H1-antihistamines Research Articles

Association of concomitant H1 antihistamine and immune checkpoint inhibitor therapy on survival outcome and safety in patients with advanced primary lung cancer: a cohort study.

Antihistamines alleviate the side effects of antitumor drugs and exert antitumor effects. This study aimed to investigate the potential impact of short-term concomitant use of antihistamines with immune checkpoint inhibitor (ICI) therapy on the efficacy and immune-related adverse events (irAEs) of immunotherapy for patients with advanced lung cancer. We retrospectively analyzed the medical records of 211 patients diagnosed with advanced primary lung cancer and treated with immunotherapy at Tianjin Medical University Cancer Institute and Hospital between January 1, 2018, and January 1, 2022. Among these patients, 109 who received H1 antihistamine during the infusion of anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) antibodies were assigned to the experimental group; meanwhile, the remaining 102 patients who did not receive H1 antihistamines were assigned to the control group. Balancing was achieved through inverse probability of treatment weight (IPTW) estimation. The data were analyzed using Kaplan-Meier curves and Cox regression analyses. The median progression-free survival (mPFS) was 12.7 months in the experimental group and 4.3 months in the control group, while the median overall survival (mOS) was 32.8 months in the experimental group and 18.1 months in the control group. In the experimental group, patients treated with only H1 antihistamines had longer mPFS and mOS compared with those who received H1 plus H2 antihistamines. Similarly, in the control group, patients who did not receive antihistamines had a longer mPFS and mOS than those who only received H2 antihistamines. After conducting multivariate analyses, we found that H1 and H2 antihistamines were respectively identified as good and poor independent prognostic factors for both progression-free survival (PFS) and overall survival (OS). The rates of irAEs in the experimental and control groups were 52.4% and 69.2%, respectively, and grade ≥3 irAEs occurred in 4.5% and 25.9% of patients, respectively. Concomitant use of H1 antihistamines can improve immunotherapy efficacy and reduce irAEs. Meanwhile, concomitant use of H2 antihistamines is associated with reduced PFS and OS time.

Efficacy and safety of switching to bilastine, an H1-antihistamine, in patients with refractory chronic spontaneous urticaria (H1-SWITCH): a multicenter, open-label, randomized, parallel-group comparative study.

For treating patients with refractory chronic spontaneous urticaria (CSU) resistant to standard doses of 2nd generation H1-antihistamines (H1AH) the International and Japanese guidelines recommend increasing H1AH dose. The latter also recommends switching to a different H1AH. This study explored if the efficacy of the standard dose of bilastine 20 mg is non-inferior to that of double-dose of H1AH in patients with refractory CSU. This phase IV, multicenter, open-label, randomized, parallel-group trial evaluated the efficacy and safety of switching treatment to bilastine compared to treatment with a 2-fold dose of H1AH in patients with CSU refractory to standard dose H1AH. The primary endpoint was the mean total symptom score (TSS) at Day 5-7 after the start of administration. Treatment efficacy and safety were evaluated in 128 patients (bilastine, n=64; 2-fold dose of H1AH, n=64). The mean TSS at Day 5-7 after the start of administration was smaller than the non-inferiority margin of 0.8, demonstrating non-inferiority of the bilastine switching group to the double-dose H1AH group (0.17 (95% CI -0.32, 0.67)). No difference in Japanese version of Epworth Sleepiness Scale (JESS), DLQI, and urticaria activity score over 7 consecutive days (UAS7) was observed between the two groups. There were no serious adverse events in either group. H1AH-related adverse events occurred in 5 subjects (8 cases) and 2 subjects (3 cases) in the double-dose H1AH and bilastine groups, respectively. Switching treatment to bilastine demonstrated non-inferiority to a double-dose of H1AH in terms of efficacy in patients with CSU refractory to standard dose H1AH with a favorable safety profile. https://jrct.niph.go.jp/latest-detail/jRCTs051180105, identifier jRCTs051180105.

53693 Dupilumab Improves Emotional Burden in Patients with Chronic Spontaneous Urticaria Uncontrolled by H1 Antihistamines

53693 Dupilumab Improves Emotional Burden in Patients with Chronic Spontaneous Urticaria Uncontrolled by H1 Antihistamines

53474 Dupilumab Improves Self-Perception and Relationships among Patients with Chronic Spontaneous Urticaria Uncontrolled by H1 Antihistamines

53474 Dupilumab Improves Self-Perception and Relationships among Patients with Chronic Spontaneous Urticaria Uncontrolled by H1 Antihistamines

53782 Dupilumab Improves Sleep Quality in Patients with Chronic Spontaneous Urticaria Inadequately Controlled with H1 Antihistamines

53782 Dupilumab Improves Sleep Quality in Patients with Chronic Spontaneous Urticaria Inadequately Controlled with H1 Antihistamines

53763 Dupilumab Improves Activity and Work Productivity Among Patients with Chronic Spontaneous Urticaria Inadequately Controlled with H1 Antihistamines

53763 Dupilumab Improves Activity and Work Productivity Among Patients with Chronic Spontaneous Urticaria Inadequately Controlled with H1 Antihistamines

The efficacy of autologous serum therapy in chronic spontaneous urticaria: A systematic literature review and meta-analysis

Chronic spontaneous urticaria (CSU) is an autoimmune disease characterised by urtica lesions and/or angioedema accompanying an itching sensation, recurring for at least six weeks without any specific trigger. Autologous serum therapy (AST) is an adjuvant therapy for CSU that is resistant to H1 antihistamines. This therapy is an economical option in developing countries. There were a few studies discussing the role of AST in CSU. This systematic review and meta-analysis were conducted to evaluate the efficacy of AST based on urticaria activity scores (UAS or UAS7) and urticaria total severity scores (TSS) so that clinicians can consider them. Data were searched systematically in Cochrane, PubMed, Google Scholar, Willey, and EMBASE from 2000 to March 2023. Data analysis using Excel 2010 (Microsoft Corp) and MedCalc version 20.218. There were 14 studies: 4 randomised controlled trials (RCT), 9 prospective, and 1 cross-sectional. The average improvement in UAS and TSS scores at the end of therapy was 42.24% and 41.24%. Results of subgroup analysis of AST administration in the group autologous serum skin test (ASST) positive and ASST negative based on the end of therapy UAS score (p=0.18). Results of subgroup analysis of AST administration in the positive ASST and negative ASST groups based on the TSS score at the end of therapy (p=<0.001). Results of subgroup analysis of AST administration versus placebo based on TSS score (p=0.861). Based on subgroup analysis, autologous serum therapy improves TSS scores in CSU patients (ASST positive). However, AST is not significantly different from placebo.

Development of a transcutaneous form of desloratadine

Introduction: For people with allergies, it is not always possible to prevent allergens admission to the body. For this reason, it is essential to create a long-acting drug that can prevent an allergic reaction. The very promising option is a transdermal therapeutic system (TTS), with H1 blockers. The aim of the study: To create a technology for the production of desloratadine-based TTS, suitable for routine use with prolonged drug releasing. Materials and Methods: Polyvinylpyrrolidone K30 (PVP) was used as the main matrix polymer for TTS, and the Kruofilm polymer membrane was used as the adhesive layer. The formation of the polymer membrane was carried out by drying a water-alcohol solution of the components at a temperature of 60ºC. Characterization of the obtained dosage forms was made by spectrophotometry. The resulting micelles size was measured by dynamic light scattering. Results and Discussion: Round shaped TTS (patches) with water-dissolved DL and its micellar form were obtained. The size of micelles with DL was 22.8±5.2 nm. The spectrophotometric method for determining DL has been developed. The containing of DL in the patches ranged from 5 to 25 mg per patch, depending on the manufacturing technology. Conclusion: We have developed TTSs containing DL by a solution and a micellar form. A top adhesive layer has been selected that has moisture resistance, strength and reliable fixation of the matrix with the active substance on the skin. A method for the spectrophotometric determination of DL in solutions and patches was developed and validated.

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

H1 antihistamines (AHs), categorized as first-generation antihistamines (FGAs) or second-generation antihistamines (SGAs), possess anticholinergic properties linked to heightened dementia risk. To explore dementia risk in patients with allergic rhinitis using AHs. Taiwanese patients with new-onsetallergic 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. 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). 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.

Efficacy and safety of combinations of H1 antihistamines in the treatment of urticaria: A scoping review.

The efficacy and safety of combining H1 antihistamines (AHs) for treating urticaria are currently unclear. This scoping review aims to provide a comprehensive overview of the evidence regarding the efficacy and safety of H1 AH combinations in the management of urticaria up to May 2023. The search encompassed databases such as PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and the China Biological Medicine Database. The inclusion criteria comprised randomised controlled trials (RCTs), non-randomised trials (NRTs), case reports, and case series focusing on urticaria treatment. Initially screening 12,887 studies, this review ultimately selected 109 studies involving 11,435 patients. These studies documented 43 different combination treatments across 11 types of urticaria. In comparison to monotherapy, combination therapy exhibited superior efficacy in 94 studies that reported treatment efficacy. Regarding adverse drug reactions (ADRs), 67 studies disclosed ADR incidences, with combination therapy showing lower ADR rates in 32 studies. Additionally, 7 studies reported similar ADR rates between combination therapy and monotherapy with AHs. Common ADRs included symptoms such as drowsiness, nausea, fatigue, dry mouth, dizziness, and headache, while less frequent side effects encompassed hypotension, otitis media, polyuria, rhinorrhoea, abnormal liver function, and rash. ADR rates ranged from 0% to 21% in the treatment group, and from 0.5% to 75% in the control group. Importantly, patients generally tolerated these ADRs well, with symptoms resolving upon discontinuation of treatment. The study's findings suggest that combining AHs leads to enhanced efficacy and reduced safety risks compared to monotherapy in the context of urticaria treatment. These results advocate for considering combination therapy as a viable option in clinical practice, especially for chronic urticaria cases. Nonetheless, caution is advised, and close monitoring for potential ADRs is crucial during treatment.

Treatment options in refractory chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) patients sometimes do not respond to second-generation antihistamine, and 10-50% patients do not even respond to four-fold the usual dose of nonsedating H1 antihistamine, which further leads to repeated courses of oral corticosteroids to abate the symptoms. There are third-line agents approved by EAACI guidelines, which include omalizumab and cyclosporine. Certain patients are even resistant to the third-line agents. In this review, various other treatment options will be discussed in patients of refractory CSU. Recently, we demonstrated azathioprine as a possible third-line option, which was found noninferior to cyclosporine in antihistamine refractory CSU. There have been trials, studies, case series and reports, which suggest other putative options for refractory CSU management. Studies on the management of refractory CSU are accumulating thereby expanding the armamentarium of dermatologists and allergologist against difficult-to-treat urticaria patients.

Urticaria Pigmentosa – A Case Report with a Review of the Literature

Mastocytosis encompasses a rare group of diseases characterized by the accumulation of mast cells, primarily in the skin or internal organs. In the 2016 revised WHO classification, mastocytosis is divided into cutaneous mastocytosis (CM), systemic mastocytosis (CM), and localized mast cell tumor. Cutaneous mastocytosis (CM) includes maculo-papular CM/urticaria pigmentosa (UP), diffuse CM and cutaneous mastocytoma. Urticaria pigmentosa is the most common skin variant. It presents with erythematous brownish macules or papules, often accompanied by pruritus. A case of a 48-year-old woman with disseminated, mildly pruritic, sharply demarcated, livid-brownish macules on the skin of the trunk and extremities is presented. A positive Darier symptom was established. Laboratory tests revealed granulocytosis (73%) and lymphocytosis (19.8%). Serum tryptase and 24-hour urine 5-hydroxyindoleacetic acid were not elevated. The diagnosis of urticaria pigmentosa was confirmed by the histopathological examination revealing perivascular infiltrates of mast cells, mainly in the deep dermis. Screening performed did not detect systemic involvement. Symptomatic treatment with H1 and H2 blockers and topical corticosteroid was carried out. Avoidance of triggers is recommended. The patient&amp;apos;s condition has improved. Both a historical review of mastocytosis and a revised classification, as well as the epidemiology, etiology with triggering factors, clinical presentation, laboratory investigations, and management of urticaria pigmentosa are presented.

A CROSS-SECTIONAL STUDY ON SELF-MEDICATION PRACTICES, PERCEPTION, AND ATTITUDES OF UNDERGRADUATE MEDICAL STUDENTS AT A GOVERNMENT TERTIARY CARE TEACHING HOSPITAL IN EASTERN INDIA

Objectives: Self-medication (SM) is common in India. It is of greater significance when practiced by medical students as they going to be medical practitioners in the future. This study was conducted to assess the pattern of SM practices, perceptions, and attitudes among students pursuing 2nd-year professional MBBS in a tertiary medical college in the year 2019. Methods: This study was a cross-sectional one based on a questionnaire. It was conducted among the 2nd-year undergraduate (MBBS) medical students in a tertiary care medical college in West Bengal, India. Results: Out of 199 students approached, 198 consented to the study and filled in the supplied study questionnaire. Thirteen incomplete questionnaires were excluded and the remaining 185 were analyzed. It was found that 81.6% (151/185) respondents practiced SM. The most common ailments for seeking SM were fever 66.2% (100/151), followed by cough cold, and sore throat 55.0% (84/151), diarrhea/nausea, and vomiting 40.4% (61/151). The most common drug used for SM was paracetamol 73.51% (111/151), followed by H1 antihistaminics and proton pump inhibitors. A small percentage of students used topical preparations of steroids, analgesics, antibiotics, and antifungals as well. Among the common reasons for seeking SM, 72.2% (109/151) felt that their illness was mild and 57% (86/151) preferred it as they had prior experience. Conclusion: Our study showed that SM is commonly practiced among the students of this institution. Therefore, medical teachers need to try even more to generate adequate awareness among the students about inherent risks of SM.

Impact of concomitant H1 antihistamine administered during initiation of immune checkpoint inhibitor therapy on survival outcome and safety in patients with advanced primary lung cancer.

e20532 Background: Antihistamines alleviate the side effects of antitumor drugs and have some antitumor effects. However, they have rarely been tested in combination with other antitumor therapies, especially immunotherapy. Methods: We compared the progression-free survival (PFS) and overall survival (OS) of patients with advanced primary lung cancer (stage III or IV) receiving immunotherapy with H1 antihistamine diphenhydramine alone (n = 40) or in combination with H2 antihistamine cimetidine (n = 69) [experimental group] to those receiving immunotherapy alone (n = 75) or with a H2 antihistamine cimetidine (n = 27) [control group]. We used the inverse probability of treatment weights (IPTW) to balance the two groups. Kaplan Meier curves were used to compare OS and PFS between the two groups. Cox regression analyses were used to describe the association between patient characteristics and OS or PFS. Results: The experimental group comprised 109 patients, while the control group comprised 102. The median PFS (mPFS) was 12.7 months in the experimental group and 4.3 months in the control group (HR 0.46, 95% CI 0.35-0.63, P &lt; 0.001). The median OS (mOS) was 32.8 months in the experimental group and 18.1 months in the control group (HR 0.63, 95% CI 0.44-0.91, P = 0.038). In the experimental group, patients treated with only H1 antihistamine had longer mPFS and mOS as compared with those who received H1 plus H2 antihistamines (mPFS: 18.0 months vs. 6.8 months, HR 1.40, 95% CI 0.26-0.63, P &lt; 0.001; mOS: not reached vs. 26.6 months, HR 0.55, 95% CI 0.32-0.94, P = 0.030). In the control group, patients who received no antihistamine had longer mPFS and mOS compared to those who received only H2 antihistamines (mPFS: 5.8 months vs. 4.1 months, HR 0.44, 95% CI 0.29-0.67, P &lt; 0.001; mOS: 25.5 vs. 16.9 months, HR 0.61, 95% CI 0.37-1.00, P = 0.049). After multivariate analyses, H1 antihistamine was the independent good prognostic factor for PFS and OS (PFS: HR 0.44, 95% CI 0.31-0.65, P &lt; 0.001; OS: HR 0.62, 95% CI 0.39-0.99, P = 0.047). Conversely, H2 antihistamine was the independent poor prognostic factor for PFS and OS (PFS: HR 2.44, 95% CI 1.67-3.57, P &lt; 0.001; OS: HR 2.38, 95% CI 1.49-3.70, P &lt; 0.001). After IPTW, the rate of any grade of irAEs in the experimental group was 52.4%, while that of the control group was 69.2% ( P = 0.015), including 4.5% for irAEs grades ≥3 in the experimental group and 25.9% for irAEs grades ≥3 in the control group ( P = 0.003). Conclusions: Concomitant H1 antihistamines can not only improve immunotherapy efficacy but also reduce irAEs. Concomitant use of H2 antihistamines may shorten PFS and OS time.

Does diphenhydramine exert a sex-dependent effect on sudomotor responses during exertional heat stress?

Introduction: The first-generation H1 antihistamine diphenhydramine hydrochloride (DPH) is a potent antimuscarinic agent which may compromise sweat output during heat stress. DPH consumption prior to exertional heat stress could further suppress the sweating response in females due to their lower postjunctional cholinergic sensitivity of the sweat glands relative to males. Objective and Hypothesis: The purpose of the present study was to test the hypothesis that DPH would reduce sweating to a greater extent in females relative to males due to differences in cholinergic sensitivity at the sweat gland. Methods: Equal groups (10 per group) of males (24±3 y; 82.6±10.1 kg; 182±5 cm) and females (22±3 y, 67.7±7.8 kg, 171±6 cm) completed two experimental trials presented in a randomized double-blind fashion. Upon arrival to lab, participants consumed either i) a placebo (PLA) pill or ii) 50 mg DPH and then rested in a room maintained at ~29.5°C &amp; 35% RH for 2 hours before conducting a 60-minute treadmill march at a fixed rate of heat production relative to body surface area (~245 W/m2). Rectal temperature (Trec), local sweat rate of the forearm (LSR), and whole body sweat loss (WBSL) were measured. Sex-segregated analysis was conducted for each outcome variable as the difference between PLA and DPH. Results: Baseline Trec did not differ within sex between PLA and DPH (males: -0.10±0.26°C; females: -0.05±0.33°C, P=0.70), however a higher absolute baseline Trec was observed in females compared to males (P=0.006). In comparison to PLA, DPH did not exert a sex-dependent effect on ΔTrec following 60-min of exercise (males: 0.04±0.11°C; females: 0.02±0.37°C, P=0.90). No sex-dependent effect on the onset of sweating was observed between DPH and PLA (males: -0.4±2.6 min; females: 0.6±2.4 min, P=0.34). DPH did not exert a sex-dependent effect on LSR at steady-state (males: 0.03±0.25 mg/cm2/min; females: -0.01±0.21 mg/cm2/min, P=0.71). Lastly, no sex-dependent effect on WBSL was observed between PLA and DPH (males: 14±34 g; females: 6±43 g, P=0.98). Conclusion: Current evidence suggests that sex does not independently modulate the sweating response during exertional heat stress following the consumption of 50 mg of DPH. This research is supported by Dr. Ravanelli’s Research Seed Grant from the Centre for Research in Occupational Safety &amp; Health, and Dr. Ravanelli’s Natural Sciences and Engineering Research Council of Canada Discovery Grant (PIN#2022-05096). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hymenoptera venom immunotherapy: Safety and efficacy of an accelerated induction regimen with depot aluminum adsorbed extracts.

Introduction: Hymenoptera venom immunotherapy (VIT) is the only therapy that protects patients with Hymenoptera venom allergy by preventing systemic reactions after a new sting. Various extracts for VIT are available and used. VIT administration consists of an induction phase and a maintenance phase. Depot preparations of Hymenoptera VIT extracts are typically used for cluster and conventional protocols, and the maintenance phase. Many patients with Hymenoptera allergy need to achieve tolerance quickly because of the high risk of re-sting and possible anaphylaxis. Objective: Our study aimed to show the safety and efficacy of an accelerated regimen with depot preparations on aluminum hydroxide by using relatively high starting doses in a heterogeneous group of patients. Methods: The research focused on a group of patients with a history of severe systemic reactions to Hymenoptera stings, with the necessity of swift immunization due to high occupational risks. Aluminum hydroxide depot extracts either of Vepula species or Apis mellifera extracts were used. Results: The induction protocol was started with the highest concentration of depot venom extract of 100,000 standard quality unit and was well tolerated by 19 of 20 patients. Onne patient presented with a mild systemic reaction during the accelerated induction schedule, which was promptly treated with intravenous steroids and intramuscular H1 antihistamine; when switched to a conventional induction protocol, he had a similar reaction but finally reached maintenance with an H1-antagonist premedication. Conclusion: If validated, the accelerated induction protocol by using depot aluminum adsorbed extracts with the highest concentration of venom from the beginning could offer a streamlined and accessible treatment modality for patients diagnosed with anaphylaxis from bee and wasp venoms in need of rapid desensitization.

The antiglycation potential of H1 receptor antagonists – in vitro studies in bovine serum albumin model and in silico molecular docking analyses

The H1 receptor belongs to the family of rhodopsin-like G-protein-coupled receptors activated by the biogenic amine histamine. H1 receptor antagonists are widely used in the treatment of allergies. However, these drugs could have a much broader spectrum of activity, including hypoglycemic effects, which can broaden the spectrum of their use. The aim of the study was to evaluate the antiglycation potential of twelve H1 receptor antagonists (diphenhydramine, antazoline, promethazine, ketotifen, clemastine, pheniramine, cetirizine, levocetirizine, bilastine, fexofenadine, desloratadine, and loratadine). Bovine serum albumin (BSA) was glycated with sugars (glucose, fructose, galactose, and ribose) and aldehydes (glyoxal and methylglyoxal) in the presence of H1 blockers. The tested substances did not induce a significant decrease in the content of albumin glycation end-products, and the inhibition rate of glycoxidation was not influenced by the chemical structure or generation of H1 blockers. None of the tested H1 receptor antagonists exhibited strong antiglycation activity. Antiglycemic potential of H1 blockers could be attributed to their antioxidant and anti-inflammatory activity, as well as their effects on carbohydrate metabolism/metabolic balance at the systemic level.

Predicting responses to omalizumab in antihistamine-refractory chronic urticaria: A real-world longitudinal study

BackgroundTreating chronic urticaria (CU) unresponsive to H1-antihistamines (H1AHs) is challenging, and the real-world effectiveness of omalizumab remains unclear. ObjectiveTo evaluate the real-world effectiveness of omalizumab, optimal response assessment timing, and predictive factors. MethodsInitially, 5,535 CU patients on ≥ 20 mg loratadine daily for ≥ 6 months (Jan 2007-Aug 2021) were screened; 386 patients receiving ≥ 6 months of omalizumab add-on treatment and were assessed for > 2 years. Predictors of treatment responses to omalizumab add-on therapy for anti-histamine refractory CU patients were identified using a generalized linear model. ResultsIn our retrospective cohort, omalizumab treatment showed cumulative response rates of 55.2% at 3 months, 71.0% at 6 months, and 81.4% at 9 months for H1AH-refractory CU patients. Longitudinal responses to omalizumab treatment revealed three distinct clusters: favorable (cluster 1, n=158), intermediate (cluster 2, n=143), and poor responses (cluster 3, n= 85). Subjects were categorized based on achieving a complete response within 3 months, identifying 213 early responders, 117 late responders, and 56 nonresponders. The initial dose of omalizumab differed significantly among the three clusters. Low total IgE (<40 kU/L) predicted non-response (OR=3.10, P=0.018). Early responders were associated with a higher initial omalizumab dose (≥300 mg, OR=2.07, P=0.016), higher basophil counts (OR=2.0, P=0.014), total IgE levels exceeding 798 kU/L (OR=0.37, P=0.047), and lower platelet-to-lymphocyte ratio (OR=0.50, P=0.050). ConclusionReal-world data reveal three distinct clusters for omalizumab treatment responses, confirm low serum total IgE (<40 kU/L) as a predictor of nonresponse, and identify potential biomarkers, including IgE, basophils, and PLR for early responders.

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.

Bilastine in Refractory Chronic Spontaneous Urticaria: Disease Control and Cytokine Modulation in an Open-label Prospective Study.

The treatment options for chronic spontaneous urticaria (CSU) primarily include second generation non-sedative antihistamine (SGAHs). Bilastine is a newer, nonsedating SGAH approved for urticaria in February 2019 by the Drugs Controller General of India. Its major advantages are in terms of superior efficacy, lack of drug interactions and adverse effects, including sedation, compared to conventional SGAHs. The role of cytokines in the pathogenesis of CSU is well known. However, there is a shortage of data regarding the change in serum levels of proinflammatory cytokines following H1 antihistamines. We conducted this trial to evaluate the role of bilastine in cytokine modulation and autoimmunity, thereby explaining its role in modifying the disease process in CSU. This prospective study was conducted in a tertiary institute in Kolkata on patients aged 12 years and above with a CSU >6 months. These patients had an unsatisfactory response, as per the Urticaria Activity Score 7 (UAS7), to previous antihistamine therapies in standard doses. Treatment effectiveness was determined by comparing the UAS7 at baseline with that at weeks 4, 8 and 12. Also, baseline serum interleukin-6 (IL-6) and IL-17 were compared with those at the end of the study, that is, 12 weeks. Thirty patients who matched the inclusion criteria and signed informed consent were included in the study. At the end of 12 weeks, 10% of patients (n = 3) achieved a complete treatment response (UAS = 0), whereas 43.33% of patients (n = 13) were labelled as having well-controlled urticaria (UAS <6). At 12 weeks, the mean UAS7 score (6.47 ± 4.45) was statistically significant compared to the baseline score (25.47 ± 7.74). The mean values of serum IL-6 (pg/ml) and IL-17 (pg/ml) at baseline were 5.96 ± 5.24 pg/ml and 6.96 ± 5.97 pg/ml, respectively. At the end of treatment, that is, 3 months, the mean values were reduced to 4.61 ± 4.56 pg/ml and 5.08 ± 3.87 pg/ml. The reduction was statistically significant for both serum IL-6 (P < 0.001) and IL-17 (P < 0.0001). We conclude that bilastine at a once-daily continuous dose of 40 mg for 3 months is safe and effective in CSU patients who are refractory to treatment at the standard doses of SGAHs. Improved symptomatic control with bilastine was also associated with better control over the inflammatory process, as suggested by the lowering of mean cytokine levels in our study.