Adherence with montelukast or fluticasone in a long-term clinical trial: Results from the Mild Asthma Montelukast Versus Inhaled Corticosteroid Trial

doi:10.1016/j.jaci.2006.12.664

Journal of Allergy and Clinical Immunology

Volume 119, Issue 4, April 2007, Pages 916-923

https://doi.org/10.1016/j.jaci.2006.12.664 Get rights and content

Background

Nonadherence with asthma therapy is common and may contribute to poor clinical outcomes.

Objective

To examine the effect of dosing frequency and mode of delivery of therapy on adherence and clinical outcomes.

Methods

We examined adherence in patients with mild persistent asthma (15-85 years) enrolled in a randomized study of montelukast (10 mg once daily) or fluticasone (88 μg, 2 puffs twice daily) during a 12-week double-blind treatment period (DB), followed by a 36-week open-label trial (OL). Adherence was monitored using eDEM for montelukast/placebo and MDILog devices for fluticasone/placebo.

Results

Participants used at least 1 puff of inhaled therapy on 83.3% DB/76.8% OL of days and at least 1 dose of oral therapy on 77.5%/71.4% of days (P < .0001). Subjects used inhaled therapy less than prescribed on 49.5%/57.5% of days, compared with 22.5%/28.6% of days for oral therapy (P < .0001). In the DB, a dose-response relationship was observed with fluticasone and asthma rescue-free days (P = .02) and FEV₁ percent predicted (P < .01) only for patients with FEV₁ ≤ 86%. In the OL period, a dose-response relationship was observed with fluticasone and FEV₁ percent predicted (P < .001).

Conclusion

Whereas subjects were more likely to use inhaled fluticasone/placebo at least once a day, subjects were more likely to take once-daily oral montelukast/placebo as prescribed. Clinical outcomes were inconsistently associated with adherence levels.

Clinical implications

Patients were less likely to be fully adherent with twice-daily therapy than with once-daily therapy, but most still achieved adequate asthma control.

Section snippets

Recruitment and eligibility

Institutional review boards at each study site (n = 39) approved the study protocol. Patients or guardians gave written informed consent before enrollment, and adolescents gave their assent. Patients age 15 to 85 years with symptoms and albuterol use consistent with mild persistent asthma for at least 4 months on the basis of the National Asthma Education Prevention Program¹³ and Global Initiative for Asthma¹⁴ definitions were recruited as detailed elsewhere.¹² Participants were excluded if

Patient demographics

Three hundred eighty patients were randomized to masked treatment with montelukast (N = 189) or fluticasone (N = 191). Patient accounting, presented elsewhere,¹² noted the groups were well balanced for all baseline parameters. Patients were predominately female (69.5%), white (80.8%), young (mean age, 35.2 ± 14.3 years), and atopic (79.6%). Mean baseline asthma severity characteristics were consistent with asthma treatment guideline definitions of mild persistent disease and have been

Discussion

We examined adherence to once-daily oral montelukast/placebo compared with adherence with twice-daily inhaled fluticasone/placebo in the same individuals and found that participants were slightly more likely to take at least 1 daily dose of their twice-daily inhaled medication than to take their once-daily dose of oral medication. However, participants were more likely to take the twice-daily inhaled therapy less than prescribed compared with once-daily oral therapy. In fact, inhaled therapy

References (21)

M. Mann et al.
A comparison of the effects of bid and qid dosing on compliance with inhaled flunisolide
Chest
(1992)
M. Iskedjian et al.
Relationship between daily dose frequency and adherence to antihypertensive pharmacotherapy: evidence from a meta-analysis
Clin Ther
(2002)
S.W. Stoloff et al.
Improved refill persistence with fluticasone propionate and salmeterol in a single inhaler compared with other controller therapies
J Allergy Clin Immunol
(2004)
J. Urquhart
Pharmacodynamics of variable patient compliance: implications for pharmaceutical value
Adv Drug Deliv Rev
(1998)
R.S. Zeiger et al.
Variability of symptoms in mild persistent asthma: baseline data from the MIAMI study
Respir Med
(2004)
R.S. Zeiger et al.
Short-term and long-term asthma control in patients with mild persistent asthma receiving montelukast or fluticasone: a randomized controlled trial
Am J Med
(2005)
A.J. Apter et al.
Testing the reliability of old and new features of a new electronic monitor for metered dose inhalers
Ann Allergy Asthma Immunol
(2001)
S.M. Julius et al.
Accuracy of three electronic monitors for metered-dose inhalers
Chest
(2002)
C.S. Rand et al.
Patient adherence to inhaled corticosteroid therapy
B.L. Mason et al.
Microprocessor-assessed adherence with once or twice-a-day dosing with sulfonylurea: no difference
West J Med
(1996)

There are more references available in the full text version of this article.

Cited by (76)

Patient experiences of as-needed budesonide-formoterol by Turbuhaler® for treatment of mild asthma; a qualitative study
2020, Respiratory Medicine
Combination low-dose budesonide-formoterol, taken as-needed for symptom relief reduces exacerbation risk and is recommended for treatment of mild asthma. The NovelQ qualitative study explored patients’ attitudes toward using this novel therapy.
Adults with mild asthma using reliever-only treatment were randomised to as-needed budesonide-formoterol Turbuhaler® in a multinational, 52-week open-label randomised controlled trial (NovelSTART-ACTRN12615000999538). A subgroup were interviewed to explore their attitudes to use of as-needed budesonide-formoterol after receiving it for ≥10 months. Semi-structured interviews were conducted until saturation, audio-recorded, and thematically analysed.
Analysis of 35 participants (66% female; mean age 43.5 [range 18–74]; mean Asthma Control Questionnaire score 1.09 ± SD0.55) interviews identified 5 themes, each including both barriers and facilitators to therapy use. Themes were: ‘Treatment effectiveness’ i.e. how well symptoms were relieved and/or prevented; ‘Lifestyle fit of the regimen’ e.g. the extent to which the treatment regimen integrated into the patient's daily life; ‘Attitudes toward medication use and safety’ e.g. openness for new reliever treatments, beliefs about treatment necessity or side effects; ‘Device attributes’ e.g. perceived ease of use; and ‘Doctor-patient relationship’ e.g. impact of health professional support on new treatment acceptance.
A wide range of factors seem to drive the opinions of mild asthma patients on as-needed budesonide-formoterol therapy. Many patients perceived both positive and negative treatment attributes, and their individual evaluation of these attributes determined their likelihood of using it after the study. Supportive patient-physician interactions appear key to addressing patient barriers. Recommendations for patient-centred discussions, developed from this research, are provided.
Roflumilast for asthma: Efficacy findings in non-placebo-controlled comparator and dosing studies
2015, Pulmonary Pharmacology and Therapeutics
Roflumilast, a phosphodiesterase-4 inhibitor, has an established place in the treatment of chronic obstructive pulmonary disease. Its potential role as a treatment for asthma is unclear.
We report the results from seven double-blind, parallel group, phase II or III studies designed to compare roflumilast with two anti-inflammatory treatments, beclomethasone dipropionate (BDP) and montelukast, in patients with asthma.
The studies of 6–12 week duration were conducted at 309 sites in Europe, North America, South Africa and Australia from 1998 to 2005. Data from 3802 patients, aged 12–70 years who received either roflumilast 100 μg, 250 μg or 500 μg once daily, BDP 400 μg or 500 μg twice daily, or 10 mg montelukast once daily was analyzed. Primary endpoints were mean change and time averaged excess area under the curve in forced expiratory volume in one second (FEV₁) over the duration of the study. Secondary endpoints included change in forced vital capacity and peak expiratory flow, asthma symptoms and the concomitant use of rescue medication.
Roflumilast was non-inferior to BDP and montelukast and consistently increased FEV₁. Use of rescue medication and all asthma symptom scores decreased significantly with all treatments, but no statistically significant between-group differences were observed. Secondary lung function endpoints generally supported the conclusions of the primary outcome measure.
Roflumilast improves FEV₁ and asthma symptoms in patients with mild to moderate asthma, and is non-inferior compared with both BDP and montelukast. It deserves further study as a potentially effective anti-inflammatory treatment for asthma.
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
Citation Excerpt :
Results of previous randomized clinical trials found greater efficacy of ICS compared with LTRA in children.27,28 Results of some studies also indicated that adults with randomized mild persistent asthma experienced greater efficacy, even with poorer adherence to ICS compared with LTRAs.29,30 One possible reason that our findings conflict with previous clinical trials is that LTRAs are just as effective as ICS in preventing asthma-related exacerbations in real-life settings.
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.
Assessment of regular drug use and inhaler technique skills in asthmatic children
2020, Allergologia et Immunopathologia
Citation Excerpt :
Some studies have shown that adherence to drugs given by mouth is higher compared with inhaled medications in asthmatic children. In our study, however, there was no difference between drugs administered orally and inhaled drugs in the regular use of long-term asthma control drugs.26–28 Factors unrelated to medications include the underestimation of severity and forgetfulness.3
This study aimed to assess the regular use of long-term asthma-control medication and to determine inhaler techniques in asthmatic children.
The study was conducted on asthmatic children aged 6–18 years. Information on rescue and controller medications was given and the proper inhalation technique was demonstrated. One month later, patients and parents were asked to answer a questionnaire on drug use and to demonstrate their inhaler techniques.
One hundred children and/or their parents were interviewed for the study. All of the patients identified long-term asthma-control medications while quick-relief asthma medications were identified by 93% of the patients. Of the patients, 34% described the dose of their quick-relief medication correctly. All steps in the inhalation technique were correctly carried out by 60.6% of patients using a metered-dose inhaler (MDI), 80% of patients using a Turbuhaler, and 58% of patients using a capsule-based dry-powder inhaler (DPI). Of the participants, 73% reported regular use of long-term asthma-control medications. While the mean age of the patients regularly using long-term asthma medications was 9.05 ± 2.5 years, that of patients not compliant with the regular treatment was 10.29 ± 3.26 years (p = 0.04). The most common reason for irregular drug use was forgetting to take the drug.
Adherence to long-term asthma-control medications tends to be better in younger patients. Since the most common cause of irregular drug use is forgetting to take the drug, repeated training is necessary to ensure asthma control and the successful treatment of asthmatic children.
Correlation of vitamin D receptor genotypes, specific IgE levels and other variables with asthma control in children
2024, Journal of Asthma
Treatment of pediatric mild persistent asthma with low-dose budesonide inhalation suspension vs. montelukast in China
2021, World Journal of Pediatrics

View all citing articles on Scopus

Supported by Merck & Co, Inc.

Disclosure of potential conflict of interest: C. Rand has consulting arrangements with Schering Plough; has received grant support from Merck; and is on the speakers' bureau for GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, and Merck. J. M. Edelman owns stock in and is employed by Merck. C. M. Hustad owns stock in and is employed by Merck. R. S. Zeiger has consulting arrangements with AstraZeneca, Genentech, Glaxo-SmithKline, Merck, Novartis, and Sanofi-Aventis; has received grant support from AstraZeneca, Genentech, GlaxoSmithKline, Merck, Novartis, and Sanofi-Aventis; and has lectured for AstraZeneca. The rest of the authors have declared that they have no conflict of interest.

^∗: A list of the members of the Mild Asthma Montelukast Versus Inhaled Corticosteroid Trial Study Research Group appears at the end of this article.

View full text

Health care education, delivery, and qualityAdherence with montelukast or fluticasone in a long-term clinical trial: Results from the Mild Asthma Montelukast Versus Inhaled Corticosteroid Trial

Background

Objective

Methods

Results

Conclusion

Clinical implications

Section snippets

Recruitment and eligibility

Patient demographics

Discussion

Chest

Clin Ther

J Allergy Clin Immunol

Adv Drug Deliv Rev

Respir Med

Am J Med

Ann Allergy Asthma Immunol

Chest

Patient adherence to inhaled corticosteroid therapy

Microprocessor-assessed adherence with once or twice-a-day dosing with sulfonylurea: no difference

West J Med

Health care education, delivery, and quality
Adherence with montelukast or fluticasone in a long-term clinical trial: Results from the Mild Asthma Montelukast Versus Inhaled Corticosteroid Trial