High-dose non-sedating antihistamines are used insufficiently in chronic urticaria patients treated with omalizumab.
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ABSTRACT: Background
The lifetime prevalence of chronic urticaria (CU) is 0.5%-1%. In some patients with CU, symptomatic control is not achieved with non-sedating second-generation H1 antihistamines (nsAH1) alone, even with quadrupled standard doses as recommended in international guidelines. In these cases, biological treatment with omalizumab can be added. Since omalizumab is expensive compared to antihistamines, lack of adherence to guidelines for high dose nsAH1 (up to four-fold standard dose per day) may be associated with substantial unnecessary costs. The aim was to measure the use nsAH1 before and during omalizumab use for the first time in an omalizumab treated CU population.Methods
We identified all Danish patients with CU who initiated omalizumab from March 2014 to December 2018 and evaluated new and ongoing nsAH1 treatments using the Danish nationwide registries.Results
A total of 955 CU patients initiated treatment with omalizumab within the study period (median age 40 years [IQR 28-50], 74.5% females). During the 12 months prior to omalizumab initiation, 95.6% of the patients filled at least one prescription with nsAH1 at some point, while 84.7% filled at least one prescription during the three months before omalizumab. From 3 months before omalizumab initiation till 3 months after, the proportions of users of high-dose nsAH1 was maximum 31.1%.Conclusions
Omalizumab was usually administered before sufficient nsAH1 treatment was tried. In despite of the labelling that omalizumab should be co-administered with high dose nsAH1, this does not happen This may lead to substantial unnecessary costs.
SUBMITTER: Madsen H
PROVIDER: S-EPMC8665689 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionChronic spontaneous urticaria (CSU) is defined as recurrent attacks of urticaria present for more than six weeks. The monoclonal anti-immunoglobulin E antibody, omalizumab, was approved for the treatment of CSU in patients who remain refractory to H1-antihistamines. Biologic agents are shown not to increase the risk of COVID-19 infection in different studies.ObjectiveIn the present study, we aimed to determine the prevalance of COVID-19 infection in relation to the age, gender, presence of other comorbidities, and treatment given for CSU.MethodsWe conducted a descriptive cross-sectional study of 233 patients diagnosed with CSU in a tertiary referral hospital. Demographical data, treatment given for CSU, the presence of COVID-19-related symptoms, history of close contact to a person with COVID-19 and COVID-19 real-time polymerase chain reaction (RT-PCR) results were determined via a telephone survey and checked from medical data records.ResultsOne hundred sixty patients were female; whereas 73 were male. The mean age was 44.76. Out of 233 patients with chronic urticaria, 125 had symptoms related to COVID-19 infection. RT-PCR testing for COVID-19 was performed in 156 patients. Of 156 patients with COVID-19 RT-PCR test, RT-PCR result was positive in 15 cases.ConclusionsNo statistically significant relationship was found between COVID-19 RT-PCR positivity and the type of treatment administered for chronic urticaria when the patients are divided into omalizumab ± oral antihistamines and only oral antihistamines treatment groups (p = 0.150). Omalizumab seems to be safe in the era of COVID-19.
| S-EPMC8661558 | biostudies-literature
Project description:PurposeThe prevalence of chronic urticaria (CU) is increasing worldwide, and it imposes a major burden on patients. Few studies have evaluated the efficacy of second-line treatments of CU, particularly for patients being considered for costly third-line treatments such as omalizumab. We compared the efficacy and safety of second-line treatments of CU refractory to standard doses of nonsedating H1-antihistamines (nsAHs).MethodsThis 4-week, prospective, randomized, open-label trial divided patients into 4 treatment groups: 4-fold updosing of nsAHs, multiple combination of 4 nsAHs, switching to other nsAHs, and adjunctive H2-receptor antagonist. The clinical outcomes included urticaria control status, symptoms, and rescue medication use.ResultsThis study included 109 patients. After 4 weeks of second-line treatment, urticaria was well-controlled, partly controlled, and uncontrolled in 43.1%, 36.7%, and 20.2% of patients, respectively. Complete control of CU was achieved in 20.4% of patients. Among the patients with high-dose nsAHs, the proportion with well-controlled status was higher compared to the patients who received standard doses (51.9% vs. 34.5%, P = 0.031). No significant difference was observed in the proportion of well-controlled cases between the updosing and combination treatment groups (57.7% vs. 46.4%, P = 0.616). However, increasing the dose of nsAHs 4-fold was associated with a higher rate of complete symptom control compared to multiple combination treatment with 4 nsAHs (40.0% vs. 10.7%, P = 0.030). Logistic regression analysis confirmed the higher efficacy of updosing of nsAHs for complete control of CU compared to the other treatment strategies (odds ratio, 0.180; P = 0.020).ConclusionsIn patients with CU refractory to standard doses of nsAHs, both updosing of nsAHs 4-fold and multiple combination treatment with 4 nsAHs increased the rate of well-controlled cases without causing significant adverse effects. Updosing of nsAHs is more effective for complete CU control than combination treatment.
| S-EPMC10359646 | biostudies-literature
Project description:BackgroundNasal symptoms frequently coexist in patients with chronic cough, and non-sedating H1-receptor antihistamines (nsH1RAs) are often prescribed for cough management in several countries. However, recommendations on the use of nsH1RAs vary among chronic cough guidelines. This study aimed to examine the efficacy of nsH1RAs over placebos in adolescents or adults with chronic cough or allergic respiratory conditions that may present as chronic cough.MethodsElectronic databases were searched for studies published until November 2020. Randomized placebo-controlled trials of nsH1RAs reporting cough endpoints in adolescents or adults with chronic cough or cough-associated allergic respiratory conditions (allergic rhinitis, allergic asthma, or atopic cough) were included.ResultsA total of 10 placebo-controlled trials were identified. Three studies (one study each involving allergic rhinitis, allergic rhinitis with comorbid asthma, and atopic cough) described baseline and post-treatment cough scores, and all reported significant improvements in subjective cough scores; however, the magnitude of improvement was greater in the 2 studies of patients with atopic cough (relative improvement in cough frequency score: -36.6 ± 8.4%) or seasonal allergic rhinitis-associated cough (cough frequency score: -44.0 ± 7.3% and cough intensity score: -65.7 ± 8.3%) than in the 1 study of allergic rhinitis patients with comorbid asthma (-4.0 ± 1.3%). Meanwhile, the other 7 trials found conflicting results but lacked information on the baseline cough score and did not use validated cough measurement tools; thus, their clinical relevance could not be determined.ConclusionDespite the widespread use of nsH1RAs in patients with chronic cough, only a few clinical trials examining their benefits on cough outcomes have been conducted. There may be a subgroup of patients, particularly those with seasonal allergic rhinitis-associated cough or atopic cough, whose cough may improve with nsH1RA treatment. However, adequately powered trials with validated cough measurement tools are warranted to confirm the role of nsH1RAs in the management of patients with allergic phenotypes of chronic cough.
| S-EPMC8322120 | biostudies-literature
Project description:Background and purposeA second-generation antihistamine, terfenadine, is known to induce arrhythmia by blocking hERG channels. In this study, we have shown that terfenadine also inhibits the activity of G-protein-gated inwardly rectifying K+ (GIRK) channels, which regulate the excitability of neurons and cardiomyocytes. To clarify the underlying mechanism(s), we examined the effects of several antihistamines on GIRK channels and identified the structural determinant for the inhibition.Experimental approachElectrophysiological recordings were made in Xenopus oocytes and rat atrial myocytes to analyse the effects of antihistamines on various GIRK subunits (Kir 3.x). Mutagenesis analyses identified the residues critical for inhibition by terfenadine and the regulation of ion selectivity. The potential docking site of terfenadine was analysed by molecular docking.Key resultsGIRK channels containing Kir 3.1 subunits heterologously expressed in oocytes and native GIRK channels in atrial myocytes were inhibited by terfenadine and other non-sedating antihistamines. In Kir 3.1 subunits, mutation of Phe137, located in the centre of the pore helix, to the corresponding Ser in Kir 3.2 subunits reduced the inhibition by terfenadine. Introduction of an amino acid with a large side chain in Kir 3.2 subunits at Ser148 increased the inhibition. When this residue was mutated to a non-polar amino acid, the channel became permeable to Na+ . Phosphoinositide-mediated activity was also decreased by terfenadine.Conclusion and implicationsThe Phe137 residue in Kir 3.1 subunits is critical for inhibition by terfenadine. This study provides novel insights into the regulation of GIRK channels by the pore helix and information for drug design.
| S-EPMC6692640 | biostudies-literature
Project description:ASTERIA I was a 40-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous omalizumab as add-on therapy for 24 weeks in patients with chronic idiopathic urticaria/spontaneous urticaria (CIU/CSU) who remained symptomatic despite H1 antihistamine treatment at licensed doses. Patients aged 12-75 years with CIU/CSU who remained symptomatic despite treatment with approved doses of H1 antihistamines were randomized (1:1:1:1) in a double-blind manner to subcutaneous omalizumab 75 mg, 150 mg, or 300 mg or placebo every 4 weeks for 24 weeks followed by 16 weeks of follow-up. The primary end point was change from baseline in weekly itch severity score (ISS) at week 12. Among randomized patients (N=319: placebo n=80, omalizumab 75 mg n=78, 150 mg n=80, 300 mg n=81), 262 (82.1%) completed the study. Compared with placebo (n=80), mean weekly ISS was reduced from baseline to week 12 by an additional 2.96 points (95% confidence interval (CI): -4.71 to -1.21; P=0.0010), 2.95 points (95% CI: -4.72 to -1.18; P=0.0012), and 5.80 points (95% CI: -7.49 to -4.10; P<0.0001) in the omalizumab 75-mg (n=77), 150-mg (n=80), and 300-mg groups (n=81), respectively. The omalizumab 300-mg group met all nine secondary end points, including a significant decrease in the duration of time to reach minimally important difference response (⩾5-point decrease) in weekly ISS (P<0.0001) and higher percentages of patients with well-controlled symptoms (urticaria activity score over 7 days (UAS7) ⩽6: 51.9% vs. 11.3%; P<0.0001) and complete response (UAS7=0: 35.8% vs. 8.8%; P<0.0001) versus placebo. During the 24-week treatment period, 2 (2.9%), 3 (3.4%), 0, and 4 (5.0%) patients in the omalizumab 75-mg, 150-mg, 300-mg, and placebo groups, respectively, experienced a serious adverse event. Omalizumab 300 mg administered subcutaneously every 4 weeks reduced weekly ISS and other symptom scores versus placebo in CIU/CSU patients who remained symptomatic despite treatment with approved doses of H1 antihistamines.
| S-EPMC4269803 | biostudies-literature
Project description:BackgroundChronic urticaria (CU) is a common skin disorder, which can be further divided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Omalizumab is effective and safe for difficult-to-treat CSU based on clinical trials. However, there are limited data comparing the therapeutic effect of omalizumab for patients with CSU, CIndU, and CSU plus CIndU. Meanwhile, there is still no reliable predictor for treatment response or relapse. Our study was conducted to collect real-world clinical data on omalizumab treatment in patients with CSU, CIndU, and both.MethodsThis was an observational, retrospective chart review of patients with CU initiating omalizumab treatment between February 2018 and May 2020 (maximum 28 months follow-up).ResultsA total of 138 patients were included, 87 with CSU alone, 33 with different forms of CIndU, and 18 with both. A total of 87.0% (n = 120/138) of the CU patients responded to omalizumab therapy, among which 65.2% (n = 90/138) of the patients showed complete response and 21.7% (n = 30/138) of the patients showed partial response. The therapeutic effect and speed of onset of effect for omalizumab were comparable among patients with CSU, CIndU, or both. Autologous serum skin test (ASST)-positive patients were more likely to show a slow response to omalizumab therapy ( P = 0.043). Non-responders had lower baseline total IgE levels (35.0 vs 121.5 kU/L, P < 0.001). The proportion of patients with low total IgE levels in non-responders was significantly higher than that of responders (61.1% vs. 14.5%, P < 0.001). Also, more non-responder patients had elevated thyroid autoantibodies than responders (50.0% vs. 23.0%, P = 0.041). The median ratio of serum IgG-anti-TPO to serum total IgE in non-responders was significantly higher compared with responders (1.22 vs. 0.09, P < 0.001). Non-responders also had shorter treatment periods (4.5 vs 6.0 months, P = 0.035) compared with responders. Two of 3 patients (67.4%, n = 29/43) experienced relapse after ceasing omalizumab therapy. These patients had longer disease durations (52.0 vs. 15.0 months, P = 0.007) and higher baseline total IgE levels (179.9 vs. 72.5 kU/L, P = 0.020) than patients who did not relapse. We reinitiated omalizumab treatment for 10 relapsed patients, all of them reported a rapid response after the first injection within the first 4 weeks of retreatment.ConclusionOmalizumab is highly effective in patients with difficult-to-treat CSU, CIndU, or both. Responders tend to have unique immunological features and longer treatment periods. Patients with higher baseline total IgE levels and longer disease durations are more likely to experience rapid relapse after discontinuation of omalizumab.
| S-EPMC7804987 | biostudies-literature
Project description:Omalizumab is effective in chronic spontaneous urticaria unresponsive to antihistamines. Of the licensed dosing schedules, Korean patients prefer a low dose, of 150 mg/month, for financial reasons. However, real-world experiences of low-dose omalizumab consumption have not been reported. The aim of this retrospective study was to assess the treatment outcomes and long-term clinical course of patients with chronic spontaneous urticaria who were treated with low-dose omalizumab. The study included 179 patients aged ≥ 20 years who were treated with omalizumab 150 mg/month for ≥ 12 weeks. Baseline disease activity was mild, moderate, and severe in 54.7%, 35.2%, and 10.1% of patients, respectively. A complete response was observed in 133 patients at 12 weeks, among whom 88 patients showed early responses within 4 weeks. Overall, 158 patients finally achieved a complete response. Multivariate analyses revealed that baseline disease activity is more likely to be mild in patients who experience early and final complete responses. The absence of atopic comorbidities correlated with an early response. Smoking was associated with a final complete response. This study shows that low-dose omalizumab provides favourable treatment outcomes in antihistamine-refractory chronic spontaneous urticaria. Disease severity, atopic comorbidity, and smoking may be predictive factors for studying the response to omalizumab.
| S-EPMC10547060 | biostudies-literature
Project description:Chronic spontaneous urticaria (CSU) is a disease with significant morbidity and relative prevalence that has important effects on the quality of life (QoL) of those who suffer from it. Omalizumab is a recombinant humanized anti-immunoglobulin E (IgE) antibody that binds to the Cε3 domain of the IgE heavy chain and prevents it from binding to its high-affinity receptor FcεRI. It has been largely studied in the field of asthma and is currently approved for the treatment of both adult and pediatric (children; >6-year-old) patients. In addition, in recent, well-controlled clinical trials in patients with CSU resistant to antihistamines, add-on therapy with subcutaneous omalizumab significantly reduced the severity of itching, and the number and size of hives, and increased patients' health-related QoL and the proportion of days free from angioedema compared with placebo, with an excellent tolerance. Thus, omalizumab is an effective and well-tolerated add-on therapy for patients with CSU who are symptomatic despite background therapy with H1 antihistamines. In this review, we cover the following points: epidemiology, pathogenesis, assessment of activity, impact on QoL, and treatment of CSU, and finally, we focus on omalizumab in the treatment of CSU including the pharmacokinetic properties and mechanism of action, and use in pregnant women, nursing infants, and children.
| S-EPMC4554406 | biostudies-literature
Project description:In chronic spontaneous urticaria (CSU), itchy wheals, angioedema, or both occur regularly, often daily, and for years. An effective therapy for CSU aims at achieving complete symptom control. The current guideline for the management of CSU patients recommends non-sedative anthistamines in standard or up to 4-fold higher dosages as 1 and 2 line treatment. For most CSU patients this treatment is not sufficient; for them, the anti-IgE antibody omalizumab is the therapy of choice. Although good to very good symptom control can be achieved in most cases, there are many patients with insufficient response. For these patients, but also as an alternative to therapy with omalizumab, numerous other biologicals are currently under development. In this review, we provide an overview of possible future biologic therapies for chronic urticaria.
| S-EPMC7890936 | biostudies-literature
Project description:BackgroundThe pathogenesis of chronic spontaneous urticaria (CSU) and the mechanism of action of omalizumab in CSU remain unclear.ObjectiveIn this study, we assessed the responsiveness and FcεRI expression of various subsets of leucocytes in patients with CSU treated with omalizumab.MethodsIn this prospective cohort study, 30 patients were treated with 6 administrations of 300 mg omalizumab every 4 weeks, followed by a follow-up period of 12 weeks. FcεRI expression and the percentage of basophils, monocytes, and dendritic cell subsets were analysed before and during treatment, and after follow-up. In addition, anti-IgE- and C5a-induced basophil degranulation was measured. The results were correlated with disease activity and response to omalizumab.ResultsIn addition to a rapid and significant reduction in FcεRI on basophils, we demonstrated a reduction in FcεRI on plasmacytoid dendritic cells during omalizumab treatment, which persisted until 3 months after discontinuation. FcεRI expression on basophils and its reduction did not correlate with the treatment response. Omalizumab led to an increased percentage of basophils in blood but not of the other FcεRI-bearing leucocytes. Basophil responsiveness was differentially affected; anti-IgE-, but not C5a-induced basophil degranulation increased during the treatment. Apart from clinical non-responders showing a stronger increase in anti-IgE-induced basophil degranulation over a period time, no differences were found in omalizumab responders vs non-responders.Conclusions/clinical relevanceFcεRI expression on basophils decreased rapidly, while anti-IgE-induced degranulation significantly increased due to omalizumab treatment in patients with CSU, persisting at least for 3 months after stopping the treatment. None of the markers were able to predict the effectiveness of treatment. Whether basophils play a role in omalizumab responsiveness in CSU remains unclear.
| S-EPMC7065003 | biostudies-literature