User login
Time to screen for liver disease in type 2 diabetes?
With high rates of fatty liver disease known to occur among people with type 2 diabetes, is it time to introduce routine liver screening into daily diabetes practice? The answer depends on whom you ask, and then there are still some important caveats.
From the hepatologist’s perspective, there is no excuse not to consider liver surveillance now that noninvasive screening methods are available, suggested Michael Trauner, MD, of the Medical University of Vienna.
“From a practical standpoint, I think every type 2 diabetic over 50 years of age is at high risk,” and consequently should be screened at diagnosis, Dr. Trauner said during a debate at the virtual annual meeting of the European Association for the Study of Diabetes. “I would screen at diagnosis and then decide on recall depending on noninvasive fibrosis markers.”
“It’s a rising problem that we are facing these days,” observed Michael Roden, MD, chair and professor of internal medicine, endocrinology and metabolic diseases at Heinrich-Heine University in Düsseldorf, Germany, and who cochaired the session. Not only do people with type 2 diabetes have an increased risk for developing liver diseases, but also there’s a higher risk for those with fatty liver diseases developing type 2 diabetes.
A meta-analysis published in Gut in just last week illustrates just how big a problem this is – nonalcoholic fatty liver disease (NAFLD) “doubled the risk of type 2 diabetes,” said Dr Rosen, who is also the director of the division of endocrinology and diabetology at University Clinics Düsseldorf. That analysis was based on more than 500,000 people, almost 28,000 of whom had incident diabetes over a 5-year period.
Screening tools scarce
This makes liver screening in type 2 diabetes patients “a formidable challenge,” cautioned Gianluca Perseghin, MD, professor of endocrinology at the Monza (Italy) Polyclinic and the University of Milano-Bicocca in Milan.
“Hepatologists generally see only the most severe cases,” Dr. Perseghin said. Diabetologists and endocrinologists would be likely to see huge numbers of patients that could potentially be at risk for liver disease and following the recommendations set out in the joint European Association for the Study of the Liver/EASD/European Association for the Study of Obesity guidelines would result in a huge number of patients being identified and potentially needing referral, he argued.
“At this stage, we need to build friendly, reliable and cost-effective screening process to be applied in the health systems,” Dr. Perseghin suggested. He proposed that liver surveillance would need to be not only personalized on a patient level, but also at the infrastructure level. Measuring liver enzymes, for example, was going to be less accurate in picking up liver disease but blood tests were widely available, whereas imaging methods were not going to be something all diabetes clinics would have immediate access to.
“There are clearly a lot of provocative decisions still to be made,” acknowledged Philip Newsome, PhD, FRCPE, an honorary consultant hepatologist at the University of Birmingham (England) and who cochaired the debate.
“We need to demonstrate that looking for the presence of liver disease in this cohort changes their outcomes in a way that is cost effective,” Dr. Newsome, who is also the secretary general of EASL.
“Tests are evolving, but more importantly, treatments are evolving. So, the decision around cost effectiveness will clearly change,” he added.
NAFLD therapies unclar
“There are still a lot of questions,” Dr. Newsome said during a Novo-Nordisk–sponsored “Meet the Expert” session discussing EASL-EASD-EASO guidelines. “We don’t have any licensed therapies at the moment. But there’s been a huge amount of investment, looking at all sorts of different approaches.”
Dr. Newsome added: “We also don’t know how to monitor these patients. Most of the noninvasive are very useful for staging patients, but we don’t really understand how useful they are for monitoring changes in fibrosis.”
Diabetologist Hannele Yki-Järvinen, MD, PhD, of the University of Helsinki, gave her thoughts on the topic during the same session.
“We should add FIB-4 [Fibrosis-4 index] to the annual exam and ask the lab to calculate FIB-4 automatically,” Dr. Yki-Järvinen said. FIB-4is calculated using the patients age and the results of readily available blood tests that measure the AST/ALT ratio and the platelet count.
Dr. Trauner has received advisory fees and grant support from various companies with an interest in developing liver-directed therapies, and is also a coinventor of 24-norursodeoxycholic acid under development for cholestatic liver disease and potentially NAFLD. Dr. Perseghin has received honoraria and grant support from various pharmaceutical companies with an interest in diabetes care. Dr. Roden did not provide any disclosures. Dr. Newsome has received research grants from Boehringer Ingelheim and Novo Nordisk and acted as a consultant to many pharmaceutical companies. Dr. Yki-Järvinen disclosed receiving consultancy fees from Eli Lilly, MSD, and Novo Nordisk.
SOURCE: Trauner M; Persghin G. EASD 2020, Session S27.
With high rates of fatty liver disease known to occur among people with type 2 diabetes, is it time to introduce routine liver screening into daily diabetes practice? The answer depends on whom you ask, and then there are still some important caveats.
From the hepatologist’s perspective, there is no excuse not to consider liver surveillance now that noninvasive screening methods are available, suggested Michael Trauner, MD, of the Medical University of Vienna.
“From a practical standpoint, I think every type 2 diabetic over 50 years of age is at high risk,” and consequently should be screened at diagnosis, Dr. Trauner said during a debate at the virtual annual meeting of the European Association for the Study of Diabetes. “I would screen at diagnosis and then decide on recall depending on noninvasive fibrosis markers.”
“It’s a rising problem that we are facing these days,” observed Michael Roden, MD, chair and professor of internal medicine, endocrinology and metabolic diseases at Heinrich-Heine University in Düsseldorf, Germany, and who cochaired the session. Not only do people with type 2 diabetes have an increased risk for developing liver diseases, but also there’s a higher risk for those with fatty liver diseases developing type 2 diabetes.
A meta-analysis published in Gut in just last week illustrates just how big a problem this is – nonalcoholic fatty liver disease (NAFLD) “doubled the risk of type 2 diabetes,” said Dr Rosen, who is also the director of the division of endocrinology and diabetology at University Clinics Düsseldorf. That analysis was based on more than 500,000 people, almost 28,000 of whom had incident diabetes over a 5-year period.
Screening tools scarce
This makes liver screening in type 2 diabetes patients “a formidable challenge,” cautioned Gianluca Perseghin, MD, professor of endocrinology at the Monza (Italy) Polyclinic and the University of Milano-Bicocca in Milan.
“Hepatologists generally see only the most severe cases,” Dr. Perseghin said. Diabetologists and endocrinologists would be likely to see huge numbers of patients that could potentially be at risk for liver disease and following the recommendations set out in the joint European Association for the Study of the Liver/EASD/European Association for the Study of Obesity guidelines would result in a huge number of patients being identified and potentially needing referral, he argued.
“At this stage, we need to build friendly, reliable and cost-effective screening process to be applied in the health systems,” Dr. Perseghin suggested. He proposed that liver surveillance would need to be not only personalized on a patient level, but also at the infrastructure level. Measuring liver enzymes, for example, was going to be less accurate in picking up liver disease but blood tests were widely available, whereas imaging methods were not going to be something all diabetes clinics would have immediate access to.
“There are clearly a lot of provocative decisions still to be made,” acknowledged Philip Newsome, PhD, FRCPE, an honorary consultant hepatologist at the University of Birmingham (England) and who cochaired the debate.
“We need to demonstrate that looking for the presence of liver disease in this cohort changes their outcomes in a way that is cost effective,” Dr. Newsome, who is also the secretary general of EASL.
“Tests are evolving, but more importantly, treatments are evolving. So, the decision around cost effectiveness will clearly change,” he added.
NAFLD therapies unclar
“There are still a lot of questions,” Dr. Newsome said during a Novo-Nordisk–sponsored “Meet the Expert” session discussing EASL-EASD-EASO guidelines. “We don’t have any licensed therapies at the moment. But there’s been a huge amount of investment, looking at all sorts of different approaches.”
Dr. Newsome added: “We also don’t know how to monitor these patients. Most of the noninvasive are very useful for staging patients, but we don’t really understand how useful they are for monitoring changes in fibrosis.”
Diabetologist Hannele Yki-Järvinen, MD, PhD, of the University of Helsinki, gave her thoughts on the topic during the same session.
“We should add FIB-4 [Fibrosis-4 index] to the annual exam and ask the lab to calculate FIB-4 automatically,” Dr. Yki-Järvinen said. FIB-4is calculated using the patients age and the results of readily available blood tests that measure the AST/ALT ratio and the platelet count.
Dr. Trauner has received advisory fees and grant support from various companies with an interest in developing liver-directed therapies, and is also a coinventor of 24-norursodeoxycholic acid under development for cholestatic liver disease and potentially NAFLD. Dr. Perseghin has received honoraria and grant support from various pharmaceutical companies with an interest in diabetes care. Dr. Roden did not provide any disclosures. Dr. Newsome has received research grants from Boehringer Ingelheim and Novo Nordisk and acted as a consultant to many pharmaceutical companies. Dr. Yki-Järvinen disclosed receiving consultancy fees from Eli Lilly, MSD, and Novo Nordisk.
SOURCE: Trauner M; Persghin G. EASD 2020, Session S27.
With high rates of fatty liver disease known to occur among people with type 2 diabetes, is it time to introduce routine liver screening into daily diabetes practice? The answer depends on whom you ask, and then there are still some important caveats.
From the hepatologist’s perspective, there is no excuse not to consider liver surveillance now that noninvasive screening methods are available, suggested Michael Trauner, MD, of the Medical University of Vienna.
“From a practical standpoint, I think every type 2 diabetic over 50 years of age is at high risk,” and consequently should be screened at diagnosis, Dr. Trauner said during a debate at the virtual annual meeting of the European Association for the Study of Diabetes. “I would screen at diagnosis and then decide on recall depending on noninvasive fibrosis markers.”
“It’s a rising problem that we are facing these days,” observed Michael Roden, MD, chair and professor of internal medicine, endocrinology and metabolic diseases at Heinrich-Heine University in Düsseldorf, Germany, and who cochaired the session. Not only do people with type 2 diabetes have an increased risk for developing liver diseases, but also there’s a higher risk for those with fatty liver diseases developing type 2 diabetes.
A meta-analysis published in Gut in just last week illustrates just how big a problem this is – nonalcoholic fatty liver disease (NAFLD) “doubled the risk of type 2 diabetes,” said Dr Rosen, who is also the director of the division of endocrinology and diabetology at University Clinics Düsseldorf. That analysis was based on more than 500,000 people, almost 28,000 of whom had incident diabetes over a 5-year period.
Screening tools scarce
This makes liver screening in type 2 diabetes patients “a formidable challenge,” cautioned Gianluca Perseghin, MD, professor of endocrinology at the Monza (Italy) Polyclinic and the University of Milano-Bicocca in Milan.
“Hepatologists generally see only the most severe cases,” Dr. Perseghin said. Diabetologists and endocrinologists would be likely to see huge numbers of patients that could potentially be at risk for liver disease and following the recommendations set out in the joint European Association for the Study of the Liver/EASD/European Association for the Study of Obesity guidelines would result in a huge number of patients being identified and potentially needing referral, he argued.
“At this stage, we need to build friendly, reliable and cost-effective screening process to be applied in the health systems,” Dr. Perseghin suggested. He proposed that liver surveillance would need to be not only personalized on a patient level, but also at the infrastructure level. Measuring liver enzymes, for example, was going to be less accurate in picking up liver disease but blood tests were widely available, whereas imaging methods were not going to be something all diabetes clinics would have immediate access to.
“There are clearly a lot of provocative decisions still to be made,” acknowledged Philip Newsome, PhD, FRCPE, an honorary consultant hepatologist at the University of Birmingham (England) and who cochaired the debate.
“We need to demonstrate that looking for the presence of liver disease in this cohort changes their outcomes in a way that is cost effective,” Dr. Newsome, who is also the secretary general of EASL.
“Tests are evolving, but more importantly, treatments are evolving. So, the decision around cost effectiveness will clearly change,” he added.
NAFLD therapies unclar
“There are still a lot of questions,” Dr. Newsome said during a Novo-Nordisk–sponsored “Meet the Expert” session discussing EASL-EASD-EASO guidelines. “We don’t have any licensed therapies at the moment. But there’s been a huge amount of investment, looking at all sorts of different approaches.”
Dr. Newsome added: “We also don’t know how to monitor these patients. Most of the noninvasive are very useful for staging patients, but we don’t really understand how useful they are for monitoring changes in fibrosis.”
Diabetologist Hannele Yki-Järvinen, MD, PhD, of the University of Helsinki, gave her thoughts on the topic during the same session.
“We should add FIB-4 [Fibrosis-4 index] to the annual exam and ask the lab to calculate FIB-4 automatically,” Dr. Yki-Järvinen said. FIB-4is calculated using the patients age and the results of readily available blood tests that measure the AST/ALT ratio and the platelet count.
Dr. Trauner has received advisory fees and grant support from various companies with an interest in developing liver-directed therapies, and is also a coinventor of 24-norursodeoxycholic acid under development for cholestatic liver disease and potentially NAFLD. Dr. Perseghin has received honoraria and grant support from various pharmaceutical companies with an interest in diabetes care. Dr. Roden did not provide any disclosures. Dr. Newsome has received research grants from Boehringer Ingelheim and Novo Nordisk and acted as a consultant to many pharmaceutical companies. Dr. Yki-Järvinen disclosed receiving consultancy fees from Eli Lilly, MSD, and Novo Nordisk.
SOURCE: Trauner M; Persghin G. EASD 2020, Session S27.
REPORTING FROM EASD 2020
Dapagliflozin’s CKD performance sends heart failure messages
The DAPA-CKD trial results, which proved dapagliflozin’s efficacy for slowing chronic kidney disease progression in patients selected for signs of worsening renal function, also have important messages for cardiologists, especially heart failure physicians.
Those messages include findings that were “consistent” with the results of the earlier DAPA-HF trial, which tested the same sodium-glucose transporter 2 (SGLT2) inhibitor in patients selected for having heart failure with reduced ejection fraction (HFrEF). In addition, a specific action of dapagliflozin (Farxiga) on the patients in DAPA-CKD, which enrolled patients based on markers of chronic kidney disease (CKD), was prevention of first and recurrent heart failure hospitalizations, John J.V. McMurray, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America, further highlighting the role that dapagliflozin has in reducing both heart failure and renal events.
What DAPA-CKD means for heart failure
The main findings from the DAPA-CKD trial, published in September in the New England Journal of Medicine, included as a secondary outcome the combined rate of death from cardiovascular causes or hospitalization for heart failure (HHF). Treatment with dapagliflozin linked with a significant 29% relative reduction in this endpoint, compared with placebo-treated patients. At the HFSA meeting, Dr. McMurray reported for the first time the specific HHF numbers, a prespecified secondary endpoint for the study.
Patients on dapagliflozin had 37 total HHF events (1.7%), including both first-time and subsequent hospitalizations, while patients in the placebo arm had a total of 71 HHF events (3.3%) during the study’s median 2.4 years of follow-up, an absolute reduction of 1.6% that translated into a relative risk reduction of 49%.
The HHF findings from DAPA-CKD importantly showed that SGLT2 inhibition in patients with signs of renal dysfunction “will not only slow progression of kidney disease but will also reduce the risk of developing heart failure, crucially in patients with or without type 2 diabetes,” explained Dr. McMurray in an interview. “Cardiologists often consult in the kidney wards and advise on management of patients with chronic kidney disease, even those without heart failure.”
The DAPA-CKD findings carry another important message for heart failure management regarding the minimum level of renal function a patient can have and still safely receive dapagliflozin or possibly another agent from the same SGLT2 inhibitor class. In DAPA-CKD, patients safely received dapagliflozin with an estimated glomerular filtration rate (eGFR) as low as 25 mL/min per 1.73 m2; 14% of enrolled patients had an eGFR of 25-29 mL/min per 1.73 m2.
“Typically, about 40%-50% of patients with heart failure have chronic kidney disease,” which makes this safety finding important to clinicians who care for heart failure patients, but it’s also important for any patient who might be a candidate for dapagliflozin or another drug from its class. “We had no strong evidence before this trial that SGLT2 inhibition could reduce hard renal endpoints,” specifically need for chronic dialysis, renal transplant, or renal death, “in patients with or without diabetes,” Dr. McMurray said.
DAPA-CKD grows the pool of eligible heart failure patients
A further consequence of the DAPA-CKD findings is that when, as expected, regulatory bodies give dapagliflozin an indication for treating the types of CKD patients enrolled in the trial, it will functionally expand this treatment to an even larger swath of heart failure patients who currently don’t qualify for this treatment, specifically patients with CKD who also have heart failure with preserved ejection fraction (HFpEF). On Oct. 2, 2020, the Food and Drug Administration fast-tracked dapagliflozin for the CKD indication by granting it Breakthrough Therapy Designation based on the DAPA-CKD results.
Results first reported in 2019 from the DAPA-HF trial led to dapagliflozin receiving a labeled indication for treating HFrEF, the types of heart failure patients enrolled in the trial. Direct evidence on the efficacy of SGLT2 inhibitors for patients with HFpEF will not be available until results from a few trials now in progress become available during the next 12 months.
In the meantime, nearly half of patients with HFpEF also have CKD, noted Dr. McMurray, and another large portion of HFpEF patients have type 2 diabetes and hence qualify for SGLT2 inhibitor treatment that way. “Obviously, we would like to know specifically about heart failure outcomes in patients with HFpEF” on SGLT2 inhibitor treatment, he acknowledged. But the recent approval of dapagliflozin for patients with HFrEF and the likely indication coming soon for treating CKD means that the number of patients with heart failure who are not eligible for SGLT2 inhibitor treatment is dwindling down to some extent.
New DAPA-HF results show no drug, device interactions
In a separate session at the HFSA virtual meeting, Dr. McMurray and several collaborators on the DAPA-HF trial presented results from some new analyses. Dr. McMurray looked at the impact of dapagliflozin treatment on the primary endpoint when patients were stratified by the diuretic dosage they received at study entry. The results showed that “the benefits from dapagliflozin were irrespective of the use of background diuretic therapy or the diuretic dose,” he reported. Study findings also showed that roughly three-quarters of patients in the study had no change in their diuretic dosage during the course of the trial, that the fraction of patients who had an increase in their dosage was about the same as those whose diuretic dosage decreased, and that this pattern was similar in both the patients on dapagliflozin and in those randomized to placebo.
Another set of new analyses from DAPA-HF looked at the impact on dapagliflozin efficacy of background medical and device therapies for heart failure, as well as background diabetes therapies. The findings showed no signal of an interaction with background therapies. “The effects of dapagliflozin are incremental and complimentary to conventional therapies for HFrEF,” concluded Lars Kober, MD, a professor and heart failure physician at Copenhagen University Hospital.
DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. McMurray’s employer, Glasgow University, has received payments from AstraZeneca and several other companies to compensate for his time overseeing various clinical trials. Dr. Kober has received honoraria for speaking on behalf of several companies including AstraZeneca.
The DAPA-CKD trial results, which proved dapagliflozin’s efficacy for slowing chronic kidney disease progression in patients selected for signs of worsening renal function, also have important messages for cardiologists, especially heart failure physicians.
Those messages include findings that were “consistent” with the results of the earlier DAPA-HF trial, which tested the same sodium-glucose transporter 2 (SGLT2) inhibitor in patients selected for having heart failure with reduced ejection fraction (HFrEF). In addition, a specific action of dapagliflozin (Farxiga) on the patients in DAPA-CKD, which enrolled patients based on markers of chronic kidney disease (CKD), was prevention of first and recurrent heart failure hospitalizations, John J.V. McMurray, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America, further highlighting the role that dapagliflozin has in reducing both heart failure and renal events.
What DAPA-CKD means for heart failure
The main findings from the DAPA-CKD trial, published in September in the New England Journal of Medicine, included as a secondary outcome the combined rate of death from cardiovascular causes or hospitalization for heart failure (HHF). Treatment with dapagliflozin linked with a significant 29% relative reduction in this endpoint, compared with placebo-treated patients. At the HFSA meeting, Dr. McMurray reported for the first time the specific HHF numbers, a prespecified secondary endpoint for the study.
Patients on dapagliflozin had 37 total HHF events (1.7%), including both first-time and subsequent hospitalizations, while patients in the placebo arm had a total of 71 HHF events (3.3%) during the study’s median 2.4 years of follow-up, an absolute reduction of 1.6% that translated into a relative risk reduction of 49%.
The HHF findings from DAPA-CKD importantly showed that SGLT2 inhibition in patients with signs of renal dysfunction “will not only slow progression of kidney disease but will also reduce the risk of developing heart failure, crucially in patients with or without type 2 diabetes,” explained Dr. McMurray in an interview. “Cardiologists often consult in the kidney wards and advise on management of patients with chronic kidney disease, even those without heart failure.”
The DAPA-CKD findings carry another important message for heart failure management regarding the minimum level of renal function a patient can have and still safely receive dapagliflozin or possibly another agent from the same SGLT2 inhibitor class. In DAPA-CKD, patients safely received dapagliflozin with an estimated glomerular filtration rate (eGFR) as low as 25 mL/min per 1.73 m2; 14% of enrolled patients had an eGFR of 25-29 mL/min per 1.73 m2.
“Typically, about 40%-50% of patients with heart failure have chronic kidney disease,” which makes this safety finding important to clinicians who care for heart failure patients, but it’s also important for any patient who might be a candidate for dapagliflozin or another drug from its class. “We had no strong evidence before this trial that SGLT2 inhibition could reduce hard renal endpoints,” specifically need for chronic dialysis, renal transplant, or renal death, “in patients with or without diabetes,” Dr. McMurray said.
DAPA-CKD grows the pool of eligible heart failure patients
A further consequence of the DAPA-CKD findings is that when, as expected, regulatory bodies give dapagliflozin an indication for treating the types of CKD patients enrolled in the trial, it will functionally expand this treatment to an even larger swath of heart failure patients who currently don’t qualify for this treatment, specifically patients with CKD who also have heart failure with preserved ejection fraction (HFpEF). On Oct. 2, 2020, the Food and Drug Administration fast-tracked dapagliflozin for the CKD indication by granting it Breakthrough Therapy Designation based on the DAPA-CKD results.
Results first reported in 2019 from the DAPA-HF trial led to dapagliflozin receiving a labeled indication for treating HFrEF, the types of heart failure patients enrolled in the trial. Direct evidence on the efficacy of SGLT2 inhibitors for patients with HFpEF will not be available until results from a few trials now in progress become available during the next 12 months.
In the meantime, nearly half of patients with HFpEF also have CKD, noted Dr. McMurray, and another large portion of HFpEF patients have type 2 diabetes and hence qualify for SGLT2 inhibitor treatment that way. “Obviously, we would like to know specifically about heart failure outcomes in patients with HFpEF” on SGLT2 inhibitor treatment, he acknowledged. But the recent approval of dapagliflozin for patients with HFrEF and the likely indication coming soon for treating CKD means that the number of patients with heart failure who are not eligible for SGLT2 inhibitor treatment is dwindling down to some extent.
New DAPA-HF results show no drug, device interactions
In a separate session at the HFSA virtual meeting, Dr. McMurray and several collaborators on the DAPA-HF trial presented results from some new analyses. Dr. McMurray looked at the impact of dapagliflozin treatment on the primary endpoint when patients were stratified by the diuretic dosage they received at study entry. The results showed that “the benefits from dapagliflozin were irrespective of the use of background diuretic therapy or the diuretic dose,” he reported. Study findings also showed that roughly three-quarters of patients in the study had no change in their diuretic dosage during the course of the trial, that the fraction of patients who had an increase in their dosage was about the same as those whose diuretic dosage decreased, and that this pattern was similar in both the patients on dapagliflozin and in those randomized to placebo.
Another set of new analyses from DAPA-HF looked at the impact on dapagliflozin efficacy of background medical and device therapies for heart failure, as well as background diabetes therapies. The findings showed no signal of an interaction with background therapies. “The effects of dapagliflozin are incremental and complimentary to conventional therapies for HFrEF,” concluded Lars Kober, MD, a professor and heart failure physician at Copenhagen University Hospital.
DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. McMurray’s employer, Glasgow University, has received payments from AstraZeneca and several other companies to compensate for his time overseeing various clinical trials. Dr. Kober has received honoraria for speaking on behalf of several companies including AstraZeneca.
The DAPA-CKD trial results, which proved dapagliflozin’s efficacy for slowing chronic kidney disease progression in patients selected for signs of worsening renal function, also have important messages for cardiologists, especially heart failure physicians.
Those messages include findings that were “consistent” with the results of the earlier DAPA-HF trial, which tested the same sodium-glucose transporter 2 (SGLT2) inhibitor in patients selected for having heart failure with reduced ejection fraction (HFrEF). In addition, a specific action of dapagliflozin (Farxiga) on the patients in DAPA-CKD, which enrolled patients based on markers of chronic kidney disease (CKD), was prevention of first and recurrent heart failure hospitalizations, John J.V. McMurray, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America, further highlighting the role that dapagliflozin has in reducing both heart failure and renal events.
What DAPA-CKD means for heart failure
The main findings from the DAPA-CKD trial, published in September in the New England Journal of Medicine, included as a secondary outcome the combined rate of death from cardiovascular causes or hospitalization for heart failure (HHF). Treatment with dapagliflozin linked with a significant 29% relative reduction in this endpoint, compared with placebo-treated patients. At the HFSA meeting, Dr. McMurray reported for the first time the specific HHF numbers, a prespecified secondary endpoint for the study.
Patients on dapagliflozin had 37 total HHF events (1.7%), including both first-time and subsequent hospitalizations, while patients in the placebo arm had a total of 71 HHF events (3.3%) during the study’s median 2.4 years of follow-up, an absolute reduction of 1.6% that translated into a relative risk reduction of 49%.
The HHF findings from DAPA-CKD importantly showed that SGLT2 inhibition in patients with signs of renal dysfunction “will not only slow progression of kidney disease but will also reduce the risk of developing heart failure, crucially in patients with or without type 2 diabetes,” explained Dr. McMurray in an interview. “Cardiologists often consult in the kidney wards and advise on management of patients with chronic kidney disease, even those without heart failure.”
The DAPA-CKD findings carry another important message for heart failure management regarding the minimum level of renal function a patient can have and still safely receive dapagliflozin or possibly another agent from the same SGLT2 inhibitor class. In DAPA-CKD, patients safely received dapagliflozin with an estimated glomerular filtration rate (eGFR) as low as 25 mL/min per 1.73 m2; 14% of enrolled patients had an eGFR of 25-29 mL/min per 1.73 m2.
“Typically, about 40%-50% of patients with heart failure have chronic kidney disease,” which makes this safety finding important to clinicians who care for heart failure patients, but it’s also important for any patient who might be a candidate for dapagliflozin or another drug from its class. “We had no strong evidence before this trial that SGLT2 inhibition could reduce hard renal endpoints,” specifically need for chronic dialysis, renal transplant, or renal death, “in patients with or without diabetes,” Dr. McMurray said.
DAPA-CKD grows the pool of eligible heart failure patients
A further consequence of the DAPA-CKD findings is that when, as expected, regulatory bodies give dapagliflozin an indication for treating the types of CKD patients enrolled in the trial, it will functionally expand this treatment to an even larger swath of heart failure patients who currently don’t qualify for this treatment, specifically patients with CKD who also have heart failure with preserved ejection fraction (HFpEF). On Oct. 2, 2020, the Food and Drug Administration fast-tracked dapagliflozin for the CKD indication by granting it Breakthrough Therapy Designation based on the DAPA-CKD results.
Results first reported in 2019 from the DAPA-HF trial led to dapagliflozin receiving a labeled indication for treating HFrEF, the types of heart failure patients enrolled in the trial. Direct evidence on the efficacy of SGLT2 inhibitors for patients with HFpEF will not be available until results from a few trials now in progress become available during the next 12 months.
In the meantime, nearly half of patients with HFpEF also have CKD, noted Dr. McMurray, and another large portion of HFpEF patients have type 2 diabetes and hence qualify for SGLT2 inhibitor treatment that way. “Obviously, we would like to know specifically about heart failure outcomes in patients with HFpEF” on SGLT2 inhibitor treatment, he acknowledged. But the recent approval of dapagliflozin for patients with HFrEF and the likely indication coming soon for treating CKD means that the number of patients with heart failure who are not eligible for SGLT2 inhibitor treatment is dwindling down to some extent.
New DAPA-HF results show no drug, device interactions
In a separate session at the HFSA virtual meeting, Dr. McMurray and several collaborators on the DAPA-HF trial presented results from some new analyses. Dr. McMurray looked at the impact of dapagliflozin treatment on the primary endpoint when patients were stratified by the diuretic dosage they received at study entry. The results showed that “the benefits from dapagliflozin were irrespective of the use of background diuretic therapy or the diuretic dose,” he reported. Study findings also showed that roughly three-quarters of patients in the study had no change in their diuretic dosage during the course of the trial, that the fraction of patients who had an increase in their dosage was about the same as those whose diuretic dosage decreased, and that this pattern was similar in both the patients on dapagliflozin and in those randomized to placebo.
Another set of new analyses from DAPA-HF looked at the impact on dapagliflozin efficacy of background medical and device therapies for heart failure, as well as background diabetes therapies. The findings showed no signal of an interaction with background therapies. “The effects of dapagliflozin are incremental and complimentary to conventional therapies for HFrEF,” concluded Lars Kober, MD, a professor and heart failure physician at Copenhagen University Hospital.
DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. McMurray’s employer, Glasgow University, has received payments from AstraZeneca and several other companies to compensate for his time overseeing various clinical trials. Dr. Kober has received honoraria for speaking on behalf of several companies including AstraZeneca.
FROM HFSA 2020
Shingrix effective in older adults with preexisting immune-mediated disorders
The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.
A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.
The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.
Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.
At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.
Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.
The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.
This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.
SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.
The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.
A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.
The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.
Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.
At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.
Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.
The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.
This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.
SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.
The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.
A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.
The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.
Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.
At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.
Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.
The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.
This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.
SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.
FROM RHEUMATOLOGY
FDA OKs combination immunotherapy for first-line mesothelioma treatment
This is the first drug regimen to receive regulatory approval for mesothelioma in 16 years and only the second systemic therapy to be approved for this indication.
“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.
“In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen,” Dr. Pazdur added.
Improved overall survival
The approval is based on efficacy results from the CheckMate 743 trial, which compared immunotherapy with a chemotherapy regimen in a cohort of more than 600 treatment-naive patients (no systemic therapies) with unresectable mesothelioma.
Patients were randomized 1:1 to nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of combination chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302).
The study results were initially presented during the presidential symposium of the World Congress on Lung Cancer 2020.
The combined immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive versus 27% in the chemotherapy group.
Overall, the trial demonstrated a statistically significant improvement in overall survival for patients who received nivolumab plus ipilimumab versus those treated with chemotherapy. Median overall survival was 18.1 months versus 14.1 months (hazard ratio, 0.74; P = .002).
Median progression-free survival per blinded independent central review was 6.8 months in the nivolumab plus ipilimumab arm and 7.2 months in the chemotherapy arm (HR, 1.0). The confirmed overall response rate was 40% versus 43% in the immunotherapy and chemotherapy arms, respectively.
Median response duration was 11.0 months in the nivolumab plus ipilimumab arm and 6.7 months in the chemotherapy arm. At 24 months, 32% of the immunotherapy patients were still experiencing a response, compared with 8% of those in the chemotherapy arm.
The recommended doses for unresectable malignant pleural mesothelioma are nivolumab 360 mg every 3 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.
The most common adverse reactions (incidence ≥20%) in patients receiving combination immunotherapy were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus.
New standard of care?
The CheckMate 743 trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported study author Paul Baas, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, at the time of its presentation.
He suggested that combination nivolumab and ipilimumab should therefore “be considered as a new standard of care.”
This article first appeared on Medscape.com.
This is the first drug regimen to receive regulatory approval for mesothelioma in 16 years and only the second systemic therapy to be approved for this indication.
“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.
“In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen,” Dr. Pazdur added.
Improved overall survival
The approval is based on efficacy results from the CheckMate 743 trial, which compared immunotherapy with a chemotherapy regimen in a cohort of more than 600 treatment-naive patients (no systemic therapies) with unresectable mesothelioma.
Patients were randomized 1:1 to nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of combination chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302).
The study results were initially presented during the presidential symposium of the World Congress on Lung Cancer 2020.
The combined immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive versus 27% in the chemotherapy group.
Overall, the trial demonstrated a statistically significant improvement in overall survival for patients who received nivolumab plus ipilimumab versus those treated with chemotherapy. Median overall survival was 18.1 months versus 14.1 months (hazard ratio, 0.74; P = .002).
Median progression-free survival per blinded independent central review was 6.8 months in the nivolumab plus ipilimumab arm and 7.2 months in the chemotherapy arm (HR, 1.0). The confirmed overall response rate was 40% versus 43% in the immunotherapy and chemotherapy arms, respectively.
Median response duration was 11.0 months in the nivolumab plus ipilimumab arm and 6.7 months in the chemotherapy arm. At 24 months, 32% of the immunotherapy patients were still experiencing a response, compared with 8% of those in the chemotherapy arm.
The recommended doses for unresectable malignant pleural mesothelioma are nivolumab 360 mg every 3 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.
The most common adverse reactions (incidence ≥20%) in patients receiving combination immunotherapy were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus.
New standard of care?
The CheckMate 743 trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported study author Paul Baas, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, at the time of its presentation.
He suggested that combination nivolumab and ipilimumab should therefore “be considered as a new standard of care.”
This article first appeared on Medscape.com.
This is the first drug regimen to receive regulatory approval for mesothelioma in 16 years and only the second systemic therapy to be approved for this indication.
“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.
“In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen,” Dr. Pazdur added.
Improved overall survival
The approval is based on efficacy results from the CheckMate 743 trial, which compared immunotherapy with a chemotherapy regimen in a cohort of more than 600 treatment-naive patients (no systemic therapies) with unresectable mesothelioma.
Patients were randomized 1:1 to nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of combination chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302).
The study results were initially presented during the presidential symposium of the World Congress on Lung Cancer 2020.
The combined immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive versus 27% in the chemotherapy group.
Overall, the trial demonstrated a statistically significant improvement in overall survival for patients who received nivolumab plus ipilimumab versus those treated with chemotherapy. Median overall survival was 18.1 months versus 14.1 months (hazard ratio, 0.74; P = .002).
Median progression-free survival per blinded independent central review was 6.8 months in the nivolumab plus ipilimumab arm and 7.2 months in the chemotherapy arm (HR, 1.0). The confirmed overall response rate was 40% versus 43% in the immunotherapy and chemotherapy arms, respectively.
Median response duration was 11.0 months in the nivolumab plus ipilimumab arm and 6.7 months in the chemotherapy arm. At 24 months, 32% of the immunotherapy patients were still experiencing a response, compared with 8% of those in the chemotherapy arm.
The recommended doses for unresectable malignant pleural mesothelioma are nivolumab 360 mg every 3 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.
The most common adverse reactions (incidence ≥20%) in patients receiving combination immunotherapy were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus.
New standard of care?
The CheckMate 743 trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported study author Paul Baas, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, at the time of its presentation.
He suggested that combination nivolumab and ipilimumab should therefore “be considered as a new standard of care.”
This article first appeared on Medscape.com.
Psoriasis and Psoriatic Arthritis
Psoriasis and Psoriatic Arthritis is a supplement to Dermatology News with commentary from Joel M. Gelfand, MD, MSCE and Alan Menter, MD.
- Exploring new guidelines and scientific advances
- ‘Loss-framed’ approach makes psoriasis patients more agreeable to treatment
- Topical PDE-4 inhibitor for psoriasis effective in phase 2b trial
- Biologics may delay psoriatic arthritis
- AAD-NPF releases guidelines for systemic nonbiologic treatments of psoriasis
- Specific markers detect psoriatic disease inflammation without elevated CRP
- Beyond PASI 100: Striving for molecular clearance
- Ultrasound improves specificity of psoriatic arthritis referrals
- Registry data reveal temporal relationship between psoriasis symptoms and PsA onset
- New psoriasis guidelines focus on topical and alternative treatments, and severity measures
- Psoriasis topical combination maintenance strategy hits mark at 1 year
Read the supplement.
Psoriasis and Psoriatic Arthritis is a supplement to Dermatology News with commentary from Joel M. Gelfand, MD, MSCE and Alan Menter, MD.
- Exploring new guidelines and scientific advances
- ‘Loss-framed’ approach makes psoriasis patients more agreeable to treatment
- Topical PDE-4 inhibitor for psoriasis effective in phase 2b trial
- Biologics may delay psoriatic arthritis
- AAD-NPF releases guidelines for systemic nonbiologic treatments of psoriasis
- Specific markers detect psoriatic disease inflammation without elevated CRP
- Beyond PASI 100: Striving for molecular clearance
- Ultrasound improves specificity of psoriatic arthritis referrals
- Registry data reveal temporal relationship between psoriasis symptoms and PsA onset
- New psoriasis guidelines focus on topical and alternative treatments, and severity measures
- Psoriasis topical combination maintenance strategy hits mark at 1 year
Read the supplement.
Psoriasis and Psoriatic Arthritis is a supplement to Dermatology News with commentary from Joel M. Gelfand, MD, MSCE and Alan Menter, MD.
- Exploring new guidelines and scientific advances
- ‘Loss-framed’ approach makes psoriasis patients more agreeable to treatment
- Topical PDE-4 inhibitor for psoriasis effective in phase 2b trial
- Biologics may delay psoriatic arthritis
- AAD-NPF releases guidelines for systemic nonbiologic treatments of psoriasis
- Specific markers detect psoriatic disease inflammation without elevated CRP
- Beyond PASI 100: Striving for molecular clearance
- Ultrasound improves specificity of psoriatic arthritis referrals
- Registry data reveal temporal relationship between psoriasis symptoms and PsA onset
- New psoriasis guidelines focus on topical and alternative treatments, and severity measures
- Psoriasis topical combination maintenance strategy hits mark at 1 year
Read the supplement.
Golimumab approval extended to polyarticular-course JIA and juvenile PsA
after the Food and Drug Administration approved the tumor necrosis factor inhibitor for these indications on Sept. 30, according to an announcement from its manufacturer, Janssen.
Results from the open-label, single-arm, multicenter, phase 3, GO-VIVA clinical trial formed the basis for the agency’s approval of IV golimumab. GO-VIVA was conducted in 127 patients aged 2-17 years with JIA with arthritis in five or more joints (despite receiving treatment with methotrexate for at least 2 months) as part of a postmarketing requirement under the Pediatric Research Equity Act after the intravenous formulation of the biologic was approved for adults with rheumatoid arthritis in 2013. It demonstrated that pediatric patients had a level of pharmacokinetic exposure to golimumab that was similar to what was observed in two pivotal phase 3 trials in adults with moderately to severely active RA and active PsA, as well as efficacy that was generally consistent with responses seen in adult patients with RA, the manufacturer said.
Besides RA, intravenous golimumab was previously approved for adults with PsA and ankylosing spondylitis. As opposed to the IV dosing for adults with RA, PsA, and ankylosing spondylitis at 2 mg/kg infused over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter, dosing for pediatric patients with pJIA and PsA is based on body surface area at 80 mg/m2, also given as an IV infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter.
The adverse reactions observed in GO-VIVA were consistent with the established safety profile of intravenous golimumab in adult patients with RA and PsA, according to Janssen.
The full prescribing information for intravenous golimumab can be found on the FDA website.
after the Food and Drug Administration approved the tumor necrosis factor inhibitor for these indications on Sept. 30, according to an announcement from its manufacturer, Janssen.
Results from the open-label, single-arm, multicenter, phase 3, GO-VIVA clinical trial formed the basis for the agency’s approval of IV golimumab. GO-VIVA was conducted in 127 patients aged 2-17 years with JIA with arthritis in five or more joints (despite receiving treatment with methotrexate for at least 2 months) as part of a postmarketing requirement under the Pediatric Research Equity Act after the intravenous formulation of the biologic was approved for adults with rheumatoid arthritis in 2013. It demonstrated that pediatric patients had a level of pharmacokinetic exposure to golimumab that was similar to what was observed in two pivotal phase 3 trials in adults with moderately to severely active RA and active PsA, as well as efficacy that was generally consistent with responses seen in adult patients with RA, the manufacturer said.
Besides RA, intravenous golimumab was previously approved for adults with PsA and ankylosing spondylitis. As opposed to the IV dosing for adults with RA, PsA, and ankylosing spondylitis at 2 mg/kg infused over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter, dosing for pediatric patients with pJIA and PsA is based on body surface area at 80 mg/m2, also given as an IV infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter.
The adverse reactions observed in GO-VIVA were consistent with the established safety profile of intravenous golimumab in adult patients with RA and PsA, according to Janssen.
The full prescribing information for intravenous golimumab can be found on the FDA website.
after the Food and Drug Administration approved the tumor necrosis factor inhibitor for these indications on Sept. 30, according to an announcement from its manufacturer, Janssen.
Results from the open-label, single-arm, multicenter, phase 3, GO-VIVA clinical trial formed the basis for the agency’s approval of IV golimumab. GO-VIVA was conducted in 127 patients aged 2-17 years with JIA with arthritis in five or more joints (despite receiving treatment with methotrexate for at least 2 months) as part of a postmarketing requirement under the Pediatric Research Equity Act after the intravenous formulation of the biologic was approved for adults with rheumatoid arthritis in 2013. It demonstrated that pediatric patients had a level of pharmacokinetic exposure to golimumab that was similar to what was observed in two pivotal phase 3 trials in adults with moderately to severely active RA and active PsA, as well as efficacy that was generally consistent with responses seen in adult patients with RA, the manufacturer said.
Besides RA, intravenous golimumab was previously approved for adults with PsA and ankylosing spondylitis. As opposed to the IV dosing for adults with RA, PsA, and ankylosing spondylitis at 2 mg/kg infused over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter, dosing for pediatric patients with pJIA and PsA is based on body surface area at 80 mg/m2, also given as an IV infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter.
The adverse reactions observed in GO-VIVA were consistent with the established safety profile of intravenous golimumab in adult patients with RA and PsA, according to Janssen.
The full prescribing information for intravenous golimumab can be found on the FDA website.
Tailoring cosmetic procedures for skin of color patients minimize risks
Based on the fact that hyperpigmentation and other adverse events associated with cosmetic dermatologic procedures are relevant to skin type, not racial identification, individualized strategies to minimize the risk of potential adverse events are always appropriate, according to an expert speaking at the virtual Skin of Color Update 2020.
There are many highly effective interventions that employ lasers, chemical peels, and topical agents to achieve excellent cosmetic results in darker skin, but results are highly dependent on first understanding the relative risks and treatment goals, Cheryl Burgess, MD, president and founder of the Center for Dermatology and Dermatologic Surgery, Washington, D.C., said at the meeting.
She stressed the importance of educating patients that “all cosmetic procedures are not for skin of color.” Her approach is to engage patients on what they are trying to accomplish and then seeking a solution that tailors treatment to skin type based on the Fitzpatrick scale, the Roberts Hyperpigmentation Scale, or other guidance.
“There are so many different methods that we can use, and these are not necessarily the ones that patients have read about in a magazine,” Dr. Burgess said.
Intense pulsed laser (IPL) for hair removal is an example. This technique is not appropriate in patients with Fitzpatrick skin type IV or higher, according to Dr. Burgess, who presented a case example of a bad outcome. In this case, a patient came to her for treatment after exposure to IPL resulted in first- and second-degree burns complicated by extensive hypopigmentation.
Ultimately, the solution in this case involved more laser therapy, but this time a strategy was selected appropriate to skin of color.
“It is hard to suggest to a patient that we are going to use a laser device” when the problem was caused by a laser, Dr. Burgess observed, but properly selected lasers are effective and should be considered in patients with dark skin.
In this case, triple cream containing 6% hydroquinone was the first step towards resolving the hyperpigmentation. Jessner’s peel was also applied to increase penetration.
Laser treatment using two different types of devices was also employed: A 1,927-nm thulium-fractionated erbium glass laser and a 650-microsecond 1,064-nm Nd:YAG laser. The excellent resolution of the hyperpigmentation demonstrates that lasers are effective in dark skin when used appropriately, she noted.
Dr. Burgess emphasized that tailored therapy is not just relevant to Black patients. She cited data indicating that the proportion of multiracial individuals in the United States is increasing, and when tailoring cosmetic procedures, she recommended considering skin characteristics, not just skin color.
Relative to white skin, pigmented skin typically has greater elasticity, greater amounts of collagen, and greater oil content. Importantly, darker skin has a greater propensity to darkening as a result of injury, she said.
In a review of the hyperpigmentation process that follows injury or other insults, Dr. Burgess reported that only three occur inside the melanocyte. There are now topically applied agents to intervene at many of these steps, including hydroquinone to reduce up-regulation of tyrosinase enzymes, and cysteamine to inhibit conversion of DOPA to dopaquinone. All of these, often used in combination, offer potential benefit in skin of color.
However, “you must understand skin of color,” Dr. Burgess emphasized. For example, most hyaluronic acid dermal fillers can be considered in patients with Fitzpatrick skin types IV or higher with low risks for hypo- or hyperpigmentation, scarring, or keloid formation, but technique is important.
“There is more postinflammatory hyperpigmentation with serial or multiple puncture injection techniques” in dark skin relative to lighter skin, according to Dr. Burgess. She recommended reducing this risk with relatively slow injection times.
When in doubt about the result with any cosmetic procedure, test spots are a reasonable strategy, Dr. Burgess said. When there is concern about risk for adverse events, she recommended using low doses and longer intervals between treatments than might otherwise be considered. Patients should participate in understanding the rationale for selecting one approach over another.
It helps for patients to know that “the desired outcome may take many more sessions than what they read about in that we might have to consider conservative measures in order to ensure that we accomplish the cosmetic effect than they want,” she said.
It is critical that clinicians who perform laser or other cosmetic procedures on darker skin be aware of these precautions, agreed Eliot F. Battle Jr., MD, CEO and cofounder of Cultura Dermatology and Laser Center, Washington, D.C. “Over the past 20 years, we have improved lasers that can safely and effectively treat patients with skin of color, but we still have a way to go,” he said at the meeting. Darker skin behaves differently in response to this energy.
“The pigment in the skin of patients of color competes for the laser light, which can cause heat-related side effects, like blistering and pigmentary changes. Skin of color also has an increased incidence of scarring and unwanted pigmentary changes from laser treatments that create irritation and inflammation,” he explained.
It is important to be aware of these differences, but practitioners also “need to treat conservatively to minimize these unwanted side effects,” Dr. Battle said.
Dr. Burgess reported financial relationships with Allergan, Merz Aesthetics, Revance Therapeutics, and Galderma. Dr. Battle had no commercial disclosures.
Based on the fact that hyperpigmentation and other adverse events associated with cosmetic dermatologic procedures are relevant to skin type, not racial identification, individualized strategies to minimize the risk of potential adverse events are always appropriate, according to an expert speaking at the virtual Skin of Color Update 2020.
There are many highly effective interventions that employ lasers, chemical peels, and topical agents to achieve excellent cosmetic results in darker skin, but results are highly dependent on first understanding the relative risks and treatment goals, Cheryl Burgess, MD, president and founder of the Center for Dermatology and Dermatologic Surgery, Washington, D.C., said at the meeting.
She stressed the importance of educating patients that “all cosmetic procedures are not for skin of color.” Her approach is to engage patients on what they are trying to accomplish and then seeking a solution that tailors treatment to skin type based on the Fitzpatrick scale, the Roberts Hyperpigmentation Scale, or other guidance.
“There are so many different methods that we can use, and these are not necessarily the ones that patients have read about in a magazine,” Dr. Burgess said.
Intense pulsed laser (IPL) for hair removal is an example. This technique is not appropriate in patients with Fitzpatrick skin type IV or higher, according to Dr. Burgess, who presented a case example of a bad outcome. In this case, a patient came to her for treatment after exposure to IPL resulted in first- and second-degree burns complicated by extensive hypopigmentation.
Ultimately, the solution in this case involved more laser therapy, but this time a strategy was selected appropriate to skin of color.
“It is hard to suggest to a patient that we are going to use a laser device” when the problem was caused by a laser, Dr. Burgess observed, but properly selected lasers are effective and should be considered in patients with dark skin.
In this case, triple cream containing 6% hydroquinone was the first step towards resolving the hyperpigmentation. Jessner’s peel was also applied to increase penetration.
Laser treatment using two different types of devices was also employed: A 1,927-nm thulium-fractionated erbium glass laser and a 650-microsecond 1,064-nm Nd:YAG laser. The excellent resolution of the hyperpigmentation demonstrates that lasers are effective in dark skin when used appropriately, she noted.
Dr. Burgess emphasized that tailored therapy is not just relevant to Black patients. She cited data indicating that the proportion of multiracial individuals in the United States is increasing, and when tailoring cosmetic procedures, she recommended considering skin characteristics, not just skin color.
Relative to white skin, pigmented skin typically has greater elasticity, greater amounts of collagen, and greater oil content. Importantly, darker skin has a greater propensity to darkening as a result of injury, she said.
In a review of the hyperpigmentation process that follows injury or other insults, Dr. Burgess reported that only three occur inside the melanocyte. There are now topically applied agents to intervene at many of these steps, including hydroquinone to reduce up-regulation of tyrosinase enzymes, and cysteamine to inhibit conversion of DOPA to dopaquinone. All of these, often used in combination, offer potential benefit in skin of color.
However, “you must understand skin of color,” Dr. Burgess emphasized. For example, most hyaluronic acid dermal fillers can be considered in patients with Fitzpatrick skin types IV or higher with low risks for hypo- or hyperpigmentation, scarring, or keloid formation, but technique is important.
“There is more postinflammatory hyperpigmentation with serial or multiple puncture injection techniques” in dark skin relative to lighter skin, according to Dr. Burgess. She recommended reducing this risk with relatively slow injection times.
When in doubt about the result with any cosmetic procedure, test spots are a reasonable strategy, Dr. Burgess said. When there is concern about risk for adverse events, she recommended using low doses and longer intervals between treatments than might otherwise be considered. Patients should participate in understanding the rationale for selecting one approach over another.
It helps for patients to know that “the desired outcome may take many more sessions than what they read about in that we might have to consider conservative measures in order to ensure that we accomplish the cosmetic effect than they want,” she said.
It is critical that clinicians who perform laser or other cosmetic procedures on darker skin be aware of these precautions, agreed Eliot F. Battle Jr., MD, CEO and cofounder of Cultura Dermatology and Laser Center, Washington, D.C. “Over the past 20 years, we have improved lasers that can safely and effectively treat patients with skin of color, but we still have a way to go,” he said at the meeting. Darker skin behaves differently in response to this energy.
“The pigment in the skin of patients of color competes for the laser light, which can cause heat-related side effects, like blistering and pigmentary changes. Skin of color also has an increased incidence of scarring and unwanted pigmentary changes from laser treatments that create irritation and inflammation,” he explained.
It is important to be aware of these differences, but practitioners also “need to treat conservatively to minimize these unwanted side effects,” Dr. Battle said.
Dr. Burgess reported financial relationships with Allergan, Merz Aesthetics, Revance Therapeutics, and Galderma. Dr. Battle had no commercial disclosures.
Based on the fact that hyperpigmentation and other adverse events associated with cosmetic dermatologic procedures are relevant to skin type, not racial identification, individualized strategies to minimize the risk of potential adverse events are always appropriate, according to an expert speaking at the virtual Skin of Color Update 2020.
There are many highly effective interventions that employ lasers, chemical peels, and topical agents to achieve excellent cosmetic results in darker skin, but results are highly dependent on first understanding the relative risks and treatment goals, Cheryl Burgess, MD, president and founder of the Center for Dermatology and Dermatologic Surgery, Washington, D.C., said at the meeting.
She stressed the importance of educating patients that “all cosmetic procedures are not for skin of color.” Her approach is to engage patients on what they are trying to accomplish and then seeking a solution that tailors treatment to skin type based on the Fitzpatrick scale, the Roberts Hyperpigmentation Scale, or other guidance.
“There are so many different methods that we can use, and these are not necessarily the ones that patients have read about in a magazine,” Dr. Burgess said.
Intense pulsed laser (IPL) for hair removal is an example. This technique is not appropriate in patients with Fitzpatrick skin type IV or higher, according to Dr. Burgess, who presented a case example of a bad outcome. In this case, a patient came to her for treatment after exposure to IPL resulted in first- and second-degree burns complicated by extensive hypopigmentation.
Ultimately, the solution in this case involved more laser therapy, but this time a strategy was selected appropriate to skin of color.
“It is hard to suggest to a patient that we are going to use a laser device” when the problem was caused by a laser, Dr. Burgess observed, but properly selected lasers are effective and should be considered in patients with dark skin.
In this case, triple cream containing 6% hydroquinone was the first step towards resolving the hyperpigmentation. Jessner’s peel was also applied to increase penetration.
Laser treatment using two different types of devices was also employed: A 1,927-nm thulium-fractionated erbium glass laser and a 650-microsecond 1,064-nm Nd:YAG laser. The excellent resolution of the hyperpigmentation demonstrates that lasers are effective in dark skin when used appropriately, she noted.
Dr. Burgess emphasized that tailored therapy is not just relevant to Black patients. She cited data indicating that the proportion of multiracial individuals in the United States is increasing, and when tailoring cosmetic procedures, she recommended considering skin characteristics, not just skin color.
Relative to white skin, pigmented skin typically has greater elasticity, greater amounts of collagen, and greater oil content. Importantly, darker skin has a greater propensity to darkening as a result of injury, she said.
In a review of the hyperpigmentation process that follows injury or other insults, Dr. Burgess reported that only three occur inside the melanocyte. There are now topically applied agents to intervene at many of these steps, including hydroquinone to reduce up-regulation of tyrosinase enzymes, and cysteamine to inhibit conversion of DOPA to dopaquinone. All of these, often used in combination, offer potential benefit in skin of color.
However, “you must understand skin of color,” Dr. Burgess emphasized. For example, most hyaluronic acid dermal fillers can be considered in patients with Fitzpatrick skin types IV or higher with low risks for hypo- or hyperpigmentation, scarring, or keloid formation, but technique is important.
“There is more postinflammatory hyperpigmentation with serial or multiple puncture injection techniques” in dark skin relative to lighter skin, according to Dr. Burgess. She recommended reducing this risk with relatively slow injection times.
When in doubt about the result with any cosmetic procedure, test spots are a reasonable strategy, Dr. Burgess said. When there is concern about risk for adverse events, she recommended using low doses and longer intervals between treatments than might otherwise be considered. Patients should participate in understanding the rationale for selecting one approach over another.
It helps for patients to know that “the desired outcome may take many more sessions than what they read about in that we might have to consider conservative measures in order to ensure that we accomplish the cosmetic effect than they want,” she said.
It is critical that clinicians who perform laser or other cosmetic procedures on darker skin be aware of these precautions, agreed Eliot F. Battle Jr., MD, CEO and cofounder of Cultura Dermatology and Laser Center, Washington, D.C. “Over the past 20 years, we have improved lasers that can safely and effectively treat patients with skin of color, but we still have a way to go,” he said at the meeting. Darker skin behaves differently in response to this energy.
“The pigment in the skin of patients of color competes for the laser light, which can cause heat-related side effects, like blistering and pigmentary changes. Skin of color also has an increased incidence of scarring and unwanted pigmentary changes from laser treatments that create irritation and inflammation,” he explained.
It is important to be aware of these differences, but practitioners also “need to treat conservatively to minimize these unwanted side effects,” Dr. Battle said.
Dr. Burgess reported financial relationships with Allergan, Merz Aesthetics, Revance Therapeutics, and Galderma. Dr. Battle had no commercial disclosures.
FROM SOC 2020
High-dose TRT: A new standard of care for LS-SCLC?
In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.
The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.
However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.
Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.
“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
Study details
Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.
The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.
All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.
Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).
The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
Efficacy
There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).
Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).
Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).
Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.
Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
Safety
There were no significant differences in toxicity between the treatment arms.
Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.
Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).
There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.
“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.
“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.
Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.
The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.
“There are some important missing data, in terms of interpretation of results,” she said.
Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.
“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.
The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.
SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.
In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.
The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.
However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.
Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.
“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
Study details
Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.
The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.
All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.
Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).
The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
Efficacy
There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).
Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).
Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).
Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.
Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
Safety
There were no significant differences in toxicity between the treatment arms.
Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.
Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).
There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.
“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.
“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.
Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.
The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.
“There are some important missing data, in terms of interpretation of results,” she said.
Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.
“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.
The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.
SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.
In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.
The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.
However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.
Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.
“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
Study details
Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.
The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.
All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.
Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).
The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
Efficacy
There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).
Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).
Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).
Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.
Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
Safety
There were no significant differences in toxicity between the treatment arms.
Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.
Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).
There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.
“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.
“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.
Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.
The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.
“There are some important missing data, in terms of interpretation of results,” she said.
Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.
“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.
The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.
SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.
FROM ESMO 2020
HPV vaccine shown to substantially reduce cervical cancer risk
It’s been shown that the vaccine (Gardasil) helps prevent genital warts and high-grade cervical lesions, but until now, data on the ability of the vaccine to prevent cervical cancer, although widely assumed, had been lacking.
“Our results extend [the] knowledge base by showing that quadrivalent HPV vaccination is also associated with a substantially reduced risk of invasive cervical cancer, which is the ultimate intent of HPV vaccination programs,” said investigators led by Jiayao Lei, PhD, a researcher in the department of medical epidemiology and biostatistics at the Karolinska Institute, Stockholm.
The study was published online Oct. 1 in the New England Journal of Medicine.
“This work provides evidence of actual cancer prevention,” commented Diane Harper, MD, an HPV expert and professor in the departments of family medicine and obstetrics & gynecology at the University of Michigan, Ann Arbor. She was the principal investigator on the original Gardasil trial.
This study “shows that the quadrivalent HPV vaccine provides prevention from the sexually transmitted HPV infection that actually reduces the incidence of cervical cancer in young women up to 30 years of age,” she said when approached for comment.
However, she also added a note of caution. These new results show “that vaccinated women still develop cervical cancer, but at a slower rate. This makes the connection between early-age vaccination and continued adult life screening incredibly important,” Dr. Harper said in an interview
Cervical cancer was diagnosed in 19 of the 527,871 women (0.004%) who had received at least one dose of the vaccine versus 538 among the 1,145,112 women (0.05%) who had not.
The cumulative incidence was 47 cases per 100,000 vaccinated women and 94 cases per 100,000 unvaccinated women. The cervical cancer incidence rate ratio for the comparison of vaccinated versus unvaccinated women was 0.37 (95% confidence interval, 0.21-0.57).
The risk reduction was even greater among women who had been vaccinated before the age of 17, with a cumulative incidence of 4 versus 54 cases per 100,000 for women vaccinated after age 17. The incidence rate ratio was 0.12 (95% CI, 0.00-0.34) for women who had been vaccinated before age 17 versus 0.47 (95% CI, 0.27-0.75) among those vaccinated from age 17 to 30 years.
Overall, “the risk of cervical cancer among participants who had initiated vaccination before the age of 17 years was 88% lower than among those who had never been vaccinated,” the investigators noted.
These results “support the recommendation to administer quadrivalent HPV vaccine before exposure to HPV infection to achieve the most substantial benefit,” the investigators wrote.
Details of the Swedish review
For their review, Dr. Lei and colleagues used several Swedish demographic and health registries to connect vaccination status to incident cervical cancers, using the personal identification numbers Sweden issues to residents.
Participants were followed starting either on their 10th birthday or on Jan. 1, 2006, whichever came later. They were followed until, among other things, diagnosis of invasive cervical cancer; their 31st birthday; or until Dec. 31, 2017, whichever came first.
The quadrivalent HPV vaccine, approved in Sweden in 2006, was used almost exclusively during the study period. Participants were considered vaccinated if they had received only one shot, but the investigators set out to analyze a relationship between the incidence of invasive cervical cancer and the number of shots given.
Among other things, the team controlled for age at follow-up, calendar year, county of residence, maternal disease history, and parental characteristics, including education and household income.
The investigators commented that it’s possible that HPV-vaccinated women could have been generally healthier than unvaccinated women and so would have been at lower risk for cervical cancer.
“Confounding by lifestyle and health factors in the women (such as smoking status, sexual activity, oral contraceptive use, and obesity) cannot be excluded; these factors are known to be associated with a risk of cervical cancer,” the investigators wrote.
HPV is also associated with other types of cancer, including anal and oropharyngeal cancers. But these cancers develop over a longer period than cervical cancer.
Dr. Harper noted that the “probability of HPV 16 cancer by time since infection peaks at 40 years after infection for anal cancers and nearly 50 years after infection for oropharyngeal cancers. This means that registries, such as in Sweden, for the next 40 years will record the evidence to say whether HPV vaccination lasts long enough to prevent [these] other HPV 16–associated cancers occurring at a much later time in life.”
The work was funded by the Swedish Foundation for Strategic Research, the Swedish Cancer Society, and the Swedish Research Council and by the China Scholarship Council. Dr. Lei and two other investigators reported HPV vaccine research funding from Merck, the maker of Gardasil. Harper disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
It’s been shown that the vaccine (Gardasil) helps prevent genital warts and high-grade cervical lesions, but until now, data on the ability of the vaccine to prevent cervical cancer, although widely assumed, had been lacking.
“Our results extend [the] knowledge base by showing that quadrivalent HPV vaccination is also associated with a substantially reduced risk of invasive cervical cancer, which is the ultimate intent of HPV vaccination programs,” said investigators led by Jiayao Lei, PhD, a researcher in the department of medical epidemiology and biostatistics at the Karolinska Institute, Stockholm.
The study was published online Oct. 1 in the New England Journal of Medicine.
“This work provides evidence of actual cancer prevention,” commented Diane Harper, MD, an HPV expert and professor in the departments of family medicine and obstetrics & gynecology at the University of Michigan, Ann Arbor. She was the principal investigator on the original Gardasil trial.
This study “shows that the quadrivalent HPV vaccine provides prevention from the sexually transmitted HPV infection that actually reduces the incidence of cervical cancer in young women up to 30 years of age,” she said when approached for comment.
However, she also added a note of caution. These new results show “that vaccinated women still develop cervical cancer, but at a slower rate. This makes the connection between early-age vaccination and continued adult life screening incredibly important,” Dr. Harper said in an interview
Cervical cancer was diagnosed in 19 of the 527,871 women (0.004%) who had received at least one dose of the vaccine versus 538 among the 1,145,112 women (0.05%) who had not.
The cumulative incidence was 47 cases per 100,000 vaccinated women and 94 cases per 100,000 unvaccinated women. The cervical cancer incidence rate ratio for the comparison of vaccinated versus unvaccinated women was 0.37 (95% confidence interval, 0.21-0.57).
The risk reduction was even greater among women who had been vaccinated before the age of 17, with a cumulative incidence of 4 versus 54 cases per 100,000 for women vaccinated after age 17. The incidence rate ratio was 0.12 (95% CI, 0.00-0.34) for women who had been vaccinated before age 17 versus 0.47 (95% CI, 0.27-0.75) among those vaccinated from age 17 to 30 years.
Overall, “the risk of cervical cancer among participants who had initiated vaccination before the age of 17 years was 88% lower than among those who had never been vaccinated,” the investigators noted.
These results “support the recommendation to administer quadrivalent HPV vaccine before exposure to HPV infection to achieve the most substantial benefit,” the investigators wrote.
Details of the Swedish review
For their review, Dr. Lei and colleagues used several Swedish demographic and health registries to connect vaccination status to incident cervical cancers, using the personal identification numbers Sweden issues to residents.
Participants were followed starting either on their 10th birthday or on Jan. 1, 2006, whichever came later. They were followed until, among other things, diagnosis of invasive cervical cancer; their 31st birthday; or until Dec. 31, 2017, whichever came first.
The quadrivalent HPV vaccine, approved in Sweden in 2006, was used almost exclusively during the study period. Participants were considered vaccinated if they had received only one shot, but the investigators set out to analyze a relationship between the incidence of invasive cervical cancer and the number of shots given.
Among other things, the team controlled for age at follow-up, calendar year, county of residence, maternal disease history, and parental characteristics, including education and household income.
The investigators commented that it’s possible that HPV-vaccinated women could have been generally healthier than unvaccinated women and so would have been at lower risk for cervical cancer.
“Confounding by lifestyle and health factors in the women (such as smoking status, sexual activity, oral contraceptive use, and obesity) cannot be excluded; these factors are known to be associated with a risk of cervical cancer,” the investigators wrote.
HPV is also associated with other types of cancer, including anal and oropharyngeal cancers. But these cancers develop over a longer period than cervical cancer.
Dr. Harper noted that the “probability of HPV 16 cancer by time since infection peaks at 40 years after infection for anal cancers and nearly 50 years after infection for oropharyngeal cancers. This means that registries, such as in Sweden, for the next 40 years will record the evidence to say whether HPV vaccination lasts long enough to prevent [these] other HPV 16–associated cancers occurring at a much later time in life.”
The work was funded by the Swedish Foundation for Strategic Research, the Swedish Cancer Society, and the Swedish Research Council and by the China Scholarship Council. Dr. Lei and two other investigators reported HPV vaccine research funding from Merck, the maker of Gardasil. Harper disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
It’s been shown that the vaccine (Gardasil) helps prevent genital warts and high-grade cervical lesions, but until now, data on the ability of the vaccine to prevent cervical cancer, although widely assumed, had been lacking.
“Our results extend [the] knowledge base by showing that quadrivalent HPV vaccination is also associated with a substantially reduced risk of invasive cervical cancer, which is the ultimate intent of HPV vaccination programs,” said investigators led by Jiayao Lei, PhD, a researcher in the department of medical epidemiology and biostatistics at the Karolinska Institute, Stockholm.
The study was published online Oct. 1 in the New England Journal of Medicine.
“This work provides evidence of actual cancer prevention,” commented Diane Harper, MD, an HPV expert and professor in the departments of family medicine and obstetrics & gynecology at the University of Michigan, Ann Arbor. She was the principal investigator on the original Gardasil trial.
This study “shows that the quadrivalent HPV vaccine provides prevention from the sexually transmitted HPV infection that actually reduces the incidence of cervical cancer in young women up to 30 years of age,” she said when approached for comment.
However, she also added a note of caution. These new results show “that vaccinated women still develop cervical cancer, but at a slower rate. This makes the connection between early-age vaccination and continued adult life screening incredibly important,” Dr. Harper said in an interview
Cervical cancer was diagnosed in 19 of the 527,871 women (0.004%) who had received at least one dose of the vaccine versus 538 among the 1,145,112 women (0.05%) who had not.
The cumulative incidence was 47 cases per 100,000 vaccinated women and 94 cases per 100,000 unvaccinated women. The cervical cancer incidence rate ratio for the comparison of vaccinated versus unvaccinated women was 0.37 (95% confidence interval, 0.21-0.57).
The risk reduction was even greater among women who had been vaccinated before the age of 17, with a cumulative incidence of 4 versus 54 cases per 100,000 for women vaccinated after age 17. The incidence rate ratio was 0.12 (95% CI, 0.00-0.34) for women who had been vaccinated before age 17 versus 0.47 (95% CI, 0.27-0.75) among those vaccinated from age 17 to 30 years.
Overall, “the risk of cervical cancer among participants who had initiated vaccination before the age of 17 years was 88% lower than among those who had never been vaccinated,” the investigators noted.
These results “support the recommendation to administer quadrivalent HPV vaccine before exposure to HPV infection to achieve the most substantial benefit,” the investigators wrote.
Details of the Swedish review
For their review, Dr. Lei and colleagues used several Swedish demographic and health registries to connect vaccination status to incident cervical cancers, using the personal identification numbers Sweden issues to residents.
Participants were followed starting either on their 10th birthday or on Jan. 1, 2006, whichever came later. They were followed until, among other things, diagnosis of invasive cervical cancer; their 31st birthday; or until Dec. 31, 2017, whichever came first.
The quadrivalent HPV vaccine, approved in Sweden in 2006, was used almost exclusively during the study period. Participants were considered vaccinated if they had received only one shot, but the investigators set out to analyze a relationship between the incidence of invasive cervical cancer and the number of shots given.
Among other things, the team controlled for age at follow-up, calendar year, county of residence, maternal disease history, and parental characteristics, including education and household income.
The investigators commented that it’s possible that HPV-vaccinated women could have been generally healthier than unvaccinated women and so would have been at lower risk for cervical cancer.
“Confounding by lifestyle and health factors in the women (such as smoking status, sexual activity, oral contraceptive use, and obesity) cannot be excluded; these factors are known to be associated with a risk of cervical cancer,” the investigators wrote.
HPV is also associated with other types of cancer, including anal and oropharyngeal cancers. But these cancers develop over a longer period than cervical cancer.
Dr. Harper noted that the “probability of HPV 16 cancer by time since infection peaks at 40 years after infection for anal cancers and nearly 50 years after infection for oropharyngeal cancers. This means that registries, such as in Sweden, for the next 40 years will record the evidence to say whether HPV vaccination lasts long enough to prevent [these] other HPV 16–associated cancers occurring at a much later time in life.”
The work was funded by the Swedish Foundation for Strategic Research, the Swedish Cancer Society, and the Swedish Research Council and by the China Scholarship Council. Dr. Lei and two other investigators reported HPV vaccine research funding from Merck, the maker of Gardasil. Harper disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Real-world safety, efficacy found for fecal transplants
Fecal microbiota transplantation (FMT) appears safe and effective as a treatment for most Clostridioides difficile infections as it is currently being administered, researchers say.
“We actually didn’t see any infections that were definitely transmissible via fecal transplant,” Colleen Kelly, MD, an associate professor of medicine at Brown University, Providence, R.I., said in an interview.
The findings, published online Oct. 1 in the journal Gastroenterology, come from the American Gastroenterological Association (AGA) NIH-funded FMT National Registry and could allay concerns about a treatment that has yet to gain full approval by the Food and Drug Administration, despite successful clinical trials.
C. diff infections are common and increasing in the United States, often can’t be cured with conventional treatments such as antibiotics, and can be deadly.
Transplanting fecal matter from a donor to the patient appears to work by restoring beneficial microorganisms to the patient’s gut. The procedure is also under investigation for a wide range of other ailments, from irritable bowel syndrome to mood disorders.
But much remains unknown. Researchers have counted a thousand bacterial species along with viruses, bacteriophages, archaea, and fungi in the human gut that interact in complex ways, not all of them beneficial.
The FDA has not enforced regulations that would prohibit the procedure, but in March, it warned about infections with enteropathogenic Escherichia coli and Shiga toxin–producing E. coli following fecal transplants.
As a result of these reports, and the theoretical risk of spreading SARS-CoV-2, OpenBiome, the largest stool bank in the United States, has suspended shipments except for emergency orders, and asked clinicians to quarantine any of its products they already have on hand.
In the meantime, long-term effects of the treatment have not been well documented. And clinical trials have excluded patients who might benefit, such as those who have been immunocompromised or have inflammatory bowel disease.
National registry follows patients outside clinical trials
To better understand how patients fare outside these trials, AGA and other organizations developed a national registry, funded by a grant from the National Institute of Allergy and Infectious Diseases.
The current report summarizes results on 259 patients enrolled between Dec. 5, 2017, and Sept. 2, 2019 at 20 sites.
At baseline, 44% of these patients suffered moderate and 36% mild C. diff infections. The duration of the diagnosis ranged from less than 1 week to 9 years, with a median duration of 20 weeks. They ranged from 1 to 15 episodes with a mean of 3.5.
Almost all had received vancomycin, and 62% had at least two courses. About 40% had received metronidazole and 28% had received fidaxomicin.
Almost all participants received stool from an unknown donor, mostly from stool banks, with OpenBiome accounting for 67%. About 85% of the transplants were administered through colonoscopy and 6% by upper endoscopy.
Out of 222 patients who returned for a 1-month follow-up, 90% met the investigators’ definition of cure: resolution of diarrhea without need for further anti–C. diff therapy. About 98% received only one transplant. An intent to treat analysis produced a cure rate of 86%.
Results were good in patients with comorbidities, including 12% who had irritable bowel syndrome, 9% who had ulcerative colitis, and 7% who had Crohn’s disease, Dr. Kelly said. “I hope everybody sees the importance of it. In these patients that are more complicated, who may have underlying comorbidities, who may not have been in the clinical trials, it looks effective in that group, and also incredibly safe.”
She added that the risk of transmitting SARS-CoV-2 is minor. “I think it would be a very, very unlikely way for someone to get a respiratory pathogen.”
Of the 112 participants who were cured at 1 month and returned for follow-up after 6 months, 4 developed recurrent C. diff infection. Eleven patients who were not cured in the first month returned after 6 months. Of these, seven were reported cured at this later follow-up.
Three complications occurred as result of the procedure: one colonoscopic perforation and two episodes of gastrointestinal bleeding.
About 45% of participants reported at least one symptom, with diarrhea not related to C. difficile the most common, followed by abdominal pain, bloating, and constipation.
Eleven patients suffered infections, including two which the investigators thought might be related to the procedure: Bacteroides fragilis in one participant with severe diarrhea, and enteropathogenic E. coli in another with loose stools. Other infections included four urinary tract infections, three cases of pneumonia, one E. coli bacteremia and one tooth infection.
Within a month of the procedure, 27 patients were hospitalized, with 3 of these cases considered possibly related to the procedure.
Findings may not apply to all clinical settings
Vincent B. Young, MD, PhD, a professor of medicine and infectious diseases at the University of Michigan, Ann Arbor, pointed out that the findings might not apply to all clinical settings. The participating clinicians were almost all gastroenterologists working in academic centers.
“Most of them are not Joe Doctor at the doctor’s office,” said Dr. Young, who was not involved with the study. Clinicians in other specialties, such as infectious diseases, might be more inclined to administer fecal transplants through capsules rather than colonoscopies.
And he added that the study does not address effects of the transplant that might develop over years. “Some people talk about how changes in the microbiota lead to increased risk for long-term complications, things like cancer or heart disease. You’re not going to see those in 6 months.”
Also, the study didn’t yield any findings on indications other than C. diff. “In no way, shape, or form does it mean you can use it for autism, depression, heart disease, or [irritable bowel syndrome],” he said.
Still, he said, the study “confirms the fact that fecal cell transplantation is an effective treatment for recurrent C. diff infection when administered as they administered it.”
The National Institute of Allergy and Infectious Diseases funded the registry. Dr. Kelly reported a relationship with Finch Therapeutics. Dr. Young reports financial relationships with Vedanta Biosciences and Bio-K+.
This story was updated on Oct. 4, 2020.
A version of this article originally appeared on Medscape.com.
Fecal microbiota transplantation (FMT) appears safe and effective as a treatment for most Clostridioides difficile infections as it is currently being administered, researchers say.
“We actually didn’t see any infections that were definitely transmissible via fecal transplant,” Colleen Kelly, MD, an associate professor of medicine at Brown University, Providence, R.I., said in an interview.
The findings, published online Oct. 1 in the journal Gastroenterology, come from the American Gastroenterological Association (AGA) NIH-funded FMT National Registry and could allay concerns about a treatment that has yet to gain full approval by the Food and Drug Administration, despite successful clinical trials.
C. diff infections are common and increasing in the United States, often can’t be cured with conventional treatments such as antibiotics, and can be deadly.
Transplanting fecal matter from a donor to the patient appears to work by restoring beneficial microorganisms to the patient’s gut. The procedure is also under investigation for a wide range of other ailments, from irritable bowel syndrome to mood disorders.
But much remains unknown. Researchers have counted a thousand bacterial species along with viruses, bacteriophages, archaea, and fungi in the human gut that interact in complex ways, not all of them beneficial.
The FDA has not enforced regulations that would prohibit the procedure, but in March, it warned about infections with enteropathogenic Escherichia coli and Shiga toxin–producing E. coli following fecal transplants.
As a result of these reports, and the theoretical risk of spreading SARS-CoV-2, OpenBiome, the largest stool bank in the United States, has suspended shipments except for emergency orders, and asked clinicians to quarantine any of its products they already have on hand.
In the meantime, long-term effects of the treatment have not been well documented. And clinical trials have excluded patients who might benefit, such as those who have been immunocompromised or have inflammatory bowel disease.
National registry follows patients outside clinical trials
To better understand how patients fare outside these trials, AGA and other organizations developed a national registry, funded by a grant from the National Institute of Allergy and Infectious Diseases.
The current report summarizes results on 259 patients enrolled between Dec. 5, 2017, and Sept. 2, 2019 at 20 sites.
At baseline, 44% of these patients suffered moderate and 36% mild C. diff infections. The duration of the diagnosis ranged from less than 1 week to 9 years, with a median duration of 20 weeks. They ranged from 1 to 15 episodes with a mean of 3.5.
Almost all had received vancomycin, and 62% had at least two courses. About 40% had received metronidazole and 28% had received fidaxomicin.
Almost all participants received stool from an unknown donor, mostly from stool banks, with OpenBiome accounting for 67%. About 85% of the transplants were administered through colonoscopy and 6% by upper endoscopy.
Out of 222 patients who returned for a 1-month follow-up, 90% met the investigators’ definition of cure: resolution of diarrhea without need for further anti–C. diff therapy. About 98% received only one transplant. An intent to treat analysis produced a cure rate of 86%.
Results were good in patients with comorbidities, including 12% who had irritable bowel syndrome, 9% who had ulcerative colitis, and 7% who had Crohn’s disease, Dr. Kelly said. “I hope everybody sees the importance of it. In these patients that are more complicated, who may have underlying comorbidities, who may not have been in the clinical trials, it looks effective in that group, and also incredibly safe.”
She added that the risk of transmitting SARS-CoV-2 is minor. “I think it would be a very, very unlikely way for someone to get a respiratory pathogen.”
Of the 112 participants who were cured at 1 month and returned for follow-up after 6 months, 4 developed recurrent C. diff infection. Eleven patients who were not cured in the first month returned after 6 months. Of these, seven were reported cured at this later follow-up.
Three complications occurred as result of the procedure: one colonoscopic perforation and two episodes of gastrointestinal bleeding.
About 45% of participants reported at least one symptom, with diarrhea not related to C. difficile the most common, followed by abdominal pain, bloating, and constipation.
Eleven patients suffered infections, including two which the investigators thought might be related to the procedure: Bacteroides fragilis in one participant with severe diarrhea, and enteropathogenic E. coli in another with loose stools. Other infections included four urinary tract infections, three cases of pneumonia, one E. coli bacteremia and one tooth infection.
Within a month of the procedure, 27 patients were hospitalized, with 3 of these cases considered possibly related to the procedure.
Findings may not apply to all clinical settings
Vincent B. Young, MD, PhD, a professor of medicine and infectious diseases at the University of Michigan, Ann Arbor, pointed out that the findings might not apply to all clinical settings. The participating clinicians were almost all gastroenterologists working in academic centers.
“Most of them are not Joe Doctor at the doctor’s office,” said Dr. Young, who was not involved with the study. Clinicians in other specialties, such as infectious diseases, might be more inclined to administer fecal transplants through capsules rather than colonoscopies.
And he added that the study does not address effects of the transplant that might develop over years. “Some people talk about how changes in the microbiota lead to increased risk for long-term complications, things like cancer or heart disease. You’re not going to see those in 6 months.”
Also, the study didn’t yield any findings on indications other than C. diff. “In no way, shape, or form does it mean you can use it for autism, depression, heart disease, or [irritable bowel syndrome],” he said.
Still, he said, the study “confirms the fact that fecal cell transplantation is an effective treatment for recurrent C. diff infection when administered as they administered it.”
The National Institute of Allergy and Infectious Diseases funded the registry. Dr. Kelly reported a relationship with Finch Therapeutics. Dr. Young reports financial relationships with Vedanta Biosciences and Bio-K+.
This story was updated on Oct. 4, 2020.
A version of this article originally appeared on Medscape.com.
Fecal microbiota transplantation (FMT) appears safe and effective as a treatment for most Clostridioides difficile infections as it is currently being administered, researchers say.
“We actually didn’t see any infections that were definitely transmissible via fecal transplant,” Colleen Kelly, MD, an associate professor of medicine at Brown University, Providence, R.I., said in an interview.
The findings, published online Oct. 1 in the journal Gastroenterology, come from the American Gastroenterological Association (AGA) NIH-funded FMT National Registry and could allay concerns about a treatment that has yet to gain full approval by the Food and Drug Administration, despite successful clinical trials.
C. diff infections are common and increasing in the United States, often can’t be cured with conventional treatments such as antibiotics, and can be deadly.
Transplanting fecal matter from a donor to the patient appears to work by restoring beneficial microorganisms to the patient’s gut. The procedure is also under investigation for a wide range of other ailments, from irritable bowel syndrome to mood disorders.
But much remains unknown. Researchers have counted a thousand bacterial species along with viruses, bacteriophages, archaea, and fungi in the human gut that interact in complex ways, not all of them beneficial.
The FDA has not enforced regulations that would prohibit the procedure, but in March, it warned about infections with enteropathogenic Escherichia coli and Shiga toxin–producing E. coli following fecal transplants.
As a result of these reports, and the theoretical risk of spreading SARS-CoV-2, OpenBiome, the largest stool bank in the United States, has suspended shipments except for emergency orders, and asked clinicians to quarantine any of its products they already have on hand.
In the meantime, long-term effects of the treatment have not been well documented. And clinical trials have excluded patients who might benefit, such as those who have been immunocompromised or have inflammatory bowel disease.
National registry follows patients outside clinical trials
To better understand how patients fare outside these trials, AGA and other organizations developed a national registry, funded by a grant from the National Institute of Allergy and Infectious Diseases.
The current report summarizes results on 259 patients enrolled between Dec. 5, 2017, and Sept. 2, 2019 at 20 sites.
At baseline, 44% of these patients suffered moderate and 36% mild C. diff infections. The duration of the diagnosis ranged from less than 1 week to 9 years, with a median duration of 20 weeks. They ranged from 1 to 15 episodes with a mean of 3.5.
Almost all had received vancomycin, and 62% had at least two courses. About 40% had received metronidazole and 28% had received fidaxomicin.
Almost all participants received stool from an unknown donor, mostly from stool banks, with OpenBiome accounting for 67%. About 85% of the transplants were administered through colonoscopy and 6% by upper endoscopy.
Out of 222 patients who returned for a 1-month follow-up, 90% met the investigators’ definition of cure: resolution of diarrhea without need for further anti–C. diff therapy. About 98% received only one transplant. An intent to treat analysis produced a cure rate of 86%.
Results were good in patients with comorbidities, including 12% who had irritable bowel syndrome, 9% who had ulcerative colitis, and 7% who had Crohn’s disease, Dr. Kelly said. “I hope everybody sees the importance of it. In these patients that are more complicated, who may have underlying comorbidities, who may not have been in the clinical trials, it looks effective in that group, and also incredibly safe.”
She added that the risk of transmitting SARS-CoV-2 is minor. “I think it would be a very, very unlikely way for someone to get a respiratory pathogen.”
Of the 112 participants who were cured at 1 month and returned for follow-up after 6 months, 4 developed recurrent C. diff infection. Eleven patients who were not cured in the first month returned after 6 months. Of these, seven were reported cured at this later follow-up.
Three complications occurred as result of the procedure: one colonoscopic perforation and two episodes of gastrointestinal bleeding.
About 45% of participants reported at least one symptom, with diarrhea not related to C. difficile the most common, followed by abdominal pain, bloating, and constipation.
Eleven patients suffered infections, including two which the investigators thought might be related to the procedure: Bacteroides fragilis in one participant with severe diarrhea, and enteropathogenic E. coli in another with loose stools. Other infections included four urinary tract infections, three cases of pneumonia, one E. coli bacteremia and one tooth infection.
Within a month of the procedure, 27 patients were hospitalized, with 3 of these cases considered possibly related to the procedure.
Findings may not apply to all clinical settings
Vincent B. Young, MD, PhD, a professor of medicine and infectious diseases at the University of Michigan, Ann Arbor, pointed out that the findings might not apply to all clinical settings. The participating clinicians were almost all gastroenterologists working in academic centers.
“Most of them are not Joe Doctor at the doctor’s office,” said Dr. Young, who was not involved with the study. Clinicians in other specialties, such as infectious diseases, might be more inclined to administer fecal transplants through capsules rather than colonoscopies.
And he added that the study does not address effects of the transplant that might develop over years. “Some people talk about how changes in the microbiota lead to increased risk for long-term complications, things like cancer or heart disease. You’re not going to see those in 6 months.”
Also, the study didn’t yield any findings on indications other than C. diff. “In no way, shape, or form does it mean you can use it for autism, depression, heart disease, or [irritable bowel syndrome],” he said.
Still, he said, the study “confirms the fact that fecal cell transplantation is an effective treatment for recurrent C. diff infection when administered as they administered it.”
The National Institute of Allergy and Infectious Diseases funded the registry. Dr. Kelly reported a relationship with Finch Therapeutics. Dr. Young reports financial relationships with Vedanta Biosciences and Bio-K+.
This story was updated on Oct. 4, 2020.
A version of this article originally appeared on Medscape.com.