Short-term and long-term asthma control in patients with mild persistent asthma receiving montelukast or fluticasone: a randomized controlled trial

doi:10.1016/j.amjmed.2005.03.003

The American Journal of Medicine

Volume 118, Issue 6, June 2005, Pages 649-657

https://doi.org/10.1016/j.amjmed.2005.03.003 Get rights and content

Abstract

Purpose

To determine whether montelukast is as effective as fluticasone in controlling mild persistent asthma as determined by rescue-free days.

Subjects and methods

Participants aged 15 to 85 years with mild persistent asthma (n = 400) were randomized to oral montelukast (10 mg once nightly) or inhaled fluticasone (88 μg twice daily) in a year-long, parallel-group, multicenter study with a 12-week, double-blind period, followed by a 36-week, open-label period.

Results

The mean percentage of rescue-free days was similar between treatments after 12 weeks (fluticasone: 74.9%, montelukast: 73.1%; difference = 1.8%, 95% confidence interval [CI]: −3.2% to 6.8%) but not during the open-label period (fluticasone: 77.3%, montelukast: 71.1%; difference = 6.2%, 95% CI: 0.8% to 11.7%). Although both fluticasone and montelukast significantly improved symptoms, quality of life, and symptom-free days during both treatment periods, greater improvements occurred with fluticasone in lung function during both periods and in asthma control during open-label treatment. Post hoc analyses revealed a difference in rescue-free days favoring fluticasone in participants in the quartiles for lowest lung function and greatest albuterol use at baseline.

Conclusion

In patients with mild persistent asthma, rescue-free days and most asthma control measures improved similarly with fluticasone or montelukast over the short term, but with prolonged open-label treatment, asthma control improved more with fluticasone. Improved asthma control with fluticasone appeared to occur in those with decreased lung function and greater albuterol use at baseline. In the remaining patients, the two treatments appeared to be comparable. These results suggest that classification criteria for mild persistent asthma may need to be re-evaluated.

Section snippets

Recruitment and eligibility

Institutional review boards at each study site (n = 39) approved the study protocol, and patients or guardians gave written informed consent. Participants aged 15 to 85 years with symptoms and albuterol use consistent with mild persistent asthma for at least 4 months, as assessed by questionnaire, were recruited. Eligibility criteria were based on National Asthma Education Prevention Program² and Global Initiative for Asthma¹ definitions of mild persistent asthma. To ensure a true mild

Patient accounting and demographics

Of the 901 participants screened, 735 entered the placebo run-in period, and 400 were randomized to treatment (Figure 2). The most common reasons for exclusion were asthma being either too mild or too severe. Due to a drug packaging error in which either both active drugs (n = 11) or both matching placebos (n = 9) were given, 20 randomized participants were discontinued from the study, and their data were excluded from analyses.

Three hundred eighty (380) patients were randomized to masked

Discussion

Epidemiologic surveys estimate that 20% to 30% of asthma patients in the United States have mild persistent asthma.25, 26, 27, 28, 29 Both Global Initiative for Asthma¹ and National Asthma Education Prevention Program² guidelines recommend daily use of controller therapy for mild persistent asthma, including inhaled corticosteroid and leukotriene modifiers. Few studies comparing different treatment options for mild persistent asthma have been done, because of the challenges in enrolling such

Acknowledgments

The following are members of the MIAMI Study Research Group Steering Committee: James Baker, MD; Steven Bird, MS; John Carl, MD; Jonathan Corren, MD; Jonathan Edelman, MD; Kathleen Harden, RN; Michael Kaplan, MD; Guillermo Mendoza, MD; E. John Orav, PhD; David Pearlman, MD; Cynthia Rand, PhD; Michael Schatz, MD, MS; Robert Zeiger, MD, PhD. We thank Arvinder Mokha, MD, for his assistance in reviewing the spirometry data. We would also like to acknowledge the medical program coordinator,

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2023, Open Respiratory Archives
The Spanish Guideline on the Management of Asthma, better known by its acronym in Spanish GEMA, has been available for more than 20 years. Twenty-one scientific societies or related groups both from Spain and internationally have participated in the preparation and development of the updated edition of GEMA, which in fact has been currently positioned as the reference guide on asthma in the Spanish language worldwide.
Its objective is to prevent and improve the clinical situation of people with asthma by increasing the knowledge of healthcare professionals involved in their care. Its purpose is to convert scientific evidence into simple and easy-to-follow practical recommendations. Therefore, it is not a monograph that brings together all the scientific knowledge about the disease, but rather a brief document with the essentials, designed to be applied quickly in routine clinical practice. The guidelines are necessarily multidisciplinary, developed to be useful and an indispensable tool for physicians of different specialties, as well as nurses and pharmacists.
Probably the most outstanding aspects of the guide are the recommendations to: establish the diagnosis of asthma using a sequential algorithm based on objective diagnostic tests; the follow-up of patients, preferably based on the strategy of achieving and maintaining control of the disease; treatment according to the level of severity of asthma, using six steps from least to greatest need of pharmaceutical drugs, and the treatment algorithm for the indication of biologics in patients with severe uncontrolled asthma based on phenotypes. And now, in addition to that, there is a novelty for easy use and follow-up through a computer application based on the chatbot-type conversational artificial intelligence (ia-GEMA).
La Guía Española para el Manejo del Asma, mejor conocida por su acrónimo en español, GEMA, está a nuestra disposición desde hace más de veinte años. Veintiuna sociedades científicas o grupos relacionados, tanto de España como de otros países, han participado en la preparación y desarrollo de la edición actualizada de GEMA que, de hecho, se ha posicionado en la actualidad a nivel mundial como la guía de referencia sobre asma en lengua española.
Su objetivo es prevenir y mejorar la situación clínica de las personas con asma, aumentando el conocimiento de los profesionales sanitarios involucrados en su cuidado. Su propósito es convertir la evidencia científica en recomendaciones prácticas sencillas y fáciles de seguir. Por lo tanto, no se trata de una monografía que reúna todo el conocimiento científico sobre la enfermedad, sino más bien de un documento conciso con lo esencial, diseñado para ser aplicado rápidamente en la práctica clínica de rutina. Las recomendaciones son necesariamente multidisciplinares, están desarrolladas para ser útiles y una herramienta indispensable para médicos de diferentes especialidades, así como para profesionales de enfermería y farmacia.
Seguramente, los aspectos más destacados de la guía son las recomendaciones para: establecer el diagnóstico del asma utilizando un algoritmo secuencial basado en pruebas diagnósticas objetivas; el seguimiento de los pacientes, preferentemente basado en la estrategia de lograr y mantener el control de la enfermedad; el tratamiento según el nivel de gravedad del asma utilizando seis escalones, desde la menor hasta la mayor necesidad de medicamentos, y el algoritmo de tratamiento basado en fenotipos para la indicación de biológicos en pacientes con asma grave no controlada. A esto se suma ahora una novedad para su fácil uso y seguimiento a través de una aplicación informática basada en la inteligencia artificial conversacional de tipo chatbot (ia-GEMA).
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2019, Respiratory Investigation
Citation Excerpt :
Table 2 enumerates the therapeutic effects of LTRAs on long-term asthma management. The therapeutic effects of LTRAs on improving the respiratory function and quality of life in patients with mild asthma are similar to those of ICSs [55–58]. These agents also possess anti-inflammatory properties and reduce the number of eosinophils, lymphocytes, and mast cells in sputum and bronchial biopsy tissue [59], while also decreasing the levels of fractional exhaled nitric oxide (FeNO), which is a biomarker that reflects airway eosinophilic inflammation [60,61].
Asthma is an allergic disorder with dominant type 2 airway inflammation, and its prevalence is increasing worldwide. Inhalation of corticosteroids is the primary treatment for asthma along with add-on drugs, including long-acting β2 agonists and/or cysteinyl leukotriene (cys-LT) receptor antagonists, in patients with poorly controlled asthma. Cys-LTs are composed of leukotriene C4 (LTC₄), LTD₄, and LTE₄, which are enzymatically metabolized from arachidonic acid. These molecules act as inflammatory mediators through different types of high-affinity receptors, namely, CysLT₁, CysLT₂, and CysLT₃ (also named as GPR99). CysLT₁ antagonists possessing anti-inflammatory and bronchodilatory effects can be orally administered to patients with asthma. Recently, molecular biology-based studies have revealed the mechanism of inflammatory responses via other receptors, such as CysLT₂ and CysLT₃, as well as the importance of upstream inflammatory regulators, including type 2 cytokines (e.g., interleukins 4 and 5), in controlling cys-LT metabolism. These findings indicate the therapeutic potential of pharmacological agents targeting cys-LT metabolism-related receptors and enzymes, and antibody drugs neutralizing or antagonizing type 2 cytokines. This review focuses on the current state and future prospect of the therapeutic strategy targeting cys-LT metabolism.
Do children with stable asthma benefit from addition of montelukast to inhaled corticosteroids: Randomized, placebo controlled trial
2015, Pulmonary Pharmacology and Therapeutics
To determine the effects of montelukast added to maintenance inhaled steroids (ICS) therapy during the school year in children with stable asthma on the ICS use, frequency of exacerbations, lung function, asthma symptoms, fractional exhaled nitric oxide (FeNO) level and exercise-induced bronchoconstriction (EIB).
Seventy six asthmatic children aged 6–14 years, allergic to house dust mites were randomized to a double-blinded trial comparing montelukast therapy to a matching placebo. We studied following end-points: the reduction in the ICS dose, the frequency of exacerbations, lung function, asthma control test score, and the change from baseline in FEV₁ during a standardized exercise treadmill challenge. ICS dose was adjusted in a stepwise fashion to determine the lowest dose necessary to control asthma symptoms.
We showed that children with baseline value of FeNO above 31 ppb and well controlled asthma symptoms on low doses of ICS, benefit the most from additive therapy with montelukast; their cumulative ICS dose is lower than in children treated with ICS only. Also, the addition of montelukast to regular treatment in asthmatic children resulted in a significant reduction in the frequency of exacerbations and EIB protection.
It is reasonable to add montelukast to ICS therapy in asthmatic children during the school year, to lower cumulative ICS dose in children with well controlled asthma symptoms, as well as to reduce number of exacerbations, and to achieve better control of EIB.
NCT01266772.
GEMA<sup>4.0.</sup> Guidelines for Asthma Management
2015, Archivos de Bronconeumologia
El principal objetivo de la presente guía es mejorar el control y calidad de vida de las personas con asma mediante el incremento de la formación técnica de los profesionales sanitarios que deben atenderles. En particular en los aspectos relacionados con la prevención y valoración diagnóstica-terapéutica de la enfermedad.
No obstante, la GEMA es una plataforma que aglutina una serie de acciones complementarias, todas diseñadas para alcanzar el objetivo antes descrito, entre las que sobresale el presente documento: una guía de práctica clínica basada en la evidencia. Posteriormente, otros documentos (GEMA de Bolsillo. GEMA de Pacientes, GEMA Educadores, Indicadores de Calidad Asistencial del Asma, etc.) irán completando la “familia” de la GEMA.
Específicamente, el presente documento (guía de práctica clínica) y toda la estrategia que conforma la plataforma GEMA^4.0, está dirigida a médicos de Atención Primaria, pediatras, neumólogos, alergólogos, pediatras neumólogos y pediatras alergólogos, otorrinolaringólogos, farmacólogos, farmacéuticos, enfermería general y especializada en patología respiratoria, educadores, profesores, pacientes y familiares de pacientes.
Búsqueda de la evidencia. Partiendo de la anterior edición de la GEMA², editada en 2009, y siguiendo las recomendaciones para la Actualización de Guías de Práctica Clínica del Sistema Nacional de Salud³, los miembros del Comité Ejecutivo realizaron una búsqueda sistemática, con evaluación y selección de las publicaciones aparecidas sobre asma desde 2009 hasta 2014 (Proyecto Pro-GEMA). Tras la revisión de las revistas de Neumología, Alergología, Pediatría, Atención Primaria, Medicina Interna y Otorrinolaringología de elevado factor de impacto, y su clasificación entre los dos primeros cuartiles de su especialidad, se seleccionó un total de 184 trabajos (resúmenes disponibles en http://www.progema-gemasma.com/foco.html) que se consideraron de interés para la actualización de la guía y que se proporcionaron a los redactores para su consideración. Además se les animó a efectuar sus propias búsquedas bibliográficas específicas para temas concretos. Para ello, se siguió el procedimiento habitualmente establecido en la elaboración de guías de práctica clínica⁴. Así mismo, se revisaron los listados de referencias de las principales guías de práctica clínica internacionales^5,6 para identificar las principales revisiones sistemáticas y ensayos clínicos. Estas guías se buscaron en bases de datos especializadas (National Guideline Clearinghouse, National Library of Guidelines) y en el metabuscador de literatura médica TRIP database. Se consultaron las bases de datos del Centre for Reviews and Dissemination (DARE y HTA database) y The Cochrane Library para identificar revisiones sistemáticas y evaluaciones de tecnologías adicionales. La búsqueda se completó con una actualización de las revisiones sistemáticas a partir de su fecha de búsqueda y de los estudios relevantes en las principales bases de datos electrónicas de estudios originales (MEDLINE, CENTRAL y EMBASE).
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Teniendo en cuenta la reciente aparición de nuevos enfoques para clasificar la calidad de la evidencia basados en otros aspectos, además del diseño de los estudios^7,8, se utilizaron algunas características marco GRADE (http://www.gradeworkinggroup.org/), aunque éste no se aplicó de una forma completa.
Clasificación de las recomendaciones. Para clasificar la relevancia y consistencia de las recomendaciones clínicas, se siguió el mismo método empleado en la anterior edición de la GEMA², que las categorizaba en dos niveles: recomendaciones robustas (R1), que representan aquellas en las que el grupo elaborador de la guía confía que conlleven más beneficios que riesgos; y recomendaciones débiles (R2), aquellas en las que existe incertidumbre sobre si su aplicación conllevará más beneficios que riesgo. Para efectuar esta distribución en R1 o R2 se ponderó la calidad de la información (a partir de la clasificación mencionada), el balance entre los riesgos y los beneficios de las intervenciones, los costes (según literatura especializada disponible), así como los valores y preferencias de los pacientes (mediante la participación de miembros de la FENAER).
La categorización del nivel de recomendación se estableció mediante consenso, primero entre todos los redactores (ver más adelante método de trabajo seguido) y finalmente, con los revisores (mediante método Delphi), cuya opinión fue vinculante para la redacción final de todas las recomendaciones.
Redacción y consenso del texto y de las recomendaciones. El desarrollo del trabajo de redacción se basó en un sistema de consenso piramidal: de miniconsenso multidisciplinar temático por capítulo, a un gran consenso final entre todos los redactores y revisores. Tomando como base el documento elaborado en la anterior edición y las nuevas referencias bibliográficas sobre asma aparecidas desde 2009 hasta 2015, un grupo de redactores y coordinadores formado por expertos provenientes de las sociedades científicas participantes efectuaron una nueva redacción (incluidas la clasificación de la evidencia y de las recomendaciones) del fragmento del capítulo que se les asignó. Los redactores enviaron sus textos a cada uno de los coordinadores de cada capítulo, formado por los miembros del Comité Ejecutivo de la GEMA. Tras la unificación y revisión de los textos por el coordinador del capítulo, éste remitió el borrador del mismo a todos los redactores del capítulo, para efectuar el primer consenso parcial. Tras las modificaciones se fusionaron todos los capítulos en un solo documento, que a su vez fue de nuevo enviado a todos los redactores y coordinadores para su discusión telemática (y cuando se precisó, en grupos de trabajo, presencial) y aprobación. El documento resultante se remitió a expertos en metodología de guías de práctica clínica del INPECS (Instituto para la Excelencia Clínica y Sanitaria), que efectuaron una revisión crítica de la metodología y redacción del texto y recomendaciones. Tras dichas modificaciones y mejoras, finalmente, las recomendaciones fueron revisadas y consensuadas (mediante método Delphi) por un grupo de expertos en asma provenientes de las sociedades participantes. Las recomendaciones que no alcanzaron un determinado nivel de consenso fueron eliminadas del documento final.
Asthma: Therapeutic update
2014, Medicina Clinica
Use of Leukotriene Receptor Antagonists Are Associated with a Similar Risk of Asthma Exacerbations as Inhaled Corticosteroids
2014, Journal of Allergy and Clinical Immunology: In Practice
Based on results of clinical trials, inhaled corticosteroids (ICS) are the most-effective controller medications for preventing asthma-related exacerbations, yet few studies in real-life populations have evaluated the comparative effectiveness of ICS.
To determine the likelihood of asthma exacerbations among children with asthma after initiation of controller medications: ICS, leukotriene antagonists (LTRA), and ICS–long-acting β-agonist (LABA) combination therapy.
This was a retrospective cohort study of subjects who were part of the Population-Based Effectiveness in Asthma and Lung Diseases Network. We conducted Cox regression analyses by adjusting for baseline covariates, adherence by using proportion of days covered, and high-dimensional propensity scores. The main outcome measurements were emergency department visits, hospitalizations, or oral corticosteroid use.
Our population included 15,567 health plan subjects and 10,624 TennCare Medicaid subjects with uncontrolled asthma. Overall adherence to controller medications was low, with no more than 50% of the subjects refilling the medication after the initial fill. For subjects with allergic rhinitis, the subjects in TennCare Medicaid treated with LTRAs were less likely to experience ED visits (hazard ratio 0.44 [95% CI, 0.21-0.93]) compared with the subjects treated with ICS. For all other groups, the subjects treated with LTRA or ICS-LABA were just as likely to experience ED visits or hospitalizations, or need oral corticosteroids as the subjects treated with ICS.
Risks of asthma-related exacerbations did not differ between children who initiated LTRA and ICS. These findings may be explainable by LTRA, which has similar effectiveness as ICS in real-life usage by residual confounding by indication or other unmeasured factors.

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: This work was supported by Merck & Co., Inc.

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Clinical research studyShort-term and long-term asthma control in patients with mild persistent asthma receiving montelukast or fluticasone: a randomized controlled trial

Abstract

Purpose

Subjects and methods

Results

Conclusion

Section snippets

Recruitment and eligibility

Patient accounting and demographics

Discussion

Acknowledgments

Respir Med.

Respir Med.

J Allergy Clin Immunol.

J Allergy Clin Immunol.

Lancet.

Respir Med.

J Allergy Clin Immunol.

Global Initiative for Asthma

Pocket Guide for Asthma Management and Prevention

Expert Panel ReportGuidelines for the Diagnosis and Management of Asthma Update on Selected Topics—2002

J Allergy Clin Immunol.

Effect of short-term treatment with low-dose inhaled fluticasone propionate on airway inflammation and remodeling in mild asthmaa placebo-controlled study

Am J Respir Crit Care Med.

Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids

Eur Respir J.

Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction

N Engl J Med.

Comparison of salmeterol with beclomethasone in adult patients with mild persistent asthma who are already on low-dose inhaled steroids

J Asthma.

Asthma drug adherence in a long-term clinical trial

Arch Dis Child.

Low dose inhaled budesonide and formoterol in mild persistent asthmathe OPTIMA randomized trial

Am J Respir Crit Care Med.

Effectiveness of montelukast versus budesonide on quality of life and bronchial reactivity in subjects with mild-persistent asthma

Int J Immunopathol Pharmacol.

Clinical research study
Short-term and long-term asthma control in patients with mild persistent asthma receiving montelukast or fluticasone: a randomized controlled trial