are not licensed for pruritus and prurigo, they are frequently used in these diseases. However, since in many diseases with pruritus and prurigo the histamine receptor does not play adecisive role in the pathogenesis of pruritus, they show limited efficacy. Two Cochrane reviews have not shown any significant antipruritic effects of H1 antihistamine treatment in atopic eczema as single therapy or in combination, e.g., with topical glucocorticosteroid therapy. Aretrospective case series with aso-called high-dose antihistamine therapy with non-sedating antihistamines was effective in treating chronic pruritus. This article summarizes the possibilities of systemic antihistamines in pruritus, especially with regard to limitations and future prospects.

Efficacy of switching to bilastine, a histamine H1 receptor antagonist, in patients with chronic spontaneous urticaria (H1-SWITCH): study protocol for a randomized controlled trial

BackgroundChronic spontaneous urticaria (CSU) is characterized by the spontaneous appearance of wheals, angioedema, or both for > 6 weeks. Continuous treatment with H1-antihistamines is used as a first-line treatment for CSU. However, H1-antihistamine treatment leads to absence of symptoms in less than 50% of patients with CSU. Although Japanese guidelines for the diagnosis and treatment of urticaria recommend an increase in the H1-antihistamine dose or a switch to other H1-antihistamines, there is no evidence supporting a switch to other H1-antihistamines in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose.MethodsWe will conduct a multicenter, open-label, non-inferiority, randomized, parallel, comparison study to determine if the efficacy of bilastine 20 mg is not inferior to that of a twofold H1-antihistamine dose increase in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose. This study will be performed at 15 academic hospitals in Japan, and the administration period (increasing the H1-antihistamine dose twofold vs. switching to bilastine 20 mg) will be 7 days. Participants (n = 150) will be randomized to either an increased H1-antihistamine dose or a switch to bilastine 20 mg at a 1:1 ratio. The primary endpoint, mean of the total symptom score of 5–7 days after the intervention, will be evaluated. The secondary objective is to determine if the safety of bilastine 20 mg regarding somnolence is superior to that of a twofold dose increase of H1-antihistamines. This will be measured by a change in the Japanese version of the Epworth Sleepiness Scale from baseline to 7 days after starting the intervention.DiscussionThis multicenter, open-label, non-inferiority, randomized, parallel, comparison study will be, to our knowledge, the first well-designed clinical study to evaluate the efficacy of a switch to other H1-antihistamines in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed doses. This trial will provide evidence of the efficacy and safety of bilastine when treatment is switched in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose.Trial registrationJapan Registry of Clinical Trials (jRCT), jRCTs051180105. Registered on 8 March 2019.

Antileishmanial activity of H1-antihistamine drugs and cellular alterations in Leishmania (L.) infantum

Leishmaniases are infectious diseases caused by protozoan parasites Leishmania and transmitted by sand flies. Drug repurposing is a therapeutic approach that has shown satisfactory results in their treatment. Analyses of antihistaminic drugs have revealed their in vitro and in vivo activity against trypanosomatids. In this way, this study evaluated the antileishmanial activity of H1-antihistamines and identified the cellular alterations in Leishmania (L.) infantum. Cinnarizine, cyproheptadine, and meclizine showed activity against promastigotes with 50% inhibitory concentration (IC50) values between 10–29 μM. These drugs also demonstrated activity and selectivity against intracellular amastigotes, with IC50 values between 20–35 μM. Fexofenadine and cetirizine lacked antileishmanial activity against both forms. Mammalian cytotoxicity studies revealed 50% cytotoxic concentration values between 52 - >200 μM. These drugs depolarized the mitochondria membrane of parasites and caused morphological alterations, including mitochondrial damage, disorganization of the intracellular content, and nuclear membrane detachment. In conclusion, the L. infantum death may be ascribed by the subcellular alterations followed by a pronounced decrease in the mitochondrial membrane potential, indicating dysfunction in the respiratory chain upon H1-antihistamine treatment. These H1-antihistamines could be used to explore new routes of cellular death in the parasite and the determination of the targets at a molecular level, would contribute to understanding the potential of these drugs as antileishmanial.

C-reactive protein (CRP) rs3093059C predicts poor mizolastine response in chronic spontaneous urticaria patients with elevated serum CRP level.

Chronic spontaneous urticaria (CSU) is a frequent disorder with recurrent itchy wheals and/or angioedema, and nearly 35% patients respond poorly to non-sedating H1 antihistamine treatment. CRP gene encodes the C-reactive protein, which is involved in the pathogenesis of CSU. To investigate the impacts of CRP polymorphisms on the susceptibility and therapeutic efficacy in the South Han CSU patients, we enrolled 145 CSU patients in our study. After 4-week non-sedating H1 antihistamine monotherapy treatment, more than 50% reduction of the severity score is considered as effective, or else non-effective. The CRP rs3093059T/C and rs2794521G/A genotypes of patients were determined by Sequenom MassARRAY. Functional studies including relative luciferase assay and β-hexosaminidase assay were conducted in HEK293T cells or RBL-2H3 cells to explore the function of variants. Forty (62.50%) CSU patients were effective when treated with mizolastine, and 55 (72.4%) patients were effective in the desloratadine group. We found that the patients carried with rs3093059TT genotype were significantly associated with good response (OR=4.20, P=0.015), had lower serum CRP, IL-6 and TNF-α levels than the CT/CC genotypes. In vitro, the rs3093059C allele exhibited significantly higher luciferase activity than wild allele (P<0.001). From the β-hexosaminidase assay, we observed the inhibiting degranulation effects by mizolastine and this effect is weakened when with a higher dose CRP in RBL-2H3 cells. Our findings suggested that CSU patients carrying the rs3093059C allele may respond poorly to mizolastine with elevated serum CRP level.

The Effectiveness of Omalizumab Treatment in Real-Life is Lower in Patients with Chronic Urticaria Longer than 18 Months’ Evolution and Prior Immunosuppressive Treatment

BackgroundThe efficacy of omalizumab in the treatment of chronic spontaneous urticaria has been demonstrated in phase iii clinical trials, but limited information is available regarding real-life effectiveness using the weekly Urticarial Activity Score (UAS7). The aim of the study was to assess clinical response (UAS7≤6) and complete response (UAS7=0) rates at weeks 12 and 24 in a real-life cohort and to identify possible predictors of response to omalizumab. MethodsClinical records of consecutive patients with moderate-to-severe chronic spontaneous urticaria (UAS≥16) treated with omalizumab at a university-affiliated reference dermatology department in Barcelona, Spain, from February 2014 to September 2017 were retrospectively reviewed. UAS7 values and patients’ evolution were assessed according to a predefined protocol. Statistical analysis of data was done using SPSS 18 statistical package (SPSS 18 Inc., Chicago, IL, USA) software. ResultsForty-eight patients were included in the study. All of them completed at least 24-weeks of treatment and follow-up. At week 12, clinical response rates (UAS7<6) were 70.8% and complete response rates (UAS7=0) were 47.9%. At week 24, clinical response rates were 64.6% and complete response rates were 52.1%. Patientswith long-term urticaria (≥18 months’ duration) were less likely to achieve a clinical response at week 12 (odds ratio: 0.25; 95% confidence interval 0.06-0.96). Previous immunosuppressive treatment tended to be associated with a lower probability of complete response at week 12 (odds ratio: 0.27 95% confidence interval: 0.07-1.02). H1-antihistamine treatment was associated with lower probability of response at week 24 (odds ratio: 0.1 95% 95% confidence interval: 0.01-0.88) ConclusionsThe effectiveness and safety of omalizumab in real life are similar to efficacy and safety in clinical trials. Duration of disease, previous immunosuppressive therapy and requirement for concomitant H1-antihistamine treatment may be helpful in predicting response to omalizumab treatment.

La efectividad del tratamiento con omalizumab en la vida real es menor en pacientes con urticaria crónica de más de 18 meses de evolución y tratamiento inmunosupresor previo

BackgroundThe efficacy of omalizumab in the treatment of chronic spontaneous urticaria has been demonstrated in phase iii clinical trials, but limited information is available regarding real-life effectiveness using the weekly Urticarial Activity Score (UAS7). The aim of the study was to assess clinical response (UAS7≤6) and complete response (UAS7=0) rates at weeks 12 and 24 in a real-life cohort and to identify possible predictors of response to omalizumab. MethodsClinical records of consecutive patients with moderate-to-severe chronic spontaneous urticaria (UAS≥16) treated with omalizumab at a university-affiliated reference dermatology department in Barcelona, Spain, from February 2014 to September 2017 were retrospectively reviewed. UAS7 values and patients’ evolution were assessed according to a predefined protocol. Statistical analysis of data was done using SPSS 18 statistical package (SPSS 18 Inc., Chicago, IL, USA) software. ResultsForty-eight patients were included in the study. All of them completed at least 24-weeks of treatment and follow-up. At week 12, clinical response rates (UAS7<6) were 70.8% and complete response rates (UAS7=0) were 47.9%. At week 24, clinical response rates were 64.6% and complete response rates were 52.1%. Patientswith long-term urticaria (≥18 months’ duration) were less likely to achieve a clinical response at week 12 (odds ratio: 0.25; 95% confidence interval 0.06-0.96). Previous immunosuppressive treatment tended to be associated with a lower probability of complete response at week 12 (odds ratio: 0.27 95% confidence interval: 0.07-1.02). H1-antihistamine treatment was associated with lower probability of response at week 24 (odds ratio: 0.1 95% 95% confidence interval: 0.01-0.88) ConclusionsThe effectiveness and safety of omalizumab in real life are similar to efficacy and safety in clinical trials. Duration of disease, previous immunosuppressive therapy and requirement for concomitant H1-antihistamine treatment may be helpful in predicting response to omalizumab treatment.

The efficacy and safety of omalizumab in refractory chronic spontaneous urticaria: real-life experience in Turkey

This study used real-world data to evaluate the effectiveness and reliability of omalizumab in treating recalcitrant chronic spontaneous urticaria in Turkish patients. Study data were collected retrospectively from eight tertiary-care hospitals in Turkey. This study included 132 patients with chronic spontaneous urticaria that were resistant to H1 antihistamine treatment in a dose up to four times the licensed dose and were treated with 300 mg/month of omalizumab for 6 months. The mean weekly urticarial activity score (UAS7) after omalizumab treatment improved significantly compared to the pre-treatment score (p < 0.001). Treatment response was detected primarily in the 1st and 2nd months after treatment. No significant association was observed between omalizumab's treatment effectiveness and disease-related parameters or laboratory data. The mean dermatology life quality index was 23.12 ± 6.15 before treatment and decreased to 3.55 ± 3.60 6 months after treatment (p < 0.001). No side effects were reported in 89.4% (118) of the patients. This study showed that UAS7 decreased significantly and quality of life improved in omalizumab-treated patients. Moreover, treatment effectiveness was mainly observed in the first 2 months after treatment. However, no association was observed between omalizumab treatment effectiveness and disease-related parameters or laboratory data.

Road traffic crash risk associated with prescription of hydroxyzine and other sedating H1-antihistamines: A responsibility and case-crossover study

BackgroundH1 antihistamines differ from each other by their ability to cross the blood-brain barrier. The resulting sedating effect can be sought in therapy but may be a driving hazard. The aim of this study was to estimate the impact of sedating H1-antihistamines on the risk of road traffic crash, with a particular focus on hydroxyzine which is also indicated as an anxiolytic in France. MethodsThe study consisted in extracting and matching data from three French nationwide databases: the national healthcare insurance database, police reports and the police national database of injurious crashes. All sedating H1-antihistamines, including hydroxyzine, were considered in the study. A case-control analysis, in which responsible drivers were cases and non-responsible were controls was performed. A case-crossover analysis, comparing for the same subject exposure during a period immediately before the crash with exposure during an earlier period, was also conducted. ResultsThe extraction and matching procedures over the July 2005-December 2011 period led to the inclusion of 142,771 drivers involved in an injurious road traffic crash. The responsibility study found an increased risk of being responsible for an injurious road traffic crash in hydroxyzine users who were registered with a long-term chronic disease (mostly psychiatric disorders) on the day of the crash (OR=1.67 [1.22–2.30]). Among them, the risk was even higher in drivers with highest exposure levels (OR=2.60 [1.23–5.50]). There was no impact of sedating H1 antihistamine treatment initiation on the risk of crash. ConclusionEven if it is difficult to disentangle the part of the increased risk that would be causally related to hydroxyzine and the part related to behaviours of patients with a heavy psychiatric disorder, our study raises the alarm on the crash risk linked to hydroxyzine utilization in countries in which the anxiolytic indication is widespread.

Increased serum soluble vascular endothelial cadherin levels in patients with chronic spontaneous urticaria

BackgroundChronic spontaneous urticaria (CSU) is a common skin disease characterized by recurrent itchy wheals with or without angioedema that lasts longer than 6 weeks. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule that plays critical roles in angiogenesis and endothelial permeability. ObjectiveTo investigate serum levels of soluble VE (sVE)-cadherin in patients with CSU. MethodsSerum levels of sVE-cadherin in patients with CSU, patients with atopic dermatitis, and healthy controls were determined by enzyme-linked immunosorbent assay. In addition, changes in sVE-cadherin serum levels were compared in patients with CSU before and after H1 antihistamine treatment. Furthermore, the effects of histamine on sVE-cadherin release by HMEC-1 cells were determined by enzyme-linked immunosorbent assay. The inhibition effects of H1 antihistamine and H2 antihistamine on sVE-cadherin release, VE-cadherin phosphorylation, and VE-cadherin disruption were evaluated in histamine-treated HMEC-1 cells by western blot and immunofluorescence. ResultsSerum levels of sVE-cadherin in patients with CSU were significantly higher than those in patients with atopic dermatitis and healthy controls. Serum sVE-cadherin levels in patients with CSU were correlated with the severity of CSU according to Urticaria Activity Scores. Furthermore, serum sVE-cadherin levels in patients with CSU at pretreatment decreased after H1 antihistamine treatment. In addition, histamine markedly induced sVE-cadherin release in HMEC-1 cells. Moreover, H1 antihistamine, but not H2 antihistamine, significantly inhibited sVE-cadherin release in histamine-treated HMEC-1 cells. Western blot data showed that histamine induced phosphorylation of VE-cadherin in HMEC-1 cells, which was blocked by H1 antihistamine. ConclusionThe present data showed serum levels of sVE-cadherin are increased in patients with CSU. Histamine-induced sVE-cadherin release from endothelial cells could play a role in the pathogenesis of CSU.

Treatment of chronic spontaneous urticaria with an inadequate response to H1-antihistamines: an expert opinion.

Chronic spontaneous urticaria (CSU) is characterized by the sudden, continuous or intermittent appearance of pruritic wheals (hives), angioedema, or both for six weeks or more, with no known specific trigger. The international EAACI/GA2LEN/EDF/WAO urticaria guideline advises standard-dose, second-generation H1-antihistamines as first-line therapy. However, H1-antihistamine treatment leads to absence of symptoms in fewer than 50% of patients. Updosing of second-generation H1-antihistamines (up to fourfold) as recommended by the EAACI/GA2LEN/EDF/WAO urticaria guideline as second-line therapy, can improve response, but many patients remain symptomatic. Definitions of response are often subjective and a consensus is needed regarding appropriate treatment targets. There is also an unmet need for biomarkers to assess CSU severity and activity and to predict treatment response. The EAACI/GA2LEN/EDF/WAO urticaria guideline recommends add-on omalizumab, ciclosporin A (CsA), or montelukast third-line treatment in patients with an inadequate response to high-dose H1-antihistamines. Omalizumab is currently the only licensed systemic biologic for use in CSU. Both omalizumab and CsA are effective third-line CSU treatments; montelukast appears to have lower efficacy in this setting. Omalizumab carries a label warning for anaphylaxis, although no cases of anaphylaxis were reported in the phase III trials of omalizumab in CSU and it is generally well tolerated in patients with CSU. Omalizumab arguably has a better safety profile than CsA.

Antihistamines for the Treatment of Allergic Rhino-conjunctivitis

Histamine plays an important role in the pathogenesis of allergic rhino-conjunctivitis (ARC). First generation antihistamines are sedative, they cause cognitive and psychomotor impairment, and they are not indicated for the treatment of ARC. Second generation H1-antihistamines, with their improved safety profile and faster and longer duration of action, meet many of the ARIA (Allergic Rhinitis and its Impact on Asthma) optimal antihistamine prerequisites for the treatment of ARC. They are recommended as first line therapy for the treatment of children and adults with ARC and are efficacious in rapidly reducing itching, sneezing and rhinorrhoea. However, they offer suboptimal relief to patients with significant nasal congestion. They are available as oral, intranasal and ocular preparations. Oral preparations are more effective when used continuously and have demonstrated a greater or similar efficacy to leukotriene receptor antagonists (LTRA), with a potentiated effect when used simultaneously. Second generation H1-antihistamines are recommended for both intermittent and persistent ARC and in combination with intranasal steroids (INS) for severe disease. Intranasal H1-antihistamine preparations have the advantage of being delivered directly to the nasal mucosa with faster onset of action (15 vs 60 min) and may be preferable when rapid symptom relief is desirable or for on-demand therapy. They are recommended for mild/intermittent disease. A better outcome is achieved when used in combination with INS. In particular, a single formulation of fluticasone with azelastine nasal spray has demonstrated superiority to monotherapy with either compound in patients with moderate/severe disease. Its use is recommended when monotherapy has proven insufficient and for the treatment of moderate/persistent disease. Ophthalmic preparations are efficacious in ameliorating ocular symptoms and can be used when oral antihistamines fail. In the management of ARC, second generation H1-antihistamine treatment reduces symptoms, improves quality of life, lessens the overall burden of disease and reduces disease-associated costs.

Efficacy and Safety of Omalizumab in Patients with Chronic Idiopathic/Spontaneous Urticaria Who Remain Symptomatic on H1 Antihistamines: A Randomized, Placebo-Controlled Study

ASTERIA I was a 40-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous omalizumab as add-on therapy for 24 weeks in patients with chronic idiopathic urticaria/spontaneous urticaria (CIU/CSU) who remained symptomatic despite H1 antihistamine treatment at licensed doses. Patients aged 12–75 years with CIU/CSU who remained symptomatic despite treatment with approved doses of H1 antihistamines were randomized (1:1:1:1) in a double-blind manner to subcutaneous omalizumab 75 mg, 150 mg, or 300 mg or placebo every 4 weeks for 24 weeks followed by 16 weeks of follow-up. The primary end point was change from baseline in weekly itch severity score (ISS) at week 12. Among randomized patients (N=319: placebo n=80, omalizumab 75 mg n=78, 150 mg n=80, 300 mg n=81), 262 (82.1%) completed the study. Compared with placebo (n=80), mean weekly ISS was reduced from baseline to week 12 by an additional 2.96 points (95% confidence interval (CI): −4.71 to −1.21; P=0.0010), 2.95 points (95% CI: −4.72 to −1.18; P=0.0012), and 5.80 points (95% CI: −7.49 to −4.10; P<0.0001) in the omalizumab 75-mg (n=77), 150-mg (n=80), and 300-mg groups (n=81), respectively. The omalizumab 300-mg group met all nine secondary end points, including a significant decrease in the duration of time to reach minimally important difference response (⩾5-point decrease) in weekly ISS (P<0.0001) and higher percentages of patients with well-controlled symptoms (urticaria activity score over 7 days (UAS7) ⩽6: 51.9% vs. 11.3% P<0.0001) and complete response (UAS7=0: 35.8% vs. 8.8% P<0.0001) versus placebo. During the 24-week treatment period, 2 (2.9%), 3 (3.4%), 0, and 4 (5.0%) patients in the omalizumab 75-mg, 150-mg, 300-mg, and placebo groups, respectively, experienced a serious adverse event. Omalizumab 300 mg administered subcutaneously every 4 weeks reduced weekly ISS and other symptom scores versus placebo in CIU/CSU patients who remained symptomatic despite treatment with approved doses of H1 antihistamines.

The influence of hepatitis C virus infection on H1 antihistamine treatment in urticaria patients

Background Considerable evidence indicates that, in addition to antiallergic effect, several H1-antihistamines also possess antiinflammatory properties. The anti-inflammatory activity of H1 antihistamine treatment in urticaria patients is based on the capacity of H1-antihistamines to inhibit the release of chemical mediators from mast cells and basophiles, to regulate the chemotaxis of neutrophils and eosinophils, to increase eosinophils apoptosis and to reduce the expression of the adhesion molecules. Viral hepatic infections may affect the efficacy of H1 antihistamines probably interfering with their hepatic metabolism through cytochrome P450 system. We proposed to analyze the effect of hepatitis C virus (HCV) infection on the therapeutic efficacy of H1 antihistamines in urticaria patients.

Improvements In Health-Related Quality Of Life From Asteria I & II: Phase III Studies To Evaluate The Efficacy and Safety Of Omalizumab In Patients With Chronic Idiopathic/Spontaneous Urticaria Who Remain Symptomatic Despite H1 Antihistamine Treatment

To describe changes in health-related quality of life (HRQOL) in patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) using pooled data from the 12-week treatment periods of the ASTERIA I & II studies. Subjects (n=640) were randomized 1:1:1:1 and received placebo or omalizumab 75, 150 or 300 mg (PLB, OMA75, OMA150, OMA 300) at Baseline and Weeks 4 and 8. HRQOL was assessed by the Dermatology Life Quality Index (DLQI; overall score and subscales for symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment) at Baseline, Weeks 4 and 12. At Baseline, patients reported substantial HRQOL impairment. All treatment arms improved from Baseline to Week 12 in many of the DLQI domains; however, the largest improvements were seen in the omalizumab-treated patients (change from Baseline to Week 12 in overall DLQI, PLB -6.11, OMA75 -6.93, OMA150 -8.15, OMA300 -10.22). Compared to placebo, change from Baseline to Week 12 in overall DLQI was statistically significant for higher doses of omalizumab (OMA150, p=0.01 and OMA300 mg, p< 0.0001). Improvements in DLQI were observed after one administration of study drug, by the first post-Baseline assessment at Week 4, with additional improvement observed at Week 12. For all DLQI domains assessed, the greatest improvements were seen in patients treated with omalizumab 300 mg. In CIU/CSU patients who are symptomatic despite H1 antihistamine treatment, omalizumab was efficacious in improving a broad array of HRQOL domains, as measured by the DLQI instrument.

Omalizumab for Chronic Urticaria

.These studies suggest that omalizumab will be a good therapeutic option for patients with CIU who do not respond to either licensed or higher doses of H1 antihistamines. Chronic idiopathic urticaria (CIU)echronic spontaneous urticaria (CSU) is defined as hives and/or angioedema that occurs daily, or almost daily, for >6 weeks independent of external stimuli. CIU has significant detrimental effects on quality of life. H1 antihistamines are the only approved treatment in CIU, but more than 50% of patients are unresponsive to licensed doses of H1 antihistamines. Add-on treatments (all unapproved by the US Food and Drug Administration) include leukotriene receptor antagonists, systemic steroids, cyclosporine, and methotrexates, but the data to support their use are not of high quality. Therefore, there is a need for new, efficacious, and well-tolerated treatments for patients with H1 antihistamine refractory CIU. Maurer et al recently reported results from 1 of the 3 phase III anti-IgE mAb omalizumab studies (Asteria-II) for treatment of CIU. They evaluated the efficacy and safety of omalizumab compared with placebo in 323 patients, 12 to 75 years of age, with moderate-to-severe refractory CIU despite receiving concomitant licensed doses of H1 antihistamine therapy. This was a global, multicenter, 1:1:1:1 randomized, doubleblind, placebo-controlled trial that compared 3 subcutaneous injections, separated by 4 weeks, of omalizumab at doses of 75 mg, 150 mg, or 300 mg, or placebo, followed by a 16-week observation period. The primary end point was the change from baseline in weekly itch severity score (ISS) at week 12. Major secondary end points included a change from baseline in a weekly number of hives score, the proportion of patients with a weekly urticaria activity score (UAS7, a composite score of the weekly ISS and weekly number of hives score [scale 0e42]) 6, change from baseline in overall Dermatology Life Quality Index (DLQI), and the proportion of angioedema-free days from week 4 to week 12. Key inclusion criteria were a CIU diagnosis for 6 months, the presence of itch and hives for 8 consecutive weeks at any time before enrollment despite the current use of H1 antihistamine treatment, weekly UAS7 score 16, and itch component of UAS7 8 (scale 0-21) during 7 days before randomization (week 0). Key exclusion criteria were clearly defined underlying etiology for chronic urticaria (cold, physical,