The FDA has approved Epidiolex (cannabidiol [CBD]) oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients age 2 and older. Epidiolex is the first FDA-approved drug that contains a derivative of marijuana. It also is the first drug approved by the FDA for the treatment of Dravet syndrome.

The approval was based on three randomized, double-blind, placebo-controlled clinical trials that included 516 patients with Lennox-Gastaut syndrome or Dravet syndrome. Epidiolex taken with other epilepsy medications reduced the frequency of seizures, compared with placebo. The most common side effects included lethargy, elevated liver enzymes, decreased appetite, diarrhea, rash, weakness, sleep disorder, and infection.

“Because of the adequate and well-controlled clinical studies that supported this approval, prescribers can have confidence in the drug’s uniform strength and consistent delivery that support appropriate dosing needed for treating patients with these complex and serious epilepsy syndromes,” said FDA Commissioner Scott Gottlieb, MD. “We will continue to support rigorous scientific research on the potential medical uses of marijuana-derived products…. But at the same time, we are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims.”

The FDA has approved Epidiolex (cannabidiol [CBD]) oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients age 2 and older. Epidiolex is the first FDA-approved drug that contains a derivative of marijuana. It also is the first drug approved by the FDA for the treatment of Dravet syndrome.

The approval was based on three randomized, double-blind, placebo-controlled clinical trials that included 516 patients with Lennox-Gastaut syndrome or Dravet syndrome. Epidiolex taken with other epilepsy medications reduced the frequency of seizures, compared with placebo. The most common side effects included lethargy, elevated liver enzymes, decreased appetite, diarrhea, rash, weakness, sleep disorder, and infection.

“Because of the adequate and well-controlled clinical studies that supported this approval, prescribers can have confidence in the drug’s uniform strength and consistent delivery that support appropriate dosing needed for treating patients with these complex and serious epilepsy syndromes,” said FDA Commissioner Scott Gottlieb, MD. “We will continue to support rigorous scientific research on the potential medical uses of marijuana-derived products…. But at the same time, we are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims.”

The FDA has approved Epidiolex (cannabidiol [CBD]) oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients age 2 and older. Epidiolex is the first FDA-approved drug that contains a derivative of marijuana. It also is the first drug approved by the FDA for the treatment of Dravet syndrome.

The approval was based on three randomized, double-blind, placebo-controlled clinical trials that included 516 patients with Lennox-Gastaut syndrome or Dravet syndrome. Epidiolex taken with other epilepsy medications reduced the frequency of seizures, compared with placebo. The most common side effects included lethargy, elevated liver enzymes, decreased appetite, diarrhea, rash, weakness, sleep disorder, and infection.

“Because of the adequate and well-controlled clinical studies that supported this approval, prescribers can have confidence in the drug’s uniform strength and consistent delivery that support appropriate dosing needed for treating patients with these complex and serious epilepsy syndromes,” said FDA Commissioner Scott Gottlieb, MD. “We will continue to support rigorous scientific research on the potential medical uses of marijuana-derived products…. But at the same time, we are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims.”

Abortion performed in an ambulatory surgery center (ASC) was not associated with a significant difference in abortion-related complications, compared with procedures performed in an office-based setting, according to results of a retrospective cohort study.

Low rates of abortion-related morbidities and adverse events were observed in both ASCs and office-based settings in the study, which was based on data for 49,287 women with U.S. private health insurance who had induced abortions between 2011 and 2014.

These findings might help inform decisions about the type of facility where induced abortions are performed, according to Sarah C. M. Roberts, DrPH, of the University of California, San Francisco, and her coauthors.

The U.S. Supreme Court ruled in 2016 that a Texas law requiring abortion facilities to meet ASC standards was unconstitutional, Dr. Roberts and her coauthors wrote in JAMA.

“Despite this ruling, 13 states currently have laws that require abortions to be provided in ASCs,” the authors wrote, noting that supporters of the laws argue that these requirements make abortions safer.

The laws have requirements such as separate procedure and recovery rooms, and specified hall and door widths. “Many of these apply only at a specific gestational week or gestational duration, typically in the second trimester,” they noted, adding that over 95% of induced abortions are performed in outpatient settings such as clinics or physician offices.

Their retrospective cohort study included a total of 50,311 induced abortions, of which 89% took place in office based settings and 11% in ASCs. Nearly half (47%) were first-trimester aspiration procedures, while 27% were first-trimester medication and 26% were second trimester or later.

Abortion-related morbidity or adverse events were reported for 3.33% of procedures overall. The adjusted incidence rate was 3.25% for ASC-based procedures, and similarly, 3.33% for office-based procedures.

The overall complication rate was higher than previous estimates based on insurance claims data, they said, but the estimate of major events was similar at 0.32%, breaking down to 0.26% for ASCs and 0.33% for office-based settings. The rate of infections was 0.58% for ASCs and 0.77% for office-based settings.

This is not the first study looking at the association between abortion-related events and the procedure setting, though the literature is limited, according to Dr. Roberts and her coauthors. One previous study showed fewer abortion-related events in clinics than in hospitals, while a recent review found similar abortion-related events following first-trimester abortions in hospitals, ASCs, and office-based settings.

One limitation of the current study is that the database included only abortions that were paid for by private insurance, which represents about 15% of the nearly 1 million procedures done each year in the United States.

“Thus, findings may not be generalizable to all abortions in the United States,” Dr. Roberts and her coauthors wrote.

The study was supported by a grant from the Society of Family Planning Research Fund. Study authors reported no conflicts of interest.

SOURCE: Roberts SCM et al. JAMA. 2018 Jun 26;319(24):2497-2506.

Abortion performed in an ambulatory surgery center (ASC) was not associated with a significant difference in abortion-related complications, compared with procedures performed in an office-based setting, according to results of a retrospective cohort study.

Low rates of abortion-related morbidities and adverse events were observed in both ASCs and office-based settings in the study, which was based on data for 49,287 women with U.S. private health insurance who had induced abortions between 2011 and 2014.

These findings might help inform decisions about the type of facility where induced abortions are performed, according to Sarah C. M. Roberts, DrPH, of the University of California, San Francisco, and her coauthors.

The U.S. Supreme Court ruled in 2016 that a Texas law requiring abortion facilities to meet ASC standards was unconstitutional, Dr. Roberts and her coauthors wrote in JAMA.

“Despite this ruling, 13 states currently have laws that require abortions to be provided in ASCs,” the authors wrote, noting that supporters of the laws argue that these requirements make abortions safer.

The laws have requirements such as separate procedure and recovery rooms, and specified hall and door widths. “Many of these apply only at a specific gestational week or gestational duration, typically in the second trimester,” they noted, adding that over 95% of induced abortions are performed in outpatient settings such as clinics or physician offices.

Their retrospective cohort study included a total of 50,311 induced abortions, of which 89% took place in office based settings and 11% in ASCs. Nearly half (47%) were first-trimester aspiration procedures, while 27% were first-trimester medication and 26% were second trimester or later.

Abortion-related morbidity or adverse events were reported for 3.33% of procedures overall. The adjusted incidence rate was 3.25% for ASC-based procedures, and similarly, 3.33% for office-based procedures.

The overall complication rate was higher than previous estimates based on insurance claims data, they said, but the estimate of major events was similar at 0.32%, breaking down to 0.26% for ASCs and 0.33% for office-based settings. The rate of infections was 0.58% for ASCs and 0.77% for office-based settings.

This is not the first study looking at the association between abortion-related events and the procedure setting, though the literature is limited, according to Dr. Roberts and her coauthors. One previous study showed fewer abortion-related events in clinics than in hospitals, while a recent review found similar abortion-related events following first-trimester abortions in hospitals, ASCs, and office-based settings.

One limitation of the current study is that the database included only abortions that were paid for by private insurance, which represents about 15% of the nearly 1 million procedures done each year in the United States.

“Thus, findings may not be generalizable to all abortions in the United States,” Dr. Roberts and her coauthors wrote.

The study was supported by a grant from the Society of Family Planning Research Fund. Study authors reported no conflicts of interest.

SOURCE: Roberts SCM et al. JAMA. 2018 Jun 26;319(24):2497-2506.

Abortion performed in an ambulatory surgery center (ASC) was not associated with a significant difference in abortion-related complications, compared with procedures performed in an office-based setting, according to results of a retrospective cohort study.

Low rates of abortion-related morbidities and adverse events were observed in both ASCs and office-based settings in the study, which was based on data for 49,287 women with U.S. private health insurance who had induced abortions between 2011 and 2014.

These findings might help inform decisions about the type of facility where induced abortions are performed, according to Sarah C. M. Roberts, DrPH, of the University of California, San Francisco, and her coauthors.

The U.S. Supreme Court ruled in 2016 that a Texas law requiring abortion facilities to meet ASC standards was unconstitutional, Dr. Roberts and her coauthors wrote in JAMA.

“Despite this ruling, 13 states currently have laws that require abortions to be provided in ASCs,” the authors wrote, noting that supporters of the laws argue that these requirements make abortions safer.

The laws have requirements such as separate procedure and recovery rooms, and specified hall and door widths. “Many of these apply only at a specific gestational week or gestational duration, typically in the second trimester,” they noted, adding that over 95% of induced abortions are performed in outpatient settings such as clinics or physician offices.

Their retrospective cohort study included a total of 50,311 induced abortions, of which 89% took place in office based settings and 11% in ASCs. Nearly half (47%) were first-trimester aspiration procedures, while 27% were first-trimester medication and 26% were second trimester or later.

Abortion-related morbidity or adverse events were reported for 3.33% of procedures overall. The adjusted incidence rate was 3.25% for ASC-based procedures, and similarly, 3.33% for office-based procedures.

The overall complication rate was higher than previous estimates based on insurance claims data, they said, but the estimate of major events was similar at 0.32%, breaking down to 0.26% for ASCs and 0.33% for office-based settings. The rate of infections was 0.58% for ASCs and 0.77% for office-based settings.

This is not the first study looking at the association between abortion-related events and the procedure setting, though the literature is limited, according to Dr. Roberts and her coauthors. One previous study showed fewer abortion-related events in clinics than in hospitals, while a recent review found similar abortion-related events following first-trimester abortions in hospitals, ASCs, and office-based settings.

One limitation of the current study is that the database included only abortions that were paid for by private insurance, which represents about 15% of the nearly 1 million procedures done each year in the United States.

“Thus, findings may not be generalizable to all abortions in the United States,” Dr. Roberts and her coauthors wrote.

The study was supported by a grant from the Society of Family Planning Research Fund. Study authors reported no conflicts of interest.

SOURCE: Roberts SCM et al. JAMA. 2018 Jun 26;319(24):2497-2506.

For the fourth consecutive year, Boston Children’s Hospital has been named the top children’s hospital by U.S. News & World Report.

The hospital finished among the top five in all 10 pediatric specialties included in the rankings: cancer (third), cardiology and heart surgery (second), diabetes and endocrinology (second), gastroenterology and GI surgery (second), neonatology (third), nephrology (first), neurology and neurosurgery (first), orthopedics (first), pulmonology (fourth), and urology (third), according to the 2018-2019 Best Children’s Hospitals rankings.

[email protected]

For the fourth consecutive year, Boston Children’s Hospital has been named the top children’s hospital by U.S. News & World Report.

The hospital finished among the top five in all 10 pediatric specialties included in the rankings: cancer (third), cardiology and heart surgery (second), diabetes and endocrinology (second), gastroenterology and GI surgery (second), neonatology (third), nephrology (first), neurology and neurosurgery (first), orthopedics (first), pulmonology (fourth), and urology (third), according to the 2018-2019 Best Children’s Hospitals rankings.

[email protected]

For the fourth consecutive year, Boston Children’s Hospital has been named the top children’s hospital by U.S. News & World Report.

The hospital finished among the top five in all 10 pediatric specialties included in the rankings: cancer (third), cardiology and heart surgery (second), diabetes and endocrinology (second), gastroenterology and GI surgery (second), neonatology (third), nephrology (first), neurology and neurosurgery (first), orthopedics (first), pulmonology (fourth), and urology (third), according to the 2018-2019 Best Children’s Hospitals rankings.

[email protected]

Physicists have strict rules about significant figures. Medical journals lack this professional discipline and it produces distortions that mislead readers.

Whenever you measure and report something in physics, the precision of the measurement is reflected in how the value is written. Writing a result with more digits implies that a higher precision was achieved. If that wasn’t the case, you are falsely claiming skill and accomplishment. You’ve entered the zone of post-truth.

This point was taught by my high school physics teacher, Mr. Gunnar Overgaard, may he rest in peace. Suppose we measured the length of the lab table with the meter stick. We repeated the action three times. We computed an average. Our table was 243.7 cm long. If we wrote 243.73 or 243.73333 we got a lower grade. Meter sticks only have markings of 0.1 cm. So the precision of the reported measurement should properly reflect that limitation.

Researchers in medicine seem to have skipped that lesson in physics lab. In medical journals, the default seems to be to report measurements with two decimal points, such as 16.67%, which is a gross distortion of the precision when I know that that really means 2 out of 12 patients had the finding.

This issue of precision came up recently in two papers published about the number of deaths caused by Hurricane Maria in Puerto Rico. The official death toll was 64. This number became a political hot potato when President Trump cited it as if it was evidence that he and the current local government had managed the emergency response better than George W. Bush did for Katrina.

On May 29, 2018, some researchers at the Harvard School of Public Health, a prestigious institution, published an article in The New England Journal of Medicine, a prestigious journal. You would presume that pair could report properly. The abstract said “This rate yielded a total of 4,645 excess deaths during this period (95% CI, 793 to 8,498).”¹ Many newspapers published the number 4,645 in a headline. Most newspapers didn’t include all of the scientific mumbo jumbo about bias and confidence intervals.

Georgijevic/E+/Getty Images

So in the spirit of thinking globally but acting locally, what can I do? I love my editor. I have hinted before about how much easier it is to read, as well as more accurate scientifically, to round the numbers that we report. We've done it a few times recently, but now that the Washington Post has done it on a major news story, should this practice become the norm for journalism? If medical journal editors won't handle precision honestly, other journalists must step up. I'm distressed when I review an article that says 14.6% agreed and 79.2% strongly agreed and I know those percentages with 3 digits really mean 7/48 and 38/48, so they should be rounded to two significant figures. And isn’t it easier to read and comprehend if reporting that three treatment groups had positive findings of 4.25%, 12.08%, and 9.84% when rounded to 4%, 12%, and 10%?

Scientists using this false precision (and peer reviewers who allow it) need to be corrected. They are trying to sell their research as a Louis Vuitton handbag when we all know it is only a cheap knockoff.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected]

References

1. N Eng J Med. 2018 May 29. doi: 10.1056/NEJMsa1803972

2. “Harvard study estimates thousands died in Puerto Rico because of Hurricane Maria,” by Arelis R. Hernández and Laurie McGinley, The Washington Post, May 29, 2018.

3. “Did exactly 4,645 people die in Hurricane Maria? Nope.” by Glenn Kessler, The Washington Post, June 1, 2018.

Physicists have strict rules about significant figures. Medical journals lack this professional discipline and it produces distortions that mislead readers.

Whenever you measure and report something in physics, the precision of the measurement is reflected in how the value is written. Writing a result with more digits implies that a higher precision was achieved. If that wasn’t the case, you are falsely claiming skill and accomplishment. You’ve entered the zone of post-truth.

This point was taught by my high school physics teacher, Mr. Gunnar Overgaard, may he rest in peace. Suppose we measured the length of the lab table with the meter stick. We repeated the action three times. We computed an average. Our table was 243.7 cm long. If we wrote 243.73 or 243.73333 we got a lower grade. Meter sticks only have markings of 0.1 cm. So the precision of the reported measurement should properly reflect that limitation.

Researchers in medicine seem to have skipped that lesson in physics lab. In medical journals, the default seems to be to report measurements with two decimal points, such as 16.67%, which is a gross distortion of the precision when I know that that really means 2 out of 12 patients had the finding.

This issue of precision came up recently in two papers published about the number of deaths caused by Hurricane Maria in Puerto Rico. The official death toll was 64. This number became a political hot potato when President Trump cited it as if it was evidence that he and the current local government had managed the emergency response better than George W. Bush did for Katrina.

On May 29, 2018, some researchers at the Harvard School of Public Health, a prestigious institution, published an article in The New England Journal of Medicine, a prestigious journal. You would presume that pair could report properly. The abstract said “This rate yielded a total of 4,645 excess deaths during this period (95% CI, 793 to 8,498).”¹ Many newspapers published the number 4,645 in a headline. Most newspapers didn’t include all of the scientific mumbo jumbo about bias and confidence intervals.

Georgijevic/E+/Getty Images

So in the spirit of thinking globally but acting locally, what can I do? I love my editor. I have hinted before about how much easier it is to read, as well as more accurate scientifically, to round the numbers that we report. We've done it a few times recently, but now that the Washington Post has done it on a major news story, should this practice become the norm for journalism? If medical journal editors won't handle precision honestly, other journalists must step up. I'm distressed when I review an article that says 14.6% agreed and 79.2% strongly agreed and I know those percentages with 3 digits really mean 7/48 and 38/48, so they should be rounded to two significant figures. And isn’t it easier to read and comprehend if reporting that three treatment groups had positive findings of 4.25%, 12.08%, and 9.84% when rounded to 4%, 12%, and 10%?

Scientists using this false precision (and peer reviewers who allow it) need to be corrected. They are trying to sell their research as a Louis Vuitton handbag when we all know it is only a cheap knockoff.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected]

References

1. N Eng J Med. 2018 May 29. doi: 10.1056/NEJMsa1803972

2. “Harvard study estimates thousands died in Puerto Rico because of Hurricane Maria,” by Arelis R. Hernández and Laurie McGinley, The Washington Post, May 29, 2018.

3. “Did exactly 4,645 people die in Hurricane Maria? Nope.” by Glenn Kessler, The Washington Post, June 1, 2018.

Physicists have strict rules about significant figures. Medical journals lack this professional discipline and it produces distortions that mislead readers.

Whenever you measure and report something in physics, the precision of the measurement is reflected in how the value is written. Writing a result with more digits implies that a higher precision was achieved. If that wasn’t the case, you are falsely claiming skill and accomplishment. You’ve entered the zone of post-truth.

This point was taught by my high school physics teacher, Mr. Gunnar Overgaard, may he rest in peace. Suppose we measured the length of the lab table with the meter stick. We repeated the action three times. We computed an average. Our table was 243.7 cm long. If we wrote 243.73 or 243.73333 we got a lower grade. Meter sticks only have markings of 0.1 cm. So the precision of the reported measurement should properly reflect that limitation.

Researchers in medicine seem to have skipped that lesson in physics lab. In medical journals, the default seems to be to report measurements with two decimal points, such as 16.67%, which is a gross distortion of the precision when I know that that really means 2 out of 12 patients had the finding.

This issue of precision came up recently in two papers published about the number of deaths caused by Hurricane Maria in Puerto Rico. The official death toll was 64. This number became a political hot potato when President Trump cited it as if it was evidence that he and the current local government had managed the emergency response better than George W. Bush did for Katrina.

On May 29, 2018, some researchers at the Harvard School of Public Health, a prestigious institution, published an article in The New England Journal of Medicine, a prestigious journal. You would presume that pair could report properly. The abstract said “This rate yielded a total of 4,645 excess deaths during this period (95% CI, 793 to 8,498).”¹ Many newspapers published the number 4,645 in a headline. Most newspapers didn’t include all of the scientific mumbo jumbo about bias and confidence intervals.

Georgijevic/E+/Getty Images

So in the spirit of thinking globally but acting locally, what can I do? I love my editor. I have hinted before about how much easier it is to read, as well as more accurate scientifically, to round the numbers that we report. We've done it a few times recently, but now that the Washington Post has done it on a major news story, should this practice become the norm for journalism? If medical journal editors won't handle precision honestly, other journalists must step up. I'm distressed when I review an article that says 14.6% agreed and 79.2% strongly agreed and I know those percentages with 3 digits really mean 7/48 and 38/48, so they should be rounded to two significant figures. And isn’t it easier to read and comprehend if reporting that three treatment groups had positive findings of 4.25%, 12.08%, and 9.84% when rounded to 4%, 12%, and 10%?

Scientists using this false precision (and peer reviewers who allow it) need to be corrected. They are trying to sell their research as a Louis Vuitton handbag when we all know it is only a cheap knockoff.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected]

References

1. N Eng J Med. 2018 May 29. doi: 10.1056/NEJMsa1803972

2. “Harvard study estimates thousands died in Puerto Rico because of Hurricane Maria,” by Arelis R. Hernández and Laurie McGinley, The Washington Post, May 29, 2018.

3. “Did exactly 4,645 people die in Hurricane Maria? Nope.” by Glenn Kessler, The Washington Post, June 1, 2018.

A cost-effective community program at Pennsylvania State University helped most participants change their behavior and significantly improve their HbA_1c and blood pressure, according to a report in Preventing Chronic Disease.

The researchers for the extension program, Dining with Diabetes, collected data on 2,738 adults with type 2 diabetes or prediabetes and adult family members without diabetes. The program consisted of 4 weekly 2-hour classes and a follow-up class conducted 3 months later. The classes included hands-on food preparation, food tastings, and physical activity.

At the follow-up class, participants who completed the program had significant improvements in diabetes-related biomarkers. A greater percentage said they were confident they could keep their diabetes under control, compared with the number at baseline (67% v 58%). At baseline, most participants were adhering to medications; the researchers found no significant change in adherence.

Participants also increased the number of days per week on which they exercised for ≥ 20 minutes (from 2.9 to 3.4 days), and slightly increased the number of days on which they ate a variety of fruits and vegetables.

Nearly half of participants with baseline and follow-up measurements had a drop in HbA_1c. At follow-up, 21% had a reduction large enough to lower their diabetes status. The changes translated to a 5.9% decrease in HbA_1c for 27% of those who had uncontrolled diabetes at baseline. More than half (59%) had a drop in blood pressure, including 60% of those with uncontrolled diabetes.

The program, which was free to participants, cost Penn State Extension $407 per person. The researchers estimate that extending the program to half of the 1.3 million people with diabetes in Pennsylvania would save the state approximately $195 million at 1 year.

A cost-effective community program at Pennsylvania State University helped most participants change their behavior and significantly improve their HbA_1c and blood pressure, according to a report in Preventing Chronic Disease.

The researchers for the extension program, Dining with Diabetes, collected data on 2,738 adults with type 2 diabetes or prediabetes and adult family members without diabetes. The program consisted of 4 weekly 2-hour classes and a follow-up class conducted 3 months later. The classes included hands-on food preparation, food tastings, and physical activity.

At the follow-up class, participants who completed the program had significant improvements in diabetes-related biomarkers. A greater percentage said they were confident they could keep their diabetes under control, compared with the number at baseline (67% v 58%). At baseline, most participants were adhering to medications; the researchers found no significant change in adherence.

Participants also increased the number of days per week on which they exercised for ≥ 20 minutes (from 2.9 to 3.4 days), and slightly increased the number of days on which they ate a variety of fruits and vegetables.

Nearly half of participants with baseline and follow-up measurements had a drop in HbA_1c. At follow-up, 21% had a reduction large enough to lower their diabetes status. The changes translated to a 5.9% decrease in HbA_1c for 27% of those who had uncontrolled diabetes at baseline. More than half (59%) had a drop in blood pressure, including 60% of those with uncontrolled diabetes.

The program, which was free to participants, cost Penn State Extension $407 per person. The researchers estimate that extending the program to half of the 1.3 million people with diabetes in Pennsylvania would save the state approximately $195 million at 1 year.

A cost-effective community program at Pennsylvania State University helped most participants change their behavior and significantly improve their HbA_1c and blood pressure, according to a report in Preventing Chronic Disease.

The researchers for the extension program, Dining with Diabetes, collected data on 2,738 adults with type 2 diabetes or prediabetes and adult family members without diabetes. The program consisted of 4 weekly 2-hour classes and a follow-up class conducted 3 months later. The classes included hands-on food preparation, food tastings, and physical activity.

At the follow-up class, participants who completed the program had significant improvements in diabetes-related biomarkers. A greater percentage said they were confident they could keep their diabetes under control, compared with the number at baseline (67% v 58%). At baseline, most participants were adhering to medications; the researchers found no significant change in adherence.

Participants also increased the number of days per week on which they exercised for ≥ 20 minutes (from 2.9 to 3.4 days), and slightly increased the number of days on which they ate a variety of fruits and vegetables.

Nearly half of participants with baseline and follow-up measurements had a drop in HbA_1c. At follow-up, 21% had a reduction large enough to lower their diabetes status. The changes translated to a 5.9% decrease in HbA_1c for 27% of those who had uncontrolled diabetes at baseline. More than half (59%) had a drop in blood pressure, including 60% of those with uncontrolled diabetes.

The program, which was free to participants, cost Penn State Extension $407 per person. The researchers estimate that extending the program to half of the 1.3 million people with diabetes in Pennsylvania would save the state approximately $195 million at 1 year.

Many things can reactivate chronic hepatitis B virus (HBV) infection—withdrawal of antiviral therapy, pregnancy, and chemotherapy, to name a few. So when a patient with stable chronic HBV virus presented with significant hepatitis flare, clinicians from Beth Israel Deaconess Medical Center in Boston, Massachusetts, had a long list to check.

They first ruled out drug-associated hepatotoxicity and screened the patient for common causes of acute hepatitis. Beyond the HBV, the patient did not have other significant medical conditions, had not had close contact with anyone ill, and was not pregnant. Tests were negative for cytomegalovirus, Epstein-Barr syndrome, HIV, hepatitis A, C, and D. The patient tested negative for both antihepatitis E virus (HEV) IgM and IgG in a visit about 9 months before.

However, she reported regularly consuming pork, including a recent barbecue meal. Thus, the clinicians focused on HEV serology, which confirmed that she had an acute HEV infection.

Pigs act as a “natural reservoir” for HEV; contaminated meats and direct contact with animals are the most common causes of HEV human infection in industrialized countries. Recent data reveal the prevalence of HEV antibodies in the US is about 6%, illustrating that it is not as uncommon as it was thought to be. Although there was no direct evidence to confirm the source of her infection, it seemed likely due to the pork consumption.

The patient was started on tenofovir but stopped it 4 months later because she felt well. After a subsequent flare, “repeated counseling” persuaded the patient to start on entecavir, with successful viral suppression.

Hepatitis E superinfection on chronic HBV can contribute to significant morbidity and mortality, the clinicians say, particularly in patients with cirrhosis. Concurrent infection with another viral hepatitis should be considered in both immunodeficient and immunocompetent patients with chronic HBV reactivation.

Source:

Aslam A, Susheela A, Iriana S, Chan SS, Lau D. BMJ Case Rep. 2018;2018. pii: bcr-2017-223616.
doi: 10.1136/bcr-2017-223616.

Many things can reactivate chronic hepatitis B virus (HBV) infection—withdrawal of antiviral therapy, pregnancy, and chemotherapy, to name a few. So when a patient with stable chronic HBV virus presented with significant hepatitis flare, clinicians from Beth Israel Deaconess Medical Center in Boston, Massachusetts, had a long list to check.

They first ruled out drug-associated hepatotoxicity and screened the patient for common causes of acute hepatitis. Beyond the HBV, the patient did not have other significant medical conditions, had not had close contact with anyone ill, and was not pregnant. Tests were negative for cytomegalovirus, Epstein-Barr syndrome, HIV, hepatitis A, C, and D. The patient tested negative for both antihepatitis E virus (HEV) IgM and IgG in a visit about 9 months before.

However, she reported regularly consuming pork, including a recent barbecue meal. Thus, the clinicians focused on HEV serology, which confirmed that she had an acute HEV infection.

Pigs act as a “natural reservoir” for HEV; contaminated meats and direct contact with animals are the most common causes of HEV human infection in industrialized countries. Recent data reveal the prevalence of HEV antibodies in the US is about 6%, illustrating that it is not as uncommon as it was thought to be. Although there was no direct evidence to confirm the source of her infection, it seemed likely due to the pork consumption.

The patient was started on tenofovir but stopped it 4 months later because she felt well. After a subsequent flare, “repeated counseling” persuaded the patient to start on entecavir, with successful viral suppression.

Hepatitis E superinfection on chronic HBV can contribute to significant morbidity and mortality, the clinicians say, particularly in patients with cirrhosis. Concurrent infection with another viral hepatitis should be considered in both immunodeficient and immunocompetent patients with chronic HBV reactivation.

Source:

Aslam A, Susheela A, Iriana S, Chan SS, Lau D. BMJ Case Rep. 2018;2018. pii: bcr-2017-223616.
doi: 10.1136/bcr-2017-223616.

Many things can reactivate chronic hepatitis B virus (HBV) infection—withdrawal of antiviral therapy, pregnancy, and chemotherapy, to name a few. So when a patient with stable chronic HBV virus presented with significant hepatitis flare, clinicians from Beth Israel Deaconess Medical Center in Boston, Massachusetts, had a long list to check.

They first ruled out drug-associated hepatotoxicity and screened the patient for common causes of acute hepatitis. Beyond the HBV, the patient did not have other significant medical conditions, had not had close contact with anyone ill, and was not pregnant. Tests were negative for cytomegalovirus, Epstein-Barr syndrome, HIV, hepatitis A, C, and D. The patient tested negative for both antihepatitis E virus (HEV) IgM and IgG in a visit about 9 months before.

However, she reported regularly consuming pork, including a recent barbecue meal. Thus, the clinicians focused on HEV serology, which confirmed that she had an acute HEV infection.

Pigs act as a “natural reservoir” for HEV; contaminated meats and direct contact with animals are the most common causes of HEV human infection in industrialized countries. Recent data reveal the prevalence of HEV antibodies in the US is about 6%, illustrating that it is not as uncommon as it was thought to be. Although there was no direct evidence to confirm the source of her infection, it seemed likely due to the pork consumption.

The patient was started on tenofovir but stopped it 4 months later because she felt well. After a subsequent flare, “repeated counseling” persuaded the patient to start on entecavir, with successful viral suppression.

Hepatitis E superinfection on chronic HBV can contribute to significant morbidity and mortality, the clinicians say, particularly in patients with cirrhosis. Concurrent infection with another viral hepatitis should be considered in both immunodeficient and immunocompetent patients with chronic HBV reactivation.

Source:

Aslam A, Susheela A, Iriana S, Chan SS, Lau D. BMJ Case Rep. 2018;2018. pii: bcr-2017-223616.
doi: 10.1136/bcr-2017-223616.

Photo from EHA

STOCKHOLM—An ongoing phase 2 study suggests voxelotor (GBT440) can benefit adolescents with sickle cell disease (SCD).

In the HOPE-KIDS 1 study, voxelotor produced sustained improvements in hemoglobin levels and a reduction in clinical measures of hemolysis in a cohort of adolescents with SCD, most of whom were also receiving hydroxyurea (HU).

The most common adverse events (AEs) related to voxelotor were nausea, vomiting, headache, and rash.

These results were presented in a poster (abstract PF709) at the 23rd Congress of the European Hematology Association (EHA).

HOPE-KIDS 1 is sponsored by Global Blood Therapeutics, Inc.

In this study, researchers are evaluating voxelotor in SCD patients ages 6 to 17. In part A, researchers evaluated a 600 mg daily dose of voxelotor. In part B, they are testing voxelotor at daily doses of 900 mg and 1500 mg in patients ages 12 to 17.

At EHA, the researchers presented data on 25 patients who received voxelotor at 900 mg/day for 24 weeks in part B. Eighty-eight percent of the patients (n=22) were also taking HU.

The patients’ median age was 14 (range, 12-17), and 56% were male. Ninety-six percent (n=24) had the HbSS genotype.

Forty-eight percent of patients had 1 to 4 vaso-occlusive crises (VOCs) in the past year, 8% had more than 4 VOCs, and 44% had 0 VOCs.

At baseline, the median hemoglobin was 8.9 g/dL, the median fetal hemoglobin was 10.8 g/dL, and the median time-averaged mean of maximum velocity was 110 cm/s.

All 25 patients were dosed with voxelotor, and 22 completed 24 weeks of dosing. One patient withdrew consent, 1 was lost to follow-up, and 1 patient discontinued due to noncompliance.

Of the 22 patients who completed 24 weeks of voxelotor treatment, all but 3 were receiving concurrent HU.

Results

Voxelotor-related AEs occurring in at least 2 patients included nausea (12%, n=3), vomiting (8%, n=2), headache (8%, n=2), and rash (8%, n=2).

There was 1 case of grade 3 urticaria, which resolved and did not recur with continued dosing. There were no discontinuations of voxelotor due to AEs.

Patients experienced increased hemoglobin levels and improved clinical measures of hemolysis at 24 weeks, as evaluated by changes from baseline in hemoglobin, percent of reticulocytes, and percent of unconjugated bilirubin.

In all, 43% of patients (9/21) achieved a hemoglobin response (>1 g/dL) at 24 weeks. The median hemoglobin change from baseline was 0.7 g/dL, the median reduction in reticulocytes was 22.9%, and the median reduction in unconjugated bilirubin was 38.6%.

Sixty-two percent of patients (13/21) had a reduction in daily symptoms at 24 weeks, as assessed by total symptom scores (TSS). There was a 39% median reduction in TSS from baseline.

Fifty-five percent of patients (11/20) had a numerical decrease in transcranial doppler (TCD) flow at 24 weeks. Among hemoglobin responders (>1 g/dL), 88% (7/8) had a numerical decrease in TCD at 24 weeks.

“We continue to be encouraged by the results of the ongoing HOPE-KIDS 1 study, which are consistent with inhibition of HbS polymerization by voxelotor and support its ongoing clinical evaluation as a potential disease-modifying therapy for both adults and adolescents with SCD,” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics.

“Results to date support our ongoing development of voxelotor in a broad range of patients, including in our phase 3 HOPE study, which is also evaluating voxelotor at doses of 900 mg and 1500 mg per day in adolescents and adults. We continue to expect to announce top-line clinical data from part A of the HOPE study by the end of this quarter.”

Photo from EHA

STOCKHOLM—An ongoing phase 2 study suggests voxelotor (GBT440) can benefit adolescents with sickle cell disease (SCD).

In the HOPE-KIDS 1 study, voxelotor produced sustained improvements in hemoglobin levels and a reduction in clinical measures of hemolysis in a cohort of adolescents with SCD, most of whom were also receiving hydroxyurea (HU).

The most common adverse events (AEs) related to voxelotor were nausea, vomiting, headache, and rash.

These results were presented in a poster (abstract PF709) at the 23rd Congress of the European Hematology Association (EHA).

HOPE-KIDS 1 is sponsored by Global Blood Therapeutics, Inc.

In this study, researchers are evaluating voxelotor in SCD patients ages 6 to 17. In part A, researchers evaluated a 600 mg daily dose of voxelotor. In part B, they are testing voxelotor at daily doses of 900 mg and 1500 mg in patients ages 12 to 17.

At EHA, the researchers presented data on 25 patients who received voxelotor at 900 mg/day for 24 weeks in part B. Eighty-eight percent of the patients (n=22) were also taking HU.

The patients’ median age was 14 (range, 12-17), and 56% were male. Ninety-six percent (n=24) had the HbSS genotype.

Forty-eight percent of patients had 1 to 4 vaso-occlusive crises (VOCs) in the past year, 8% had more than 4 VOCs, and 44% had 0 VOCs.

At baseline, the median hemoglobin was 8.9 g/dL, the median fetal hemoglobin was 10.8 g/dL, and the median time-averaged mean of maximum velocity was 110 cm/s.

All 25 patients were dosed with voxelotor, and 22 completed 24 weeks of dosing. One patient withdrew consent, 1 was lost to follow-up, and 1 patient discontinued due to noncompliance.

Of the 22 patients who completed 24 weeks of voxelotor treatment, all but 3 were receiving concurrent HU.

Results

Voxelotor-related AEs occurring in at least 2 patients included nausea (12%, n=3), vomiting (8%, n=2), headache (8%, n=2), and rash (8%, n=2).

There was 1 case of grade 3 urticaria, which resolved and did not recur with continued dosing. There were no discontinuations of voxelotor due to AEs.

Patients experienced increased hemoglobin levels and improved clinical measures of hemolysis at 24 weeks, as evaluated by changes from baseline in hemoglobin, percent of reticulocytes, and percent of unconjugated bilirubin.

In all, 43% of patients (9/21) achieved a hemoglobin response (>1 g/dL) at 24 weeks. The median hemoglobin change from baseline was 0.7 g/dL, the median reduction in reticulocytes was 22.9%, and the median reduction in unconjugated bilirubin was 38.6%.

Sixty-two percent of patients (13/21) had a reduction in daily symptoms at 24 weeks, as assessed by total symptom scores (TSS). There was a 39% median reduction in TSS from baseline.

Fifty-five percent of patients (11/20) had a numerical decrease in transcranial doppler (TCD) flow at 24 weeks. Among hemoglobin responders (>1 g/dL), 88% (7/8) had a numerical decrease in TCD at 24 weeks.

“We continue to be encouraged by the results of the ongoing HOPE-KIDS 1 study, which are consistent with inhibition of HbS polymerization by voxelotor and support its ongoing clinical evaluation as a potential disease-modifying therapy for both adults and adolescents with SCD,” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics.

“Results to date support our ongoing development of voxelotor in a broad range of patients, including in our phase 3 HOPE study, which is also evaluating voxelotor at doses of 900 mg and 1500 mg per day in adolescents and adults. We continue to expect to announce top-line clinical data from part A of the HOPE study by the end of this quarter.”

Photo from EHA

STOCKHOLM—An ongoing phase 2 study suggests voxelotor (GBT440) can benefit adolescents with sickle cell disease (SCD).

In the HOPE-KIDS 1 study, voxelotor produced sustained improvements in hemoglobin levels and a reduction in clinical measures of hemolysis in a cohort of adolescents with SCD, most of whom were also receiving hydroxyurea (HU).

The most common adverse events (AEs) related to voxelotor were nausea, vomiting, headache, and rash.

These results were presented in a poster (abstract PF709) at the 23rd Congress of the European Hematology Association (EHA).

HOPE-KIDS 1 is sponsored by Global Blood Therapeutics, Inc.

In this study, researchers are evaluating voxelotor in SCD patients ages 6 to 17. In part A, researchers evaluated a 600 mg daily dose of voxelotor. In part B, they are testing voxelotor at daily doses of 900 mg and 1500 mg in patients ages 12 to 17.

At EHA, the researchers presented data on 25 patients who received voxelotor at 900 mg/day for 24 weeks in part B. Eighty-eight percent of the patients (n=22) were also taking HU.

The patients’ median age was 14 (range, 12-17), and 56% were male. Ninety-six percent (n=24) had the HbSS genotype.

Forty-eight percent of patients had 1 to 4 vaso-occlusive crises (VOCs) in the past year, 8% had more than 4 VOCs, and 44% had 0 VOCs.

At baseline, the median hemoglobin was 8.9 g/dL, the median fetal hemoglobin was 10.8 g/dL, and the median time-averaged mean of maximum velocity was 110 cm/s.

All 25 patients were dosed with voxelotor, and 22 completed 24 weeks of dosing. One patient withdrew consent, 1 was lost to follow-up, and 1 patient discontinued due to noncompliance.

Of the 22 patients who completed 24 weeks of voxelotor treatment, all but 3 were receiving concurrent HU.

Results

Voxelotor-related AEs occurring in at least 2 patients included nausea (12%, n=3), vomiting (8%, n=2), headache (8%, n=2), and rash (8%, n=2).

There was 1 case of grade 3 urticaria, which resolved and did not recur with continued dosing. There were no discontinuations of voxelotor due to AEs.

Patients experienced increased hemoglobin levels and improved clinical measures of hemolysis at 24 weeks, as evaluated by changes from baseline in hemoglobin, percent of reticulocytes, and percent of unconjugated bilirubin.

In all, 43% of patients (9/21) achieved a hemoglobin response (>1 g/dL) at 24 weeks. The median hemoglobin change from baseline was 0.7 g/dL, the median reduction in reticulocytes was 22.9%, and the median reduction in unconjugated bilirubin was 38.6%.

Sixty-two percent of patients (13/21) had a reduction in daily symptoms at 24 weeks, as assessed by total symptom scores (TSS). There was a 39% median reduction in TSS from baseline.

Fifty-five percent of patients (11/20) had a numerical decrease in transcranial doppler (TCD) flow at 24 weeks. Among hemoglobin responders (>1 g/dL), 88% (7/8) had a numerical decrease in TCD at 24 weeks.

“We continue to be encouraged by the results of the ongoing HOPE-KIDS 1 study, which are consistent with inhibition of HbS polymerization by voxelotor and support its ongoing clinical evaluation as a potential disease-modifying therapy for both adults and adolescents with SCD,” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics.

“Results to date support our ongoing development of voxelotor in a broad range of patients, including in our phase 3 HOPE study, which is also evaluating voxelotor at doses of 900 mg and 1500 mg per day in adolescents and adults. We continue to expect to announce top-line clinical data from part A of the HOPE study by the end of this quarter.”

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for ibrutinib (Imbruvica®) to be used in combination with rituximab in patients with Waldenström’s macroglobulinemia (WM).

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Ibrutinib is a first-in-class Bruton’s tyrosine kinase inhibitor jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

Ibrutinib is already FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, previously treated mantle cell lymphoma, previously treated marginal zone lymphoma, previously treated chronic graft-versus-host disease, and WM.

If the new sNDA is approved, the use of ibrutinib in WM will extend beyond its current approved use as a single agent.

Phase 3 trial

The sNDA for ibrutinib and rituximab in WM is supported by data from the phase 3 iNNOVATE study. Results from this trial were presented at the 2018 ASCO Annual Meeting (abstract 8003) and were simultaneously published in NEJM.

iNNOVATE is a placebo-controlled, double-blind, phase 3 study that enrolled 150 patients with relapsed/refractory and treatment-naïve WM.

All patients received rituximab at 375 mg/m² with weekly infusions at weeks 1 to 4 and 17 to 20. They also received either ibrutinib (420 mg) or placebo once daily continuously until criteria for permanent discontinuation were met.

Overall response rates were significantly higher in the ibrutinib arm than the placebo arm—92% and 47%, respectively (P<0.0001). Complete response rates were 3% and 1%, respectively.

The median time to next treatment was not reached for the ibrutinib arm and was 18 months for the placebo arm (hazard ratio=0.096; P<0.0001). Of the patients randomized to ibrutinib plus rituximab, 75% continued on treatment at last follow-up.

The 30-month progression-free survival rates were 82% in the ibrutinib arm and 28% in the placebo arm. The median progression-free survival was not reached in the ibrutinib arm and was 20.3 months in the placebo arm (hazard ratio=0.20; P<0.0001).

The 30-month overall survival rates were 94% in the ibrutinib arm and 92% in the placebo arm.

Grade 3 or higher treatment-emergent adverse events (AEs) occurred in 60% of patients in the ibrutinib arm and 61% in the placebo arm.

Serious AEs occurred in 43% and 33% of patients, respectively. There were no fatal AEs in the ibrutinib arm and 3 in the rituximab arm.

Grade 3 or higher AEs that occurred more frequently in the ibrutinib arm than the placebo arm included atrial fibrillation (12% vs 1%) and hypertension (13% vs 4%).

AEs that occurred less frequently in the ibrutinib arm than the placebo arm included grade 3 or higher infusion reactions (1% vs 16%) and any-grade IgM flare (8% vs 47%).

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for ibrutinib (Imbruvica®) to be used in combination with rituximab in patients with Waldenström’s macroglobulinemia (WM).

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Ibrutinib is a first-in-class Bruton’s tyrosine kinase inhibitor jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

Ibrutinib is already FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, previously treated mantle cell lymphoma, previously treated marginal zone lymphoma, previously treated chronic graft-versus-host disease, and WM.

If the new sNDA is approved, the use of ibrutinib in WM will extend beyond its current approved use as a single agent.

Phase 3 trial

The sNDA for ibrutinib and rituximab in WM is supported by data from the phase 3 iNNOVATE study. Results from this trial were presented at the 2018 ASCO Annual Meeting (abstract 8003) and were simultaneously published in NEJM.

iNNOVATE is a placebo-controlled, double-blind, phase 3 study that enrolled 150 patients with relapsed/refractory and treatment-naïve WM.

All patients received rituximab at 375 mg/m² with weekly infusions at weeks 1 to 4 and 17 to 20. They also received either ibrutinib (420 mg) or placebo once daily continuously until criteria for permanent discontinuation were met.

Overall response rates were significantly higher in the ibrutinib arm than the placebo arm—92% and 47%, respectively (P<0.0001). Complete response rates were 3% and 1%, respectively.

The median time to next treatment was not reached for the ibrutinib arm and was 18 months for the placebo arm (hazard ratio=0.096; P<0.0001). Of the patients randomized to ibrutinib plus rituximab, 75% continued on treatment at last follow-up.

The 30-month progression-free survival rates were 82% in the ibrutinib arm and 28% in the placebo arm. The median progression-free survival was not reached in the ibrutinib arm and was 20.3 months in the placebo arm (hazard ratio=0.20; P<0.0001).

The 30-month overall survival rates were 94% in the ibrutinib arm and 92% in the placebo arm.

Grade 3 or higher treatment-emergent adverse events (AEs) occurred in 60% of patients in the ibrutinib arm and 61% in the placebo arm.

Serious AEs occurred in 43% and 33% of patients, respectively. There were no fatal AEs in the ibrutinib arm and 3 in the rituximab arm.

Grade 3 or higher AEs that occurred more frequently in the ibrutinib arm than the placebo arm included atrial fibrillation (12% vs 1%) and hypertension (13% vs 4%).

AEs that occurred less frequently in the ibrutinib arm than the placebo arm included grade 3 or higher infusion reactions (1% vs 16%) and any-grade IgM flare (8% vs 47%).

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for ibrutinib (Imbruvica®) to be used in combination with rituximab in patients with Waldenström’s macroglobulinemia (WM).

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Ibrutinib is a first-in-class Bruton’s tyrosine kinase inhibitor jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

Ibrutinib is already FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, previously treated mantle cell lymphoma, previously treated marginal zone lymphoma, previously treated chronic graft-versus-host disease, and WM.

If the new sNDA is approved, the use of ibrutinib in WM will extend beyond its current approved use as a single agent.

Phase 3 trial

The sNDA for ibrutinib and rituximab in WM is supported by data from the phase 3 iNNOVATE study. Results from this trial were presented at the 2018 ASCO Annual Meeting (abstract 8003) and were simultaneously published in NEJM.

iNNOVATE is a placebo-controlled, double-blind, phase 3 study that enrolled 150 patients with relapsed/refractory and treatment-naïve WM.

All patients received rituximab at 375 mg/m² with weekly infusions at weeks 1 to 4 and 17 to 20. They also received either ibrutinib (420 mg) or placebo once daily continuously until criteria for permanent discontinuation were met.

Overall response rates were significantly higher in the ibrutinib arm than the placebo arm—92% and 47%, respectively (P<0.0001). Complete response rates were 3% and 1%, respectively.

The median time to next treatment was not reached for the ibrutinib arm and was 18 months for the placebo arm (hazard ratio=0.096; P<0.0001). Of the patients randomized to ibrutinib plus rituximab, 75% continued on treatment at last follow-up.

The 30-month progression-free survival rates were 82% in the ibrutinib arm and 28% in the placebo arm. The median progression-free survival was not reached in the ibrutinib arm and was 20.3 months in the placebo arm (hazard ratio=0.20; P<0.0001).

The 30-month overall survival rates were 94% in the ibrutinib arm and 92% in the placebo arm.

Grade 3 or higher treatment-emergent adverse events (AEs) occurred in 60% of patients in the ibrutinib arm and 61% in the placebo arm.

Serious AEs occurred in 43% and 33% of patients, respectively. There were no fatal AEs in the ibrutinib arm and 3 in the rituximab arm.

Grade 3 or higher AEs that occurred more frequently in the ibrutinib arm than the placebo arm included atrial fibrillation (12% vs 1%) and hypertension (13% vs 4%).

AEs that occurred less frequently in the ibrutinib arm than the placebo arm included grade 3 or higher infusion reactions (1% vs 16%) and any-grade IgM flare (8% vs 47%).

Gene and Cell Therapy

George Stamatoyannopoulos, MD, who conducted important research into hemoglobinopathies, passed away this month at the age of 84.

Dr Stamatoyannopoulos’s research encompassed human genetics and hematology, including the structure and function of hemoglobinopathies, the genetics of thalassemia, and the molecular and cellular control of globin gene switching.

For much of his career, Dr Stamatoyannopoulos focused on the development of gene therapy for hemoglobinopathies and other disorders.

Dr Stamatoyannopoulos was born in Athens, Greece, on March 11, 1934. He entered medical school in Athens at age 17 and graduated at the top of his class 7 years later.

After his medical training, Dr Stamatoyannopoulos pursued thesis research on inherited blood disorders, particularly anemias.

Dr Stamatoyannopoulos performed the first large-scale molecular geographical survey of a genetic trait, which revealed the relationship between malaria and both thalassemia and sickle cell traits.

Dr Stamatoyannopoulos also discovered that fetal hemoglobin could ameliorate the effects of thalassemia. His theory that thalassemia and sickle cell anemia could be treated by re-activating fetal hemoglobin has underpinned decades of efforts to cure these disorders.

As a young investigator, Dr Stamatoyannopoulos expanded genetic studies of blood diseases in Greece, where his work drew the attention of medical genetics pioneer Arno Motulsky, MD.

Dr Motulsky recruited Dr Stamatoyannopoulos to the University of Washington (Seattle) in 1964. Dr Stamatoyannopoulos became a full professor there in 1973, founded the Markey Molecular Medicine Center, and was chief of medical genetics from 1989 to 2005.

Dr Stamatoyannopoulos organized the founding of the American Society of Gene and Cell Therapy. His contributions were recognized by establishment of the Stamatoyannopoulos lecture, the society’s highest award.

Dr Stamatoyannopoulos also served as president of the American Society of Hematology (1992) and president of the American Society of Gene and Cell Therapy (1996). He held leadership positions in other medical and scientific societies as well.

Dr Stamatoyannopoulos authored more than 420 scientific papers and 14 books, including The Molecular Basis of Blood Diseases.

Dr Stamatoyannopoulos died June 16, 2018. He is survived by his wife and collaborator Thalia Papayannopoulou, MD, (a professor of medicine and internationally recognized hematologist), 2 sons, and 3 grandchildren.

Gene and Cell Therapy

George Stamatoyannopoulos, MD, who conducted important research into hemoglobinopathies, passed away this month at the age of 84.

Dr Stamatoyannopoulos’s research encompassed human genetics and hematology, including the structure and function of hemoglobinopathies, the genetics of thalassemia, and the molecular and cellular control of globin gene switching.

For much of his career, Dr Stamatoyannopoulos focused on the development of gene therapy for hemoglobinopathies and other disorders.

Dr Stamatoyannopoulos was born in Athens, Greece, on March 11, 1934. He entered medical school in Athens at age 17 and graduated at the top of his class 7 years later.

After his medical training, Dr Stamatoyannopoulos pursued thesis research on inherited blood disorders, particularly anemias.

Dr Stamatoyannopoulos performed the first large-scale molecular geographical survey of a genetic trait, which revealed the relationship between malaria and both thalassemia and sickle cell traits.

Dr Stamatoyannopoulos also discovered that fetal hemoglobin could ameliorate the effects of thalassemia. His theory that thalassemia and sickle cell anemia could be treated by re-activating fetal hemoglobin has underpinned decades of efforts to cure these disorders.

As a young investigator, Dr Stamatoyannopoulos expanded genetic studies of blood diseases in Greece, where his work drew the attention of medical genetics pioneer Arno Motulsky, MD.

Dr Motulsky recruited Dr Stamatoyannopoulos to the University of Washington (Seattle) in 1964. Dr Stamatoyannopoulos became a full professor there in 1973, founded the Markey Molecular Medicine Center, and was chief of medical genetics from 1989 to 2005.

Dr Stamatoyannopoulos organized the founding of the American Society of Gene and Cell Therapy. His contributions were recognized by establishment of the Stamatoyannopoulos lecture, the society’s highest award.

Dr Stamatoyannopoulos also served as president of the American Society of Hematology (1992) and president of the American Society of Gene and Cell Therapy (1996). He held leadership positions in other medical and scientific societies as well.

Dr Stamatoyannopoulos authored more than 420 scientific papers and 14 books, including The Molecular Basis of Blood Diseases.

Dr Stamatoyannopoulos died June 16, 2018. He is survived by his wife and collaborator Thalia Papayannopoulou, MD, (a professor of medicine and internationally recognized hematologist), 2 sons, and 3 grandchildren.

Gene and Cell Therapy

George Stamatoyannopoulos, MD, who conducted important research into hemoglobinopathies, passed away this month at the age of 84.

Dr Stamatoyannopoulos’s research encompassed human genetics and hematology, including the structure and function of hemoglobinopathies, the genetics of thalassemia, and the molecular and cellular control of globin gene switching.

For much of his career, Dr Stamatoyannopoulos focused on the development of gene therapy for hemoglobinopathies and other disorders.

Dr Stamatoyannopoulos was born in Athens, Greece, on March 11, 1934. He entered medical school in Athens at age 17 and graduated at the top of his class 7 years later.

After his medical training, Dr Stamatoyannopoulos pursued thesis research on inherited blood disorders, particularly anemias.

Dr Stamatoyannopoulos performed the first large-scale molecular geographical survey of a genetic trait, which revealed the relationship between malaria and both thalassemia and sickle cell traits.

Dr Stamatoyannopoulos also discovered that fetal hemoglobin could ameliorate the effects of thalassemia. His theory that thalassemia and sickle cell anemia could be treated by re-activating fetal hemoglobin has underpinned decades of efforts to cure these disorders.

As a young investigator, Dr Stamatoyannopoulos expanded genetic studies of blood diseases in Greece, where his work drew the attention of medical genetics pioneer Arno Motulsky, MD.

Dr Motulsky recruited Dr Stamatoyannopoulos to the University of Washington (Seattle) in 1964. Dr Stamatoyannopoulos became a full professor there in 1973, founded the Markey Molecular Medicine Center, and was chief of medical genetics from 1989 to 2005.

Dr Stamatoyannopoulos organized the founding of the American Society of Gene and Cell Therapy. His contributions were recognized by establishment of the Stamatoyannopoulos lecture, the society’s highest award.

Dr Stamatoyannopoulos also served as president of the American Society of Hematology (1992) and president of the American Society of Gene and Cell Therapy (1996). He held leadership positions in other medical and scientific societies as well.

Dr Stamatoyannopoulos authored more than 420 scientific papers and 14 books, including The Molecular Basis of Blood Diseases.

Dr Stamatoyannopoulos died June 16, 2018. He is survived by his wife and collaborator Thalia Papayannopoulou, MD, (a professor of medicine and internationally recognized hematologist), 2 sons, and 3 grandchildren.

AMSTERDAM – In patients with autoimmune diseases, cancer treatment with checkpoint inhibitor immunotherapy increases the risk of flares, but these flares are associated with improved cancer outcomes, according to a multicenter, retrospective study presented at the European Congress of Rheumatology.

“Survival was longer in patients who experienced a flare of their preexisting autoimmune disease or any other immune-related adverse event, but this gain was lost if an immunosuppressive therapy was used,” reported Alice Tison, a resident in rheumatology at the Centre Hospitalier Universitaire, Brest, France.

These were some of the mixed messages from this evaluation, which involved 112 patients with preexisting autoimmune disease (PAD) whose data were collected from 11 tertiary care centers in France. Of the cases of PAD represented, the majority involved joint diseases, including psoriatic arthritis (28%), rheumatoid arthritis (18%), and spondyloarthritis (4.5%). However, other types of PAD, including inflammatory bowel disease (13%), were included in the series.

Only 33% of the patients had active disease at the time that checkpoint inhibitor therapy was initiated, and only 21% were taking an immunosuppressive therapy for their disease. Of those on therapy, the majority were taking steroids, but about a third of those on therapy were taking a disease-modifying antirheumatic drug, such as methotrexate.

With the initiation of checkpoint inhibitors, which were offered primarily for the treatment of melanoma (59%) and non–small cell lung cancer (36%), 42% of patients with PAD developed a disease flare. Of these, 30% were considered severe. Other immune-related events not considered related to the underlying disease, such as colitis, were also observed but at rates not clearly different than those observed in patients without PAD.

The activity of checkpoint inhibitors did not appear to be different than that observed in non-PAD patients. For example, the overall response rate was 48% in those with melanoma and 54% in those with non–small cell lung cancer. After a median of 8 months of follow-up, the median progression-free survival was 12.4 months and 9.7 months for the two diseases, respectively. Median overall survival had not been reached in either disease.

However, those with a flare or another immune-related adverse event had significantly better progression-free survival (P = .016) and overall survival (P = .004) when compared with those who did not flare or have an immune-related adverse event. According to Ms. Tison, this has been reported before, but a more surprising finding was that the gain in progression-free survival and overall survival was lost in those treated with an immunosuppressive drug.

Even though non-PAD patients commonly receive steroids for immune-related adverse events such as colitis, the loss of benefit in PAD patients who received immunosuppressive therapies may be caused by, at least in part, cross-reactivity between tumor antigens and autoantigens, Ms. Tison speculated.

Ms. Tison was cautious in drawing conclusions about specific strategies to optimize benefits from checkpoint inhibitors in PAD based on this limited series of patients. However, she did suggest that discontinuation of immunosuppressive therapies prior to initiating checkpoint inhibitors may be prudent in PAD patients, particularly those with inactive disease.

Overall, she emphasized that checkpoint inhibitors “have revolutionized the management of several cancers” and should not be denied to PAD patients who are otherwise appropriate candidates. Although flares are common, more than half of PAD patients in this series did not flare and flares were mild to moderate in most of those who did.

“The response to checkpoint inhibitors in PAD patients is good,” Ms. Tison advised. For those who do flare, “we need prospective studies to understand which strategies provide a good balance of benefit to risk” for cancer immunotherapy and for the options to manage immune-related adverse events.

The study was not industry funded. Ms. Tison reported no potential conflicts of interest.

SOURCE: Tison A et al. Ann Rheum Dis. 2018;77(Suppl 2):147. EULAR Congress 2018, Abstract OP0196.

AMSTERDAM – In patients with autoimmune diseases, cancer treatment with checkpoint inhibitor immunotherapy increases the risk of flares, but these flares are associated with improved cancer outcomes, according to a multicenter, retrospective study presented at the European Congress of Rheumatology.

“Survival was longer in patients who experienced a flare of their preexisting autoimmune disease or any other immune-related adverse event, but this gain was lost if an immunosuppressive therapy was used,” reported Alice Tison, a resident in rheumatology at the Centre Hospitalier Universitaire, Brest, France.

These were some of the mixed messages from this evaluation, which involved 112 patients with preexisting autoimmune disease (PAD) whose data were collected from 11 tertiary care centers in France. Of the cases of PAD represented, the majority involved joint diseases, including psoriatic arthritis (28%), rheumatoid arthritis (18%), and spondyloarthritis (4.5%). However, other types of PAD, including inflammatory bowel disease (13%), were included in the series.

Only 33% of the patients had active disease at the time that checkpoint inhibitor therapy was initiated, and only 21% were taking an immunosuppressive therapy for their disease. Of those on therapy, the majority were taking steroids, but about a third of those on therapy were taking a disease-modifying antirheumatic drug, such as methotrexate.

With the initiation of checkpoint inhibitors, which were offered primarily for the treatment of melanoma (59%) and non–small cell lung cancer (36%), 42% of patients with PAD developed a disease flare. Of these, 30% were considered severe. Other immune-related events not considered related to the underlying disease, such as colitis, were also observed but at rates not clearly different than those observed in patients without PAD.

The activity of checkpoint inhibitors did not appear to be different than that observed in non-PAD patients. For example, the overall response rate was 48% in those with melanoma and 54% in those with non–small cell lung cancer. After a median of 8 months of follow-up, the median progression-free survival was 12.4 months and 9.7 months for the two diseases, respectively. Median overall survival had not been reached in either disease.

However, those with a flare or another immune-related adverse event had significantly better progression-free survival (P = .016) and overall survival (P = .004) when compared with those who did not flare or have an immune-related adverse event. According to Ms. Tison, this has been reported before, but a more surprising finding was that the gain in progression-free survival and overall survival was lost in those treated with an immunosuppressive drug.

Even though non-PAD patients commonly receive steroids for immune-related adverse events such as colitis, the loss of benefit in PAD patients who received immunosuppressive therapies may be caused by, at least in part, cross-reactivity between tumor antigens and autoantigens, Ms. Tison speculated.

Ms. Tison was cautious in drawing conclusions about specific strategies to optimize benefits from checkpoint inhibitors in PAD based on this limited series of patients. However, she did suggest that discontinuation of immunosuppressive therapies prior to initiating checkpoint inhibitors may be prudent in PAD patients, particularly those with inactive disease.

Overall, she emphasized that checkpoint inhibitors “have revolutionized the management of several cancers” and should not be denied to PAD patients who are otherwise appropriate candidates. Although flares are common, more than half of PAD patients in this series did not flare and flares were mild to moderate in most of those who did.

“The response to checkpoint inhibitors in PAD patients is good,” Ms. Tison advised. For those who do flare, “we need prospective studies to understand which strategies provide a good balance of benefit to risk” for cancer immunotherapy and for the options to manage immune-related adverse events.

The study was not industry funded. Ms. Tison reported no potential conflicts of interest.

SOURCE: Tison A et al. Ann Rheum Dis. 2018;77(Suppl 2):147. EULAR Congress 2018, Abstract OP0196.

AMSTERDAM – In patients with autoimmune diseases, cancer treatment with checkpoint inhibitor immunotherapy increases the risk of flares, but these flares are associated with improved cancer outcomes, according to a multicenter, retrospective study presented at the European Congress of Rheumatology.

“Survival was longer in patients who experienced a flare of their preexisting autoimmune disease or any other immune-related adverse event, but this gain was lost if an immunosuppressive therapy was used,” reported Alice Tison, a resident in rheumatology at the Centre Hospitalier Universitaire, Brest, France.

These were some of the mixed messages from this evaluation, which involved 112 patients with preexisting autoimmune disease (PAD) whose data were collected from 11 tertiary care centers in France. Of the cases of PAD represented, the majority involved joint diseases, including psoriatic arthritis (28%), rheumatoid arthritis (18%), and spondyloarthritis (4.5%). However, other types of PAD, including inflammatory bowel disease (13%), were included in the series.

Only 33% of the patients had active disease at the time that checkpoint inhibitor therapy was initiated, and only 21% were taking an immunosuppressive therapy for their disease. Of those on therapy, the majority were taking steroids, but about a third of those on therapy were taking a disease-modifying antirheumatic drug, such as methotrexate.

With the initiation of checkpoint inhibitors, which were offered primarily for the treatment of melanoma (59%) and non–small cell lung cancer (36%), 42% of patients with PAD developed a disease flare. Of these, 30% were considered severe. Other immune-related events not considered related to the underlying disease, such as colitis, were also observed but at rates not clearly different than those observed in patients without PAD.

The activity of checkpoint inhibitors did not appear to be different than that observed in non-PAD patients. For example, the overall response rate was 48% in those with melanoma and 54% in those with non–small cell lung cancer. After a median of 8 months of follow-up, the median progression-free survival was 12.4 months and 9.7 months for the two diseases, respectively. Median overall survival had not been reached in either disease.

However, those with a flare or another immune-related adverse event had significantly better progression-free survival (P = .016) and overall survival (P = .004) when compared with those who did not flare or have an immune-related adverse event. According to Ms. Tison, this has been reported before, but a more surprising finding was that the gain in progression-free survival and overall survival was lost in those treated with an immunosuppressive drug.

Even though non-PAD patients commonly receive steroids for immune-related adverse events such as colitis, the loss of benefit in PAD patients who received immunosuppressive therapies may be caused by, at least in part, cross-reactivity between tumor antigens and autoantigens, Ms. Tison speculated.

Ms. Tison was cautious in drawing conclusions about specific strategies to optimize benefits from checkpoint inhibitors in PAD based on this limited series of patients. However, she did suggest that discontinuation of immunosuppressive therapies prior to initiating checkpoint inhibitors may be prudent in PAD patients, particularly those with inactive disease.

Overall, she emphasized that checkpoint inhibitors “have revolutionized the management of several cancers” and should not be denied to PAD patients who are otherwise appropriate candidates. Although flares are common, more than half of PAD patients in this series did not flare and flares were mild to moderate in most of those who did.

“The response to checkpoint inhibitors in PAD patients is good,” Ms. Tison advised. For those who do flare, “we need prospective studies to understand which strategies provide a good balance of benefit to risk” for cancer immunotherapy and for the options to manage immune-related adverse events.

The study was not industry funded. Ms. Tison reported no potential conflicts of interest.

SOURCE: Tison A et al. Ann Rheum Dis. 2018;77(Suppl 2):147. EULAR Congress 2018, Abstract OP0196.