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Christopher J Cates - One of the best experts on this subject based on the ideXlab platform.
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long acting Beta2 Agonist in addition to tiotropium versus either tiotropium or long acting Beta2 Agonist alone for chronic obstructive pulmonary disease
Cochrane Database of Systematic Reviews, 2015Co-Authors: Hugo Farne, Christopher J CatesAbstract:Background Long-acting bronchodilators, comprising long-acting Beta2-Agonists (LABA) and long-acting anti-muscarinic agents (LAMA, principally tiotropium), are commonly used for managing persistent symptoms of chronic obstructive pulmonary disease (COPD). Combining these treatments, which have different mechanisms of action, may be more effective than the individual components. However, the benefits and risks of combining tiotropium and LABAs for the treatment of COPD are unclear. Objectives To compare the relative effects on markers of quality of life, exacerbations, symptoms, lung function and serious adverse events in people with COPD randomised to LABA plus tiotropium versus tiotropium alone; or LABA plus tiotropium versus LABA alone. Search methods We searched the Cochrane Airways Group Specialised Register of trials and ClinicalTrials.gov up to July 2015. Selection criteria We included parallel-group, randomised controlled trials of three months or longer comparing treatment with tiotropium in addition to LABA against tiotropium or LABA alone for people with COPD. Data collection and analysis Two review authors independently assessed trials for inclusion and then extracted data on trial quality and the outcome results. We contacted study authors for additional information. We collected information on adverse effects from the trials. Main results This review included 10 trials on 10,894 participants, mostly recruiting participants with moderate or severe COPD. All of the trials compared tiotropium in addition to LABA to tiotropium alone, and four trials additionally compared LAMA plus LABA with LABA alone. Four studies used the LABA olodaterol, three used indacaterol, two used formoterol, and one used salmeterol. Compared to tiotropium alone, treatment with tiotropium plus LABA resulted in a slightly larger improvement in mean health-related quality of life (St George's Respiratory Questionnaire (SGRQ) (mean difference (MD) -1.34, 95% confidence interval (CI) -1.87 to -0.80; 6709 participants; 5 studies). The MD was smaller than the four units that is considered clinically important, but a responder analysis indicated that 7% more participants receiving tiotropium plus LABA had a noticeable benefit (greater than four units) from treatment in comparison to tiotropium alone. In the control arm in one study, which was tiotropium alone, the SGRQ improved by falling 4.5 units from baseline and with tiotropium plus LABA the improvement was a fall of a further 1.3 units (on average). Most of the data came from studies using olodaterol. High withdrawal rates in the trials increased the uncertainty in this result, and the GRADE assessment for this outcome was therefore moderate. There were no significant differences in the other primary outcomes (hospital admission or mortality). The secondary outcome of pre-bronchodilator forced expiratory volume in one second (FEV1) showed a small mean increase with the addition of LABA over the control arm (MD 0.06, 95% CI 0.05 to 0.07; 9573 participants; 10 studies), which showed a change from baseline ranging from 0.03 L to 0.13 L with tiotropium alone. None of the other secondary outcomes (exacerbations, symptom scores, serious adverse events, and withdrawals) showed any statistically significant differences between the groups. There was moderate heterogeneity for both exacerbations and withdrawals. This review included data on four LABAs: two administered twice daily (salmeterol, formoterol) and two once daily (indacaterol, olodaterol). The results were largely from studies of olodaterol and there was insufficient information to assess whether the other LABAs were equivalent to olodaterol or each other. Comparing LABA plus tiotropium treatment with LABA alone, there was a small but significant improvement in SGRQ (MD -1.25, 95% CI -2.14 to -0.37; 3378 participants; 4 studies). The data came mostly from studies using olodaterol and, although the difference was smaller than four units, this still represented an increase of 10 people with a clinically important improvement for 100 treated. There was also an improvement in FEV1 (MD 0.07, 95% CI 0.06 to 0.09; 3513 participants; 4 studies), and in addition an improvement in exacerbation rates (odds ratio (OR) 0.80, 95% CI 0.69 to 0.93; 3514 participants; 3 studies). Authors' conclusions The results from this review indicated a small mean improvement in health-related quality of life and FEV1 for participants on a combination of tiotropium and LABA compared to either agent alone, and this translated into a small increase in the number of responders on combination treatment. In addition, adding tiotropium to LABA reduced exacerbations, although adding LABA to tiotropium did not. Hospital admission and mortality were not altered by adding LABA to tiotropium, although there may not be enough data. While it is possible that this is affected by higher attrition in the tiotropium group, one would expect that participants withdrawn from the study would have had less favourable outcomes; this means that the expected direction of attrition bias would be to reduce the estimated benefit of the combination treatment. The results were largely from studies of olodaterol and there was insufficient information to assess whether the other LABAs were equivalent to olodaterol or each other.
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indacaterol a once daily Beta2 Agonist versus twice daily Beta2 Agonists or placebo for chronic obstructive pulmonary disease
Cochrane Database of Systematic Reviews, 2015Co-Authors: James B Geake, Eli Dabscheck, R Woodbaker, Christopher J CatesAbstract:Background Indacaterol is an inhaled long-acting Beta2-Agonist that is administered once daily and has been investigated as a treatment for chronic obstructive pulmonary disease (COPD). Four different doses have been investigated (75 mcg, 150 mcg, 300 mcg and 600 mcg). The relative effects of different doses of once-daily indacaterol in the management of patients with COPD are uncertain. Objectives To compare the efficacy and safety of indacaterol versus placebo and alternative twice-daily long-acting Beta2-Agonists for the treatment of patients with stable COPD. Search methods We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), handsearched respiratory journals and meeting abstracts and searched the Novartis trials registry and ClinicalTrials.gov. The date of the most recent search was 8 November 2014. Selection criteria We included all randomised controlled trials comparing indacaterol at any dose versus placebo or alternative long-acting Beta2-Agonists. Trials were required to be of at least 12 weeks' duration and had to include adults older than 18 years with a confirmed spirometric diagnosis of COPD. Data collection and analysis Two review authors (JBG, EJD) independently assessed for possible inclusion all citations identified as a result of the search. Disagreements were resolved through discussion or, if required, through resolution by a third review author (RWB). One review author (JBG) extracted data from trials identified by the search and entered these data into Review Manager 5.1 for statistical analysis. Data entry was cross-checked by a second review author (EJD, CJC). Main results A total of 13 trials with 9961 participants were included in the review. Ten trials with a total of 8562 participants involved an indacaterol versus placebo comparison. Five trials with a total of 4133 participants involved an indacaterol versus twice-daily Beta2-Agonist comparison. The comparator Beta2-Agonists were salmeterol, formoterol and eformoterol. One of these trials, with a total of 90 participants, provided no data that could be used in this review. Two trials included both indacaterol versus placebo and indacaterol versus twice-daily Beta2-Agonist comparisons. Trials were between 12 weeks and 52 weeks in duration. Overall the quality of the evidence was strong, and risk of significant bias was minimal in most of the included studies. Enrolled participants had stable COPD across a range of spirometric severities. Forced expiratory volume in 1 second (FEV1) was generally between 30% and 80% predicted, and a mean FEV1 of approximately 50% was predicted in most studies. Patients with concurrent respiratory disease, including asthma, were excluded. Concomitant use of inhaled corticosteroids was permitted. The primary objectives were to compare trough FEV1 at the end of dosing, exacerbation rates and quality of life. Significant adverse events, mortality and dyspnoea were included as secondary outcomes. Compared with placebo, a significant and clinically relevant improvement in trough FEV1 was noted with indacaterol (mean difference (MD) 149.11, 95% confidence interval (CI) 137.09 to 161.12). In addition, compared with placebo, a significant improvement in mean St George Respiratory Questionaire (SGRQ) score (MD -3.60, 95% CI -4.36 to -2.83) was reported, and the proportion of participants experiencing clinically relevant improvement in SGRQ score was significantly greater (odds ratio (OR) 1.64, 95% CI 1.46 to 1.845. Compared with twice-daily Beta2-Agonists, a small but statistically significant increase in trough FEV1 was seen with indacaterol (MD 61.71 mL, 95% CI 41.24 to 82.17). Differences between indacaterol and twice-daily Beta2-Agonists in mean SGRQ scores (MD -0.81, 95% CI -2.28 to 0.66) and in the proportions of participants achieving clinically relevant improvements in SGRQ scores (OR 1.07, 95% CI 0.87 to 1.32) were not statistically significant, but the confidence intervals are too wide to permit the conclusion that the treatments were equivalent. Authors' conclusions For patients with stable COPD, use of indacaterol versus placebo results in statistically significant and clinically meaningful improvements in lung function and quality of life. The clinical benefit for lung function is at least as good as that seen with twice-daily long-acting Beta2-Agonists, but the comparative effect on quality of life remains uncertain, as important differences cannot be excluded.
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combination inhaled steroid and long acting Beta2 Agonist versus tiotropium for chronic obstructive pulmonary disease
Cochrane Database of Systematic Reviews, 2013Co-Authors: Emma J Welsh, Christopher J Cates, Phillippa PooleAbstract:Background Combination therapy (inhaled corticosteroids and long-acting beta(2)-Agonists) and tiotropium are both used in the treatment of chronic obstructive pulmonary disease (COPD). There is uncertainty about the relative benefits and harms of these treatments. Objectives To assess the relative effects of inhaled combination therapy and tiotropium on patients with COPD. Search strategy We searched the Cochrane Airways Group Specialised Register of trials (March 2010) and reference lists of articles. We also contacted authors of the studies.Selection criteriaWe included only parallel, randomised controlled trials comparing inhaled combination corticosteroid and long-acting beta(2)-Agonist against inhaled tiotropium bromide. Data collection and analysis Two authors independently assessed trials for inclusion and then extracted data on trial quality and outcome results. We contacted study authors for additional information. Discrepancies were resolved through discussion. Main results One large two year trial (INSPIRE) and two smaller, shorter trials (Dawber 2005; SCO40034) were found. The results from these trials were not pooled. The number of withdrawals from each arm of the INSPIRE trial was large and imbalanced and outcome data was not collected for patients who withdrew, raising concerns about the reliability of data from this study.In INSPIRE, there were more deaths on tiotropium than on fluticasone/salmeterol (Peto OR 0.55; 95% CI 0.33 to 0.93). This was a statistically significant difference, however the number of withdrawals from each of the arms was eleven times larger than the observed number of deaths for participants on fluticasone/salmeterol and seven times larger for participants on tiotropium. There were more all cause hospital admissions in patents on fluticasone/salmeterol than those on tiotropium in INSPIRE (Peto OR 1.32; 95% CI 1.04 to 1.67). There was no statistically significant difference in hospital admissions due to exacerbations, the primary outcome of INSPIRE. There was no significant difference in exacerbations in patients on fluticasone/salmeterol compared to tiotropium. Exacerbations requiring treatment with oral corticosteroids were less frequent in patients on fluticasone/salmeterol (Rate Ratio 0.81; 95% CI 0.67 to 0.99). Conversely exacerbations requiring treatment with antibiotics were more frequent in patients treated with fluticasone/salmeterol (Rate Ratio 1.19; 95% CI 1.02 to 1.38). There were more cases of pneumonia in patients on fluticasone/salmeterol than those on tiotropium (Peto OR 2.13; 95% CI 1.33 to 3.40). Confidence intervals for these outcomes do not reflect the additional uncertainty arising from unknown outcome data for patients who withdrew. Authors' conclusions Since the proportion of missing outcome data compared to the observed outcome data is enough to induce a clinically relevant bias in the intervention effect, the relative efficacy and safety of combined inhalers and tiotropium remains uncertain. Further large, long-term randomised controlled trials comparing combination therapy to tiotropium are required, including adequate follow-up of all participants randomised (similar to the procedures undertaken in TORCH and UPLIFT). Additional studies comparing alternative inhaled LABA/steroid combination therapies with tiotropium are also required.
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combination formoterol and inhaled steroid versus Beta2 Agonist as relief medication for chronic asthma in adults and children
Cochrane Database of Systematic Reviews, 2009Co-Authors: Christopher J Cates, Toby J LassersonAbstract:Background Formoterol has a fast onset of action and can therefore be used to relieve symptoms of asthma. A combination inhaler can deliver formoterol with different doses of inhaled corticosteroid; when used as a reliever both drugs will be delivered more frequently when asthma symptoms increase. This has the potential to treat both bronchoconstriction and inflammation in the early stages of exacerbations. Objectives To assess the efficacy and safety of combined inhalers containing both formoterol and an inhaled corticosteroid when used for reliever therapy in adults and children with chronic asthma. Search methods We last searched the Cochrane Airways Group trials register in April 2009, and no new studies were found for inclusion in the review. Selection criteria Randomised trials in adults and children with chronic asthma, where a combination inhaler containing formoterol and inhaled corticosteroid is compared with fast-acting Beta2-Agonist alone for the relief of asthma symptoms. This should be the only planned difference between the trial arms. Data collection and analysis Two review authors independently extracted the characteristics and results of each study. Authors or manufacturers were asked to supply unpublished data in relation to primary outcomes. Main results Three trials involving 5905 participants were included. In patients with mild asthma who do not need maintenance treatment, no clinically important advantages of budesonide/formoterol as reliever were found in comparison to formoterol as reliever. Two studies enrolled patients with more severe asthma who were not controlled on high doses of inhaled corticosteroids (around 700 mcg/day in adults), and had suffered a clinically important asthma exacerbation in the past year. Hospitalisations related to asthma in the two studies comparing budesonide/formoterol for maintenance and relief with the same dose of budesonide/formoterol for maintenance with terbutaline for relief yielded an odds ratio of 0.68 (95% CI 0.40 to 1.16), which was not a statistically significant reduction. In adults there was a reduction in exacerbations requiring oral corticosteroids compared to terbutaline, odds ratio 0.54 (95% CI 0.44 to 0.65), which translates into a number needed to treat over 12 months of 15 (95% CI 13 to 21). The study in children found less serious adverse events with budesonide/formoterol used for maintenance and relief. There was no significant difference in annual growth in children using budesonide/formoterol reliever in comparison to terbutaline. Authors' conclusions In mild asthma it is not yet known whether patients who use a budesonide/formoterol inhaler for relief of asthma symptoms derive any clinically important benefits. In more severe asthma, two studies enrolled patients who were not controlled on inhaled corticosteroids, and had suffered an exacerbation in the previous year, and then had their maintenance inhaled corticosteroids reduced in both arms of the study. Under these conditions the studies demonstrated a reduction in the risk of exacerbations that require oral corticosteroids with budesonide/formoterol for maintenance and relief in comparison with budesonide/formoterol for maintenance and terbutaline or formoterol for relief. The incidence of serious adverse events in children was also less using budesonide/formoterol for maintenance and relief in one study, which similarly enrolled children who were not controlled on inhaled corticosteroids, and who had their maintenance inhaled corticosteroids reduced at the start of the study. This study also compared an explorative maintenance dose of budesonide/formoterol that is not approved for treatment.
Solomon Iyasu - One of the best experts on this subject based on the ideXlab platform.
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the us food and drug administration s drug safety recommendations and long acting Beta2 Agonist dispensing pattern changes in adult asthma patients 2003 2012
Journal of Asthma and Allergy, 2017Co-Authors: Esther H Zhou, Sally Seymour, Margie R Goulding, Elizabeth M Kang, Jacqueline M Major, Solomon IyasuAbstract:Background Emerging safety issues associated with long-acting Beta2-Agonist (LABA) have led to multiple regulatory activities by the US Food and Drug Administration (FDA) since 2003, including Drug Safety Communications (DSCs) in 2010. These DSCs had three specific recommendations for the safe use of LABA products in adult asthma treatment.
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the us food and drug administration s drug safety recommendations and long acting Beta2 Agonist dispensing pattern changes in adult asthma patients 2003 2012
Journal of Asthma and Allergy, 2017Co-Authors: Esther H Zhou, Sally Seymour, Margie R Goulding, Elizabeth M Kang, Jacqueline M Major, Solomon IyasuAbstract:BACKGROUND Emerging safety issues associated with long-acting Beta2-Agonist (LABA) have led to multiple regulatory activities by the US Food and Drug Administration (FDA) since 2003, including Drug Safety Communications (DSCs) in 2010. These DSCs had three specific recommendations for the safe use of LABA products in adult asthma treatment. METHODS We examined the initiation of LABA-containing products for adult asthma treatment using an intermittent time series approach in a claims database from 2003 to 2012. We assessed the alignment of dispensing patterns with the following 2010 FDA recommendations: 1) contraindicated use of single-ingredient (SI)-LABA without an asthma controller medication (ACM); 2) a LABA should only be used when asthma is not adequately controlled on inhaled corticosteroids (ICSs) or ACM; and 3) step-down asthma therapy (e.g., discontinue LABA) when asthma control is achieved. RESULTS There were 477,922 adults (18-64 years old) dispensed a new LABA during 2003-2012. Among LABA initiators, patients who initiated an SI-LABA and who did "not" have an ACM dispensed on the same date decreased from >9% in 2003 (the initial labeling change) to <2% post 2010 DSCs (p-value <0.0001 in the segmented regression model). The proportion of asthma patients dispensed an ICS in 6 months prior to initiating LABA treatment did not increase. The proportion of patients with longer than 4 months of continuous treatment did not decrease over the study period. CONCLUSION Although the decrease in SI-LABA initiation is consistent with FDA's recommendations, low ICS dispensing before initiating a LABA and LABA continuation practices require further efforts to move toward the recommended safe practices.
Yoichi Nakanishi - One of the best experts on this subject based on the ideXlab platform.
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in vivo effects of corticosteroid plus long acting Beta2 Agonist on the expression of b7 h1 pd l1 in double stranded rna induced lung inflammation
European Respiratory Journal, 2014Co-Authors: Saaka Hamano, Koichiro Matsumoto, Satoru Fukuyama, Keiko Kano, Nanae Seki, Ken Tonai, Takako Nakano, Hiromasa Inoue, Yoichi NakanishiAbstract:Background and Aim: Airway viral infection exacerbates asthma and COPD. B7-H1/PD-L1 is a coinhibitory molecule implicated in an escape mechanism of viruses from the host immune systems. This escape may induce viral persistence and lead to the exacerbation. In ERS international congress 2013, we showed that an analog of viral double-strand RNA, polyinosinic-polycytidylic acid (poly I:C), upregulated the expression of B7-H1/PD-L1 on airway epithelial cells in vitro, which was resistant to corticosteroid treatment. Although this resistance was overcome by addition of long-acting Beta2-Agonist (LABA), in vivo evidence remained uncertain. We examined the effect of corticosteroid plus LABA on the expression of B7-H1/PD-L1 in vivo. Methods: We established a murine model of double-stranded RNA-induced inflammation by an intratracheal administration (i.t.) of poly I:C. The expression of B7-H1/PD-L1 in epithelial cells was assessed by flow cytometry as well as assessment of inflammation in bronchoalveolar lavage fluid (BALF). The effects of ciclesonide and/or indacaterol (i.t.) were examined. Results: Poly I:C induced upregulation of B7-H1/PD-L1 in epithelial cells and neutrophilia in BALF. The upregulation was suppressed by low-concentration ciclesonide in combination with indacaterol. This combination also suppressed neutrophilia in BALF. Conclusion: Corticosteroid plus LABA attenuates double-stranded RNA-induced upregulation of B7-H1/PD-L1 in vivo. This mechanism may partly explain a beneficial effect of combination therapy on virus-associated exacerbation of asthma and COPD.
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corticosteroid plus long acting Beta2 Agonist prevent virus associated upregulation of b7 h1 pd l1 on airway epithelium
European Respiratory Journal, 2013Co-Authors: Saaka Hamano, Koichiro Matsumoto, Satoru Fukuyama, Keiko Kano, Hiromasa Inoue, Yukari Asai, Yoichi NakanishiAbstract:Background: Airway viral infections exacerbate asthma and chronic obstructive pulmonary disease. B7-H1/PD-L1 is a coinhibitory molecule implicated in an escape mechanism of viruses from the host immune systems. This escape may induce viral persistence and lead to exacerbation of the underlying diseases. We previously showed that an analog of viral double-stranded RNA, polyinosinic-polycytidylic acid (poly IC), upregulated the expression of B7-H1 on airway epithelial cells, which was corticosteroid-resistant. We investigated the effects of corticosteroid plus long-acting beta 2 -Agonist (LABA) on the expression of B7-H1. Methods: BEAS-2B cells were stimulated with poly IC or the respiratory syncytial virus. B7-H1 expression was assessed by flow cytometry. Results: Poly IC-induced upregulation of B7-H1 was suppressed by high-concentration fluticasone but not by salmeterol. The upregulation was suppressed by low-concentration fluticasone when used in combination with salmeterol. Similar results were obtained from experiments using other combination of corticosteroid and LABA. Their combination also suppressed the virus-induced upregulation of B7-H1. Poly IC stimulation induced the nuclear translocation of the nuclear factor kB (NF-kB). The inhibitors of NF-kB activation prevented the poly IC-induced upregulation of B7-H1. The corticosteroid in combination with LABA enhanced the de novo induction of IkBa, the endogenous inhibitor of NF-kB activation. Conclusion: Corticosteroid plus LABA attenuates virus-associated upregulation of B7-H1 on airway epithelial cells via suppression of NF-kB activation.
Theodore F Reiss - One of the best experts on this subject based on the ideXlab platform.
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montelukast a potent leukotriene receptor antAgonist causes dose related improvements in chronic asthma montelukast asthma study group
European Respiratory Journal, 1998Co-Authors: M J Noonan, M Brandon, J Mcburney, Paul Chervinsky, Ji Zhang, S Kundu, Theodore F ReissAbstract:The leukotrienes are known to be important mediators of bronchial asthma. The ability of montelukast, a potent and selective CysLT1 leukotriene receptor antAgonist, to cause a dose-related improvement in chronic asthma was investigated in a placebo-controlled, multicentre, parallel-group study. After a two week placebo run-in period, chronic asthmatic patients with a forced expiratory volume in one second (FEV1) 40-80% predicted with > or = 15% increase (absolute value) after Beta2-Agonist were randomly assigned to one of four treatment groups (placebo or montelukast 2, 10, or 50 mg once daily in the evening) for a three week, double-blind treatment period. For patient-reported end-points (daytime symptom score, use of as needed inhaled Beta2 Agonist, asthma-specific quality of life) and frequency of asthma exacerbations, montelukast 10 and 50 mg caused similar responses, superior to 2 mg and significantly (p
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montelukast a potent leukotriene receptor antAgonist causes dose related improvements in chronic asthma montelukast asthma study group
European Respiratory Journal, 1998Co-Authors: M J Noonan, M Brandon, J Mcburney, Paul Chervinsky, Ji Zhang, S Kundu, Theodore F ReissAbstract:The leukotrienes are known to be important mediators of bronchial asthma. The ability of montelukast, a potent and selective CysLT1 leukotriene receptor antAgonist, to cause a dose-related improvement in chronic asthma was investigated in a placebo-controlled, multicentre, parallel-group study. After a two week placebo run-in period, chronic asthmatic patients with a forced expiratory volume in one second (FEV1) 40-80% predicted with > or = 15% increase (absolute value) after Beta2-Agonist were randomly assigned to one of four treatment groups (placebo or montelukast 2, 10, or 50 mg once daily in the evening) for a three week, double-blind treatment period. For patient-reported end-points (daytime symptom score, use of as needed inhaled Beta2 Agonist, asthma-specific quality of life) and frequency of asthma exacerbations, montelukast 10 and 50 mg caused similar responses, superior to 2 mg and significantly (p<0.05; linear trend test) different from placebo. All three doses caused improvements in FEV1 and morning and evening peak expiratory flow rate (PEFR) that were significantly (p<0.05) different from placebo. Differences (least square mean) between the pooled 10 and 50 mg montelukast treatment groups and placebo were: 7.1% change from baseline in FEV1, 19.23 L x min(-1) in morning PEFR, -0.29 in daytime asthma symptom score (absolute value), and -0.82 in Beta2-Agonist use (puff x day(-1)). The incidence of adverse experiences was neither dose-related nor different between montelukast and placebo treatments. We conclude that montelukast causes a dose-related improvement in patient-reported asthma end-points over the range 2-50 mg. Montelukast causes benefit to chronic asthmatic patients by improving asthma control end-points.
Esther H Zhou - One of the best experts on this subject based on the ideXlab platform.
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the us food and drug administration s drug safety recommendations and long acting Beta2 Agonist dispensing pattern changes in adult asthma patients 2003 2012
Journal of Asthma and Allergy, 2017Co-Authors: Esther H Zhou, Sally Seymour, Margie R Goulding, Elizabeth M Kang, Jacqueline M Major, Solomon IyasuAbstract:Background Emerging safety issues associated with long-acting Beta2-Agonist (LABA) have led to multiple regulatory activities by the US Food and Drug Administration (FDA) since 2003, including Drug Safety Communications (DSCs) in 2010. These DSCs had three specific recommendations for the safe use of LABA products in adult asthma treatment.
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the us food and drug administration s drug safety recommendations and long acting Beta2 Agonist dispensing pattern changes in adult asthma patients 2003 2012
Journal of Asthma and Allergy, 2017Co-Authors: Esther H Zhou, Sally Seymour, Margie R Goulding, Elizabeth M Kang, Jacqueline M Major, Solomon IyasuAbstract:BACKGROUND Emerging safety issues associated with long-acting Beta2-Agonist (LABA) have led to multiple regulatory activities by the US Food and Drug Administration (FDA) since 2003, including Drug Safety Communications (DSCs) in 2010. These DSCs had three specific recommendations for the safe use of LABA products in adult asthma treatment. METHODS We examined the initiation of LABA-containing products for adult asthma treatment using an intermittent time series approach in a claims database from 2003 to 2012. We assessed the alignment of dispensing patterns with the following 2010 FDA recommendations: 1) contraindicated use of single-ingredient (SI)-LABA without an asthma controller medication (ACM); 2) a LABA should only be used when asthma is not adequately controlled on inhaled corticosteroids (ICSs) or ACM; and 3) step-down asthma therapy (e.g., discontinue LABA) when asthma control is achieved. RESULTS There were 477,922 adults (18-64 years old) dispensed a new LABA during 2003-2012. Among LABA initiators, patients who initiated an SI-LABA and who did "not" have an ACM dispensed on the same date decreased from >9% in 2003 (the initial labeling change) to <2% post 2010 DSCs (p-value <0.0001 in the segmented regression model). The proportion of asthma patients dispensed an ICS in 6 months prior to initiating LABA treatment did not increase. The proportion of patients with longer than 4 months of continuous treatment did not decrease over the study period. CONCLUSION Although the decrease in SI-LABA initiation is consistent with FDA's recommendations, low ICS dispensing before initiating a LABA and LABA continuation practices require further efforts to move toward the recommended safe practices.