Current insights on gut microbiome and chronic urticaria: progress in the pathogenesis and opportunities for novel therapeutic approaches.

Chronic urticaria (CU) is a prevalent skin disorder greatly impacting the patients' life quality, in which immune dysregulation mediated by gut microbiome plays a significant role. Several studies have found the gut dysbiosis exists in patients with CU. In addition, infection may also be one of the causes of CU. The primary treatment currently used for CU is the second-generation non-sedating H1-antihistamines (nsAH). However, there are some limitations in current therapies. Based on the latest evidence, this review provides an updated overview of how the gut dysbiosis influences CU development, explores potential therapeutic approaches based on the gut microbiota and summarizes the interaction between gut microbiota and current treatment.

Cumulative Dose Effects of H1 Antihistamine Use on the Risk of Dementia in Patients With Allergic Rhinitis.

BACKGROUND: H1 antihistamines (AHs), categorized as first-generation antihistamines (FGAs) or second-generation antihistamines (SGAs), possess anticholinergic properties linked to heightened dementia risk. OBJECTIVES: To explore dementia risk in patients with allergic rhinitis using AHs. METHODS: Taiwanese patients with new-onset allergic rhinitis (2011-2017) constituted the study population (677,971 with FGAs or SGAs, 36,081 without AHs). AH use was measured in cumulative defined daily dose (cDDD). Patients were grouped by cDDD (nonuser, <60 cDDD, 60-120 cDDD, and >120 cDDD). A Cox proportional hazard model assessed the AH-dementia association. Sensitivity analysis explored AH effects on dementia risk across subgroups and associations between specific AHs and dementia types. RESULTS: FGAs in patients with allergic rhinitis were associated with elevated dementia risk. At less than 60 cDDD, adjusted hazard ratio (aHR) was 1.13 (95% CI, 1.09-1.17); at 60 to 120 cDDD, aHR was 1.29 (95% CI, 1.21-1.38); and at more than 120 cDDD, aHR was 1.51 (95% CI, 1.42-1.62). SGAs also raised dementia risk. At less than 60 cDDD, aHR was 1.11 (95% CI, 1.05-1.17); at 60 to 120 cDDD, aHR was 1.19 (95% CI, 1.12-1.26); and at more than 120 cDDD, aHR was 1.26 (95% CI, 1.19-1.33). CONCLUSIONS: Patients with allergic rhinitis on FGAs or SGAs face an escalating dementia risk with increasing cumulative dosage. Moreover, FGAs exhibit a higher dementia risk compared with SGAs. Nevertheless, extensive clinical trials are imperative for confirming the association between FGA use, SGA use, and dementia risk.

Effect of Switching the Histamine-1 Receptor Antagonist Clemastine to Cetirizine in Paclitaxel Premedication Regimens: The H1-Switch Study.

PURPOSE: Premedication, including a histamine-1 receptor (H1) antagonist, is recommended to all patients treated with paclitaxel chemotherapy to reduce the incidence of hypersensitivity reactions (HSRs). However, the scientific basis for this premedication is not robust, which provides opportunities for optimization. Substitution of intravenously administered first-generation H1 antagonist for orally administered second-generation H1 antagonist could reduce side effects, and improve efficiency and sustainability. This study investigates the efficacy and safety of substituting intravenous clemastine for oral cetirizine as prophylaxis for paclitaxel-induced HSRs. METHODS: This single-center, prospective, noninferiority study compares a historic cohort receiving a premedication regimen with intravenous clemastine to a prospective cohort receiving oral cetirizine. Primary end point of the study is HSR grade ≥3. The difference in incidence was calculated together with the 90% CI. We determined that the two-sided 90% CI of HSR grade ≥3 incidence in the oral cetirizine cohort should not be more than 4% higher (ie, the noninferiority margin) compared with the intravenous clemastine cohort. RESULTS: Two hundred and twelve patients were included in the oral cetirizine cohort (June 2022 and May 2023) and 183 in the intravenous clemastine cohort. HSR grade ≥3 incidence was 1.6% (n = 3) in the intravenous clemastine cohort and 0.5% (n = 1) in the oral cetirizine cohort, resulting in a difference of -1.2% (90% CI, -3.4 to 1.1). CONCLUSION: Premedication containing oral cetirizine is as safe as premedication containing intravenous clemastine in preventing paclitaxel-induced HSR grade ≥3. These findings could contribute to optimization of care for patients and improve efficiency and sustainability.

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.

Blockade of histamine receptor H1 augments immune checkpoint therapy by enhancing MHC-I expression in pancreatic cancer cells.

BACKGROUND: Although immune checkpoint blockade (ICB) therapy has proven to be extremely effective at managing certain cancers, its efficacy in treating pancreatic ductal adenocarcinoma (PDAC) has been limited. Therefore, enhancing the effect of ICB could improve the prognosis of PDAC. In this study, we focused on the histamine receptor H1 (HRH1) and investigated its impact on ICB therapy for PDAC. METHODS: We assessed HRH1 expression in pancreatic cancer cell (PCC) specimens from PDAC patients through public data analysis and immunohistochemical (IHC) staining. The impact of HRH1 in PCCs was evaluated using HRH1 antagonists and small hairpin RNA (shRNA). Techniques including Western blot, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-PCR), and microarray analyses were performed to identify the relationships between HRH1 and major histocompatibility complex class I (MHC-I) expression in cancer cells. We combined HRH1 antagonism or knockdown with anti-programmed death receptor 1 (αPD-1) therapy in orthotopic models, employing IHC, immunofluorescence, and hematoxylin and eosin staining for assessment. RESULTS: HRH1 expression in cancer cells was negatively correlated with HLA-ABC expression, CD8+ T cells, and cytotoxic CD8+ T cells. Our findings indicate that HRH1 blockade upregulates MHC-I expression in PCCs via cholesterol biosynthesis signaling. In the orthotopic model, the combined inhibition of HRH1 and αPD-1 blockade enhanced cytotoxic CD8+ T cell penetration and efficacy, overcoming resistance to ICB therapy. CONCLUSIONS: HRH1 plays an immunosuppressive role in cancer cells. Consequently, HRH1 intervention may be a promising method to amplify the responsiveness of PDAC to immunotherapy.

Advances in clinical application of H1 antihistamines in the treatment of skin diseases. / H1æŠ—ç»„èƒºè¯åœ¨çš®è‚¤ç— æ²»ç–—ä¸­çš„ä¸´åºŠåº”ç”¨è¿›å±•.

Histamine receptors are classified into 4 types: H1, H2, H3, and H4, each mediating distinct physiological effects and possessing its corresponding antagonistshat that can be used for the prevention and treatment of various diseases. Among them, H1 antihistamines are the fundamental medications in dermatology and are widely used in many diseases such as urticaria and atopic dermatitis. In recent years, with the emergence of novel antihistamines and the discovery of new potential indications for traditional H1 antihistamines, the clinical application of antihistamines is facing new challenges. Further investigation of the novel mechanism for H1 antihistamines, the use of multiple doses of common drugs and potential indications will furnish vital insights for practical clinical application.

Update on Urticaria and Angioedema.

Urticaria and angioedema are caused by immunoglobulin E- and non-immunoglobulin E-mediated release of histamine and other inflammatory mediators from mast cells and basophils. Diagnosis is made clinically, and anaphylaxis must be ruled out if urticaria or angioedema is present. A limited nonspecific laboratory workup should be considered unless elements of the history or physical examination suggest specific underlying conditions. The mainstay of treatment is avoidance of triggers when and if triggers are identified. The first-line pharmacotherapy is second-generation H1 antihistamines, which can be titrated to greater than standard doses.

A Pilot Study of Ketotifen in Patients Aged 8-17 Years with Functional Dyspepsia Associated with Mucosal Eosinophilia.

BACKGROUND AND OBJECTIVE: Mast cells have been implicated in abdominal pain-associated disorders of gut-brain interaction, such as functional dyspepsia. As such, ketotifen, a second-generation antihistamine and mast cell stabilizer, could represent a viable treatment option in these conditions. The primary aim of the current pilot study was to assess clinical response to ketotifen and assess pharmacokinetics in youth with functional dyspepsia. METHODS: We conducted a pilot randomized, double-blind, placebo-controlled, cross-over trial of ketotifen in 11 youth with functional dyspepsia and duodenal mucosal eosinophilia with 4 weeks of active treatment at a dose of 1 mg twice daily. Global clinical response was graded on a 5-point Likert Scale. A single plasma sample was obtained at steady state for pharmacokinetic analysis. RESULTS: Ketotifen was not superior to placebo with regard to global clinical response. Only 18% of patients demonstrated a complete or near-complete clinical response. The estimated half-life was 3.3 h. CONCLUSIONS: While ketotifen was not superior to placebo, this study highlights several important challenges for developing drug trials for youth with chronic abdominal pain. Recommendations are made for designing a larger treatment trial for ketotifen in this patient group. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov: NCT02484248.

Diphenhydramine and Migraine Treatment Failure in Pediatric Patients Receiving Prochlorperazine.

OBJECTIVES: The objectives are to determine whether diphenhydramine coadministered with prochlorperazine versus prochlorperazine only is associated with a difference in the risk of migraine treatment failure, as measured by the need for additional therapy, hospitalization rates, and 72-hour return rates, and to compare extrapyramidal adverse effects between groups. METHODS: Retrospective cohort of patients aged 7 to 18 years treated in the emergency department for migraines using prochlorperazine with or without diphenhydramine between 2013 and 2019. Patients were included if they had International Classification of Diseases, Ninth or Tenth Revision, codes for migraine or unspecified headache and were treated with prochlorperazine as part of their initial migraine therapy. Data collected included demographics, medications administered, pain scores, neuroimaging, disposition, return visits, and documentation of extrapyramidal adverse effects. Multivariable logistic regression was used to estimate the association between diphenhydramine coadministration and each of the outcomes. RESULTS: A total of 1683 patients were included. Overall, 13% required additional therapy with a 16.7% admission rate and a 72-hour return rate of 5.3%. There was no association between initial treatment with diphenhydramine and the odds of additional therapy (adjusted odds ratio [aOR], 0.74 [95% confidence interval {CI}, 0.53-1.03]), admission rates (aOR, 1.22 [95% CI, 0.89-1.67]), or return visit rates (aOR, 0.91 [95% CI, 0.55-1.51]). Extrapyramidal adverse effects occurred in 2.4% of patients in the prochlorperazine group and 0% in the prochlorperazine with diphenhydramine group. CONCLUSIONS: There was no association between diphenhydramine coadministration and the need for additional therapy, 72-hour return visit rates or admission rates. Extrapyramidal effects did not occur in patients treated with diphenhydramine.

Leukotriene receptor antagonists as adjuvant therapy of antihistamines in chronic urticaria: a systematic review and meta-analysis.

Certain guidelines recommend a second-generation H1-antihistamine (AH) as first-line treatment for patients with chronic urticaria (CU). However, some patients show insufficient response to a standard dose of this therapy and might benefit from adding leukotriene receptor antagonists (LTA). Therefore, we aimed to perform a systematic review and meta-analysis comparing LTA plus antihistamines with antihistamines alone. We performed a systematic review and meta-analysis, searching PubMed, EMBASE, and Cochrane Central for randomized clinical trial (RCT) data comparing LTA plus AH treatment to AH alone in patients with CU. Statistical analysis was performed using R Studio 4.3.2. Heterogeneity was assessed with I2 statistics. Three studies comprising 234 patients with urticaria were included. The mean age was 37.23 years in the leukotriene antagonist + antihistamines (LTA + AH) group and 39.14 years in the antihistamines (AH) group. Follow-up ranged from 2 to 18 months between studies. There was no statistically significant difference between groups in terms of TSS level (SMD: -74.82; 95% CI: -222.66 to 73.02; P = 0.32; I2 = 98%), neither in terms of pruritus (MD: -0.07; 95% CI: -0.42 to 0.28; P = 0.70; I2 = 74%). After sensitivity analysis, with the systematic exclusion of each study from the grouped estimates, the result for TSS level did not change. These findings suggest that leukotriene receptor antagonists with antihistamines do not have better outcomes than antihistamines alone regarding TSS and pruritus in patients with CU.

UCOMB-real life data: treatment strategies for chronic urticaria patients with comorbidities.

BACKGROUND: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities. METHODS: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines. RESULTS: Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria. CONCLUSIONS: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.

Allergic Rhinitis: A Review.

Importance: Allergic rhinitis affects an estimated 15% of the US population (approximately 50 million individuals) and is associated with the presence of asthma, eczema, chronic or recurrent sinusitis, cough, and both tension and migraine headaches. Observations: Allergic rhinitis occurs when disruption of the epithelial barrier allows allergens to penetrate the mucosal epithelium of nasal passages, inducing a T-helper type 2 inflammatory response and production of allergen-specific IgE. Allergic rhinitis typically presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and itching of the eyes, nose, and throat. In an international study, the most common symptoms of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%). Patients with nonallergic rhinitis present primarily with nasal congestion and postnasal drainage frequently associated with sinus pressure, ear plugging, muffled sounds and pain, and eustachian tube dysfunction that is less responsive to nasal corticosteroids. Patients with seasonal allergic rhinitis typically have physical examination findings of edematous and pale turbinates. Patients with perennial allergic rhinitis typically have erythematous and inflamed turbinates with serous secretions that appear similar to other forms of chronic rhinitis at physical examination. Patients with nonallergic rhinitis have negative test results for specific IgE aeroallergens. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 consecutive days/week or less than 4 consecutive weeks/year. Persistent allergic rhinitis is defined as symptoms occurring more often than 4 consecutive days/week and for more than 4 consecutive weeks/year. Patients with allergic rhinitis should avoid inciting allergens. In addition, first-line treatment for mild intermittent or mild persistent allergic rhinitis may include a second-generation H1 antihistamine (eg, cetirizine, fexofenadine, desloratadine, loratadine) or an intranasal antihistamine (eg, azelastine, olopatadine), whereas patients with persistent moderate to severe allergic rhinitis should be treated initially with an intranasal corticosteroid (eg, fluticasone, triamcinolone, budesonide, mometasone) either alone or in combination with an intranasal antihistamine. In contrast, first-line therapy for patients with nonallergic rhinitis consists of an intranasal antihistamine as monotherapy or in combination with an intranasal corticosteroid. Conclusions and Relevance: Allergic rhinitis is associated with symptoms of nasal congestion, sneezing, and itching of the eyes, nose, and throat. Patients with allergic rhinitis should be instructed to avoid inciting allergens. Therapies include second-generation H1 antihistamines (eg, cetirizine, fexofenadine, desloratadine, loratadine), intranasal antihistamines (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, fluticasone, triamcinolone, budesonide, mometasone) and should be selected based on the severity and frequency of symptoms and patient preference.

Shedding light on dermographism: a narrative review.

Dermographism is a common subtype of chronic urticaria. It generally manifests as a linear wheal after scratching or friction, with or without angioedema. The pathophysiology is not clear, but currently, we believe that the stimulation of the skin by mechanical stress leads to the activation of mast cells, which provoke the release of histamine and pro-inflammatory mediators, ultimately forming wheal along the stressed area. The gold standard for diagnosis is a medical history and provocation test or dermatographic test. As one of the subtypes of chronic urticaria, the Urticaria Control Test (UCT), Chronic Urticaria Quality of Life questionnaire (CU-Q2oL), and Dermatology Life Quality Index (DLQI) are also effective tools for evaluating disease control in dermographism patients. In addition to avoiding triggers, nonsedating H1 antihistamines are the first-line medications recommended by EAACI and other guidelines; for those who do not respond to standard doses, the recommended dosage can be increased up to 4 times. When necessary, the off-label use of omalizumab can be considered, and some drugs with potential therapeutic effects are still being explored. However, there is still a lack of biomarkers for predicting disease severity, efficacy, and prognosis. Here, we review what we know about dermographism and some points that need exploration in the future.

Discovery of the novel and potent histamine H1 receptor antagonists for treatment of allergic diseases.

Desloratadine, a second-generation histamine H1 receptor antagonist, has established itself as a first-line drug for the treatment of allergic diseases. Despite its effectiveness, desloratadine exhibits an antagonistic effect on muscarinic M3 receptor, which can cause side effects such as dry mouth and urinary retention, ultimately limiting its clinical application. Herein, we describe the discovery of compound Ⅲ-4, a novel H1 receptor antagonist with significant H1 receptor antagonistic activity (IC50 = 24.12 nM) and enhanced selectivity towards peripheral H1 receptor. In particular, Ⅲ-4 exhibits reduced M3 receptor inhibitory potency (IC50 > 10,000 nM) and acceptable hERG inhibitory activity (17.6 ± 2.1 µM) compare with desloratadine. Additionally, Ⅲ-4 exhibits favorable pharmacokinetic properties, as well as in vivo efficacy and safety profiles. All of these reveal that Ⅲ-4 has potential to emerge as a novel H1 receptor antagonist for the treatment of allergic diseases. More importantly, the compound Ⅲ-4 (HY-078020) has recently been granted clinical approval.

A systematic review and meta-analysis of efficacy and safety of compound glycyrrhizin combined with second-generation non-sedated antihistamine for the treatment of chronic urticaria.

BACKGROUND: Chronic urticaria (CU) is a prevalent dermatologic disease that negatively affects life, current therapies remain suboptimal. Hence, there is an urgent need to identify effective and safe treatment. OBJECTIVE: Assess the efficacy and safety of compound glycyrrhizin (CG) combined with second-generation nonsedated antihistamine for the treatment of CU. METHODS: Nine databases were queried to screen RCTs related. Two reviewers independently assessed the risk of bias using Cochrane Collaboration. Primary objective was the total efficiency rate, while secondary was rate of recurrence, adverse events, and cure. Statistical analyses using Review Manager 5.4 and Stata17. RESULTS: Twenty-four RCTs were identified. Significant differences were noted in rate of total efficiency (n = 2649, RR = 1.36, 95%CI:1.30-1.43, p < 0.00001), cure (n = 2649, RR = 1.54, 95%CI:1.42-1.66, p < 0.00001) and recurrence (n = 446, RR = 0.34, 95%CI:0.20-0.58, p < 0.00001) between the combination of CG with second-generation non-sedated antihistamine and antihistamine monotherapy. Contrastingly, adverse events rate (n = 2317, RR = 0.76, 95% CI:0.59-0.97, p = 0.03) was comparable between the two groups. Our results indicated that CG combined with second-generation non-sedated antihistamine could significantly mitigate the symptoms in CU compared with antihistamine monotherapy. No serious adverse events were reported. CONCLUSIONS: CG combined with second-generation nonsedated antihistamine is effective for CU. Nevertheless, higher-quality studies are warranted to validate our results.

Evaluation of Pharmacological Treatments for Acute Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness and safety of pharmacological treatments for acute urticaria remain unclear. OBJECTIVE: To systematically review and meta-analyze the efficacy and safety of pharmacological treatments for acute urticaria in emergency department (ED) and non-ED settings. METHODS: We searched electronic databases and gray literature up to July 8, 2023, without language restrictions. Randomized clinical trials (RCTs) relating to pharmacological interventions in patients with acute urticaria, regardless of age, were eligible for inclusion. The relevant outcomes of interest were the treatment efficacy and safety profiles. The results are presented as standardized mean differences (SMDs) or odds ratios (ORs). RESULTS: We identified 8 RCTs comprising 680 patients. Regarding the ED setting (2 trials, n = 118), intramuscular first-generation H1-antihistamine (fgAH) was more efficacious in decreasing pruritus symptoms (SMD, -0.38; 95% confidence interval [CI], -0.75 to -0.02) but had higher sedative effects than H2-blockers. With comparable pruritus symptom improvement (2 trials, n = 295), intravenous second-generation H1-antihistamine (sgAH) had favorable clinical outcomes compared with intravenous fgAH in the ED setting with a lower risk of return to any ED/clinic (OR, 0.31; 95% CI, 0.12-0.83) and lower risk of any adverse event (OR, 0.24; 95% CI, 0.09-0.63). The efficacy of adjunctive therapy with a short course of systemic glucocorticosteroids in ED and non-ED settings remains unclear. No serious concerns regarding the safety profiles were observed in any of the treatment comparisons. CONCLUSIONS: H1-antihistamine is a crucial and effective component of acute urticaria treatment, and intravenous sgAH is preferred as an initial treatment option.

Effectiveness of promethazine on preoperative and intraoperative sequelae in cleft palate surgeries.

INTRODUCTION: Anxiety and nosocomial infection are the most common reported problems in children undergoing cleft surgeries. Research shows that there is an enigma in the use of antihistamine therapy in children for the management of upper respiratory tract infection. 'Promethazine' is a first-generation H1 receptor antagonist, and antihistamine also has strong sedative effects. Our study aims at evaluating the Effectiveness of Promethazine (Phenergan) in preoperative and intra operative sequelae in cleft surgeries. MATERIALS AND METHODS: This is a single-centre, parallel, randomized, double-blinded randomized control clinical trial, which was conducted among 128 children between 2 and 4 years of age undergoing cleft palate surgery under general anaesthesia. After randomization, the case group was subjected to promethazine syrup 1 mg/kg body weight twice a day, orally for 3 days. The primary outcomes were preoperative anxiety levels which were recorded by children fear scale. The secondary outcomes include preoperative sleep quality and cough rate of children which are recorded by using sleep and cough objective scale respectively. The intraoperative heart rate is monitored with an ECG connected to a monitor. RESULTS: Promethazine causes a reduction in the anxiety level by 70%, 64% reduction in cold and cough, improvement in sleep score by 70% and the heart rate was found to be stable throughout the surgery when compared to the control group. CONCLUSION: As the benefits of promethazine in cleft palate surgery rule over its adverse effects, promethazine is considered safe to be used as premedication for children undergoing cleft palate surgeries.

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

BACKGROUND: 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. OBJECTIVE: We sought to evaluate long-term safety and efficacy of remibrutinib in patients with CSU inadequately controlled with H1 antihistamines. METHODS: 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. RESULTS: 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. CONCLUSIONS: Remibrutinib demonstrated a consistent favorable safety profile with fast and sustained efficacy for up to 52 weeks in patients with CSU.