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FDA grants accelerated approval for treatment of Chagas disease in children
The Food and Drug Administration announced Aug. 29 the accelerated approval of benznidazole for use in children aged 2-12 years who have Chagas disease.
In two placebo-controlled clinical trials, researchers examined pediatric patients aged 6-12 with Chagas disease. In the first trial, about 60% of children treated with benznidazole had an antibody test change from positive to negative, compared with about 14% children who received a placebo. Similar findings were found in the second trial. In that one, about 55% of children treated with benznidazole had an antibody test change from positive to negative, compared with 5% who received a placebo. Also, a different study of the safety and pharmacokinetics of benznidazole in pediatric patients aged 2-12 provided information for dosing recommendations down to 2 years of age.
“The FDA is committed to making available safe and effective therapeutic options to treat tropical diseases,” Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in a press release.
This is the first treatment approved in the United States for Chagas disease. According to the agency, additional study is needed to “verify and describe the anticipated clinical benefit of benznidazole.”
Read the full press release on the FDA’s website.
The Food and Drug Administration announced Aug. 29 the accelerated approval of benznidazole for use in children aged 2-12 years who have Chagas disease.
In two placebo-controlled clinical trials, researchers examined pediatric patients aged 6-12 with Chagas disease. In the first trial, about 60% of children treated with benznidazole had an antibody test change from positive to negative, compared with about 14% children who received a placebo. Similar findings were found in the second trial. In that one, about 55% of children treated with benznidazole had an antibody test change from positive to negative, compared with 5% who received a placebo. Also, a different study of the safety and pharmacokinetics of benznidazole in pediatric patients aged 2-12 provided information for dosing recommendations down to 2 years of age.
“The FDA is committed to making available safe and effective therapeutic options to treat tropical diseases,” Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in a press release.
This is the first treatment approved in the United States for Chagas disease. According to the agency, additional study is needed to “verify and describe the anticipated clinical benefit of benznidazole.”
Read the full press release on the FDA’s website.
The Food and Drug Administration announced Aug. 29 the accelerated approval of benznidazole for use in children aged 2-12 years who have Chagas disease.
In two placebo-controlled clinical trials, researchers examined pediatric patients aged 6-12 with Chagas disease. In the first trial, about 60% of children treated with benznidazole had an antibody test change from positive to negative, compared with about 14% children who received a placebo. Similar findings were found in the second trial. In that one, about 55% of children treated with benznidazole had an antibody test change from positive to negative, compared with 5% who received a placebo. Also, a different study of the safety and pharmacokinetics of benznidazole in pediatric patients aged 2-12 provided information for dosing recommendations down to 2 years of age.
“The FDA is committed to making available safe and effective therapeutic options to treat tropical diseases,” Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in a press release.
This is the first treatment approved in the United States for Chagas disease. According to the agency, additional study is needed to “verify and describe the anticipated clinical benefit of benznidazole.”
Read the full press release on the FDA’s website.
DoD, VA Join Federal Response to Harvey
The VA announced medical centers open in Houston and central Arkansas are providing assistance to veterans affected by Hurricane Harvey across southeastern Texas, Arkansas, Mississippi, Louisiana, and Oklahoma. It also has deployed Mobile Vet Centers to veterans in Corpus Christi, Texas and other effected areas to provide counselling services.
Due to the State of Emergency declared in Louisiana and Texas, TRICARE has implemented emergency refill procedures from August 23rd - September 5th. Phone numbers and advice have been provided to assist in refilling prescriptions. The referral requirement also has been waived for those who have been evacuated in southeastern Texas counties from August 24th- September 5th.
The DoD has deployed about 3,000 Texas National Guardsmen and Guardsmen from other states for search and rescue. Director of domestic operations for the National Guard Bureau, Air Force Maj Gen. James C. Witham, says the bureau has identified “20,000 to 30,000 additional soldiers and airmen that could be used.” The Texas National Guardsmen has its personnel and about 16 aircrafts conducting day and night searches. National Guardsmen from all over the country have been involved in the rescue of more than 3,500 people and 300 pets through boats, vehicles, and helicopters. The DoD also is providing 11 generators, and 50,000 gallons of gasoline and diesel fuel through the Defense Logistics Agency for.
On Tuesday alone, 2 U.S. Navy helicopter squadron detachments rescued 227 flood victims while flying from Fort Worth, Texas. Helicopter Sea Combat Squadrons 7 and 28 have relocated to be closer to the epicenter of the flooding in and around Houston.
In order to drastically reduce response time, the 112 Sailors from the Dusty Dogs and Ghostriders of Helicopter Sea Combat Squadrons (HSC) 7 and 28 (respectively) moved their staging site and six MH-60S Knighthawk helicopters in order to be even closer to the disaster zone in the wake of Hurricane Harvey. USA.gov has provided resources on what to do now that the hurricane has subsided for residents in the affected areas. A list of recommendations from federal officials, advice on how to replace vital documents, and the latest news on the storm are provided with links.
FEMA has provided a list of emergency phone numbers to County Emergency Operation centers and the U.S. Coast Guard Sector Huston Command Center for life-threating situations. Other resources for safety tips, the National Flood Insurance Program, how to apply for assistance, and how to help others needing assistance are provided as well.
The VA announced medical centers open in Houston and central Arkansas are providing assistance to veterans affected by Hurricane Harvey across southeastern Texas, Arkansas, Mississippi, Louisiana, and Oklahoma. It also has deployed Mobile Vet Centers to veterans in Corpus Christi, Texas and other effected areas to provide counselling services.
Due to the State of Emergency declared in Louisiana and Texas, TRICARE has implemented emergency refill procedures from August 23rd - September 5th. Phone numbers and advice have been provided to assist in refilling prescriptions. The referral requirement also has been waived for those who have been evacuated in southeastern Texas counties from August 24th- September 5th.
The DoD has deployed about 3,000 Texas National Guardsmen and Guardsmen from other states for search and rescue. Director of domestic operations for the National Guard Bureau, Air Force Maj Gen. James C. Witham, says the bureau has identified “20,000 to 30,000 additional soldiers and airmen that could be used.” The Texas National Guardsmen has its personnel and about 16 aircrafts conducting day and night searches. National Guardsmen from all over the country have been involved in the rescue of more than 3,500 people and 300 pets through boats, vehicles, and helicopters. The DoD also is providing 11 generators, and 50,000 gallons of gasoline and diesel fuel through the Defense Logistics Agency for.
On Tuesday alone, 2 U.S. Navy helicopter squadron detachments rescued 227 flood victims while flying from Fort Worth, Texas. Helicopter Sea Combat Squadrons 7 and 28 have relocated to be closer to the epicenter of the flooding in and around Houston.
In order to drastically reduce response time, the 112 Sailors from the Dusty Dogs and Ghostriders of Helicopter Sea Combat Squadrons (HSC) 7 and 28 (respectively) moved their staging site and six MH-60S Knighthawk helicopters in order to be even closer to the disaster zone in the wake of Hurricane Harvey. USA.gov has provided resources on what to do now that the hurricane has subsided for residents in the affected areas. A list of recommendations from federal officials, advice on how to replace vital documents, and the latest news on the storm are provided with links.
FEMA has provided a list of emergency phone numbers to County Emergency Operation centers and the U.S. Coast Guard Sector Huston Command Center for life-threating situations. Other resources for safety tips, the National Flood Insurance Program, how to apply for assistance, and how to help others needing assistance are provided as well.
The VA announced medical centers open in Houston and central Arkansas are providing assistance to veterans affected by Hurricane Harvey across southeastern Texas, Arkansas, Mississippi, Louisiana, and Oklahoma. It also has deployed Mobile Vet Centers to veterans in Corpus Christi, Texas and other effected areas to provide counselling services.
Due to the State of Emergency declared in Louisiana and Texas, TRICARE has implemented emergency refill procedures from August 23rd - September 5th. Phone numbers and advice have been provided to assist in refilling prescriptions. The referral requirement also has been waived for those who have been evacuated in southeastern Texas counties from August 24th- September 5th.
The DoD has deployed about 3,000 Texas National Guardsmen and Guardsmen from other states for search and rescue. Director of domestic operations for the National Guard Bureau, Air Force Maj Gen. James C. Witham, says the bureau has identified “20,000 to 30,000 additional soldiers and airmen that could be used.” The Texas National Guardsmen has its personnel and about 16 aircrafts conducting day and night searches. National Guardsmen from all over the country have been involved in the rescue of more than 3,500 people and 300 pets through boats, vehicles, and helicopters. The DoD also is providing 11 generators, and 50,000 gallons of gasoline and diesel fuel through the Defense Logistics Agency for.
On Tuesday alone, 2 U.S. Navy helicopter squadron detachments rescued 227 flood victims while flying from Fort Worth, Texas. Helicopter Sea Combat Squadrons 7 and 28 have relocated to be closer to the epicenter of the flooding in and around Houston.
In order to drastically reduce response time, the 112 Sailors from the Dusty Dogs and Ghostriders of Helicopter Sea Combat Squadrons (HSC) 7 and 28 (respectively) moved their staging site and six MH-60S Knighthawk helicopters in order to be even closer to the disaster zone in the wake of Hurricane Harvey. USA.gov has provided resources on what to do now that the hurricane has subsided for residents in the affected areas. A list of recommendations from federal officials, advice on how to replace vital documents, and the latest news on the storm are provided with links.
FEMA has provided a list of emergency phone numbers to County Emergency Operation centers and the U.S. Coast Guard Sector Huston Command Center for life-threating situations. Other resources for safety tips, the National Flood Insurance Program, how to apply for assistance, and how to help others needing assistance are provided as well.
Allopurinol extension trial backs treat-to-target approach in gout
In the treatment of gout, dose escalation of allopurinol to achieve target serum urate levels at or below 6 mg/dL appears safe and effective, even among patients with chronic kidney disease, according to a new open-label, extension study. The results build on a 12-month study that had shown safety and efficacy of the strategy.
The new results compared adverse events and serum urate levels between patients who stayed at increased allopurinol doses after achieving target serum urate levels, and control patients who were switched to a strategy of treating to target.
Dr. Stamp did emphasize the need to monitor liver and kidney function, as well as for rashes.
Allopurinol is approved at doses as high as 800 mg/day in the United States, and 900 mg/day in Europe, but most physicians rarely exceed 300 mg/day for fear of side effects. Existing guidelines and recommendations offer different opinions. The European League Against Rheumatism (EULAR) recommends switching to another urate-lowering therapy if the maximum dose adjusted to creatinine clearance (CrCl) isn’t effective, while the American College of Rheumatology recommends gradual dose escalation (DE) beyond CrCl-based doses, even in patients with chronic kidney disease.
The earlier study included 183 patients who had failed to achieve serum urate target levels at CrCl dose, which is intended to avoid allopurinol hypersensitivity syndrome and other potential adverse events. The short-term study results favored the DE approach. At 1 year, there was no difference in adverse events between the 93 control subjects and the 90 DE subjects. The DE group experienced an average serum urate reduction of 1.5 mg/dL, compared with 0.35 mg/dL in the control group (P less than .001). Overall, 32% of controls and 69% of the dose escalation group had achieved serum urate of 6.0 mg/dL or less.
In the extension study, subjects in the control group were switched to a strategy of dose escalation (control/DE), while the patients in the original treatment group remained at their existing allopurinol doses (DE/DE). Those who switched had a mean reduction in serum urate of 1.1 mg/dL, compared with an increase of 0.1 mg/dL in the DE/DE group (P less than .001).
From baseline to month 24, the control/DE group experienced a change in serum urate from 7.13 mg/dL to 5.7 mg/dL, while the DE/DE group experienced a change from 7.18 mg/dL to 5.4 mg/dL.
Both groups had a significant reduction in gout flares, but there was no difference in flare reduction between the two groups at 24 months.
Of those with a tophus at baseline, 6 (16%) of 37 of the control/DE group and 4 (13%) of 31 of the DE/DE group had complete resolution of all tophi between months 12 and 24. Measurable tophi completely resolved between baseline and 24 months in the same percentage of patients (29%) in each group. Tophus size decline significantly overall in both groups together, and there was no difference between the randomized groups.
In the control/DE group, there were 38 serious adverse events in 14 patients, compared with 33 serious adverse events in 22 patients in the DE/DE group. None of the serious adverse events were believed to be related to allopurinol. There were four deaths in the control/DE group and three in the DE/DE group between months 12 and 24, but none of the deaths were believed to be related to allopurinol.
“It is common that people don’t respond to allopurinol at doses based on kidney function and then the dose is not increased. This should give prescribers more confidence to increase the dose,” Dr. Stamp said.
The Health Research Council of New Zealand funded the study. Dr. Stamp has received grants from Ardea Biosciences. One coauthor reported receiving grants and personal fees from AstraZeneca and Ardea Biosciences; personal fees from Takeda, Teijin, and Menarini; grants from Fonterra; and personal fees from Pfizer, Crealta, and Cymabay.
In the treatment of gout, dose escalation of allopurinol to achieve target serum urate levels at or below 6 mg/dL appears safe and effective, even among patients with chronic kidney disease, according to a new open-label, extension study. The results build on a 12-month study that had shown safety and efficacy of the strategy.
The new results compared adverse events and serum urate levels between patients who stayed at increased allopurinol doses after achieving target serum urate levels, and control patients who were switched to a strategy of treating to target.
Dr. Stamp did emphasize the need to monitor liver and kidney function, as well as for rashes.
Allopurinol is approved at doses as high as 800 mg/day in the United States, and 900 mg/day in Europe, but most physicians rarely exceed 300 mg/day for fear of side effects. Existing guidelines and recommendations offer different opinions. The European League Against Rheumatism (EULAR) recommends switching to another urate-lowering therapy if the maximum dose adjusted to creatinine clearance (CrCl) isn’t effective, while the American College of Rheumatology recommends gradual dose escalation (DE) beyond CrCl-based doses, even in patients with chronic kidney disease.
The earlier study included 183 patients who had failed to achieve serum urate target levels at CrCl dose, which is intended to avoid allopurinol hypersensitivity syndrome and other potential adverse events. The short-term study results favored the DE approach. At 1 year, there was no difference in adverse events between the 93 control subjects and the 90 DE subjects. The DE group experienced an average serum urate reduction of 1.5 mg/dL, compared with 0.35 mg/dL in the control group (P less than .001). Overall, 32% of controls and 69% of the dose escalation group had achieved serum urate of 6.0 mg/dL or less.
In the extension study, subjects in the control group were switched to a strategy of dose escalation (control/DE), while the patients in the original treatment group remained at their existing allopurinol doses (DE/DE). Those who switched had a mean reduction in serum urate of 1.1 mg/dL, compared with an increase of 0.1 mg/dL in the DE/DE group (P less than .001).
From baseline to month 24, the control/DE group experienced a change in serum urate from 7.13 mg/dL to 5.7 mg/dL, while the DE/DE group experienced a change from 7.18 mg/dL to 5.4 mg/dL.
Both groups had a significant reduction in gout flares, but there was no difference in flare reduction between the two groups at 24 months.
Of those with a tophus at baseline, 6 (16%) of 37 of the control/DE group and 4 (13%) of 31 of the DE/DE group had complete resolution of all tophi between months 12 and 24. Measurable tophi completely resolved between baseline and 24 months in the same percentage of patients (29%) in each group. Tophus size decline significantly overall in both groups together, and there was no difference between the randomized groups.
In the control/DE group, there were 38 serious adverse events in 14 patients, compared with 33 serious adverse events in 22 patients in the DE/DE group. None of the serious adverse events were believed to be related to allopurinol. There were four deaths in the control/DE group and three in the DE/DE group between months 12 and 24, but none of the deaths were believed to be related to allopurinol.
“It is common that people don’t respond to allopurinol at doses based on kidney function and then the dose is not increased. This should give prescribers more confidence to increase the dose,” Dr. Stamp said.
The Health Research Council of New Zealand funded the study. Dr. Stamp has received grants from Ardea Biosciences. One coauthor reported receiving grants and personal fees from AstraZeneca and Ardea Biosciences; personal fees from Takeda, Teijin, and Menarini; grants from Fonterra; and personal fees from Pfizer, Crealta, and Cymabay.
In the treatment of gout, dose escalation of allopurinol to achieve target serum urate levels at or below 6 mg/dL appears safe and effective, even among patients with chronic kidney disease, according to a new open-label, extension study. The results build on a 12-month study that had shown safety and efficacy of the strategy.
The new results compared adverse events and serum urate levels between patients who stayed at increased allopurinol doses after achieving target serum urate levels, and control patients who were switched to a strategy of treating to target.
Dr. Stamp did emphasize the need to monitor liver and kidney function, as well as for rashes.
Allopurinol is approved at doses as high as 800 mg/day in the United States, and 900 mg/day in Europe, but most physicians rarely exceed 300 mg/day for fear of side effects. Existing guidelines and recommendations offer different opinions. The European League Against Rheumatism (EULAR) recommends switching to another urate-lowering therapy if the maximum dose adjusted to creatinine clearance (CrCl) isn’t effective, while the American College of Rheumatology recommends gradual dose escalation (DE) beyond CrCl-based doses, even in patients with chronic kidney disease.
The earlier study included 183 patients who had failed to achieve serum urate target levels at CrCl dose, which is intended to avoid allopurinol hypersensitivity syndrome and other potential adverse events. The short-term study results favored the DE approach. At 1 year, there was no difference in adverse events between the 93 control subjects and the 90 DE subjects. The DE group experienced an average serum urate reduction of 1.5 mg/dL, compared with 0.35 mg/dL in the control group (P less than .001). Overall, 32% of controls and 69% of the dose escalation group had achieved serum urate of 6.0 mg/dL or less.
In the extension study, subjects in the control group were switched to a strategy of dose escalation (control/DE), while the patients in the original treatment group remained at their existing allopurinol doses (DE/DE). Those who switched had a mean reduction in serum urate of 1.1 mg/dL, compared with an increase of 0.1 mg/dL in the DE/DE group (P less than .001).
From baseline to month 24, the control/DE group experienced a change in serum urate from 7.13 mg/dL to 5.7 mg/dL, while the DE/DE group experienced a change from 7.18 mg/dL to 5.4 mg/dL.
Both groups had a significant reduction in gout flares, but there was no difference in flare reduction between the two groups at 24 months.
Of those with a tophus at baseline, 6 (16%) of 37 of the control/DE group and 4 (13%) of 31 of the DE/DE group had complete resolution of all tophi between months 12 and 24. Measurable tophi completely resolved between baseline and 24 months in the same percentage of patients (29%) in each group. Tophus size decline significantly overall in both groups together, and there was no difference between the randomized groups.
In the control/DE group, there were 38 serious adverse events in 14 patients, compared with 33 serious adverse events in 22 patients in the DE/DE group. None of the serious adverse events were believed to be related to allopurinol. There were four deaths in the control/DE group and three in the DE/DE group between months 12 and 24, but none of the deaths were believed to be related to allopurinol.
“It is common that people don’t respond to allopurinol at doses based on kidney function and then the dose is not increased. This should give prescribers more confidence to increase the dose,” Dr. Stamp said.
The Health Research Council of New Zealand funded the study. Dr. Stamp has received grants from Ardea Biosciences. One coauthor reported receiving grants and personal fees from AstraZeneca and Ardea Biosciences; personal fees from Takeda, Teijin, and Menarini; grants from Fonterra; and personal fees from Pfizer, Crealta, and Cymabay.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point: An extension study showed continued safety and efficacy of heightened allopurinol doses using a dose-escalation approach.
Major finding: A treat-to-target dosing strategy had a safety profile similar to that of a maximum dose adjusted to creatinine clearance.
Data source: Open-label extension study (n = 183).
Disclosures: The Health Research Council of New Zealand funded the study. Dr. Stamp has received grants from Ardea Biosciences. One coauthor reported receiving grants and personal fees from AstraZeneca and Ardea Biosciences; personal fees from Takeda, Teijin, and Menarini; grants from Fonterra; and personal fees from Pfizer, Crealta, and Cymabay.
Young adults lead the ranks of recently insured
The uninsured rate for young adults fell 50% from 2010 to 2016, according to the Agency for Healthcare Research and Quality.
In the first quarter of 2010, 30.6% of adults aged 18-29 years did not have health insurance at the time they were interviewed for the National Health Interview Survey. By the last quarter of 2016, that figure was down to 15.4%, a drop of nearly 50%, the AHRQ said in its annual National Healthcare Quality and Disparities Report.
For the total population under age 65 years, the uninsured rate dropped from 17.5% in the first quarter of 2010 to 10.8% in the fourth quarter of 2016, the AHRQ said, for an overall decline of 38%.
The uninsured rate for young adults fell 50% from 2010 to 2016, according to the Agency for Healthcare Research and Quality.
In the first quarter of 2010, 30.6% of adults aged 18-29 years did not have health insurance at the time they were interviewed for the National Health Interview Survey. By the last quarter of 2016, that figure was down to 15.4%, a drop of nearly 50%, the AHRQ said in its annual National Healthcare Quality and Disparities Report.
For the total population under age 65 years, the uninsured rate dropped from 17.5% in the first quarter of 2010 to 10.8% in the fourth quarter of 2016, the AHRQ said, for an overall decline of 38%.
The uninsured rate for young adults fell 50% from 2010 to 2016, according to the Agency for Healthcare Research and Quality.
In the first quarter of 2010, 30.6% of adults aged 18-29 years did not have health insurance at the time they were interviewed for the National Health Interview Survey. By the last quarter of 2016, that figure was down to 15.4%, a drop of nearly 50%, the AHRQ said in its annual National Healthcare Quality and Disparities Report.
For the total population under age 65 years, the uninsured rate dropped from 17.5% in the first quarter of 2010 to 10.8% in the fourth quarter of 2016, the AHRQ said, for an overall decline of 38%.
Tivozanib gets EU approval for advanced RCC
The European Commission has approved tivozanib for the treatment of advanced renal cell carcinoma (RCC) in adult patients in the European Union, Norway, and Iceland.
Tivozanib (Fotivda) is a vascular endothelial growth factor receptor tyrosine kinase inhibitor, taken orally once daily. It is indicated for first-line treatment of patients, naive to both vascular endothelial growth factor receptors and mTOR pathway inhibitors, experiencing disease progression following one cytokine therapy treatment, according to the press release.
Its approval is based on superior progression-free survival (PFS) in TIVO-1, a phase 3 trial comparing the efficacy and tolerability of tivozanib (1.5 mg once daily) with that of sorafenib (400 mg twice daily). In the overall trial population of 517 patients with advanced RCC, PFS was 11.9 months for patients treated with tivozanib, compared with 9.1 months for those treated with sorafenib (hazard ratio, 0.797; 95% confidence interval, 0.639-0.993; P = .042).
Patients in the tivozanib arm also experienced fewer cases of diarrhea and hand-foot syndrome, and required fewer dose reductions because of adverse effects than did those taking sorafenib.
The approval follows a recommendation from the Committee for Medical Products for Human Use.
The Food and Drug Administration rejected the New Drug Application for tivozanib in 2013, based on TIVO-1 data. Aveo Oncology plans to reapply in the United States with data from TIVO-3, expected in early 2018, they said in the press release.
The European Commission has approved tivozanib for the treatment of advanced renal cell carcinoma (RCC) in adult patients in the European Union, Norway, and Iceland.
Tivozanib (Fotivda) is a vascular endothelial growth factor receptor tyrosine kinase inhibitor, taken orally once daily. It is indicated for first-line treatment of patients, naive to both vascular endothelial growth factor receptors and mTOR pathway inhibitors, experiencing disease progression following one cytokine therapy treatment, according to the press release.
Its approval is based on superior progression-free survival (PFS) in TIVO-1, a phase 3 trial comparing the efficacy and tolerability of tivozanib (1.5 mg once daily) with that of sorafenib (400 mg twice daily). In the overall trial population of 517 patients with advanced RCC, PFS was 11.9 months for patients treated with tivozanib, compared with 9.1 months for those treated with sorafenib (hazard ratio, 0.797; 95% confidence interval, 0.639-0.993; P = .042).
Patients in the tivozanib arm also experienced fewer cases of diarrhea and hand-foot syndrome, and required fewer dose reductions because of adverse effects than did those taking sorafenib.
The approval follows a recommendation from the Committee for Medical Products for Human Use.
The Food and Drug Administration rejected the New Drug Application for tivozanib in 2013, based on TIVO-1 data. Aveo Oncology plans to reapply in the United States with data from TIVO-3, expected in early 2018, they said in the press release.
The European Commission has approved tivozanib for the treatment of advanced renal cell carcinoma (RCC) in adult patients in the European Union, Norway, and Iceland.
Tivozanib (Fotivda) is a vascular endothelial growth factor receptor tyrosine kinase inhibitor, taken orally once daily. It is indicated for first-line treatment of patients, naive to both vascular endothelial growth factor receptors and mTOR pathway inhibitors, experiencing disease progression following one cytokine therapy treatment, according to the press release.
Its approval is based on superior progression-free survival (PFS) in TIVO-1, a phase 3 trial comparing the efficacy and tolerability of tivozanib (1.5 mg once daily) with that of sorafenib (400 mg twice daily). In the overall trial population of 517 patients with advanced RCC, PFS was 11.9 months for patients treated with tivozanib, compared with 9.1 months for those treated with sorafenib (hazard ratio, 0.797; 95% confidence interval, 0.639-0.993; P = .042).
Patients in the tivozanib arm also experienced fewer cases of diarrhea and hand-foot syndrome, and required fewer dose reductions because of adverse effects than did those taking sorafenib.
The approval follows a recommendation from the Committee for Medical Products for Human Use.
The Food and Drug Administration rejected the New Drug Application for tivozanib in 2013, based on TIVO-1 data. Aveo Oncology plans to reapply in the United States with data from TIVO-3, expected in early 2018, they said in the press release.
Five outside-the-box ideas for fixing the individual insurance market
With Republican efforts to “repeal and replace” the Affordable Care Act stalled, tentative bipartisan initiatives are in the works to shore up the fragile individual insurance market that serves roughly 17 million Americans.
The Senate Health, Education, Labor and Pensions Committee launches hearings the week Congress returns in September on “stabilizing premiums in the individual insurance market” that will feature state governors and insurance commissioners. A bipartisan group in the House is also working to come up with compromise proposals.
Both before and after implementation of the federal health law, this market – serving people who don’t get coverage through work or the government – has proved problematic. Before the law, many people with preexisting health conditions could not get insurance at any price. Now, consumers in the individual market often face higher out-of-pocket costs and fewer choices of health care providers and insurers than in past years. More than 12 million people buy that insurance through the ACA’s marketplaces, while another 5 million buy it outside of the exchanges.
Policy makers generally agree on what immediate efforts to stabilize the market might include. At the top of most lists is ensuring federal payment of subsidies to insurers to pay the out-of-pocket expenses – such as deductibles and copayments – to protect customers with the lowest incomes. Insurers also want the federal government to continue enforcing the requirement that most Americans either have insurance or pay a tax penalty, and continuing efforts to get uninsured people to sign up for coverage during the upcoming open enrollment period, from Nov. 1 to Dec. 15. Those efforts are essential, insurers say, to help keep healthy customers in their risk pools to defray the costs of beneficiaries with medical needs.
But what about ideas that go beyond the oft-repeated ones? Here are five proposals that are more controversial but generating buzz.
1. Allow people into Medicare starting at age 55.
Getting slightly younger people into Medicare, the federal program for the disabled and Americans 65 and older, is a longtime goal of Democrats. It dates at least to the Clinton administration and was nearly included in the Affordable Care Act in 2010. A Medicare buy-in is not exactly the same as a “public option,” which many Democrats, including former President Barack Obama, have embraced. A true public option would offer government coverage to those of any age.
Lowering the age for Medicare eligibility (whether by allowing people to purchase coverage early or letting them join on the same terms as those aged 65) is controversial. Some Democrats support it as a first step toward a single-payer, Medicare-for-all system. Most Republicans oppose it on those same grounds – as a step toward government-run health care.
But proponents argue it would help the current individual market by excluding the oldest people, thereby lowering the average age of the risk pool. Since older patients, on average, cost more to insure, the change could lower premiums for everyone left in the ACA market. That’s the stated goal of a Medicare buy-in bill introduced earlier this month by Sen. Debbie Stabenow (D-Mich.) and seven other Democratic senators. That bill would allow Obamacare market customers ages 55-64 to purchase Medicare coverage instead, but would also let them use ACA tax credits if they are eligible for those. The cost of such policies, however, has not been worked out.
“The way we’ve structured it actually both helps Medicare by having younger people in that pool, and it helps private insurance by taking higher-cost individuals out of their pool,” Sen. Stabenow told The Detroit News.
Conservative health analysts don’t buy that, though. “This is just a way of saying we’re going to take these people out of the exchanges and put them where there are bigger subsidies,” said Joseph Antos of the conservative-leaning American Enterprise Institute (AEI).
2. Allow people to ‘buy in’ to Medicaid.
An alternative to letting people buy in to Medicare is letting them buy in to Medicaid, the joint federal-state program for those with low incomes.
Medicaid buy-ins already exist – for example, in 2005 Congress passed the Family Opportunity Act, which allows families earning up to three times the poverty level to purchase Medicaid coverage for their disabled children who aren’t otherwise eligible. Medicaid has typically provided richer benefits for those with disabilities than private health insurance.
Earlier this year, Gov. Brian Sandoval (R-Nev.) vetoed a bill that would have allowed Nevada residents to buy Medicaid coverage through the state’s insurance exchange.
Now Sen. Brian Schatz (D-Hawaii) is pushing a federal Medicaid buy-in plan, which he described to Vox.com last week. It would give states the option to allow people with incomes over current Medicaid eligibility thresholds to pay a premium to join the program. Like the Medicare buy-in bill, it would allow those who qualify for federal tax credits to use them to pay the premiums.
The proposal would also raise the amounts Medicaid pays to doctors, hospitals and other health care providers to the same level as it pays for Medicare patients. Traditionally, low Medicaid payment rates have kept many doctors, particularly specialists, from taking Medicaid.
As with the Medicare expansion, the idea of a further Medicaid expansion does not sit well with conservative policy analysts. “It’s completely unworkable,” Avik Roy of the Foundation for Research on Equal Opportunity, told Vox. He predicted it would raise Medicaid spending by $2 trillion over 10 years.
3. Get younger adults off their parents’ insurance and back into the individual market.
Allowing young adults up to age 26 to stay on their parents’ health plans is unquestionably one of the most popular ACA provisions. Democrats have touted it proudly while Republicans have dared not touch it in almost any of their overhaul proposals.
Yet what has been a boon to 3 million young adults (and a relief to their parents) has come at a cost to the individual marketplace itself, where only an estimated 28% of those buying coverage in state exchanges were ages 18-34 in 2016. That is well below the 40% most analysts said was necessary to keep the market stable.
“Frankly, it was really stupid,” to keep those young people out of the individual market, said Mr. Antos of AEI. The result has been a lack of people in the risk pool who are “young, healthy and whose parents will pay their premiums.”
But rolling back that piece of the law might be nearly impossible, said Mr. Antos, because “this is a middle-class giveaway.”
4. Require insurers who participate in other government programs to offer marketplace coverage.
One clear shortcoming of the individual marketplace is a lack of insurer competition, particularly in rural areas. While there appear to be no counties left with no company offering coverage for the coming year, the percentage of counties with only one insurer seems certain to rise from 2017’s 33%.
In an effort to more strongly encourage private companies to step up and offer coverage, several analysts have suggested tying access to participation in other government programs to a willingness to offer individual ACA policies as well.
For example, some have suggested insurers be required to provide policies in the marketplaces as a condition of being able to offer coverage to federal workers. Others have suggested that private insurers who offer profitable Medicare Advantage plans could also be required to offer individual exchange coverage, although the same rural areas with a lack of private individual market insurers also tend to lack Medicare Advantage coverage.
5. Let people use HSA contributions to pay health insurance premiums.
A little-noticed provision in one of the versions of the Senate GOP health bill that failed to pass in July would have allowed people to use money from tax-preferred health savings accounts (HSAs) to pay their insurance premiums. A little-noticed proposal from a group of ideologically diverse health care experts included a similar idea.
HSAs are linked to high-deductible insurance plans, and consumers use the money in the account to pay their out-of-pocket expenses. The money put into the account and the earnings are not taxable.
With a few exceptions, people with HSAs have not been allowed to use those funds to pay monthly premiums. But the change would be one way to provide relief to people who buy their own insurance, earn too much to get federal premium subsidies, and cannot deduct premiums from their taxes because they are not technically self-employed. Such people, though likely small in number, have been disproportionately hurt by rising premiums in the individual market since the ACA took full effect.
Still, the change would involve some trade-offs.
Roy Ramthun, who helped design HSAs as a Senate staffer in the early 2000s and helped implement them while at the Treasury Department during the George W. Bush administration, said that, generally, “Republicans have preferred to subsidize insurance premiums through tax deductions and credits and leave the HSA for out-of-pocket expenses.” Allowing premiums to be paid from HSA funds, he said, “could eat up the entire balance of the account and leave nothing for out-of-pocket expenses.” There are limits to how much money can be put into an HSA. For 2017, the maximum is $3,400 for an individual and $6,750 for a family.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
With Republican efforts to “repeal and replace” the Affordable Care Act stalled, tentative bipartisan initiatives are in the works to shore up the fragile individual insurance market that serves roughly 17 million Americans.
The Senate Health, Education, Labor and Pensions Committee launches hearings the week Congress returns in September on “stabilizing premiums in the individual insurance market” that will feature state governors and insurance commissioners. A bipartisan group in the House is also working to come up with compromise proposals.
Both before and after implementation of the federal health law, this market – serving people who don’t get coverage through work or the government – has proved problematic. Before the law, many people with preexisting health conditions could not get insurance at any price. Now, consumers in the individual market often face higher out-of-pocket costs and fewer choices of health care providers and insurers than in past years. More than 12 million people buy that insurance through the ACA’s marketplaces, while another 5 million buy it outside of the exchanges.
Policy makers generally agree on what immediate efforts to stabilize the market might include. At the top of most lists is ensuring federal payment of subsidies to insurers to pay the out-of-pocket expenses – such as deductibles and copayments – to protect customers with the lowest incomes. Insurers also want the federal government to continue enforcing the requirement that most Americans either have insurance or pay a tax penalty, and continuing efforts to get uninsured people to sign up for coverage during the upcoming open enrollment period, from Nov. 1 to Dec. 15. Those efforts are essential, insurers say, to help keep healthy customers in their risk pools to defray the costs of beneficiaries with medical needs.
But what about ideas that go beyond the oft-repeated ones? Here are five proposals that are more controversial but generating buzz.
1. Allow people into Medicare starting at age 55.
Getting slightly younger people into Medicare, the federal program for the disabled and Americans 65 and older, is a longtime goal of Democrats. It dates at least to the Clinton administration and was nearly included in the Affordable Care Act in 2010. A Medicare buy-in is not exactly the same as a “public option,” which many Democrats, including former President Barack Obama, have embraced. A true public option would offer government coverage to those of any age.
Lowering the age for Medicare eligibility (whether by allowing people to purchase coverage early or letting them join on the same terms as those aged 65) is controversial. Some Democrats support it as a first step toward a single-payer, Medicare-for-all system. Most Republicans oppose it on those same grounds – as a step toward government-run health care.
But proponents argue it would help the current individual market by excluding the oldest people, thereby lowering the average age of the risk pool. Since older patients, on average, cost more to insure, the change could lower premiums for everyone left in the ACA market. That’s the stated goal of a Medicare buy-in bill introduced earlier this month by Sen. Debbie Stabenow (D-Mich.) and seven other Democratic senators. That bill would allow Obamacare market customers ages 55-64 to purchase Medicare coverage instead, but would also let them use ACA tax credits if they are eligible for those. The cost of such policies, however, has not been worked out.
“The way we’ve structured it actually both helps Medicare by having younger people in that pool, and it helps private insurance by taking higher-cost individuals out of their pool,” Sen. Stabenow told The Detroit News.
Conservative health analysts don’t buy that, though. “This is just a way of saying we’re going to take these people out of the exchanges and put them where there are bigger subsidies,” said Joseph Antos of the conservative-leaning American Enterprise Institute (AEI).
2. Allow people to ‘buy in’ to Medicaid.
An alternative to letting people buy in to Medicare is letting them buy in to Medicaid, the joint federal-state program for those with low incomes.
Medicaid buy-ins already exist – for example, in 2005 Congress passed the Family Opportunity Act, which allows families earning up to three times the poverty level to purchase Medicaid coverage for their disabled children who aren’t otherwise eligible. Medicaid has typically provided richer benefits for those with disabilities than private health insurance.
Earlier this year, Gov. Brian Sandoval (R-Nev.) vetoed a bill that would have allowed Nevada residents to buy Medicaid coverage through the state’s insurance exchange.
Now Sen. Brian Schatz (D-Hawaii) is pushing a federal Medicaid buy-in plan, which he described to Vox.com last week. It would give states the option to allow people with incomes over current Medicaid eligibility thresholds to pay a premium to join the program. Like the Medicare buy-in bill, it would allow those who qualify for federal tax credits to use them to pay the premiums.
The proposal would also raise the amounts Medicaid pays to doctors, hospitals and other health care providers to the same level as it pays for Medicare patients. Traditionally, low Medicaid payment rates have kept many doctors, particularly specialists, from taking Medicaid.
As with the Medicare expansion, the idea of a further Medicaid expansion does not sit well with conservative policy analysts. “It’s completely unworkable,” Avik Roy of the Foundation for Research on Equal Opportunity, told Vox. He predicted it would raise Medicaid spending by $2 trillion over 10 years.
3. Get younger adults off their parents’ insurance and back into the individual market.
Allowing young adults up to age 26 to stay on their parents’ health plans is unquestionably one of the most popular ACA provisions. Democrats have touted it proudly while Republicans have dared not touch it in almost any of their overhaul proposals.
Yet what has been a boon to 3 million young adults (and a relief to their parents) has come at a cost to the individual marketplace itself, where only an estimated 28% of those buying coverage in state exchanges were ages 18-34 in 2016. That is well below the 40% most analysts said was necessary to keep the market stable.
“Frankly, it was really stupid,” to keep those young people out of the individual market, said Mr. Antos of AEI. The result has been a lack of people in the risk pool who are “young, healthy and whose parents will pay their premiums.”
But rolling back that piece of the law might be nearly impossible, said Mr. Antos, because “this is a middle-class giveaway.”
4. Require insurers who participate in other government programs to offer marketplace coverage.
One clear shortcoming of the individual marketplace is a lack of insurer competition, particularly in rural areas. While there appear to be no counties left with no company offering coverage for the coming year, the percentage of counties with only one insurer seems certain to rise from 2017’s 33%.
In an effort to more strongly encourage private companies to step up and offer coverage, several analysts have suggested tying access to participation in other government programs to a willingness to offer individual ACA policies as well.
For example, some have suggested insurers be required to provide policies in the marketplaces as a condition of being able to offer coverage to federal workers. Others have suggested that private insurers who offer profitable Medicare Advantage plans could also be required to offer individual exchange coverage, although the same rural areas with a lack of private individual market insurers also tend to lack Medicare Advantage coverage.
5. Let people use HSA contributions to pay health insurance premiums.
A little-noticed provision in one of the versions of the Senate GOP health bill that failed to pass in July would have allowed people to use money from tax-preferred health savings accounts (HSAs) to pay their insurance premiums. A little-noticed proposal from a group of ideologically diverse health care experts included a similar idea.
HSAs are linked to high-deductible insurance plans, and consumers use the money in the account to pay their out-of-pocket expenses. The money put into the account and the earnings are not taxable.
With a few exceptions, people with HSAs have not been allowed to use those funds to pay monthly premiums. But the change would be one way to provide relief to people who buy their own insurance, earn too much to get federal premium subsidies, and cannot deduct premiums from their taxes because they are not technically self-employed. Such people, though likely small in number, have been disproportionately hurt by rising premiums in the individual market since the ACA took full effect.
Still, the change would involve some trade-offs.
Roy Ramthun, who helped design HSAs as a Senate staffer in the early 2000s and helped implement them while at the Treasury Department during the George W. Bush administration, said that, generally, “Republicans have preferred to subsidize insurance premiums through tax deductions and credits and leave the HSA for out-of-pocket expenses.” Allowing premiums to be paid from HSA funds, he said, “could eat up the entire balance of the account and leave nothing for out-of-pocket expenses.” There are limits to how much money can be put into an HSA. For 2017, the maximum is $3,400 for an individual and $6,750 for a family.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
With Republican efforts to “repeal and replace” the Affordable Care Act stalled, tentative bipartisan initiatives are in the works to shore up the fragile individual insurance market that serves roughly 17 million Americans.
The Senate Health, Education, Labor and Pensions Committee launches hearings the week Congress returns in September on “stabilizing premiums in the individual insurance market” that will feature state governors and insurance commissioners. A bipartisan group in the House is also working to come up with compromise proposals.
Both before and after implementation of the federal health law, this market – serving people who don’t get coverage through work or the government – has proved problematic. Before the law, many people with preexisting health conditions could not get insurance at any price. Now, consumers in the individual market often face higher out-of-pocket costs and fewer choices of health care providers and insurers than in past years. More than 12 million people buy that insurance through the ACA’s marketplaces, while another 5 million buy it outside of the exchanges.
Policy makers generally agree on what immediate efforts to stabilize the market might include. At the top of most lists is ensuring federal payment of subsidies to insurers to pay the out-of-pocket expenses – such as deductibles and copayments – to protect customers with the lowest incomes. Insurers also want the federal government to continue enforcing the requirement that most Americans either have insurance or pay a tax penalty, and continuing efforts to get uninsured people to sign up for coverage during the upcoming open enrollment period, from Nov. 1 to Dec. 15. Those efforts are essential, insurers say, to help keep healthy customers in their risk pools to defray the costs of beneficiaries with medical needs.
But what about ideas that go beyond the oft-repeated ones? Here are five proposals that are more controversial but generating buzz.
1. Allow people into Medicare starting at age 55.
Getting slightly younger people into Medicare, the federal program for the disabled and Americans 65 and older, is a longtime goal of Democrats. It dates at least to the Clinton administration and was nearly included in the Affordable Care Act in 2010. A Medicare buy-in is not exactly the same as a “public option,” which many Democrats, including former President Barack Obama, have embraced. A true public option would offer government coverage to those of any age.
Lowering the age for Medicare eligibility (whether by allowing people to purchase coverage early or letting them join on the same terms as those aged 65) is controversial. Some Democrats support it as a first step toward a single-payer, Medicare-for-all system. Most Republicans oppose it on those same grounds – as a step toward government-run health care.
But proponents argue it would help the current individual market by excluding the oldest people, thereby lowering the average age of the risk pool. Since older patients, on average, cost more to insure, the change could lower premiums for everyone left in the ACA market. That’s the stated goal of a Medicare buy-in bill introduced earlier this month by Sen. Debbie Stabenow (D-Mich.) and seven other Democratic senators. That bill would allow Obamacare market customers ages 55-64 to purchase Medicare coverage instead, but would also let them use ACA tax credits if they are eligible for those. The cost of such policies, however, has not been worked out.
“The way we’ve structured it actually both helps Medicare by having younger people in that pool, and it helps private insurance by taking higher-cost individuals out of their pool,” Sen. Stabenow told The Detroit News.
Conservative health analysts don’t buy that, though. “This is just a way of saying we’re going to take these people out of the exchanges and put them where there are bigger subsidies,” said Joseph Antos of the conservative-leaning American Enterprise Institute (AEI).
2. Allow people to ‘buy in’ to Medicaid.
An alternative to letting people buy in to Medicare is letting them buy in to Medicaid, the joint federal-state program for those with low incomes.
Medicaid buy-ins already exist – for example, in 2005 Congress passed the Family Opportunity Act, which allows families earning up to three times the poverty level to purchase Medicaid coverage for their disabled children who aren’t otherwise eligible. Medicaid has typically provided richer benefits for those with disabilities than private health insurance.
Earlier this year, Gov. Brian Sandoval (R-Nev.) vetoed a bill that would have allowed Nevada residents to buy Medicaid coverage through the state’s insurance exchange.
Now Sen. Brian Schatz (D-Hawaii) is pushing a federal Medicaid buy-in plan, which he described to Vox.com last week. It would give states the option to allow people with incomes over current Medicaid eligibility thresholds to pay a premium to join the program. Like the Medicare buy-in bill, it would allow those who qualify for federal tax credits to use them to pay the premiums.
The proposal would also raise the amounts Medicaid pays to doctors, hospitals and other health care providers to the same level as it pays for Medicare patients. Traditionally, low Medicaid payment rates have kept many doctors, particularly specialists, from taking Medicaid.
As with the Medicare expansion, the idea of a further Medicaid expansion does not sit well with conservative policy analysts. “It’s completely unworkable,” Avik Roy of the Foundation for Research on Equal Opportunity, told Vox. He predicted it would raise Medicaid spending by $2 trillion over 10 years.
3. Get younger adults off their parents’ insurance and back into the individual market.
Allowing young adults up to age 26 to stay on their parents’ health plans is unquestionably one of the most popular ACA provisions. Democrats have touted it proudly while Republicans have dared not touch it in almost any of their overhaul proposals.
Yet what has been a boon to 3 million young adults (and a relief to their parents) has come at a cost to the individual marketplace itself, where only an estimated 28% of those buying coverage in state exchanges were ages 18-34 in 2016. That is well below the 40% most analysts said was necessary to keep the market stable.
“Frankly, it was really stupid,” to keep those young people out of the individual market, said Mr. Antos of AEI. The result has been a lack of people in the risk pool who are “young, healthy and whose parents will pay their premiums.”
But rolling back that piece of the law might be nearly impossible, said Mr. Antos, because “this is a middle-class giveaway.”
4. Require insurers who participate in other government programs to offer marketplace coverage.
One clear shortcoming of the individual marketplace is a lack of insurer competition, particularly in rural areas. While there appear to be no counties left with no company offering coverage for the coming year, the percentage of counties with only one insurer seems certain to rise from 2017’s 33%.
In an effort to more strongly encourage private companies to step up and offer coverage, several analysts have suggested tying access to participation in other government programs to a willingness to offer individual ACA policies as well.
For example, some have suggested insurers be required to provide policies in the marketplaces as a condition of being able to offer coverage to federal workers. Others have suggested that private insurers who offer profitable Medicare Advantage plans could also be required to offer individual exchange coverage, although the same rural areas with a lack of private individual market insurers also tend to lack Medicare Advantage coverage.
5. Let people use HSA contributions to pay health insurance premiums.
A little-noticed provision in one of the versions of the Senate GOP health bill that failed to pass in July would have allowed people to use money from tax-preferred health savings accounts (HSAs) to pay their insurance premiums. A little-noticed proposal from a group of ideologically diverse health care experts included a similar idea.
HSAs are linked to high-deductible insurance plans, and consumers use the money in the account to pay their out-of-pocket expenses. The money put into the account and the earnings are not taxable.
With a few exceptions, people with HSAs have not been allowed to use those funds to pay monthly premiums. But the change would be one way to provide relief to people who buy their own insurance, earn too much to get federal premium subsidies, and cannot deduct premiums from their taxes because they are not technically self-employed. Such people, though likely small in number, have been disproportionately hurt by rising premiums in the individual market since the ACA took full effect.
Still, the change would involve some trade-offs.
Roy Ramthun, who helped design HSAs as a Senate staffer in the early 2000s and helped implement them while at the Treasury Department during the George W. Bush administration, said that, generally, “Republicans have preferred to subsidize insurance premiums through tax deductions and credits and leave the HSA for out-of-pocket expenses.” Allowing premiums to be paid from HSA funds, he said, “could eat up the entire balance of the account and leave nothing for out-of-pocket expenses.” There are limits to how much money can be put into an HSA. For 2017, the maximum is $3,400 for an individual and $6,750 for a family.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
FDA expands approval of fulvestrant for HR+/HER2– advanced breast cancer
The Food and Drug Administration has approved fulvestrant (Faslodex) as monotherapy for women with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2–) advanced breast cancer who are postmenopausal and previously untreated.
Approval was based on improved progression-free survival (PFS) in the phase 3 FALCON trial of 462 postmenopausal women with HR+/HER2– metastatic or locally advanced breast cancer who had not previously received hormonal therapy, drug maker AstraZeneca said in a press release.
The most common adverse events were arthralgia (16.7% of patients on fulvestrant vs. 10.3% on anastrozole), and hot flushes/flashes (11.4% vs. 10.3%).
Grade 3 or greater adverse events occurred in 22.4% vs. 17.7%. Deaths from adverse events occurred in six patients on fulvestrant vs. seven on anastrozole, according to results published in The Lancet.
The Food and Drug Administration has approved fulvestrant (Faslodex) as monotherapy for women with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2–) advanced breast cancer who are postmenopausal and previously untreated.
Approval was based on improved progression-free survival (PFS) in the phase 3 FALCON trial of 462 postmenopausal women with HR+/HER2– metastatic or locally advanced breast cancer who had not previously received hormonal therapy, drug maker AstraZeneca said in a press release.
The most common adverse events were arthralgia (16.7% of patients on fulvestrant vs. 10.3% on anastrozole), and hot flushes/flashes (11.4% vs. 10.3%).
Grade 3 or greater adverse events occurred in 22.4% vs. 17.7%. Deaths from adverse events occurred in six patients on fulvestrant vs. seven on anastrozole, according to results published in The Lancet.
The Food and Drug Administration has approved fulvestrant (Faslodex) as monotherapy for women with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2–) advanced breast cancer who are postmenopausal and previously untreated.
Approval was based on improved progression-free survival (PFS) in the phase 3 FALCON trial of 462 postmenopausal women with HR+/HER2– metastatic or locally advanced breast cancer who had not previously received hormonal therapy, drug maker AstraZeneca said in a press release.
The most common adverse events were arthralgia (16.7% of patients on fulvestrant vs. 10.3% on anastrozole), and hot flushes/flashes (11.4% vs. 10.3%).
Grade 3 or greater adverse events occurred in 22.4% vs. 17.7%. Deaths from adverse events occurred in six patients on fulvestrant vs. seven on anastrozole, according to results published in The Lancet.
Office-based tests can have questionable value
Office based-testing is convenient and often useful.
Often, but not always.
Sadly, a number of practices are increasingly turning to tests of questionable value as a way to make up for decreasing reimbursements. While I have nothing against making money, I have to question where this trend is going. I see many of them even being done by physicians outside of their fields.
I get ads all the time from companies selling gadgets to test balance (“Be the first in your area! Fully reimbursed!”). I see reports from family doctors with the results of a pseudo-EMG/NCV surface test done there by an assistant saying a patient with diabetes has a neuropathy (shocker!).
I have nothing against tests. Lord knows I order plenty of them. But I always try to ask myself if the results will change my management plan or answer another crucial question. If the answer is “no” to both, why bother?
Test are shiny. They impress patients and their families. They represent technological progress in medicine to many. But a lot of time we forget that clinical skills are pretty useful, too. If a diabetic patient comes in with numb feet and an exam that shows decreased distal sensation, do we really need a pseudo-surface EMG/NCV (especially when done by someone who isn’t a neurologist or physiatrist) or skin punch biopsy to tell us they have a neuropathy?
If the patient is stumbling all over and is clearly ataxic, do we need a machine to say, “Hey, you’re off balance. You could fall.”
An old mentor always told me “clinical correlation is advised.” (Al, I hated you then and miss you now.)
And convenience doesn’t always mean something is good. Remember Theranos?
Like all doctors, I worry about my bottom line and keeping my practice afloat. These tests are alluring in that they promise to increase practice revenue without much change in your overhead (if you believe that). But they can also be a siren song that lures you to put money ahead of what’s best for a patient. That’s never the right course.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Office based-testing is convenient and often useful.
Often, but not always.
Sadly, a number of practices are increasingly turning to tests of questionable value as a way to make up for decreasing reimbursements. While I have nothing against making money, I have to question where this trend is going. I see many of them even being done by physicians outside of their fields.
I get ads all the time from companies selling gadgets to test balance (“Be the first in your area! Fully reimbursed!”). I see reports from family doctors with the results of a pseudo-EMG/NCV surface test done there by an assistant saying a patient with diabetes has a neuropathy (shocker!).
I have nothing against tests. Lord knows I order plenty of them. But I always try to ask myself if the results will change my management plan or answer another crucial question. If the answer is “no” to both, why bother?
Test are shiny. They impress patients and their families. They represent technological progress in medicine to many. But a lot of time we forget that clinical skills are pretty useful, too. If a diabetic patient comes in with numb feet and an exam that shows decreased distal sensation, do we really need a pseudo-surface EMG/NCV (especially when done by someone who isn’t a neurologist or physiatrist) or skin punch biopsy to tell us they have a neuropathy?
If the patient is stumbling all over and is clearly ataxic, do we need a machine to say, “Hey, you’re off balance. You could fall.”
An old mentor always told me “clinical correlation is advised.” (Al, I hated you then and miss you now.)
And convenience doesn’t always mean something is good. Remember Theranos?
Like all doctors, I worry about my bottom line and keeping my practice afloat. These tests are alluring in that they promise to increase practice revenue without much change in your overhead (if you believe that). But they can also be a siren song that lures you to put money ahead of what’s best for a patient. That’s never the right course.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Office based-testing is convenient and often useful.
Often, but not always.
Sadly, a number of practices are increasingly turning to tests of questionable value as a way to make up for decreasing reimbursements. While I have nothing against making money, I have to question where this trend is going. I see many of them even being done by physicians outside of their fields.
I get ads all the time from companies selling gadgets to test balance (“Be the first in your area! Fully reimbursed!”). I see reports from family doctors with the results of a pseudo-EMG/NCV surface test done there by an assistant saying a patient with diabetes has a neuropathy (shocker!).
I have nothing against tests. Lord knows I order plenty of them. But I always try to ask myself if the results will change my management plan or answer another crucial question. If the answer is “no” to both, why bother?
Test are shiny. They impress patients and their families. They represent technological progress in medicine to many. But a lot of time we forget that clinical skills are pretty useful, too. If a diabetic patient comes in with numb feet and an exam that shows decreased distal sensation, do we really need a pseudo-surface EMG/NCV (especially when done by someone who isn’t a neurologist or physiatrist) or skin punch biopsy to tell us they have a neuropathy?
If the patient is stumbling all over and is clearly ataxic, do we need a machine to say, “Hey, you’re off balance. You could fall.”
An old mentor always told me “clinical correlation is advised.” (Al, I hated you then and miss you now.)
And convenience doesn’t always mean something is good. Remember Theranos?
Like all doctors, I worry about my bottom line and keeping my practice afloat. These tests are alluring in that they promise to increase practice revenue without much change in your overhead (if you believe that). But they can also be a siren song that lures you to put money ahead of what’s best for a patient. That’s never the right course.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
FDA approves first gene therapy – tisagenlecleucel for ALL
The U.S. Food and Drug Administration has approved tisagenlecleucel (Kymriah), a first-of-its-kind chimeric antigen receptor T-cell (CAR T) therapy, for the treatment of children and young adults up to age 25 years with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.
Tisagenlecleucel will carry a boxed warning regarding the CRS risk. Additionally, due to the CRS risk and risk of neurological events, the approval requires a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use, according to an FDA press release.
Special certification will be required for hospitals and associated clinics that dispense tisagenlecleucel. As part of certification, staff will be trained in the prescribing, dispensing, or administering of the therapy, and to recognize and manage CRS and neurological events.
Novartis, the maker of tisagenlecleucel, will be required to conduct postmarketing observational study.
Indeed, FDA commissioner Scott Gottlieb, MD, said the approval marks the entry to a “new frontier in medical innovation.”
“New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses,” he said in the press statement.
Tisagenlecleucel is a genetically modified autologous T-cell immunotherapy involving customized treatment created using a patient’s own T cells. The T cells are genetically modified to include a chimeric antigen receptor that directs the T cells to target and kill leukemia cells with CD19 surface antigen, and are then infused back into the patient.
In a phase 2 clinical trial, the overall remission rate with tisagenlecleucel therapy was 83% in 63 children and young adults with relapsed/refractory B-cell precursor ALL for whom at least two prior lines of therapy had failed; the therapy was granted Fast Track, Priority Review, and Breakthrough Therapy designations.
“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research said in the press statement.
“Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that shows promising remission and survival rates in clinical trials.”
At its meeting in July, the FDA ODAC agreed nearly unanimously that the risk mitigation plan put forward by Novartis, including planned 15-year follow-up and other mitigation measures, would be adequate for detecting serious consequences of CAR T-cell therapy.
This article was updated August 30, 2017.
The U.S. Food and Drug Administration has approved tisagenlecleucel (Kymriah), a first-of-its-kind chimeric antigen receptor T-cell (CAR T) therapy, for the treatment of children and young adults up to age 25 years with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.
Tisagenlecleucel will carry a boxed warning regarding the CRS risk. Additionally, due to the CRS risk and risk of neurological events, the approval requires a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use, according to an FDA press release.
Special certification will be required for hospitals and associated clinics that dispense tisagenlecleucel. As part of certification, staff will be trained in the prescribing, dispensing, or administering of the therapy, and to recognize and manage CRS and neurological events.
Novartis, the maker of tisagenlecleucel, will be required to conduct postmarketing observational study.
Indeed, FDA commissioner Scott Gottlieb, MD, said the approval marks the entry to a “new frontier in medical innovation.”
“New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses,” he said in the press statement.
Tisagenlecleucel is a genetically modified autologous T-cell immunotherapy involving customized treatment created using a patient’s own T cells. The T cells are genetically modified to include a chimeric antigen receptor that directs the T cells to target and kill leukemia cells with CD19 surface antigen, and are then infused back into the patient.
In a phase 2 clinical trial, the overall remission rate with tisagenlecleucel therapy was 83% in 63 children and young adults with relapsed/refractory B-cell precursor ALL for whom at least two prior lines of therapy had failed; the therapy was granted Fast Track, Priority Review, and Breakthrough Therapy designations.
“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research said in the press statement.
“Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that shows promising remission and survival rates in clinical trials.”
At its meeting in July, the FDA ODAC agreed nearly unanimously that the risk mitigation plan put forward by Novartis, including planned 15-year follow-up and other mitigation measures, would be adequate for detecting serious consequences of CAR T-cell therapy.
This article was updated August 30, 2017.
The U.S. Food and Drug Administration has approved tisagenlecleucel (Kymriah), a first-of-its-kind chimeric antigen receptor T-cell (CAR T) therapy, for the treatment of children and young adults up to age 25 years with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.
Tisagenlecleucel will carry a boxed warning regarding the CRS risk. Additionally, due to the CRS risk and risk of neurological events, the approval requires a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use, according to an FDA press release.
Special certification will be required for hospitals and associated clinics that dispense tisagenlecleucel. As part of certification, staff will be trained in the prescribing, dispensing, or administering of the therapy, and to recognize and manage CRS and neurological events.
Novartis, the maker of tisagenlecleucel, will be required to conduct postmarketing observational study.
Indeed, FDA commissioner Scott Gottlieb, MD, said the approval marks the entry to a “new frontier in medical innovation.”
“New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses,” he said in the press statement.
Tisagenlecleucel is a genetically modified autologous T-cell immunotherapy involving customized treatment created using a patient’s own T cells. The T cells are genetically modified to include a chimeric antigen receptor that directs the T cells to target and kill leukemia cells with CD19 surface antigen, and are then infused back into the patient.
In a phase 2 clinical trial, the overall remission rate with tisagenlecleucel therapy was 83% in 63 children and young adults with relapsed/refractory B-cell precursor ALL for whom at least two prior lines of therapy had failed; the therapy was granted Fast Track, Priority Review, and Breakthrough Therapy designations.
“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research said in the press statement.
“Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that shows promising remission and survival rates in clinical trials.”
At its meeting in July, the FDA ODAC agreed nearly unanimously that the risk mitigation plan put forward by Novartis, including planned 15-year follow-up and other mitigation measures, would be adequate for detecting serious consequences of CAR T-cell therapy.
This article was updated August 30, 2017.
VIDEO: Clopidogrel bests ticagrelor in PCI for ACS in real-world study
BARCELONA – Patients who underwent percutaneous coronary intervention for acute coronary syndrome using newer-generation drug-eluting stents backed by ticagrelor-based dual-antiplatelet therapy had significantly higher net adverse event rates at 1 year than did those with clopidogrel-based DAPT in the CHANGE DAPT study, Clemens von Birgelen, MD, reported at the annual congress of the European Society of Cardiology.
Based upon the CHANGE DAPT findings and those from other recent studies, it would be appropriate to revise ESC and American College of Cardiology/American Heart Association guidelines, which now give the newer, more potent platelet inhibitors ticagrelor (Brilinta) or prasugrel (Effient) preferential status as the P2Y12 inhibitor of choice over clopidogrel, added Dr. von Birgelen, professor of cardiology at the University of Twente in Enschede, the Netherlands, and codirector of the department of cardiology at Thoraxcentrum Twente.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“With the newer drug-eluting stents we see lower ischemic event rates, so the DAPT side effects due to bleeding become more important at this time. It could be that patients with ACS who are undergoing PCI may no longer need the most potent DAPT. Perhaps less potent DAPT with clopidogrel may be sufficient when using these more modern devices,” Dr. von Birgelen said in an interview.
CHANGE DAPT was a prospective, observational registry study that compared 1-year clinical outcomes in 2,062 consecutive ACS patients treated by PCI at Thoraxcentrum Twente, a high-volume PCI center. Half of the patients were treated before the primary DAPT regimen in the region changed from clopidogrel-based to ticagrelor-based DAPT on May 1, 2014, while the other half underwent PCI after the switch. This unique registry study design avoids selection bias, whereby cardiologists might preferentially use clopidogrel – the less potent P2Y12 inhibitor – in frailer patients.
The primary endpoint was the 1-year composite of all-cause mortality, any MI, stroke, or major bleeding. The rate was 7.8% in the ticagrelor period and significantly lower at 5.1% in the clopidogrel period. This difference was driven by the significantly lower major bleeding rate in the clopidogrel group: 1.2% versus 2.7% with ticagrelor-based DAPT.
The increased risk of bleeding associated with ticagrelor wasn’t offset by any advantage in term of ischemic events; indeed, the rate of such events was actually numerically lower with clopidogrel-based DAPT, albeit not statistically significantly so. Definite or probable stent thrombosis occurred in 0.6% of the clopidogrel group and 0.8% of the ticagrelor group, while the composite of cardiac death, MI, or stroke occurred in 3.7% of patients on clopidogrel-based DAPT compared with 4.7% on ticagrelor.
The two patient groups were closely similar at baseline in most respects, although the ticagrelor group was, on average, 1 year older, reflecting the more recent increased willingness of interventional cardiologists to utilize PCI in patients of advanced age. In terms of procedural differences, the ticagrelor group was more likely to undergo a transradial rather than transfemoral approach, less likely to receive a glycoprotein IIb/IIIa inhibitor, and more likely to get a proton pump inhibitor.
“All three of those factors should have reduced the bleeding risk during that second period,” Dr. von Birgelen observed.
In a propensity score–adjusted analysis taking account of the few between-group differences, ticagrelor-based DAPT was associated with a 1.75-fold increased risk of the primary endpoint and a 2.75-fold increased risk of major bleeding.
He noted that the CHANGE DAPT results are consistent with those of TOPIC, a 646-patient, single-center randomized trial conducted in Marseille. In TOPIC, after 1 month on ticagrelor- or prasugrel-backed DAPT, half of patients were switched to vastly less expensive clopidogrel for the remaining 11 months of DAPT. The result in the switched group was a marked decrease in bleeding with no increased risk of ischemic events.
“I see our study as a piece in a mosaic of studies and real-world registries with a similar message that have recently been reported,” the cardiologist said. “I hope the ESC looks carefully at these data.”
Session cochair Laura Mauri, MD, said that while it’s important to look at real-world observational data such as CHANGE DAPT to see if the results of randomized trials are generalizable, she’s not surprised by the evidence of increased risk of bleeding with a more potent agent such as ticagrelor.
“Why there’s a lack of benefit demonstrated, I think, is the bigger question,” said Dr. Mauri, professor of medicine at Harvard Medical School, Boston. “It could be related to changes in procedures over time, with procedures being conducted in a more complex manner, or some other residual confounding. I think whenever we see an observational study that changes the nature of the benefit that we see, it needs to be investigated more deeply. I don’t think it’s time to dismiss the results of very large randomized trials that show a meaningful benefit for the potent agents in the setting of ACS.”
CHANGE DAPT was an investigator-initiated study conducted without external funding. Dr. von Birgelen reported having no financial conflicts of interest.
BARCELONA – Patients who underwent percutaneous coronary intervention for acute coronary syndrome using newer-generation drug-eluting stents backed by ticagrelor-based dual-antiplatelet therapy had significantly higher net adverse event rates at 1 year than did those with clopidogrel-based DAPT in the CHANGE DAPT study, Clemens von Birgelen, MD, reported at the annual congress of the European Society of Cardiology.
Based upon the CHANGE DAPT findings and those from other recent studies, it would be appropriate to revise ESC and American College of Cardiology/American Heart Association guidelines, which now give the newer, more potent platelet inhibitors ticagrelor (Brilinta) or prasugrel (Effient) preferential status as the P2Y12 inhibitor of choice over clopidogrel, added Dr. von Birgelen, professor of cardiology at the University of Twente in Enschede, the Netherlands, and codirector of the department of cardiology at Thoraxcentrum Twente.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“With the newer drug-eluting stents we see lower ischemic event rates, so the DAPT side effects due to bleeding become more important at this time. It could be that patients with ACS who are undergoing PCI may no longer need the most potent DAPT. Perhaps less potent DAPT with clopidogrel may be sufficient when using these more modern devices,” Dr. von Birgelen said in an interview.
CHANGE DAPT was a prospective, observational registry study that compared 1-year clinical outcomes in 2,062 consecutive ACS patients treated by PCI at Thoraxcentrum Twente, a high-volume PCI center. Half of the patients were treated before the primary DAPT regimen in the region changed from clopidogrel-based to ticagrelor-based DAPT on May 1, 2014, while the other half underwent PCI after the switch. This unique registry study design avoids selection bias, whereby cardiologists might preferentially use clopidogrel – the less potent P2Y12 inhibitor – in frailer patients.
The primary endpoint was the 1-year composite of all-cause mortality, any MI, stroke, or major bleeding. The rate was 7.8% in the ticagrelor period and significantly lower at 5.1% in the clopidogrel period. This difference was driven by the significantly lower major bleeding rate in the clopidogrel group: 1.2% versus 2.7% with ticagrelor-based DAPT.
The increased risk of bleeding associated with ticagrelor wasn’t offset by any advantage in term of ischemic events; indeed, the rate of such events was actually numerically lower with clopidogrel-based DAPT, albeit not statistically significantly so. Definite or probable stent thrombosis occurred in 0.6% of the clopidogrel group and 0.8% of the ticagrelor group, while the composite of cardiac death, MI, or stroke occurred in 3.7% of patients on clopidogrel-based DAPT compared with 4.7% on ticagrelor.
The two patient groups were closely similar at baseline in most respects, although the ticagrelor group was, on average, 1 year older, reflecting the more recent increased willingness of interventional cardiologists to utilize PCI in patients of advanced age. In terms of procedural differences, the ticagrelor group was more likely to undergo a transradial rather than transfemoral approach, less likely to receive a glycoprotein IIb/IIIa inhibitor, and more likely to get a proton pump inhibitor.
“All three of those factors should have reduced the bleeding risk during that second period,” Dr. von Birgelen observed.
In a propensity score–adjusted analysis taking account of the few between-group differences, ticagrelor-based DAPT was associated with a 1.75-fold increased risk of the primary endpoint and a 2.75-fold increased risk of major bleeding.
He noted that the CHANGE DAPT results are consistent with those of TOPIC, a 646-patient, single-center randomized trial conducted in Marseille. In TOPIC, after 1 month on ticagrelor- or prasugrel-backed DAPT, half of patients were switched to vastly less expensive clopidogrel for the remaining 11 months of DAPT. The result in the switched group was a marked decrease in bleeding with no increased risk of ischemic events.
“I see our study as a piece in a mosaic of studies and real-world registries with a similar message that have recently been reported,” the cardiologist said. “I hope the ESC looks carefully at these data.”
Session cochair Laura Mauri, MD, said that while it’s important to look at real-world observational data such as CHANGE DAPT to see if the results of randomized trials are generalizable, she’s not surprised by the evidence of increased risk of bleeding with a more potent agent such as ticagrelor.
“Why there’s a lack of benefit demonstrated, I think, is the bigger question,” said Dr. Mauri, professor of medicine at Harvard Medical School, Boston. “It could be related to changes in procedures over time, with procedures being conducted in a more complex manner, or some other residual confounding. I think whenever we see an observational study that changes the nature of the benefit that we see, it needs to be investigated more deeply. I don’t think it’s time to dismiss the results of very large randomized trials that show a meaningful benefit for the potent agents in the setting of ACS.”
CHANGE DAPT was an investigator-initiated study conducted without external funding. Dr. von Birgelen reported having no financial conflicts of interest.
BARCELONA – Patients who underwent percutaneous coronary intervention for acute coronary syndrome using newer-generation drug-eluting stents backed by ticagrelor-based dual-antiplatelet therapy had significantly higher net adverse event rates at 1 year than did those with clopidogrel-based DAPT in the CHANGE DAPT study, Clemens von Birgelen, MD, reported at the annual congress of the European Society of Cardiology.
Based upon the CHANGE DAPT findings and those from other recent studies, it would be appropriate to revise ESC and American College of Cardiology/American Heart Association guidelines, which now give the newer, more potent platelet inhibitors ticagrelor (Brilinta) or prasugrel (Effient) preferential status as the P2Y12 inhibitor of choice over clopidogrel, added Dr. von Birgelen, professor of cardiology at the University of Twente in Enschede, the Netherlands, and codirector of the department of cardiology at Thoraxcentrum Twente.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“With the newer drug-eluting stents we see lower ischemic event rates, so the DAPT side effects due to bleeding become more important at this time. It could be that patients with ACS who are undergoing PCI may no longer need the most potent DAPT. Perhaps less potent DAPT with clopidogrel may be sufficient when using these more modern devices,” Dr. von Birgelen said in an interview.
CHANGE DAPT was a prospective, observational registry study that compared 1-year clinical outcomes in 2,062 consecutive ACS patients treated by PCI at Thoraxcentrum Twente, a high-volume PCI center. Half of the patients were treated before the primary DAPT regimen in the region changed from clopidogrel-based to ticagrelor-based DAPT on May 1, 2014, while the other half underwent PCI after the switch. This unique registry study design avoids selection bias, whereby cardiologists might preferentially use clopidogrel – the less potent P2Y12 inhibitor – in frailer patients.
The primary endpoint was the 1-year composite of all-cause mortality, any MI, stroke, or major bleeding. The rate was 7.8% in the ticagrelor period and significantly lower at 5.1% in the clopidogrel period. This difference was driven by the significantly lower major bleeding rate in the clopidogrel group: 1.2% versus 2.7% with ticagrelor-based DAPT.
The increased risk of bleeding associated with ticagrelor wasn’t offset by any advantage in term of ischemic events; indeed, the rate of such events was actually numerically lower with clopidogrel-based DAPT, albeit not statistically significantly so. Definite or probable stent thrombosis occurred in 0.6% of the clopidogrel group and 0.8% of the ticagrelor group, while the composite of cardiac death, MI, or stroke occurred in 3.7% of patients on clopidogrel-based DAPT compared with 4.7% on ticagrelor.
The two patient groups were closely similar at baseline in most respects, although the ticagrelor group was, on average, 1 year older, reflecting the more recent increased willingness of interventional cardiologists to utilize PCI in patients of advanced age. In terms of procedural differences, the ticagrelor group was more likely to undergo a transradial rather than transfemoral approach, less likely to receive a glycoprotein IIb/IIIa inhibitor, and more likely to get a proton pump inhibitor.
“All three of those factors should have reduced the bleeding risk during that second period,” Dr. von Birgelen observed.
In a propensity score–adjusted analysis taking account of the few between-group differences, ticagrelor-based DAPT was associated with a 1.75-fold increased risk of the primary endpoint and a 2.75-fold increased risk of major bleeding.
He noted that the CHANGE DAPT results are consistent with those of TOPIC, a 646-patient, single-center randomized trial conducted in Marseille. In TOPIC, after 1 month on ticagrelor- or prasugrel-backed DAPT, half of patients were switched to vastly less expensive clopidogrel for the remaining 11 months of DAPT. The result in the switched group was a marked decrease in bleeding with no increased risk of ischemic events.
“I see our study as a piece in a mosaic of studies and real-world registries with a similar message that have recently been reported,” the cardiologist said. “I hope the ESC looks carefully at these data.”
Session cochair Laura Mauri, MD, said that while it’s important to look at real-world observational data such as CHANGE DAPT to see if the results of randomized trials are generalizable, she’s not surprised by the evidence of increased risk of bleeding with a more potent agent such as ticagrelor.
“Why there’s a lack of benefit demonstrated, I think, is the bigger question,” said Dr. Mauri, professor of medicine at Harvard Medical School, Boston. “It could be related to changes in procedures over time, with procedures being conducted in a more complex manner, or some other residual confounding. I think whenever we see an observational study that changes the nature of the benefit that we see, it needs to be investigated more deeply. I don’t think it’s time to dismiss the results of very large randomized trials that show a meaningful benefit for the potent agents in the setting of ACS.”
CHANGE DAPT was an investigator-initiated study conducted without external funding. Dr. von Birgelen reported having no financial conflicts of interest.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The 1-year composite endpoint of all-cause mortality, MI, stroke, or major bleeding occurred in 5.1% of ACS patients who underwent PCI using newer-generation drug-eluting stents followed by clopidogrel-based DAPT, compared with 7.8% who received ticagrelor-based DAPT.
Data source: This unique design for a prospective observational registry study compared 1-year outcomes in 2,062 consecutive ACS patients who underwent PCI at a single high-volume center, half before a regional switch from clopidogrel- to ticagrelor-based DAPT and half afterward.
Disclosures: CHANGE DAPT was an investigator-initiated study conducted without external funding. The presenter reported having no financial conflicts of interest.