Efficacy and Safety of Up-dosing Antihistamines in Chronic Spontaneous Urticaria: A Systematic Review of the Literature

Sotés, Pilar Iriarte; Armisén, Margarita; Usero-Bárcena, Teresa; Fernández, A Rodriguez; Rivas, María Mercedes Otero; Gonzalez, Marta-Sonia; Calderón, Á Meijide; Veleiro, Beatriz

doi:10.18176/jiaci.0649

Cited by 27 publications

(12 citation statements)

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“…The findings of our meta-analysis suggest that high-dose treatment up to a maximum of double the standard dose of sgAHs might provide a better response rate when compared with conventional treatment in patients suffering from CSU. A systematic review of observational studies and RCTs by Iriarte et al [41] suggested that higher doses of sgAHs for better efficacy in CSU, which is consistent with our conclusions. We differ from them in that Iriarte et al [41] reviewed and analyzed the safety and efficacy of sgAHs in CSU, whereas we only included RCTs and performed quantitative analysis through meta-analysis.…”

Section: Discussionsupporting

confidence: 92%

The efficacy and safety of high-dose nonsedating antihistamines in chronic spontaneous urticaria: a systematic review and meta-analysis of randomized clinical trials

Xiao

Xue

Shi

et al. 2023

BMC Pharmacol Toxicol

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Background Standard doses of second-generation H1-antihistamines (sgAHs) as first-line treatment are not always effective in treating chronic spontaneous urticaria (CSU), and hence an increase in the dose of sgAHs is recommended. However, literature evaluating the efficacy and safety of this treatment remains inconclusive, highlighting the need for a systematic review and meta-analysis. The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of high-dose sgAHs compared with standard-dose sgAHs in treating CSU. Methods A systematic literature search of double-blind, randomized controlled trials (RCT) utilizing multiple doses of sgAHs was performed by searching the electronic databases Medline, Embase, PsycInfo, Cochrane databases, and Web of Science. Bibliographies were also manually searched. The Cochrane Risk of Bias Tool for assessing risk of bias was used to assess the quality of randomized controlled trials (RCTs). Two reviewers screened studies, extracted data, and evaluated the risk of bias independently. The response rate, the number of adverse events, somnolence, and withdrawal due to adverse events were extracted from each article. The data were combined and analyzed to quantify the safety and efficacy of the treatment. RevMan (V5.3) software was used for data synthesis. Results A total of 13 studies were identified, seven of which met the eligibility criteria for the meta-analysis. Our pooled meta-analyses showed that high-dose sgAHs was associated with a significantly higher response rate than standard-dose (RR 1.13, 95% CI 1.02 to 1.26; P = 0.02). Conversely, high doses of sgAHs were associated with significantly higher somnolence rates than standard dose (RD 0.05, 95% CI 0.01 to 0.09; P = 0.02). There was no significant difference in adverse events or withdrawal due to adverse events between standard- and high-dose treatments. Conclusions Our analyses showed that a high dose of sgAHs (up to two times the standard dose) might be more effective than a standard dose in CSU treatment. High-dose and standard-dose sgAHs showed similar adverse events, except for somnolence, where incidence was found to be dose-dependent in some studies. However, given the limited number of studies, our meta-analysis results should be interpreted with caution.

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Section: Discussionsupporting

confidence: 92%

The efficacy and safety of high-dose nonsedating antihistamines in chronic spontaneous urticaria: a systematic review and meta-analysis of randomized clinical trials

Xiao

Xue

Shi

et al. 2023

BMC Pharmacol Toxicol

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“…These trials were mainly based on chronic inducible urticaria and were not well defined in terms of refractory CSU . Hence, according to current evidence, it is unclear whether the up-dosing of second-generation H 1 antihistamines is effective for H 1 antihistamine–refractory CSU …”

Section: Discussionmentioning

confidence: 99%

Evaluation of Pharmacologic Treatments for H₁ Antihistamine–Refractory Chronic Spontaneous Urticaria

et al. 2021

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IMPORTANCEThe comparative benefits and harms of all available treatments for H 1 antihistamine-refractory chronic spontaneous urticaria (CSU) have not been established. OBJECTIVE To evaluate different treatment effects of pharmacologic treatments among patients with H 1 antihistamine-refractory CSU.DATA SOURCES Searches were conducted of MEDLINE, Embase, PubMed, Cochrane Library, Web of Science, Scopus, and CINAHL from inception to April 19, 2021, with no language restrictions. Gray literature from Google Scholar, ongoing trial registers, and preprint reports was added to the searches of electronic databases.STUDY SELECTION Randomized clinical trials using validated measurement tools that investigated the benefits and harms of pharmacologic treatments among adolescent or adult patients with CSU who had an inadequate response to H 1 antihistamines were screened for inclusion independently by 2 investigators. DATA EXTRACTION AND SYNTHESISTwo investigators independently extracted study data according to the predefined list of interests. A random-effects model was used to calculate the network estimates reported as standardized mean differences and odds ratios with corresponding 95% CIs. MAIN OUTCOMES AND MEASURESThe primary outcomes that reflect the patient's perspective included changes in urticaria symptoms from baseline and unacceptability of treatment (all-cause dropouts).RESULTS Twenty-three randomized clinical trials with 2480 participants that compared 18 different interventions or dosages and placebo were included. The standardized mean differences for change in urticaria symptoms were −1.05 (95% CI, −1.37 to −0.73) for ligelizumab, 72 mg; −1.07 (95% CI, −1.39 to −0.75) for ligelizumab, 240 mg; −0.77 (95% CI, −0.91 to −0.63) for omalizumab, 300 mg; and −0.59 (95% CI, −1.10 to −0.08) for omalizumab, 600 mg. No significant differences in treatment unacceptability were observed. With respect to benefits and harms, the network estimates illustrated that the most efficacious treatments were achieved with ligelizumab, 72 or 240 mg (large beneficial effect) and omalizumab, 300 or 600 mg (moderate beneficial effect). CONCLUSIONS AND RELEVANCEThe findings in this meta-analysis suggest that the biologic agents ligelizumab, 72 or 240 mg, and omalizumab, 300 or 600 mg, can be recommended as effective treatments for patients with CSU who have had an inadequate response to H 1 antihistamines. Head-to-head trials with high methodologic quality and harmonized design and outcome definitions are needed to help inform subsequent international guidelines for the management of CSU.

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“…Desloratadine is an antihistaminic drug that suppresses allergic reactions, e.g., urticaria, rhinitis, and allergic inflammatory diseases [ 37 , 38 ]. Remarkably, desloratadine has been also reported to improve the survival time of patients suffering from melanoma or breast cancer [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Anthracycline Resistance Genes and Their Inhibitors

et al. 2021

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Differentially expressed genes have been previously identified by us in multidrug-resistant tumor cells mainly resistant to doxorubicin. In the present study, we exemplarily focused on some of these genes to investigate their causative relationship with drug resistance. HMOX1, NEIL2, and PRKCA were overexpressed by lentiviral-plasmid-based transfection of HEK293 cells. An in silico drug repurposing approach was applied using virtual screening and molecular docking of FDA-approved drugs to identify inhibitors of these new drug-resistant genes. Overexpression of the selected genes conferred resistance to doxorubicin and daunorubicin but not to vincristine, docetaxel, and cisplatin, indicating the involvement of these genes in resistance to anthracyclines but not to a broader MDR phenotype. Using virtual drug screening and molecular docking analyses, we identified FDA-approved compounds (conivaptan, bexarotene, and desloratadine) that were interacting with HMOX1 and PRKCA at even stronger binding affinities than 1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethenone and ellagic acid as known inhibitors of HMOX1 and PRKCA, respectively. Conivaptan treatment increased doxorubicin sensitivity of both HMOX1- and PRKCA-transfected cell lines. Bexarotene treatment had a comparable doxorubicin-sensitizing effect in HMOX1-transfected cells and desloratadine in PRKCA-transfected cells. Novel drug resistance mechanisms independent of ABC transporters have been identified that contribute to anthracycline resistance in MDR cells.

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Efficacy and Safety of Up-dosing Antihistamines in Chronic Spontaneous Urticaria: A Systematic Review of the Literature

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 27 publications

References 21 publications

The efficacy and safety of high-dose nonsedating antihistamines in chronic spontaneous urticaria: a systematic review and meta-analysis of randomized clinical trials

The efficacy and safety of high-dose nonsedating antihistamines in chronic spontaneous urticaria: a systematic review and meta-analysis of randomized clinical trials

Evaluation of Pharmacologic Treatments for H₁ Antihistamine–Refractory Chronic Spontaneous Urticaria

Identification of Novel Anthracycline Resistance Genes and Their Inhibitors

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Efficacy and Safety of Up-dosing Antihistamines in Chronic Spontaneous Urticaria: A Systematic Review of the Literature

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 27 publications

References 21 publications

The efficacy and safety of high-dose nonsedating antihistamines in chronic spontaneous urticaria: a systematic review and meta-analysis of randomized clinical trials

The efficacy and safety of high-dose nonsedating antihistamines in chronic spontaneous urticaria: a systematic review and meta-analysis of randomized clinical trials

Evaluation of Pharmacologic Treatments for H1 Antihistamine–Refractory Chronic Spontaneous Urticaria

Identification of Novel Anthracycline Resistance Genes and Their Inhibitors

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Evaluation of Pharmacologic Treatments for H₁ Antihistamine–Refractory Chronic Spontaneous Urticaria