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Survival ‘excellent’ after rituximab-bendamustine induction in transplant-eligible MCL
The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.
The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.
By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.
“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.
The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.
In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.
The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.
Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.
With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.
The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.
MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.
In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.
The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.
SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.
The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.
The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.
By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.
“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.
The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.
In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.
The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.
Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.
With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.
The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.
MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.
In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.
The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.
SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.
The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.
The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.
By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.
“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.
The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.
In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.
The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.
Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.
With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.
The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.
MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.
In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.
The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.
SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.
FROM BLOOD ADVANCES
Inhaled nitric oxide improves activity in pulmonary fibrosis patients at risk of PH
NEW ORLEANS – In patients with interstitial lung diseases at risk of pulmonary hypertension, inhaled nitric oxide produced meaningful improvements in activity that have been maintained over the long term, an investigator reported here.
Inhaled nitric oxide, which improved moderate to vigorous physical activity by 34% versus placebo in an 8-week controlled trial, has demonstrated long-term maintenance of activity parameters in open-label extension data, presented at the annual meeting of the American College of Chest Physicians.
The treatment was safe and well tolerated in this cohort of subjects at risk of pulmonary hypertension associated with pulmonary fibrosis (PH-PF), said Steven D. Nathan, MD, director of the advanced lung disease and lung transplant program at Inova Fairfax (Va.) Hospital.
The findings to date suggest inhaled nitric oxide (iNO) is a potentially effective treatment option for patients at risk for pulmonary hypertension, which is associated with poor outcomes in various forms of interstitial lung disease, Dr. Nathan said in his presentation, adding that a second cohort of PH-PF patients has been fully recruited and continue to be followed.
“Hopefully, once we show that iNO is positive and validate what we’ve seen with cohort one, then we’ll be moving on to cohort three, which will be a pivotal phase 3 clinical study with actigraphy activity–monitoring being the primary endpoint, and that has been agreed upon by the Food and Drug Administration,” he said.
The actigraph device used in the study, worn on the wrist of the nondominant arm, continuously measures patient movement in acceleration units and allows for categorization of intensity, from sedentary to vigorous, Dr. Nathan explained in this presentation.
“To me, actigraphy activity–monitoring is kind of a step beyond the 6-minute walk test,” he said. “We get a sense of how [patients] might function, based on the 6-minute walk test, but what actigraphy gives us is actually how they do function once they leave the clinic. So I think this is emerging as a very viable and valuable endpoint in clinical trials.”
Dr. Nathan reported on 23 patients with a variety of pulmonary fibrotic interstitial lung diseases randomized to receive iNO 30 mcg/kg based on their ideal body weight (IBW) per hour, and 18 who were randomized to placebo, for 8 weeks of blinded treatment. After that, patients from both arms transitioned to open-label treatment, stepping up to 45 mcg/kg IBW/hr for at least 8 weeks, and then to 75 mcg/kg IBW/hr.
After the 8 weeks of blinded treatment, activity as measured by actigraphy was maintained in the patients receiving iNO, and decreased in the placebo arm (P = .05), according to Dr. Nathan, who added that this difference was largely driven by changes in levels of moderate to vigorous physical activity, which improved in the treatment arm, while declining substantially in the placebo arm.
Clinically significant improvements in moderate to vigorous physical activity were seen in 23.1% of patients in the treatment arm and 0% of the placebo arm, while clinically significant declines in that measure were seen in 38.5% of the treatment group versus 71.4% of the placebo group.
Data from the open-label extension phase, which included a total of 18 patients, show that activity was “well maintained” over a total of 20 weeks, with patients formerly in the placebo arm demonstrating levels of activity comparable to what was achieved in the patients randomized to treatment: “We felt like this supports the clinical efficacy of the nitric oxide effect, that the placebo arm started to behave like the treatment arm,” Dr. Nathan said.
Some adverse events were reported in the study, but none were felt to be attributable to the iNO, according to Dr. Nathan.
Dr. Nathan provided disclosures related to Roche-Genentech, Boehringer Ingelheim, Promedior, Bellerophon, and United Therapeutics.
SOURCE: Nathan SD et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.308.
NEW ORLEANS – In patients with interstitial lung diseases at risk of pulmonary hypertension, inhaled nitric oxide produced meaningful improvements in activity that have been maintained over the long term, an investigator reported here.
Inhaled nitric oxide, which improved moderate to vigorous physical activity by 34% versus placebo in an 8-week controlled trial, has demonstrated long-term maintenance of activity parameters in open-label extension data, presented at the annual meeting of the American College of Chest Physicians.
The treatment was safe and well tolerated in this cohort of subjects at risk of pulmonary hypertension associated with pulmonary fibrosis (PH-PF), said Steven D. Nathan, MD, director of the advanced lung disease and lung transplant program at Inova Fairfax (Va.) Hospital.
The findings to date suggest inhaled nitric oxide (iNO) is a potentially effective treatment option for patients at risk for pulmonary hypertension, which is associated with poor outcomes in various forms of interstitial lung disease, Dr. Nathan said in his presentation, adding that a second cohort of PH-PF patients has been fully recruited and continue to be followed.
“Hopefully, once we show that iNO is positive and validate what we’ve seen with cohort one, then we’ll be moving on to cohort three, which will be a pivotal phase 3 clinical study with actigraphy activity–monitoring being the primary endpoint, and that has been agreed upon by the Food and Drug Administration,” he said.
The actigraph device used in the study, worn on the wrist of the nondominant arm, continuously measures patient movement in acceleration units and allows for categorization of intensity, from sedentary to vigorous, Dr. Nathan explained in this presentation.
“To me, actigraphy activity–monitoring is kind of a step beyond the 6-minute walk test,” he said. “We get a sense of how [patients] might function, based on the 6-minute walk test, but what actigraphy gives us is actually how they do function once they leave the clinic. So I think this is emerging as a very viable and valuable endpoint in clinical trials.”
Dr. Nathan reported on 23 patients with a variety of pulmonary fibrotic interstitial lung diseases randomized to receive iNO 30 mcg/kg based on their ideal body weight (IBW) per hour, and 18 who were randomized to placebo, for 8 weeks of blinded treatment. After that, patients from both arms transitioned to open-label treatment, stepping up to 45 mcg/kg IBW/hr for at least 8 weeks, and then to 75 mcg/kg IBW/hr.
After the 8 weeks of blinded treatment, activity as measured by actigraphy was maintained in the patients receiving iNO, and decreased in the placebo arm (P = .05), according to Dr. Nathan, who added that this difference was largely driven by changes in levels of moderate to vigorous physical activity, which improved in the treatment arm, while declining substantially in the placebo arm.
Clinically significant improvements in moderate to vigorous physical activity were seen in 23.1% of patients in the treatment arm and 0% of the placebo arm, while clinically significant declines in that measure were seen in 38.5% of the treatment group versus 71.4% of the placebo group.
Data from the open-label extension phase, which included a total of 18 patients, show that activity was “well maintained” over a total of 20 weeks, with patients formerly in the placebo arm demonstrating levels of activity comparable to what was achieved in the patients randomized to treatment: “We felt like this supports the clinical efficacy of the nitric oxide effect, that the placebo arm started to behave like the treatment arm,” Dr. Nathan said.
Some adverse events were reported in the study, but none were felt to be attributable to the iNO, according to Dr. Nathan.
Dr. Nathan provided disclosures related to Roche-Genentech, Boehringer Ingelheim, Promedior, Bellerophon, and United Therapeutics.
SOURCE: Nathan SD et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.308.
NEW ORLEANS – In patients with interstitial lung diseases at risk of pulmonary hypertension, inhaled nitric oxide produced meaningful improvements in activity that have been maintained over the long term, an investigator reported here.
Inhaled nitric oxide, which improved moderate to vigorous physical activity by 34% versus placebo in an 8-week controlled trial, has demonstrated long-term maintenance of activity parameters in open-label extension data, presented at the annual meeting of the American College of Chest Physicians.
The treatment was safe and well tolerated in this cohort of subjects at risk of pulmonary hypertension associated with pulmonary fibrosis (PH-PF), said Steven D. Nathan, MD, director of the advanced lung disease and lung transplant program at Inova Fairfax (Va.) Hospital.
The findings to date suggest inhaled nitric oxide (iNO) is a potentially effective treatment option for patients at risk for pulmonary hypertension, which is associated with poor outcomes in various forms of interstitial lung disease, Dr. Nathan said in his presentation, adding that a second cohort of PH-PF patients has been fully recruited and continue to be followed.
“Hopefully, once we show that iNO is positive and validate what we’ve seen with cohort one, then we’ll be moving on to cohort three, which will be a pivotal phase 3 clinical study with actigraphy activity–monitoring being the primary endpoint, and that has been agreed upon by the Food and Drug Administration,” he said.
The actigraph device used in the study, worn on the wrist of the nondominant arm, continuously measures patient movement in acceleration units and allows for categorization of intensity, from sedentary to vigorous, Dr. Nathan explained in this presentation.
“To me, actigraphy activity–monitoring is kind of a step beyond the 6-minute walk test,” he said. “We get a sense of how [patients] might function, based on the 6-minute walk test, but what actigraphy gives us is actually how they do function once they leave the clinic. So I think this is emerging as a very viable and valuable endpoint in clinical trials.”
Dr. Nathan reported on 23 patients with a variety of pulmonary fibrotic interstitial lung diseases randomized to receive iNO 30 mcg/kg based on their ideal body weight (IBW) per hour, and 18 who were randomized to placebo, for 8 weeks of blinded treatment. After that, patients from both arms transitioned to open-label treatment, stepping up to 45 mcg/kg IBW/hr for at least 8 weeks, and then to 75 mcg/kg IBW/hr.
After the 8 weeks of blinded treatment, activity as measured by actigraphy was maintained in the patients receiving iNO, and decreased in the placebo arm (P = .05), according to Dr. Nathan, who added that this difference was largely driven by changes in levels of moderate to vigorous physical activity, which improved in the treatment arm, while declining substantially in the placebo arm.
Clinically significant improvements in moderate to vigorous physical activity were seen in 23.1% of patients in the treatment arm and 0% of the placebo arm, while clinically significant declines in that measure were seen in 38.5% of the treatment group versus 71.4% of the placebo group.
Data from the open-label extension phase, which included a total of 18 patients, show that activity was “well maintained” over a total of 20 weeks, with patients formerly in the placebo arm demonstrating levels of activity comparable to what was achieved in the patients randomized to treatment: “We felt like this supports the clinical efficacy of the nitric oxide effect, that the placebo arm started to behave like the treatment arm,” Dr. Nathan said.
Some adverse events were reported in the study, but none were felt to be attributable to the iNO, according to Dr. Nathan.
Dr. Nathan provided disclosures related to Roche-Genentech, Boehringer Ingelheim, Promedior, Bellerophon, and United Therapeutics.
SOURCE: Nathan SD et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.308.
REPORTING FROM CHEST 2019
Emicizumab effective in children with hemophilia A and inhibitors
Emicizumab (Hemlibra) is well tolerated and has substantial, clinically meaningful efficacy in pediatric patients with hemophilia A and factor VIII inhibitors, according to an analysis of data from the HAVEN 2 trial in this bispecific humanized monoclonal antibody.
Among those receiving once-weekly emicizumab prophylaxis, 77% had no treated bleeding events and 100% of evaluable target joints resolved in the HAVEN 2 study, which investigators say is the largest prospective study so far of bleed prevention in pediatric patients with hemophilia A and inhibitors.
Moreover, emicizumab resulted in a 99% reduction in bleeding rate versus previous bypassing agent prophylaxis, subsequent, according to an intraindividual comparison described in the report.
Based on these results, emicizumab stands to become the “next-generation standard of care” for pediatric patients with hemophilia A and factor VIII inhibitors, reported Guy Young, MD, of Children’s Hospital Los Angeles and University of Southern California Keck School of Medicine, and his coinvestigators.
“Despite a rapidly evolving treatment landscape in hemophilia, children have been largely excluded from recent trials of novel agents,” they said in the report, which appears in the journal Blood.
Before emicizumab, current treatment options for pediatric patients with factor VIII inhibitors were limited to immune tolerance induction, or use of bypassing agents with efficacy that “can be suboptimal and unpredictable,” said Dr. Young and colleagues.
“More effective prophylactic options with reduced treatment burden are needed,” they said.
Emicizumab works in hemophilia A by bridging activated factor IX and factor X, restoring the function of missing factor VIIIa, according to the report.
A total of 88 male pediatric patients with congenital hemophilia A were enrolled in HAVEN 2, an ongoing phase 3 multicenter study that is nonrandomized and open label. The median age of patients was 7 years (range, 1-15 years). Most participants (97%) had severe hemophilia A, 72% had previously undergone immune tolerance induction, and 75% were receiving treatment with prophylactic bypassing agents.
Most participants received 4 once-weekly loading doses of 3 mg/kg body weight of emicizumab subcutaneously, followed by a maintenance regimen of 1.5 mg/kg weekly.
The annualized bleed rate was 0.3, with 77% of participants having zero bleeding events, for the 65 participants in the trial who were under 12 and received emicizumab 1.5 mg/kg weekly, according to the report.
In the subset of those patients with target joints, the mean annualized bleed rate was 3.3 for the first 24 weeks, and 0 for the next 24 weeks; these findings suggest that bleed rates decrease over time with continuing emicizumab treatment “even in patients with a more severe phenotype,” the investigators wrote.
For 15 patients younger than 12 years of age receiving bypassing agent prophylaxis, emicizumab 1.5 mg/kg once weekly resulted in an annualized bleed rate of 0.3, compared to 21.1 for the prior bypassing agent, which translates into a 99% reduction in bleeding risk, according to investigators.
Annualized bleed rates for patients receiving emicizumab 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks were 0.2 and 2.2, respectively; hover, the numerically higher annualized bleed rate in the 6 mg/kg every-4-weeks group was based on 2 out of the 10 patients treated with that maintenance regimen, including one who had 6 target joint bleeds in the 24 weeks before enrolling in the study, and another who developed antidrug antibodies within the first 8 weeks of emicizumab treatment.
Out of 23 patients who had target joints and received emicizumab prophylaxis for at least 52 weeks, 100% (45 of 45) target joints resolved, according to the report.
“Notably, this is the first report of a treatment resolving target joints in an inhibitor population, which until now has only been reported when using factor VIII products in patients without inhibitors,” Dr. Young and colleagues said.
The most common of the 721 adverse events reported in HAVEN 2 were nasopharyngitis and injection-site reactions. Of 21 serious adverse events, only 1 (antidrug antibodies with neutralizing potential) was thought by investigators to be related to emicizumab.
The Food and Drug Administration (FDA) initially approved emicizumab in November 2017 on the basis of the HAVEN 2 pediatric trial, and on HAVEN 1, a randomized, multicenter, open-label, phase 3 trial including 109 adult and adolescent males with hemophilia A and FVIII inhibitors. The indication for emicizumab was expanded to include patients without inhibitors in October 2018, on the basis of the HAVEN 3 and HAVEN 4 randomized phase 3 trials.
Dr. Young reported disclosures related to Alnylam, Bayer, Bioverativ, CSL Behring, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Shire, Spark, and uniQure.
SOURCE: Young G, et al. Blood. 2019 Oct 10. doi: 10.1182/blood.2019001869.
Emicizumab (Hemlibra) is well tolerated and has substantial, clinically meaningful efficacy in pediatric patients with hemophilia A and factor VIII inhibitors, according to an analysis of data from the HAVEN 2 trial in this bispecific humanized monoclonal antibody.
Among those receiving once-weekly emicizumab prophylaxis, 77% had no treated bleeding events and 100% of evaluable target joints resolved in the HAVEN 2 study, which investigators say is the largest prospective study so far of bleed prevention in pediatric patients with hemophilia A and inhibitors.
Moreover, emicizumab resulted in a 99% reduction in bleeding rate versus previous bypassing agent prophylaxis, subsequent, according to an intraindividual comparison described in the report.
Based on these results, emicizumab stands to become the “next-generation standard of care” for pediatric patients with hemophilia A and factor VIII inhibitors, reported Guy Young, MD, of Children’s Hospital Los Angeles and University of Southern California Keck School of Medicine, and his coinvestigators.
“Despite a rapidly evolving treatment landscape in hemophilia, children have been largely excluded from recent trials of novel agents,” they said in the report, which appears in the journal Blood.
Before emicizumab, current treatment options for pediatric patients with factor VIII inhibitors were limited to immune tolerance induction, or use of bypassing agents with efficacy that “can be suboptimal and unpredictable,” said Dr. Young and colleagues.
“More effective prophylactic options with reduced treatment burden are needed,” they said.
Emicizumab works in hemophilia A by bridging activated factor IX and factor X, restoring the function of missing factor VIIIa, according to the report.
A total of 88 male pediatric patients with congenital hemophilia A were enrolled in HAVEN 2, an ongoing phase 3 multicenter study that is nonrandomized and open label. The median age of patients was 7 years (range, 1-15 years). Most participants (97%) had severe hemophilia A, 72% had previously undergone immune tolerance induction, and 75% were receiving treatment with prophylactic bypassing agents.
Most participants received 4 once-weekly loading doses of 3 mg/kg body weight of emicizumab subcutaneously, followed by a maintenance regimen of 1.5 mg/kg weekly.
The annualized bleed rate was 0.3, with 77% of participants having zero bleeding events, for the 65 participants in the trial who were under 12 and received emicizumab 1.5 mg/kg weekly, according to the report.
In the subset of those patients with target joints, the mean annualized bleed rate was 3.3 for the first 24 weeks, and 0 for the next 24 weeks; these findings suggest that bleed rates decrease over time with continuing emicizumab treatment “even in patients with a more severe phenotype,” the investigators wrote.
For 15 patients younger than 12 years of age receiving bypassing agent prophylaxis, emicizumab 1.5 mg/kg once weekly resulted in an annualized bleed rate of 0.3, compared to 21.1 for the prior bypassing agent, which translates into a 99% reduction in bleeding risk, according to investigators.
Annualized bleed rates for patients receiving emicizumab 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks were 0.2 and 2.2, respectively; hover, the numerically higher annualized bleed rate in the 6 mg/kg every-4-weeks group was based on 2 out of the 10 patients treated with that maintenance regimen, including one who had 6 target joint bleeds in the 24 weeks before enrolling in the study, and another who developed antidrug antibodies within the first 8 weeks of emicizumab treatment.
Out of 23 patients who had target joints and received emicizumab prophylaxis for at least 52 weeks, 100% (45 of 45) target joints resolved, according to the report.
“Notably, this is the first report of a treatment resolving target joints in an inhibitor population, which until now has only been reported when using factor VIII products in patients without inhibitors,” Dr. Young and colleagues said.
The most common of the 721 adverse events reported in HAVEN 2 were nasopharyngitis and injection-site reactions. Of 21 serious adverse events, only 1 (antidrug antibodies with neutralizing potential) was thought by investigators to be related to emicizumab.
The Food and Drug Administration (FDA) initially approved emicizumab in November 2017 on the basis of the HAVEN 2 pediatric trial, and on HAVEN 1, a randomized, multicenter, open-label, phase 3 trial including 109 adult and adolescent males with hemophilia A and FVIII inhibitors. The indication for emicizumab was expanded to include patients without inhibitors in October 2018, on the basis of the HAVEN 3 and HAVEN 4 randomized phase 3 trials.
Dr. Young reported disclosures related to Alnylam, Bayer, Bioverativ, CSL Behring, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Shire, Spark, and uniQure.
SOURCE: Young G, et al. Blood. 2019 Oct 10. doi: 10.1182/blood.2019001869.
Emicizumab (Hemlibra) is well tolerated and has substantial, clinically meaningful efficacy in pediatric patients with hemophilia A and factor VIII inhibitors, according to an analysis of data from the HAVEN 2 trial in this bispecific humanized monoclonal antibody.
Among those receiving once-weekly emicizumab prophylaxis, 77% had no treated bleeding events and 100% of evaluable target joints resolved in the HAVEN 2 study, which investigators say is the largest prospective study so far of bleed prevention in pediatric patients with hemophilia A and inhibitors.
Moreover, emicizumab resulted in a 99% reduction in bleeding rate versus previous bypassing agent prophylaxis, subsequent, according to an intraindividual comparison described in the report.
Based on these results, emicizumab stands to become the “next-generation standard of care” for pediatric patients with hemophilia A and factor VIII inhibitors, reported Guy Young, MD, of Children’s Hospital Los Angeles and University of Southern California Keck School of Medicine, and his coinvestigators.
“Despite a rapidly evolving treatment landscape in hemophilia, children have been largely excluded from recent trials of novel agents,” they said in the report, which appears in the journal Blood.
Before emicizumab, current treatment options for pediatric patients with factor VIII inhibitors were limited to immune tolerance induction, or use of bypassing agents with efficacy that “can be suboptimal and unpredictable,” said Dr. Young and colleagues.
“More effective prophylactic options with reduced treatment burden are needed,” they said.
Emicizumab works in hemophilia A by bridging activated factor IX and factor X, restoring the function of missing factor VIIIa, according to the report.
A total of 88 male pediatric patients with congenital hemophilia A were enrolled in HAVEN 2, an ongoing phase 3 multicenter study that is nonrandomized and open label. The median age of patients was 7 years (range, 1-15 years). Most participants (97%) had severe hemophilia A, 72% had previously undergone immune tolerance induction, and 75% were receiving treatment with prophylactic bypassing agents.
Most participants received 4 once-weekly loading doses of 3 mg/kg body weight of emicizumab subcutaneously, followed by a maintenance regimen of 1.5 mg/kg weekly.
The annualized bleed rate was 0.3, with 77% of participants having zero bleeding events, for the 65 participants in the trial who were under 12 and received emicizumab 1.5 mg/kg weekly, according to the report.
In the subset of those patients with target joints, the mean annualized bleed rate was 3.3 for the first 24 weeks, and 0 for the next 24 weeks; these findings suggest that bleed rates decrease over time with continuing emicizumab treatment “even in patients with a more severe phenotype,” the investigators wrote.
For 15 patients younger than 12 years of age receiving bypassing agent prophylaxis, emicizumab 1.5 mg/kg once weekly resulted in an annualized bleed rate of 0.3, compared to 21.1 for the prior bypassing agent, which translates into a 99% reduction in bleeding risk, according to investigators.
Annualized bleed rates for patients receiving emicizumab 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks were 0.2 and 2.2, respectively; hover, the numerically higher annualized bleed rate in the 6 mg/kg every-4-weeks group was based on 2 out of the 10 patients treated with that maintenance regimen, including one who had 6 target joint bleeds in the 24 weeks before enrolling in the study, and another who developed antidrug antibodies within the first 8 weeks of emicizumab treatment.
Out of 23 patients who had target joints and received emicizumab prophylaxis for at least 52 weeks, 100% (45 of 45) target joints resolved, according to the report.
“Notably, this is the first report of a treatment resolving target joints in an inhibitor population, which until now has only been reported when using factor VIII products in patients without inhibitors,” Dr. Young and colleagues said.
The most common of the 721 adverse events reported in HAVEN 2 were nasopharyngitis and injection-site reactions. Of 21 serious adverse events, only 1 (antidrug antibodies with neutralizing potential) was thought by investigators to be related to emicizumab.
The Food and Drug Administration (FDA) initially approved emicizumab in November 2017 on the basis of the HAVEN 2 pediatric trial, and on HAVEN 1, a randomized, multicenter, open-label, phase 3 trial including 109 adult and adolescent males with hemophilia A and FVIII inhibitors. The indication for emicizumab was expanded to include patients without inhibitors in October 2018, on the basis of the HAVEN 3 and HAVEN 4 randomized phase 3 trials.
Dr. Young reported disclosures related to Alnylam, Bayer, Bioverativ, CSL Behring, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Shire, Spark, and uniQure.
SOURCE: Young G, et al. Blood. 2019 Oct 10. doi: 10.1182/blood.2019001869.
FROM Blood
Virtual visits may cut no-show rate for follow-up HF appointment
PHILADELPHIA – For patients transitioning to home after a heart failure hospitalization, substituting in-person visits with virtual, video-based visits is feasible, safe, and may reduce appointment no-show rates, results of a randomized study suggest.
Connecting patients with clinicians over secure video cut no-show rates at 7 days post-discharge by about one-third, with no difference in risk of readmission, emergency department visits, or death, compared with the traditional in-person follow-up visit, investigator Eiran Z. Gorodeski, MD, MPH, reported here at the annual scientific meeting of the Heart Failure Society of America.
While the video meet-up doesn’t allow for a physical exam, it’s still possible to collect history of what happened since hospital discharge, assess breathing, and complete other aspects of the follow-up visit, according to Dr. Gorodeski, director of advanced heart failure section at the University Hospitals Cleveland Medical Center.
“The way we view use of virtual visits 7 days post-discharge is, in many ways, as a screening platform,” he said in a panel discussion. “If someone seems to be doing poorly, you can always invite them to come in, but most patients post discharge are not congested, and they’re doing quite well. Probably the more relevant issues are things like: Do they have their medications? Do they understand what their follow-up appointments are?”
During the virtual visit, patients are asked to hold their medication bottles up to the camera so the clinician can see what they are taking.
“Frequently, we are able to catch mistakes,” Dr. Gorodeski said. “Of note, most patients don’t bring their pill bottles to the clinic, so in some ways doing the virtual visit for that aspect was more valuable.”
Patients who opt for a virtual visit can do so from any smart phone, laptop, or desktop computer. Once logged in, they enter a virtual waiting room as the clinician receives a text notification to log in and begin the visit.
“It’s very efficient with time, and my questions were answered quickly,” said a patient in a short video Dr. Gorodeski played to illustrate the technology.
“I still feel the same connectivity with the patient,” a clinician in the video said.
There is currently no way to bill insurance companies for this type of visit, Dr. Gorodeski said when asked what initial barriers other institutions might have implementing a similar approach.
In the randomized, single-center clinical trial Dr. Gorodeski presented here at the HFSA meeting, called VIV-HF (Virtual Visits in Heart Failure Care Transitions), a total of 108 patients were randomized to the virtual visit (52 patients) or an in-person visit (56 patients).
The majority of patients (over 60%) had heart failure with reduced ejection fraction, according to the reported study results.
No-show rates were 50% for the in-person visit, and 34.6% for the virtual visit, for a relative risk reduction of 31%. However, this difference did not reach statistical significance, likely because the study was underpowered, according to Dr. Gorodeski.
“This strategy may reduce postdischarge appointment no-show rates, and this needs to be studied further in larger and appropriately powered clinical trials,” he said in presenting the results.
The 7-day postdischarge outpatient clinic visit is recommended in guidelines and viewed as a way to increase care engagement while reducing risk of poor outcomes, according to VIV-HF investigators.
Support for the study came from the Hunnell Fund. Dr. Gorodeski reported being a consultant and advisor to Abbott.
cardnews@mdedge
SOURCE: Gorodeski EZ, et al. HFSA 2019. Late-Breaking Clinical Trials session.
PHILADELPHIA – For patients transitioning to home after a heart failure hospitalization, substituting in-person visits with virtual, video-based visits is feasible, safe, and may reduce appointment no-show rates, results of a randomized study suggest.
Connecting patients with clinicians over secure video cut no-show rates at 7 days post-discharge by about one-third, with no difference in risk of readmission, emergency department visits, or death, compared with the traditional in-person follow-up visit, investigator Eiran Z. Gorodeski, MD, MPH, reported here at the annual scientific meeting of the Heart Failure Society of America.
While the video meet-up doesn’t allow for a physical exam, it’s still possible to collect history of what happened since hospital discharge, assess breathing, and complete other aspects of the follow-up visit, according to Dr. Gorodeski, director of advanced heart failure section at the University Hospitals Cleveland Medical Center.
“The way we view use of virtual visits 7 days post-discharge is, in many ways, as a screening platform,” he said in a panel discussion. “If someone seems to be doing poorly, you can always invite them to come in, but most patients post discharge are not congested, and they’re doing quite well. Probably the more relevant issues are things like: Do they have their medications? Do they understand what their follow-up appointments are?”
During the virtual visit, patients are asked to hold their medication bottles up to the camera so the clinician can see what they are taking.
“Frequently, we are able to catch mistakes,” Dr. Gorodeski said. “Of note, most patients don’t bring their pill bottles to the clinic, so in some ways doing the virtual visit for that aspect was more valuable.”
Patients who opt for a virtual visit can do so from any smart phone, laptop, or desktop computer. Once logged in, they enter a virtual waiting room as the clinician receives a text notification to log in and begin the visit.
“It’s very efficient with time, and my questions were answered quickly,” said a patient in a short video Dr. Gorodeski played to illustrate the technology.
“I still feel the same connectivity with the patient,” a clinician in the video said.
There is currently no way to bill insurance companies for this type of visit, Dr. Gorodeski said when asked what initial barriers other institutions might have implementing a similar approach.
In the randomized, single-center clinical trial Dr. Gorodeski presented here at the HFSA meeting, called VIV-HF (Virtual Visits in Heart Failure Care Transitions), a total of 108 patients were randomized to the virtual visit (52 patients) or an in-person visit (56 patients).
The majority of patients (over 60%) had heart failure with reduced ejection fraction, according to the reported study results.
No-show rates were 50% for the in-person visit, and 34.6% for the virtual visit, for a relative risk reduction of 31%. However, this difference did not reach statistical significance, likely because the study was underpowered, according to Dr. Gorodeski.
“This strategy may reduce postdischarge appointment no-show rates, and this needs to be studied further in larger and appropriately powered clinical trials,” he said in presenting the results.
The 7-day postdischarge outpatient clinic visit is recommended in guidelines and viewed as a way to increase care engagement while reducing risk of poor outcomes, according to VIV-HF investigators.
Support for the study came from the Hunnell Fund. Dr. Gorodeski reported being a consultant and advisor to Abbott.
cardnews@mdedge
SOURCE: Gorodeski EZ, et al. HFSA 2019. Late-Breaking Clinical Trials session.
PHILADELPHIA – For patients transitioning to home after a heart failure hospitalization, substituting in-person visits with virtual, video-based visits is feasible, safe, and may reduce appointment no-show rates, results of a randomized study suggest.
Connecting patients with clinicians over secure video cut no-show rates at 7 days post-discharge by about one-third, with no difference in risk of readmission, emergency department visits, or death, compared with the traditional in-person follow-up visit, investigator Eiran Z. Gorodeski, MD, MPH, reported here at the annual scientific meeting of the Heart Failure Society of America.
While the video meet-up doesn’t allow for a physical exam, it’s still possible to collect history of what happened since hospital discharge, assess breathing, and complete other aspects of the follow-up visit, according to Dr. Gorodeski, director of advanced heart failure section at the University Hospitals Cleveland Medical Center.
“The way we view use of virtual visits 7 days post-discharge is, in many ways, as a screening platform,” he said in a panel discussion. “If someone seems to be doing poorly, you can always invite them to come in, but most patients post discharge are not congested, and they’re doing quite well. Probably the more relevant issues are things like: Do they have their medications? Do they understand what their follow-up appointments are?”
During the virtual visit, patients are asked to hold their medication bottles up to the camera so the clinician can see what they are taking.
“Frequently, we are able to catch mistakes,” Dr. Gorodeski said. “Of note, most patients don’t bring their pill bottles to the clinic, so in some ways doing the virtual visit for that aspect was more valuable.”
Patients who opt for a virtual visit can do so from any smart phone, laptop, or desktop computer. Once logged in, they enter a virtual waiting room as the clinician receives a text notification to log in and begin the visit.
“It’s very efficient with time, and my questions were answered quickly,” said a patient in a short video Dr. Gorodeski played to illustrate the technology.
“I still feel the same connectivity with the patient,” a clinician in the video said.
There is currently no way to bill insurance companies for this type of visit, Dr. Gorodeski said when asked what initial barriers other institutions might have implementing a similar approach.
In the randomized, single-center clinical trial Dr. Gorodeski presented here at the HFSA meeting, called VIV-HF (Virtual Visits in Heart Failure Care Transitions), a total of 108 patients were randomized to the virtual visit (52 patients) or an in-person visit (56 patients).
The majority of patients (over 60%) had heart failure with reduced ejection fraction, according to the reported study results.
No-show rates were 50% for the in-person visit, and 34.6% for the virtual visit, for a relative risk reduction of 31%. However, this difference did not reach statistical significance, likely because the study was underpowered, according to Dr. Gorodeski.
“This strategy may reduce postdischarge appointment no-show rates, and this needs to be studied further in larger and appropriately powered clinical trials,” he said in presenting the results.
The 7-day postdischarge outpatient clinic visit is recommended in guidelines and viewed as a way to increase care engagement while reducing risk of poor outcomes, according to VIV-HF investigators.
Support for the study came from the Hunnell Fund. Dr. Gorodeski reported being a consultant and advisor to Abbott.
cardnews@mdedge
SOURCE: Gorodeski EZ, et al. HFSA 2019. Late-Breaking Clinical Trials session.
REPORTING FROM HFSA 2019
Patients have good recall on lung cancer screening scan benefits, not risks
NEW ORLEANS – in a recent survey, underscoring the need for ongoing patient education beyond the initial shared decision-making encounter, a researcher said.
While about 9 in 10 patients recalled key information on the benefits, only about 4 in 10 recalled information on risks, according to Erin Hirsch, MSPH, of the Colorado School of Public Health in Aurora.
“This may mean we need ongoing clinician involvement or continued education about this important information, especially if the patients aren’t screening annually,” Ms. Hirsch said in a podium presentation at the annual meeting of the American College of Chest Physicians.
Even fewer patients could correctly recall eligibility criteria for lung cancer screening, which suggests “ongoing clinician involvement” is needed to identify appropriate patients, Hirsch added in her presentation.
Shared decision making about lung cancer screening, which is supposed to entail a balanced patient-provider conversation about eligibility, risks, and benefits, is required by the Centers for Medicare & Medicaid Services to cover the cost of lung cancer screening as a preventative service, Hirsch noted in her presentation.
However, it’s largely unknown to what extent patients due for an annual screening recall information that should have been imparted in that initial discussion.
“The gap in knowledge centers around the fact that shared decision making is only required for baseline scan, but screening is recommended on an annual basis,” she said.
To test patient recall, Hirsch and colleagues developed a knowledge survey including 34 questions about lung cancer screening eligibility, risks, and benefits. The surveys went out by mail or email to 228 patients who had a baseline screening CT scan 6-12 months earlier; a total of 53 complete responses were included in the analysis, which focused on seven key questions about benefit, risk, and eligibility.
Recall was “excellent” for the benefit questions, Ms. Hirsch said, with 91% of patients able to recall that a computed tomography (CT) scan is better at detecting a possible lung cancer than a chest x-ray, while 87% recalled that without screening lung cancer is often found at a later stage when cure is less likely.
By contrast, a “moderate” amount (40%) remembered that a CT scan can suggest the patient has lung cancer when in fact they do not, she said, and only 38% recalled that radiation exposure was one of the harms of lung cancer screening, she added.
Eligibility recall was “poor,” she added, with only 21% affirming that not all current and former smokers need to be screened for lung cancer. Just 8% recalled that 55 years is the age at which beginning lung cancer screening is recommended, and 4% knew that 30 is the minimum number of pack-years required to be eligible for screening.
While these results may have clinical implications, Ms. Hirsch acknowledged a number of limitations to this pilot study. Among those was the fact that the content of the initial shared decision-making conversation could not be assessed: “We assumed that the patients were exposed to the information asked about in the survey ahead of time, but we can’t say for sure if that was true,” she explained.
Ms. Hirsch and coauthors disclosed no relationships relevant to their study.
SOURCE: Hirsch E et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.107.
NEW ORLEANS – in a recent survey, underscoring the need for ongoing patient education beyond the initial shared decision-making encounter, a researcher said.
While about 9 in 10 patients recalled key information on the benefits, only about 4 in 10 recalled information on risks, according to Erin Hirsch, MSPH, of the Colorado School of Public Health in Aurora.
“This may mean we need ongoing clinician involvement or continued education about this important information, especially if the patients aren’t screening annually,” Ms. Hirsch said in a podium presentation at the annual meeting of the American College of Chest Physicians.
Even fewer patients could correctly recall eligibility criteria for lung cancer screening, which suggests “ongoing clinician involvement” is needed to identify appropriate patients, Hirsch added in her presentation.
Shared decision making about lung cancer screening, which is supposed to entail a balanced patient-provider conversation about eligibility, risks, and benefits, is required by the Centers for Medicare & Medicaid Services to cover the cost of lung cancer screening as a preventative service, Hirsch noted in her presentation.
However, it’s largely unknown to what extent patients due for an annual screening recall information that should have been imparted in that initial discussion.
“The gap in knowledge centers around the fact that shared decision making is only required for baseline scan, but screening is recommended on an annual basis,” she said.
To test patient recall, Hirsch and colleagues developed a knowledge survey including 34 questions about lung cancer screening eligibility, risks, and benefits. The surveys went out by mail or email to 228 patients who had a baseline screening CT scan 6-12 months earlier; a total of 53 complete responses were included in the analysis, which focused on seven key questions about benefit, risk, and eligibility.
Recall was “excellent” for the benefit questions, Ms. Hirsch said, with 91% of patients able to recall that a computed tomography (CT) scan is better at detecting a possible lung cancer than a chest x-ray, while 87% recalled that without screening lung cancer is often found at a later stage when cure is less likely.
By contrast, a “moderate” amount (40%) remembered that a CT scan can suggest the patient has lung cancer when in fact they do not, she said, and only 38% recalled that radiation exposure was one of the harms of lung cancer screening, she added.
Eligibility recall was “poor,” she added, with only 21% affirming that not all current and former smokers need to be screened for lung cancer. Just 8% recalled that 55 years is the age at which beginning lung cancer screening is recommended, and 4% knew that 30 is the minimum number of pack-years required to be eligible for screening.
While these results may have clinical implications, Ms. Hirsch acknowledged a number of limitations to this pilot study. Among those was the fact that the content of the initial shared decision-making conversation could not be assessed: “We assumed that the patients were exposed to the information asked about in the survey ahead of time, but we can’t say for sure if that was true,” she explained.
Ms. Hirsch and coauthors disclosed no relationships relevant to their study.
SOURCE: Hirsch E et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.107.
NEW ORLEANS – in a recent survey, underscoring the need for ongoing patient education beyond the initial shared decision-making encounter, a researcher said.
While about 9 in 10 patients recalled key information on the benefits, only about 4 in 10 recalled information on risks, according to Erin Hirsch, MSPH, of the Colorado School of Public Health in Aurora.
“This may mean we need ongoing clinician involvement or continued education about this important information, especially if the patients aren’t screening annually,” Ms. Hirsch said in a podium presentation at the annual meeting of the American College of Chest Physicians.
Even fewer patients could correctly recall eligibility criteria for lung cancer screening, which suggests “ongoing clinician involvement” is needed to identify appropriate patients, Hirsch added in her presentation.
Shared decision making about lung cancer screening, which is supposed to entail a balanced patient-provider conversation about eligibility, risks, and benefits, is required by the Centers for Medicare & Medicaid Services to cover the cost of lung cancer screening as a preventative service, Hirsch noted in her presentation.
However, it’s largely unknown to what extent patients due for an annual screening recall information that should have been imparted in that initial discussion.
“The gap in knowledge centers around the fact that shared decision making is only required for baseline scan, but screening is recommended on an annual basis,” she said.
To test patient recall, Hirsch and colleagues developed a knowledge survey including 34 questions about lung cancer screening eligibility, risks, and benefits. The surveys went out by mail or email to 228 patients who had a baseline screening CT scan 6-12 months earlier; a total of 53 complete responses were included in the analysis, which focused on seven key questions about benefit, risk, and eligibility.
Recall was “excellent” for the benefit questions, Ms. Hirsch said, with 91% of patients able to recall that a computed tomography (CT) scan is better at detecting a possible lung cancer than a chest x-ray, while 87% recalled that without screening lung cancer is often found at a later stage when cure is less likely.
By contrast, a “moderate” amount (40%) remembered that a CT scan can suggest the patient has lung cancer when in fact they do not, she said, and only 38% recalled that radiation exposure was one of the harms of lung cancer screening, she added.
Eligibility recall was “poor,” she added, with only 21% affirming that not all current and former smokers need to be screened for lung cancer. Just 8% recalled that 55 years is the age at which beginning lung cancer screening is recommended, and 4% knew that 30 is the minimum number of pack-years required to be eligible for screening.
While these results may have clinical implications, Ms. Hirsch acknowledged a number of limitations to this pilot study. Among those was the fact that the content of the initial shared decision-making conversation could not be assessed: “We assumed that the patients were exposed to the information asked about in the survey ahead of time, but we can’t say for sure if that was true,” she explained.
Ms. Hirsch and coauthors disclosed no relationships relevant to their study.
SOURCE: Hirsch E et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.107.
REPORTING FROM CHEST 2019
Readmission for COPD exacerbation upped in-hospital mortality risk
NEW ORLEANS – Reduction of readmission rates among individuals hospitalized for an acute exacerbation of COPD could reduce mortality and health care expenditures, results of a large, retrospective study suggest.
said researcher Anand Muthu Krishnan, MBBS, an from the University of Connecticut, Farmington.
“This is not a small problem,” Dr. Krishnan said in a podium presentation at the annual meeting of the American College of Chest Physicians. “The amount of money that can be saved can be put into primary care for curbing COPD and better patient outcomes, basically, if you’re able to put in checkpoints to stop this problem.”
Bundled care interventions by interdisciplinary teams have thus far proven effective at improving quality of care and improving process measures in this setting, said Dr. Krishnan.
The retrospective cohort study by Dr. Krishnan and colleagues included 530,229 adult patients in the 2016 National Readmission Database who had a principal diagnosis of acute COPD exacerbation. The mean age of the patients was 68 years, and 58% were female.
The rates of readmission at 30 days after discharge were 16.3% for any cause and 5.4% specifically for COPD, the researchers found. Of note, the in-hospital mortality rate increased from 1.1% to 3.8% during readmission (P less than .01), Dr. Krishnan said.
Readmissions were linked to a cumulative length of stay of 458,677 days, with corresponding hospital costs of $0.97 billion and charges of $4.0 billion; the COPD-specific readmissions were associated with cumulative length of stay of 132,026 days, costs of $253 million, and charges of $1 billion, Dr. Krishnan reported.
Dr. Krishnan and coauthors disclosed no relationships relevant to their study.
SOURCE: Krishnan AM et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.229.
NEW ORLEANS – Reduction of readmission rates among individuals hospitalized for an acute exacerbation of COPD could reduce mortality and health care expenditures, results of a large, retrospective study suggest.
said researcher Anand Muthu Krishnan, MBBS, an from the University of Connecticut, Farmington.
“This is not a small problem,” Dr. Krishnan said in a podium presentation at the annual meeting of the American College of Chest Physicians. “The amount of money that can be saved can be put into primary care for curbing COPD and better patient outcomes, basically, if you’re able to put in checkpoints to stop this problem.”
Bundled care interventions by interdisciplinary teams have thus far proven effective at improving quality of care and improving process measures in this setting, said Dr. Krishnan.
The retrospective cohort study by Dr. Krishnan and colleagues included 530,229 adult patients in the 2016 National Readmission Database who had a principal diagnosis of acute COPD exacerbation. The mean age of the patients was 68 years, and 58% were female.
The rates of readmission at 30 days after discharge were 16.3% for any cause and 5.4% specifically for COPD, the researchers found. Of note, the in-hospital mortality rate increased from 1.1% to 3.8% during readmission (P less than .01), Dr. Krishnan said.
Readmissions were linked to a cumulative length of stay of 458,677 days, with corresponding hospital costs of $0.97 billion and charges of $4.0 billion; the COPD-specific readmissions were associated with cumulative length of stay of 132,026 days, costs of $253 million, and charges of $1 billion, Dr. Krishnan reported.
Dr. Krishnan and coauthors disclosed no relationships relevant to their study.
SOURCE: Krishnan AM et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.229.
NEW ORLEANS – Reduction of readmission rates among individuals hospitalized for an acute exacerbation of COPD could reduce mortality and health care expenditures, results of a large, retrospective study suggest.
said researcher Anand Muthu Krishnan, MBBS, an from the University of Connecticut, Farmington.
“This is not a small problem,” Dr. Krishnan said in a podium presentation at the annual meeting of the American College of Chest Physicians. “The amount of money that can be saved can be put into primary care for curbing COPD and better patient outcomes, basically, if you’re able to put in checkpoints to stop this problem.”
Bundled care interventions by interdisciplinary teams have thus far proven effective at improving quality of care and improving process measures in this setting, said Dr. Krishnan.
The retrospective cohort study by Dr. Krishnan and colleagues included 530,229 adult patients in the 2016 National Readmission Database who had a principal diagnosis of acute COPD exacerbation. The mean age of the patients was 68 years, and 58% were female.
The rates of readmission at 30 days after discharge were 16.3% for any cause and 5.4% specifically for COPD, the researchers found. Of note, the in-hospital mortality rate increased from 1.1% to 3.8% during readmission (P less than .01), Dr. Krishnan said.
Readmissions were linked to a cumulative length of stay of 458,677 days, with corresponding hospital costs of $0.97 billion and charges of $4.0 billion; the COPD-specific readmissions were associated with cumulative length of stay of 132,026 days, costs of $253 million, and charges of $1 billion, Dr. Krishnan reported.
Dr. Krishnan and coauthors disclosed no relationships relevant to their study.
SOURCE: Krishnan AM et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.229.
REPORTING FROM CHEST 2019
Next-gen genomic test plus bronchoscopy may improve lung nodule management
NEW ORLEANS – The use of a results of a recent clinical validation study suggest.
The Percepta Genomic Sequencing Classifier (GSC) was able to up- and down-classify probability of malignancy for a considerable proportion of nondiagnostic bronchoscopies in the study, Peter J. Mazzone MD, FCCP, reported at the annual meeting of the American College of Chest Physicians.
The test is seen as complementary to bronchoscopy, improving the sensitivity of bronchoscopy overall and showing a combined sensitivity of greater than 95% in low- and intermediate-risk groups, according to Dr. Mazzone.
While the clinical utility of this genomic test needs to be further tested, the eventual goal is to improve clinician decision making when bronchoscopy results don’t clearly classify nodules as malignant or benign, Dr. Mazzone said in an interview.
“In that situation, you’re often left wondering, ‘what should I do next? Can I just watch this, and see if it grows and changes, or do I have to be even more aggressive – do another biopsy, or have a surgery to take it out?’ ” he explained. “So the test hopes to help make a more informed decision by further stratifying those patients as being quite low risk and maybe safe to follow, or quite high risk and maybe you should be considering more aggressive management.”
The GSC improves on the performance of an earlier molecular test, the Percepta Bronchial Genomic Classifier, which uses a brushing of bronchial epithelium to enhance nodule management in smokers, according to the researcher.
The next-generation GSC uses 1,232 gene transcripts from whole-transcriptome RNA sequencing, along with clinical factors, to help with nodule diagnosis, he said.
To establish the diagnostic accuracy of the GSC, Dr. Mazzone and colleagues evaluated data on 412 patients from three independent cohorts, all of whom had bronchoscopies for lung nodule evaluation that were nondiagnostic. Of those patients, 5% had nodules that physicians had deemed as low probability of malignancy prior to bronchoscopy, 28% deemed intermediate risk, and 74% high risk.
They found that the Percepta GSC down-classified the low–pretest risk patients with 100% negative predictive value (NPV) and down-classified intermediate–pretest risk patients with a 91.0% NPV, Dr. Mazzone reported, while patients with intermediate pretest risk were up-classified with a 65.4% positive predictive value (PPV) and patients with high pretest risk were upclassified with a 91.5% PPV.
The proportion of patients reclassified was about 55% for the low-risk group, 42% for the intermediate-risk group, and 27% for the high-risk group, according to the report at the meeting.
These results suggest the Percepta GSC could help in the “sticky situation” where a bronchoscopy result is inconclusive, Dr. Mazzone told attendees.
“When a bronchoscopy is recommended, despite fantastic advances in navigation systems to get to those nodules, we often come back without a solid answer, and that leaves the clinician in a bit of a predicament,” he said in a late-breaking clinical trial presentation.
Dr. Mazzone provided disclosures related to Veracyte, Exact Sciences, SEER, Tencent, and PCORI (research support to institution).
SOURCE: Mazzone PJ et al. CHEST 2019, Abstract. doi: 10.1016/j.chest.2019.08.307.
NEW ORLEANS – The use of a results of a recent clinical validation study suggest.
The Percepta Genomic Sequencing Classifier (GSC) was able to up- and down-classify probability of malignancy for a considerable proportion of nondiagnostic bronchoscopies in the study, Peter J. Mazzone MD, FCCP, reported at the annual meeting of the American College of Chest Physicians.
The test is seen as complementary to bronchoscopy, improving the sensitivity of bronchoscopy overall and showing a combined sensitivity of greater than 95% in low- and intermediate-risk groups, according to Dr. Mazzone.
While the clinical utility of this genomic test needs to be further tested, the eventual goal is to improve clinician decision making when bronchoscopy results don’t clearly classify nodules as malignant or benign, Dr. Mazzone said in an interview.
“In that situation, you’re often left wondering, ‘what should I do next? Can I just watch this, and see if it grows and changes, or do I have to be even more aggressive – do another biopsy, or have a surgery to take it out?’ ” he explained. “So the test hopes to help make a more informed decision by further stratifying those patients as being quite low risk and maybe safe to follow, or quite high risk and maybe you should be considering more aggressive management.”
The GSC improves on the performance of an earlier molecular test, the Percepta Bronchial Genomic Classifier, which uses a brushing of bronchial epithelium to enhance nodule management in smokers, according to the researcher.
The next-generation GSC uses 1,232 gene transcripts from whole-transcriptome RNA sequencing, along with clinical factors, to help with nodule diagnosis, he said.
To establish the diagnostic accuracy of the GSC, Dr. Mazzone and colleagues evaluated data on 412 patients from three independent cohorts, all of whom had bronchoscopies for lung nodule evaluation that were nondiagnostic. Of those patients, 5% had nodules that physicians had deemed as low probability of malignancy prior to bronchoscopy, 28% deemed intermediate risk, and 74% high risk.
They found that the Percepta GSC down-classified the low–pretest risk patients with 100% negative predictive value (NPV) and down-classified intermediate–pretest risk patients with a 91.0% NPV, Dr. Mazzone reported, while patients with intermediate pretest risk were up-classified with a 65.4% positive predictive value (PPV) and patients with high pretest risk were upclassified with a 91.5% PPV.
The proportion of patients reclassified was about 55% for the low-risk group, 42% for the intermediate-risk group, and 27% for the high-risk group, according to the report at the meeting.
These results suggest the Percepta GSC could help in the “sticky situation” where a bronchoscopy result is inconclusive, Dr. Mazzone told attendees.
“When a bronchoscopy is recommended, despite fantastic advances in navigation systems to get to those nodules, we often come back without a solid answer, and that leaves the clinician in a bit of a predicament,” he said in a late-breaking clinical trial presentation.
Dr. Mazzone provided disclosures related to Veracyte, Exact Sciences, SEER, Tencent, and PCORI (research support to institution).
SOURCE: Mazzone PJ et al. CHEST 2019, Abstract. doi: 10.1016/j.chest.2019.08.307.
NEW ORLEANS – The use of a results of a recent clinical validation study suggest.
The Percepta Genomic Sequencing Classifier (GSC) was able to up- and down-classify probability of malignancy for a considerable proportion of nondiagnostic bronchoscopies in the study, Peter J. Mazzone MD, FCCP, reported at the annual meeting of the American College of Chest Physicians.
The test is seen as complementary to bronchoscopy, improving the sensitivity of bronchoscopy overall and showing a combined sensitivity of greater than 95% in low- and intermediate-risk groups, according to Dr. Mazzone.
While the clinical utility of this genomic test needs to be further tested, the eventual goal is to improve clinician decision making when bronchoscopy results don’t clearly classify nodules as malignant or benign, Dr. Mazzone said in an interview.
“In that situation, you’re often left wondering, ‘what should I do next? Can I just watch this, and see if it grows and changes, or do I have to be even more aggressive – do another biopsy, or have a surgery to take it out?’ ” he explained. “So the test hopes to help make a more informed decision by further stratifying those patients as being quite low risk and maybe safe to follow, or quite high risk and maybe you should be considering more aggressive management.”
The GSC improves on the performance of an earlier molecular test, the Percepta Bronchial Genomic Classifier, which uses a brushing of bronchial epithelium to enhance nodule management in smokers, according to the researcher.
The next-generation GSC uses 1,232 gene transcripts from whole-transcriptome RNA sequencing, along with clinical factors, to help with nodule diagnosis, he said.
To establish the diagnostic accuracy of the GSC, Dr. Mazzone and colleagues evaluated data on 412 patients from three independent cohorts, all of whom had bronchoscopies for lung nodule evaluation that were nondiagnostic. Of those patients, 5% had nodules that physicians had deemed as low probability of malignancy prior to bronchoscopy, 28% deemed intermediate risk, and 74% high risk.
They found that the Percepta GSC down-classified the low–pretest risk patients with 100% negative predictive value (NPV) and down-classified intermediate–pretest risk patients with a 91.0% NPV, Dr. Mazzone reported, while patients with intermediate pretest risk were up-classified with a 65.4% positive predictive value (PPV) and patients with high pretest risk were upclassified with a 91.5% PPV.
The proportion of patients reclassified was about 55% for the low-risk group, 42% for the intermediate-risk group, and 27% for the high-risk group, according to the report at the meeting.
These results suggest the Percepta GSC could help in the “sticky situation” where a bronchoscopy result is inconclusive, Dr. Mazzone told attendees.
“When a bronchoscopy is recommended, despite fantastic advances in navigation systems to get to those nodules, we often come back without a solid answer, and that leaves the clinician in a bit of a predicament,” he said in a late-breaking clinical trial presentation.
Dr. Mazzone provided disclosures related to Veracyte, Exact Sciences, SEER, Tencent, and PCORI (research support to institution).
SOURCE: Mazzone PJ et al. CHEST 2019, Abstract. doi: 10.1016/j.chest.2019.08.307.
REPORTING FROM CHEST 2019
Vitamin C–based regimens in sepsis plausible, need more data, expert says
NEW ORLEANS – While further data are awaited on the role of vitamin C, thiamine, and steroids in sepsis, there is at least biologic plausibility for using the combination, and clinical equipoise that supports continued enrollment of patients in the ongoing randomized, controlled VICTAS trial, according to that study’s principal investigator.
“There is tremendous biologic plausibility for giving vitamin C in sepsis,” said Jon Sevransky, MD, professor of medicine at Emory University in Atlanta. But until more data are available on vitamin C–based regimens, those who choose to use vitamin C with thiamine and steroids in this setting need to ensure that glucose is being measured appropriately, he warned.
“If you decide that vitamin C is right for your patient, prior to having enough data – so if you’re doing a Hail Mary, or a ‘this patient is sick, and it’s probably not going to hurt them’ – please make sure that you measure your glucose with something that uses whole blood, which is either a blood gas or sending it down to the core lab, because otherwise, you might get an inaccurate result,” Dr. Sevransky said at the annual meeting of the American College of Chest Physicians.
Results from the randomized, placebo-controlled Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) trial may be available within the next few months, according to Dr. Sevransky, who noted that the trial was funded for 500 patients, which provides an 80% probability of showing an absolute risk reduction of 10% in mortality.
The primary endpoint of the phase 3 trial is vasopressor and ventilator-free days at 30 days after randomization, while 30-day mortality has been described as “the key secondary outcome” by Dr. Sevransky and colleagues in a recent report on the trial design.
Clinicians have been “captivated” by the potential benefit of vitamin C, thiamine, and hydrocortisone in patients with severe sepsis and septic shock, as published in CHEST in June 2017, Dr. Sevransky said. In that study, reported by Paul E. Marik, MD, and colleagues, hospital mortality was 8.5% for the treatment group, versus 40.4% in the control group, a significant difference.
That retrospective, single-center study had a number of limitations, however, including its before-and-after design and the use of steroids in the comparator arm. In addition, little information was available on antibiotics or fluids given at the time of the intervention, according to Dr. Sevransky.
In results of the CITRIS-ALI randomized clinical trial, just published in JAMA, intravenous administration of high-dose vitamin C in patients with sepsis and acute respiratory distress syndrome (ARDS) failed to significantly reduce organ failure scores or biomarkers of inflammation and vascular injury.
In an exploratory analysis of CITRIS-ALI, mortality at day 28 was 29.8% for the treatment group and 46.3% for placebo, with a statistically significant difference between Kaplan-Meier survival curves for the two arms, according to the investigators.
That exploratory result from CITRIS-ALI, however, is indicative of “something that needs further study,” Dr. Sevransky cautioned. “In summary, I hope I told you that biologic plausibility is present for vitamin C, thiamine, and steroids. I think that, and this is my own personal opinion, that evidence to date allows for randomization of patients, that there’s current equipoise.”
Dr. Sevransky disclosed current grant support from the Biomedical Advanced Research and Development Authority (BARDA) and the Marcus Foundation, as well as a stipend from Critical Care Medicine related to work as an associate editor. He is also a medical advisor to Project Hope and ARDS Foundation and a member of the Surviving Sepsis guideline committees.
SOURCE: Sevransky J et al. Chest 2019.
NEW ORLEANS – While further data are awaited on the role of vitamin C, thiamine, and steroids in sepsis, there is at least biologic plausibility for using the combination, and clinical equipoise that supports continued enrollment of patients in the ongoing randomized, controlled VICTAS trial, according to that study’s principal investigator.
“There is tremendous biologic plausibility for giving vitamin C in sepsis,” said Jon Sevransky, MD, professor of medicine at Emory University in Atlanta. But until more data are available on vitamin C–based regimens, those who choose to use vitamin C with thiamine and steroids in this setting need to ensure that glucose is being measured appropriately, he warned.
“If you decide that vitamin C is right for your patient, prior to having enough data – so if you’re doing a Hail Mary, or a ‘this patient is sick, and it’s probably not going to hurt them’ – please make sure that you measure your glucose with something that uses whole blood, which is either a blood gas or sending it down to the core lab, because otherwise, you might get an inaccurate result,” Dr. Sevransky said at the annual meeting of the American College of Chest Physicians.
Results from the randomized, placebo-controlled Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) trial may be available within the next few months, according to Dr. Sevransky, who noted that the trial was funded for 500 patients, which provides an 80% probability of showing an absolute risk reduction of 10% in mortality.
The primary endpoint of the phase 3 trial is vasopressor and ventilator-free days at 30 days after randomization, while 30-day mortality has been described as “the key secondary outcome” by Dr. Sevransky and colleagues in a recent report on the trial design.
Clinicians have been “captivated” by the potential benefit of vitamin C, thiamine, and hydrocortisone in patients with severe sepsis and septic shock, as published in CHEST in June 2017, Dr. Sevransky said. In that study, reported by Paul E. Marik, MD, and colleagues, hospital mortality was 8.5% for the treatment group, versus 40.4% in the control group, a significant difference.
That retrospective, single-center study had a number of limitations, however, including its before-and-after design and the use of steroids in the comparator arm. In addition, little information was available on antibiotics or fluids given at the time of the intervention, according to Dr. Sevransky.
In results of the CITRIS-ALI randomized clinical trial, just published in JAMA, intravenous administration of high-dose vitamin C in patients with sepsis and acute respiratory distress syndrome (ARDS) failed to significantly reduce organ failure scores or biomarkers of inflammation and vascular injury.
In an exploratory analysis of CITRIS-ALI, mortality at day 28 was 29.8% for the treatment group and 46.3% for placebo, with a statistically significant difference between Kaplan-Meier survival curves for the two arms, according to the investigators.
That exploratory result from CITRIS-ALI, however, is indicative of “something that needs further study,” Dr. Sevransky cautioned. “In summary, I hope I told you that biologic plausibility is present for vitamin C, thiamine, and steroids. I think that, and this is my own personal opinion, that evidence to date allows for randomization of patients, that there’s current equipoise.”
Dr. Sevransky disclosed current grant support from the Biomedical Advanced Research and Development Authority (BARDA) and the Marcus Foundation, as well as a stipend from Critical Care Medicine related to work as an associate editor. He is also a medical advisor to Project Hope and ARDS Foundation and a member of the Surviving Sepsis guideline committees.
SOURCE: Sevransky J et al. Chest 2019.
NEW ORLEANS – While further data are awaited on the role of vitamin C, thiamine, and steroids in sepsis, there is at least biologic plausibility for using the combination, and clinical equipoise that supports continued enrollment of patients in the ongoing randomized, controlled VICTAS trial, according to that study’s principal investigator.
“There is tremendous biologic plausibility for giving vitamin C in sepsis,” said Jon Sevransky, MD, professor of medicine at Emory University in Atlanta. But until more data are available on vitamin C–based regimens, those who choose to use vitamin C with thiamine and steroids in this setting need to ensure that glucose is being measured appropriately, he warned.
“If you decide that vitamin C is right for your patient, prior to having enough data – so if you’re doing a Hail Mary, or a ‘this patient is sick, and it’s probably not going to hurt them’ – please make sure that you measure your glucose with something that uses whole blood, which is either a blood gas or sending it down to the core lab, because otherwise, you might get an inaccurate result,” Dr. Sevransky said at the annual meeting of the American College of Chest Physicians.
Results from the randomized, placebo-controlled Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) trial may be available within the next few months, according to Dr. Sevransky, who noted that the trial was funded for 500 patients, which provides an 80% probability of showing an absolute risk reduction of 10% in mortality.
The primary endpoint of the phase 3 trial is vasopressor and ventilator-free days at 30 days after randomization, while 30-day mortality has been described as “the key secondary outcome” by Dr. Sevransky and colleagues in a recent report on the trial design.
Clinicians have been “captivated” by the potential benefit of vitamin C, thiamine, and hydrocortisone in patients with severe sepsis and septic shock, as published in CHEST in June 2017, Dr. Sevransky said. In that study, reported by Paul E. Marik, MD, and colleagues, hospital mortality was 8.5% for the treatment group, versus 40.4% in the control group, a significant difference.
That retrospective, single-center study had a number of limitations, however, including its before-and-after design and the use of steroids in the comparator arm. In addition, little information was available on antibiotics or fluids given at the time of the intervention, according to Dr. Sevransky.
In results of the CITRIS-ALI randomized clinical trial, just published in JAMA, intravenous administration of high-dose vitamin C in patients with sepsis and acute respiratory distress syndrome (ARDS) failed to significantly reduce organ failure scores or biomarkers of inflammation and vascular injury.
In an exploratory analysis of CITRIS-ALI, mortality at day 28 was 29.8% for the treatment group and 46.3% for placebo, with a statistically significant difference between Kaplan-Meier survival curves for the two arms, according to the investigators.
That exploratory result from CITRIS-ALI, however, is indicative of “something that needs further study,” Dr. Sevransky cautioned. “In summary, I hope I told you that biologic plausibility is present for vitamin C, thiamine, and steroids. I think that, and this is my own personal opinion, that evidence to date allows for randomization of patients, that there’s current equipoise.”
Dr. Sevransky disclosed current grant support from the Biomedical Advanced Research and Development Authority (BARDA) and the Marcus Foundation, as well as a stipend from Critical Care Medicine related to work as an associate editor. He is also a medical advisor to Project Hope and ARDS Foundation and a member of the Surviving Sepsis guideline committees.
SOURCE: Sevransky J et al. Chest 2019.
EXPERT ANALYSIS FROM CHEST 2019
Recent COPD exacerbation did not affect aclidinium’s efficacy in high-risk patients
NEW ORLEANS – A history of recent exacerbations did not significantly affect the safety or efficacy of aclidinium bromide (Tudorza) in patients with moderate to severe chronic obstructive pulmonary disease and high cardiovascular risk, analysis of a postmarketing surveillance trial suggests.
Regardless of exacerbation history, the long-acting muscarinic antagonist reduced the rate of moderate or severe COPD exacerbations versus placebo in this subgroup analysis of the phase IV ASCENT-COPD trial, presented here at the annual meeting of the American College of Chest Physicians.
At the same time, there were no significant increases in the risk of mortality or major cardiac adverse events (MACE) for those patients who had an exacerbation in the past year versus those who did not, according to investigator Robert A. Wise, MD.
Those findings may be reassuring, given that COPD patients commonly have comorbidities and cardiovascular risk factors, according to Dr. Wise, professor of medicine at the Johns Hopkins University, Baltimore.
“There’s a concern and some evidence that patients who have a propensity to COPD exacerbations may also have an increased risk for cardiovascular events,” Dr. Wise said in a podium presentation.
Accordingly, he and coinvestigators sought to tease out the impact of COPD exacerbations on safety as well as efficacy in the randomized, placebo-controlled ASCENT-COPD trial, which included 3,630 patients with moderate to severe COPD plus a cardiovascular disease history or multiple atherothrombotic risk factors.
Of the patients who were analyzed in the study, 1,433 patients had at least one treated COPD exacerbation in the year before screening for the study, while 2,156 had no exacerbations in the prior year, Dr. Wise said.
Top-line results of that study, published several months ago, showed that aclidinium did not increase MACE risk over 3 years, and reduced the rate of moderate to severe COPD exacerbations over the first year (JAMA. 2019 7 May 7;321[17]:1693-701).
In this latest analysis, presented at the meeting, risk of MACE with aclidinium treatment was not increased versus placebo, irrespective of whether they had exacerbations in the prior year (interaction P = .233); likewise, the risk of all-cause mortality was similar between groups (P = .154).
In terms of reduction in moderate or severe COPD exacerbations in the first year, aclidinium was superior to placebo both for the patients who had at least one or exacerbation in the prior year (rate ratio, 0.80) and those who had no exacerbations in the prior year (RR, 0.69).
“This translates into a number-needed-to-treat to prevent one exacerbation of about 11 patients for those without an exacerbation, compared to about 6 patients for those with a prior exacerbation,” Dr. Wise said in his presentation.
The ASCENT-COPD study was funded initially by Forest Laboratories and later by AstraZeneca and Circassia. Dr. Wise provided disclosures related to AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Sunovion, Mylan/Theravance, Contrafect, Pearl, Merck, Verona, Novartis, AbbVie, Syneos, Regeneron, and Kiniksa.
SOURCE: Wise R et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.231.
NEW ORLEANS – A history of recent exacerbations did not significantly affect the safety or efficacy of aclidinium bromide (Tudorza) in patients with moderate to severe chronic obstructive pulmonary disease and high cardiovascular risk, analysis of a postmarketing surveillance trial suggests.
Regardless of exacerbation history, the long-acting muscarinic antagonist reduced the rate of moderate or severe COPD exacerbations versus placebo in this subgroup analysis of the phase IV ASCENT-COPD trial, presented here at the annual meeting of the American College of Chest Physicians.
At the same time, there were no significant increases in the risk of mortality or major cardiac adverse events (MACE) for those patients who had an exacerbation in the past year versus those who did not, according to investigator Robert A. Wise, MD.
Those findings may be reassuring, given that COPD patients commonly have comorbidities and cardiovascular risk factors, according to Dr. Wise, professor of medicine at the Johns Hopkins University, Baltimore.
“There’s a concern and some evidence that patients who have a propensity to COPD exacerbations may also have an increased risk for cardiovascular events,” Dr. Wise said in a podium presentation.
Accordingly, he and coinvestigators sought to tease out the impact of COPD exacerbations on safety as well as efficacy in the randomized, placebo-controlled ASCENT-COPD trial, which included 3,630 patients with moderate to severe COPD plus a cardiovascular disease history or multiple atherothrombotic risk factors.
Of the patients who were analyzed in the study, 1,433 patients had at least one treated COPD exacerbation in the year before screening for the study, while 2,156 had no exacerbations in the prior year, Dr. Wise said.
Top-line results of that study, published several months ago, showed that aclidinium did not increase MACE risk over 3 years, and reduced the rate of moderate to severe COPD exacerbations over the first year (JAMA. 2019 7 May 7;321[17]:1693-701).
In this latest analysis, presented at the meeting, risk of MACE with aclidinium treatment was not increased versus placebo, irrespective of whether they had exacerbations in the prior year (interaction P = .233); likewise, the risk of all-cause mortality was similar between groups (P = .154).
In terms of reduction in moderate or severe COPD exacerbations in the first year, aclidinium was superior to placebo both for the patients who had at least one or exacerbation in the prior year (rate ratio, 0.80) and those who had no exacerbations in the prior year (RR, 0.69).
“This translates into a number-needed-to-treat to prevent one exacerbation of about 11 patients for those without an exacerbation, compared to about 6 patients for those with a prior exacerbation,” Dr. Wise said in his presentation.
The ASCENT-COPD study was funded initially by Forest Laboratories and later by AstraZeneca and Circassia. Dr. Wise provided disclosures related to AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Sunovion, Mylan/Theravance, Contrafect, Pearl, Merck, Verona, Novartis, AbbVie, Syneos, Regeneron, and Kiniksa.
SOURCE: Wise R et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.231.
NEW ORLEANS – A history of recent exacerbations did not significantly affect the safety or efficacy of aclidinium bromide (Tudorza) in patients with moderate to severe chronic obstructive pulmonary disease and high cardiovascular risk, analysis of a postmarketing surveillance trial suggests.
Regardless of exacerbation history, the long-acting muscarinic antagonist reduced the rate of moderate or severe COPD exacerbations versus placebo in this subgroup analysis of the phase IV ASCENT-COPD trial, presented here at the annual meeting of the American College of Chest Physicians.
At the same time, there were no significant increases in the risk of mortality or major cardiac adverse events (MACE) for those patients who had an exacerbation in the past year versus those who did not, according to investigator Robert A. Wise, MD.
Those findings may be reassuring, given that COPD patients commonly have comorbidities and cardiovascular risk factors, according to Dr. Wise, professor of medicine at the Johns Hopkins University, Baltimore.
“There’s a concern and some evidence that patients who have a propensity to COPD exacerbations may also have an increased risk for cardiovascular events,” Dr. Wise said in a podium presentation.
Accordingly, he and coinvestigators sought to tease out the impact of COPD exacerbations on safety as well as efficacy in the randomized, placebo-controlled ASCENT-COPD trial, which included 3,630 patients with moderate to severe COPD plus a cardiovascular disease history or multiple atherothrombotic risk factors.
Of the patients who were analyzed in the study, 1,433 patients had at least one treated COPD exacerbation in the year before screening for the study, while 2,156 had no exacerbations in the prior year, Dr. Wise said.
Top-line results of that study, published several months ago, showed that aclidinium did not increase MACE risk over 3 years, and reduced the rate of moderate to severe COPD exacerbations over the first year (JAMA. 2019 7 May 7;321[17]:1693-701).
In this latest analysis, presented at the meeting, risk of MACE with aclidinium treatment was not increased versus placebo, irrespective of whether they had exacerbations in the prior year (interaction P = .233); likewise, the risk of all-cause mortality was similar between groups (P = .154).
In terms of reduction in moderate or severe COPD exacerbations in the first year, aclidinium was superior to placebo both for the patients who had at least one or exacerbation in the prior year (rate ratio, 0.80) and those who had no exacerbations in the prior year (RR, 0.69).
“This translates into a number-needed-to-treat to prevent one exacerbation of about 11 patients for those without an exacerbation, compared to about 6 patients for those with a prior exacerbation,” Dr. Wise said in his presentation.
The ASCENT-COPD study was funded initially by Forest Laboratories and later by AstraZeneca and Circassia. Dr. Wise provided disclosures related to AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Sunovion, Mylan/Theravance, Contrafect, Pearl, Merck, Verona, Novartis, AbbVie, Syneos, Regeneron, and Kiniksa.
SOURCE: Wise R et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.231.
REPORTING FROM CHEST 2019
In-hospital flu shot reduced readmissions in pneumonia patients
NEW ORLEANS – In-hospital flu shots were rare, yet linked to a lower readmission rate for patients hospitalized with community-acquired pneumonia in a recent retrospective study, suggesting a “missed opportunity” to improve outcomes for these patients, an investigator said.
Less than 2% of patients admitted for community-acquired pneumonia (CAP) received in-hospital influenza vaccination, yet receiving it was linked to a 20% reduction in readmissions, according to investigator Kam Sing Ho, MD, a resident at Mount Sinai St. Luke’s, New York.
Those patients who were readmitted had a significantly higher death rate vs. index admissions, Dr. Ho said in a poster discussion session at the annual meeting of the American College of Chest Physicians.
“I know (vaccines) are pretty much pushed out to the outpatient setting, but given what we showed here in this abstract, I think there’s a role for influenza vaccines to be a discussion in the hospital,” Dr. Ho said in his presentation.
The retrospective analysis was based on 825,906 adult hospital admissions with a primary diagnosis of CAP in data from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project (HCUP). Of that large cohort, just 14,047 (1.91%) received in-hospital influenza vaccination, according to Dr. Ho.
In-hospital influenza vaccination independently predicted a lower risk of readmission (hazard ratio, 0.821; 95% confidence interval, 0.69-0.98; P less than .02) in a propensity score matching analysis that included 9,777 CAP patients who received the vaccination and 9,777 with similar demographic and clinical characteristics.
Private insurance and high-income status also predicted lower risk of readmission in the analysis, while by contrast, factors associated with higher risk of readmission included advanced age, Medicare insurance, and respiratory failure, among other factors, Dr. Ho reported.
The overall 30-day rate of readmission in the study was 11.9%, and of those readmissions, the great majority (about 80%) were due to pneumonia, he said.
The rate of death in the hospital was 2.96% for CAP patients who were readmitted, versus 1.11% for the index admissions (P less than .001), Dr. Ho reported. Moreover, readmissions were associated with nearly half a million hospital days and $1 billion in costs and $3.67 billion in charges.
Based on these findings, Dr. Ho and colleagues hope to incorporate routine influenza vaccination for all adults hospitalized with CAP.
“We’re always under pressure to do so much for patients that we can’t comprehensively do everything. But the 20% reduction in the risk of coming back, I think that’s significant,” Dr. Ho said in an interview.
The authors reported having no disclosures related to this research.
This article was updated 10/23/2019.
SOURCE: Ho KS, et al. CHEST 2019. doi: 10.1016/j.chest.2019.08.450.
NEW ORLEANS – In-hospital flu shots were rare, yet linked to a lower readmission rate for patients hospitalized with community-acquired pneumonia in a recent retrospective study, suggesting a “missed opportunity” to improve outcomes for these patients, an investigator said.
Less than 2% of patients admitted for community-acquired pneumonia (CAP) received in-hospital influenza vaccination, yet receiving it was linked to a 20% reduction in readmissions, according to investigator Kam Sing Ho, MD, a resident at Mount Sinai St. Luke’s, New York.
Those patients who were readmitted had a significantly higher death rate vs. index admissions, Dr. Ho said in a poster discussion session at the annual meeting of the American College of Chest Physicians.
“I know (vaccines) are pretty much pushed out to the outpatient setting, but given what we showed here in this abstract, I think there’s a role for influenza vaccines to be a discussion in the hospital,” Dr. Ho said in his presentation.
The retrospective analysis was based on 825,906 adult hospital admissions with a primary diagnosis of CAP in data from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project (HCUP). Of that large cohort, just 14,047 (1.91%) received in-hospital influenza vaccination, according to Dr. Ho.
In-hospital influenza vaccination independently predicted a lower risk of readmission (hazard ratio, 0.821; 95% confidence interval, 0.69-0.98; P less than .02) in a propensity score matching analysis that included 9,777 CAP patients who received the vaccination and 9,777 with similar demographic and clinical characteristics.
Private insurance and high-income status also predicted lower risk of readmission in the analysis, while by contrast, factors associated with higher risk of readmission included advanced age, Medicare insurance, and respiratory failure, among other factors, Dr. Ho reported.
The overall 30-day rate of readmission in the study was 11.9%, and of those readmissions, the great majority (about 80%) were due to pneumonia, he said.
The rate of death in the hospital was 2.96% for CAP patients who were readmitted, versus 1.11% for the index admissions (P less than .001), Dr. Ho reported. Moreover, readmissions were associated with nearly half a million hospital days and $1 billion in costs and $3.67 billion in charges.
Based on these findings, Dr. Ho and colleagues hope to incorporate routine influenza vaccination for all adults hospitalized with CAP.
“We’re always under pressure to do so much for patients that we can’t comprehensively do everything. But the 20% reduction in the risk of coming back, I think that’s significant,” Dr. Ho said in an interview.
The authors reported having no disclosures related to this research.
This article was updated 10/23/2019.
SOURCE: Ho KS, et al. CHEST 2019. doi: 10.1016/j.chest.2019.08.450.
NEW ORLEANS – In-hospital flu shots were rare, yet linked to a lower readmission rate for patients hospitalized with community-acquired pneumonia in a recent retrospective study, suggesting a “missed opportunity” to improve outcomes for these patients, an investigator said.
Less than 2% of patients admitted for community-acquired pneumonia (CAP) received in-hospital influenza vaccination, yet receiving it was linked to a 20% reduction in readmissions, according to investigator Kam Sing Ho, MD, a resident at Mount Sinai St. Luke’s, New York.
Those patients who were readmitted had a significantly higher death rate vs. index admissions, Dr. Ho said in a poster discussion session at the annual meeting of the American College of Chest Physicians.
“I know (vaccines) are pretty much pushed out to the outpatient setting, but given what we showed here in this abstract, I think there’s a role for influenza vaccines to be a discussion in the hospital,” Dr. Ho said in his presentation.
The retrospective analysis was based on 825,906 adult hospital admissions with a primary diagnosis of CAP in data from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project (HCUP). Of that large cohort, just 14,047 (1.91%) received in-hospital influenza vaccination, according to Dr. Ho.
In-hospital influenza vaccination independently predicted a lower risk of readmission (hazard ratio, 0.821; 95% confidence interval, 0.69-0.98; P less than .02) in a propensity score matching analysis that included 9,777 CAP patients who received the vaccination and 9,777 with similar demographic and clinical characteristics.
Private insurance and high-income status also predicted lower risk of readmission in the analysis, while by contrast, factors associated with higher risk of readmission included advanced age, Medicare insurance, and respiratory failure, among other factors, Dr. Ho reported.
The overall 30-day rate of readmission in the study was 11.9%, and of those readmissions, the great majority (about 80%) were due to pneumonia, he said.
The rate of death in the hospital was 2.96% for CAP patients who were readmitted, versus 1.11% for the index admissions (P less than .001), Dr. Ho reported. Moreover, readmissions were associated with nearly half a million hospital days and $1 billion in costs and $3.67 billion in charges.
Based on these findings, Dr. Ho and colleagues hope to incorporate routine influenza vaccination for all adults hospitalized with CAP.
“We’re always under pressure to do so much for patients that we can’t comprehensively do everything. But the 20% reduction in the risk of coming back, I think that’s significant,” Dr. Ho said in an interview.
The authors reported having no disclosures related to this research.
This article was updated 10/23/2019.
SOURCE: Ho KS, et al. CHEST 2019. doi: 10.1016/j.chest.2019.08.450.
REPORTING FROM CHEST 2019