ATS: Inhaled corticosteroid regimens being used in mild COPD

DENVER – Inhaled corticosteroid plus long-acting beta₂-agonist therapy is overused in patients with mild COPD, based on a post hoc analysis of two pivotal phase III studies.

At entry in the phase III TONADO studies, nearly 40% of patients who were classified as having GOLD A or B disease were receiving ICS maintenance therapy either alone, in free combination, or as fixed-dose combination therapy, Dr. Henrik Watz of the Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany, and his colleagues reported at an international conference of the American Thoracic Society.

Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend that use of inhaled corticosteroids (ICS) and long-acting beta₂-agonist (LABA) therapy be restricted to patients with severe or very severe COPD (category C or D disease) with frequent exacerbations.

The post-hoc analysis “confirms previous reports highlighting that treatment regimens containing ICS therapy are being used early in the management of patients with COPD, which may not be appropriate based on current GOLD recommendations. Furthermore, consistent improvements in lung function with tiotropium plus olodaterol versus the monocomponents were demonstrated in GOLD A, B, C, and D, regardless of previous ICS use,” Dr. Watz and his associates concluded.

The replicate TONADO studies (TONADO 1 and 2) were multicenter, randomized, double-blind, active-controlled studies evaluating the once-daily long-acting muscarinic agent (LAMA) tiotropium and the LABA olodaterol. The 5,162 patients were randomized to once-daily treatment with inhaled tiotropium plus olodaterol (Respimat FDC), to tiotropium, or to olodaterol for 52 weeks.

Of the study participants, 2,132 had GOLD A/B disease, and 3,030 had GOLD C/D disease, based on exacerbation history and lung function. All had postbronchodilator forced expiratory volume in 1 second (FEV₁) that was less than 80% of predicted normal, and FEV₁/forced vital capacity of less than 70%. All were current or exsmokers with a history of more than 10 pack-years.

At study entry, 7.2% of the GOLD A/B patients were treated with ICS without a LABA, and 31.1% were receiving ICS and a LABA. Of the GOLD C/D patients, 8.8% were receiving ICS without a LABA and 45% were receiving ICS with a LABA.

During the study, those who received both tiotropium and olodaterol had significant improvements in lung function, compared with those receiving only tiotropium. Among patients who had previously used ICS and received both drugs, the FEV₁ area under the curve at 0-3 hours was 0.310 L for GOLD A/B patients and 0.236 L for GOLD C/D patients. For those with no prior ICS use, the FEV₁ area under the curve at 0-3 hours was 0.277 L for GOLD A/B patients and 0.251 L for GOLD C/D patients.

For those with prior ICS use, trough FEV₁ was 0.160 L for GOLD A/B patients and 0.122 L for GOLD C/D patients receiving both tiotropium and olodaterol. For those with no prior ICS use, trough FEV₁ was 0.142 L for GOLD A/B patients and 0.149 L for GOLD C/D patients.

The TONADO studies included patients with moderate to very severe disease, but were conducted when the GOLD guidelines recommended that ICS plus LABA therapy be restricted to those with severe or very severe COPD and repeated exacerbations – before the guidelines were updated to take into account COPD symptoms. The updated guidelines call for ICS plus LABA maintenance therapy for patients in categories C and D disease with frequent exacerbations.

This study was supported by Boehringer Ingelheim, the maker of Respimat FDC.

[email protected]

DENVER – Inhaled corticosteroid plus long-acting beta₂-agonist therapy is overused in patients with mild COPD, based on a post hoc analysis of two pivotal phase III studies.

At entry in the phase III TONADO studies, nearly 40% of patients who were classified as having GOLD A or B disease were receiving ICS maintenance therapy either alone, in free combination, or as fixed-dose combination therapy, Dr. Henrik Watz of the Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany, and his colleagues reported at an international conference of the American Thoracic Society.

Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend that use of inhaled corticosteroids (ICS) and long-acting beta₂-agonist (LABA) therapy be restricted to patients with severe or very severe COPD (category C or D disease) with frequent exacerbations.

The post-hoc analysis “confirms previous reports highlighting that treatment regimens containing ICS therapy are being used early in the management of patients with COPD, which may not be appropriate based on current GOLD recommendations. Furthermore, consistent improvements in lung function with tiotropium plus olodaterol versus the monocomponents were demonstrated in GOLD A, B, C, and D, regardless of previous ICS use,” Dr. Watz and his associates concluded.

The replicate TONADO studies (TONADO 1 and 2) were multicenter, randomized, double-blind, active-controlled studies evaluating the once-daily long-acting muscarinic agent (LAMA) tiotropium and the LABA olodaterol. The 5,162 patients were randomized to once-daily treatment with inhaled tiotropium plus olodaterol (Respimat FDC), to tiotropium, or to olodaterol for 52 weeks.

Of the study participants, 2,132 had GOLD A/B disease, and 3,030 had GOLD C/D disease, based on exacerbation history and lung function. All had postbronchodilator forced expiratory volume in 1 second (FEV₁) that was less than 80% of predicted normal, and FEV₁/forced vital capacity of less than 70%. All were current or exsmokers with a history of more than 10 pack-years.

At study entry, 7.2% of the GOLD A/B patients were treated with ICS without a LABA, and 31.1% were receiving ICS and a LABA. Of the GOLD C/D patients, 8.8% were receiving ICS without a LABA and 45% were receiving ICS with a LABA.

During the study, those who received both tiotropium and olodaterol had significant improvements in lung function, compared with those receiving only tiotropium. Among patients who had previously used ICS and received both drugs, the FEV₁ area under the curve at 0-3 hours was 0.310 L for GOLD A/B patients and 0.236 L for GOLD C/D patients. For those with no prior ICS use, the FEV₁ area under the curve at 0-3 hours was 0.277 L for GOLD A/B patients and 0.251 L for GOLD C/D patients.

For those with prior ICS use, trough FEV₁ was 0.160 L for GOLD A/B patients and 0.122 L for GOLD C/D patients receiving both tiotropium and olodaterol. For those with no prior ICS use, trough FEV₁ was 0.142 L for GOLD A/B patients and 0.149 L for GOLD C/D patients.

The TONADO studies included patients with moderate to very severe disease, but were conducted when the GOLD guidelines recommended that ICS plus LABA therapy be restricted to those with severe or very severe COPD and repeated exacerbations – before the guidelines were updated to take into account COPD symptoms. The updated guidelines call for ICS plus LABA maintenance therapy for patients in categories C and D disease with frequent exacerbations.

This study was supported by Boehringer Ingelheim, the maker of Respimat FDC.

[email protected]

DENVER – Inhaled corticosteroid plus long-acting beta₂-agonist therapy is overused in patients with mild COPD, based on a post hoc analysis of two pivotal phase III studies.

At entry in the phase III TONADO studies, nearly 40% of patients who were classified as having GOLD A or B disease were receiving ICS maintenance therapy either alone, in free combination, or as fixed-dose combination therapy, Dr. Henrik Watz of the Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany, and his colleagues reported at an international conference of the American Thoracic Society.

Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend that use of inhaled corticosteroids (ICS) and long-acting beta₂-agonist (LABA) therapy be restricted to patients with severe or very severe COPD (category C or D disease) with frequent exacerbations.

The post-hoc analysis “confirms previous reports highlighting that treatment regimens containing ICS therapy are being used early in the management of patients with COPD, which may not be appropriate based on current GOLD recommendations. Furthermore, consistent improvements in lung function with tiotropium plus olodaterol versus the monocomponents were demonstrated in GOLD A, B, C, and D, regardless of previous ICS use,” Dr. Watz and his associates concluded.

The replicate TONADO studies (TONADO 1 and 2) were multicenter, randomized, double-blind, active-controlled studies evaluating the once-daily long-acting muscarinic agent (LAMA) tiotropium and the LABA olodaterol. The 5,162 patients were randomized to once-daily treatment with inhaled tiotropium plus olodaterol (Respimat FDC), to tiotropium, or to olodaterol for 52 weeks.

Of the study participants, 2,132 had GOLD A/B disease, and 3,030 had GOLD C/D disease, based on exacerbation history and lung function. All had postbronchodilator forced expiratory volume in 1 second (FEV₁) that was less than 80% of predicted normal, and FEV₁/forced vital capacity of less than 70%. All were current or exsmokers with a history of more than 10 pack-years.

At study entry, 7.2% of the GOLD A/B patients were treated with ICS without a LABA, and 31.1% were receiving ICS and a LABA. Of the GOLD C/D patients, 8.8% were receiving ICS without a LABA and 45% were receiving ICS with a LABA.

During the study, those who received both tiotropium and olodaterol had significant improvements in lung function, compared with those receiving only tiotropium. Among patients who had previously used ICS and received both drugs, the FEV₁ area under the curve at 0-3 hours was 0.310 L for GOLD A/B patients and 0.236 L for GOLD C/D patients. For those with no prior ICS use, the FEV₁ area under the curve at 0-3 hours was 0.277 L for GOLD A/B patients and 0.251 L for GOLD C/D patients.

For those with prior ICS use, trough FEV₁ was 0.160 L for GOLD A/B patients and 0.122 L for GOLD C/D patients receiving both tiotropium and olodaterol. For those with no prior ICS use, trough FEV₁ was 0.142 L for GOLD A/B patients and 0.149 L for GOLD C/D patients.

The TONADO studies included patients with moderate to very severe disease, but were conducted when the GOLD guidelines recommended that ICS plus LABA therapy be restricted to those with severe or very severe COPD and repeated exacerbations – before the guidelines were updated to take into account COPD symptoms. The updated guidelines call for ICS plus LABA maintenance therapy for patients in categories C and D disease with frequent exacerbations.

This study was supported by Boehringer Ingelheim, the maker of Respimat FDC.

[email protected]