As-needed budesonide-formoterol prevented exacerbations in mild asthma

 

Formoterol plus budesonide prevented exacerbations when inhaled as needed by patients with mild persistent asthma, according to the results of two large, double-blind, 52-week, randomized phase 3 trials.

In the SYGMA1 (Symbicort Given as Needed in Mild Asthma) trial, the regimen outperformed as-needed terbutaline in terms of asthma control (34.4% vs. 31.1% of weeks; P = .046) and exacerbations (rate ratio, 0.36; 95% confidence interval, 0.27-0.49). In the SYGMA2 study, it was noninferior to twice-daily budesonide for preventing severe exacerbations (RR, 0.97; upper one-sided 95% CI, 1.16). The findings were published in two reports in the New England Journal of Medicine.

tupungato/Thinkstock

Asthma often is undertreated because many patients adhere poorly to maintenance glucocorticoids, noted Paul M. O’Byrne, MD, of McMaster University in Hamilton, Ont., and his associates from SYGMA1 (NCT02149199). Instead, patients often rely on short-acting beta₂-agonists for symptom control, but these drugs don’t stop exacerbations or treat underlying inflammation. “One potential strategy to address these issues is the use of a combination of a fast-acting beta₂-agonist and an inhaled glucocorticoid taken only on an as-needed basis,” the researchers wrote.

Accordingly, they randomly assigned 3,849 patients aged 12 years and up who had mild persistent asthma (mean forced expiratory volume in 1 second [FEV₁] before bronchodilator use, 84% of predicted value) to receive one of three regimens: twice-daily placebo plus terbutaline (0.5 mg) used as needed, twice-daily placebo plus budesonide-formoterol (200 mcg of budesonide and 6 mcg of formoterol) used as needed, or maintenance twice-daily budesonide (200 mcg) plus as-needed terbutaline (0.5 mg), all for 52 weeks.

In the final analysis of 3,836 patients, annual rates of severe exacerbations were 0.20 with terbutaline, significantly worse than with budesonide-formoterol (0.07) or maintenance budesonide (0.09). Using budesonide-formoterol (Symbicort) as needed improved the odds of having well-controlled asthma by about 14%, when compared with using terbutaline as needed (odds ratio, 1.14; 95% CI, 1.00-1.30; P = .046).

Although maintenance budesonide controlled asthma best (44.4% of weeks; OR vs. budesonide-formoterol, 0.64; 95% CI, 0.57-0.73), 21% of patients did not adhere to it, the researchers reported. “Patients are often more concerned [than their health care providers] about adverse effects of inhaled glucocorticoids, even when low inhaled doses are used,” they wrote. Notably, the budesonide-formoterol as-needed group received a median daily dose of only 57 mcg inhaled glucocorticoid, 17% of that received by the budesonide maintenance group.

In SYGMA2 (NCT02224157), 4,215 patients with mild persistent asthma aged 12 years and up were randomly assigned to receive either twice-daily placebo plus as-needed budesonide-formoterol or twice-daily maintenance budesonide plus as-needed terbutaline. Doses were the same as in the SYGMA1 trial. The regimens resembled each other in terms of severe exacerbations (annualized rates, 0.11 and 0.12, respectively) and time to first exacerbation, even though budesonide-formoterol patients received a 75% lower median daily dose of inhaled glucocorticoid, reported Eric D. Bateman, MD, of the University of Cape Town, South Africa, and his associates.

 

Results from both trials suggested that as-needed budesonide-formoterol provided better symptom control than did terbutaline but worse symptom control than did twice-daily budesonide. In SYGMA1, the change from baseline on the Asthma Control Questionnaire-5 (ACQ-5) favored budesonide-formoterol over terbutaline by an average of 0.15 units and similarly favored twice-daily budesonide over budesonide-formoterol. In SYGMA2, the budesonide maintenance group averaged 0.11 units greater improvement on the ACQ-5 and 0.10 better improvement on the standardized Asthma Quality of Life Questionnaire, compared with as-needed budesonide-formoterol recipients.

Finally, lung function assessments favored as-needed budesonide-formoterol over terbutaline but not over maintenance budesonide. SYGMA1, mean changes (from baseline) in FEV₁ before bronchodilator use were 11.2 mL with terbutaline, 65.0 mL with budesonide-formoterol, and 119.3 mL with maintenance budesonide. In SYGMA2, these values were 104 mL with budesonide-formoterol and 136.6 mL with maintenance budesonide.

AstraZeneca provided funding. For SYGMA1, Dr. Byrne disclosed ties to AstraZeneca, Novartis, GlaxoSmithKline, Medimmune, and Genentech. For SYGMA2, Dr. Bateman disclosed ties to AstraZeneca, Novartis, Cipla, Vectura, Boehringer Ingelheim, and a number of other pharmaceutical companies.

SOURCES: O’Byrne PM et al. N Engl J Med. 2018;378(20):1865-76.Bateman ED et al. N Engl J Med. 2018;378(20):1877-87.

 

Formoterol plus budesonide prevented exacerbations when inhaled as needed by patients with mild persistent asthma, according to the results of two large, double-blind, 52-week, randomized phase 3 trials.

In the SYGMA1 (Symbicort Given as Needed in Mild Asthma) trial, the regimen outperformed as-needed terbutaline in terms of asthma control (34.4% vs. 31.1% of weeks; P = .046) and exacerbations (rate ratio, 0.36; 95% confidence interval, 0.27-0.49). In the SYGMA2 study, it was noninferior to twice-daily budesonide for preventing severe exacerbations (RR, 0.97; upper one-sided 95% CI, 1.16). The findings were published in two reports in the New England Journal of Medicine.

tupungato/Thinkstock

Asthma often is undertreated because many patients adhere poorly to maintenance glucocorticoids, noted Paul M. O’Byrne, MD, of McMaster University in Hamilton, Ont., and his associates from SYGMA1 (NCT02149199). Instead, patients often rely on short-acting beta₂-agonists for symptom control, but these drugs don’t stop exacerbations or treat underlying inflammation. “One potential strategy to address these issues is the use of a combination of a fast-acting beta₂-agonist and an inhaled glucocorticoid taken only on an as-needed basis,” the researchers wrote.

Accordingly, they randomly assigned 3,849 patients aged 12 years and up who had mild persistent asthma (mean forced expiratory volume in 1 second [FEV₁] before bronchodilator use, 84% of predicted value) to receive one of three regimens: twice-daily placebo plus terbutaline (0.5 mg) used as needed, twice-daily placebo plus budesonide-formoterol (200 mcg of budesonide and 6 mcg of formoterol) used as needed, or maintenance twice-daily budesonide (200 mcg) plus as-needed terbutaline (0.5 mg), all for 52 weeks.

In the final analysis of 3,836 patients, annual rates of severe exacerbations were 0.20 with terbutaline, significantly worse than with budesonide-formoterol (0.07) or maintenance budesonide (0.09). Using budesonide-formoterol (Symbicort) as needed improved the odds of having well-controlled asthma by about 14%, when compared with using terbutaline as needed (odds ratio, 1.14; 95% CI, 1.00-1.30; P = .046).

Although maintenance budesonide controlled asthma best (44.4% of weeks; OR vs. budesonide-formoterol, 0.64; 95% CI, 0.57-0.73), 21% of patients did not adhere to it, the researchers reported. “Patients are often more concerned [than their health care providers] about adverse effects of inhaled glucocorticoids, even when low inhaled doses are used,” they wrote. Notably, the budesonide-formoterol as-needed group received a median daily dose of only 57 mcg inhaled glucocorticoid, 17% of that received by the budesonide maintenance group.

In SYGMA2 (NCT02224157), 4,215 patients with mild persistent asthma aged 12 years and up were randomly assigned to receive either twice-daily placebo plus as-needed budesonide-formoterol or twice-daily maintenance budesonide plus as-needed terbutaline. Doses were the same as in the SYGMA1 trial. The regimens resembled each other in terms of severe exacerbations (annualized rates, 0.11 and 0.12, respectively) and time to first exacerbation, even though budesonide-formoterol patients received a 75% lower median daily dose of inhaled glucocorticoid, reported Eric D. Bateman, MD, of the University of Cape Town, South Africa, and his associates.

 

Results from both trials suggested that as-needed budesonide-formoterol provided better symptom control than did terbutaline but worse symptom control than did twice-daily budesonide. In SYGMA1, the change from baseline on the Asthma Control Questionnaire-5 (ACQ-5) favored budesonide-formoterol over terbutaline by an average of 0.15 units and similarly favored twice-daily budesonide over budesonide-formoterol. In SYGMA2, the budesonide maintenance group averaged 0.11 units greater improvement on the ACQ-5 and 0.10 better improvement on the standardized Asthma Quality of Life Questionnaire, compared with as-needed budesonide-formoterol recipients.

Finally, lung function assessments favored as-needed budesonide-formoterol over terbutaline but not over maintenance budesonide. SYGMA1, mean changes (from baseline) in FEV₁ before bronchodilator use were 11.2 mL with terbutaline, 65.0 mL with budesonide-formoterol, and 119.3 mL with maintenance budesonide. In SYGMA2, these values were 104 mL with budesonide-formoterol and 136.6 mL with maintenance budesonide.

AstraZeneca provided funding. For SYGMA1, Dr. Byrne disclosed ties to AstraZeneca, Novartis, GlaxoSmithKline, Medimmune, and Genentech. For SYGMA2, Dr. Bateman disclosed ties to AstraZeneca, Novartis, Cipla, Vectura, Boehringer Ingelheim, and a number of other pharmaceutical companies.

SOURCES: O’Byrne PM et al. N Engl J Med. 2018;378(20):1865-76.Bateman ED et al. N Engl J Med. 2018;378(20):1877-87.

 

Formoterol plus budesonide prevented exacerbations when inhaled as needed by patients with mild persistent asthma, according to the results of two large, double-blind, 52-week, randomized phase 3 trials.

In the SYGMA1 (Symbicort Given as Needed in Mild Asthma) trial, the regimen outperformed as-needed terbutaline in terms of asthma control (34.4% vs. 31.1% of weeks; P = .046) and exacerbations (rate ratio, 0.36; 95% confidence interval, 0.27-0.49). In the SYGMA2 study, it was noninferior to twice-daily budesonide for preventing severe exacerbations (RR, 0.97; upper one-sided 95% CI, 1.16). The findings were published in two reports in the New England Journal of Medicine.

tupungato/Thinkstock

Asthma often is undertreated because many patients adhere poorly to maintenance glucocorticoids, noted Paul M. O’Byrne, MD, of McMaster University in Hamilton, Ont., and his associates from SYGMA1 (NCT02149199). Instead, patients often rely on short-acting beta₂-agonists for symptom control, but these drugs don’t stop exacerbations or treat underlying inflammation. “One potential strategy to address these issues is the use of a combination of a fast-acting beta₂-agonist and an inhaled glucocorticoid taken only on an as-needed basis,” the researchers wrote.

Accordingly, they randomly assigned 3,849 patients aged 12 years and up who had mild persistent asthma (mean forced expiratory volume in 1 second [FEV₁] before bronchodilator use, 84% of predicted value) to receive one of three regimens: twice-daily placebo plus terbutaline (0.5 mg) used as needed, twice-daily placebo plus budesonide-formoterol (200 mcg of budesonide and 6 mcg of formoterol) used as needed, or maintenance twice-daily budesonide (200 mcg) plus as-needed terbutaline (0.5 mg), all for 52 weeks.

In the final analysis of 3,836 patients, annual rates of severe exacerbations were 0.20 with terbutaline, significantly worse than with budesonide-formoterol (0.07) or maintenance budesonide (0.09). Using budesonide-formoterol (Symbicort) as needed improved the odds of having well-controlled asthma by about 14%, when compared with using terbutaline as needed (odds ratio, 1.14; 95% CI, 1.00-1.30; P = .046).

Although maintenance budesonide controlled asthma best (44.4% of weeks; OR vs. budesonide-formoterol, 0.64; 95% CI, 0.57-0.73), 21% of patients did not adhere to it, the researchers reported. “Patients are often more concerned [than their health care providers] about adverse effects of inhaled glucocorticoids, even when low inhaled doses are used,” they wrote. Notably, the budesonide-formoterol as-needed group received a median daily dose of only 57 mcg inhaled glucocorticoid, 17% of that received by the budesonide maintenance group.

In SYGMA2 (NCT02224157), 4,215 patients with mild persistent asthma aged 12 years and up were randomly assigned to receive either twice-daily placebo plus as-needed budesonide-formoterol or twice-daily maintenance budesonide plus as-needed terbutaline. Doses were the same as in the SYGMA1 trial. The regimens resembled each other in terms of severe exacerbations (annualized rates, 0.11 and 0.12, respectively) and time to first exacerbation, even though budesonide-formoterol patients received a 75% lower median daily dose of inhaled glucocorticoid, reported Eric D. Bateman, MD, of the University of Cape Town, South Africa, and his associates.

 

Results from both trials suggested that as-needed budesonide-formoterol provided better symptom control than did terbutaline but worse symptom control than did twice-daily budesonide. In SYGMA1, the change from baseline on the Asthma Control Questionnaire-5 (ACQ-5) favored budesonide-formoterol over terbutaline by an average of 0.15 units and similarly favored twice-daily budesonide over budesonide-formoterol. In SYGMA2, the budesonide maintenance group averaged 0.11 units greater improvement on the ACQ-5 and 0.10 better improvement on the standardized Asthma Quality of Life Questionnaire, compared with as-needed budesonide-formoterol recipients.

Finally, lung function assessments favored as-needed budesonide-formoterol over terbutaline but not over maintenance budesonide. SYGMA1, mean changes (from baseline) in FEV₁ before bronchodilator use were 11.2 mL with terbutaline, 65.0 mL with budesonide-formoterol, and 119.3 mL with maintenance budesonide. In SYGMA2, these values were 104 mL with budesonide-formoterol and 136.6 mL with maintenance budesonide.

AstraZeneca provided funding. For SYGMA1, Dr. Byrne disclosed ties to AstraZeneca, Novartis, GlaxoSmithKline, Medimmune, and Genentech. For SYGMA2, Dr. Bateman disclosed ties to AstraZeneca, Novartis, Cipla, Vectura, Boehringer Ingelheim, and a number of other pharmaceutical companies.

SOURCES: O’Byrne PM et al. N Engl J Med. 2018;378(20):1865-76.Bateman ED et al. N Engl J Med. 2018;378(20):1877-87.