User login
Race mismatch may affect survival in lung transplant setting
NEW ORLEANS – Race compatibility is a factor that can affect survival and needs to be considered when matching lung transplant candidates to potential donors, results from a large retrospective analysis suggest.
Specifically, whites had significantly worse survival when receiving lungs from African American donors in this registry analysis, according to study investigator Alexis Kofi Okoh, MD.
By contrast, donor-to-recipient race compatibility (DRRC) did not affect posttransplant survival among African American or Hispanic patients, said Dr. Okoh, who is with the lung transplant division at the Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J.
While race mismatch has been shown to affect outcomes in kidney, heart, and liver transplant settings, the data for DRRC in lung transplant prior to this analysis generally has been limited to small, single-center studies, according to Dr. Okoh.
“If you do have the option, [race compatibility] should highly be considered, because it clearly has an impact on outcomes,” Dr. Okoh said in an interview here at the annual meeting of the American College of Chest Physicians.
Considering the race of both donor and recipient is especially important now that the lung transplant population is becoming more ethnically diverse, he added.
The study was based on an analysis of 19,504 lung transplant recipients in the prospectively maintained United Network for Organ Sharing (UNOS) database during 2006-2018. In that cohort, 16,485 recipients were white, 1,787 were African American, and 1,232 were Hispanic.
Race-matched donor organs were used in two-thirds (66.2%) of white recipients, about one-quarter (26.8%) of African American recipients, and one-third (33.0%) of Hispanic recipients.
Overall, survival post–lung transplant was significantly poorer among recipients who did not receive a race-matched organ in Kaplan-Meier survival estimates, Dr. Okoh said, though, that this effect was diminished after they adjusted for patient baseline characteristics (P = 0.2809).
For African American recipients, the unadjusted and adjusted survival estimates were no different regardless of donor race, and likewise, there were no apparent survival differences between Hispanic recipients who received race matched or mismatched organs.
Survival among white recipients, however, was significantly affected by race of the recipient, with decreased survival estimates noted even after adjustment for patient characteristics, according to Dr. Okoh’s presentation.
Results of regression analysis showed that white recipient/African American donor was the only race mismatch to significantly affect survival, Dr. Okoh said in the interview.
The posttransplant survival hazard ratios (and 95% confidence intervals) reported by Dr. Okoh with a no race mismatch serving as reference were 1.15 (1.08-1.23) for whites with African American donors, and 1.09 (1.01-1.18) for whites with Hispanic donors.
Dr. Okoh and coinvestigators reported no relevant conflicts in relation to their study.
SOURCE: Okoh A et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.220.
NEW ORLEANS – Race compatibility is a factor that can affect survival and needs to be considered when matching lung transplant candidates to potential donors, results from a large retrospective analysis suggest.
Specifically, whites had significantly worse survival when receiving lungs from African American donors in this registry analysis, according to study investigator Alexis Kofi Okoh, MD.
By contrast, donor-to-recipient race compatibility (DRRC) did not affect posttransplant survival among African American or Hispanic patients, said Dr. Okoh, who is with the lung transplant division at the Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J.
While race mismatch has been shown to affect outcomes in kidney, heart, and liver transplant settings, the data for DRRC in lung transplant prior to this analysis generally has been limited to small, single-center studies, according to Dr. Okoh.
“If you do have the option, [race compatibility] should highly be considered, because it clearly has an impact on outcomes,” Dr. Okoh said in an interview here at the annual meeting of the American College of Chest Physicians.
Considering the race of both donor and recipient is especially important now that the lung transplant population is becoming more ethnically diverse, he added.
The study was based on an analysis of 19,504 lung transplant recipients in the prospectively maintained United Network for Organ Sharing (UNOS) database during 2006-2018. In that cohort, 16,485 recipients were white, 1,787 were African American, and 1,232 were Hispanic.
Race-matched donor organs were used in two-thirds (66.2%) of white recipients, about one-quarter (26.8%) of African American recipients, and one-third (33.0%) of Hispanic recipients.
Overall, survival post–lung transplant was significantly poorer among recipients who did not receive a race-matched organ in Kaplan-Meier survival estimates, Dr. Okoh said, though, that this effect was diminished after they adjusted for patient baseline characteristics (P = 0.2809).
For African American recipients, the unadjusted and adjusted survival estimates were no different regardless of donor race, and likewise, there were no apparent survival differences between Hispanic recipients who received race matched or mismatched organs.
Survival among white recipients, however, was significantly affected by race of the recipient, with decreased survival estimates noted even after adjustment for patient characteristics, according to Dr. Okoh’s presentation.
Results of regression analysis showed that white recipient/African American donor was the only race mismatch to significantly affect survival, Dr. Okoh said in the interview.
The posttransplant survival hazard ratios (and 95% confidence intervals) reported by Dr. Okoh with a no race mismatch serving as reference were 1.15 (1.08-1.23) for whites with African American donors, and 1.09 (1.01-1.18) for whites with Hispanic donors.
Dr. Okoh and coinvestigators reported no relevant conflicts in relation to their study.
SOURCE: Okoh A et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.220.
NEW ORLEANS – Race compatibility is a factor that can affect survival and needs to be considered when matching lung transplant candidates to potential donors, results from a large retrospective analysis suggest.
Specifically, whites had significantly worse survival when receiving lungs from African American donors in this registry analysis, according to study investigator Alexis Kofi Okoh, MD.
By contrast, donor-to-recipient race compatibility (DRRC) did not affect posttransplant survival among African American or Hispanic patients, said Dr. Okoh, who is with the lung transplant division at the Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J.
While race mismatch has been shown to affect outcomes in kidney, heart, and liver transplant settings, the data for DRRC in lung transplant prior to this analysis generally has been limited to small, single-center studies, according to Dr. Okoh.
“If you do have the option, [race compatibility] should highly be considered, because it clearly has an impact on outcomes,” Dr. Okoh said in an interview here at the annual meeting of the American College of Chest Physicians.
Considering the race of both donor and recipient is especially important now that the lung transplant population is becoming more ethnically diverse, he added.
The study was based on an analysis of 19,504 lung transplant recipients in the prospectively maintained United Network for Organ Sharing (UNOS) database during 2006-2018. In that cohort, 16,485 recipients were white, 1,787 were African American, and 1,232 were Hispanic.
Race-matched donor organs were used in two-thirds (66.2%) of white recipients, about one-quarter (26.8%) of African American recipients, and one-third (33.0%) of Hispanic recipients.
Overall, survival post–lung transplant was significantly poorer among recipients who did not receive a race-matched organ in Kaplan-Meier survival estimates, Dr. Okoh said, though, that this effect was diminished after they adjusted for patient baseline characteristics (P = 0.2809).
For African American recipients, the unadjusted and adjusted survival estimates were no different regardless of donor race, and likewise, there were no apparent survival differences between Hispanic recipients who received race matched or mismatched organs.
Survival among white recipients, however, was significantly affected by race of the recipient, with decreased survival estimates noted even after adjustment for patient characteristics, according to Dr. Okoh’s presentation.
Results of regression analysis showed that white recipient/African American donor was the only race mismatch to significantly affect survival, Dr. Okoh said in the interview.
The posttransplant survival hazard ratios (and 95% confidence intervals) reported by Dr. Okoh with a no race mismatch serving as reference were 1.15 (1.08-1.23) for whites with African American donors, and 1.09 (1.01-1.18) for whites with Hispanic donors.
Dr. Okoh and coinvestigators reported no relevant conflicts in relation to their study.
SOURCE: Okoh A et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.220.
REPORTING FROM CHEST 2019
Dogs steal the show again at CHEST 2019
NEW ORLEANS – Wellness among physicians begins with a focus on reducing stress. Attendees of the CHEST annual meeting were given the opportunity to spend some time with the ultimate stress reliever - puppies. A local animal rescue organization, “Take Paws Rescue,” set up a venue for visiting with (and holding and petting) a litter of adoptable puppies. Several attendees decided on the spot to adopt one of these pups. Others just took the opportunity to cuddle.
Christopher Carroll, MD, a specialist in pediatric critical care with Connecticut Children’s Medical Center in Hartford, knows the value of animals to relieve stress in both patients and doctors. He convinced his medical center to allow dogs into the pediatric ICU, with appropriate cautions, to provide stress relief and joy to both young patients and staff.
The puppies will be in the Exhibit Hall every day at the meeting between 11:30 a.m. and 1 p.m.
NEW ORLEANS – Wellness among physicians begins with a focus on reducing stress. Attendees of the CHEST annual meeting were given the opportunity to spend some time with the ultimate stress reliever - puppies. A local animal rescue organization, “Take Paws Rescue,” set up a venue for visiting with (and holding and petting) a litter of adoptable puppies. Several attendees decided on the spot to adopt one of these pups. Others just took the opportunity to cuddle.
Christopher Carroll, MD, a specialist in pediatric critical care with Connecticut Children’s Medical Center in Hartford, knows the value of animals to relieve stress in both patients and doctors. He convinced his medical center to allow dogs into the pediatric ICU, with appropriate cautions, to provide stress relief and joy to both young patients and staff.
The puppies will be in the Exhibit Hall every day at the meeting between 11:30 a.m. and 1 p.m.
NEW ORLEANS – Wellness among physicians begins with a focus on reducing stress. Attendees of the CHEST annual meeting were given the opportunity to spend some time with the ultimate stress reliever - puppies. A local animal rescue organization, “Take Paws Rescue,” set up a venue for visiting with (and holding and petting) a litter of adoptable puppies. Several attendees decided on the spot to adopt one of these pups. Others just took the opportunity to cuddle.
Christopher Carroll, MD, a specialist in pediatric critical care with Connecticut Children’s Medical Center in Hartford, knows the value of animals to relieve stress in both patients and doctors. He convinced his medical center to allow dogs into the pediatric ICU, with appropriate cautions, to provide stress relief and joy to both young patients and staff.
The puppies will be in the Exhibit Hall every day at the meeting between 11:30 a.m. and 1 p.m.
REPORTING FROM CHEST 2019
Digital inhaler reveals uncontrolled asthma
NEW ORLEANS – Data collected by the ProAir Digihaler suggest .
Researchers studied asthma patients who had experienced exacerbations in the previous year. Patients who also had exacerbations while on study used the ProAir Digihaler about twice a day, on average. Patients without on-study exacerbations used the ProAir Digihaler an average of 1.14 times per day.
The daily use among patients without exacerbations suggests their asthma is “still quite uncontrolled,” and, according to guidelines, they may require additional therapy, said Roy Pleasants, PharmD, of the University of North Carolina at Chapel Hill.
Dr. Pleasants presented these findings at the annual meeting of the American College of Chest Physicians.
He and his colleagues conducted a phase 3 study (NCT02969408) of ProAir Digihaler use in adults who had at least one severe clinical asthma exacerbation in the previous 12 months. They had an Asthma Control Questionnaire score of 1.5 or greater, were on moderate-dose inhaled corticosteroids (with or without a long-acting beta-agonist), and had stable asthma controller dosing for at least 3 months.
For this study, the ProAir Digihaler replaced patients’ other rescue medications. The ProAir Digihaler is a digital inhaler that delivers 90 mcg of albuterol per dose, detects the date and time a dose was prepared, and records the inhalation profile. Over a 12-week period, the ProAir Digihaler recorded each use, which was defined as consecutive inhalations within 60 seconds.
Of the 381 patients enrolled in the study, 360 (94.5%) made at least one valid inhalation. The mean age of these patients was 50 years, and 80.6% were female. Of the 360 patients, 64 experienced 78 exacerbations while on study.
Most episodes of inhaler use consisted of a single inhalation (58.9%), although 35.8% consisted of two inhalations, 3.5% consisted of three inhalations, and 1.8% consisted of four or more inhalations.
The mean peak inspiratory flow was 73.18 L/min (standard deviation [SD] 20.33) in patients without exacerbations. Among patients with exacerbations, the mean peak inspiratory flow was 71.36 (SD 23.80) during exacerbation and 74.71 L/min (SD 22.46) outside the exacerbation window, which was 14 days before and after the exacerbation peak.
The mean inhalation volume was 1.45 L (SD 0.75) among patients without exacerbations, 1.44 L (SD 0.66) outside the exacerbation window, and 1.44 L (SD 0.76) during exacerbation. The mean inhalation duration was 1.62 sec (SD 0.88), 1.59 sec (SD 0.77), and 1.61 sec (SD 0.82), respectively.
“If you look at the inhalation volume in the 64 patients who exacerbated, it really didn’t change during exacerbation,” Dr. Pleasants noted. “Essentially, you can say the same thing about inhalation duration.”
Patients without exacerbations used the ProAir Digihaler an average of 1.14 (SD 2.35) times per day. Patients who had at least one exacerbation used the ProAir Digihaler an average of 1.87 (SD 2.78) times per day outside the exacerbation window and 2.43 (SD 3.67) times during exacerbation.
“As you would predict, those exacerbating patients were using more albuterol than patients who were not exacerbating,” Dr. Pleasants said. “Even when they weren’t exacerbating, that frequency of daily albuterol use is pretty much indicating these patients were not so well controlled.”
Dr. Pleasants went on to say that data from the ProAir Digihaler could help identify, in real time, patients with poor asthma control and those with impending exacerbations.
This study was sponsored by Teva, makers of the ProAir Digihaler. Dr. Pleasants disclosed relationships with Teva, Grifols, Sunovion, and Boehringer Ingelheim.
SOURCE: Pleasants R et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.273.
NEW ORLEANS – Data collected by the ProAir Digihaler suggest .
Researchers studied asthma patients who had experienced exacerbations in the previous year. Patients who also had exacerbations while on study used the ProAir Digihaler about twice a day, on average. Patients without on-study exacerbations used the ProAir Digihaler an average of 1.14 times per day.
The daily use among patients without exacerbations suggests their asthma is “still quite uncontrolled,” and, according to guidelines, they may require additional therapy, said Roy Pleasants, PharmD, of the University of North Carolina at Chapel Hill.
Dr. Pleasants presented these findings at the annual meeting of the American College of Chest Physicians.
He and his colleagues conducted a phase 3 study (NCT02969408) of ProAir Digihaler use in adults who had at least one severe clinical asthma exacerbation in the previous 12 months. They had an Asthma Control Questionnaire score of 1.5 or greater, were on moderate-dose inhaled corticosteroids (with or without a long-acting beta-agonist), and had stable asthma controller dosing for at least 3 months.
For this study, the ProAir Digihaler replaced patients’ other rescue medications. The ProAir Digihaler is a digital inhaler that delivers 90 mcg of albuterol per dose, detects the date and time a dose was prepared, and records the inhalation profile. Over a 12-week period, the ProAir Digihaler recorded each use, which was defined as consecutive inhalations within 60 seconds.
Of the 381 patients enrolled in the study, 360 (94.5%) made at least one valid inhalation. The mean age of these patients was 50 years, and 80.6% were female. Of the 360 patients, 64 experienced 78 exacerbations while on study.
Most episodes of inhaler use consisted of a single inhalation (58.9%), although 35.8% consisted of two inhalations, 3.5% consisted of three inhalations, and 1.8% consisted of four or more inhalations.
The mean peak inspiratory flow was 73.18 L/min (standard deviation [SD] 20.33) in patients without exacerbations. Among patients with exacerbations, the mean peak inspiratory flow was 71.36 (SD 23.80) during exacerbation and 74.71 L/min (SD 22.46) outside the exacerbation window, which was 14 days before and after the exacerbation peak.
The mean inhalation volume was 1.45 L (SD 0.75) among patients without exacerbations, 1.44 L (SD 0.66) outside the exacerbation window, and 1.44 L (SD 0.76) during exacerbation. The mean inhalation duration was 1.62 sec (SD 0.88), 1.59 sec (SD 0.77), and 1.61 sec (SD 0.82), respectively.
“If you look at the inhalation volume in the 64 patients who exacerbated, it really didn’t change during exacerbation,” Dr. Pleasants noted. “Essentially, you can say the same thing about inhalation duration.”
Patients without exacerbations used the ProAir Digihaler an average of 1.14 (SD 2.35) times per day. Patients who had at least one exacerbation used the ProAir Digihaler an average of 1.87 (SD 2.78) times per day outside the exacerbation window and 2.43 (SD 3.67) times during exacerbation.
“As you would predict, those exacerbating patients were using more albuterol than patients who were not exacerbating,” Dr. Pleasants said. “Even when they weren’t exacerbating, that frequency of daily albuterol use is pretty much indicating these patients were not so well controlled.”
Dr. Pleasants went on to say that data from the ProAir Digihaler could help identify, in real time, patients with poor asthma control and those with impending exacerbations.
This study was sponsored by Teva, makers of the ProAir Digihaler. Dr. Pleasants disclosed relationships with Teva, Grifols, Sunovion, and Boehringer Ingelheim.
SOURCE: Pleasants R et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.273.
NEW ORLEANS – Data collected by the ProAir Digihaler suggest .
Researchers studied asthma patients who had experienced exacerbations in the previous year. Patients who also had exacerbations while on study used the ProAir Digihaler about twice a day, on average. Patients without on-study exacerbations used the ProAir Digihaler an average of 1.14 times per day.
The daily use among patients without exacerbations suggests their asthma is “still quite uncontrolled,” and, according to guidelines, they may require additional therapy, said Roy Pleasants, PharmD, of the University of North Carolina at Chapel Hill.
Dr. Pleasants presented these findings at the annual meeting of the American College of Chest Physicians.
He and his colleagues conducted a phase 3 study (NCT02969408) of ProAir Digihaler use in adults who had at least one severe clinical asthma exacerbation in the previous 12 months. They had an Asthma Control Questionnaire score of 1.5 or greater, were on moderate-dose inhaled corticosteroids (with or without a long-acting beta-agonist), and had stable asthma controller dosing for at least 3 months.
For this study, the ProAir Digihaler replaced patients’ other rescue medications. The ProAir Digihaler is a digital inhaler that delivers 90 mcg of albuterol per dose, detects the date and time a dose was prepared, and records the inhalation profile. Over a 12-week period, the ProAir Digihaler recorded each use, which was defined as consecutive inhalations within 60 seconds.
Of the 381 patients enrolled in the study, 360 (94.5%) made at least one valid inhalation. The mean age of these patients was 50 years, and 80.6% were female. Of the 360 patients, 64 experienced 78 exacerbations while on study.
Most episodes of inhaler use consisted of a single inhalation (58.9%), although 35.8% consisted of two inhalations, 3.5% consisted of three inhalations, and 1.8% consisted of four or more inhalations.
The mean peak inspiratory flow was 73.18 L/min (standard deviation [SD] 20.33) in patients without exacerbations. Among patients with exacerbations, the mean peak inspiratory flow was 71.36 (SD 23.80) during exacerbation and 74.71 L/min (SD 22.46) outside the exacerbation window, which was 14 days before and after the exacerbation peak.
The mean inhalation volume was 1.45 L (SD 0.75) among patients without exacerbations, 1.44 L (SD 0.66) outside the exacerbation window, and 1.44 L (SD 0.76) during exacerbation. The mean inhalation duration was 1.62 sec (SD 0.88), 1.59 sec (SD 0.77), and 1.61 sec (SD 0.82), respectively.
“If you look at the inhalation volume in the 64 patients who exacerbated, it really didn’t change during exacerbation,” Dr. Pleasants noted. “Essentially, you can say the same thing about inhalation duration.”
Patients without exacerbations used the ProAir Digihaler an average of 1.14 (SD 2.35) times per day. Patients who had at least one exacerbation used the ProAir Digihaler an average of 1.87 (SD 2.78) times per day outside the exacerbation window and 2.43 (SD 3.67) times during exacerbation.
“As you would predict, those exacerbating patients were using more albuterol than patients who were not exacerbating,” Dr. Pleasants said. “Even when they weren’t exacerbating, that frequency of daily albuterol use is pretty much indicating these patients were not so well controlled.”
Dr. Pleasants went on to say that data from the ProAir Digihaler could help identify, in real time, patients with poor asthma control and those with impending exacerbations.
This study was sponsored by Teva, makers of the ProAir Digihaler. Dr. Pleasants disclosed relationships with Teva, Grifols, Sunovion, and Boehringer Ingelheim.
SOURCE: Pleasants R et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.273.
REPORTING FROM CHEST 2019
Patiromer allows more CKD patients to continue on spironolactone
PHILADELPHIA – Among patients with chronic kidney disease with resistant hypertension, coadministration of patiromer enables more patients to stay on spironolactone, Bryan Williams, MD, of University College London, said at the scientific meeting of the Heart Failure Society of America.
Having the potassium-binding polymer on board allowed for more persistent use of spironolactone, both in the subgroup of patients with heart failure, and those without, he said in a late-breaking clinical trials session.
In the international, phase 2 AMBER (Spironolactone With Patiromer in the Treatment of Resistant Hypertension in Chronic Kidney Disease) trial, 295 patients with chronic kidney disease (estimated glomerular filtration rate from 25 to 45 mL/min per 1.73 m2) were randomly assigned to treatment with spironolactone either placebo (148) or patiromer (147).
, for a significant between-group difference of 19.5% (P less than .0001). In addition, blood pressure lowering was significantly greater in the patiromer (–11.7 mm Hg) than in the placebo (–10.8 mm Hg) group. Results of the AMBER trial were published concurrently with Dr. Williams’ presentation (Lancet 2019 Sep 15; doi: 10.1016/S0140-6736(19)32135-X).
While spironolactone is a “highly effective” drug, studies supporting guideline recommendations for its use in resistant hypertension have largely excluded patients with advanced chronic kidney disease because of increased risk of developing spironolactone-induced hyperkalemia, Dr. Williams told attendees. It remains unclear, however, whether coadministration of patiromer will improve long-term outcomes. Also, many placebo-treated patients in AMBER were able to continue on spironolactone without the help of patiromer, prompting one attendee to question whether there was a smarter way to target the drug, rather than treating all patients up front.
“I don’t think it’s going to be easy to say, ‘this patient’s going to respond, and this patient’s not going to respond,’ ” Dr. Williams said in response, “but at least we have an opportunity to try now in a group of patients who simply may be denied treatment because of a perception that it is difficult to use spironolactone in them.”
That perception is actually not unreasonable, he added, given that 66% of patients in the placebo group in AMBER developed hyperkalemia, suggesting that spironolactone is “not an easy drug to use” in chronic kidney disease patients.
John Teerlink, MD, of the San Francisco VA Medical Center, said the AMBER study is “another building block” in a series of developments of enabling therapies.
“I think it’s a great message for all of us to begin thinking about other therapies we can use to help modify our use of these potential life-saving therapies,” he said in a panel discussion of the results.
Patiromer’s impact on longer-term outcomes is the focus of DIAMOND, a phase 3, randomized, placebo controlled trial that is currently recruiting. DIAMOND will determine whether giving patiromer to patients who developed hyperkalemia on renin-angiotensin-aldosterone system (RAAS) inhibitors decreases cardiovascular deaths and hospitalizations, by virtue of enabling continued RAAS inhibitor use.
Funding for AMBER came from Relypsa, which markets patiromer (Veltassa). Dr. Williams reported consulting for Relypsa during the conduct of the study, along with disclosures outside the scope of the AMBER study (Daiichi Sankyo, Pfizer, Novartis, Servier, Boehringer Ingelheim, and Vascular Dynamics).
SOURCE: Williams B. HFSA 2019.
PHILADELPHIA – Among patients with chronic kidney disease with resistant hypertension, coadministration of patiromer enables more patients to stay on spironolactone, Bryan Williams, MD, of University College London, said at the scientific meeting of the Heart Failure Society of America.
Having the potassium-binding polymer on board allowed for more persistent use of spironolactone, both in the subgroup of patients with heart failure, and those without, he said in a late-breaking clinical trials session.
In the international, phase 2 AMBER (Spironolactone With Patiromer in the Treatment of Resistant Hypertension in Chronic Kidney Disease) trial, 295 patients with chronic kidney disease (estimated glomerular filtration rate from 25 to 45 mL/min per 1.73 m2) were randomly assigned to treatment with spironolactone either placebo (148) or patiromer (147).
, for a significant between-group difference of 19.5% (P less than .0001). In addition, blood pressure lowering was significantly greater in the patiromer (–11.7 mm Hg) than in the placebo (–10.8 mm Hg) group. Results of the AMBER trial were published concurrently with Dr. Williams’ presentation (Lancet 2019 Sep 15; doi: 10.1016/S0140-6736(19)32135-X).
While spironolactone is a “highly effective” drug, studies supporting guideline recommendations for its use in resistant hypertension have largely excluded patients with advanced chronic kidney disease because of increased risk of developing spironolactone-induced hyperkalemia, Dr. Williams told attendees. It remains unclear, however, whether coadministration of patiromer will improve long-term outcomes. Also, many placebo-treated patients in AMBER were able to continue on spironolactone without the help of patiromer, prompting one attendee to question whether there was a smarter way to target the drug, rather than treating all patients up front.
“I don’t think it’s going to be easy to say, ‘this patient’s going to respond, and this patient’s not going to respond,’ ” Dr. Williams said in response, “but at least we have an opportunity to try now in a group of patients who simply may be denied treatment because of a perception that it is difficult to use spironolactone in them.”
That perception is actually not unreasonable, he added, given that 66% of patients in the placebo group in AMBER developed hyperkalemia, suggesting that spironolactone is “not an easy drug to use” in chronic kidney disease patients.
John Teerlink, MD, of the San Francisco VA Medical Center, said the AMBER study is “another building block” in a series of developments of enabling therapies.
“I think it’s a great message for all of us to begin thinking about other therapies we can use to help modify our use of these potential life-saving therapies,” he said in a panel discussion of the results.
Patiromer’s impact on longer-term outcomes is the focus of DIAMOND, a phase 3, randomized, placebo controlled trial that is currently recruiting. DIAMOND will determine whether giving patiromer to patients who developed hyperkalemia on renin-angiotensin-aldosterone system (RAAS) inhibitors decreases cardiovascular deaths and hospitalizations, by virtue of enabling continued RAAS inhibitor use.
Funding for AMBER came from Relypsa, which markets patiromer (Veltassa). Dr. Williams reported consulting for Relypsa during the conduct of the study, along with disclosures outside the scope of the AMBER study (Daiichi Sankyo, Pfizer, Novartis, Servier, Boehringer Ingelheim, and Vascular Dynamics).
SOURCE: Williams B. HFSA 2019.
PHILADELPHIA – Among patients with chronic kidney disease with resistant hypertension, coadministration of patiromer enables more patients to stay on spironolactone, Bryan Williams, MD, of University College London, said at the scientific meeting of the Heart Failure Society of America.
Having the potassium-binding polymer on board allowed for more persistent use of spironolactone, both in the subgroup of patients with heart failure, and those without, he said in a late-breaking clinical trials session.
In the international, phase 2 AMBER (Spironolactone With Patiromer in the Treatment of Resistant Hypertension in Chronic Kidney Disease) trial, 295 patients with chronic kidney disease (estimated glomerular filtration rate from 25 to 45 mL/min per 1.73 m2) were randomly assigned to treatment with spironolactone either placebo (148) or patiromer (147).
, for a significant between-group difference of 19.5% (P less than .0001). In addition, blood pressure lowering was significantly greater in the patiromer (–11.7 mm Hg) than in the placebo (–10.8 mm Hg) group. Results of the AMBER trial were published concurrently with Dr. Williams’ presentation (Lancet 2019 Sep 15; doi: 10.1016/S0140-6736(19)32135-X).
While spironolactone is a “highly effective” drug, studies supporting guideline recommendations for its use in resistant hypertension have largely excluded patients with advanced chronic kidney disease because of increased risk of developing spironolactone-induced hyperkalemia, Dr. Williams told attendees. It remains unclear, however, whether coadministration of patiromer will improve long-term outcomes. Also, many placebo-treated patients in AMBER were able to continue on spironolactone without the help of patiromer, prompting one attendee to question whether there was a smarter way to target the drug, rather than treating all patients up front.
“I don’t think it’s going to be easy to say, ‘this patient’s going to respond, and this patient’s not going to respond,’ ” Dr. Williams said in response, “but at least we have an opportunity to try now in a group of patients who simply may be denied treatment because of a perception that it is difficult to use spironolactone in them.”
That perception is actually not unreasonable, he added, given that 66% of patients in the placebo group in AMBER developed hyperkalemia, suggesting that spironolactone is “not an easy drug to use” in chronic kidney disease patients.
John Teerlink, MD, of the San Francisco VA Medical Center, said the AMBER study is “another building block” in a series of developments of enabling therapies.
“I think it’s a great message for all of us to begin thinking about other therapies we can use to help modify our use of these potential life-saving therapies,” he said in a panel discussion of the results.
Patiromer’s impact on longer-term outcomes is the focus of DIAMOND, a phase 3, randomized, placebo controlled trial that is currently recruiting. DIAMOND will determine whether giving patiromer to patients who developed hyperkalemia on renin-angiotensin-aldosterone system (RAAS) inhibitors decreases cardiovascular deaths and hospitalizations, by virtue of enabling continued RAAS inhibitor use.
Funding for AMBER came from Relypsa, which markets patiromer (Veltassa). Dr. Williams reported consulting for Relypsa during the conduct of the study, along with disclosures outside the scope of the AMBER study (Daiichi Sankyo, Pfizer, Novartis, Servier, Boehringer Ingelheim, and Vascular Dynamics).
SOURCE: Williams B. HFSA 2019.
REPORTING FROM HFSA 2019
Dapagliflozin approved for reducing HF hospitalization in diabetes
The Food And Drug Administration has approved the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) for reducing the risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors, according to a statement from AstraZeneca.
The approval was based on results from the DECLARE-TIMI 58 cardiovascular outcomes trial, which evaluated dapagliflozin in more than 17,000 patients with type 2 diabetes and cardiovascular risk factors or cardiovascular disease. They showed that dapagliflozin significantly reduced the risk of the primary composite endpoint of hospitalization for heart failure by 27%, compared with placebo (2.5% vs. 3.3%; HR, 0.73; 95% confidence interval, 0.61-0.88).
The drug is an oral, once-daily SGLT2 inhibitor initially approved as a monotherapy or combination therapy for glycemic control in adults with type 2 diabetes. It has additional benefits of weight loss and reduction in blood pressure in concert with diet and exercise in the same population.
“,” Ruud Dobber, PhD, executive vice president of the company’s biopharmaceuticals business unit, said in the statement. “This is promising news for the 30 million people living with type 2 diabetes in the U.S., as heart failure is one of the earliest cardiovascular complications for them, before heart attack or stroke. [Dapagliflozin] now offers the opportunity for physicians to act sooner and reduce the risk of hospitalization for heart failure.”
In September, the agency granted dapagliflozin a Fast Track designation to reduce the risk of cardiovascular death, or the worsening of heart failure in adults with heart failure with reduced ejection fraction or preserved ejection fraction, based on the phase 3 DAPA-HF and DELIVER trials. It also gave the drug Fast Track designation to delay the progression of renal failure and prevent CV and renal death in patients with chronic kidney disease based on the phase 3 DAPA-CKD trial, the statement noted.
The Food And Drug Administration has approved the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) for reducing the risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors, according to a statement from AstraZeneca.
The approval was based on results from the DECLARE-TIMI 58 cardiovascular outcomes trial, which evaluated dapagliflozin in more than 17,000 patients with type 2 diabetes and cardiovascular risk factors or cardiovascular disease. They showed that dapagliflozin significantly reduced the risk of the primary composite endpoint of hospitalization for heart failure by 27%, compared with placebo (2.5% vs. 3.3%; HR, 0.73; 95% confidence interval, 0.61-0.88).
The drug is an oral, once-daily SGLT2 inhibitor initially approved as a monotherapy or combination therapy for glycemic control in adults with type 2 diabetes. It has additional benefits of weight loss and reduction in blood pressure in concert with diet and exercise in the same population.
“,” Ruud Dobber, PhD, executive vice president of the company’s biopharmaceuticals business unit, said in the statement. “This is promising news for the 30 million people living with type 2 diabetes in the U.S., as heart failure is one of the earliest cardiovascular complications for them, before heart attack or stroke. [Dapagliflozin] now offers the opportunity for physicians to act sooner and reduce the risk of hospitalization for heart failure.”
In September, the agency granted dapagliflozin a Fast Track designation to reduce the risk of cardiovascular death, or the worsening of heart failure in adults with heart failure with reduced ejection fraction or preserved ejection fraction, based on the phase 3 DAPA-HF and DELIVER trials. It also gave the drug Fast Track designation to delay the progression of renal failure and prevent CV and renal death in patients with chronic kidney disease based on the phase 3 DAPA-CKD trial, the statement noted.
The Food And Drug Administration has approved the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) for reducing the risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors, according to a statement from AstraZeneca.
The approval was based on results from the DECLARE-TIMI 58 cardiovascular outcomes trial, which evaluated dapagliflozin in more than 17,000 patients with type 2 diabetes and cardiovascular risk factors or cardiovascular disease. They showed that dapagliflozin significantly reduced the risk of the primary composite endpoint of hospitalization for heart failure by 27%, compared with placebo (2.5% vs. 3.3%; HR, 0.73; 95% confidence interval, 0.61-0.88).
The drug is an oral, once-daily SGLT2 inhibitor initially approved as a monotherapy or combination therapy for glycemic control in adults with type 2 diabetes. It has additional benefits of weight loss and reduction in blood pressure in concert with diet and exercise in the same population.
“,” Ruud Dobber, PhD, executive vice president of the company’s biopharmaceuticals business unit, said in the statement. “This is promising news for the 30 million people living with type 2 diabetes in the U.S., as heart failure is one of the earliest cardiovascular complications for them, before heart attack or stroke. [Dapagliflozin] now offers the opportunity for physicians to act sooner and reduce the risk of hospitalization for heart failure.”
In September, the agency granted dapagliflozin a Fast Track designation to reduce the risk of cardiovascular death, or the worsening of heart failure in adults with heart failure with reduced ejection fraction or preserved ejection fraction, based on the phase 3 DAPA-HF and DELIVER trials. It also gave the drug Fast Track designation to delay the progression of renal failure and prevent CV and renal death in patients with chronic kidney disease based on the phase 3 DAPA-CKD trial, the statement noted.
Study suggests physicians and patients overestimate asthma control
NEW ORLEANS – according to an observational study.
More than half (53%) of cases physicians rated as controlled were actually uncontrolled according to the Asthma Control Test (ACT), and 30% of patients who considered their asthma controlled actually had uncontrolled asthma according to the ACT.
Reynold A. Panettieri Jr., MD, of Rutgers University in New Brunswick, N.J., presented these findings at the annual meeting of the American College of Chest Physicians.
The findings are from the CHRONICLE study, an ongoing observational study of adults with severe asthma who are being treated by U.S. allergists or pulmonologists. The study enrolled 796 patients from Feb. 2018 to Feb. 2019, and 482 of them were evaluable because they completed the necessary surveys.
The patients’ median age at enrollment was 55 years, and 68% of patients were female. Most were white (82%), 12% were black, 6% were an “other” race, and 7% had Hispanic ethnicity. The median body mass index was 31 kg/m2.
Patients received care from an allergist (49%), a pulmonologist (38%), or both (13%). Patients were treated with biologics (n = 370), maintenance systemic corticosteroids (n = 64), or high-dosage inhaled corticosteroids with additional controllers (n = 90).
At patient enrollment, physicians reported their assessment of patients’ asthma control and completed the 5-point Global Evaluation of Treatment Effectiveness (GETE). The physicians’ assessments of patients were informed by patients’ verbal reports (50%), lung function testing (44%), in-office ACT (41%), and recent exacerbations (39%).
Patients also completed the ACT and GETE online at the time of enrollment. Neither patients nor physicians were privy to the other group’s responses.
Overall, physicians said 279 patients had controlled asthma. However, according to the ACT, 27% of these cases were very poorly controlled, 26% were not well controlled, and 47% were well controlled.
“So [when] we as a provider say the patient’s controlled, we’re wrong half the time,” Dr. Panettieri said.
However, physicians were more accurate when deeming patients’ asthma uncontrolled. Physicians said 201 cases of asthma were uncontrolled, and the ACT said 64% of these cases were very poorly controlled, 22% were not well controlled, and 13% were well controlled.
Compared with the physicians’ results, the patients’ reports were more in line with ACT results. However, the patients still overestimated control.
In all, 222 patients said their asthma was controlled. According to the ACT, 70% of these cases were well controlled, 23% were not well controlled, and 7% were very poorly controlled.
Patients were even more accurate when deeming their asthma uncontrolled. A total of 258 patients said their asthma was uncontrolled. According to the ACT, 74% of these cases were very poorly controlled, 25% were not well controlled, and 1% were well controlled.
“About 99% of the time, when a patient tells you they’re uncontrolled, they’re uncontrolled by the ACT,” Dr. Panettieri said.
Though patients were fairly accurate when assessing asthma control, they were less accurate when gauging treatment effectiveness. A majority of patients overestimated the effectiveness of treatment.
There were 124 patients who did not have any improvement after treatment, according to physicians. Although 23% of the patients concurred with this assessment, 77% said they did experience some improvement.
On the other hand, there were 355 patients who had some improvement after treatment according to physicians, and most of these patients (96%) agreed that they had some improvement.
Dr. Panettieri said these results support use of the ACT and similar tools. When using these tools isn’t feasible, Dr. Panettieri recommends simply asking patients how they are feeling. However, he said, providers should not rely on a patient’s report of treatment effectiveness to assess asthma control.
This study is supported by AstraZeneca. Dr. Panettieri disclosed relationships with AstraZeneca, Sanofi, Regeneron, Genentech, and Novartis.
SOURCE: Panettieri R et al. CHEST 2019. Abstract, doi. 10.1016/j.chest.2019.08.272.
NEW ORLEANS – according to an observational study.
More than half (53%) of cases physicians rated as controlled were actually uncontrolled according to the Asthma Control Test (ACT), and 30% of patients who considered their asthma controlled actually had uncontrolled asthma according to the ACT.
Reynold A. Panettieri Jr., MD, of Rutgers University in New Brunswick, N.J., presented these findings at the annual meeting of the American College of Chest Physicians.
The findings are from the CHRONICLE study, an ongoing observational study of adults with severe asthma who are being treated by U.S. allergists or pulmonologists. The study enrolled 796 patients from Feb. 2018 to Feb. 2019, and 482 of them were evaluable because they completed the necessary surveys.
The patients’ median age at enrollment was 55 years, and 68% of patients were female. Most were white (82%), 12% were black, 6% were an “other” race, and 7% had Hispanic ethnicity. The median body mass index was 31 kg/m2.
Patients received care from an allergist (49%), a pulmonologist (38%), or both (13%). Patients were treated with biologics (n = 370), maintenance systemic corticosteroids (n = 64), or high-dosage inhaled corticosteroids with additional controllers (n = 90).
At patient enrollment, physicians reported their assessment of patients’ asthma control and completed the 5-point Global Evaluation of Treatment Effectiveness (GETE). The physicians’ assessments of patients were informed by patients’ verbal reports (50%), lung function testing (44%), in-office ACT (41%), and recent exacerbations (39%).
Patients also completed the ACT and GETE online at the time of enrollment. Neither patients nor physicians were privy to the other group’s responses.
Overall, physicians said 279 patients had controlled asthma. However, according to the ACT, 27% of these cases were very poorly controlled, 26% were not well controlled, and 47% were well controlled.
“So [when] we as a provider say the patient’s controlled, we’re wrong half the time,” Dr. Panettieri said.
However, physicians were more accurate when deeming patients’ asthma uncontrolled. Physicians said 201 cases of asthma were uncontrolled, and the ACT said 64% of these cases were very poorly controlled, 22% were not well controlled, and 13% were well controlled.
Compared with the physicians’ results, the patients’ reports were more in line with ACT results. However, the patients still overestimated control.
In all, 222 patients said their asthma was controlled. According to the ACT, 70% of these cases were well controlled, 23% were not well controlled, and 7% were very poorly controlled.
Patients were even more accurate when deeming their asthma uncontrolled. A total of 258 patients said their asthma was uncontrolled. According to the ACT, 74% of these cases were very poorly controlled, 25% were not well controlled, and 1% were well controlled.
“About 99% of the time, when a patient tells you they’re uncontrolled, they’re uncontrolled by the ACT,” Dr. Panettieri said.
Though patients were fairly accurate when assessing asthma control, they were less accurate when gauging treatment effectiveness. A majority of patients overestimated the effectiveness of treatment.
There were 124 patients who did not have any improvement after treatment, according to physicians. Although 23% of the patients concurred with this assessment, 77% said they did experience some improvement.
On the other hand, there were 355 patients who had some improvement after treatment according to physicians, and most of these patients (96%) agreed that they had some improvement.
Dr. Panettieri said these results support use of the ACT and similar tools. When using these tools isn’t feasible, Dr. Panettieri recommends simply asking patients how they are feeling. However, he said, providers should not rely on a patient’s report of treatment effectiveness to assess asthma control.
This study is supported by AstraZeneca. Dr. Panettieri disclosed relationships with AstraZeneca, Sanofi, Regeneron, Genentech, and Novartis.
SOURCE: Panettieri R et al. CHEST 2019. Abstract, doi. 10.1016/j.chest.2019.08.272.
NEW ORLEANS – according to an observational study.
More than half (53%) of cases physicians rated as controlled were actually uncontrolled according to the Asthma Control Test (ACT), and 30% of patients who considered their asthma controlled actually had uncontrolled asthma according to the ACT.
Reynold A. Panettieri Jr., MD, of Rutgers University in New Brunswick, N.J., presented these findings at the annual meeting of the American College of Chest Physicians.
The findings are from the CHRONICLE study, an ongoing observational study of adults with severe asthma who are being treated by U.S. allergists or pulmonologists. The study enrolled 796 patients from Feb. 2018 to Feb. 2019, and 482 of them were evaluable because they completed the necessary surveys.
The patients’ median age at enrollment was 55 years, and 68% of patients were female. Most were white (82%), 12% were black, 6% were an “other” race, and 7% had Hispanic ethnicity. The median body mass index was 31 kg/m2.
Patients received care from an allergist (49%), a pulmonologist (38%), or both (13%). Patients were treated with biologics (n = 370), maintenance systemic corticosteroids (n = 64), or high-dosage inhaled corticosteroids with additional controllers (n = 90).
At patient enrollment, physicians reported their assessment of patients’ asthma control and completed the 5-point Global Evaluation of Treatment Effectiveness (GETE). The physicians’ assessments of patients were informed by patients’ verbal reports (50%), lung function testing (44%), in-office ACT (41%), and recent exacerbations (39%).
Patients also completed the ACT and GETE online at the time of enrollment. Neither patients nor physicians were privy to the other group’s responses.
Overall, physicians said 279 patients had controlled asthma. However, according to the ACT, 27% of these cases were very poorly controlled, 26% were not well controlled, and 47% were well controlled.
“So [when] we as a provider say the patient’s controlled, we’re wrong half the time,” Dr. Panettieri said.
However, physicians were more accurate when deeming patients’ asthma uncontrolled. Physicians said 201 cases of asthma were uncontrolled, and the ACT said 64% of these cases were very poorly controlled, 22% were not well controlled, and 13% were well controlled.
Compared with the physicians’ results, the patients’ reports were more in line with ACT results. However, the patients still overestimated control.
In all, 222 patients said their asthma was controlled. According to the ACT, 70% of these cases were well controlled, 23% were not well controlled, and 7% were very poorly controlled.
Patients were even more accurate when deeming their asthma uncontrolled. A total of 258 patients said their asthma was uncontrolled. According to the ACT, 74% of these cases were very poorly controlled, 25% were not well controlled, and 1% were well controlled.
“About 99% of the time, when a patient tells you they’re uncontrolled, they’re uncontrolled by the ACT,” Dr. Panettieri said.
Though patients were fairly accurate when assessing asthma control, they were less accurate when gauging treatment effectiveness. A majority of patients overestimated the effectiveness of treatment.
There were 124 patients who did not have any improvement after treatment, according to physicians. Although 23% of the patients concurred with this assessment, 77% said they did experience some improvement.
On the other hand, there were 355 patients who had some improvement after treatment according to physicians, and most of these patients (96%) agreed that they had some improvement.
Dr. Panettieri said these results support use of the ACT and similar tools. When using these tools isn’t feasible, Dr. Panettieri recommends simply asking patients how they are feeling. However, he said, providers should not rely on a patient’s report of treatment effectiveness to assess asthma control.
This study is supported by AstraZeneca. Dr. Panettieri disclosed relationships with AstraZeneca, Sanofi, Regeneron, Genentech, and Novartis.
SOURCE: Panettieri R et al. CHEST 2019. Abstract, doi. 10.1016/j.chest.2019.08.272.
REPORTING FROM CHEST 2019
FDA approves ustekinumab for ulcerative colitis
. This is the human interleukin-12 and IL-23 antagonist’s fourth indication since it was first approved by the FDA in 2009.
The approval is based on findings from the phase 3 UNIFI clinical trial, which achieved its primary endpoint of clinical remission over the course of both induction and maintenance. The 8-week induction study saw 19% of patients achieve clinical remission and 58% demonstrating clinical response; at the 1 year mark, after 44 weeks of maintenance therapy, 43% of patients were in clinical remission without steroids. The trial also assessed a novel histologic-endoscopic mucosal improvement endpoint that examined cellular improvement through both histologic examination and images observed during colonoscopy; 17% of treated patients achieved this endpoint at week 8, and 44% had by 1 year.
“The FDA approval of Stelara for [ulcerative colitis] represents an exciting milestone, offering patients a new option that has demonstrated improvement of the histology and endoscopic appearance of the intestinal lining, while also offering patients the potential for response and remission without the need for steroids,” said William J. Sandborn, MD, chief of the division of gastroenterology and professor of medicine at University of California, San Diego, and a study investigator.
Because of ustekinumab’s effects on the immune system, it may increase the risk of serious infection; as such, patients and health care professionals should discuss any signs of infection before initiation and continue discussions afterward. There are also concerns about risks of cancers, serious allergic reactions, and lung inflammation.
Full prescribing information is available on the Janssen website, as is the full press release regarding the approval
. This is the human interleukin-12 and IL-23 antagonist’s fourth indication since it was first approved by the FDA in 2009.
The approval is based on findings from the phase 3 UNIFI clinical trial, which achieved its primary endpoint of clinical remission over the course of both induction and maintenance. The 8-week induction study saw 19% of patients achieve clinical remission and 58% demonstrating clinical response; at the 1 year mark, after 44 weeks of maintenance therapy, 43% of patients were in clinical remission without steroids. The trial also assessed a novel histologic-endoscopic mucosal improvement endpoint that examined cellular improvement through both histologic examination and images observed during colonoscopy; 17% of treated patients achieved this endpoint at week 8, and 44% had by 1 year.
“The FDA approval of Stelara for [ulcerative colitis] represents an exciting milestone, offering patients a new option that has demonstrated improvement of the histology and endoscopic appearance of the intestinal lining, while also offering patients the potential for response and remission without the need for steroids,” said William J. Sandborn, MD, chief of the division of gastroenterology and professor of medicine at University of California, San Diego, and a study investigator.
Because of ustekinumab’s effects on the immune system, it may increase the risk of serious infection; as such, patients and health care professionals should discuss any signs of infection before initiation and continue discussions afterward. There are also concerns about risks of cancers, serious allergic reactions, and lung inflammation.
Full prescribing information is available on the Janssen website, as is the full press release regarding the approval
. This is the human interleukin-12 and IL-23 antagonist’s fourth indication since it was first approved by the FDA in 2009.
The approval is based on findings from the phase 3 UNIFI clinical trial, which achieved its primary endpoint of clinical remission over the course of both induction and maintenance. The 8-week induction study saw 19% of patients achieve clinical remission and 58% demonstrating clinical response; at the 1 year mark, after 44 weeks of maintenance therapy, 43% of patients were in clinical remission without steroids. The trial also assessed a novel histologic-endoscopic mucosal improvement endpoint that examined cellular improvement through both histologic examination and images observed during colonoscopy; 17% of treated patients achieved this endpoint at week 8, and 44% had by 1 year.
“The FDA approval of Stelara for [ulcerative colitis] represents an exciting milestone, offering patients a new option that has demonstrated improvement of the histology and endoscopic appearance of the intestinal lining, while also offering patients the potential for response and remission without the need for steroids,” said William J. Sandborn, MD, chief of the division of gastroenterology and professor of medicine at University of California, San Diego, and a study investigator.
Because of ustekinumab’s effects on the immune system, it may increase the risk of serious infection; as such, patients and health care professionals should discuss any signs of infection before initiation and continue discussions afterward. There are also concerns about risks of cancers, serious allergic reactions, and lung inflammation.
Full prescribing information is available on the Janssen website, as is the full press release regarding the approval
Checklist may improve quality measures in the surgical ICU
NEW ORLEANS – A standardized checklist may help reduce errors and improve common quality measures in critically ill patients, results of a recent retrospective analysis of 200 consecutive patients suggest.
Use of the checklist was linked to significantly shorter hospital length of stay and ICU length of stay as well as fewer days on a ventilator in the analysis, which was presented here at the annual meeting of the American College of Chest Physicians. The 10-item standardized checklist covered a variety topics ranging from comfort, prophylaxis, and sedation to infection control and prevention, nutrition, and medication management review.
Although health economics weren’t evaluated in this analysis, changes in those quality measures might also impact the bottom line, according to study coauthor Priscilla Chow, DO, a resident at Suburban Community Hospital in East Norriton, Pa.
“Obviously, if the patient is spending less time in the hospital and fewer days on the ventilator and in the ICU, then we can potentially also be more cost effective in our care,” Dr. Chow said in a podium presentation at the meeting.
The use of checklists to standardize processes and reduce errors is a “relatively simple approach” that was adopted from the airline industry and now has been evaluated in a variety of medical care settings, according to Dr. Chow.
Previous studies have demonstrated that checklist-driven care may reduce the incidence of postoperative complications, central line–associated bloodstream infection, ventilator-associated pneumonia, and catheter associated–urinary tract infection.
The present retrospective data analysis by Dr. Chow and colleagues included 200 consecutive patients admitted to the surgical ICU at an urban level 1 trauma center, including 100 patients managed according to the checklist and 100 managed according to standard processes.
Though survival to discharge was comparable between the groups, use of the checklist was associated with a significantly shorter hospital length of stay versus standard care (23.9 vs. 9.5 days). Likewise, the ICU length of stay was shorter in the checklist group (13.0 vs. 6.5 days), and the checklist group had fewer ventilator days (7.7 to 2.8).
Injury Severity Score did not differ between groups, though overall, use of the checklist resulted in more of the underlying topics being addressed in clinical documentation (5.0 vs. 8.7 items).
Dr. Chow and colleagues disclosed that they had no relationships relevant to their study.
SOURCE: Akella K et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.201.
NEW ORLEANS – A standardized checklist may help reduce errors and improve common quality measures in critically ill patients, results of a recent retrospective analysis of 200 consecutive patients suggest.
Use of the checklist was linked to significantly shorter hospital length of stay and ICU length of stay as well as fewer days on a ventilator in the analysis, which was presented here at the annual meeting of the American College of Chest Physicians. The 10-item standardized checklist covered a variety topics ranging from comfort, prophylaxis, and sedation to infection control and prevention, nutrition, and medication management review.
Although health economics weren’t evaluated in this analysis, changes in those quality measures might also impact the bottom line, according to study coauthor Priscilla Chow, DO, a resident at Suburban Community Hospital in East Norriton, Pa.
“Obviously, if the patient is spending less time in the hospital and fewer days on the ventilator and in the ICU, then we can potentially also be more cost effective in our care,” Dr. Chow said in a podium presentation at the meeting.
The use of checklists to standardize processes and reduce errors is a “relatively simple approach” that was adopted from the airline industry and now has been evaluated in a variety of medical care settings, according to Dr. Chow.
Previous studies have demonstrated that checklist-driven care may reduce the incidence of postoperative complications, central line–associated bloodstream infection, ventilator-associated pneumonia, and catheter associated–urinary tract infection.
The present retrospective data analysis by Dr. Chow and colleagues included 200 consecutive patients admitted to the surgical ICU at an urban level 1 trauma center, including 100 patients managed according to the checklist and 100 managed according to standard processes.
Though survival to discharge was comparable between the groups, use of the checklist was associated with a significantly shorter hospital length of stay versus standard care (23.9 vs. 9.5 days). Likewise, the ICU length of stay was shorter in the checklist group (13.0 vs. 6.5 days), and the checklist group had fewer ventilator days (7.7 to 2.8).
Injury Severity Score did not differ between groups, though overall, use of the checklist resulted in more of the underlying topics being addressed in clinical documentation (5.0 vs. 8.7 items).
Dr. Chow and colleagues disclosed that they had no relationships relevant to their study.
SOURCE: Akella K et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.201.
NEW ORLEANS – A standardized checklist may help reduce errors and improve common quality measures in critically ill patients, results of a recent retrospective analysis of 200 consecutive patients suggest.
Use of the checklist was linked to significantly shorter hospital length of stay and ICU length of stay as well as fewer days on a ventilator in the analysis, which was presented here at the annual meeting of the American College of Chest Physicians. The 10-item standardized checklist covered a variety topics ranging from comfort, prophylaxis, and sedation to infection control and prevention, nutrition, and medication management review.
Although health economics weren’t evaluated in this analysis, changes in those quality measures might also impact the bottom line, according to study coauthor Priscilla Chow, DO, a resident at Suburban Community Hospital in East Norriton, Pa.
“Obviously, if the patient is spending less time in the hospital and fewer days on the ventilator and in the ICU, then we can potentially also be more cost effective in our care,” Dr. Chow said in a podium presentation at the meeting.
The use of checklists to standardize processes and reduce errors is a “relatively simple approach” that was adopted from the airline industry and now has been evaluated in a variety of medical care settings, according to Dr. Chow.
Previous studies have demonstrated that checklist-driven care may reduce the incidence of postoperative complications, central line–associated bloodstream infection, ventilator-associated pneumonia, and catheter associated–urinary tract infection.
The present retrospective data analysis by Dr. Chow and colleagues included 200 consecutive patients admitted to the surgical ICU at an urban level 1 trauma center, including 100 patients managed according to the checklist and 100 managed according to standard processes.
Though survival to discharge was comparable between the groups, use of the checklist was associated with a significantly shorter hospital length of stay versus standard care (23.9 vs. 9.5 days). Likewise, the ICU length of stay was shorter in the checklist group (13.0 vs. 6.5 days), and the checklist group had fewer ventilator days (7.7 to 2.8).
Injury Severity Score did not differ between groups, though overall, use of the checklist resulted in more of the underlying topics being addressed in clinical documentation (5.0 vs. 8.7 items).
Dr. Chow and colleagues disclosed that they had no relationships relevant to their study.
SOURCE: Akella K et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.201.
REPORTING FROM CHEST 2019
Certain diabetes drugs may thwart dementia
COPENHAGEN – Selected antidiabetes medications appear to blunt the increased risk of dementia associated with type 2 diabetes, according to a Danish national case control registry study.
This benefit applies to the newer antidiabetic agents – specifically, the dipeptidyl peptidase 4 (DPP4) inhibitors, the glucagon-like peptide 1 (GLP1) analogs, and the sodium-glucose transport protein 2 (SGLT2) inhibitors – and metformin as well, Merete Osler, MD, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.
In contrast, neither insulin nor the sulfonylureas showed any signal of a protective effect against development of dementia. In fact, the use of sulfonylureas was associated with a small but statistically significant 7% increased risk, added Dr. Osler, of the University of Copenhagen.
Elsewhere at the meeting, investigators tapped a Swedish national registry to demonstrate that individuals with type 1 diabetes have a sharply reduced risk of developing schizophrenia.
Type 2 diabetes medications and dementia
Dr. Osler and colleagues are among several groups of investigators who have previously shown that patients with type 2 diabetes have an increased risk of dementia.
“This has raised the question of the role of dysregulated glucose metabolism in the development of this neurodegenerative disorder, and the possible effect of antidiabetic medications,” she noted.
To further explore this issue, which links two great ongoing global epidemics, Dr. Osler and coinvestigators conducted a nested case-control study including all 176,250 patients with type 2 diabetes in the comprehensive Danish National Diabetes Register for 1995-2012. The 11,619 patients with type 2 diabetes who received a dementia diagnosis were matched with 46,476 type 2 diabetes patients without dementia. The objective was to determine associations between dementia and ever-use and cumulative dose of antidiabetes drugs, alone and in combination, in logistic regression analyses adjusted for demographics, comorbid conditions, marital status, diabetic complications, and year of dementia diagnosis.
Patients who had ever used metformin had an adjusted 6% reduction in the likelihood of dementia compared with metformin nonusers, a modest but statistically significant difference. Those on a DPP4 inhibitor had a 20% reduction in risk. The GLP1 analogs were associated with a 42% decrease in risk. So were the SGLT2 inhibitors. A dose-response relationship was evident: The higher the cumulative exposure to these agents, the lower the odds of dementia.
Combination therapy is common in type 2 diabetes, so the investigators scrutinized the impact of a variety of multidrug combinations. Combinations including a DPP4 inhibitor or GLP1 analog were also associated with significantly reduced dementia risk.
Records of glycemic control in the form of hemoglobin A1c values were available on only 1,446 type 2 diabetic dementia patients and 4,003 matched controls. An analysis that incorporated this variable showed that the observed anti-dementia effect of selected diabetes drugs was independent of glycemic control, according to Dr. Osler.
The protective effect appeared to extend to both Alzheimer’s disease and vascular dementias, although firm conclusions can’t be drawn on this score because the study was insufficiently powered to address that issue.
Dr. Osler noted that the Danish study confirms a recent Taiwanese study showing an apparent protective effect against dementia for metformin in patients with type 2 diabetes (Aging Dis. 2019 Feb 1;10(1):37-48).
“Ours is the first study on the newer diabetic drugs, so our results need to be confirmed,” she pointed out.
If confirmed, however, it would warrant exploration of these drugs more generally as potential interventions to prevent dementia. That could open a whole new chapter in the remarkable story of the SGLT2 inhibitors, a class of drugs originally developed for treatment of type 2 diabetes but which in major randomized clinical trials later proved to be so effective in the treatment of heart failure that they are now considered cardiology drugs first.
Asked if she thinks these antidiabetes agents have a general neuroprotective effect or, instead, that the observed reduced risk of dementia is a function of patients being treated better early on with modern drugs, the psychiatrist replied, “I think it might be a combination of both, especially because we find different risk estimates between the drugs.”
Dr. Osler reported having no financial conflicts of interest regarding the study, which was funded by the Danish Diabetes Foundation, the Danish Medical Association, and several other foundations.
The full study details were published online shortly before her presentation at ECNP 2019 (Eur J Endocrinol. 2019 Aug 1. pii: EJE-19-0259.R1. doi: 10.1530/EJE-19-0259).
Type 1 diabetes and schizophrenia risk
Kristina Melkersson, MD, PhD, presented a cohort study that utilized Swedish national registries to examine the relationship between type 1 diabetes and schizophrenia. The study comprised 1,745,977 individuals, of whom 10,117 had type 1 diabetes, who were followed for a median of 9.7 and maximum of 18 years from their 13th birthday. During follow-up, 1,280 individuals were diagnosed with schizophrenia and 649 others with schizoaffective disorder. The adjusted risk of schizophrenia was 70% lower in patients with type 1 diabetes. However, there was no difference in the risk of schizoaffective disorder in the type 1 diabetic versus nondiabetic subjects.
The Swedish data confirm the findings of an earlier Finnish national study showing that the risk of schizophrenia is reduced in patients with type 1 diabetes (Arch Gen Psychiatry. 2007 Aug;64(8):894-9). These findings raise the intriguing possibility that autoimmunity somehow figures into the etiology of the psychiatric disorder. Other investigators have previously reported a reduced prevalence of rheumatoid arthritis in patients with schizophrenia, noted Dr. Melkersson of the Karolinska Institute in Stockholm.
She reported having no financial conflicts regarding her study.
SOURCE: Osler M. ECNP Abstract P180. Melkersson K. Abstract 81.
COPENHAGEN – Selected antidiabetes medications appear to blunt the increased risk of dementia associated with type 2 diabetes, according to a Danish national case control registry study.
This benefit applies to the newer antidiabetic agents – specifically, the dipeptidyl peptidase 4 (DPP4) inhibitors, the glucagon-like peptide 1 (GLP1) analogs, and the sodium-glucose transport protein 2 (SGLT2) inhibitors – and metformin as well, Merete Osler, MD, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.
In contrast, neither insulin nor the sulfonylureas showed any signal of a protective effect against development of dementia. In fact, the use of sulfonylureas was associated with a small but statistically significant 7% increased risk, added Dr. Osler, of the University of Copenhagen.
Elsewhere at the meeting, investigators tapped a Swedish national registry to demonstrate that individuals with type 1 diabetes have a sharply reduced risk of developing schizophrenia.
Type 2 diabetes medications and dementia
Dr. Osler and colleagues are among several groups of investigators who have previously shown that patients with type 2 diabetes have an increased risk of dementia.
“This has raised the question of the role of dysregulated glucose metabolism in the development of this neurodegenerative disorder, and the possible effect of antidiabetic medications,” she noted.
To further explore this issue, which links two great ongoing global epidemics, Dr. Osler and coinvestigators conducted a nested case-control study including all 176,250 patients with type 2 diabetes in the comprehensive Danish National Diabetes Register for 1995-2012. The 11,619 patients with type 2 diabetes who received a dementia diagnosis were matched with 46,476 type 2 diabetes patients without dementia. The objective was to determine associations between dementia and ever-use and cumulative dose of antidiabetes drugs, alone and in combination, in logistic regression analyses adjusted for demographics, comorbid conditions, marital status, diabetic complications, and year of dementia diagnosis.
Patients who had ever used metformin had an adjusted 6% reduction in the likelihood of dementia compared with metformin nonusers, a modest but statistically significant difference. Those on a DPP4 inhibitor had a 20% reduction in risk. The GLP1 analogs were associated with a 42% decrease in risk. So were the SGLT2 inhibitors. A dose-response relationship was evident: The higher the cumulative exposure to these agents, the lower the odds of dementia.
Combination therapy is common in type 2 diabetes, so the investigators scrutinized the impact of a variety of multidrug combinations. Combinations including a DPP4 inhibitor or GLP1 analog were also associated with significantly reduced dementia risk.
Records of glycemic control in the form of hemoglobin A1c values were available on only 1,446 type 2 diabetic dementia patients and 4,003 matched controls. An analysis that incorporated this variable showed that the observed anti-dementia effect of selected diabetes drugs was independent of glycemic control, according to Dr. Osler.
The protective effect appeared to extend to both Alzheimer’s disease and vascular dementias, although firm conclusions can’t be drawn on this score because the study was insufficiently powered to address that issue.
Dr. Osler noted that the Danish study confirms a recent Taiwanese study showing an apparent protective effect against dementia for metformin in patients with type 2 diabetes (Aging Dis. 2019 Feb 1;10(1):37-48).
“Ours is the first study on the newer diabetic drugs, so our results need to be confirmed,” she pointed out.
If confirmed, however, it would warrant exploration of these drugs more generally as potential interventions to prevent dementia. That could open a whole new chapter in the remarkable story of the SGLT2 inhibitors, a class of drugs originally developed for treatment of type 2 diabetes but which in major randomized clinical trials later proved to be so effective in the treatment of heart failure that they are now considered cardiology drugs first.
Asked if she thinks these antidiabetes agents have a general neuroprotective effect or, instead, that the observed reduced risk of dementia is a function of patients being treated better early on with modern drugs, the psychiatrist replied, “I think it might be a combination of both, especially because we find different risk estimates between the drugs.”
Dr. Osler reported having no financial conflicts of interest regarding the study, which was funded by the Danish Diabetes Foundation, the Danish Medical Association, and several other foundations.
The full study details were published online shortly before her presentation at ECNP 2019 (Eur J Endocrinol. 2019 Aug 1. pii: EJE-19-0259.R1. doi: 10.1530/EJE-19-0259).
Type 1 diabetes and schizophrenia risk
Kristina Melkersson, MD, PhD, presented a cohort study that utilized Swedish national registries to examine the relationship between type 1 diabetes and schizophrenia. The study comprised 1,745,977 individuals, of whom 10,117 had type 1 diabetes, who were followed for a median of 9.7 and maximum of 18 years from their 13th birthday. During follow-up, 1,280 individuals were diagnosed with schizophrenia and 649 others with schizoaffective disorder. The adjusted risk of schizophrenia was 70% lower in patients with type 1 diabetes. However, there was no difference in the risk of schizoaffective disorder in the type 1 diabetic versus nondiabetic subjects.
The Swedish data confirm the findings of an earlier Finnish national study showing that the risk of schizophrenia is reduced in patients with type 1 diabetes (Arch Gen Psychiatry. 2007 Aug;64(8):894-9). These findings raise the intriguing possibility that autoimmunity somehow figures into the etiology of the psychiatric disorder. Other investigators have previously reported a reduced prevalence of rheumatoid arthritis in patients with schizophrenia, noted Dr. Melkersson of the Karolinska Institute in Stockholm.
She reported having no financial conflicts regarding her study.
SOURCE: Osler M. ECNP Abstract P180. Melkersson K. Abstract 81.
COPENHAGEN – Selected antidiabetes medications appear to blunt the increased risk of dementia associated with type 2 diabetes, according to a Danish national case control registry study.
This benefit applies to the newer antidiabetic agents – specifically, the dipeptidyl peptidase 4 (DPP4) inhibitors, the glucagon-like peptide 1 (GLP1) analogs, and the sodium-glucose transport protein 2 (SGLT2) inhibitors – and metformin as well, Merete Osler, MD, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.
In contrast, neither insulin nor the sulfonylureas showed any signal of a protective effect against development of dementia. In fact, the use of sulfonylureas was associated with a small but statistically significant 7% increased risk, added Dr. Osler, of the University of Copenhagen.
Elsewhere at the meeting, investigators tapped a Swedish national registry to demonstrate that individuals with type 1 diabetes have a sharply reduced risk of developing schizophrenia.
Type 2 diabetes medications and dementia
Dr. Osler and colleagues are among several groups of investigators who have previously shown that patients with type 2 diabetes have an increased risk of dementia.
“This has raised the question of the role of dysregulated glucose metabolism in the development of this neurodegenerative disorder, and the possible effect of antidiabetic medications,” she noted.
To further explore this issue, which links two great ongoing global epidemics, Dr. Osler and coinvestigators conducted a nested case-control study including all 176,250 patients with type 2 diabetes in the comprehensive Danish National Diabetes Register for 1995-2012. The 11,619 patients with type 2 diabetes who received a dementia diagnosis were matched with 46,476 type 2 diabetes patients without dementia. The objective was to determine associations between dementia and ever-use and cumulative dose of antidiabetes drugs, alone and in combination, in logistic regression analyses adjusted for demographics, comorbid conditions, marital status, diabetic complications, and year of dementia diagnosis.
Patients who had ever used metformin had an adjusted 6% reduction in the likelihood of dementia compared with metformin nonusers, a modest but statistically significant difference. Those on a DPP4 inhibitor had a 20% reduction in risk. The GLP1 analogs were associated with a 42% decrease in risk. So were the SGLT2 inhibitors. A dose-response relationship was evident: The higher the cumulative exposure to these agents, the lower the odds of dementia.
Combination therapy is common in type 2 diabetes, so the investigators scrutinized the impact of a variety of multidrug combinations. Combinations including a DPP4 inhibitor or GLP1 analog were also associated with significantly reduced dementia risk.
Records of glycemic control in the form of hemoglobin A1c values were available on only 1,446 type 2 diabetic dementia patients and 4,003 matched controls. An analysis that incorporated this variable showed that the observed anti-dementia effect of selected diabetes drugs was independent of glycemic control, according to Dr. Osler.
The protective effect appeared to extend to both Alzheimer’s disease and vascular dementias, although firm conclusions can’t be drawn on this score because the study was insufficiently powered to address that issue.
Dr. Osler noted that the Danish study confirms a recent Taiwanese study showing an apparent protective effect against dementia for metformin in patients with type 2 diabetes (Aging Dis. 2019 Feb 1;10(1):37-48).
“Ours is the first study on the newer diabetic drugs, so our results need to be confirmed,” she pointed out.
If confirmed, however, it would warrant exploration of these drugs more generally as potential interventions to prevent dementia. That could open a whole new chapter in the remarkable story of the SGLT2 inhibitors, a class of drugs originally developed for treatment of type 2 diabetes but which in major randomized clinical trials later proved to be so effective in the treatment of heart failure that they are now considered cardiology drugs first.
Asked if she thinks these antidiabetes agents have a general neuroprotective effect or, instead, that the observed reduced risk of dementia is a function of patients being treated better early on with modern drugs, the psychiatrist replied, “I think it might be a combination of both, especially because we find different risk estimates between the drugs.”
Dr. Osler reported having no financial conflicts of interest regarding the study, which was funded by the Danish Diabetes Foundation, the Danish Medical Association, and several other foundations.
The full study details were published online shortly before her presentation at ECNP 2019 (Eur J Endocrinol. 2019 Aug 1. pii: EJE-19-0259.R1. doi: 10.1530/EJE-19-0259).
Type 1 diabetes and schizophrenia risk
Kristina Melkersson, MD, PhD, presented a cohort study that utilized Swedish national registries to examine the relationship between type 1 diabetes and schizophrenia. The study comprised 1,745,977 individuals, of whom 10,117 had type 1 diabetes, who were followed for a median of 9.7 and maximum of 18 years from their 13th birthday. During follow-up, 1,280 individuals were diagnosed with schizophrenia and 649 others with schizoaffective disorder. The adjusted risk of schizophrenia was 70% lower in patients with type 1 diabetes. However, there was no difference in the risk of schizoaffective disorder in the type 1 diabetic versus nondiabetic subjects.
The Swedish data confirm the findings of an earlier Finnish national study showing that the risk of schizophrenia is reduced in patients with type 1 diabetes (Arch Gen Psychiatry. 2007 Aug;64(8):894-9). These findings raise the intriguing possibility that autoimmunity somehow figures into the etiology of the psychiatric disorder. Other investigators have previously reported a reduced prevalence of rheumatoid arthritis in patients with schizophrenia, noted Dr. Melkersson of the Karolinska Institute in Stockholm.
She reported having no financial conflicts regarding her study.
SOURCE: Osler M. ECNP Abstract P180. Melkersson K. Abstract 81.
REPORTING FROM ECNP 2019
Immunotherapy enables nephrectomy with good outcomes in advanced RCC
Some patients with advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICIs) can safely undergo nephrectomy and experience favorable surgical outcomes and pathologic responses, a cohort study suggests.
“The introduction of several novel classes of systemic therapies, including targeted therapies and most recently ICI, has revolutionized the management of metastatic RCC over the last decade,” noted the investigators, who were led by Nirmish Singla, MD, from the department of urology at the University of Texas Southwestern Medical Center, Dallas. “With these new therapies, the role of nephrectomy in the treatment paradigm for advanced RCC has continued to evolve.”
The investigators undertook a single-center retrospective cohort study, assessing outcomes of 11 nephrectomies (10 radical, 1 partial) in 10 patients with advanced RCC who had received ICIs. Half had received nivolumab (Opdivo) alone, while the other half had received nivolumab in combination with ipilimumab (Yervoy); in six patients, these therapies were given first line.
Study results reported in Urologic Oncology showed that, at the time of nephrectomy, the patients had a median age of 64 years, with a range from 41 years to 83 years. Surgery was performed laparoscopically in five cases, and four patients had a concomitant thrombectomy.
The median operative time was 180 minutes, and the median estimated blood loss was 100 mL. None of the patients experienced major intraoperative complications. Four experienced postoperative complications; in three, they were addressed with interventional radiology procedures. The median length of stay was 4 days.
Pathology findings showed that one patient achieved a response to immunotherapy in the primary tumor (pT0), and three of four patients who underwent resection of hepatic, pulmonary, or adrenal metastases had no detectable cancer (pM0). All surgical margins were negative.
During a median postoperative follow-up of 180 days, one patient died of progressive disease more than 3 months after surgery, and another died of pulmonary embolism complicated by sepsis. Six patients did not have any complications or readmissions.
“In our experience, nephrectomy following ICI for RCC is both safe and technically feasible. Surgical and postoperative outcomes are encouraging, and pathologic response to ICI is strikingly favorable in both the primary tumor and metastatic sites,” Dr. Singla and coinvestigators wrote. “Biopsies of lesions responding radiographically to ICIs should be considered prior to surgical excision.”
“As multimodal management in the immunotherapy era continues to evolve, the utility and timing of nephrectomy combined with ICI in selected patients warrants further study,” they conclude.
Dr. Singla disclosed that he had no relevant conflicts of interest. The study did not receive any specific funding.
SOURCE: Singla N et al. Urol Oncol. 2019 Sep 12. doi: 10.1016/j.urolonc.2019.08.012.
Some patients with advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICIs) can safely undergo nephrectomy and experience favorable surgical outcomes and pathologic responses, a cohort study suggests.
“The introduction of several novel classes of systemic therapies, including targeted therapies and most recently ICI, has revolutionized the management of metastatic RCC over the last decade,” noted the investigators, who were led by Nirmish Singla, MD, from the department of urology at the University of Texas Southwestern Medical Center, Dallas. “With these new therapies, the role of nephrectomy in the treatment paradigm for advanced RCC has continued to evolve.”
The investigators undertook a single-center retrospective cohort study, assessing outcomes of 11 nephrectomies (10 radical, 1 partial) in 10 patients with advanced RCC who had received ICIs. Half had received nivolumab (Opdivo) alone, while the other half had received nivolumab in combination with ipilimumab (Yervoy); in six patients, these therapies were given first line.
Study results reported in Urologic Oncology showed that, at the time of nephrectomy, the patients had a median age of 64 years, with a range from 41 years to 83 years. Surgery was performed laparoscopically in five cases, and four patients had a concomitant thrombectomy.
The median operative time was 180 minutes, and the median estimated blood loss was 100 mL. None of the patients experienced major intraoperative complications. Four experienced postoperative complications; in three, they were addressed with interventional radiology procedures. The median length of stay was 4 days.
Pathology findings showed that one patient achieved a response to immunotherapy in the primary tumor (pT0), and three of four patients who underwent resection of hepatic, pulmonary, or adrenal metastases had no detectable cancer (pM0). All surgical margins were negative.
During a median postoperative follow-up of 180 days, one patient died of progressive disease more than 3 months after surgery, and another died of pulmonary embolism complicated by sepsis. Six patients did not have any complications or readmissions.
“In our experience, nephrectomy following ICI for RCC is both safe and technically feasible. Surgical and postoperative outcomes are encouraging, and pathologic response to ICI is strikingly favorable in both the primary tumor and metastatic sites,” Dr. Singla and coinvestigators wrote. “Biopsies of lesions responding radiographically to ICIs should be considered prior to surgical excision.”
“As multimodal management in the immunotherapy era continues to evolve, the utility and timing of nephrectomy combined with ICI in selected patients warrants further study,” they conclude.
Dr. Singla disclosed that he had no relevant conflicts of interest. The study did not receive any specific funding.
SOURCE: Singla N et al. Urol Oncol. 2019 Sep 12. doi: 10.1016/j.urolonc.2019.08.012.
Some patients with advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICIs) can safely undergo nephrectomy and experience favorable surgical outcomes and pathologic responses, a cohort study suggests.
“The introduction of several novel classes of systemic therapies, including targeted therapies and most recently ICI, has revolutionized the management of metastatic RCC over the last decade,” noted the investigators, who were led by Nirmish Singla, MD, from the department of urology at the University of Texas Southwestern Medical Center, Dallas. “With these new therapies, the role of nephrectomy in the treatment paradigm for advanced RCC has continued to evolve.”
The investigators undertook a single-center retrospective cohort study, assessing outcomes of 11 nephrectomies (10 radical, 1 partial) in 10 patients with advanced RCC who had received ICIs. Half had received nivolumab (Opdivo) alone, while the other half had received nivolumab in combination with ipilimumab (Yervoy); in six patients, these therapies were given first line.
Study results reported in Urologic Oncology showed that, at the time of nephrectomy, the patients had a median age of 64 years, with a range from 41 years to 83 years. Surgery was performed laparoscopically in five cases, and four patients had a concomitant thrombectomy.
The median operative time was 180 minutes, and the median estimated blood loss was 100 mL. None of the patients experienced major intraoperative complications. Four experienced postoperative complications; in three, they were addressed with interventional radiology procedures. The median length of stay was 4 days.
Pathology findings showed that one patient achieved a response to immunotherapy in the primary tumor (pT0), and three of four patients who underwent resection of hepatic, pulmonary, or adrenal metastases had no detectable cancer (pM0). All surgical margins were negative.
During a median postoperative follow-up of 180 days, one patient died of progressive disease more than 3 months after surgery, and another died of pulmonary embolism complicated by sepsis. Six patients did not have any complications or readmissions.
“In our experience, nephrectomy following ICI for RCC is both safe and technically feasible. Surgical and postoperative outcomes are encouraging, and pathologic response to ICI is strikingly favorable in both the primary tumor and metastatic sites,” Dr. Singla and coinvestigators wrote. “Biopsies of lesions responding radiographically to ICIs should be considered prior to surgical excision.”
“As multimodal management in the immunotherapy era continues to evolve, the utility and timing of nephrectomy combined with ICI in selected patients warrants further study,” they conclude.
Dr. Singla disclosed that he had no relevant conflicts of interest. The study did not receive any specific funding.
SOURCE: Singla N et al. Urol Oncol. 2019 Sep 12. doi: 10.1016/j.urolonc.2019.08.012.
FROM UROLOGIC ONCOLOGY