Second-generation H1-antihistamines Research Articles

Clinicodemographic Profile of Adult Patients With Chronic Urticaria in an Allergy Specialty Clinic

Background: There is variability among the prevalence and characteristics of chronic urticaria. Objectives: This study aimed to determine clinicodemographic characteristics of adult patients diagnosed with chronic urticaria in an allergy clinic in Metro Manila, Philippines, from 2019 to 2023. Methodology: A cross-sectional review of medical records from patients aged 19 and above at an allergy clinic in Metro Manila was conducted from 2019 to 2023. Clinicodemographic features, along with their frequencies and percentages, were obtained. Results: Seventy-five patients with chronic urticaria were investigated. The majority were women (72%) aged 30 to 39 (30.7%) from the National Capital Region (85.3%). Most were married (36%), college graduates (30.7%), and employed (54.7%), with 62.7% seeking their initial consultation 2 to 12 months after the onset of the disease. Fifty-seven percent of patients had a personal history of atopy and 54.7% had a family history of atopy. Thirty-seven percent of patients had comorbidities, with hypertension as the most frequent (18.7%). Thirty-three percent of patients were suspected with chronic inducible urticaria with dermographism as the most common suspected trigger (21.3%). Fifty-eight percent of patients had urticaria before COVID-19 vaccination, while 42% had a previous history of COVID-19 vaccine before the onset of symptoms. However, no further tests were done to confirm its association with the disease. Fifteen patients underwent skin prick tests, and all demonstrated positive skin test reactivity to some form of aeroallergen or food allergens. All patients were given second-generation H1-antihistamine at varying doses. The majority of patients (65.3%) reported an improvement in symptoms. Only 26.7% of patients used the 7-day Urticaria Activity Score, while 29.3% used the Urticaria Control Test to monitor their symptoms. Conclusion: The prevalence of chronic urticaria (13%) was higher than the global estimate of 1%. Most chronic urticaria patients were female, aged 30 to 39, married, college graduates, and employed who showed symptoms within 2 to 12 months after the onset of the disease. Approximately 50% of them had a personal and family history of atopy. Most patients do not have comorbidities and suspected inducible triggers. All patients who underwent skin prick tests showed reactivity to some allergens (aeroallergens, food allergens). All patients were given second-generation H1-antihistamines at varying doses. Many patients experienced symptom improvement with the prescribed medications despite poor compliance with the recommended monitoring tools. According to clinical history, the onset of chronic urticaria was not attributed to COVID-19 vaccination in most cases.

Mortality in adult patients with chronic spontaneous urticaria: Areal-world cohort study.

Chronic spontaneous urticaria (CSU), a common and debilitating disease, is widely held not to be life limiting, but the mortality of CSU has not been investigated. We sought to assess all-cause mortality in patients with CSU, risk for comorbidities that are leading causes of death, and impact of guideline-recommended urticaria treatments on mortality rates. This was a retrospective population-based cohort study of electronic health records of 272,190 adult patients with CSU and 12,728,913 controls without urticaria from the US collaborative network TriNetX. The study included 264,680 propensity score-matched patients with CSU (mean [SD] age= 47.5 [19.8] years; 71.5% female) and a corresponding number of controls without urticaria. Patients with CSU had higher 3-month (hazard ratio [HR] 2.10, 95% CI 1.97-2.22), 1-year (HR 1.77, 95% CI 1.71-1.83), and 5-year (HR 1.69, 95% CI 1.65-1.73) all-cause mortality (all P< .0001). Compared with controls, patients with CSU exhibited higher risk and rates of the leading causes of death in the United States, including suicidal ideations/suicide attempts (HR 3.14, 95% CI 3.00-3.28) and malignant neoplasms (HR 2.09, 95% CI 2.02-2.16). The risk of mortality appeared to be more pronounced in White and younger patients with CSU. All-cause mortality rates at 5 years were significantly lower in patients treated with second-generation H1 antihistamines versus untreated patients (1.0% vs 2.3%; HR 1.84, P< .0001) and omalizumab-treated patients versus antihistamine-treated patients (0.7% vs 2.6%; HR 3.99, P=.0003). CSU is associated with increased mortality likelydue to comorbidities, especially suicide, and effective CSUtreatment may reduce mortality. These findings shouldbeinvestigated in additional studies and in other populations.

Managing Urticarial Vasculitis: A Clinical Decision-Making Algorithm Based on Expert Consensus.

Urticarial vasculitis (UV) is a rare and difficult-to-treat, small-vessel leukocytoclastic vasculitis presenting with recurrent long-lasting wheals. So far, no guidelines and treatment algorithms exist that could help clinicians with the management of UV. In this review, we describe evidence on systemic treatments used for UV and propose a clinical decision-making algorithm for UV management based on the Urticarial Vasculitis Activity Score assessed for 7 days (UVAS7). Patients with occasional UV-like urticarial lesions and patients with UV with skin-limited manifestations and/or mild arthralgia/malaise (total UVAS7 ≤7 of 70) can be initially treated using the step-wise algorithm for chronic urticaria including second-generation H1-antihistamines, omalizumab, and cyclosporine A. Patients with UV with more severe symptoms (UVAS7 >7), especially those with hypocomplementemic UV, may require a multidisciplinary approach, particularly if underlying diseases, for example, systemic lupus erythematosus, cancer, or infection, are present. Immunomodulatory therapy is based on clinical signs and symptoms, and the drug availability and safety profile, and includes systemic corticosteroids, dapsone, hydroxychloroquine, anti-interleukin-1 agents, and other therapies. The level of evidence for all UV treatments is low. Prospective studies with current and novel drugs are needed and could provide further insights into UV pathogenesis and treatment.

Therapies for Chronic Spontaneous Urticaria: Present and Future Developments.

Chronic spontaneous urticaria (CSU) is a complex dermatological condition characterized by recurrent wheals and/or angioedema lasting for more than six weeks, significantly impairing patients' quality of life. According to European guidelines, the first step in treatment involves second-generation H1-antihistamines (sgAHs), which block peripheral H1 receptors to alleviate symptoms. In cases with inadequate responses, the dose of antihistamines can be increased by up to fourfold. If symptoms persist despite this adjustment, the next step involves the use of omalizumab, a monoclonal anti-IgE antibody, which has shown efficacy in the majority of cases. However, a subset of patients remains refractory, necessitating alternative treatments such as immunosuppressive agents like cyclosporine or azathioprine. To address these unmet needs, several new therapeutic targets are being explored. Among them, significant attention is being given to drugs that block Bruton's tyrosine kinase (BTK), such as remibrutinib, which reduces mast cell activation. Therapies like dupilumab, which target the interleukin-4 (IL-4) and IL-13 pathways, are also under investigation. Additionally, molecules targeting the Mas-related G protein-coupled receptor X2 (MRGPRX2), and those inhibiting the tyrosine kinase receptor Kit, such as barzolvolimab, show promise in clinical studies. These emerging treatments offer new options for patients with difficult-to-treat CSU and have the potential to modify the natural course of the disease by targeting key immune pathways, helping to achieve longer-term remission. Further research is essential to better elucidate the pathophysiology of CSU and optimize treatment protocols to achieve long-term benefits in managing this condition. Altogether, the future of CSU treatments that target pathogenetic mechanisms seems promising.

Bilastine Reimagined: A Comprehensive Exploration of Pruritus Management With a Novel Antihistamine.

Managing pruritic conditions is essential due to their significant impact on patients' quality of life. Chronic urticaria (CU), characterized by persistent itching and hives, severely affects daily activities and sleep. CU includes chronic inducible urticaria and chronic spontaneous urticaria, with the latter lacking identifiable triggers, making treatment especially challenging.CUis a condition that occurs across all age groups, with a higher prevalence among young adults and middle-aged women. Current antihistamine treatments include first-generation antihistamines, which are associated with sedation, and second-generation antihistamines such as cetirizine and fexofenadine, which cause less sedation but have varying efficacy and safety profiles. Bilastine, a novel second-generation H1-antihistamine, offers advantages due to its potent antihistaminic activity, rapid onset of action, and minimal sedation. This narrative review thoroughly synthesizes the evidence for the efficacy and safety of bilastine in treating CU and other pruritic conditions. By analyzing clinical trials, real-world evidence, and comparative studies, this review aims to provide a comprehensive understanding of the role of bilastine in managing pruritic conditions, emphasizing its pharmacokinetic properties, clinical efficacy, and safety profile compared to other antihistamines.

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.

Correlation between the expression of the iNOS, caspase-3 and α-SMA genes in the parotid glands of albino rats following the administration of two antihistamines from two different generations.

Several medications, including antihistamines, can alter salivary gland function, causing dry mouth or xerostomia. Antihistamines are commonly used for treating allergic rhinitis. The aim of the present study was to compare and correlate the effects of first-generation vs. second-generation H1-antihistamines on the parotid glands of rats. Twelve adult male albino rats were used; 4 rats served as a control group (group I) and the remaining rats were divided into 2 groups: group II received promethazine hydrochloride; and group III received cetirizine dihydrochloride for 3 weeks. The parotid salivary glands were dissected, and examined histologically and analyzed histomorphometrically for the acinar area percentage. In addition, mRNA gene expression of iNOS, caspase-3 and α-SMA was assessed using quantitative realtime polymerase chain reaction (qRT-PCR). Finally, all the obtained data was statistically analyzed. Histologically, group I showed the typical architecture of the gland. In group II, degenerative changes were noticed, including acinar degeneration and shrinkage with widened connective tissue septa, intracellular vacuolization, and increased inflammatory cell infiltration. In group III, similar histological features were detected as in group II, but to a lesser extent. Histomorphometric results revealed significant differences in the acinar area percentage between various groups. In addition, qRT-PCR results showed a significant increase in iNOS expression in both groups II and III as compared to group I, caspase-3 gene expression was significantly increased in group II, while in group III, it increased non-significantly. Finally, α-SMA gene expression non-significantly decreased in both groups II and III. A significant positive correlation was observed between caspase-3 and iNOS gene expression, while an inverse correlation was noticed between caspase-3 and α-SMA gene expression. The administration of antihistamines resulted in changes in the rat salivary glands, which could be due to the induction of oxidative stress and the resultant apoptotic effect. These changes were suggested to occur mainly through action on muscarinic receptors; yet, action on histamine receptors could not be excluded. However; these effects were less marked with the second-generation antihistamine.

Unveiling Treatment Response Predictors in Predominant Subtypes of Chronic Inducible Urticaria

Introduction: Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria (CU), which requires specific triggers to occur. Despite their common occurrence, treatment response rates and predictors of treatment responses are largely lacking in the literature. This study evaluates antihistamine (AH) and omalizumab response rates in the most common CIndU subtypes and examines whether certain features can predict treatment responses. Methods: We retrospectively analyzed CU patients with at least one CIndU subtype and performed comparisons between subgroups, in a total of 423 patients (70% CIndU, 30% chronic spontaneous urticaria [CSU] plus CIndU). Results: The treatment response rates in CIndU were 51.6%, 51.5%, and 86.5% with standard-dose second-generation H1-antihistamines (sgAHs), updosed/combined sgAH, and omalizumab, respectively. Overall AH response was higher in CIndU than CSU plus CIndU (78.3% vs. 62%, p = 0.002) and in symptomatic dermographism (SD) and cold urticaria (ColdU) than cholinergic urticaria (ChoU) (83.2% vs. 78.3 vs. 60.9%, p = 0.04). AH-refractory patients had a longer disease duration (45.2 ± 56.7 months vs. 37 ± 51.9 months, p = 0.04), more angioedema, accompanying CSU, mixed CIndU subtypes (37.5% vs. 21.1%, p = 0.003; 45.1% vs. 27.1%, p = 0.002; 8.8% vs. 2.4%, p = 0.014), and lower baseline urticaria control test scores (5.86 ± 3.3 vs. 8.6 ± 3.6, p < 0.001) than AH-responsive patients. Conclusion: CIndU exhibits a good response to both AHs and omalizumab. Notably, the response to AHs is more pronounced in SD and ColdU compared to ChoU. Disease duration, angioedema, accompanying CSU, mixed CIndU, and lower baseline UCT scores may be used to predict AH treatment outcome in CIndU.

Clinical Characteristics, Investigations and Treatment in Children with Chronic Urticaria: An Observational Study.

Background and Objectives: The guidelines for chronic urticaria in children contain recommendations that are often based on adult studies. The diagnostic pathway has not been standardized and the effectiveness of anti-H1, omalizumab, montelukast, and systemic glucocorticoids is rarely reported in the pediatric population. There is a wide variation in the rate of remission of chronic urticaria between studies. The aim of this study is to enhance our understanding of pediatric chronic urticaria. Materials and Methods: This study enrolled 37 children with chronic urticaria aged from 0 to 18 years. Demographic parameters, medical history, clinical features, laboratory data and treatment information were collected. Children were treated with the recommended dosage of second-generation H1-antihistamines, which was increased by up to twofold. Omalizumab was added for refractory anti-H1 patients. A three-day course with systemic glucocorticoids was administered for severe exacerbations. Montelukast was administered to some children. Results: Wheals without angioedema were common. Chronic urticaria was spontaneous in 32 children (86.48%), inducible in 2 (5.41%), induced by a parasite in 1 and vasculitic in 2. Treatment of the potential causes of chronic urticaria was of no benefit, except for eradication of Dientamoeba fragilis. Chronic urticaria was resolved within three years in 45.9% of cases. Allergic diseases were present in nine children (24.32%) and autoimmune diseases were present in three (8.11%). All children were treated with anti-H1 at the licensed dose or at a higher dose. A partial or complete response to anti-H1 was observed in 29 (78.38%) patients. Montelukast showed no benefit. All children treated with omalizumab responded. Systemic glucocorticoids were successfully used to treat exacerbations. Conclusions: Our findings indicate that laboratory tests should not be routinely performed in children with chronic urticaria without clinical suspicion. However, comorbidities such as thyroid autoimmune disease and coeliac disease are suggested to be monitored over the chronic urticaria course. These clinical conditions could be diagnosed from the diagnostic framework of chronic urticaria. Increasing the dosage of anti-H1 and omalizumab was effective in children resistant to standard treatment but we still need further studies to generate a standard patient-centered treatment.

Identification of pyruvic and maleic acid as potential markers for disease activity and prognosis in chronic urticaria

BackgroundPopulation-based studies have highlighted the link between chronic urticaria (CU) and metabolic syndrome, and metabolic alterations have been revealed in CU. However, to our knowledge, a comprehensive metabolomics study on a large cohort of CU patients has not been reported. ObjectiveTo explore the underlying metabolic subtypes and novel metabolite biomarkers for CU diagnosis and therapy. MethodsPlasma samples from 80 CU patients and 82 healthy controls (HCs) were collected for metabolomics quantification and performed bioinformatics analysis. Another independent cohort consisting of 144 CU patients was studied to validate the findings. Bone marrow-derived mast cells (BMMCs) and IgE-induced passive cutaneous anaphylaxis (PCA) mice were utilized for in vitro and in vivo experiments, respectively. ResultsWe observed clear metabolomics difference between CU and HC. Meanwhile, differential metabolites N6-acetyl-l-lysine, L-aspartate, maleic acid and pyruvic acid were used to respectively construct random forest classifiers, and achieved AUCs greater than 0.85, suggesting their potential as diagnostic biomarkers of CU. More importantly, by exploring the underlying metabolic subtypes of CU, we found that the low abundance of pyruvic acid and maleic acid was significantly related to the activity of CU, poor efficacy of second-generation H1-antihistamines (sgAHs), and short relapse-free time. The results were validated in the independent cohort. Moreover, supplementation with pyruvate or maleate could significantly attenuate IgE-mediated mast cells activation in vitro and in vivo. ConclusionsThe combination of plasma pyruvic acid and maleic acid may be effective biomarkers for predicting the disease activity, therapeutic efficacy as well as prognosis for CU patients.

Intravenous Cetirizine Premedication to Mitigate Infusion-Related Reactions.

Infusion-related reactions (IRRs) are a recognized concern for chemotherapy, biologic agents, and newer immunotherapies. Antihistamines are frequently recommended to prevent or manage these reactions. For over 60 years, diphenhydramine has been the only H1 antihistamine for intravenous (IV) administration. It has been considered the standard of care as part of premedication regimens to prevent IRRs associated with these therapies despite the lack of a US Food and Drug Administration (FDA)-approved indication and no evidence of efficacy data. Intravenous cetirizine was approved in 2019 for acute urticaria treatment, making it the only second-generation H1 antihistamine that can be administered intravenously. Compared with diphenhydramine, cetirizine has an improved safety profile with less sedation, fewer contraindications, lower incidence of anticholinergic side effects, and minimal risk of adverse events in elderly patients. A head-to-head study demonstrated that IV cetirizine is as effective as IV diphenhydramine in reducing IRRs and may decrease chair time, treatment center visits, and the need for rescue medication. Over the past 3 decades, the FDA has addressed the issue of IRRs by mandating language regarding the requirement or recommendation for premedication in the label of over 50 FDA-approved infusion products. As more therapeutics have premedication required or recommended, IV cetirizine should be considered an antihistamine for preventing and treating IRRs. In this article, we describe a patient whose IRR was successfully managed with IV cetirizine and discuss first- vs. second-generation H1 antihistamines and their use in treating and preventing IRRs.

Targeting histamine receptor 4 in cholinergic urticaria with izuforant (LEO 152020): results from a phase IIa randomized double-blind placebo-controlled multicentre crossover trial.

Cholinergic urticaria (CholU) is a common subtype of chronic inducible urticaria, where signs and symptoms (e.g. pruritic wheals and angioedema) are triggered by sweating due to physical exercise, passive warming and by other sweat-inducing situations. While guidelines recommend treatment with second-generation H1 antihistamines, approximately 90% of patients report uncontrolled disease. Targeting the histamine 4 receptor (H4R) has shown promise in preclinical/clinical studies of allergic/inflammatory diseases. Izuforant (LEO 152020) is a selective oral H4R antagonist with expected dual antipruritic and anti-inflammatory effects. To assess the effects of izuforant in adults with CholU, a common type of chronic urticaria driven by histamine and characterized by high skin levels of H4R expression. This was a phase IIa randomized double-blind placebo-controlled multicentre crossover trial where patients with CholU with an inadequate response to ≥ 1 standard dose of H1 antihistamine received izuforant 100 mg twice daily or placebo (EUCTR2020-004961-38-DE; NCT04853992). The primary endpoint was change from baseline in Urticaria Activity Score. Exploratory endpoints included CholU activity score over 7 days, urticaria control test, Physician Global Assessment, patient global assessment of severity (PGA-S), provocation tests, Dermatology Life Quality Index and CholU quality of life (CholU-QoL). Pharmacokinetic and pharmacodynamic parameters, and serum biomarkers were assessed, as well as safety and tolerability. Nineteen patients were randomized and included in the full analysis set; 18 completed treatment [mean (SD) age 29.5 (9.8) years; mean (SD) CholU duration 8.0 (6.3) years]. The primary and most of prespecified exploratory endpoints were not met; there were significant improvements in PGA-S for izuforant vs. placebo (P = 0.02), and nonsignificant improvements for other endpoints in quality of life and histamine skin prick test. All adverse events (AEs) experienced with izuforant were considered mild. The most frequently reported (> 1 patient) were nausea (three patients) and upper abdominal pain (two patients), occurring more frequently with izuforant vs. placebo (one patient each). There were no treatment-related serious AEs and no patient receiving izuforant discontinued the study. Treatment with izuforant did not cause downregulation of H4R. This is the first study to explore the role of H4R as a therapeutic target in urticaria. Targeting H4R with izuforant was well tolerated but did not demonstrate significant improvements vs. placebo in the primary endpoint and all but one prespecified exploratory endpoint in CholU.

Особливості анестезіологічної допомоги хворим на холодову кропивницю (огляд літератури)

Cold urticaria (CU) is an allergic reaction that manifests itself as hives-like rashes or red spots in response to general or local cooling of the body. Th e disease can be acquired or hereditary, and in the cold season it can affect all segments of the population. Th is pathological condition, at first glance, does not seem to be a very dangerous variant of a local cold injury, but in persons who are prone to exposure to low temperatures, especially with a burdened cold history, it may be accompanied by chronicity of the process and complicated by neurovasculitis, obliterating endarteritis and secondary Raynaud’s syndrome, may decrease the quality of life of the victims and become a cause of disability. The pathophysiology of CU is largely unknown, but it is likely to be related to immunoglobulin E (IgE) and mast cell activation. Cooling has been reported to induce the release of neutrophilic and eosinophilic chemotactic factors, prostaglandin D2, and tumor necrosis factor (TNF-α). Less common immunologic fi ndings in patients with CU include cryoglobulinemia consisting of monoclonal IgG and mixed IgG/IgM and IgG/IgA cryoglobulin types. The mechanisms of development of CU are mainly determined by the formation of cryoglobulins (cold hemolysins) and subsequent degranulation of mast cells. Th e diagnosis of CU depends on the patient’s history and the results of cold provocation tests. Patients with CU are recommended first of all not to overcool, to take warm showers, to wear warm clothes and a hat, and not to consume cold food and drinks. Treatment options include second-generation H1 antihistamines and glucocorticosteroids. New promising option is omalizumab, a humanized monoclonal antibody derived from a recombinant DNA molecule that targets and selectively binds to circulating IgE and affects mast cells function. In patients with CU undergoing general anesthesia, premedication including antihistamines and corticosteroids is recommended, along with strict maintenance of perioperative normotermia.

Therapeutics of urticaria: Results from a hospital-based multicenter study in China

Background: Therapeutics of urticaria in Chinese outpatients remain to be illustrated. Objectives: To investigate clinical treatment of outpatients with urticaria, and provide real-world evidence for selection of medication regimens. Methods: In this hospital-based multicenter study, urticaria outpatients filled in a questionnaire at initial visit and were followed-up (once per week, for 4 weeks). Results: We recruited 1715 urticaria outpatients and 647 completed 4 week’s follow-up. Their total UAS7 was reduced (27.44 at baseline, 16.87 in 1 week, 12.39 in 2 weeks, 7.21 in 3 weeks, 4.2 in 4 weeks). 71.8% patients recovered from urticaria (therapy was highly effective in 11%, whereas effective in 14.2%). The second-generation H1 antihistamines (sgAHs) (at conventional dose) were the most commonly prescribed drugs, with ebastine, levocetirizine and olopatadine being the leading ones (41.1%, 36.2%, and 16%, respectively). Combinations of several antihistamines (649 cases, 37.8%) at conventional dose were far more common than a single drug at escalated dose (59 cases, 3.4%). The combination of ebastine with levocetirizine was the most frequent options (18.25%, 313 cases), followed by combination of ebastine with compound glycyrrhizin (18.2%, 312 cases). The usage rates of tripterygium glycoside (19.6%), hydroxychloroquine (17.2%) and system application glucocorticoids (5.5%) in angioedema were much higher than in symptomatic dermographism and chronic spontaneous urticaria. Conclusions: This study identifies curative therapy for Chinese outpatients with urticaria. The sgAHs, especially ebastine, are the most commonly prescribed drugs. Olopatadine has fast-acting and curative effects. Compound glycyrrhizin holds potential as a versatile collaborator. Combinations of several antihistamines at conventional dose is common.

Efficacy evaluation of acupuncture combined with pricking blood therapy in the treatment of chronic spontaneous urticaria: a randomized controlled trial.

To assess the efficacy of combining acupuncture with pricking blood therapy to treat chronic spontaneous urticaria (CSU) and compare its outcomes with those of second-generation H1-antihistamines. Seventy CSU patients were enrolled and randomly assigned to receive treatment with either oral loratadine tablets or a combination of acupuncture and pricking blood therapy (n=35 each). Evaluations were conducted at baseline, at the conclusion of the 4-week treatment period, and at the 4th and 8th weeks post-treatment time points. We used six scales to gauge the severity of the skin lesions, itchiness, quality of life, and emotional and sleep states of the CSU patients. Upon completion of the treatment, both groups demonstrated a significant reduction in the scores of six scales from the baseline (P < 0.05). Notably, the scores of the itch visual analog scale (VAS), Hamilton Anxiety Scale, and Hamilton Depression Scale in the acupuncture and pricking blood therapy group were lower than those in the loratadine group (all P < 0.05). At the 8-week follow-up, the scores for all six scales were reduced from baseline in both groups (all P < 0.05), though the acupuncture and pricking blood therapy group showed significantly lower scores on the 7-day urticaria activity scale, with the Dermatology Life Quality Index, and the itchiness VAS compared with the loratadine group (all P < 0.05). Acupuncture combined with pricking blood therapy significantly ameliorated skin lesions, itchiness, and the associated psychological distress in CSU patients. This integrative approach not only matched the short-term efficacy of oral loratadine but surpassed its long-term benefits.

Safety of omalizumab in chronic urticaria during pregnancy: a real-life study.

Managing a pregnant patient with chronic spontaneous urticaria (CSU) is often challenging. Recent data have shown that most CSU treatments in pregnant patients are second-generation H1 antihistamines (sgAHs), while data on the safety of omalizumab are scant. To evaluate, in a routine clinical practice setting, the efficacy and safety of omalizumab in patients with severe CSU refractory to sgAHs who either became pregnant during treatment or who started the drug during pregnancy. We conducted a retrospective study of women aged ≥ 18 years who were pregnant, who received one or more doses of omalizumab at any time during their pregnancy or who were taking omalizumab at the time of, or in the 8 weeks before, conception. Twenty-nine pregnant patients were evaluated: 23 (79%) conceived a child while taking omalizumab (group A), while 6 (21%) started omalizumab treatment during pregnancy (group B). Among patients in group A, we observed 23 births (21 liveborn singletons and 1 liveborn twin pair) and 1 miscarriage. Fifteen (65%) patients discontinued omalizumab after confirming their pregnancy, while eight (35%) were exposed to omalizumab during their entire pregnancy. In group B, omalizumab was introduced at a mean (SD) 10.83 (3.60) weeks' gestation and all patients were exposed to it until the end of pregnancy. In this group, there were seven liveborn infants (five singletons and one twin pair). No adverse events, pregnancy complications or congenital anomalies in newborns were recorded in either group. Omalizumab for CSU treatment before and during pregnancy does not appear to have negative effects on maternal or fetal outcomes.

Role of Bilastine in Allergic Rhinitis: A Narrative Review.

Allergic rhinitis (AR) is considered a trivial disease and is often self-treated with over-the-counter drugs and home remedies. However, AR is a contributing risk factor for asthma associated with complications, including chronic cough, eosinophilic esophagitis, and otitis media with effusion. In AR, inflammation is primarily mediated by histamines. Guidelines advise using second-generation oral H1 antihistamines as the primary treatment for AR. Second-generation H1 antihistamines strongly prefer the H1 receptor, limiting their ability to enter the central nervous system. Thus, they have minimal adverse effects. Among these H1 antihistamines, bilastine is highly specific for H1 receptors with a slight affinity for other receptors. It has a rapid and prolonged action, which reduces the need for frequent dosing and has better compliance. In the long term, bilastine is well-tolerated with minimal adverse effects. It is not associated with drug interactions, so dosage adjustment is unnecessary. Bilastine does not penetrate the brain and is nonsedating at 80 mg once daily. The low possibility of drug-drug interactions and pharmacokinetics of bilastine makes it suitable for elderly patients, even with compromised hepatic and renal function, without dose adjustment. This review comprehensively discusses the guidelines and the role of bilastine in treating AR. How to cite this article: Tiwaskar M, Vora A, Tewary K, et al. Role of Bilastine in Allergic Rhinitis: A Narrative Review. J Assoc Physicians India 2023;71(11):58-61.

Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks

Remibrutinib (LOU064), an oral, highly selective Bruton tyrosine kinase inhibitor, offers fast disease control in patients with chronic spontaneous urticaria (CSU) who remain symptomatic despite treatment with second-generation H1 antihistamines. It is currently in phase 3 development for CSU. We sought to evaluate long-term safety and efficacy of remibrutinib in patients with CSU inadequately controlled with H1 antihistamines. In this phase 2b extension study, patients who completed the core study and had a weekly Urticaria Activity Score (UAS7) ≥16 at the beginning of the extension study received remibrutinib 100 mg twice daily for 52 weeks. The primary objective was to assess long-term safety and tolerability. Key efficacy end points included change from baseline in UAS7 and proportion of patients with complete response to treatment (UAS7= 0) and well-controlled disease (UAS7 ≤6) at week 4 and over 52 weeks. Overall, 84.3% (194/230) of patients entered the treatment period and received ≥1 doses of remibrutinib. The overall safety profile of remibrutinib was comparable between the extension and core studies. Most treatment-emergent adverse events were mild to moderate and considered unrelated to remibrutinib by investigators. The 3 most common treatment-emergent adverse events by system organ class were infections (30.9%), skin and subcutaneous tissue (26.8%), and gastrointestinal disorders (16.5%). At week 4 and 52, mean± SD change from baseline in UAS7 was -17.6± 13.40 and -21.8± 10.70; UAS7= 0 (as observed) was achieved in 28.2% and 55.8% and UAS7 ≤6 (as observed) was achieved in 52.7% and 68.0% of patients, respectively. Remibrutinib demonstrated a consistent favorablesafety profile with fast and sustained efficacy for up to 52 weeks in patients with CSU.

Comparative analysis of clinical efficacy and safety of omalizumab biosimilar in the treatment of patients with chronic spontaneous urticaria

BACKGROUND: Importance of optimizing strategy for treatment of chronic spontaneous urticaria is highly becoming relevance for the clinicians. Nowadays monoclonal antibodies are preferred option of treatment the refractory chronic spontaneous urticaria, main of that is omalizumab.&#x0D; AIM: to establish comparative analysis of the efficacy and safety of Genolair (JSC Generium, Russia) and Xolair (Novartis Pharma AG, Switzerland) in the treatment of patients with chronic spontaneous urticaria.&#x0D; MATERIALS AND METHODS: A 36-week, open parallel-group study was conducted. Were included 43 adult patients with chronic spontaneous urticaria who were resistant to ongoing therapy with standard and escalated doses of second-generation H1-antihistamines. All patients were divided into 2 groups: the main group (MG; n=18) ― patients who administrated Genolair; the comparison group (CG; n=25) ― patients who firstly administrated Xolair and then switching therapy to Genolair. Throughout the study period, patients completed questionnaires on the assessment of disease activity (UAS 7), urticaria control (UCT), quality of life index (DLQI). Additionally, the level of total IgE in blood serum was assessed. For statistical data processing, EXCEL 2010 and STATISTICA 7.0 software packages were used.&#x0D; RESULTS: After 4 weeks from the start of monoclonal antibody therapy, patients in both groups were responders to omalizumab. At the same time, there were no significant differences when comparing scores on the UAS 7, UCT scale between patients of the MG and the CG during the entire observation period (p 0.05). The change in treatment paradigm in CG also did not have a statistically significant effect on the indicators of urticaria activity and disease control (p 0.05). At the same time, the quality of everyday life changed more positively in the MG, which was reflected in a more pronounced change in the DLQI index at the time of the control assessment since 20 weeks of therapy (p=0.032). An increase in the level of total IgE in the blood serum of all patients with chronic spontaneous urticaria after the initiation of a course of immunobiological therapy was demonstrated, while there were no statistically significant intergroup differences in relation to changes in this laboratory parameter (p 0.05).&#x0D; CONCLUSION: During the treatment of patients with severe chronic spontaneous urticaria, resistant to ongoing therapy with standard and escalated doses of second-generation H1-antihistamines, comparable clinical efficacy and safety of the study drug Genolair and the reference drug Xolair were shown.

Chronic spontaneous urticaria—status quo and future

AbstractChronic spontaneous urticaria (CsU) is a chronic inflammatory dermatosis whose etiology is not yet fully understood. In affected patients, it is often associated with a high limitation of health-related quality of life, which necessitates effective therapeutic management. Different immune cell populations such as mast cells, eosinophilic and basophilic granulocytes, and T cells are involved in the pathogenesis of CsU, whereby mast cells playing a key role. In addition, type I autoallergic reactions with auto IgE antibodies or type IIb autoimmune reactions with auto IgG antibodies have been identified in a proportion of patients. The current international guideline initially recommends the use of second-generation H1 antihistamines, first in standard, then in off-label quadruple dosing. Subsequently, the anti-IgE antibody omalizumab should be added. However, this therapy algorithm does not lead to freedom from manifestations in all patients. Therefore, various targeted therapies are currently being evaluated for their efficacy in CsU, such as off-label use of the anti-interleukin receptor alpha (IL4Rα) antibody dupilumab, the anti-IL-17A antibody secukinumab, or interleukin‑5 blockade using mepolizumab, reslizumab, or benralizumab. In addition, new promising compounds such as the Bruton tyrosine kinase (BTK) inhibitors remibrutinib and fenebrutinib, the anti-cKIT antibody barzolvolimab, the anti-SIGLEC8 antibody lirentelimab, the anti-TSLP antibody tezepelumab, the anti-C5aR1 antibody advoralimab, or the topical application of Syk kinase inhibitors are being tested, which were developed according to new insights into the pathogenesis of CsU. The BTK inhibitor fenebrutinib is currently not being pursued due to a less favorable side effect profile compared to remibrutinib, as well as the anti-IgE antibody ligelizumab, which was inferior to omalizumab therapy in a phase 3 study. Overall, there is a high need for new therapeutic strategies to better treat CsU both symptomatically and curatively. This requires a more comprehensive understanding of pathogenesis of the disease in order to develop new targeted therapies.