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Asthma patients who struggle with poor control despite using inhaled corticosteroids can benefit from additional treatment with long-acting muscarinic antagonists (LAMAs) or single maintenance and reliever therapy, suggest data from a pair of systematic reviews and meta-analyses.
Asthma control remains a problem for many patients despite the daily use of inhaled corticosteroids. The current preferred adjunct therapy for patients aged 12 years and older is long-acting beta-agonists (LABAs), wrote Diana M. Sobieraj, PharmD, of the University of Connecticut School of Pharmacy, Storrs, and her colleagues in a study published in JAMA. The researchers examined the efficacy of other adjunct therapies and therapeutic regimes, including the use of a LAMA, in two studies of patients with persistent asthma.
Overall, patients who took a LAMA had a lower risk of asthma exacerbation requiring systemic corticosteroids and improved spirometry measures than did the patients who took a placebo or used another controller as an adjunct therapy.
In trials that compared LAMAs with placebo as an add-on to inhaled corticosteroids, LAMA patients experienced a significantly reduced risk of exacerbation requiring systemic corticosteroids (–1.8) and a significantly reduced risk of asthma worsening (–4.8). Another benefit seen in the patients who used a LAMA rather than those who used a placebo was improved spirometry measures, but the differences between these two patient groups’ numbers did not reach statistical significance.
The analysis also included studies that compared “triple therapy” – defined as use of a LAMA as add-on therapy to inhaled corticosteroids and LABAs – to LABA plus use of inhaled corticosteroids.
Triple therapy was significantly associated with a lower risk of asthma worsening, compared with inhaled corticosteroids and LABAs, but not with a reduced risk of exacerbation. In addition, no significant differences appeared in Asthma Control Questionnaire-7 scores or overall Asthma Quality of Life Questionnaire scores between the two patient groups.
“Triple therapy was not significantly associated with improvements in rescue medication use vs. combined inhaled corticosteroids and LABA therapy,” the researchers added.
The review of LAMAs used as add-on therapy was limited by several factors, including a primary focus on tiotropium, a lack of analysis of harms or the costs of the various therapies, the lack of data for children, and an inability to perform a subgroup analysis, the researchers said. Although LAMA use was associated with a lower risk of asthma exacerbation, compared with placebo use, the review could not adequately compare LAMA with controllers other than LABA, they added.
In the second analysis, which also was published in JAMA, the researchers evaluated the use of inhaled corticosteroids and LABAs as both a controller and quick-relief treatment, a strategy known as SMART, or Single Maintenance and Reliever Therapy. The SMART protocol, which is not approved in the United States, involved taking a combination of the corticosteroid budesonide and the LABA formoterol in a dry-powder inhaler in most of the studies reviewed.
Overall, in the analysis of 22,524 patients aged 12 years and older, an absolute risk difference of –2.8% for asthma exacerbations was seen in those who used the SMART protocol versus those who used a higher dose of inhaled corticosteroids and inhaled LABA as controller therapy.
In addition, data from 341 children aged 4-11 years showed a –12% absolute difference in risk of asthma exacerbation with the SMART therapy.
In trials that compared patients using the SMART protocol with those taking only the dose of inhaled corticosteroids called for by SMART, the protocol was associated with an improvement in forced expiratory volume in 1 second (FEV1) and a reduction in the need for rescue medication.
The SMART protocol also demonstrated advantages over taking the same dose of inhaled corticosteroid called for by SMART plus a LABA controller therapy or a higher dose of inhaled corticosteroids with a LABA controller therapy. Specifically, SMART patients experienced a –6.4% risk of asthma exacerbations, versus the first comparator group; and a –2.7% risk of asthma, compared with the group who took a higher dose of inhaled corticosteroids with LABA controller therapy.
No significant associations appeared in any of the studies between the SMART protocol and outcomes that included all-cause mortality or changes in FEV1, forced vital capacity, or the percentage of predicted FEV1, when compared with those for patients who used a LABA controller therapy plus inhaled corticosteroids at either dose.
The SMART protocol review was limited by factors that included a lack of data on adverse events, a lack of subgroup analysis, and the potential for bias, because of the open label nature of some of the studies, the researchers noted.
However, despite the limitations in both reviews, the results support the SMART strategy and LAMAs as alternatives for patients with persistent asthma, and highlight the need for further research, they noted.
The reviews were supported by the Agency for Healthcare Research and Quality. Dr. Sobieraj had no financial conflicts to disclose.
SOURCE: Sobieraj D et al. JAMA. 2018;319(14):1473-84. Sobieraj D et al. JAMA. 2018;319(14):1485-96.
Asthma remains a major public health problem in the United States, but 11 years have passed since the last update to treatment guidelines, and an update to the current guidelines for asthma treatment is needed, wrote Jerry A. Krishnan, MD, and David H. Au, MD, in an accompanying editorial (JAMA. 2018;319[14]:1441-3). “It is time to connect the efforts of the FDA, the evidence presented by Sobieraj et al., and the support from the National Education and Prevention Program to update the 2007 [Expert Panel Report 3] guidelines on asthma.”
Both reviews showed effectiveness for the treatments being assessed, compared with placebo, but each had limitations, the editorialists noted.
The study findings in the report on the efficacy of inhaled long-acting muscarinic antagonists (LAMAs) in adolescents and adults with uncontrolled asthma were limited by several factors including a focus primarily on tiotropium, absence of data on potential harms and relative costs of treatment, and a lack of data on children younger than 12 years, they noted. The findings in the analysis of the strategy known as Single Maintenance and Reliever Therapy (SMART) containing formoterol, a long-acting beta2-agonist, were similarly limited by a lack of assessment of potential harm and a data on children within the same age group, they said.
However, the effectiveness of the treatments seen in both reviews suggest that the forthcoming revision of the Expert Panel Report 3 guidelines on asthma from the National Asthma Education and Prevention Program should include the option for inhaled tiotropium, a LAMA, and for the formoterol-based SMART protocol, the editorialists wrote.
“For patients and clinicians, the results from these meta-analyses suggest that dual therapy with scheduled doses of inhaled corticosteroids and LABA or inhaled corticosteroids and LAMA should help reduce the risk of future asthma exacerbations in patients with inadequate asthma control while using inhaled corticosteroids alone,” they said. The new guidelines should include evidence for the SMART therapy as well, but “studies assessing the efficacy of SMART using combination formoterol and budesonide via a metered-dose inhaler are needed,” they concluded.
Dr. Krishnan is affiliated with the division of pulmonary, critical care, sleep, and allergy at the University of Illinois, Chicago, and disclosed having received compensation from Sanofi for participation on an independent data-monitoring committee. Dr. Au is affiliated with the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and disclosed having received compensation from Novartis for participation on a data-monitoring committee and for serving as a consultant to Gilead Sciences.
Asthma remains a major public health problem in the United States, but 11 years have passed since the last update to treatment guidelines, and an update to the current guidelines for asthma treatment is needed, wrote Jerry A. Krishnan, MD, and David H. Au, MD, in an accompanying editorial (JAMA. 2018;319[14]:1441-3). “It is time to connect the efforts of the FDA, the evidence presented by Sobieraj et al., and the support from the National Education and Prevention Program to update the 2007 [Expert Panel Report 3] guidelines on asthma.”
Both reviews showed effectiveness for the treatments being assessed, compared with placebo, but each had limitations, the editorialists noted.
The study findings in the report on the efficacy of inhaled long-acting muscarinic antagonists (LAMAs) in adolescents and adults with uncontrolled asthma were limited by several factors including a focus primarily on tiotropium, absence of data on potential harms and relative costs of treatment, and a lack of data on children younger than 12 years, they noted. The findings in the analysis of the strategy known as Single Maintenance and Reliever Therapy (SMART) containing formoterol, a long-acting beta2-agonist, were similarly limited by a lack of assessment of potential harm and a data on children within the same age group, they said.
However, the effectiveness of the treatments seen in both reviews suggest that the forthcoming revision of the Expert Panel Report 3 guidelines on asthma from the National Asthma Education and Prevention Program should include the option for inhaled tiotropium, a LAMA, and for the formoterol-based SMART protocol, the editorialists wrote.
“For patients and clinicians, the results from these meta-analyses suggest that dual therapy with scheduled doses of inhaled corticosteroids and LABA or inhaled corticosteroids and LAMA should help reduce the risk of future asthma exacerbations in patients with inadequate asthma control while using inhaled corticosteroids alone,” they said. The new guidelines should include evidence for the SMART therapy as well, but “studies assessing the efficacy of SMART using combination formoterol and budesonide via a metered-dose inhaler are needed,” they concluded.
Dr. Krishnan is affiliated with the division of pulmonary, critical care, sleep, and allergy at the University of Illinois, Chicago, and disclosed having received compensation from Sanofi for participation on an independent data-monitoring committee. Dr. Au is affiliated with the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and disclosed having received compensation from Novartis for participation on a data-monitoring committee and for serving as a consultant to Gilead Sciences.
Asthma remains a major public health problem in the United States, but 11 years have passed since the last update to treatment guidelines, and an update to the current guidelines for asthma treatment is needed, wrote Jerry A. Krishnan, MD, and David H. Au, MD, in an accompanying editorial (JAMA. 2018;319[14]:1441-3). “It is time to connect the efforts of the FDA, the evidence presented by Sobieraj et al., and the support from the National Education and Prevention Program to update the 2007 [Expert Panel Report 3] guidelines on asthma.”
Both reviews showed effectiveness for the treatments being assessed, compared with placebo, but each had limitations, the editorialists noted.
The study findings in the report on the efficacy of inhaled long-acting muscarinic antagonists (LAMAs) in adolescents and adults with uncontrolled asthma were limited by several factors including a focus primarily on tiotropium, absence of data on potential harms and relative costs of treatment, and a lack of data on children younger than 12 years, they noted. The findings in the analysis of the strategy known as Single Maintenance and Reliever Therapy (SMART) containing formoterol, a long-acting beta2-agonist, were similarly limited by a lack of assessment of potential harm and a data on children within the same age group, they said.
However, the effectiveness of the treatments seen in both reviews suggest that the forthcoming revision of the Expert Panel Report 3 guidelines on asthma from the National Asthma Education and Prevention Program should include the option for inhaled tiotropium, a LAMA, and for the formoterol-based SMART protocol, the editorialists wrote.
“For patients and clinicians, the results from these meta-analyses suggest that dual therapy with scheduled doses of inhaled corticosteroids and LABA or inhaled corticosteroids and LAMA should help reduce the risk of future asthma exacerbations in patients with inadequate asthma control while using inhaled corticosteroids alone,” they said. The new guidelines should include evidence for the SMART therapy as well, but “studies assessing the efficacy of SMART using combination formoterol and budesonide via a metered-dose inhaler are needed,” they concluded.
Dr. Krishnan is affiliated with the division of pulmonary, critical care, sleep, and allergy at the University of Illinois, Chicago, and disclosed having received compensation from Sanofi for participation on an independent data-monitoring committee. Dr. Au is affiliated with the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and disclosed having received compensation from Novartis for participation on a data-monitoring committee and for serving as a consultant to Gilead Sciences.
Asthma patients who struggle with poor control despite using inhaled corticosteroids can benefit from additional treatment with long-acting muscarinic antagonists (LAMAs) or single maintenance and reliever therapy, suggest data from a pair of systematic reviews and meta-analyses.
Asthma control remains a problem for many patients despite the daily use of inhaled corticosteroids. The current preferred adjunct therapy for patients aged 12 years and older is long-acting beta-agonists (LABAs), wrote Diana M. Sobieraj, PharmD, of the University of Connecticut School of Pharmacy, Storrs, and her colleagues in a study published in JAMA. The researchers examined the efficacy of other adjunct therapies and therapeutic regimes, including the use of a LAMA, in two studies of patients with persistent asthma.
Overall, patients who took a LAMA had a lower risk of asthma exacerbation requiring systemic corticosteroids and improved spirometry measures than did the patients who took a placebo or used another controller as an adjunct therapy.
In trials that compared LAMAs with placebo as an add-on to inhaled corticosteroids, LAMA patients experienced a significantly reduced risk of exacerbation requiring systemic corticosteroids (–1.8) and a significantly reduced risk of asthma worsening (–4.8). Another benefit seen in the patients who used a LAMA rather than those who used a placebo was improved spirometry measures, but the differences between these two patient groups’ numbers did not reach statistical significance.
The analysis also included studies that compared “triple therapy” – defined as use of a LAMA as add-on therapy to inhaled corticosteroids and LABAs – to LABA plus use of inhaled corticosteroids.
Triple therapy was significantly associated with a lower risk of asthma worsening, compared with inhaled corticosteroids and LABAs, but not with a reduced risk of exacerbation. In addition, no significant differences appeared in Asthma Control Questionnaire-7 scores or overall Asthma Quality of Life Questionnaire scores between the two patient groups.
“Triple therapy was not significantly associated with improvements in rescue medication use vs. combined inhaled corticosteroids and LABA therapy,” the researchers added.
The review of LAMAs used as add-on therapy was limited by several factors, including a primary focus on tiotropium, a lack of analysis of harms or the costs of the various therapies, the lack of data for children, and an inability to perform a subgroup analysis, the researchers said. Although LAMA use was associated with a lower risk of asthma exacerbation, compared with placebo use, the review could not adequately compare LAMA with controllers other than LABA, they added.
In the second analysis, which also was published in JAMA, the researchers evaluated the use of inhaled corticosteroids and LABAs as both a controller and quick-relief treatment, a strategy known as SMART, or Single Maintenance and Reliever Therapy. The SMART protocol, which is not approved in the United States, involved taking a combination of the corticosteroid budesonide and the LABA formoterol in a dry-powder inhaler in most of the studies reviewed.
Overall, in the analysis of 22,524 patients aged 12 years and older, an absolute risk difference of –2.8% for asthma exacerbations was seen in those who used the SMART protocol versus those who used a higher dose of inhaled corticosteroids and inhaled LABA as controller therapy.
In addition, data from 341 children aged 4-11 years showed a –12% absolute difference in risk of asthma exacerbation with the SMART therapy.
In trials that compared patients using the SMART protocol with those taking only the dose of inhaled corticosteroids called for by SMART, the protocol was associated with an improvement in forced expiratory volume in 1 second (FEV1) and a reduction in the need for rescue medication.
The SMART protocol also demonstrated advantages over taking the same dose of inhaled corticosteroid called for by SMART plus a LABA controller therapy or a higher dose of inhaled corticosteroids with a LABA controller therapy. Specifically, SMART patients experienced a –6.4% risk of asthma exacerbations, versus the first comparator group; and a –2.7% risk of asthma, compared with the group who took a higher dose of inhaled corticosteroids with LABA controller therapy.
No significant associations appeared in any of the studies between the SMART protocol and outcomes that included all-cause mortality or changes in FEV1, forced vital capacity, or the percentage of predicted FEV1, when compared with those for patients who used a LABA controller therapy plus inhaled corticosteroids at either dose.
The SMART protocol review was limited by factors that included a lack of data on adverse events, a lack of subgroup analysis, and the potential for bias, because of the open label nature of some of the studies, the researchers noted.
However, despite the limitations in both reviews, the results support the SMART strategy and LAMAs as alternatives for patients with persistent asthma, and highlight the need for further research, they noted.
The reviews were supported by the Agency for Healthcare Research and Quality. Dr. Sobieraj had no financial conflicts to disclose.
SOURCE: Sobieraj D et al. JAMA. 2018;319(14):1473-84. Sobieraj D et al. JAMA. 2018;319(14):1485-96.
Asthma patients who struggle with poor control despite using inhaled corticosteroids can benefit from additional treatment with long-acting muscarinic antagonists (LAMAs) or single maintenance and reliever therapy, suggest data from a pair of systematic reviews and meta-analyses.
Asthma control remains a problem for many patients despite the daily use of inhaled corticosteroids. The current preferred adjunct therapy for patients aged 12 years and older is long-acting beta-agonists (LABAs), wrote Diana M. Sobieraj, PharmD, of the University of Connecticut School of Pharmacy, Storrs, and her colleagues in a study published in JAMA. The researchers examined the efficacy of other adjunct therapies and therapeutic regimes, including the use of a LAMA, in two studies of patients with persistent asthma.
Overall, patients who took a LAMA had a lower risk of asthma exacerbation requiring systemic corticosteroids and improved spirometry measures than did the patients who took a placebo or used another controller as an adjunct therapy.
In trials that compared LAMAs with placebo as an add-on to inhaled corticosteroids, LAMA patients experienced a significantly reduced risk of exacerbation requiring systemic corticosteroids (–1.8) and a significantly reduced risk of asthma worsening (–4.8). Another benefit seen in the patients who used a LAMA rather than those who used a placebo was improved spirometry measures, but the differences between these two patient groups’ numbers did not reach statistical significance.
The analysis also included studies that compared “triple therapy” – defined as use of a LAMA as add-on therapy to inhaled corticosteroids and LABAs – to LABA plus use of inhaled corticosteroids.
Triple therapy was significantly associated with a lower risk of asthma worsening, compared with inhaled corticosteroids and LABAs, but not with a reduced risk of exacerbation. In addition, no significant differences appeared in Asthma Control Questionnaire-7 scores or overall Asthma Quality of Life Questionnaire scores between the two patient groups.
“Triple therapy was not significantly associated with improvements in rescue medication use vs. combined inhaled corticosteroids and LABA therapy,” the researchers added.
The review of LAMAs used as add-on therapy was limited by several factors, including a primary focus on tiotropium, a lack of analysis of harms or the costs of the various therapies, the lack of data for children, and an inability to perform a subgroup analysis, the researchers said. Although LAMA use was associated with a lower risk of asthma exacerbation, compared with placebo use, the review could not adequately compare LAMA with controllers other than LABA, they added.
In the second analysis, which also was published in JAMA, the researchers evaluated the use of inhaled corticosteroids and LABAs as both a controller and quick-relief treatment, a strategy known as SMART, or Single Maintenance and Reliever Therapy. The SMART protocol, which is not approved in the United States, involved taking a combination of the corticosteroid budesonide and the LABA formoterol in a dry-powder inhaler in most of the studies reviewed.
Overall, in the analysis of 22,524 patients aged 12 years and older, an absolute risk difference of –2.8% for asthma exacerbations was seen in those who used the SMART protocol versus those who used a higher dose of inhaled corticosteroids and inhaled LABA as controller therapy.
In addition, data from 341 children aged 4-11 years showed a –12% absolute difference in risk of asthma exacerbation with the SMART therapy.
In trials that compared patients using the SMART protocol with those taking only the dose of inhaled corticosteroids called for by SMART, the protocol was associated with an improvement in forced expiratory volume in 1 second (FEV1) and a reduction in the need for rescue medication.
The SMART protocol also demonstrated advantages over taking the same dose of inhaled corticosteroid called for by SMART plus a LABA controller therapy or a higher dose of inhaled corticosteroids with a LABA controller therapy. Specifically, SMART patients experienced a –6.4% risk of asthma exacerbations, versus the first comparator group; and a –2.7% risk of asthma, compared with the group who took a higher dose of inhaled corticosteroids with LABA controller therapy.
No significant associations appeared in any of the studies between the SMART protocol and outcomes that included all-cause mortality or changes in FEV1, forced vital capacity, or the percentage of predicted FEV1, when compared with those for patients who used a LABA controller therapy plus inhaled corticosteroids at either dose.
The SMART protocol review was limited by factors that included a lack of data on adverse events, a lack of subgroup analysis, and the potential for bias, because of the open label nature of some of the studies, the researchers noted.
However, despite the limitations in both reviews, the results support the SMART strategy and LAMAs as alternatives for patients with persistent asthma, and highlight the need for further research, they noted.
The reviews were supported by the Agency for Healthcare Research and Quality. Dr. Sobieraj had no financial conflicts to disclose.
SOURCE: Sobieraj D et al. JAMA. 2018;319(14):1473-84. Sobieraj D et al. JAMA. 2018;319(14):1485-96.
FROM JAMA
Key clinical point:
Major finding: LAMA patients had a risk difference of –1.8 for asthma exacerbations, compared with placebo users, while patients using the SMART protocol had an absolute risk difference of –2.8%, compared with those taking a higher dose of inhaled corticosteroids plus LABAs as a controller.
Study details: The data came from two reviews of randomized clinical trials; the first included 7,122 patients and the second included 22,524 patients.
Disclosures: The reviews were supported in part by the Agency for Healthcare Research and Quality. Dr. Sobieraj had no financial conflicts to disclose.
Source: Sobieraj D et al. JAMA. 2018;319(14):1473-84. Sobieraj D et al. JAMA. 2018;319(14):1485-96.