American Thoracic Society (ATS): International Conference 2015

DENVER – Obesity and weight gain of more than 5 kg during the first trimester in women with asthma are significant predictors of asthma exacerbation during pregnancy, according to findings from the Management of Asthma during Pregnancy (MAP) study.

Of 1,018 women in the prospective study, 370 experienced a total of 407 asthma exacerbations. The risk of exacerbation was greatest in those with body mass index over 30 kg/m² (odds ratio, 2.2) and in those with gestational weight gain of more than 5 kg in the first trimester (OR, 8.2), Zarqa Ali of Hvidovre Hospital, Copenhagen, and colleagues reported in a poster at an international conference of the American Thoracic Society.

©JGI/Thinkstock.com

Other risk factors for exacerbation included previous asthma exacerbations (OR, 1.3), uncontrolled asthma (OR, 2), inhaled corticosteroid treatment (OR, 5.8), and current and former smoking (OR, 1.9), the investigators said.

Risk factors for severe exacerbation of asthma, which occurred in 157 women, included gestational weight gain of greater than 5 kg (OR, 4.1), and age (OR, 1.1).

After excluding women with a prepregnancy body mass index above the mean of 24.1, risk factors for exacerbation included first-trimester weight gain greater than 5 kg (OR, 13.1) and lower prepregnancy body weight (OR, 0.9), they noted.

Women included in the study had a diagnosis of asthma, had been prescribed rescue bronchodilator therapy, had their first outpatient clinic visit within the first 18 weeks of pregnancy, and were seen for scheduled visits about every 4 weeks during pregnancy and for 3 months post partum. The women had a mean age of 31 years, 73% had never smoked, and their mean forced expiratory volume in 1 second (FEV₁) % predicted was 92, and mean exhaled nitric oxide was 20 ppb.

FEV₁% predicted was significantly greater at baseline in those without exacerbations vs. with exacerbations (93 vs. 90), and exhaled nitric oxide was significantly lower in the groups, respectively (18 vs. 23 ppb).

The findings are important, as acute exacerbations of asthma during pregnancy may be the most significant risk factor for unfavorable pregnancy outcomes in women with asthma, the investigators said, noting that exacerbations occur in about 30% of pregnant women with asthma and are associated with complications such as preterm delivery, low birth weight, excessive antepartum hemorrhage, and cesarean delivery.

Risk factors for exacerbation identified in prior studies include severe asthma, viral infections, nonadherence to controller medication, tobacco exposure, and possibly fetal gender and maternal body mass index, the investigators said.

The investigators reported having no disclosures.

[email protected]

DENVER – Obesity and weight gain of more than 5 kg during the first trimester in women with asthma are significant predictors of asthma exacerbation during pregnancy, according to findings from the Management of Asthma during Pregnancy (MAP) study.

Of 1,018 women in the prospective study, 370 experienced a total of 407 asthma exacerbations. The risk of exacerbation was greatest in those with body mass index over 30 kg/m² (odds ratio, 2.2) and in those with gestational weight gain of more than 5 kg in the first trimester (OR, 8.2), Zarqa Ali of Hvidovre Hospital, Copenhagen, and colleagues reported in a poster at an international conference of the American Thoracic Society.

©JGI/Thinkstock.com

Other risk factors for exacerbation included previous asthma exacerbations (OR, 1.3), uncontrolled asthma (OR, 2), inhaled corticosteroid treatment (OR, 5.8), and current and former smoking (OR, 1.9), the investigators said.

Risk factors for severe exacerbation of asthma, which occurred in 157 women, included gestational weight gain of greater than 5 kg (OR, 4.1), and age (OR, 1.1).

After excluding women with a prepregnancy body mass index above the mean of 24.1, risk factors for exacerbation included first-trimester weight gain greater than 5 kg (OR, 13.1) and lower prepregnancy body weight (OR, 0.9), they noted.

Women included in the study had a diagnosis of asthma, had been prescribed rescue bronchodilator therapy, had their first outpatient clinic visit within the first 18 weeks of pregnancy, and were seen for scheduled visits about every 4 weeks during pregnancy and for 3 months post partum. The women had a mean age of 31 years, 73% had never smoked, and their mean forced expiratory volume in 1 second (FEV₁) % predicted was 92, and mean exhaled nitric oxide was 20 ppb.

FEV₁% predicted was significantly greater at baseline in those without exacerbations vs. with exacerbations (93 vs. 90), and exhaled nitric oxide was significantly lower in the groups, respectively (18 vs. 23 ppb).

The findings are important, as acute exacerbations of asthma during pregnancy may be the most significant risk factor for unfavorable pregnancy outcomes in women with asthma, the investigators said, noting that exacerbations occur in about 30% of pregnant women with asthma and are associated with complications such as preterm delivery, low birth weight, excessive antepartum hemorrhage, and cesarean delivery.

Risk factors for exacerbation identified in prior studies include severe asthma, viral infections, nonadherence to controller medication, tobacco exposure, and possibly fetal gender and maternal body mass index, the investigators said.

The investigators reported having no disclosures.

[email protected]

DENVER – Obesity and weight gain of more than 5 kg during the first trimester in women with asthma are significant predictors of asthma exacerbation during pregnancy, according to findings from the Management of Asthma during Pregnancy (MAP) study.

Of 1,018 women in the prospective study, 370 experienced a total of 407 asthma exacerbations. The risk of exacerbation was greatest in those with body mass index over 30 kg/m² (odds ratio, 2.2) and in those with gestational weight gain of more than 5 kg in the first trimester (OR, 8.2), Zarqa Ali of Hvidovre Hospital, Copenhagen, and colleagues reported in a poster at an international conference of the American Thoracic Society.

©JGI/Thinkstock.com

Other risk factors for exacerbation included previous asthma exacerbations (OR, 1.3), uncontrolled asthma (OR, 2), inhaled corticosteroid treatment (OR, 5.8), and current and former smoking (OR, 1.9), the investigators said.

Risk factors for severe exacerbation of asthma, which occurred in 157 women, included gestational weight gain of greater than 5 kg (OR, 4.1), and age (OR, 1.1).

After excluding women with a prepregnancy body mass index above the mean of 24.1, risk factors for exacerbation included first-trimester weight gain greater than 5 kg (OR, 13.1) and lower prepregnancy body weight (OR, 0.9), they noted.

Women included in the study had a diagnosis of asthma, had been prescribed rescue bronchodilator therapy, had their first outpatient clinic visit within the first 18 weeks of pregnancy, and were seen for scheduled visits about every 4 weeks during pregnancy and for 3 months post partum. The women had a mean age of 31 years, 73% had never smoked, and their mean forced expiratory volume in 1 second (FEV₁) % predicted was 92, and mean exhaled nitric oxide was 20 ppb.

FEV₁% predicted was significantly greater at baseline in those without exacerbations vs. with exacerbations (93 vs. 90), and exhaled nitric oxide was significantly lower in the groups, respectively (18 vs. 23 ppb).

The findings are important, as acute exacerbations of asthma during pregnancy may be the most significant risk factor for unfavorable pregnancy outcomes in women with asthma, the investigators said, noting that exacerbations occur in about 30% of pregnant women with asthma and are associated with complications such as preterm delivery, low birth weight, excessive antepartum hemorrhage, and cesarean delivery.

Risk factors for exacerbation identified in prior studies include severe asthma, viral infections, nonadherence to controller medication, tobacco exposure, and possibly fetal gender and maternal body mass index, the investigators said.

The investigators reported having no disclosures.

[email protected]

DENVER – Men with previously undiagnosed severe obstructive sleep apnea and excessive daytime sleepiness have a more than four-fold increase in the risk of depression, compared with those without either condition, according to findings from a population-based cohort study.

Those with both severe obstructive sleep apnea (OSA) and excessive daytime sleepiness (EDS) also have a 3.5 times greater risk of depression than do those with either OSA or EDS alone, Carol Lang, Ph.D., reported during a press briefing at an international conference of the American Thoracic Society.

The findings have important implications for clinicians treating patients with depression; clinicians should recognize the risk of OSA in men with depression, and should screen those presenting with OSA – regardless of whether sleepiness is present, said Dr. Lang of the University of Adelaide, Australia.

Study subjects were 1,875 community dwelling Australian men aged 35-83 years who were assessed for depression using the Beck Depression Inventory/Centre for Epidemiological Studies Depression Scale (CES-D) at two times points about 5 years apart. A random sample of 857 men without previously diagnosed OSA underwent at-home polysomnography and completed the Epworth Sleepiness Scale questionnaire, and 1,660 men without depression at baseline were included in the analysis of incident depression.

Previously undiagnosed mild-to-moderate and severe OSA were associated with depression prevalence (adjusted odds ratio 2.1), and this was true even after adjusting for confounders and EDS.

EDS also was associated with depression (adjusted OR, 1.1). she said.

Patients with previously undiagnosed OSA and EDS had greater odds of depression than did those without OSA and EDS (OR, 4.2), and had greater odds of depression than did those with either condition alone (OR, 3.5).

Further, previously diagnosed OSA and previously undiagnosed severe OSA at follow-up were significantly associated with depression onset over a 5-year period (OR, 2.1 and 2.9, respectively), Dr. Lang said.

The findings support those of prior studies that have demonstrated a link between sleep apnea and depression.

As many as 22% of those with OSA also have clinically significant depressive symptoms, compared with 5% of the general population. Daytime sleepiness can occur in those with OSA, but not everyone with OSA reports daytime sleepiness, she said, noting that few prior studies have looked at the relationship between OSA and depression in a community-based population.

“Our study, in a large community-based sample of men, confirms a strong relationship even after adjustment for a number of other potential risk factors,” she said.

The mechanisms underlying the association remain unclear, but it may be that many of the symptoms of and risk factors for OSA and depression overlap.

“Sleep apnea is also associated with lower oxygen levels in the body, and this causes a range of physiological consequences, including altered inflammatory responses, hormonal stimulation, as well as neurological changes in the brain that just happen to be in the same region of the brain that might actually impact depression, feelings of guilt, worthlessness, and suicidal tendencies,” she said.

The message to clinicians based on these findings is that patients who present with symptoms of either OSA or depression should be screened for both.

“Often, I think, when people present with depression, it’s easy to just assume the sleep problems are related to the depression itself ... but there may actually be benefit for the patient if both are investigated and treated,” she concluded.

Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, who moderated the press conference, added that additional data exist to suggest that sleep apnea leads to “more severe, and actually refractory depression,” and further stressed that lack of awareness of the association can be harmful for patients.

“These people just get more antidepressants, including benzodiazepines, which are really detrimental for the obstructive sleep apnea pathogenesis, worsening depression. So it’s very important for the community to be aware about sleep apnea as a potential aggravator and contributor to depression,” she said.

Dr. Lang reported having no relevant financial disclosures.

[email protected]

DENVER – Men with previously undiagnosed severe obstructive sleep apnea and excessive daytime sleepiness have a more than four-fold increase in the risk of depression, compared with those without either condition, according to findings from a population-based cohort study.

Those with both severe obstructive sleep apnea (OSA) and excessive daytime sleepiness (EDS) also have a 3.5 times greater risk of depression than do those with either OSA or EDS alone, Carol Lang, Ph.D., reported during a press briefing at an international conference of the American Thoracic Society.

The findings have important implications for clinicians treating patients with depression; clinicians should recognize the risk of OSA in men with depression, and should screen those presenting with OSA – regardless of whether sleepiness is present, said Dr. Lang of the University of Adelaide, Australia.

Study subjects were 1,875 community dwelling Australian men aged 35-83 years who were assessed for depression using the Beck Depression Inventory/Centre for Epidemiological Studies Depression Scale (CES-D) at two times points about 5 years apart. A random sample of 857 men without previously diagnosed OSA underwent at-home polysomnography and completed the Epworth Sleepiness Scale questionnaire, and 1,660 men without depression at baseline were included in the analysis of incident depression.

Previously undiagnosed mild-to-moderate and severe OSA were associated with depression prevalence (adjusted odds ratio 2.1), and this was true even after adjusting for confounders and EDS.

EDS also was associated with depression (adjusted OR, 1.1). she said.

Patients with previously undiagnosed OSA and EDS had greater odds of depression than did those without OSA and EDS (OR, 4.2), and had greater odds of depression than did those with either condition alone (OR, 3.5).

Further, previously diagnosed OSA and previously undiagnosed severe OSA at follow-up were significantly associated with depression onset over a 5-year period (OR, 2.1 and 2.9, respectively), Dr. Lang said.

The findings support those of prior studies that have demonstrated a link between sleep apnea and depression.

As many as 22% of those with OSA also have clinically significant depressive symptoms, compared with 5% of the general population. Daytime sleepiness can occur in those with OSA, but not everyone with OSA reports daytime sleepiness, she said, noting that few prior studies have looked at the relationship between OSA and depression in a community-based population.

“Our study, in a large community-based sample of men, confirms a strong relationship even after adjustment for a number of other potential risk factors,” she said.

The mechanisms underlying the association remain unclear, but it may be that many of the symptoms of and risk factors for OSA and depression overlap.

“Sleep apnea is also associated with lower oxygen levels in the body, and this causes a range of physiological consequences, including altered inflammatory responses, hormonal stimulation, as well as neurological changes in the brain that just happen to be in the same region of the brain that might actually impact depression, feelings of guilt, worthlessness, and suicidal tendencies,” she said.

The message to clinicians based on these findings is that patients who present with symptoms of either OSA or depression should be screened for both.

“Often, I think, when people present with depression, it’s easy to just assume the sleep problems are related to the depression itself ... but there may actually be benefit for the patient if both are investigated and treated,” she concluded.

Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, who moderated the press conference, added that additional data exist to suggest that sleep apnea leads to “more severe, and actually refractory depression,” and further stressed that lack of awareness of the association can be harmful for patients.

“These people just get more antidepressants, including benzodiazepines, which are really detrimental for the obstructive sleep apnea pathogenesis, worsening depression. So it’s very important for the community to be aware about sleep apnea as a potential aggravator and contributor to depression,” she said.

Dr. Lang reported having no relevant financial disclosures.

[email protected]

DENVER – Men with previously undiagnosed severe obstructive sleep apnea and excessive daytime sleepiness have a more than four-fold increase in the risk of depression, compared with those without either condition, according to findings from a population-based cohort study.

Those with both severe obstructive sleep apnea (OSA) and excessive daytime sleepiness (EDS) also have a 3.5 times greater risk of depression than do those with either OSA or EDS alone, Carol Lang, Ph.D., reported during a press briefing at an international conference of the American Thoracic Society.

The findings have important implications for clinicians treating patients with depression; clinicians should recognize the risk of OSA in men with depression, and should screen those presenting with OSA – regardless of whether sleepiness is present, said Dr. Lang of the University of Adelaide, Australia.

Study subjects were 1,875 community dwelling Australian men aged 35-83 years who were assessed for depression using the Beck Depression Inventory/Centre for Epidemiological Studies Depression Scale (CES-D) at two times points about 5 years apart. A random sample of 857 men without previously diagnosed OSA underwent at-home polysomnography and completed the Epworth Sleepiness Scale questionnaire, and 1,660 men without depression at baseline were included in the analysis of incident depression.

Previously undiagnosed mild-to-moderate and severe OSA were associated with depression prevalence (adjusted odds ratio 2.1), and this was true even after adjusting for confounders and EDS.

EDS also was associated with depression (adjusted OR, 1.1). she said.

Patients with previously undiagnosed OSA and EDS had greater odds of depression than did those without OSA and EDS (OR, 4.2), and had greater odds of depression than did those with either condition alone (OR, 3.5).

Further, previously diagnosed OSA and previously undiagnosed severe OSA at follow-up were significantly associated with depression onset over a 5-year period (OR, 2.1 and 2.9, respectively), Dr. Lang said.

The findings support those of prior studies that have demonstrated a link between sleep apnea and depression.

As many as 22% of those with OSA also have clinically significant depressive symptoms, compared with 5% of the general population. Daytime sleepiness can occur in those with OSA, but not everyone with OSA reports daytime sleepiness, she said, noting that few prior studies have looked at the relationship between OSA and depression in a community-based population.

“Our study, in a large community-based sample of men, confirms a strong relationship even after adjustment for a number of other potential risk factors,” she said.

The mechanisms underlying the association remain unclear, but it may be that many of the symptoms of and risk factors for OSA and depression overlap.

“Sleep apnea is also associated with lower oxygen levels in the body, and this causes a range of physiological consequences, including altered inflammatory responses, hormonal stimulation, as well as neurological changes in the brain that just happen to be in the same region of the brain that might actually impact depression, feelings of guilt, worthlessness, and suicidal tendencies,” she said.

The message to clinicians based on these findings is that patients who present with symptoms of either OSA or depression should be screened for both.

“Often, I think, when people present with depression, it’s easy to just assume the sleep problems are related to the depression itself ... but there may actually be benefit for the patient if both are investigated and treated,” she concluded.

Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, who moderated the press conference, added that additional data exist to suggest that sleep apnea leads to “more severe, and actually refractory depression,” and further stressed that lack of awareness of the association can be harmful for patients.

“These people just get more antidepressants, including benzodiazepines, which are really detrimental for the obstructive sleep apnea pathogenesis, worsening depression. So it’s very important for the community to be aware about sleep apnea as a potential aggravator and contributor to depression,” she said.

Dr. Lang reported having no relevant financial disclosures.

[email protected]

DENVER – In patients with stable COPD, a fixed-dose combination of aclidinium/formoterol provided significantly greater improvements in bronchodilation compared with a fixed-dose combination of salmeterol/fluticasone, with equivalent benefits in symptom control and reduction in exacerbation risk, a randomized, controlled trial showed.

“This study will be important to building further evidence for the clinical use of inhaled long-acting muscarinic antagonist (LAMA) and long-acting beta agonist (LABA) fixed-dose combinations as a valuable tool in the treatment armamentarium for COPD,” Dr. Claus Vogelmeier said in an interview in advance of an international conference of the American Thoracic Society, where the work was presented during a poster session.

“While there have been other positive studies showing benefits in LAMA/LABA fixed-dose combinations over the specific ICS/LABA fixed-dose combination of salmeterol/fluticasone, this is the first head-to-head study that compares the efficacy and safety of aclidinium/formoterol with salmeterol/fluticasone in COPD patients,” he said.

For the phase III study, Dr. Vogelmeier, professor of medicine and head of the pulmonary division at Marburg University Hospital, Germany, and his associates randomized 933 symptomatic COPD patients 1:1 to 24 weeks of treatment with aclidinium/formoterol 400/12 mcg twice daily via Genuair/Pressair (AstraZeneca) or salmeterol/fluticasone 50/500 mcg twice daily via Accuhaler (GlaxoSmithKline).

The primary efficacy endpoint was peak forced expiratory volume in 1 second (FEV₁) at week 24. Other efficacy endpoints included peak FEV₁ at each visit, Transition Dyspnea Index (TDI) focal score and COPD Assessment Test (CAT) score at week 24, and the proportion of patients who experienced at least one exacerbation defined by health care resource utilization (HCRU) or identified using the Exacerbations of Chronic Pulmonary Disease Tool (EXACT). Adverse events and serious adverse events were monitored throughout the study.

Of the 933 patients, 788 (85%) completed the study. Their mean age was 63 years and 65% were male. Dr. Vogelmeier reported that peak FEV₁ was significantly greater with aclidinium/formoterol versus salmeterol/fluticasone after the first dose on day 1, an improvement that was maintained at week 24 (treatment differences of 83 mL and 93 mL, respectively; both P less than .0001).

Improvements in TDI focal score at week 24 were similar in both groups (a mean of 1.88 for both), and there were no significant differences between groups in CAT total score at week 24 (15.81 vs. 16.11). The proportion of patients who experienced one exacerbation or more was comparable between groups when assessed via HCRU (odds ratio .95) or EXACT (OR .94).

The incidence of adverse events was similar among the aclidinium/formoterol and the salmeterol/fluticasone groups (50% vs. 57%, respectively), as were serious adverse events, (7.5% vs. 7.1%), and adverse events leading to study discontinuation (5.4% vs. 7.3%). Adverse events related to inhaled corticosteroid use, including pneumonia and osteoporosis/osteopenia, were more common in patients receiving salmeterol/fluticasone than in patients receiving aclidinium/formoterol (10.7% vs. 4.3%).

“For clinicians like me, it is helpful to have choices available to address our patients’ needs,” Dr. Vogelmeier said. “Knowing that aclidinium/formoterol has shown greater bronchodilation compared to salmeterol/fluticasone will give us confidence in prescribing. These data offer physicians a new perspective and option for treating symptomatic patients at a time when the role of LAMA/LABA fixed-dose combinations is being increasingly recognized in the management of symptomatic COPD.”

He acknowledged certain limitations of the study, including the fact that it was limited to COPD patients who may have experienced up to one exacerbation in the year before the study. The study did not include frequent exacerbators.

The study was funded by Almirall, Barcelona, Spain, and Forest Laboratories, a subsidiary of Actavis. Dr. Vogelmeier disclosed ties with Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Grifols, Janssen, Mundipharma, Novartis, and Takeda.

[email protected]

On Twitter @dougbrunk

DENVER – In patients with stable COPD, a fixed-dose combination of aclidinium/formoterol provided significantly greater improvements in bronchodilation compared with a fixed-dose combination of salmeterol/fluticasone, with equivalent benefits in symptom control and reduction in exacerbation risk, a randomized, controlled trial showed.

“This study will be important to building further evidence for the clinical use of inhaled long-acting muscarinic antagonist (LAMA) and long-acting beta agonist (LABA) fixed-dose combinations as a valuable tool in the treatment armamentarium for COPD,” Dr. Claus Vogelmeier said in an interview in advance of an international conference of the American Thoracic Society, where the work was presented during a poster session.

“While there have been other positive studies showing benefits in LAMA/LABA fixed-dose combinations over the specific ICS/LABA fixed-dose combination of salmeterol/fluticasone, this is the first head-to-head study that compares the efficacy and safety of aclidinium/formoterol with salmeterol/fluticasone in COPD patients,” he said.

For the phase III study, Dr. Vogelmeier, professor of medicine and head of the pulmonary division at Marburg University Hospital, Germany, and his associates randomized 933 symptomatic COPD patients 1:1 to 24 weeks of treatment with aclidinium/formoterol 400/12 mcg twice daily via Genuair/Pressair (AstraZeneca) or salmeterol/fluticasone 50/500 mcg twice daily via Accuhaler (GlaxoSmithKline).

The primary efficacy endpoint was peak forced expiratory volume in 1 second (FEV₁) at week 24. Other efficacy endpoints included peak FEV₁ at each visit, Transition Dyspnea Index (TDI) focal score and COPD Assessment Test (CAT) score at week 24, and the proportion of patients who experienced at least one exacerbation defined by health care resource utilization (HCRU) or identified using the Exacerbations of Chronic Pulmonary Disease Tool (EXACT). Adverse events and serious adverse events were monitored throughout the study.

Of the 933 patients, 788 (85%) completed the study. Their mean age was 63 years and 65% were male. Dr. Vogelmeier reported that peak FEV₁ was significantly greater with aclidinium/formoterol versus salmeterol/fluticasone after the first dose on day 1, an improvement that was maintained at week 24 (treatment differences of 83 mL and 93 mL, respectively; both P less than .0001).

Improvements in TDI focal score at week 24 were similar in both groups (a mean of 1.88 for both), and there were no significant differences between groups in CAT total score at week 24 (15.81 vs. 16.11). The proportion of patients who experienced one exacerbation or more was comparable between groups when assessed via HCRU (odds ratio .95) or EXACT (OR .94).

The incidence of adverse events was similar among the aclidinium/formoterol and the salmeterol/fluticasone groups (50% vs. 57%, respectively), as were serious adverse events, (7.5% vs. 7.1%), and adverse events leading to study discontinuation (5.4% vs. 7.3%). Adverse events related to inhaled corticosteroid use, including pneumonia and osteoporosis/osteopenia, were more common in patients receiving salmeterol/fluticasone than in patients receiving aclidinium/formoterol (10.7% vs. 4.3%).

“For clinicians like me, it is helpful to have choices available to address our patients’ needs,” Dr. Vogelmeier said. “Knowing that aclidinium/formoterol has shown greater bronchodilation compared to salmeterol/fluticasone will give us confidence in prescribing. These data offer physicians a new perspective and option for treating symptomatic patients at a time when the role of LAMA/LABA fixed-dose combinations is being increasingly recognized in the management of symptomatic COPD.”

He acknowledged certain limitations of the study, including the fact that it was limited to COPD patients who may have experienced up to one exacerbation in the year before the study. The study did not include frequent exacerbators.

The study was funded by Almirall, Barcelona, Spain, and Forest Laboratories, a subsidiary of Actavis. Dr. Vogelmeier disclosed ties with Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Grifols, Janssen, Mundipharma, Novartis, and Takeda.

[email protected]

On Twitter @dougbrunk

DENVER – In patients with stable COPD, a fixed-dose combination of aclidinium/formoterol provided significantly greater improvements in bronchodilation compared with a fixed-dose combination of salmeterol/fluticasone, with equivalent benefits in symptom control and reduction in exacerbation risk, a randomized, controlled trial showed.

“This study will be important to building further evidence for the clinical use of inhaled long-acting muscarinic antagonist (LAMA) and long-acting beta agonist (LABA) fixed-dose combinations as a valuable tool in the treatment armamentarium for COPD,” Dr. Claus Vogelmeier said in an interview in advance of an international conference of the American Thoracic Society, where the work was presented during a poster session.

“While there have been other positive studies showing benefits in LAMA/LABA fixed-dose combinations over the specific ICS/LABA fixed-dose combination of salmeterol/fluticasone, this is the first head-to-head study that compares the efficacy and safety of aclidinium/formoterol with salmeterol/fluticasone in COPD patients,” he said.

For the phase III study, Dr. Vogelmeier, professor of medicine and head of the pulmonary division at Marburg University Hospital, Germany, and his associates randomized 933 symptomatic COPD patients 1:1 to 24 weeks of treatment with aclidinium/formoterol 400/12 mcg twice daily via Genuair/Pressair (AstraZeneca) or salmeterol/fluticasone 50/500 mcg twice daily via Accuhaler (GlaxoSmithKline).

The primary efficacy endpoint was peak forced expiratory volume in 1 second (FEV₁) at week 24. Other efficacy endpoints included peak FEV₁ at each visit, Transition Dyspnea Index (TDI) focal score and COPD Assessment Test (CAT) score at week 24, and the proportion of patients who experienced at least one exacerbation defined by health care resource utilization (HCRU) or identified using the Exacerbations of Chronic Pulmonary Disease Tool (EXACT). Adverse events and serious adverse events were monitored throughout the study.

Of the 933 patients, 788 (85%) completed the study. Their mean age was 63 years and 65% were male. Dr. Vogelmeier reported that peak FEV₁ was significantly greater with aclidinium/formoterol versus salmeterol/fluticasone after the first dose on day 1, an improvement that was maintained at week 24 (treatment differences of 83 mL and 93 mL, respectively; both P less than .0001).

Improvements in TDI focal score at week 24 were similar in both groups (a mean of 1.88 for both), and there were no significant differences between groups in CAT total score at week 24 (15.81 vs. 16.11). The proportion of patients who experienced one exacerbation or more was comparable between groups when assessed via HCRU (odds ratio .95) or EXACT (OR .94).

The incidence of adverse events was similar among the aclidinium/formoterol and the salmeterol/fluticasone groups (50% vs. 57%, respectively), as were serious adverse events, (7.5% vs. 7.1%), and adverse events leading to study discontinuation (5.4% vs. 7.3%). Adverse events related to inhaled corticosteroid use, including pneumonia and osteoporosis/osteopenia, were more common in patients receiving salmeterol/fluticasone than in patients receiving aclidinium/formoterol (10.7% vs. 4.3%).

“For clinicians like me, it is helpful to have choices available to address our patients’ needs,” Dr. Vogelmeier said. “Knowing that aclidinium/formoterol has shown greater bronchodilation compared to salmeterol/fluticasone will give us confidence in prescribing. These data offer physicians a new perspective and option for treating symptomatic patients at a time when the role of LAMA/LABA fixed-dose combinations is being increasingly recognized in the management of symptomatic COPD.”

He acknowledged certain limitations of the study, including the fact that it was limited to COPD patients who may have experienced up to one exacerbation in the year before the study. The study did not include frequent exacerbators.

The study was funded by Almirall, Barcelona, Spain, and Forest Laboratories, a subsidiary of Actavis. Dr. Vogelmeier disclosed ties with Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Grifols, Janssen, Mundipharma, Novartis, and Takeda.

[email protected]

On Twitter @dougbrunk

DENVER – The higher the power of an e-cigarette, the higher the concentrations of potentially hazardous substances the device produces, including acetaldehyde, acrolein, and formaldehyde.

Those are among the findings presented at an international conference of the American Thoracic Society by lead study author Dr. Daniel Sullivan, an internal medicine resident at the University of Texas Southwestern Medical Center. During his previous training at the University of Alabama, Birmingham, Dr. Sullivan and his associates used a variety of methods including liquid chromatography–mass spectrometry and enzyme-linked immunosorbent assay (ELISA) to study components and nicotine formulations typical of e-cigarette users. Under some test conditions, formaldehyde levels were comparable to those seen in traditional tobacco cigarettes, he said in a video interview.

Dr. Sullivan reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

DENVER – The higher the power of an e-cigarette, the higher the concentrations of potentially hazardous substances the device produces, including acetaldehyde, acrolein, and formaldehyde.

Those are among the findings presented at an international conference of the American Thoracic Society by lead study author Dr. Daniel Sullivan, an internal medicine resident at the University of Texas Southwestern Medical Center. During his previous training at the University of Alabama, Birmingham, Dr. Sullivan and his associates used a variety of methods including liquid chromatography–mass spectrometry and enzyme-linked immunosorbent assay (ELISA) to study components and nicotine formulations typical of e-cigarette users. Under some test conditions, formaldehyde levels were comparable to those seen in traditional tobacco cigarettes, he said in a video interview.

Dr. Sullivan reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

DENVER – The higher the power of an e-cigarette, the higher the concentrations of potentially hazardous substances the device produces, including acetaldehyde, acrolein, and formaldehyde.

Those are among the findings presented at an international conference of the American Thoracic Society by lead study author Dr. Daniel Sullivan, an internal medicine resident at the University of Texas Southwestern Medical Center. During his previous training at the University of Alabama, Birmingham, Dr. Sullivan and his associates used a variety of methods including liquid chromatography–mass spectrometry and enzyme-linked immunosorbent assay (ELISA) to study components and nicotine formulations typical of e-cigarette users. Under some test conditions, formaldehyde levels were comparable to those seen in traditional tobacco cigarettes, he said in a video interview.

Dr. Sullivan reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

DENVER – Although electronic cigarettes are widely promoted as a smoking cessation tool, no sound data exist to support their use beyond 1 month as a way to kick the smoking habit, results from the largest meta-analysis of its kind suggest.

In an interview at an international conference of the America Thoracic Society, study author Dr. Matthew B. Stanbrook highlighted results from the review, which included 297 articles published to May 2014.

The meta-analysis showed that point prevalence abstinence was significantly better for e-cigarettes, compared with placebo, at 1 month (relative risk, 1.71). That effect, however, was no longer observed at 3- or 6-month follow-ups.

The most common adverse events noted in the studies were dry cough, throat irritation, and shortness of breath.

Dr. Stanbrook reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

DENVER – Although electronic cigarettes are widely promoted as a smoking cessation tool, no sound data exist to support their use beyond 1 month as a way to kick the smoking habit, results from the largest meta-analysis of its kind suggest.

In an interview at an international conference of the America Thoracic Society, study author Dr. Matthew B. Stanbrook highlighted results from the review, which included 297 articles published to May 2014.

The meta-analysis showed that point prevalence abstinence was significantly better for e-cigarettes, compared with placebo, at 1 month (relative risk, 1.71). That effect, however, was no longer observed at 3- or 6-month follow-ups.

The most common adverse events noted in the studies were dry cough, throat irritation, and shortness of breath.

Dr. Stanbrook reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

DENVER – Although electronic cigarettes are widely promoted as a smoking cessation tool, no sound data exist to support their use beyond 1 month as a way to kick the smoking habit, results from the largest meta-analysis of its kind suggest.

In an interview at an international conference of the America Thoracic Society, study author Dr. Matthew B. Stanbrook highlighted results from the review, which included 297 articles published to May 2014.

The meta-analysis showed that point prevalence abstinence was significantly better for e-cigarettes, compared with placebo, at 1 month (relative risk, 1.71). That effect, however, was no longer observed at 3- or 6-month follow-ups.

The most common adverse events noted in the studies were dry cough, throat irritation, and shortness of breath.

Dr. Stanbrook reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

DENVER – Intermittent high-dose nitric oxide (NO) inhalation therapy appears safe and shows clear signals of efficacy in infants hospitalized with bronchiolitis, a randomized controlled trial showed.

“Further larger scale clinical trials are needed to establish its role in lower respiratory tract infections such as viral bronchiolitis, pneumonia, cystic fibrosis, viral-related asthma, COPD [chronic obstructive pulmonary disease], and more,” one of the study authors, Yossef Av-Gay, Ph.D., said in an interview in advance of an international conference of the American Thoracic Society.

In what they said is the first human study of its kind, researchers led by Dr. Asher Tal, head of the pediatric pulmonary unit at Soroka University Medical Center, Beer Sheva, Israel, set out to determine the safety and tolerability of intermittent high-dose inhaled NO for the treatment of hospitalized infants aged 2-12 months with bronchiolitis. Patients received either 160 parts per million (ppm) of NO five times per day for 30 minutes each time or oxygen only.

At lower concentrations, nitric oxide is a pulmonary vasodilator. It has been studied in the 1-60 ppm range and received Food and Drug Administration approval in 1999.* "Nitric oxide gas is used to treat neonates at lower dose, and in this study we investigated its antimicrobial dosage, which is higher than current treatment,” said Dr. Av-Gay, professor of the division of infectious diseases at the University of British Columbia, Vancouver.

“Previous in-vitro and in animal studies support the antimicrobial effect of intermittent inhalations of 160 ppm of NO to treat lower respiratory tract infections, both viral and bacterial. Bronchiolitis is a viral-related [infection] that causes significant morbidity and even mortality in infants around the world. Presently the treatment protocol for hospitalized infants is supportive care only, because despite many years of research as there is not yet an available treatment or specific anti-viral drug. Inhaled NO is thus an exciting potential novel drug for the treatment of acute bronchiolitis,” he said.

Of 43 infants initially enrolled, 25 were hospitalized for more than 24 hours and were considered evaluable for efficacy. Of these, 14 received intermittent high-dose inhaled NO and 11 received oxygen only. The researchers observed no significant differences between the NO and oxygen groups in the number of adverse events or in the number of serious adverse events. Patients who received NO, however, spent significantly fewer hours in the hospital, compared with the oxygen group (mean of 46 hours vs. 74 hours, respectively; P = .032) and reached 92% oxygen saturation in significantly faster time (mean of 26 hours vs. 61 hours; P = .032).

Dr. Av-Gay acknowledged certain limitations of the analysis, including the fact that the study’s primary outcome was safety and tolerability. “Therefore, the study was not powered to show efficacy,” he said.

The study was funded by Advanced Inhalation Therapies, an Israeli-based company that holds the rights to the NO technology. Dr. Av-Gay is the company’s chief scientific officer, and Dr. Tal is employed by the company.

[email protected]

On Twitter @dougbrunk

*This article was added to on 6/25/15.

DENVER – Intermittent high-dose nitric oxide (NO) inhalation therapy appears safe and shows clear signals of efficacy in infants hospitalized with bronchiolitis, a randomized controlled trial showed.

“Further larger scale clinical trials are needed to establish its role in lower respiratory tract infections such as viral bronchiolitis, pneumonia, cystic fibrosis, viral-related asthma, COPD [chronic obstructive pulmonary disease], and more,” one of the study authors, Yossef Av-Gay, Ph.D., said in an interview in advance of an international conference of the American Thoracic Society.

In what they said is the first human study of its kind, researchers led by Dr. Asher Tal, head of the pediatric pulmonary unit at Soroka University Medical Center, Beer Sheva, Israel, set out to determine the safety and tolerability of intermittent high-dose inhaled NO for the treatment of hospitalized infants aged 2-12 months with bronchiolitis. Patients received either 160 parts per million (ppm) of NO five times per day for 30 minutes each time or oxygen only.

At lower concentrations, nitric oxide is a pulmonary vasodilator. It has been studied in the 1-60 ppm range and received Food and Drug Administration approval in 1999.* "Nitric oxide gas is used to treat neonates at lower dose, and in this study we investigated its antimicrobial dosage, which is higher than current treatment,” said Dr. Av-Gay, professor of the division of infectious diseases at the University of British Columbia, Vancouver.

“Previous in-vitro and in animal studies support the antimicrobial effect of intermittent inhalations of 160 ppm of NO to treat lower respiratory tract infections, both viral and bacterial. Bronchiolitis is a viral-related [infection] that causes significant morbidity and even mortality in infants around the world. Presently the treatment protocol for hospitalized infants is supportive care only, because despite many years of research as there is not yet an available treatment or specific anti-viral drug. Inhaled NO is thus an exciting potential novel drug for the treatment of acute bronchiolitis,” he said.

Of 43 infants initially enrolled, 25 were hospitalized for more than 24 hours and were considered evaluable for efficacy. Of these, 14 received intermittent high-dose inhaled NO and 11 received oxygen only. The researchers observed no significant differences between the NO and oxygen groups in the number of adverse events or in the number of serious adverse events. Patients who received NO, however, spent significantly fewer hours in the hospital, compared with the oxygen group (mean of 46 hours vs. 74 hours, respectively; P = .032) and reached 92% oxygen saturation in significantly faster time (mean of 26 hours vs. 61 hours; P = .032).

Dr. Av-Gay acknowledged certain limitations of the analysis, including the fact that the study’s primary outcome was safety and tolerability. “Therefore, the study was not powered to show efficacy,” he said.

The study was funded by Advanced Inhalation Therapies, an Israeli-based company that holds the rights to the NO technology. Dr. Av-Gay is the company’s chief scientific officer, and Dr. Tal is employed by the company.

[email protected]

On Twitter @dougbrunk

*This article was added to on 6/25/15.

DENVER – Intermittent high-dose nitric oxide (NO) inhalation therapy appears safe and shows clear signals of efficacy in infants hospitalized with bronchiolitis, a randomized controlled trial showed.

“Further larger scale clinical trials are needed to establish its role in lower respiratory tract infections such as viral bronchiolitis, pneumonia, cystic fibrosis, viral-related asthma, COPD [chronic obstructive pulmonary disease], and more,” one of the study authors, Yossef Av-Gay, Ph.D., said in an interview in advance of an international conference of the American Thoracic Society.

In what they said is the first human study of its kind, researchers led by Dr. Asher Tal, head of the pediatric pulmonary unit at Soroka University Medical Center, Beer Sheva, Israel, set out to determine the safety and tolerability of intermittent high-dose inhaled NO for the treatment of hospitalized infants aged 2-12 months with bronchiolitis. Patients received either 160 parts per million (ppm) of NO five times per day for 30 minutes each time or oxygen only.

At lower concentrations, nitric oxide is a pulmonary vasodilator. It has been studied in the 1-60 ppm range and received Food and Drug Administration approval in 1999.* "Nitric oxide gas is used to treat neonates at lower dose, and in this study we investigated its antimicrobial dosage, which is higher than current treatment,” said Dr. Av-Gay, professor of the division of infectious diseases at the University of British Columbia, Vancouver.

“Previous in-vitro and in animal studies support the antimicrobial effect of intermittent inhalations of 160 ppm of NO to treat lower respiratory tract infections, both viral and bacterial. Bronchiolitis is a viral-related [infection] that causes significant morbidity and even mortality in infants around the world. Presently the treatment protocol for hospitalized infants is supportive care only, because despite many years of research as there is not yet an available treatment or specific anti-viral drug. Inhaled NO is thus an exciting potential novel drug for the treatment of acute bronchiolitis,” he said.

Of 43 infants initially enrolled, 25 were hospitalized for more than 24 hours and were considered evaluable for efficacy. Of these, 14 received intermittent high-dose inhaled NO and 11 received oxygen only. The researchers observed no significant differences between the NO and oxygen groups in the number of adverse events or in the number of serious adverse events. Patients who received NO, however, spent significantly fewer hours in the hospital, compared with the oxygen group (mean of 46 hours vs. 74 hours, respectively; P = .032) and reached 92% oxygen saturation in significantly faster time (mean of 26 hours vs. 61 hours; P = .032).

Dr. Av-Gay acknowledged certain limitations of the analysis, including the fact that the study’s primary outcome was safety and tolerability. “Therefore, the study was not powered to show efficacy,” he said.

The study was funded by Advanced Inhalation Therapies, an Israeli-based company that holds the rights to the NO technology. Dr. Av-Gay is the company’s chief scientific officer, and Dr. Tal is employed by the company.

[email protected]

On Twitter @dougbrunk

*This article was added to on 6/25/15.

DENVER – The use of nintedanib 150 mg twice daily has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis up to 76 weeks of treatment, with an acceptable safety and tolerability profile, according to results from a novel study.

Marketed by Boehringer Ingelheim, nintedanib (Ofev)was approved by the FDA in October of 2014 for the treatment of idiopathic pulmonary fibrosis. Data from period 1 of the dose-finding, phase II TOMORROW trial (N. Engl. J. Med. 2011;365:1079–87) and the two replicate Phase III INPULSIS trials (N. Engl. J. Med. 2014;370:2071-82) demonstrated the efficacy and safety of nintedanib 150 mg twice daily over 52 weeks in patients with IPF. After completing period 1 of the TOMORROW trial, study participants had the option to continue treatment in a further blinded treatment phase (period 2).

“Clinicians are always interested in the long-term efficacy and safety of a new drug in patients suffering from a chronic, progressive disease like IPF,” lead study author Dr. Luca Richeldi said in an interview in advance of an international conference of the American Thoracic Society. “These data from period 2 of the TOMORROW trial are the first data to be generated on long-term treatment with nintedanib, i.e., beyond 52 weeks.” In period 2, patients treated with nintedanib in period 1 continued their dose, while placebo-treated patients were switched to nintedanib 50 mg once daily. The researchers evaluated change in forced vital capacity (FVC), acute exacerbations, mortality and adverse events in the nintedanib 150 mg twice daily group vs. the comparator group (placebo/nintedanib 50 mg once daily).

Of the 428 patients treated in period 1, 316 patients completed period 1 and 286 patients continued treatment in period 2. Of these 286 patients, 48 continued to receive nintedanib 150 mg twice daily and 54 were switched from placebo to nintedanib 50 mg once daily (comparator group), said Dr. Richeldi, professor of respiratory medicine and chair of interstitial lung disease at the University of Southampton (United Kingdom).

Dr. Richeldi reported results from a mean exposure of 14.2 months for the nintedanib 150 mg twice daily group and 16.8 months for the comparator group. Across periods 1 and 2, the researchers observed that the mean change in forced vital capacity (FVC) was consistently lower in the nintedanib 150 mg twice daily group, compared with the comparator group, such that by week 76 the absolute change in the percentage of predicted FVC was -3.1% vs. -6.3%, respectively. In addition, the incidence of acute exacerbations at week 76 was lower in the nintedanib 150 mg twice daily group, compared with the comparator group (3.2 vs. 13.4 per 100 patient-years).

A total of 14 patients (16.3%) died in the nintedanib 150 mg twice daily group, compared with 19 patients (21.8%) in the comparator group. However, the proportion of patients with at least one adverse event across period 1 and 2 was similar between both groups (97.6% vs. 96.5%, respectively), as was the proportion of patients with at least one serious adverse event (30.6% vs. 35.3%).

“It was not a surprise to see that the effect of nintedanib 150 mg twice daily on slowing disease progression (as shown by a reduced decline in FVC) was maintained up to week 76,” Dr. Richeldi said. “In addition, we expected that no relevant changes in the safety and tolerability of nintedanib would be observed in period 2 compared with period 1. We were impressed to see that over 90% of patients who completed the first 52 weeks of treatment in the TOMORROW trial (period 1) chose to continue to receive treatment in period 2.”

One limitation of the study was its small sample size, he said, “with FVC data only being available for 80 patients treated with nintedanib twice daily or comparator at week 76. Data from the open-label extension of the INPULSIS trials, INPULSIS-ON, will provide additional data on the long-term efficacy and safety of nintedanib 150 mg twice daily in patients with IPF.”

The study was supported by Boehringer Ingelheim. Dr. Richeldi disclosed that he has received consultation and speaker’s fees from the company. He was also a member of the steering committee for the TOMORROW trial.

[email protected]

On Twitter @dougbrunk

DENVER – The use of nintedanib 150 mg twice daily has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis up to 76 weeks of treatment, with an acceptable safety and tolerability profile, according to results from a novel study.

Marketed by Boehringer Ingelheim, nintedanib (Ofev)was approved by the FDA in October of 2014 for the treatment of idiopathic pulmonary fibrosis. Data from period 1 of the dose-finding, phase II TOMORROW trial (N. Engl. J. Med. 2011;365:1079–87) and the two replicate Phase III INPULSIS trials (N. Engl. J. Med. 2014;370:2071-82) demonstrated the efficacy and safety of nintedanib 150 mg twice daily over 52 weeks in patients with IPF. After completing period 1 of the TOMORROW trial, study participants had the option to continue treatment in a further blinded treatment phase (period 2).

“Clinicians are always interested in the long-term efficacy and safety of a new drug in patients suffering from a chronic, progressive disease like IPF,” lead study author Dr. Luca Richeldi said in an interview in advance of an international conference of the American Thoracic Society. “These data from period 2 of the TOMORROW trial are the first data to be generated on long-term treatment with nintedanib, i.e., beyond 52 weeks.” In period 2, patients treated with nintedanib in period 1 continued their dose, while placebo-treated patients were switched to nintedanib 50 mg once daily. The researchers evaluated change in forced vital capacity (FVC), acute exacerbations, mortality and adverse events in the nintedanib 150 mg twice daily group vs. the comparator group (placebo/nintedanib 50 mg once daily).

Of the 428 patients treated in period 1, 316 patients completed period 1 and 286 patients continued treatment in period 2. Of these 286 patients, 48 continued to receive nintedanib 150 mg twice daily and 54 were switched from placebo to nintedanib 50 mg once daily (comparator group), said Dr. Richeldi, professor of respiratory medicine and chair of interstitial lung disease at the University of Southampton (United Kingdom).

Dr. Richeldi reported results from a mean exposure of 14.2 months for the nintedanib 150 mg twice daily group and 16.8 months for the comparator group. Across periods 1 and 2, the researchers observed that the mean change in forced vital capacity (FVC) was consistently lower in the nintedanib 150 mg twice daily group, compared with the comparator group, such that by week 76 the absolute change in the percentage of predicted FVC was -3.1% vs. -6.3%, respectively. In addition, the incidence of acute exacerbations at week 76 was lower in the nintedanib 150 mg twice daily group, compared with the comparator group (3.2 vs. 13.4 per 100 patient-years).

A total of 14 patients (16.3%) died in the nintedanib 150 mg twice daily group, compared with 19 patients (21.8%) in the comparator group. However, the proportion of patients with at least one adverse event across period 1 and 2 was similar between both groups (97.6% vs. 96.5%, respectively), as was the proportion of patients with at least one serious adverse event (30.6% vs. 35.3%).

“It was not a surprise to see that the effect of nintedanib 150 mg twice daily on slowing disease progression (as shown by a reduced decline in FVC) was maintained up to week 76,” Dr. Richeldi said. “In addition, we expected that no relevant changes in the safety and tolerability of nintedanib would be observed in period 2 compared with period 1. We were impressed to see that over 90% of patients who completed the first 52 weeks of treatment in the TOMORROW trial (period 1) chose to continue to receive treatment in period 2.”

One limitation of the study was its small sample size, he said, “with FVC data only being available for 80 patients treated with nintedanib twice daily or comparator at week 76. Data from the open-label extension of the INPULSIS trials, INPULSIS-ON, will provide additional data on the long-term efficacy and safety of nintedanib 150 mg twice daily in patients with IPF.”

The study was supported by Boehringer Ingelheim. Dr. Richeldi disclosed that he has received consultation and speaker’s fees from the company. He was also a member of the steering committee for the TOMORROW trial.

[email protected]

On Twitter @dougbrunk

DENVER – The use of nintedanib 150 mg twice daily has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis up to 76 weeks of treatment, with an acceptable safety and tolerability profile, according to results from a novel study.

Marketed by Boehringer Ingelheim, nintedanib (Ofev)was approved by the FDA in October of 2014 for the treatment of idiopathic pulmonary fibrosis. Data from period 1 of the dose-finding, phase II TOMORROW trial (N. Engl. J. Med. 2011;365:1079–87) and the two replicate Phase III INPULSIS trials (N. Engl. J. Med. 2014;370:2071-82) demonstrated the efficacy and safety of nintedanib 150 mg twice daily over 52 weeks in patients with IPF. After completing period 1 of the TOMORROW trial, study participants had the option to continue treatment in a further blinded treatment phase (period 2).

“Clinicians are always interested in the long-term efficacy and safety of a new drug in patients suffering from a chronic, progressive disease like IPF,” lead study author Dr. Luca Richeldi said in an interview in advance of an international conference of the American Thoracic Society. “These data from period 2 of the TOMORROW trial are the first data to be generated on long-term treatment with nintedanib, i.e., beyond 52 weeks.” In period 2, patients treated with nintedanib in period 1 continued their dose, while placebo-treated patients were switched to nintedanib 50 mg once daily. The researchers evaluated change in forced vital capacity (FVC), acute exacerbations, mortality and adverse events in the nintedanib 150 mg twice daily group vs. the comparator group (placebo/nintedanib 50 mg once daily).

Of the 428 patients treated in period 1, 316 patients completed period 1 and 286 patients continued treatment in period 2. Of these 286 patients, 48 continued to receive nintedanib 150 mg twice daily and 54 were switched from placebo to nintedanib 50 mg once daily (comparator group), said Dr. Richeldi, professor of respiratory medicine and chair of interstitial lung disease at the University of Southampton (United Kingdom).

Dr. Richeldi reported results from a mean exposure of 14.2 months for the nintedanib 150 mg twice daily group and 16.8 months for the comparator group. Across periods 1 and 2, the researchers observed that the mean change in forced vital capacity (FVC) was consistently lower in the nintedanib 150 mg twice daily group, compared with the comparator group, such that by week 76 the absolute change in the percentage of predicted FVC was -3.1% vs. -6.3%, respectively. In addition, the incidence of acute exacerbations at week 76 was lower in the nintedanib 150 mg twice daily group, compared with the comparator group (3.2 vs. 13.4 per 100 patient-years).

A total of 14 patients (16.3%) died in the nintedanib 150 mg twice daily group, compared with 19 patients (21.8%) in the comparator group. However, the proportion of patients with at least one adverse event across period 1 and 2 was similar between both groups (97.6% vs. 96.5%, respectively), as was the proportion of patients with at least one serious adverse event (30.6% vs. 35.3%).

“It was not a surprise to see that the effect of nintedanib 150 mg twice daily on slowing disease progression (as shown by a reduced decline in FVC) was maintained up to week 76,” Dr. Richeldi said. “In addition, we expected that no relevant changes in the safety and tolerability of nintedanib would be observed in period 2 compared with period 1. We were impressed to see that over 90% of patients who completed the first 52 weeks of treatment in the TOMORROW trial (period 1) chose to continue to receive treatment in period 2.”

One limitation of the study was its small sample size, he said, “with FVC data only being available for 80 patients treated with nintedanib twice daily or comparator at week 76. Data from the open-label extension of the INPULSIS trials, INPULSIS-ON, will provide additional data on the long-term efficacy and safety of nintedanib 150 mg twice daily in patients with IPF.”

The study was supported by Boehringer Ingelheim. Dr. Richeldi disclosed that he has received consultation and speaker’s fees from the company. He was also a member of the steering committee for the TOMORROW trial.

[email protected]

On Twitter @dougbrunk