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As-needed budesonide-formoterol prevented exacerbations in mild 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.
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.
In the SYGMA1 and SYGMA2 trials, as-needed budesonide-formoterol (Symbicort) prevented exacerbations and loss of lung function, the two worst outcomes of poorly controlled asthma, concluded Stephen C. Lazarus, MD, in an editorial accompanying the studies in the New England Journal of Medicine.
“As-needed treatment was similar, or at least noninferior, to regular maintenance therapy with inhaled glucocorticoids with regard to the prevention of exacerbations, and exacerbations are the main contributor to loss of lung function, death, and cost,” wrote Dr. Lazarus.
Patients typically received only 17%-25% as much inhaled glucocorticoid as did those on maintenance budesonide, which would help prevent side effects and would make the regimen more acceptable to “glucocorticoid-averse patients,” he added. Another benefit to patients with mild persistent asthma using as-needed budesonide-formoterol instead of inhaled glucocorticoid maintenance therapy is that it would result in nearly $1 billion in cost savings in the United States yearly.
Budesonide-formoterol did not control symptoms as well as did maintenance budesonide, but patients might accept “occasional mild symptoms and inhaler use if it [freed] them from daily use of inhaled glucocorticoids while preventing loss of lung function and exacerbations,” he concluded. “For these patients, ‘Two out of three ain’t bad!’ ”
Dr. Lazarus is in the department of medicine and at the Cardiovascular Research Institute, University of California, San Francisco. He reported having no conflicts of interest. This comments are from his editorial (N Engl J Med. 2018 May 17. doi: 10.1056/NEJMe1802680).
In the SYGMA1 and SYGMA2 trials, as-needed budesonide-formoterol (Symbicort) prevented exacerbations and loss of lung function, the two worst outcomes of poorly controlled asthma, concluded Stephen C. Lazarus, MD, in an editorial accompanying the studies in the New England Journal of Medicine.
“As-needed treatment was similar, or at least noninferior, to regular maintenance therapy with inhaled glucocorticoids with regard to the prevention of exacerbations, and exacerbations are the main contributor to loss of lung function, death, and cost,” wrote Dr. Lazarus.
Patients typically received only 17%-25% as much inhaled glucocorticoid as did those on maintenance budesonide, which would help prevent side effects and would make the regimen more acceptable to “glucocorticoid-averse patients,” he added. Another benefit to patients with mild persistent asthma using as-needed budesonide-formoterol instead of inhaled glucocorticoid maintenance therapy is that it would result in nearly $1 billion in cost savings in the United States yearly.
Budesonide-formoterol did not control symptoms as well as did maintenance budesonide, but patients might accept “occasional mild symptoms and inhaler use if it [freed] them from daily use of inhaled glucocorticoids while preventing loss of lung function and exacerbations,” he concluded. “For these patients, ‘Two out of three ain’t bad!’ ”
Dr. Lazarus is in the department of medicine and at the Cardiovascular Research Institute, University of California, San Francisco. He reported having no conflicts of interest. This comments are from his editorial (N Engl J Med. 2018 May 17. doi: 10.1056/NEJMe1802680).
In the SYGMA1 and SYGMA2 trials, as-needed budesonide-formoterol (Symbicort) prevented exacerbations and loss of lung function, the two worst outcomes of poorly controlled asthma, concluded Stephen C. Lazarus, MD, in an editorial accompanying the studies in the New England Journal of Medicine.
“As-needed treatment was similar, or at least noninferior, to regular maintenance therapy with inhaled glucocorticoids with regard to the prevention of exacerbations, and exacerbations are the main contributor to loss of lung function, death, and cost,” wrote Dr. Lazarus.
Patients typically received only 17%-25% as much inhaled glucocorticoid as did those on maintenance budesonide, which would help prevent side effects and would make the regimen more acceptable to “glucocorticoid-averse patients,” he added. Another benefit to patients with mild persistent asthma using as-needed budesonide-formoterol instead of inhaled glucocorticoid maintenance therapy is that it would result in nearly $1 billion in cost savings in the United States yearly.
Budesonide-formoterol did not control symptoms as well as did maintenance budesonide, but patients might accept “occasional mild symptoms and inhaler use if it [freed] them from daily use of inhaled glucocorticoids while preventing loss of lung function and exacerbations,” he concluded. “For these patients, ‘Two out of three ain’t bad!’ ”
Dr. Lazarus is in the department of medicine and at the Cardiovascular Research Institute, University of California, San Francisco. He reported having no conflicts of interest. This comments are from his editorial (N Engl J Med. 2018 May 17. doi: 10.1056/NEJMe1802680).
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.
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.
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.
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.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: As-needed budesonide-formoterol (Symbicort) prevented exacerbations in patients with mild persistent asthma.
Major finding: In the SYGMA1 trial, the regimen outperformed as-needed terbutaline for asthma control (34.4% vs. 31.1% of weeks; P = .046) and exacerbations (RR, 0.36; 95% CI, 0.27-0.49). In SYGMA2, the regimen was noninferior to twice-daily budesonide for preventing severe exacerbations (RR, 0.97; upper one-sided 95% confidence limit, 1.16).
Study details: SYGMA1 and SYGMA2, randomized phase 3 trials of 8,012 patients aged 12 years and older with mild persistent asthma.
Disclosures: 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 May 17;378(20);1865-76. Bateman ED et al. N Engl J Med. 2018 May 17;378(20):1877-87.
E-cigarette usage has changed
, according to a study published online on May 15 by JAMA.
The prevalence of ever use of e-cigarettes among adults aged 18 years and older rose significantly from 12.6% in 2014 to 15.3% in 2016, while the prevalence of current use (defined as use every day or some days) decreased significantly from 3.7% to 3.2% over that same period, suggesting “that some individuals are trying but not continuing use of e-cigarettes,” Wei Bao, MD, PhD, and his associates said in a research letter.
None of the investigators reported any conflicts of interest.
SOURCE: Bao W et al. JAMA. 2018 May 15;319(19):2039-41.
, according to a study published online on May 15 by JAMA.
The prevalence of ever use of e-cigarettes among adults aged 18 years and older rose significantly from 12.6% in 2014 to 15.3% in 2016, while the prevalence of current use (defined as use every day or some days) decreased significantly from 3.7% to 3.2% over that same period, suggesting “that some individuals are trying but not continuing use of e-cigarettes,” Wei Bao, MD, PhD, and his associates said in a research letter.
None of the investigators reported any conflicts of interest.
SOURCE: Bao W et al. JAMA. 2018 May 15;319(19):2039-41.
, according to a study published online on May 15 by JAMA.
The prevalence of ever use of e-cigarettes among adults aged 18 years and older rose significantly from 12.6% in 2014 to 15.3% in 2016, while the prevalence of current use (defined as use every day or some days) decreased significantly from 3.7% to 3.2% over that same period, suggesting “that some individuals are trying but not continuing use of e-cigarettes,” Wei Bao, MD, PhD, and his associates said in a research letter.
None of the investigators reported any conflicts of interest.
SOURCE: Bao W et al. JAMA. 2018 May 15;319(19):2039-41.
FROM JAMA
Parents smoke less tobacco, more cannabis at home
Children are increasingly less likely to be exposed to secondhand cigarette smoke in the home, but cannabis seems to be picking up some of the slack, according to Renee D. Goodwin, PhD, and her associates.
Using a study population of 169,259 adults with data available from the National Survey on Drug Use and Health, the researchers found that from 2002 to 2015, the prevalence of parents with children in the home who were also current smokers dropped from 27.6% to 20.2%. By contrast, the rate of cannabis usage increased from 4.9% to 6.8% over the same time period. Overall, the rate of children living in a home with secondhand smoke fell from 29.7% to 23.5%.
“Public health efforts that have shown success in decreasing exposure to STS [secondhand tobacco smoke] in the home may be complicated by increased use of other smoked products, such as cannabis. Parents may benefit from education about protecting children from marijuana products, paraphernalia, waste, and smoke,” the investigators concluded.
SOURCE: Goodwin RD et al. Pediatrics. 2018 May 14. doi: 10.1542/peds.2017-3506.
Children are increasingly less likely to be exposed to secondhand cigarette smoke in the home, but cannabis seems to be picking up some of the slack, according to Renee D. Goodwin, PhD, and her associates.
Using a study population of 169,259 adults with data available from the National Survey on Drug Use and Health, the researchers found that from 2002 to 2015, the prevalence of parents with children in the home who were also current smokers dropped from 27.6% to 20.2%. By contrast, the rate of cannabis usage increased from 4.9% to 6.8% over the same time period. Overall, the rate of children living in a home with secondhand smoke fell from 29.7% to 23.5%.
“Public health efforts that have shown success in decreasing exposure to STS [secondhand tobacco smoke] in the home may be complicated by increased use of other smoked products, such as cannabis. Parents may benefit from education about protecting children from marijuana products, paraphernalia, waste, and smoke,” the investigators concluded.
SOURCE: Goodwin RD et al. Pediatrics. 2018 May 14. doi: 10.1542/peds.2017-3506.
Children are increasingly less likely to be exposed to secondhand cigarette smoke in the home, but cannabis seems to be picking up some of the slack, according to Renee D. Goodwin, PhD, and her associates.
Using a study population of 169,259 adults with data available from the National Survey on Drug Use and Health, the researchers found that from 2002 to 2015, the prevalence of parents with children in the home who were also current smokers dropped from 27.6% to 20.2%. By contrast, the rate of cannabis usage increased from 4.9% to 6.8% over the same time period. Overall, the rate of children living in a home with secondhand smoke fell from 29.7% to 23.5%.
“Public health efforts that have shown success in decreasing exposure to STS [secondhand tobacco smoke] in the home may be complicated by increased use of other smoked products, such as cannabis. Parents may benefit from education about protecting children from marijuana products, paraphernalia, waste, and smoke,” the investigators concluded.
SOURCE: Goodwin RD et al. Pediatrics. 2018 May 14. doi: 10.1542/peds.2017-3506.
FROM PEDIATRICS
Patients with CF at increased risk for GI cancers
Patients with cystic fibrosis have a significantly greater risk for developing cancers of the gastrointestinal tract compared with the general population, results of a systematic review and meta-analysis indicate.
Among persons with cystic fibrosis (CF) the standardized incidence ratio (SIR) for any gastrointestinal cancer compared with the general population was 8.13 (P less than .0001). Patients with CF were at significantly elevated risk for cancers of the small bowel, colon, biliary tract, and pancreas, reported Atsushi Sakuraba, MD, PhD, of the University of Chicago, and his colleagues.
“Additionally, our findings suggest that patients who had an organ transplant have a higher risk of developing gastrointestinal cancer than those who did not. Although further studies are needed to monitor gastrointestinal cancer incidence over time in patients with cystic fibrosis, the development of a screening strategy for gastrointestinal cancer in these patients is warranted,” they wrote in Lancet Oncology.
As patients with CF live longer because of improvements in therapies and management of comorbidities, their risks for cancer and other diseases will increase, the authors noted.
To get a more accurate estimate of the degree of risk than what smaller cohort studies could provide, the investigators conducted a systematic review and meta-analysis. They narrowed their search to six cohort studies including 99,925 patients with CF followed for a total of 5,444,695 person-years.
As noted, patients with CF overall had an eightfold higher risk for gastrointestinal cancers compared with the general population, and for the subgroup of patients who had undergone a lung transplant, the SIR was 21.13 compared with 4.18 for those with CF but no lung transplant (P less than .0001).
- The SIRs for site-specific gastrointestinal cancers were as follows:
- Small bowel: SIR= 18.94 (P less than .0001).
- Colon: SIR = 10.91 (P less than .0001).
- Biliary tract: SIR = 17.87 (P less than .0001).
- Pancreas: SIR = 6.18 (P = .022).
The investigators recommend screening for gastrointestinal cancers in patients with CF in general, and especially for patients who have undergone lung transplantation and are receiving immunosuppressive therapies.
Because of the elevated risk of pancreatic and biliary tract cancers, the authors propose a screening program including magnetic resonance cholangiopancreatography, endoscopic ultrasound, or abdominal ultrasound and measurement of cancer antigen 19-9.
The authors reported that the study had no funding source, and they declared no competing interests.
SOURCE: Yamada A et al. Lancet Oncol. 2018 Apr 26. doi: 10.1016/S1470-2045(18)30188-8.
The emergence of gastrointestinal cancer as a clinical complication in adults with cystic fibrosis is a consequence of the substantial improvement in life expectancy. Novel CFTR modulator therapies, which correct the malfunctioning protein and increase its expression at the apical surface, might decrease the incidence of gastrointestinal cancers in patients with cystic fibrosis.
In conclusion, the meta-analysis by Yamada and colleagues shows that cystic fibrosis can be considered a gastrointestinal cancer syndrome, for which screening and surveillance protocols should be implemented. Oncologists and gastroenterologists managing patients with cystic fibrosis should consider the best methods for screening of the small bowel, biliary tract, pancreas, and colon to prevent gastrointestinal malignancies in these patients.
Mordechai Slae, MD, and Michael Wilschanski, MD, are with the Hadassah Medical Center in Jerusalem. These comments are condensed from their editorial in The Lancet Oncology.
The emergence of gastrointestinal cancer as a clinical complication in adults with cystic fibrosis is a consequence of the substantial improvement in life expectancy. Novel CFTR modulator therapies, which correct the malfunctioning protein and increase its expression at the apical surface, might decrease the incidence of gastrointestinal cancers in patients with cystic fibrosis.
In conclusion, the meta-analysis by Yamada and colleagues shows that cystic fibrosis can be considered a gastrointestinal cancer syndrome, for which screening and surveillance protocols should be implemented. Oncologists and gastroenterologists managing patients with cystic fibrosis should consider the best methods for screening of the small bowel, biliary tract, pancreas, and colon to prevent gastrointestinal malignancies in these patients.
Mordechai Slae, MD, and Michael Wilschanski, MD, are with the Hadassah Medical Center in Jerusalem. These comments are condensed from their editorial in The Lancet Oncology.
The emergence of gastrointestinal cancer as a clinical complication in adults with cystic fibrosis is a consequence of the substantial improvement in life expectancy. Novel CFTR modulator therapies, which correct the malfunctioning protein and increase its expression at the apical surface, might decrease the incidence of gastrointestinal cancers in patients with cystic fibrosis.
In conclusion, the meta-analysis by Yamada and colleagues shows that cystic fibrosis can be considered a gastrointestinal cancer syndrome, for which screening and surveillance protocols should be implemented. Oncologists and gastroenterologists managing patients with cystic fibrosis should consider the best methods for screening of the small bowel, biliary tract, pancreas, and colon to prevent gastrointestinal malignancies in these patients.
Mordechai Slae, MD, and Michael Wilschanski, MD, are with the Hadassah Medical Center in Jerusalem. These comments are condensed from their editorial in The Lancet Oncology.
Patients with cystic fibrosis have a significantly greater risk for developing cancers of the gastrointestinal tract compared with the general population, results of a systematic review and meta-analysis indicate.
Among persons with cystic fibrosis (CF) the standardized incidence ratio (SIR) for any gastrointestinal cancer compared with the general population was 8.13 (P less than .0001). Patients with CF were at significantly elevated risk for cancers of the small bowel, colon, biliary tract, and pancreas, reported Atsushi Sakuraba, MD, PhD, of the University of Chicago, and his colleagues.
“Additionally, our findings suggest that patients who had an organ transplant have a higher risk of developing gastrointestinal cancer than those who did not. Although further studies are needed to monitor gastrointestinal cancer incidence over time in patients with cystic fibrosis, the development of a screening strategy for gastrointestinal cancer in these patients is warranted,” they wrote in Lancet Oncology.
As patients with CF live longer because of improvements in therapies and management of comorbidities, their risks for cancer and other diseases will increase, the authors noted.
To get a more accurate estimate of the degree of risk than what smaller cohort studies could provide, the investigators conducted a systematic review and meta-analysis. They narrowed their search to six cohort studies including 99,925 patients with CF followed for a total of 5,444,695 person-years.
As noted, patients with CF overall had an eightfold higher risk for gastrointestinal cancers compared with the general population, and for the subgroup of patients who had undergone a lung transplant, the SIR was 21.13 compared with 4.18 for those with CF but no lung transplant (P less than .0001).
- The SIRs for site-specific gastrointestinal cancers were as follows:
- Small bowel: SIR= 18.94 (P less than .0001).
- Colon: SIR = 10.91 (P less than .0001).
- Biliary tract: SIR = 17.87 (P less than .0001).
- Pancreas: SIR = 6.18 (P = .022).
The investigators recommend screening for gastrointestinal cancers in patients with CF in general, and especially for patients who have undergone lung transplantation and are receiving immunosuppressive therapies.
Because of the elevated risk of pancreatic and biliary tract cancers, the authors propose a screening program including magnetic resonance cholangiopancreatography, endoscopic ultrasound, or abdominal ultrasound and measurement of cancer antigen 19-9.
The authors reported that the study had no funding source, and they declared no competing interests.
SOURCE: Yamada A et al. Lancet Oncol. 2018 Apr 26. doi: 10.1016/S1470-2045(18)30188-8.
Patients with cystic fibrosis have a significantly greater risk for developing cancers of the gastrointestinal tract compared with the general population, results of a systematic review and meta-analysis indicate.
Among persons with cystic fibrosis (CF) the standardized incidence ratio (SIR) for any gastrointestinal cancer compared with the general population was 8.13 (P less than .0001). Patients with CF were at significantly elevated risk for cancers of the small bowel, colon, biliary tract, and pancreas, reported Atsushi Sakuraba, MD, PhD, of the University of Chicago, and his colleagues.
“Additionally, our findings suggest that patients who had an organ transplant have a higher risk of developing gastrointestinal cancer than those who did not. Although further studies are needed to monitor gastrointestinal cancer incidence over time in patients with cystic fibrosis, the development of a screening strategy for gastrointestinal cancer in these patients is warranted,” they wrote in Lancet Oncology.
As patients with CF live longer because of improvements in therapies and management of comorbidities, their risks for cancer and other diseases will increase, the authors noted.
To get a more accurate estimate of the degree of risk than what smaller cohort studies could provide, the investigators conducted a systematic review and meta-analysis. They narrowed their search to six cohort studies including 99,925 patients with CF followed for a total of 5,444,695 person-years.
As noted, patients with CF overall had an eightfold higher risk for gastrointestinal cancers compared with the general population, and for the subgroup of patients who had undergone a lung transplant, the SIR was 21.13 compared with 4.18 for those with CF but no lung transplant (P less than .0001).
- The SIRs for site-specific gastrointestinal cancers were as follows:
- Small bowel: SIR= 18.94 (P less than .0001).
- Colon: SIR = 10.91 (P less than .0001).
- Biliary tract: SIR = 17.87 (P less than .0001).
- Pancreas: SIR = 6.18 (P = .022).
The investigators recommend screening for gastrointestinal cancers in patients with CF in general, and especially for patients who have undergone lung transplantation and are receiving immunosuppressive therapies.
Because of the elevated risk of pancreatic and biliary tract cancers, the authors propose a screening program including magnetic resonance cholangiopancreatography, endoscopic ultrasound, or abdominal ultrasound and measurement of cancer antigen 19-9.
The authors reported that the study had no funding source, and they declared no competing interests.
SOURCE: Yamada A et al. Lancet Oncol. 2018 Apr 26. doi: 10.1016/S1470-2045(18)30188-8.
FROM THE LANCET ONCOLOGY
Key clinical point: Patients with cystic fibrosis, especially those who have received a lung transplant, are at increased risk for gastrointestinal tract cancers.
Major finding: The standard incidence ratio for GI cancers among patients with CF was 8.13 compared with the general population.
Study details: Systematic review and meta-analysis of published studies including 99,925 patients with CF followed for 5,444,695 person-years.
Disclosures: The authors reported that the study had no funding source, and they declared no competing interests.
Source: Yamada A et al. Lancet Oncol 2018 Apr 26. doi: 10.1016/S1470-2045(18)30188-8.
Ivacaftor reduced hospitalizations in CF
with a variety of mutations, according to results published May 7 in Health Affairs.
The study involved 143 patients being treated with ivacaftor between February 2012 and February 2015. In 2014, the FDA expanded its approval for the use of ivacaftor by cystic fibrosis patients to include nine additional mutations, and patients with these mutations were included in this study.
Ms. Feng, who is senior director for policy and advocacy at the Cystic Fibrosis Foundation and her colleagues analyzed administrative claims data from the Truven Health Analytics Market Scan Commercial Research Database. All of the claims were for patients from the United States with employer-sponsored insurance plans. Eligibility criteria included an ICD-9 CM diagnosis of cystic fibrosis on one or more inpatient claims or two or more outpatient claims at least 30 days apart, a prescription claim for ivacaftor monotherapy, being at least 6 years of age at the time of the first filled prescription, and 12 months of continuous enrollment before and after the first filled prescription.
The “pre-ivacaftor” period was defined as the 12 months before the first filled prescription. The “post-ivacaftor” period was defined as the 12 months after the first filled prescription. For each period, the numbers and percentages of patients hospitalized were calculated, for any reason and for cystic fibrosis–related reasons. Hospitalization rates also were calculated as numbers of admissions per person-year, the authors said.
Data also were analyzed for two subcohorts: the 86 patients who started using ivacaftor between Feb. 6, 2012, and Feb. 21, 2014, under the initial Food and Drug Administration label; and the 57 patients who initiated use between Feb. 22, 2014, and Dec. 31, 2015, under the expanded FDA label, which included nine additional genetic mutations.
Of the 143 patients who had filled prescriptions for ivacaftor, 63% were aged 18 years or older. The rate of overall inpatient admissions decreased 55%, from 0.57 admissions per person-year in the pre-ivacaftor period to 0.26 admissions per person-year in the post-ivacaftor period, the investigators reported.
The declines in hospital admissions also were similar between the initial label and the expanded FDA label groups, with declines in overall admissions of 59% and 57%, respectively.
Hospital admissions related to cystic fibrosis also decreased significantly, by 78%. Admissions with principal diagnosis codes for cystic fibrosis decreased from 42 in the preprescription period, to 8 after filling the prescription. Rates per person per year decreased by 82% in patients aged 6-17 years and 80% among adults aged 18 years and older. Additionally, patients who filled at least 10 prescriptions during the study period experienced a 68% reduction in inpatient admissions, compared with 45% for those with three to nine prescriptions filled.
Ivacaftor also was associated with 60% lower per-person inpatient spending overall, with a greater proportional reduction in hospital costs for adults (68%) than for children (45%), and an absolute per-person reduction of $10,567, the authors reported.
“Treatments that target the protein defect that causes cystic fibrosis illustrate the promise of precision medicine,” the authors wrote. “To deliver the right care to the right patient, cystic fibrosis care must continue to account for other aspects unique to individuals such as environment, physiology, patients’ preferences, and lifestyle,” they concluded.
Ivacaftor (Kalydeco) is manufactured for Vertex Pharmaceuticals. No disclosures or conflicts of interest were reported.
SOURCE: Feng LB et al. Health Aff. 2018 May 8. doi: 10.1377/hlthaff.2017.1554
with a variety of mutations, according to results published May 7 in Health Affairs.
The study involved 143 patients being treated with ivacaftor between February 2012 and February 2015. In 2014, the FDA expanded its approval for the use of ivacaftor by cystic fibrosis patients to include nine additional mutations, and patients with these mutations were included in this study.
Ms. Feng, who is senior director for policy and advocacy at the Cystic Fibrosis Foundation and her colleagues analyzed administrative claims data from the Truven Health Analytics Market Scan Commercial Research Database. All of the claims were for patients from the United States with employer-sponsored insurance plans. Eligibility criteria included an ICD-9 CM diagnosis of cystic fibrosis on one or more inpatient claims or two or more outpatient claims at least 30 days apart, a prescription claim for ivacaftor monotherapy, being at least 6 years of age at the time of the first filled prescription, and 12 months of continuous enrollment before and after the first filled prescription.
The “pre-ivacaftor” period was defined as the 12 months before the first filled prescription. The “post-ivacaftor” period was defined as the 12 months after the first filled prescription. For each period, the numbers and percentages of patients hospitalized were calculated, for any reason and for cystic fibrosis–related reasons. Hospitalization rates also were calculated as numbers of admissions per person-year, the authors said.
Data also were analyzed for two subcohorts: the 86 patients who started using ivacaftor between Feb. 6, 2012, and Feb. 21, 2014, under the initial Food and Drug Administration label; and the 57 patients who initiated use between Feb. 22, 2014, and Dec. 31, 2015, under the expanded FDA label, which included nine additional genetic mutations.
Of the 143 patients who had filled prescriptions for ivacaftor, 63% were aged 18 years or older. The rate of overall inpatient admissions decreased 55%, from 0.57 admissions per person-year in the pre-ivacaftor period to 0.26 admissions per person-year in the post-ivacaftor period, the investigators reported.
The declines in hospital admissions also were similar between the initial label and the expanded FDA label groups, with declines in overall admissions of 59% and 57%, respectively.
Hospital admissions related to cystic fibrosis also decreased significantly, by 78%. Admissions with principal diagnosis codes for cystic fibrosis decreased from 42 in the preprescription period, to 8 after filling the prescription. Rates per person per year decreased by 82% in patients aged 6-17 years and 80% among adults aged 18 years and older. Additionally, patients who filled at least 10 prescriptions during the study period experienced a 68% reduction in inpatient admissions, compared with 45% for those with three to nine prescriptions filled.
Ivacaftor also was associated with 60% lower per-person inpatient spending overall, with a greater proportional reduction in hospital costs for adults (68%) than for children (45%), and an absolute per-person reduction of $10,567, the authors reported.
“Treatments that target the protein defect that causes cystic fibrosis illustrate the promise of precision medicine,” the authors wrote. “To deliver the right care to the right patient, cystic fibrosis care must continue to account for other aspects unique to individuals such as environment, physiology, patients’ preferences, and lifestyle,” they concluded.
Ivacaftor (Kalydeco) is manufactured for Vertex Pharmaceuticals. No disclosures or conflicts of interest were reported.
SOURCE: Feng LB et al. Health Aff. 2018 May 8. doi: 10.1377/hlthaff.2017.1554
with a variety of mutations, according to results published May 7 in Health Affairs.
The study involved 143 patients being treated with ivacaftor between February 2012 and February 2015. In 2014, the FDA expanded its approval for the use of ivacaftor by cystic fibrosis patients to include nine additional mutations, and patients with these mutations were included in this study.
Ms. Feng, who is senior director for policy and advocacy at the Cystic Fibrosis Foundation and her colleagues analyzed administrative claims data from the Truven Health Analytics Market Scan Commercial Research Database. All of the claims were for patients from the United States with employer-sponsored insurance plans. Eligibility criteria included an ICD-9 CM diagnosis of cystic fibrosis on one or more inpatient claims or two or more outpatient claims at least 30 days apart, a prescription claim for ivacaftor monotherapy, being at least 6 years of age at the time of the first filled prescription, and 12 months of continuous enrollment before and after the first filled prescription.
The “pre-ivacaftor” period was defined as the 12 months before the first filled prescription. The “post-ivacaftor” period was defined as the 12 months after the first filled prescription. For each period, the numbers and percentages of patients hospitalized were calculated, for any reason and for cystic fibrosis–related reasons. Hospitalization rates also were calculated as numbers of admissions per person-year, the authors said.
Data also were analyzed for two subcohorts: the 86 patients who started using ivacaftor between Feb. 6, 2012, and Feb. 21, 2014, under the initial Food and Drug Administration label; and the 57 patients who initiated use between Feb. 22, 2014, and Dec. 31, 2015, under the expanded FDA label, which included nine additional genetic mutations.
Of the 143 patients who had filled prescriptions for ivacaftor, 63% were aged 18 years or older. The rate of overall inpatient admissions decreased 55%, from 0.57 admissions per person-year in the pre-ivacaftor period to 0.26 admissions per person-year in the post-ivacaftor period, the investigators reported.
The declines in hospital admissions also were similar between the initial label and the expanded FDA label groups, with declines in overall admissions of 59% and 57%, respectively.
Hospital admissions related to cystic fibrosis also decreased significantly, by 78%. Admissions with principal diagnosis codes for cystic fibrosis decreased from 42 in the preprescription period, to 8 after filling the prescription. Rates per person per year decreased by 82% in patients aged 6-17 years and 80% among adults aged 18 years and older. Additionally, patients who filled at least 10 prescriptions during the study period experienced a 68% reduction in inpatient admissions, compared with 45% for those with three to nine prescriptions filled.
Ivacaftor also was associated with 60% lower per-person inpatient spending overall, with a greater proportional reduction in hospital costs for adults (68%) than for children (45%), and an absolute per-person reduction of $10,567, the authors reported.
“Treatments that target the protein defect that causes cystic fibrosis illustrate the promise of precision medicine,” the authors wrote. “To deliver the right care to the right patient, cystic fibrosis care must continue to account for other aspects unique to individuals such as environment, physiology, patients’ preferences, and lifestyle,” they concluded.
Ivacaftor (Kalydeco) is manufactured for Vertex Pharmaceuticals. No disclosures or conflicts of interest were reported.
SOURCE: Feng LB et al. Health Aff. 2018 May 8. doi: 10.1377/hlthaff.2017.1554
FROM HEALTH AFFAIRS
Key clinical point: Ivacaftor significantly reduced hospital admission rates in patients with cystic fibrosis.
Major finding: Overall rate of inpatient admissions dropped by 55% and cystic fibrosis related admissions rates by 78% (P less than .0001).
Study details: A study of 143 patients treated with ivacaftor between February 2012 and February 2015.
Disclosures: No disclosures or conflicts of interest were reported.
Source: Feng LB et al. Health Aff. 2018 May 8. doi: 10.1377/hlthaff.2017.1554.
In PAH trials, clinical worsening risk rose with time
Current clinical trials evaluating combination therapy for pulmonary artery hypertension (PAH) may be longer than what is needed to demonstrate treatment benefit, results of a recent meta-analysis suggest.
, according to results of the study published in the May issue of the journal Chest®.
The meta-analysis by Dr. Lajoie and her colleagues included 3,801 patients enrolled in one of 15 previously published randomized clinical trials. Of those trials, four were long-term, event driven studies, with a mean duration of 87 weeks, while the remainder were shorter studies with a mean duration of 15 weeks.
For the long-term, event-driven trials, the mean number needed to treat (NNT) was 17.4 at week 16, gradually decreasing to 8.8 at 52 weeks of follow-up, remaining stable after that, according to investigators.
Consistent with that finding, the mean relative risk of clinical worsening was 0.38 at 16 weeks, and similarly, 0.41 at 26 weeks, investigators reported. After that, the relative risk progressively increased to 0.54 at 52 weeks and 0.68 at 104 weeks.
Looking at all trials combined, Dr. Lajoie and her colleagues observed that longer trial duration had a positive correlation with relative risk of clinical worsening (P = .0002).
Pragmatically, these results raise the possibility that PAH combination therapy trials could be shorter in duration. Some recent event-driven studies have lasted up to 6 years, with patients on treatment for about 2 of those years, investigators noted.
“In the context of an orphan disease with limited and competing recruitment for trials and the rapidly changing treatment paradigm in PAH, the optimal duration of future trials should be revisited,” Dr. Lajoie and her colleagues wrote in a discussion of their findings.
They also cautioned that NNT, a measure of how many patient treatments are needed to prevent one additional adverse event, could be “misleading” despite its value as a simple measure of treatment impact.
Likewise, relative risk can be misleading; for example, a treatment reducing event risk from 30% to 20% represents a relative risk reduction of approximately 35%, but so does a treatment reducing event risk from 3% to 2%, the researchers noted.
“Multiple factors, in addition to the efficacy of the therapy and the comparator, may directly influence the NNT and relative risk and should be taken into account in their interpretation,” they said in their report.
Dr. Lajoie had no disclosures related to the study. Her coauthors had disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among others.
SOURCE: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.
Key clinical point: A meta-analysis calls into question the need to perform pulmonary arterial hypertension (PAH) trials beyond 6 to 12 months of treatment in the future.
Major finding: The mean number needed to treat was stable at 52 weeks of follow-up and thereafter, while the mean relative risk of clinical worsening progressively increased from approximately 0.38 at week 16 to 0.68 at week 104.
Study details: A systematic review of 3,801 patients enrolled in 15 randomized clinical trials.
Disclosures: The authors reported disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among other entities.
Source: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.
Key clinical point: A meta-analysis calls into question the need to perform pulmonary arterial hypertension (PAH) trials beyond 6 to 12 months of treatment in the future.
Major finding: The mean number needed to treat was stable at 52 weeks of follow-up and thereafter, while the mean relative risk of clinical worsening progressively increased from approximately 0.38 at week 16 to 0.68 at week 104.
Study details: A systematic review of 3,801 patients enrolled in 15 randomized clinical trials.
Disclosures: The authors reported disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among other entities.
Source: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.
Key clinical point: A meta-analysis calls into question the need to perform pulmonary arterial hypertension (PAH) trials beyond 6 to 12 months of treatment in the future.
Major finding: The mean number needed to treat was stable at 52 weeks of follow-up and thereafter, while the mean relative risk of clinical worsening progressively increased from approximately 0.38 at week 16 to 0.68 at week 104.
Study details: A systematic review of 3,801 patients enrolled in 15 randomized clinical trials.
Disclosures: The authors reported disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among other entities.
Source: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.
Current clinical trials evaluating combination therapy for pulmonary artery hypertension (PAH) may be longer than what is needed to demonstrate treatment benefit, results of a recent meta-analysis suggest.
, according to results of the study published in the May issue of the journal Chest®.
The meta-analysis by Dr. Lajoie and her colleagues included 3,801 patients enrolled in one of 15 previously published randomized clinical trials. Of those trials, four were long-term, event driven studies, with a mean duration of 87 weeks, while the remainder were shorter studies with a mean duration of 15 weeks.
For the long-term, event-driven trials, the mean number needed to treat (NNT) was 17.4 at week 16, gradually decreasing to 8.8 at 52 weeks of follow-up, remaining stable after that, according to investigators.
Consistent with that finding, the mean relative risk of clinical worsening was 0.38 at 16 weeks, and similarly, 0.41 at 26 weeks, investigators reported. After that, the relative risk progressively increased to 0.54 at 52 weeks and 0.68 at 104 weeks.
Looking at all trials combined, Dr. Lajoie and her colleagues observed that longer trial duration had a positive correlation with relative risk of clinical worsening (P = .0002).
Pragmatically, these results raise the possibility that PAH combination therapy trials could be shorter in duration. Some recent event-driven studies have lasted up to 6 years, with patients on treatment for about 2 of those years, investigators noted.
“In the context of an orphan disease with limited and competing recruitment for trials and the rapidly changing treatment paradigm in PAH, the optimal duration of future trials should be revisited,” Dr. Lajoie and her colleagues wrote in a discussion of their findings.
They also cautioned that NNT, a measure of how many patient treatments are needed to prevent one additional adverse event, could be “misleading” despite its value as a simple measure of treatment impact.
Likewise, relative risk can be misleading; for example, a treatment reducing event risk from 30% to 20% represents a relative risk reduction of approximately 35%, but so does a treatment reducing event risk from 3% to 2%, the researchers noted.
“Multiple factors, in addition to the efficacy of the therapy and the comparator, may directly influence the NNT and relative risk and should be taken into account in their interpretation,” they said in their report.
Dr. Lajoie had no disclosures related to the study. Her coauthors had disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among others.
SOURCE: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.
Current clinical trials evaluating combination therapy for pulmonary artery hypertension (PAH) may be longer than what is needed to demonstrate treatment benefit, results of a recent meta-analysis suggest.
, according to results of the study published in the May issue of the journal Chest®.
The meta-analysis by Dr. Lajoie and her colleagues included 3,801 patients enrolled in one of 15 previously published randomized clinical trials. Of those trials, four were long-term, event driven studies, with a mean duration of 87 weeks, while the remainder were shorter studies with a mean duration of 15 weeks.
For the long-term, event-driven trials, the mean number needed to treat (NNT) was 17.4 at week 16, gradually decreasing to 8.8 at 52 weeks of follow-up, remaining stable after that, according to investigators.
Consistent with that finding, the mean relative risk of clinical worsening was 0.38 at 16 weeks, and similarly, 0.41 at 26 weeks, investigators reported. After that, the relative risk progressively increased to 0.54 at 52 weeks and 0.68 at 104 weeks.
Looking at all trials combined, Dr. Lajoie and her colleagues observed that longer trial duration had a positive correlation with relative risk of clinical worsening (P = .0002).
Pragmatically, these results raise the possibility that PAH combination therapy trials could be shorter in duration. Some recent event-driven studies have lasted up to 6 years, with patients on treatment for about 2 of those years, investigators noted.
“In the context of an orphan disease with limited and competing recruitment for trials and the rapidly changing treatment paradigm in PAH, the optimal duration of future trials should be revisited,” Dr. Lajoie and her colleagues wrote in a discussion of their findings.
They also cautioned that NNT, a measure of how many patient treatments are needed to prevent one additional adverse event, could be “misleading” despite its value as a simple measure of treatment impact.
Likewise, relative risk can be misleading; for example, a treatment reducing event risk from 30% to 20% represents a relative risk reduction of approximately 35%, but so does a treatment reducing event risk from 3% to 2%, the researchers noted.
“Multiple factors, in addition to the efficacy of the therapy and the comparator, may directly influence the NNT and relative risk and should be taken into account in their interpretation,” they said in their report.
Dr. Lajoie had no disclosures related to the study. Her coauthors had disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among others.
SOURCE: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.
FROM CHEST®
When and how to suspect asthma misdiagnosis
NEW ORLEANS – Kyle I. Happel, MD, said at the annual meeting of the American College of Physicians.
“Asthma is a disease whose symptoms are caused by variable airflow obstruction. It varies throughout the day, usually, and certainly by the week or by the month. I want you to think about the variability of a patient’s disease symptoms in forming your index of suspicion for this disease,” urged Dr. Happel, of the section of pulmonary, critical care, and allergy/immunology at Louisiana State University Medical Center in New Orleans.
These phenomena occur often. In a Canadian multicenter study of more than 700 patients with a history of physician-diagnosed asthma within the past 5 years, current asthma was ruled out in fully 33% of them on the basis of no deterioration of asthma symptoms, no evidence of reversible airway obstruction, and no bronchial hyperresponsiveness after all asthma drugs were tapered off (JAMA. 2017 Jan 17;317[3]:269-79).
Wheezing is the most specific symptom of asthma, although it is not, in fact, terribly specific. In descending order, the next most specific symptoms are breathlessness, chest tightness, and cough.
The top seven diseases that mimic asthma symptoms are chronic obstructive pulmonary disease, rhinosinusitis, heart failure with preserved or reduced ejection fraction, gastroesophageal reflux disease, angina, anxiety, and vocal cord dysfunction syndrome.
Strike two for an asthma diagnosis is a patient’s report that albuterol doesn’t improve the symptoms. That definitely raises questions about the diagnosis.
“Most asthmatics get symptomatic relief from their disease,” Dr. Happel observed.
And, if there is no indication in the patient’s chart that the asthma diagnosis was based upon demonstration of airflow obstruction on spirometry, the diagnosis is thrown further into doubt. In the recent Canadian study, patients who didn’t undergo pulmonary function testing (PFT) to establish airflow limitation at their time of diagnosis were significantly less likely to have current asthma.
“I would strongly suggest everyone with the diagnosis of asthma get spirometry with bronchodilator testing,” Dr. Happel said. “Good-quality PFTs are critical in forming a solid diagnosis of asthma.”
In a patient who has symptoms consistent with asthma, a 200-cc and 12% or more improvement in forced expiratory volume in 1 second (FEV1) in response to bronchodilator challenge is supportive of the diagnosis. However, absence of reversible airway obstruction doesn’t exclude the possibility of asthma.
In the setting of low to-moderate clinical suspicion of asthma plus no demonstrable obstruction on spirometry, Dr. Happel recommends moving on to bronchial hyperreactivity testing via a methacholine challenge.
“The beauty of a methacholine challenge is that is has a high negative predictive value to help exclude the diagnosis of asthma, particularly in people who are having symptoms suggestive of asthma,” Dr. Happel explained. “If it takes more than 8 mg/mL of methacholine to elicit a 20% or greater decrease in FEV1, it’s probably something else. It’s not a particularly specific test, though; you can get false positives from a methacholine challenge.”
NEW ORLEANS – Kyle I. Happel, MD, said at the annual meeting of the American College of Physicians.
“Asthma is a disease whose symptoms are caused by variable airflow obstruction. It varies throughout the day, usually, and certainly by the week or by the month. I want you to think about the variability of a patient’s disease symptoms in forming your index of suspicion for this disease,” urged Dr. Happel, of the section of pulmonary, critical care, and allergy/immunology at Louisiana State University Medical Center in New Orleans.
These phenomena occur often. In a Canadian multicenter study of more than 700 patients with a history of physician-diagnosed asthma within the past 5 years, current asthma was ruled out in fully 33% of them on the basis of no deterioration of asthma symptoms, no evidence of reversible airway obstruction, and no bronchial hyperresponsiveness after all asthma drugs were tapered off (JAMA. 2017 Jan 17;317[3]:269-79).
Wheezing is the most specific symptom of asthma, although it is not, in fact, terribly specific. In descending order, the next most specific symptoms are breathlessness, chest tightness, and cough.
The top seven diseases that mimic asthma symptoms are chronic obstructive pulmonary disease, rhinosinusitis, heart failure with preserved or reduced ejection fraction, gastroesophageal reflux disease, angina, anxiety, and vocal cord dysfunction syndrome.
Strike two for an asthma diagnosis is a patient’s report that albuterol doesn’t improve the symptoms. That definitely raises questions about the diagnosis.
“Most asthmatics get symptomatic relief from their disease,” Dr. Happel observed.
And, if there is no indication in the patient’s chart that the asthma diagnosis was based upon demonstration of airflow obstruction on spirometry, the diagnosis is thrown further into doubt. In the recent Canadian study, patients who didn’t undergo pulmonary function testing (PFT) to establish airflow limitation at their time of diagnosis were significantly less likely to have current asthma.
“I would strongly suggest everyone with the diagnosis of asthma get spirometry with bronchodilator testing,” Dr. Happel said. “Good-quality PFTs are critical in forming a solid diagnosis of asthma.”
In a patient who has symptoms consistent with asthma, a 200-cc and 12% or more improvement in forced expiratory volume in 1 second (FEV1) in response to bronchodilator challenge is supportive of the diagnosis. However, absence of reversible airway obstruction doesn’t exclude the possibility of asthma.
In the setting of low to-moderate clinical suspicion of asthma plus no demonstrable obstruction on spirometry, Dr. Happel recommends moving on to bronchial hyperreactivity testing via a methacholine challenge.
“The beauty of a methacholine challenge is that is has a high negative predictive value to help exclude the diagnosis of asthma, particularly in people who are having symptoms suggestive of asthma,” Dr. Happel explained. “If it takes more than 8 mg/mL of methacholine to elicit a 20% or greater decrease in FEV1, it’s probably something else. It’s not a particularly specific test, though; you can get false positives from a methacholine challenge.”
NEW ORLEANS – Kyle I. Happel, MD, said at the annual meeting of the American College of Physicians.
“Asthma is a disease whose symptoms are caused by variable airflow obstruction. It varies throughout the day, usually, and certainly by the week or by the month. I want you to think about the variability of a patient’s disease symptoms in forming your index of suspicion for this disease,” urged Dr. Happel, of the section of pulmonary, critical care, and allergy/immunology at Louisiana State University Medical Center in New Orleans.
These phenomena occur often. In a Canadian multicenter study of more than 700 patients with a history of physician-diagnosed asthma within the past 5 years, current asthma was ruled out in fully 33% of them on the basis of no deterioration of asthma symptoms, no evidence of reversible airway obstruction, and no bronchial hyperresponsiveness after all asthma drugs were tapered off (JAMA. 2017 Jan 17;317[3]:269-79).
Wheezing is the most specific symptom of asthma, although it is not, in fact, terribly specific. In descending order, the next most specific symptoms are breathlessness, chest tightness, and cough.
The top seven diseases that mimic asthma symptoms are chronic obstructive pulmonary disease, rhinosinusitis, heart failure with preserved or reduced ejection fraction, gastroesophageal reflux disease, angina, anxiety, and vocal cord dysfunction syndrome.
Strike two for an asthma diagnosis is a patient’s report that albuterol doesn’t improve the symptoms. That definitely raises questions about the diagnosis.
“Most asthmatics get symptomatic relief from their disease,” Dr. Happel observed.
And, if there is no indication in the patient’s chart that the asthma diagnosis was based upon demonstration of airflow obstruction on spirometry, the diagnosis is thrown further into doubt. In the recent Canadian study, patients who didn’t undergo pulmonary function testing (PFT) to establish airflow limitation at their time of diagnosis were significantly less likely to have current asthma.
“I would strongly suggest everyone with the diagnosis of asthma get spirometry with bronchodilator testing,” Dr. Happel said. “Good-quality PFTs are critical in forming a solid diagnosis of asthma.”
In a patient who has symptoms consistent with asthma, a 200-cc and 12% or more improvement in forced expiratory volume in 1 second (FEV1) in response to bronchodilator challenge is supportive of the diagnosis. However, absence of reversible airway obstruction doesn’t exclude the possibility of asthma.
In the setting of low to-moderate clinical suspicion of asthma plus no demonstrable obstruction on spirometry, Dr. Happel recommends moving on to bronchial hyperreactivity testing via a methacholine challenge.
“The beauty of a methacholine challenge is that is has a high negative predictive value to help exclude the diagnosis of asthma, particularly in people who are having symptoms suggestive of asthma,” Dr. Happel explained. “If it takes more than 8 mg/mL of methacholine to elicit a 20% or greater decrease in FEV1, it’s probably something else. It’s not a particularly specific test, though; you can get false positives from a methacholine challenge.”
REPORTING FROM ACP INTERNAL MEDICINE
ED visits higher among pediatric asthma patients with comorbid depression, anxiety
TORONTO – Children with asthma who have a comorbid diagnosis of anxiety or depression are significantly more likely to make asthma-related visits to the emergency department, compared with their peers who do not have a mental health condition, results from a large administrative data analysis showed.
“There has been a fair bit of research on how comorbid mental health conditions can affect health care utilization for asthma in adults, but few studies have examined how comorbid mental health conditions like anxiety or depression can affect children with asthma,” one of the study authors, Caroline Neel, said in an interview in advance of the Pediatric Academic Societies meeting.
In all, the researchers identified 71,326 patients with asthma, with an overall rate of 16.3 ED visits per 100 child-years. Among these, children with a diagnosis of depression had significantly higher rates of ED visits (21.5 visits per 100 child-years; P less than .01), as did those with a diagnosis of anxiety (19.5 ED visits per 100 child-years; P less than .01). Being enrolled in a Medicaid managed care plan or Medicaid fee-for-service plan also increased the rates of asthma-related ED visits (20.3 and 21.5 ED visits per 100 child-years, respectively; P less than .01 for both associations.)
“We were surprised to see that anxiety and depression seemed to increase asthma emergency department visits as much as other medical chronic illnesses like cystic fibrosis or sickle cell disease, and that kids on Medicaid, who tend to be our poorer kids, also had an independent risk of going to the emergency department,” Ms. Neel said. “Having Medicaid as well as anxiety or depression were independently related to going to the emergency room for asthma, so the study suggests that some of our highest-risk kids for asthma have multiple different contributors to getting sick and needing to go to the emergency room for an asthma attack.”
She acknowledged certain limitations of the analysis, including its reliance on administrative claims data to identify whether or not children had a diagnosis of anxiety or depression. “This doesn’t necessarily identify all the kids who may have these mental health conditions, since sometimes providers are less likely to document a diagnosis of a mental health conditions for children,” she said. “However, we still saw a significant association between a comorbid mental health condition and emergency department use for asthma, despite the potential that mental health conditions may have been under reported.”
The study’s senior author was Naomi Bardach, MD. The researchers reported having no financial disclosures.
TORONTO – Children with asthma who have a comorbid diagnosis of anxiety or depression are significantly more likely to make asthma-related visits to the emergency department, compared with their peers who do not have a mental health condition, results from a large administrative data analysis showed.
“There has been a fair bit of research on how comorbid mental health conditions can affect health care utilization for asthma in adults, but few studies have examined how comorbid mental health conditions like anxiety or depression can affect children with asthma,” one of the study authors, Caroline Neel, said in an interview in advance of the Pediatric Academic Societies meeting.
In all, the researchers identified 71,326 patients with asthma, with an overall rate of 16.3 ED visits per 100 child-years. Among these, children with a diagnosis of depression had significantly higher rates of ED visits (21.5 visits per 100 child-years; P less than .01), as did those with a diagnosis of anxiety (19.5 ED visits per 100 child-years; P less than .01). Being enrolled in a Medicaid managed care plan or Medicaid fee-for-service plan also increased the rates of asthma-related ED visits (20.3 and 21.5 ED visits per 100 child-years, respectively; P less than .01 for both associations.)
“We were surprised to see that anxiety and depression seemed to increase asthma emergency department visits as much as other medical chronic illnesses like cystic fibrosis or sickle cell disease, and that kids on Medicaid, who tend to be our poorer kids, also had an independent risk of going to the emergency department,” Ms. Neel said. “Having Medicaid as well as anxiety or depression were independently related to going to the emergency room for asthma, so the study suggests that some of our highest-risk kids for asthma have multiple different contributors to getting sick and needing to go to the emergency room for an asthma attack.”
She acknowledged certain limitations of the analysis, including its reliance on administrative claims data to identify whether or not children had a diagnosis of anxiety or depression. “This doesn’t necessarily identify all the kids who may have these mental health conditions, since sometimes providers are less likely to document a diagnosis of a mental health conditions for children,” she said. “However, we still saw a significant association between a comorbid mental health condition and emergency department use for asthma, despite the potential that mental health conditions may have been under reported.”
The study’s senior author was Naomi Bardach, MD. The researchers reported having no financial disclosures.
TORONTO – Children with asthma who have a comorbid diagnosis of anxiety or depression are significantly more likely to make asthma-related visits to the emergency department, compared with their peers who do not have a mental health condition, results from a large administrative data analysis showed.
“There has been a fair bit of research on how comorbid mental health conditions can affect health care utilization for asthma in adults, but few studies have examined how comorbid mental health conditions like anxiety or depression can affect children with asthma,” one of the study authors, Caroline Neel, said in an interview in advance of the Pediatric Academic Societies meeting.
In all, the researchers identified 71,326 patients with asthma, with an overall rate of 16.3 ED visits per 100 child-years. Among these, children with a diagnosis of depression had significantly higher rates of ED visits (21.5 visits per 100 child-years; P less than .01), as did those with a diagnosis of anxiety (19.5 ED visits per 100 child-years; P less than .01). Being enrolled in a Medicaid managed care plan or Medicaid fee-for-service plan also increased the rates of asthma-related ED visits (20.3 and 21.5 ED visits per 100 child-years, respectively; P less than .01 for both associations.)
“We were surprised to see that anxiety and depression seemed to increase asthma emergency department visits as much as other medical chronic illnesses like cystic fibrosis or sickle cell disease, and that kids on Medicaid, who tend to be our poorer kids, also had an independent risk of going to the emergency department,” Ms. Neel said. “Having Medicaid as well as anxiety or depression were independently related to going to the emergency room for asthma, so the study suggests that some of our highest-risk kids for asthma have multiple different contributors to getting sick and needing to go to the emergency room for an asthma attack.”
She acknowledged certain limitations of the analysis, including its reliance on administrative claims data to identify whether or not children had a diagnosis of anxiety or depression. “This doesn’t necessarily identify all the kids who may have these mental health conditions, since sometimes providers are less likely to document a diagnosis of a mental health conditions for children,” she said. “However, we still saw a significant association between a comorbid mental health condition and emergency department use for asthma, despite the potential that mental health conditions may have been under reported.”
The study’s senior author was Naomi Bardach, MD. The researchers reported having no financial disclosures.
Key clinical point: Anxiety and depression are associated with higher rates of ED use in children with asthma.
Major finding: (21.5 visits per 100 child-years; P less than .01), as did those with a diagnosis of anxiety (19.5 ED visits per 100 child-years; P less than .01).
Study details: An analysis of 71,326 patients with asthma from the Massachusetts All Payer Claims Database for 2014-2015.
Disclosures: The researchers reported having no financial disclosures.
Interferon-gamma release assay trumps tuberculin skin test in school-aged children
The interferon-gamma release assay (IGRA) was significantly more sensitive than a tuberculin skin test as an adjunct tuberculosis diagnosis of children aged 5 years and older, according to data from a population-based study of 778 cases.
IGRAs have shown greater specificity than tuberculin skin tests (TSTs), but data on their sensitivity to TB in children are limited, wrote Alexander W. Kay, MD, of the California Department of Public Health and his colleagues in a study published in Pediatrics.
Children younger than 1 year of age and those with CNS disease were significantly more likely to have indeterminate IGRA results, the researchers noted.
The study results were limited by the use of mainly enzyme-linked immunosorbent assay–based IGRA, which limited the data on enzyme-linked immunospot tests, the researchers said. The findings also were limited by the small number of children younger than 5 years.
However, the study is the largest North American analysis of IGRA in children, and based on the findings, “we argue that an IGRA should be considered the test of choice when evaluating children 5-18 years old for TB disease in high-resource, low-TB burden settings,” Dr. Kay and his associates wrote.
The study was funded by the Centers for Disease Control and Prevention. Coauthor Shamim Islam, MD, disclosed financial support from Qiagen, maker of the QuantiFERON test. Dr. Kay and the other investigators had no financial conflicts to disclose.
SOURCE: Kay A et al. Pediatrics. 2018 May 4. doi: 10.1542/peds.2017-3918.
The interferon-gamma release assay (IGRA) was significantly more sensitive than a tuberculin skin test as an adjunct tuberculosis diagnosis of children aged 5 years and older, according to data from a population-based study of 778 cases.
IGRAs have shown greater specificity than tuberculin skin tests (TSTs), but data on their sensitivity to TB in children are limited, wrote Alexander W. Kay, MD, of the California Department of Public Health and his colleagues in a study published in Pediatrics.
Children younger than 1 year of age and those with CNS disease were significantly more likely to have indeterminate IGRA results, the researchers noted.
The study results were limited by the use of mainly enzyme-linked immunosorbent assay–based IGRA, which limited the data on enzyme-linked immunospot tests, the researchers said. The findings also were limited by the small number of children younger than 5 years.
However, the study is the largest North American analysis of IGRA in children, and based on the findings, “we argue that an IGRA should be considered the test of choice when evaluating children 5-18 years old for TB disease in high-resource, low-TB burden settings,” Dr. Kay and his associates wrote.
The study was funded by the Centers for Disease Control and Prevention. Coauthor Shamim Islam, MD, disclosed financial support from Qiagen, maker of the QuantiFERON test. Dr. Kay and the other investigators had no financial conflicts to disclose.
SOURCE: Kay A et al. Pediatrics. 2018 May 4. doi: 10.1542/peds.2017-3918.
The interferon-gamma release assay (IGRA) was significantly more sensitive than a tuberculin skin test as an adjunct tuberculosis diagnosis of children aged 5 years and older, according to data from a population-based study of 778 cases.
IGRAs have shown greater specificity than tuberculin skin tests (TSTs), but data on their sensitivity to TB in children are limited, wrote Alexander W. Kay, MD, of the California Department of Public Health and his colleagues in a study published in Pediatrics.
Children younger than 1 year of age and those with CNS disease were significantly more likely to have indeterminate IGRA results, the researchers noted.
The study results were limited by the use of mainly enzyme-linked immunosorbent assay–based IGRA, which limited the data on enzyme-linked immunospot tests, the researchers said. The findings also were limited by the small number of children younger than 5 years.
However, the study is the largest North American analysis of IGRA in children, and based on the findings, “we argue that an IGRA should be considered the test of choice when evaluating children 5-18 years old for TB disease in high-resource, low-TB burden settings,” Dr. Kay and his associates wrote.
The study was funded by the Centers for Disease Control and Prevention. Coauthor Shamim Islam, MD, disclosed financial support from Qiagen, maker of the QuantiFERON test. Dr. Kay and the other investigators had no financial conflicts to disclose.
SOURCE: Kay A et al. Pediatrics. 2018 May 4. doi: 10.1542/peds.2017-3918.
FROM PEDIATRICS
Key clinical point:
Major finding: Sensitivity was 96% for IGRA versus 83% for TST among children aged 5-18 years.
Study details: The data come from TB patients aged 18 years and younger enrolled in the California TB registry during 2010-2015.
Disclosures: The study was funded by the Centers for Disease Control and Prevention. Coauthor Shamim Islam, MD, disclosed financial support from Qiagen, maker of the QuantiFERON test; Dr. Kay and the other investigators had no financial conflicts to disclose.
Source: Kay A et al. Pediatrics. 2018 May 4. doi: 10. 1542/ peds. 2017- 3918.
In COPD, tai chi confers long-term benefit
and seems to confer better long-term improvement, suggests a study published online in the journal CHEST®.
Following 12 weeks of participation in tai chi or pulmonary rehabilitation, patients improved in most of the measurements taken, although no significant between-group differences were observed at that time. However, further improvements were observed in the tai chi group 12 weeks after the intervention had ended. These improvements manifested as a statistically significant 4.5 between-group difference in St. George’s Respiratory Questionnaire points in favor of tai chi (P less than .001)
“This observation, supported also by improvements in dyspnea and exercise performance, suggests that tai chi could be substituted for PR [pulmonary rehabilitation] in the treatment of COPD with greater convenience for patients,” the researchers concluded.
SOURCE: Polkey MI et al. CHEST. 2018 May;153[5]:1116-24.
and seems to confer better long-term improvement, suggests a study published online in the journal CHEST®.
Following 12 weeks of participation in tai chi or pulmonary rehabilitation, patients improved in most of the measurements taken, although no significant between-group differences were observed at that time. However, further improvements were observed in the tai chi group 12 weeks after the intervention had ended. These improvements manifested as a statistically significant 4.5 between-group difference in St. George’s Respiratory Questionnaire points in favor of tai chi (P less than .001)
“This observation, supported also by improvements in dyspnea and exercise performance, suggests that tai chi could be substituted for PR [pulmonary rehabilitation] in the treatment of COPD with greater convenience for patients,” the researchers concluded.
SOURCE: Polkey MI et al. CHEST. 2018 May;153[5]:1116-24.
and seems to confer better long-term improvement, suggests a study published online in the journal CHEST®.
Following 12 weeks of participation in tai chi or pulmonary rehabilitation, patients improved in most of the measurements taken, although no significant between-group differences were observed at that time. However, further improvements were observed in the tai chi group 12 weeks after the intervention had ended. These improvements manifested as a statistically significant 4.5 between-group difference in St. George’s Respiratory Questionnaire points in favor of tai chi (P less than .001)
“This observation, supported also by improvements in dyspnea and exercise performance, suggests that tai chi could be substituted for PR [pulmonary rehabilitation] in the treatment of COPD with greater convenience for patients,” the researchers concluded.
SOURCE: Polkey MI et al. CHEST. 2018 May;153[5]:1116-24.
FROM THE JOURNAL CHEST®