Biologic agents and the therapy of chronic spontaneous urticaria

Kaplan, Allen P.; Popov, Todor A.

doi:10.1097/aci.0000000000000083

Cited by 12 publications

(12 citation statements)

References 41 publications

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“…Although second-generation H 1 -antihistamines are a first-line therapy for CSU, 30–50% of patients fail to achieve symptom control with antihistamines alone [2-4]. Cyclosporine, sulfasalazine, dapsone, Plaquenil, and mycophenolate mofetil have been used in more severe cases of CSU, but each has the potential for significant toxicities that require frequent laboratory monitoring [4, 5]. Omalizumab has been approved for antihistamine-refractory CSU by the US Food and Drug Administration (FDA) at 150 or 300 mg every 4 weeks, and by the European Medicines Agency (EMA) at 300 mg every 4 weeks.…”

Section: Introductionmentioning

confidence: 99%

“…Omalizumab has been approved for antihistamine-refractory CSU by the US Food and Drug Administration (FDA) at 150 or 300 mg every 4 weeks, and by the European Medicines Agency (EMA) at 300 mg every 4 weeks. The optimal dose of omalizumab is 300 mg every 4 weeks [6, 7]; yet 47–66% of patients treated fail to achieve complete symptom control (urticaria activity score over 7 days [UAS7] = 0) at this dosage [4, 6-8]. The disadvantages of omalizumab treatment include the high cost of a biologic agent, the requirement for subcutaneous injection in a physician’s office, and the need for an epinephrine autoinjector prescription due to the risk of drug-related anaphylaxis of up to 0.2% [9, 10].…”

Section: Introductionmentioning

confidence: 99%

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Effects of an Oral CRTh2 Antagonist (AZD1981) on Eosinophil Activity and Symptoms in Chronic Spontaneous Urticaria

Oliver

Chichester

Devine

et al. 2019

Int Arch Allergy Immunol

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Background: Approximately 50% of patients with chronic spontaneous urticaria (CSU) experience symptoms that are not fully controlled by antihistamines, indicating an unmet clinical need. Objective: To evaluate the effects of the selective CRTh2 antagonist AZD1981 on symptoms and targeted leukocytes in adults with persistent CSU despite treatment with H₁-antihistamines. Methods: We performed a single-center, randomized, placebo-controlled study involving adult CSU subjects with symptoms despite daily antihistamines. The subjects underwent a 2-week placebo run-in and 4 weeks of double-blinded therapy with either AZD1981 40 mg TID or placebo, followed by a 2-week placebo washout. The primary objective was to assess the effect of AZD1981 on CSU signs and symptoms. Secondary objectives included the effects of AZD1981 on prostaglandin D₂ (PGD₂)-induced eosinophil shape change, circulating leukocyte subsets, CRTh2 expression on blood leukocytes, and total blood leukocyte histamine content. Results: Twenty-eight subjects were randomized to AZD1981 or placebo, with 26 subjects completing the study. The urticaria activity scores declined during the treatment phase in both groups, and they were significantly reduced in the AZD1981 group at the end of washout. AZD1981 treatment increased circulating eosinophils and significantly impaired PGD₂-mediated eosinophil shape change. CRTh2 surface expression rose significantly on blood basophils during active treatment. No serious adverse events were observed. Conclusions: This is the first study to examine the efficacy of a CRTh2 antagonist in antihistamine-refractory CSU. AZD1981 treatment was well tolerated, effectively inhibited PGD₂-mediated eosinophil shape change, shifted numbers of circulating eosinophils, and reduced weekly itch scores more than hives during treatment and into washout. Further studies are needed to determine whether inhibition of the PGD₂/CRTh2 pathway will be an effective treatment for CSU.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of an Oral CRTh2 Antagonist (AZD1981) on Eosinophil Activity and Symptoms in Chronic Spontaneous Urticaria

Oliver

Chichester

Devine

et al. 2019

Int Arch Allergy Immunol

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“…Existe ainda a possibilidade de hirsutismo, imunossupressão e risco potencial de doenças malignas. [2][3][4]16,171 Ainda assim, a razão risco/benefício tem mostrado ser bastante superior à utilização de corticóides a longo prazo. 1,138 Dado o expectável aumento de efeitos adversos com o tempo de utilização, alguns autores recomendam este tratamento apenas por três meses, 16 mas outros utilizam a ciclosporina em tratamentos mais longos, [139][140][141][142] havendo mesmo recomendações para tratamentos prolongados quando necessário.…”

unclassified

Abordagem Diagnóstica e Terapêutica da Urticária Crónica Espontânea: Recomendações em Portugal

Costa

Gonçalo

Urticária³

2016

Acta Med Port

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RESUMOA urticária crónica espontânea é uma doença complexa, de etiologia mal-esclarecida, de diagnóstico fácil mas de abordagem terapêutica por vezes difícil. Tem um impacto significativo na qualidade de vida do doente e resulta em elevados custos diretos e indiretos. O diagnóstico da urticária crónica espontânea é essencialmente clínico, sendo recomendado um número limitado de exames complementares para diagnóstico diferencial e/ou para a investigação/exclusão de possível causa para a urticária crónica espontânea. Além do hemograma e da proteína C reativa, e/ou velocidade de sedimentação, os exames adicionais devem ser selecionados de acordo com critérios clínicos. O objetivo da terapêutica é o controlo clínico total da urticária crónica espontânea. A evolução deve ser documentada através do registo semanal do score de sintomas -Weekly Urticaria Activity Score (UAS7) -, assim como da avaliação de qualidade de vida. A abordagem terapêutica é baseada nos anti-histamínicos H1 (anti-H1) de segunda geração administrados de forma contínua nas doses aprovadas (primeira linha) e, na ausência de resposta clínica, até quatro vezes a dose diária aprovada (segunda linha). Os anti-H1 de primeira geração não são recomendados. Cerca de 30% dos doentes não ficam controlados com a terapêutica de segunda linha, pelo que é recomendado adicionar uma terapêutica de terceira linha. Das duas opções, omalizumab e ciclosporina, o omalizumab é a única opção com autorização de introdução no mercado para a urticária crónica espontânea, e possui melhor perfil de segurança, sendo assim recomendado preferencialmente. Em Portugal não existem recomendações nacionais aplicáveis à prática clínica. A elaboração destas recomendações é justificada pela necessidade de uniformização tanto da abordagem diagnóstica como da abordagem terapêutica dos doentes com urticária crónica espontânea em Portugal, e para a referenciação a centros especializados, nos casos mais graves.

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“…This abrogation is the proposed mechanism by which symptoms of CSU may be alleviated [1, 3]. Functional IgG autoantibodies against FcεR1α, and less commonly against IgE have been reported in patients with CSU [4].…”

mentioning

confidence: 99%

“…However, it has been proposed that CSU might be due to autoimmune/autoreactive mechanisms. Based on these findings, some biologic agents have been proposed to control CSU with variable results [1, 3]. …”

mentioning

confidence: 99%

Rituximab in Refractory Chronic Spontaneous Urticaria: An Encouraging Therapeutic Approach

Combalía

Prieto-González

et al. 2018

Skin Pharmacol Physiol

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Background: Chronic spontaneous urticaria (CSU) is a frequent mast cell-driven disease that affects approximately 0.5–1% of the population. Antihistamines are currently the drugs of choice in patients with CSU. Omalizumab has been shown to be very effective in CSU and has been recently approved as second-line therapy. However, although its introduction has markedly improved the therapeutic possibilities for CSU, there is still a hard core of patients who do not respond and require effective treatment. Methods: We report the case of a patient who achieved an 8-month remission of refractory CSU following the use of rituximab, and perform a review of the literature regarding the use of rituximab in CSU. Results: There was a remarkable improvement in her CSU after the administration of rituximab maintained over time. Conclusion: Rituximab is a chimeric murine/human monoclonal antibody directed against CD20, which depletes memory B-lymphocytes that are necessary for autoantibody production. The abrogation of the autoantibody production is the proposed mechanism by which it may alleviate the symptoms of CSU.

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Biologic agents and the therapy of chronic spontaneous urticaria

Abstract: New convincing evidence in support of the efficacy and safety of omalizumab in the treatment of CSU has accumulated over the past year, providing another tool for coping with the antihistamine-resistant cases.

Cited by 12 publications

References 41 publications

Effects of an Oral CRTh2 Antagonist (AZD1981) on Eosinophil Activity and Symptoms in Chronic Spontaneous Urticaria

Effects of an Oral CRTh2 Antagonist (AZD1981) on Eosinophil Activity and Symptoms in Chronic Spontaneous Urticaria

Abordagem Diagnóstica e Terapêutica da Urticária Crónica Espontânea: Recomendações em Portugal

Rituximab in Refractory Chronic Spontaneous Urticaria: An Encouraging Therapeutic Approach

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