RESUMO
BACKGROUND: The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents. OBJECTIVE: ARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals. METHODS: Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non-daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics. RESULTS: Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n = 256; PTAH-naive, n = 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non-daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non-daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm. CONCLUSIONS: Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.
Assuntos
Hipersensibilidade a Amendoim , Administração Oral , Adolescente , Alérgenos , Arachis , Criança , Dessensibilização Imunológica , Método Duplo-Cego , Humanos , Hipersensibilidade a Amendoim/terapiaRESUMO
Allergic rhinitis is a very common disorder that affects people of all ages, peaking in the teenage years. It is frequently ignored, underdiagnosed, misdiagnosed, and mistreated, which not only is detrimental to health but also has societal costs. Although allergic rhinitis is not a serious illness, it is clinically relevant because it underlies many complications, is a major risk factor for poor asthma control, and affects quality of life and productivity at work or school. Management of allergic rhinitis is best when directed by guidelines. A diagnostic trial of a pharmacotherapeutic agent could be started in people with clinically identified allergic rhinitis; however, to confirm the diagnosis, specific IgE reactivity needs to be recorded. Documented IgE reactivity has the added benefit of guiding implementation of environmental controls, which could substantially ameliorate symptoms of allergic rhinitis and might prevent development of asthma, especially in an occupational setting. Many classes of drug are available, effective, and safe. In meta-analyses, intranasal corticosteroids are superior to other treatments, have a good safety profile, and treat all symptoms of allergic rhinitis effectively. First-generation antihistamines are associated with sedation, psychomotor retardation, and reduced academic performance. Only immunotherapy with individually targeted allergens has the potential to alter the natural history of allergic rhinitis. Patients' education is a vital component of treatment. Even with the best pharmacotherapy, one in five affected individuals remains highly symptomatic, and further research is needed in this area.
Assuntos
Rinite Alérgica Perene , Rinite Alérgica Sazonal , Asma/etiologia , Diagnóstico Diferencial , Humanos , Doenças Profissionais/etiologia , Rinite Alérgica Perene/complicações , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/fisiopatologia , Rinite Alérgica Perene/terapia , Rinite Alérgica Sazonal/complicações , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/fisiopatologia , Rinite Alérgica Sazonal/terapiaRESUMO
Allergic rhinitis (AR) and nonallergic rhinopathy (NAR) represent common nasal conditions affecting millions of individuals across the world. Although patients present with similar symptomatology, those with NAR are frequently affected only after childhood and present with a lack of other comorbid atopic disorders such as asthma, atopic dermatitis, and food allergies. Patients with pure NAR usually have no identifiable specific allergen sensitivity, whereas those with mixed (allergic and nonallergic) rhinitis are sensitized to aeroallergens in a manner that does not fully explain the duration or extent of their symptoms. This review presents the diverse options of currently available pharmacologic agents for the treatment of AR and NAR, including intranasal corticosteroids, H(1)-antihistamines, decongestants, cromolyn sodium, antileukotrienes, anticholinergics, capsaicin, anti-IgE, and intranasal saline, in addition to subcutaneous immunotherapy. Furthermore, treatment algorithms for AR and NAR are presented with a stepped-up, stepped-down scheme to aid the clinician in choosing appropriate therapy.
Assuntos
Antialérgicos/uso terapêutico , Rinite Alérgica Perene/tratamento farmacológico , Rinite Alérgica Sazonal/tratamento farmacológico , Rinite Atrófica/tratamento farmacológico , Rinite Vasomotora/tratamento farmacológico , Alérgenos/efeitos adversos , Alérgenos/imunologia , Anti-Inflamatórios/uso terapêutico , Doença Crônica , Quimioterapia Combinada , Monitoramento Ambiental , Monitoramento Epidemiológico , Feminino , Seguimentos , Humanos , Imunização/métodos , Masculino , Descongestionantes Nasais/uso terapêutico , Rinite Alérgica Perene/imunologia , Rinite Alérgica Perene/fisiopatologia , Rinite Alérgica Sazonal/epidemiologia , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/fisiopatologia , Rinite Atrófica/diagnóstico , Rinite Atrófica/fisiopatologia , Rinite Vasomotora/diagnóstico , Rinite Vasomotora/fisiopatologia , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Allergic rhinitis (AR) and perennial nonallergic rhinitis (PNAR) represent conditions affecting millions of individuals across the world. Although the diagnosis of AR might be presumptively based on the types of symptoms and the history of allergen triggers, confirmation requires documentation of specific IgE reactivity. In contrast, PNAR is a condition with similar symptomatology but in which the patient has no identifiable specific allergic sensitivities. This review presents the diverse options of currently available pharmacologic agents for the treatment of AR and PNAR, including intranasal corticosteroids, H1-antihistamines, decongestants, cromolyn sodium, antileukotrienes, anticholinergics, capsaicin, anti-IgE, and intranasal saline. Furthermore, appropriate stepped-up, stepped-down pharmacotherapeutic algorithms are described for the various forms of rhinitis.
Assuntos
Rinite Alérgica Perene/tratamento farmacológico , Rinite Alérgica Sazonal/tratamento farmacológico , Rinite/tratamento farmacológico , Humanos , Rinite/classificação , Rinite/diagnóstico , Rinite/epidemiologia , Rinite Alérgica Perene/imunologia , Rinite Alérgica Sazonal/imunologiaRESUMO
AR is a common condition affecting individuals of all ages. Those afflicted with AR often suffer from associated inflammatory conditions of the mucosa,such as AC, rhinosinusitis, asthma, otitis media with effusion, and other atopic conditions, such as eczema and food allergies. Lack of treatment or treatment with suboptimal therapy may result in reduced quality of life and compromise productivity at work or school. Although environmental controls may prove difficult to implement, and not all controls appear adequately to mitigate symptoms of AR, they continue to represent a foundation for treatment. Many different classes of medications are now available, and they have been shown to be effective and safe in a large number of well-designed, double-blind, placebo-controlled clinical trials. Some of the over-the-counter medi-cations have been associated with increased sedation, potentially leading to accidents and fatalities at work or while operating complex machinery, such as automobiles. Only immunotherapy with increasing doses of individually targeted allergens results in sustained changes in the immune system. Although anti-IgE is probably only the first successful immunomodulator commercially available to treat AR, monoclonal antibodies will remain too costly, at least in the near future, to find their way into routine AR treatment.