The risk of hip fracture was higher among patients treated with tramadol for chronic noncancer pain than among those treated with other commonly used NSAIDs in a large population-based cohort in the United Kingdom.

iStock/Thinkstock

The incidence of hip fracture over a 12-month period among 293,912 propensity score-matched tramadol and codeine recipients in The Health Improvement Network (THIN) database during 2000-2017 was 3.7 vs. 2.9 per 1,000 person-years, respectively (hazard ratio for hip fracture, 1.28), Jie Wei, PhD, of Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in the Journal of Bone and Mineral Research.

Hip fracture incidence per 1,000 person-years was also higher in propensity score–matched cohorts of patients receiving tramadol vs. naproxen (2.9 vs. 1.7; HR, 1.69), ibuprofen (3.4 vs. 2.0; HR, 1.65), celecoxib (3.4 vs. 1.8; HR, 1.85), or etoricoxib (2.9 vs. 1.5; HR, 1.96), the investigators found.

Tramadol is considered a weak opioid and is commonly used for the treatment of pain based on a lower perceived risk of serious cardiovascular and gastrointestinal effects versus NSAIDs, and of addiction and respiratory depression versus traditional opioids, they explained. Several professional organizations also have “strongly or conditionally recommended tramadol” as a first- or second-line treatment for conditions such as osteoarthritis, fibromyalgia, and chronic low back pain.

The potential mechanisms for the association between tramadol and hip fracture require further study, but “[c]onsidering the significant impact of hip fracture on morbidity, mortality, and health care costs, our results point to the need to consider tramadol’s associated risk of fracture in clinical practice and treatment guidelines,” they concluded.

This study was supported by the National Institutes of Health, the National Natural Science Foundation of China, and the Postdoctoral Science Foundation of Central South University. The authors reported having no conflicts of interest.

[email protected]

SOURCE: Wei J et al. J Bone Miner Res. 2019 Feb 5. doi: 10.1002/jbmr.3935.

The risk of hip fracture was higher among patients treated with tramadol for chronic noncancer pain than among those treated with other commonly used NSAIDs in a large population-based cohort in the United Kingdom.

iStock/Thinkstock

The incidence of hip fracture over a 12-month period among 293,912 propensity score-matched tramadol and codeine recipients in The Health Improvement Network (THIN) database during 2000-2017 was 3.7 vs. 2.9 per 1,000 person-years, respectively (hazard ratio for hip fracture, 1.28), Jie Wei, PhD, of Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in the Journal of Bone and Mineral Research.

Hip fracture incidence per 1,000 person-years was also higher in propensity score–matched cohorts of patients receiving tramadol vs. naproxen (2.9 vs. 1.7; HR, 1.69), ibuprofen (3.4 vs. 2.0; HR, 1.65), celecoxib (3.4 vs. 1.8; HR, 1.85), or etoricoxib (2.9 vs. 1.5; HR, 1.96), the investigators found.

Tramadol is considered a weak opioid and is commonly used for the treatment of pain based on a lower perceived risk of serious cardiovascular and gastrointestinal effects versus NSAIDs, and of addiction and respiratory depression versus traditional opioids, they explained. Several professional organizations also have “strongly or conditionally recommended tramadol” as a first- or second-line treatment for conditions such as osteoarthritis, fibromyalgia, and chronic low back pain.

The potential mechanisms for the association between tramadol and hip fracture require further study, but “[c]onsidering the significant impact of hip fracture on morbidity, mortality, and health care costs, our results point to the need to consider tramadol’s associated risk of fracture in clinical practice and treatment guidelines,” they concluded.

This study was supported by the National Institutes of Health, the National Natural Science Foundation of China, and the Postdoctoral Science Foundation of Central South University. The authors reported having no conflicts of interest.

[email protected]

SOURCE: Wei J et al. J Bone Miner Res. 2019 Feb 5. doi: 10.1002/jbmr.3935.

The risk of hip fracture was higher among patients treated with tramadol for chronic noncancer pain than among those treated with other commonly used NSAIDs in a large population-based cohort in the United Kingdom.

iStock/Thinkstock

The incidence of hip fracture over a 12-month period among 293,912 propensity score-matched tramadol and codeine recipients in The Health Improvement Network (THIN) database during 2000-2017 was 3.7 vs. 2.9 per 1,000 person-years, respectively (hazard ratio for hip fracture, 1.28), Jie Wei, PhD, of Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in the Journal of Bone and Mineral Research.

Hip fracture incidence per 1,000 person-years was also higher in propensity score–matched cohorts of patients receiving tramadol vs. naproxen (2.9 vs. 1.7; HR, 1.69), ibuprofen (3.4 vs. 2.0; HR, 1.65), celecoxib (3.4 vs. 1.8; HR, 1.85), or etoricoxib (2.9 vs. 1.5; HR, 1.96), the investigators found.

Tramadol is considered a weak opioid and is commonly used for the treatment of pain based on a lower perceived risk of serious cardiovascular and gastrointestinal effects versus NSAIDs, and of addiction and respiratory depression versus traditional opioids, they explained. Several professional organizations also have “strongly or conditionally recommended tramadol” as a first- or second-line treatment for conditions such as osteoarthritis, fibromyalgia, and chronic low back pain.

The potential mechanisms for the association between tramadol and hip fracture require further study, but “[c]onsidering the significant impact of hip fracture on morbidity, mortality, and health care costs, our results point to the need to consider tramadol’s associated risk of fracture in clinical practice and treatment guidelines,” they concluded.

This study was supported by the National Institutes of Health, the National Natural Science Foundation of China, and the Postdoctoral Science Foundation of Central South University. The authors reported having no conflicts of interest.

[email protected]

SOURCE: Wei J et al. J Bone Miner Res. 2019 Feb 5. doi: 10.1002/jbmr.3935.

Compared with their colleagues, cardiologists are in the middle when it comes to happiness both in and outside the workplace, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

About 28% of cardiologists reported that they were very happy in the workplace, according to the Medscape report, with dermatologists taking the top spot at 41%; 51% of cardiologists said that they were very happy outside of work, 9 percentage points behind rheumatologists at 60%.

The burnout rate for cardiologists was 29%, well below the 41% average for all physicians. About 15% of cardiologists reported that they were both burned out and depressed. An overabundance of bureaucratic tasks was the most commonly reported contributing factor to burnout at 64%, followed by spending too many hours at work at 39% and increased usage of EHRs at 33%.

Cardiologists most commonly dealt with burnout by exercising (45%), talking with friends/family (43%), and isolating themselves from others (42%). In addition, 47% of cardiologists reported taking 3-4 weeks of vacation, slightly more than the 44% average for all physicians; only 29% said they had taken less than 3 weeks’ vacation.

About 10% of cardiologists said that they’d contemplated suicide and 1% reported that they’d attempted it; 83% reported that they’d never thought about suicide. Only 10% of cardiologists reported that they were either currently seeking help or were planning to seek professional help for symptoms of burnout and/or depression, while 76% said they had no plans to consult help and had not done so in the past.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

[email protected]

Compared with their colleagues, cardiologists are in the middle when it comes to happiness both in and outside the workplace, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

About 28% of cardiologists reported that they were very happy in the workplace, according to the Medscape report, with dermatologists taking the top spot at 41%; 51% of cardiologists said that they were very happy outside of work, 9 percentage points behind rheumatologists at 60%.

The burnout rate for cardiologists was 29%, well below the 41% average for all physicians. About 15% of cardiologists reported that they were both burned out and depressed. An overabundance of bureaucratic tasks was the most commonly reported contributing factor to burnout at 64%, followed by spending too many hours at work at 39% and increased usage of EHRs at 33%.

Cardiologists most commonly dealt with burnout by exercising (45%), talking with friends/family (43%), and isolating themselves from others (42%). In addition, 47% of cardiologists reported taking 3-4 weeks of vacation, slightly more than the 44% average for all physicians; only 29% said they had taken less than 3 weeks’ vacation.

About 10% of cardiologists said that they’d contemplated suicide and 1% reported that they’d attempted it; 83% reported that they’d never thought about suicide. Only 10% of cardiologists reported that they were either currently seeking help or were planning to seek professional help for symptoms of burnout and/or depression, while 76% said they had no plans to consult help and had not done so in the past.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

[email protected]

Compared with their colleagues, cardiologists are in the middle when it comes to happiness both in and outside the workplace, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

About 28% of cardiologists reported that they were very happy in the workplace, according to the Medscape report, with dermatologists taking the top spot at 41%; 51% of cardiologists said that they were very happy outside of work, 9 percentage points behind rheumatologists at 60%.

The burnout rate for cardiologists was 29%, well below the 41% average for all physicians. About 15% of cardiologists reported that they were both burned out and depressed. An overabundance of bureaucratic tasks was the most commonly reported contributing factor to burnout at 64%, followed by spending too many hours at work at 39% and increased usage of EHRs at 33%.

Cardiologists most commonly dealt with burnout by exercising (45%), talking with friends/family (43%), and isolating themselves from others (42%). In addition, 47% of cardiologists reported taking 3-4 weeks of vacation, slightly more than the 44% average for all physicians; only 29% said they had taken less than 3 weeks’ vacation.

About 10% of cardiologists said that they’d contemplated suicide and 1% reported that they’d attempted it; 83% reported that they’d never thought about suicide. Only 10% of cardiologists reported that they were either currently seeking help or were planning to seek professional help for symptoms of burnout and/or depression, while 76% said they had no plans to consult help and had not done so in the past.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

[email protected]

As I write this, the 2019 novel coronavirus* continues to spread, exceeding 59,000 cases and 1,300 deaths worldwide. With it spreads fear. In the modern world of social media, misinformation spreads even faster than disease.

Delpixel/Shutterstock

The news about a novel and deadly illness crowds out more substantial worries. Humans are not particularly good at assessing risk or responding rationally and consistently to it. Risk is hard to fully define. If you look up “risk” in Merriam Webster’s online dictionary, you get the simple definition of “possibility of loss or injury; peril.” If you look up risk in Wikipedia, you get 12 pages of explanation and 8 more pages of links and references.

People handle risk differently. Some people are more risk adverse than others. Some get a pleasurable thrill from risk, whether a slot machine or a parachute jump. Most people really don’t comprehend small probabilities, with tens of billions of dollars spent annually on U.S. lotteries.

Because 98% of people who get COVID-19 are recovering, this is not an extinction-level event or the zombie apocalypse. It is a major health hazard, and one where morbidity and mortality might be assuaged by an early and effective public health response, including the population’s adoption of good habits such as hand washing, cough etiquette, and staying home when ill. But fear, discrimination, and misinformation may do more damage than the virus itself.

Three key factors may help reduce the fear factor.

One key factor is accurate communication of health information to the public. This has been severely harmed in the last few years by the promotion of gossip on social media, such as Facebook, within newsfeeds without any vetting, along with a smaller component of deliberate misinformation from untraceable sources. Compare this situation with the decision in May 1988 when Surgeon General C. Everett Koop chose to snail mail a brochure on AIDS to every household in America. It was unprecedented. One element of this communication is the public’s belief that government and health care officials will responsibly and timely convey the information. There are accusations that the Chinese government initially impeded early warnings about COVID-19. Dr. Koop, to his great credit and lifesaving leadership, overcame queasiness within the Reagan administration about issues of morality and taste in discussing some of the HIV information. Alas, no similar leadership occurred in the decade of the 2010s when deaths from the opioid epidemic in the United States skyrocketed to claim more lives annually than car accidents or suicide.

A second factor is the credibility of the scientists. Antivaxxers, climate change deniers, and mercenary scientists have severely damaged that credibility of science, compared with the trust in scientists 50 years ago during the Apollo moon shot.

A third factor is perspective. Poor journalism and clickbait can focus excessively on the rare events as news. Airline crashes make the front page while fatal car accidents, claiming a hundred times more lives annually, don’t even merit a story in local media. Someone wins the lottery weekly but few pay attention to those suffering from gambling debts.

Influenza is killing many times more people than the 2019 novel coronavirus, but the news is focused on cruise ships. In the United States, influenza annually will strike tens of millions, with about 10 per 1,000 hospitalized and 0.5 per 1,000 dying. The novel coronavirus is more lethal. SARS (a coronavirus epidemic in 2003) had 8,000 cases with a mortality rate of 96 per 1,000 while the novel 2019 strain so far is killing about 20 per 1,000. That value may be an overestimate, because there may be a significant fraction of COVID-19 patients with symptoms mild enough that they do not seek medical care and do not get tested and counted.

For perspective, in 1952 the United States reported 50,000 cases of polio (meningitis or paralytic) annually with 3,000 deaths. As many as 95% of cases of poliovirus infection have no or mild symptoms and would not have been reported, so the case fatality rate estimate is skewed. In the 1950s, the United States averaged about 500,000 cases of measles per year, with about 500 deaths annually for a case fatality rate of about 1 per 1,000 in a population that was well nourished with good medical care. In malnourished children without access to modern health care, the case fatality rate can be as high as 100 per 1,000, which is why globally measles killed 142,000 people in 2018, a substantial improvement from 536,000 deaths globally in 2000, but still a leading killer of children worldwide. Vaccines had reduced the annual death toll of polio and measles in the U.S. to zero.

In comparison, in this country the annual incidences are about 70,000 overdose deaths, 50,000 suicides, and 40,000 traffic deaths.

Reassurance is the most common product sold by pediatricians. We look for low-probability, high-impact bad things. Usually we don’t find them and can reassure parents that the child will be okay. Sometimes we spot a higher-risk situation and intervene. My job is to worry professionally so that parents can worry less.

COVID-19 worries me, but irrational people worry me more. The real enemies are fear, disinformation, discrimination, and economic warfare.
 

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

*This article was updated 2/21/2020.

As I write this, the 2019 novel coronavirus* continues to spread, exceeding 59,000 cases and 1,300 deaths worldwide. With it spreads fear. In the modern world of social media, misinformation spreads even faster than disease.

Delpixel/Shutterstock

The news about a novel and deadly illness crowds out more substantial worries. Humans are not particularly good at assessing risk or responding rationally and consistently to it. Risk is hard to fully define. If you look up “risk” in Merriam Webster’s online dictionary, you get the simple definition of “possibility of loss or injury; peril.” If you look up risk in Wikipedia, you get 12 pages of explanation and 8 more pages of links and references.

People handle risk differently. Some people are more risk adverse than others. Some get a pleasurable thrill from risk, whether a slot machine or a parachute jump. Most people really don’t comprehend small probabilities, with tens of billions of dollars spent annually on U.S. lotteries.

Because 98% of people who get COVID-19 are recovering, this is not an extinction-level event or the zombie apocalypse. It is a major health hazard, and one where morbidity and mortality might be assuaged by an early and effective public health response, including the population’s adoption of good habits such as hand washing, cough etiquette, and staying home when ill. But fear, discrimination, and misinformation may do more damage than the virus itself.

Three key factors may help reduce the fear factor.

One key factor is accurate communication of health information to the public. This has been severely harmed in the last few years by the promotion of gossip on social media, such as Facebook, within newsfeeds without any vetting, along with a smaller component of deliberate misinformation from untraceable sources. Compare this situation with the decision in May 1988 when Surgeon General C. Everett Koop chose to snail mail a brochure on AIDS to every household in America. It was unprecedented. One element of this communication is the public’s belief that government and health care officials will responsibly and timely convey the information. There are accusations that the Chinese government initially impeded early warnings about COVID-19. Dr. Koop, to his great credit and lifesaving leadership, overcame queasiness within the Reagan administration about issues of morality and taste in discussing some of the HIV information. Alas, no similar leadership occurred in the decade of the 2010s when deaths from the opioid epidemic in the United States skyrocketed to claim more lives annually than car accidents or suicide.

A second factor is the credibility of the scientists. Antivaxxers, climate change deniers, and mercenary scientists have severely damaged that credibility of science, compared with the trust in scientists 50 years ago during the Apollo moon shot.

A third factor is perspective. Poor journalism and clickbait can focus excessively on the rare events as news. Airline crashes make the front page while fatal car accidents, claiming a hundred times more lives annually, don’t even merit a story in local media. Someone wins the lottery weekly but few pay attention to those suffering from gambling debts.

Influenza is killing many times more people than the 2019 novel coronavirus, but the news is focused on cruise ships. In the United States, influenza annually will strike tens of millions, with about 10 per 1,000 hospitalized and 0.5 per 1,000 dying. The novel coronavirus is more lethal. SARS (a coronavirus epidemic in 2003) had 8,000 cases with a mortality rate of 96 per 1,000 while the novel 2019 strain so far is killing about 20 per 1,000. That value may be an overestimate, because there may be a significant fraction of COVID-19 patients with symptoms mild enough that they do not seek medical care and do not get tested and counted.

For perspective, in 1952 the United States reported 50,000 cases of polio (meningitis or paralytic) annually with 3,000 deaths. As many as 95% of cases of poliovirus infection have no or mild symptoms and would not have been reported, so the case fatality rate estimate is skewed. In the 1950s, the United States averaged about 500,000 cases of measles per year, with about 500 deaths annually for a case fatality rate of about 1 per 1,000 in a population that was well nourished with good medical care. In malnourished children without access to modern health care, the case fatality rate can be as high as 100 per 1,000, which is why globally measles killed 142,000 people in 2018, a substantial improvement from 536,000 deaths globally in 2000, but still a leading killer of children worldwide. Vaccines had reduced the annual death toll of polio and measles in the U.S. to zero.

In comparison, in this country the annual incidences are about 70,000 overdose deaths, 50,000 suicides, and 40,000 traffic deaths.

Reassurance is the most common product sold by pediatricians. We look for low-probability, high-impact bad things. Usually we don’t find them and can reassure parents that the child will be okay. Sometimes we spot a higher-risk situation and intervene. My job is to worry professionally so that parents can worry less.

COVID-19 worries me, but irrational people worry me more. The real enemies are fear, disinformation, discrimination, and economic warfare.
 

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

*This article was updated 2/21/2020.

As I write this, the 2019 novel coronavirus* continues to spread, exceeding 59,000 cases and 1,300 deaths worldwide. With it spreads fear. In the modern world of social media, misinformation spreads even faster than disease.

Delpixel/Shutterstock

The news about a novel and deadly illness crowds out more substantial worries. Humans are not particularly good at assessing risk or responding rationally and consistently to it. Risk is hard to fully define. If you look up “risk” in Merriam Webster’s online dictionary, you get the simple definition of “possibility of loss or injury; peril.” If you look up risk in Wikipedia, you get 12 pages of explanation and 8 more pages of links and references.

People handle risk differently. Some people are more risk adverse than others. Some get a pleasurable thrill from risk, whether a slot machine or a parachute jump. Most people really don’t comprehend small probabilities, with tens of billions of dollars spent annually on U.S. lotteries.

Because 98% of people who get COVID-19 are recovering, this is not an extinction-level event or the zombie apocalypse. It is a major health hazard, and one where morbidity and mortality might be assuaged by an early and effective public health response, including the population’s adoption of good habits such as hand washing, cough etiquette, and staying home when ill. But fear, discrimination, and misinformation may do more damage than the virus itself.

Three key factors may help reduce the fear factor.

One key factor is accurate communication of health information to the public. This has been severely harmed in the last few years by the promotion of gossip on social media, such as Facebook, within newsfeeds without any vetting, along with a smaller component of deliberate misinformation from untraceable sources. Compare this situation with the decision in May 1988 when Surgeon General C. Everett Koop chose to snail mail a brochure on AIDS to every household in America. It was unprecedented. One element of this communication is the public’s belief that government and health care officials will responsibly and timely convey the information. There are accusations that the Chinese government initially impeded early warnings about COVID-19. Dr. Koop, to his great credit and lifesaving leadership, overcame queasiness within the Reagan administration about issues of morality and taste in discussing some of the HIV information. Alas, no similar leadership occurred in the decade of the 2010s when deaths from the opioid epidemic in the United States skyrocketed to claim more lives annually than car accidents or suicide.

A second factor is the credibility of the scientists. Antivaxxers, climate change deniers, and mercenary scientists have severely damaged that credibility of science, compared with the trust in scientists 50 years ago during the Apollo moon shot.

A third factor is perspective. Poor journalism and clickbait can focus excessively on the rare events as news. Airline crashes make the front page while fatal car accidents, claiming a hundred times more lives annually, don’t even merit a story in local media. Someone wins the lottery weekly but few pay attention to those suffering from gambling debts.

Influenza is killing many times more people than the 2019 novel coronavirus, but the news is focused on cruise ships. In the United States, influenza annually will strike tens of millions, with about 10 per 1,000 hospitalized and 0.5 per 1,000 dying. The novel coronavirus is more lethal. SARS (a coronavirus epidemic in 2003) had 8,000 cases with a mortality rate of 96 per 1,000 while the novel 2019 strain so far is killing about 20 per 1,000. That value may be an overestimate, because there may be a significant fraction of COVID-19 patients with symptoms mild enough that they do not seek medical care and do not get tested and counted.

For perspective, in 1952 the United States reported 50,000 cases of polio (meningitis or paralytic) annually with 3,000 deaths. As many as 95% of cases of poliovirus infection have no or mild symptoms and would not have been reported, so the case fatality rate estimate is skewed. In the 1950s, the United States averaged about 500,000 cases of measles per year, with about 500 deaths annually for a case fatality rate of about 1 per 1,000 in a population that was well nourished with good medical care. In malnourished children without access to modern health care, the case fatality rate can be as high as 100 per 1,000, which is why globally measles killed 142,000 people in 2018, a substantial improvement from 536,000 deaths globally in 2000, but still a leading killer of children worldwide. Vaccines had reduced the annual death toll of polio and measles in the U.S. to zero.

In comparison, in this country the annual incidences are about 70,000 overdose deaths, 50,000 suicides, and 40,000 traffic deaths.

Reassurance is the most common product sold by pediatricians. We look for low-probability, high-impact bad things. Usually we don’t find them and can reassure parents that the child will be okay. Sometimes we spot a higher-risk situation and intervene. My job is to worry professionally so that parents can worry less.

COVID-19 worries me, but irrational people worry me more. The real enemies are fear, disinformation, discrimination, and economic warfare.
 

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

*This article was updated 2/21/2020.

The gene therapy etranacogene dezaparvovec (AMT-061) continues to demonstrate safety and efficacy in patients with hemophilia B, according to a 1-year update of a phase 2b trial.

All three patients in this trial experienced sustained increases in factor IX (FIX) activity and were able to stop prophylaxis without suffering any bleeds. Adverse events related to treatment were mild and transient.

These favorable results are particularly noteworthy because all three patients had anti-AAV5 neutralizing antibodies at baseline, according to Steven W. Pipe, MD, of the University of Michigan, Ann Arbor. He noted that studies of etranacogene dezaparvovec and its predecessor, AMT-060, are the only studies that have not excluded hemophilia patients based on preexisting immunity.

Dr. Pipe presented the latest phase 2b results with etranacogene dezaparvovec at the annual congress of the European Association for Haemophilia and Allied Disorders.

Etranacogene dezaparvovec uses an AAV5 serotype with a transgene expression cassette that codes for the hyperactive Padua FIX variant, Dr. Pipe explained. Etranacogene dezaparvovec has a structure that is nearly identical to that of AMT-060, except for two nucleotide substitutions in the coding sequence for FIX.

AMT-060 enabled stable expression of FIX that has persisted for up to 4 years without any late-emergent safety signals (Blood 2019. 134 Supplement 1: 2059). Dr. Pipe said the “enhanced version” of AMT-060, etranacogene dezaparvovec, has produced even higher levels of FIX activity in the phase 2b study (NCT03489291).

The ongoing study enrolled three men with moderate to severe FIX deficiency at baseline. The patients were 43, 50, and 47 years of age, respectively. Two patients are HIV positive, and all had hepatitis C that resolved.

All three patients were receiving FIX prophylaxis and on-demand treatment at baseline. In the year prior to screening, patients had one, three, and five bleeds, respectively. All three patients had anti-AAV5 neutralizing antibodies.

Efficacy

Patients received a single dose of etranacogene dezaparvovec at 2 x 10¹³ genome copies/kg. All three patients achieved the primary endpoint, which was FIX activity of at least 5% at 6 weeks.

At 52 weeks, the mean FIX activity was 41%. Patients 1 and 3 have maintained FIX activity of 40% or greater, which is in the nonhemophilic range. Patient 2 has maintained FIX activity in the mild range. At 52 weeks, FIX activity levels were 50.2%, 40.8%, and 31.3%, respectively.

All patients remain free of prophylaxis and bleeds. Patient 3 received a single FIX infusion as a precaution in the perioperative setting. There was no evidence of a bleed in this patient.
 

Safety

Etranacogene dezaparvovec was generally well tolerated, Dr. Pipe said. One patient had two adverse events that were possibly related to etranacogene dezaparvovec. Both events – transient, self-limiting headache and slightly elevated C-reactive protein – resolved without intervention.

There was one serious adverse event, but it was considered unrelated to treatment. Patient 3 required hip surgery for preexisting avascular necrosis.

Dr. Pipe said there was no evidence of transaminitis. There were modest, transient elevations in liver enzymes, but this was not enough to trigger protocol-specified immunosuppression.

Specifically, one patient had ALT elevations at weeks 22 and 44, and one patient had AST elevations at weeks 2, 4, and 31. All of these resolved quickly without treatment or an impact on FIX activity, Dr. Pipe noted.
 

Next steps

This study is ongoing, and patients will be followed for 5 years. Dr. Pipe said the main focus of follow-up will be to determine if patients maintain durable expression of FIX.

A phase 3 trial of etranacogene dezaparvovec is ongoing as well. The trial, HOPE-B (NCT03569891), is fully enrolled, and dosing is planned for 55 patients.

“We’re looking forward to data analysis later this year,” Dr. Pipe said. “This will be the only phase 3 study, and really the only platform so far, that is not planning to exclude patients based on preexisting immunity.”

If all goes well in the phase 3 study, etranacogene dezaparvovec could be approved by the Food and Drug Administration very soon, Dr. Pipe added.

UniQure, the company developing etranacogene dezaparvovec, is planning to submit the biologics license application to the FDA next year. Etranacogene dezaparvovec was granted breakthrough designation from the FDA and is therefore eligible for priority review, so the gene therapy could be approved as early as 2021.

The phase 2b trial of etranacogene dezaparvovec is sponsored by uniQure. Dr. Pipe disclosed relationships with uniQure and other companies.

[email protected]

SOURCE: Pipe SW et al. EAHAD 2020, Abstract OR10.

The gene therapy etranacogene dezaparvovec (AMT-061) continues to demonstrate safety and efficacy in patients with hemophilia B, according to a 1-year update of a phase 2b trial.

All three patients in this trial experienced sustained increases in factor IX (FIX) activity and were able to stop prophylaxis without suffering any bleeds. Adverse events related to treatment were mild and transient.

These favorable results are particularly noteworthy because all three patients had anti-AAV5 neutralizing antibodies at baseline, according to Steven W. Pipe, MD, of the University of Michigan, Ann Arbor. He noted that studies of etranacogene dezaparvovec and its predecessor, AMT-060, are the only studies that have not excluded hemophilia patients based on preexisting immunity.

Dr. Pipe presented the latest phase 2b results with etranacogene dezaparvovec at the annual congress of the European Association for Haemophilia and Allied Disorders.

Etranacogene dezaparvovec uses an AAV5 serotype with a transgene expression cassette that codes for the hyperactive Padua FIX variant, Dr. Pipe explained. Etranacogene dezaparvovec has a structure that is nearly identical to that of AMT-060, except for two nucleotide substitutions in the coding sequence for FIX.

AMT-060 enabled stable expression of FIX that has persisted for up to 4 years without any late-emergent safety signals (Blood 2019. 134 Supplement 1: 2059). Dr. Pipe said the “enhanced version” of AMT-060, etranacogene dezaparvovec, has produced even higher levels of FIX activity in the phase 2b study (NCT03489291).

The ongoing study enrolled three men with moderate to severe FIX deficiency at baseline. The patients were 43, 50, and 47 years of age, respectively. Two patients are HIV positive, and all had hepatitis C that resolved.

All three patients were receiving FIX prophylaxis and on-demand treatment at baseline. In the year prior to screening, patients had one, three, and five bleeds, respectively. All three patients had anti-AAV5 neutralizing antibodies.

Efficacy

Patients received a single dose of etranacogene dezaparvovec at 2 x 10¹³ genome copies/kg. All three patients achieved the primary endpoint, which was FIX activity of at least 5% at 6 weeks.

At 52 weeks, the mean FIX activity was 41%. Patients 1 and 3 have maintained FIX activity of 40% or greater, which is in the nonhemophilic range. Patient 2 has maintained FIX activity in the mild range. At 52 weeks, FIX activity levels were 50.2%, 40.8%, and 31.3%, respectively.

All patients remain free of prophylaxis and bleeds. Patient 3 received a single FIX infusion as a precaution in the perioperative setting. There was no evidence of a bleed in this patient.
 

Safety

Etranacogene dezaparvovec was generally well tolerated, Dr. Pipe said. One patient had two adverse events that were possibly related to etranacogene dezaparvovec. Both events – transient, self-limiting headache and slightly elevated C-reactive protein – resolved without intervention.

There was one serious adverse event, but it was considered unrelated to treatment. Patient 3 required hip surgery for preexisting avascular necrosis.

Dr. Pipe said there was no evidence of transaminitis. There were modest, transient elevations in liver enzymes, but this was not enough to trigger protocol-specified immunosuppression.

Specifically, one patient had ALT elevations at weeks 22 and 44, and one patient had AST elevations at weeks 2, 4, and 31. All of these resolved quickly without treatment or an impact on FIX activity, Dr. Pipe noted.
 

Next steps

This study is ongoing, and patients will be followed for 5 years. Dr. Pipe said the main focus of follow-up will be to determine if patients maintain durable expression of FIX.

A phase 3 trial of etranacogene dezaparvovec is ongoing as well. The trial, HOPE-B (NCT03569891), is fully enrolled, and dosing is planned for 55 patients.

“We’re looking forward to data analysis later this year,” Dr. Pipe said. “This will be the only phase 3 study, and really the only platform so far, that is not planning to exclude patients based on preexisting immunity.”

If all goes well in the phase 3 study, etranacogene dezaparvovec could be approved by the Food and Drug Administration very soon, Dr. Pipe added.

UniQure, the company developing etranacogene dezaparvovec, is planning to submit the biologics license application to the FDA next year. Etranacogene dezaparvovec was granted breakthrough designation from the FDA and is therefore eligible for priority review, so the gene therapy could be approved as early as 2021.

The phase 2b trial of etranacogene dezaparvovec is sponsored by uniQure. Dr. Pipe disclosed relationships with uniQure and other companies.

[email protected]

SOURCE: Pipe SW et al. EAHAD 2020, Abstract OR10.

The gene therapy etranacogene dezaparvovec (AMT-061) continues to demonstrate safety and efficacy in patients with hemophilia B, according to a 1-year update of a phase 2b trial.

All three patients in this trial experienced sustained increases in factor IX (FIX) activity and were able to stop prophylaxis without suffering any bleeds. Adverse events related to treatment were mild and transient.

These favorable results are particularly noteworthy because all three patients had anti-AAV5 neutralizing antibodies at baseline, according to Steven W. Pipe, MD, of the University of Michigan, Ann Arbor. He noted that studies of etranacogene dezaparvovec and its predecessor, AMT-060, are the only studies that have not excluded hemophilia patients based on preexisting immunity.

Dr. Pipe presented the latest phase 2b results with etranacogene dezaparvovec at the annual congress of the European Association for Haemophilia and Allied Disorders.

Etranacogene dezaparvovec uses an AAV5 serotype with a transgene expression cassette that codes for the hyperactive Padua FIX variant, Dr. Pipe explained. Etranacogene dezaparvovec has a structure that is nearly identical to that of AMT-060, except for two nucleotide substitutions in the coding sequence for FIX.

AMT-060 enabled stable expression of FIX that has persisted for up to 4 years without any late-emergent safety signals (Blood 2019. 134 Supplement 1: 2059). Dr. Pipe said the “enhanced version” of AMT-060, etranacogene dezaparvovec, has produced even higher levels of FIX activity in the phase 2b study (NCT03489291).

The ongoing study enrolled three men with moderate to severe FIX deficiency at baseline. The patients were 43, 50, and 47 years of age, respectively. Two patients are HIV positive, and all had hepatitis C that resolved.

All three patients were receiving FIX prophylaxis and on-demand treatment at baseline. In the year prior to screening, patients had one, three, and five bleeds, respectively. All three patients had anti-AAV5 neutralizing antibodies.

Efficacy

Patients received a single dose of etranacogene dezaparvovec at 2 x 10¹³ genome copies/kg. All three patients achieved the primary endpoint, which was FIX activity of at least 5% at 6 weeks.

At 52 weeks, the mean FIX activity was 41%. Patients 1 and 3 have maintained FIX activity of 40% or greater, which is in the nonhemophilic range. Patient 2 has maintained FIX activity in the mild range. At 52 weeks, FIX activity levels were 50.2%, 40.8%, and 31.3%, respectively.

All patients remain free of prophylaxis and bleeds. Patient 3 received a single FIX infusion as a precaution in the perioperative setting. There was no evidence of a bleed in this patient.
 

Safety

Etranacogene dezaparvovec was generally well tolerated, Dr. Pipe said. One patient had two adverse events that were possibly related to etranacogene dezaparvovec. Both events – transient, self-limiting headache and slightly elevated C-reactive protein – resolved without intervention.

There was one serious adverse event, but it was considered unrelated to treatment. Patient 3 required hip surgery for preexisting avascular necrosis.

Dr. Pipe said there was no evidence of transaminitis. There were modest, transient elevations in liver enzymes, but this was not enough to trigger protocol-specified immunosuppression.

Specifically, one patient had ALT elevations at weeks 22 and 44, and one patient had AST elevations at weeks 2, 4, and 31. All of these resolved quickly without treatment or an impact on FIX activity, Dr. Pipe noted.
 

Next steps

This study is ongoing, and patients will be followed for 5 years. Dr. Pipe said the main focus of follow-up will be to determine if patients maintain durable expression of FIX.

A phase 3 trial of etranacogene dezaparvovec is ongoing as well. The trial, HOPE-B (NCT03569891), is fully enrolled, and dosing is planned for 55 patients.

“We’re looking forward to data analysis later this year,” Dr. Pipe said. “This will be the only phase 3 study, and really the only platform so far, that is not planning to exclude patients based on preexisting immunity.”

If all goes well in the phase 3 study, etranacogene dezaparvovec could be approved by the Food and Drug Administration very soon, Dr. Pipe added.

UniQure, the company developing etranacogene dezaparvovec, is planning to submit the biologics license application to the FDA next year. Etranacogene dezaparvovec was granted breakthrough designation from the FDA and is therefore eligible for priority review, so the gene therapy could be approved as early as 2021.

The phase 2b trial of etranacogene dezaparvovec is sponsored by uniQure. Dr. Pipe disclosed relationships with uniQure and other companies.

[email protected]

SOURCE: Pipe SW et al. EAHAD 2020, Abstract OR10.

Shorter time to metastatic development was associated with shorter time to treatment failure and shorter overall survival in an international review of over 7,000 renal cell carcinoma (RCC) patients treated with first-line tyrosine kinase inhibitors.

“Patients with synchronous disease, compared with patients with metachronous disease, have more adverse prognostic features, significantly shorter TTF [time to treatment failure], and poorer survival. This may help in patient counseling and may be taken into consideration in clinical trial designs in the future, in order to avoid an imbalance between treatment arms,” wrote investigators led by Frede Donskov, MD, a clinical professor at Aarhus (Denmark) University Hospital, in European Urology Oncology.

In the largest study to date to address the impact of timing of metastases on outcomes from tyrosine kinase inhibitor (TKI) treatment, something that’s been unclear until now, Dr. Donskov and associates turned to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare outcomes of 3,906 patients with synchronous metastases, meaning metastases within 3 months of initial RCC diagnosis, with 3,480 with metachronous disease, meaning metastases after that point.

They found that more patients with synchronous versus metachronous disease had higher T stage (T1-2, 19% vs. 34%), N1 disease (21% vs. 6%), presence of sarcomatoid differentiation (15.8% vs. 7.9%), Karnofsky performance status less than 80 (25.9% vs. 15.1%), anemia (62.5% vs. 42.3%), elevated neutrophils (18.9% vs. 10.9%), elevated platelets (21.6% vs. 11.4%), bone metastases (40.4% vs. 29.8%); and IMDC poor risk (40.6% vs.11.3%).

Synchronous versus metachronous disease by intervals of more than 3-12 months, more than 1-2 years, more than 2-7 years, and more than 7 years correlated with poor TTF (5.6 months vs. 7.3, 8.0, 10.8, and 13.3 months; P less than .0001) and poor overall survival (median, 16.7 months vs. 23.8, 30.2, 34.8, and 41.7 months; P less than .0001).

On multivariable regressions adjusting for baseline variables, metachronous disease was protective versus synchronous RCC on overall survival and TTF, with a greater protective effect the longer it took for the disease to metastasize.

“Synchronous disease may represent a distinct pathologic and molecular phenotype ... a high proportion of patients with synchronous disease have tumors with punctuated evolution, harboring aggressive disease features, consolidating in worse risk factors, requiring systemic therapy earlier, and having almost half the expected survival after the initiation of targeted therapy, compared with the latest metastatic timing, as shown in our study,” the investigators wrote.

The findings “reflect the underlying aggressive tumor biology. Whether [time to metastasis] impacts outcome to checkpoint immunotherapy is yet to be elucidated,” they added.

Patients were a median of 59 years at diagnosis, and 72.9% were men. None of the synchronous patients had a surgical nephrectomy, compared with 95.4% of metachronous patients; 67.2% of patients in both groups were treated with the TKI sunitinib (Sutent).

The work was funded by the IMDC. The lead investigator reported institutional grants from Ipsen and Pfizer, maker of sunitinib.
 

[email protected]

SOURCE: Donskov F et al. Eur Urol Oncol. 2020 Feb 6. doi: 10.1016/j.euo.2020.01.001.

Shorter time to metastatic development was associated with shorter time to treatment failure and shorter overall survival in an international review of over 7,000 renal cell carcinoma (RCC) patients treated with first-line tyrosine kinase inhibitors.

“Patients with synchronous disease, compared with patients with metachronous disease, have more adverse prognostic features, significantly shorter TTF [time to treatment failure], and poorer survival. This may help in patient counseling and may be taken into consideration in clinical trial designs in the future, in order to avoid an imbalance between treatment arms,” wrote investigators led by Frede Donskov, MD, a clinical professor at Aarhus (Denmark) University Hospital, in European Urology Oncology.

In the largest study to date to address the impact of timing of metastases on outcomes from tyrosine kinase inhibitor (TKI) treatment, something that’s been unclear until now, Dr. Donskov and associates turned to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare outcomes of 3,906 patients with synchronous metastases, meaning metastases within 3 months of initial RCC diagnosis, with 3,480 with metachronous disease, meaning metastases after that point.

They found that more patients with synchronous versus metachronous disease had higher T stage (T1-2, 19% vs. 34%), N1 disease (21% vs. 6%), presence of sarcomatoid differentiation (15.8% vs. 7.9%), Karnofsky performance status less than 80 (25.9% vs. 15.1%), anemia (62.5% vs. 42.3%), elevated neutrophils (18.9% vs. 10.9%), elevated platelets (21.6% vs. 11.4%), bone metastases (40.4% vs. 29.8%); and IMDC poor risk (40.6% vs.11.3%).

Synchronous versus metachronous disease by intervals of more than 3-12 months, more than 1-2 years, more than 2-7 years, and more than 7 years correlated with poor TTF (5.6 months vs. 7.3, 8.0, 10.8, and 13.3 months; P less than .0001) and poor overall survival (median, 16.7 months vs. 23.8, 30.2, 34.8, and 41.7 months; P less than .0001).

On multivariable regressions adjusting for baseline variables, metachronous disease was protective versus synchronous RCC on overall survival and TTF, with a greater protective effect the longer it took for the disease to metastasize.

“Synchronous disease may represent a distinct pathologic and molecular phenotype ... a high proportion of patients with synchronous disease have tumors with punctuated evolution, harboring aggressive disease features, consolidating in worse risk factors, requiring systemic therapy earlier, and having almost half the expected survival after the initiation of targeted therapy, compared with the latest metastatic timing, as shown in our study,” the investigators wrote.

The findings “reflect the underlying aggressive tumor biology. Whether [time to metastasis] impacts outcome to checkpoint immunotherapy is yet to be elucidated,” they added.

Patients were a median of 59 years at diagnosis, and 72.9% were men. None of the synchronous patients had a surgical nephrectomy, compared with 95.4% of metachronous patients; 67.2% of patients in both groups were treated with the TKI sunitinib (Sutent).

The work was funded by the IMDC. The lead investigator reported institutional grants from Ipsen and Pfizer, maker of sunitinib.
 

[email protected]

SOURCE: Donskov F et al. Eur Urol Oncol. 2020 Feb 6. doi: 10.1016/j.euo.2020.01.001.

Shorter time to metastatic development was associated with shorter time to treatment failure and shorter overall survival in an international review of over 7,000 renal cell carcinoma (RCC) patients treated with first-line tyrosine kinase inhibitors.

“Patients with synchronous disease, compared with patients with metachronous disease, have more adverse prognostic features, significantly shorter TTF [time to treatment failure], and poorer survival. This may help in patient counseling and may be taken into consideration in clinical trial designs in the future, in order to avoid an imbalance between treatment arms,” wrote investigators led by Frede Donskov, MD, a clinical professor at Aarhus (Denmark) University Hospital, in European Urology Oncology.

In the largest study to date to address the impact of timing of metastases on outcomes from tyrosine kinase inhibitor (TKI) treatment, something that’s been unclear until now, Dr. Donskov and associates turned to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare outcomes of 3,906 patients with synchronous metastases, meaning metastases within 3 months of initial RCC diagnosis, with 3,480 with metachronous disease, meaning metastases after that point.

They found that more patients with synchronous versus metachronous disease had higher T stage (T1-2, 19% vs. 34%), N1 disease (21% vs. 6%), presence of sarcomatoid differentiation (15.8% vs. 7.9%), Karnofsky performance status less than 80 (25.9% vs. 15.1%), anemia (62.5% vs. 42.3%), elevated neutrophils (18.9% vs. 10.9%), elevated platelets (21.6% vs. 11.4%), bone metastases (40.4% vs. 29.8%); and IMDC poor risk (40.6% vs.11.3%).

Synchronous versus metachronous disease by intervals of more than 3-12 months, more than 1-2 years, more than 2-7 years, and more than 7 years correlated with poor TTF (5.6 months vs. 7.3, 8.0, 10.8, and 13.3 months; P less than .0001) and poor overall survival (median, 16.7 months vs. 23.8, 30.2, 34.8, and 41.7 months; P less than .0001).

On multivariable regressions adjusting for baseline variables, metachronous disease was protective versus synchronous RCC on overall survival and TTF, with a greater protective effect the longer it took for the disease to metastasize.

“Synchronous disease may represent a distinct pathologic and molecular phenotype ... a high proportion of patients with synchronous disease have tumors with punctuated evolution, harboring aggressive disease features, consolidating in worse risk factors, requiring systemic therapy earlier, and having almost half the expected survival after the initiation of targeted therapy, compared with the latest metastatic timing, as shown in our study,” the investigators wrote.

The findings “reflect the underlying aggressive tumor biology. Whether [time to metastasis] impacts outcome to checkpoint immunotherapy is yet to be elucidated,” they added.

Patients were a median of 59 years at diagnosis, and 72.9% were men. None of the synchronous patients had a surgical nephrectomy, compared with 95.4% of metachronous patients; 67.2% of patients in both groups were treated with the TKI sunitinib (Sutent).

The work was funded by the IMDC. The lead investigator reported institutional grants from Ipsen and Pfizer, maker of sunitinib.
 

[email protected]

SOURCE: Donskov F et al. Eur Urol Oncol. 2020 Feb 6. doi: 10.1016/j.euo.2020.01.001.

The standard intradermal route of delivery for Bacille Calmette–Guérin (BCG) does not necessarily generate a strong enough response from lung T-cells, the researchers say. They hypothesized that administering BCG by IV or aerosol might be more effective.

They gave a group of rhesus macaques the BGC vaccine by intradermal, aerosol, or IV routes, then assessed immune responses in blood and fluid drawn from the lungs over a 24-week follow-up. Six months after vaccination, the researchers injected the vaccinated animals with a virulent strain of Mycobacterium tuberculosis (M tuberculosis) and tracked infection and disease development over 3 months.

The IV vaccination resulted in the highest durable levels of T-cells in blood and lungs. Nine of 10 animals vaccinated via IV were highly protected; 6 showed no detectable infection in any tissue tested and 3 had only very low counts of M tuberculosis in lung tissue. All unvaccinated animals and those immunized via intradermal or aerosol routes showed signs of significantly greater infection.

Upping the dose did not improve protection. The IV BCG group showed 90% protection at a threshold as low as 50 colony-forming units (the standard human ID dose is 5 x 10⁵ CFUs).

The researchers say several unique quantitative and qualitative differences in the immune responses may underlie protection. Perhaps most noteworthy, they say, was the large population of T- cells in the tissue across all lung parenchyma lobes.

The study provides a “paradigm shift,” the researchers conclude, adding that the IV route may also improve the protective capacity of other vaccines.

The standard intradermal route of delivery for Bacille Calmette–Guérin (BCG) does not necessarily generate a strong enough response from lung T-cells, the researchers say. They hypothesized that administering BCG by IV or aerosol might be more effective.

They gave a group of rhesus macaques the BGC vaccine by intradermal, aerosol, or IV routes, then assessed immune responses in blood and fluid drawn from the lungs over a 24-week follow-up. Six months after vaccination, the researchers injected the vaccinated animals with a virulent strain of Mycobacterium tuberculosis (M tuberculosis) and tracked infection and disease development over 3 months.

The IV vaccination resulted in the highest durable levels of T-cells in blood and lungs. Nine of 10 animals vaccinated via IV were highly protected; 6 showed no detectable infection in any tissue tested and 3 had only very low counts of M tuberculosis in lung tissue. All unvaccinated animals and those immunized via intradermal or aerosol routes showed signs of significantly greater infection.

Upping the dose did not improve protection. The IV BCG group showed 90% protection at a threshold as low as 50 colony-forming units (the standard human ID dose is 5 x 10⁵ CFUs).

The researchers say several unique quantitative and qualitative differences in the immune responses may underlie protection. Perhaps most noteworthy, they say, was the large population of T- cells in the tissue across all lung parenchyma lobes.

The study provides a “paradigm shift,” the researchers conclude, adding that the IV route may also improve the protective capacity of other vaccines.

The standard intradermal route of delivery for Bacille Calmette–Guérin (BCG) does not necessarily generate a strong enough response from lung T-cells, the researchers say. They hypothesized that administering BCG by IV or aerosol might be more effective.

They gave a group of rhesus macaques the BGC vaccine by intradermal, aerosol, or IV routes, then assessed immune responses in blood and fluid drawn from the lungs over a 24-week follow-up. Six months after vaccination, the researchers injected the vaccinated animals with a virulent strain of Mycobacterium tuberculosis (M tuberculosis) and tracked infection and disease development over 3 months.

The IV vaccination resulted in the highest durable levels of T-cells in blood and lungs. Nine of 10 animals vaccinated via IV were highly protected; 6 showed no detectable infection in any tissue tested and 3 had only very low counts of M tuberculosis in lung tissue. All unvaccinated animals and those immunized via intradermal or aerosol routes showed signs of significantly greater infection.

Upping the dose did not improve protection. The IV BCG group showed 90% protection at a threshold as low as 50 colony-forming units (the standard human ID dose is 5 x 10⁵ CFUs).

The researchers say several unique quantitative and qualitative differences in the immune responses may underlie protection. Perhaps most noteworthy, they say, was the large population of T- cells in the tissue across all lung parenchyma lobes.

The study provides a “paradigm shift,” the researchers conclude, adding that the IV route may also improve the protective capacity of other vaccines.

The Food and Drug Administration asked Eisai to voluntary withdraw the weight-loss drug lorcaserin (Belviq and Belviq XR) on Feb. 13 after a post-marketing trial with more than 12,000 subjects revealed an increased occurrence of cancer.

In a Drug Safety Communication, the agency said “health care professionals should stop prescribing and dispensing lorcaserin to patients. Contact patients currently taking lorcaserin, inform them of the increased occurrence of cancer seen in the clinical trial, and ask them to stop taking the medicine. Discuss alternative weight-loss medicines or strategies with your patients.”

Eisai is complying with the withdrawal request.

The decision is based on the agency’s review of the 5-year trial, which was designed to evaluate cardiac risk with the drug and ended in June 2018. In total, 7.7% of patients randomized to 10 mg lorcaserin twice daily were diagnosed with 520 primary cancers, compared with 7.1% of placebo subjects diagnosed with 470 cancers, over a median follow-up of 3 years and 3 months. There was one additional cancer observed for every 470 patients treated for 1 year.

“There was no apparent difference in the incidence of cancer over the initial months of treatment, but the imbalance increased with longer duration on lorcaserin,” FDA said. Pancreatic, colorectal, and lung cancers were among those diagnosed.

In short, “we believe that the risks of lorcaserin outweigh its benefits based on our completed review of” the data, the agency said. The FDA is not recommending special cancer screenings for patients who have taken lorcaserin.

The action follows an FDA alert in January about a possible elevated cancer risk based on its preliminary analysis of the study.

Patients were also advised Feb. 13 to stop taking the drug and talk to their providers about alternative weight-loss medications and weight-management programs.

They were also told to dispose of the pills at a drug take-back location if available, but if not, to mix them with an “unappealing substance” such as dirt, cat litter, or used coffee grounds; seal them in plastic bag; and put them in the trash.

[email protected]

The Food and Drug Administration asked Eisai to voluntary withdraw the weight-loss drug lorcaserin (Belviq and Belviq XR) on Feb. 13 after a post-marketing trial with more than 12,000 subjects revealed an increased occurrence of cancer.

In a Drug Safety Communication, the agency said “health care professionals should stop prescribing and dispensing lorcaserin to patients. Contact patients currently taking lorcaserin, inform them of the increased occurrence of cancer seen in the clinical trial, and ask them to stop taking the medicine. Discuss alternative weight-loss medicines or strategies with your patients.”

Eisai is complying with the withdrawal request.

The decision is based on the agency’s review of the 5-year trial, which was designed to evaluate cardiac risk with the drug and ended in June 2018. In total, 7.7% of patients randomized to 10 mg lorcaserin twice daily were diagnosed with 520 primary cancers, compared with 7.1% of placebo subjects diagnosed with 470 cancers, over a median follow-up of 3 years and 3 months. There was one additional cancer observed for every 470 patients treated for 1 year.

“There was no apparent difference in the incidence of cancer over the initial months of treatment, but the imbalance increased with longer duration on lorcaserin,” FDA said. Pancreatic, colorectal, and lung cancers were among those diagnosed.

In short, “we believe that the risks of lorcaserin outweigh its benefits based on our completed review of” the data, the agency said. The FDA is not recommending special cancer screenings for patients who have taken lorcaserin.

The action follows an FDA alert in January about a possible elevated cancer risk based on its preliminary analysis of the study.

Patients were also advised Feb. 13 to stop taking the drug and talk to their providers about alternative weight-loss medications and weight-management programs.

They were also told to dispose of the pills at a drug take-back location if available, but if not, to mix them with an “unappealing substance” such as dirt, cat litter, or used coffee grounds; seal them in plastic bag; and put them in the trash.

[email protected]

The Food and Drug Administration asked Eisai to voluntary withdraw the weight-loss drug lorcaserin (Belviq and Belviq XR) on Feb. 13 after a post-marketing trial with more than 12,000 subjects revealed an increased occurrence of cancer.

In a Drug Safety Communication, the agency said “health care professionals should stop prescribing and dispensing lorcaserin to patients. Contact patients currently taking lorcaserin, inform them of the increased occurrence of cancer seen in the clinical trial, and ask them to stop taking the medicine. Discuss alternative weight-loss medicines or strategies with your patients.”

Eisai is complying with the withdrawal request.

The decision is based on the agency’s review of the 5-year trial, which was designed to evaluate cardiac risk with the drug and ended in June 2018. In total, 7.7% of patients randomized to 10 mg lorcaserin twice daily were diagnosed with 520 primary cancers, compared with 7.1% of placebo subjects diagnosed with 470 cancers, over a median follow-up of 3 years and 3 months. There was one additional cancer observed for every 470 patients treated for 1 year.

“There was no apparent difference in the incidence of cancer over the initial months of treatment, but the imbalance increased with longer duration on lorcaserin,” FDA said. Pancreatic, colorectal, and lung cancers were among those diagnosed.

In short, “we believe that the risks of lorcaserin outweigh its benefits based on our completed review of” the data, the agency said. The FDA is not recommending special cancer screenings for patients who have taken lorcaserin.

The action follows an FDA alert in January about a possible elevated cancer risk based on its preliminary analysis of the study.

Patients were also advised Feb. 13 to stop taking the drug and talk to their providers about alternative weight-loss medications and weight-management programs.

They were also told to dispose of the pills at a drug take-back location if available, but if not, to mix them with an “unappealing substance” such as dirt, cat litter, or used coffee grounds; seal them in plastic bag; and put them in the trash.

[email protected]

An accelerated path to surgery after hip fracture did not improve mortality or major complications, according to a new international randomized trial. However, a fast track to surgery hastened mobilization, weight-bearing, and hospital discharge, and reduced the risk of urinary tract infection and delirium.

The HIP ATTACK (Hip Fracture Accelerated Surgical Treatment and Care Track) study enrolled 2,970 patients (median age, 79 years; 69% women) during March 2014-May 2019. The study excluded patients younger than 45 years, as well as those who were on nonreversible anticoagulation and who had high-energy or more complex hip fractures. In all, 1,487 patients were randomly assigned to the accelerated-surgery group, which received early medical evaluation with a goal of heading to surgery within 6 hours of a hip fracture diagnosis. The goal was achieved, with patients in the intervention arm receiving care at a median 6 hours after diagnosis. Patients in the 69 participating hospitals in 17 countries who were assigned to standard of care received surgery at a median 24 hours after diagnosis (P less than .001).

“Observational data, clinical experience, and biological rationale suggest that the longer a patient is immobile and lying in a bed, the higher the risk of poor outcomes,” wrote principal investigators Philip J. Devereaux, MD, PhD, and Mohit Bhandari, MD, PhD, of McMaster University, Hamilton, Ont., and their colleagues on the HIP ATTACK writing committee.

The study was the first large, randomized trial that directly compared accelerated surgery with standard of care, noted the authors. Previous observational studies had shown worse outcomes for those usual-care patients who waited longer for surgery.

In HIP ATTACK, there was no difference in the primary outcome measures of 90-day mortality and major complications for patients receiving surgery within 6 hours after hip fracture diagnosis, compared with those who received surgery within 24 hours. The coprimary outcome measures included serious complications, such as MI, stroke, venous thromboembolism, sepsis, pneumonia, and life-threatening or major bleeding.

In practice, the researchers found that patients in the accelerated-surgery group received medical clearance in a median time of 2 hours after a diagnosis of hip fracture, whereas the standard of care group was cleared in 4 hours.

At 90 days, 9% of patients in the accelerated-surgery group and 10% of those in the usual-care group had died, a nonsignificant difference between the two groups. In both groups, 22% of patients experienced a major complication. A post hoc analysis that looked for any site-clustering effects did not detect different outcomes, the investigators wrote.

Delirium occurred in 132 patients (9%) of the accelerated-surgery group and in 175 patients (12%) in the usual-care group (odds ratio, 0.72; 95% confidence interval, 0.58-0.92). Infection without sepsis and urinary tract infection were both less common in the accelerated-surgery group (hazard ratio, 0.80 and 0.78, respectively).

The authors noted that the potential benefits of a speedy course to surgery, including reduced immobility and less pain, could be negated if physicians had less time to optimize medical care for older patients with multiple comorbidities and who make up a significant proportion of those who sustain low-energy hip fractures. However, medical complications, such as MI and new-onset atrial fibrillation, were not seen more frequently in the accelerated-surgery group.

In an editorial accompanying the study, Alejandro Lizaur-Utrilla, MD, and Fernando Lopez-Prats, MD, of the Universidad Miguel Hernández, Alicante, Spain, observed that the 6-hour window for hip fracture surgery may be difficult to achieve given clinical practicalities and that, in some cases, the 6-hour window might be unavoidable if severe comorbidities and overall poor health make early surgery inadvisable.

They also expressed concern that, despite the lack of harm shown in the patients who underwent accelerated surgery, the surgery “might negatively affect patients’ outcomes by preventing or limiting the opportunity for optimization of patients’ medical conditions before surgery.” They called for further study to delineate how fitness for surgery affects outcomes in accelerated surgery and to further examine whether the better outcomes are associated with improved cost-effectiveness.

Multiple HIP ATTACK coinvestigators reported relationships with pharmaceutical and medical device companies, including companies that manufacture hip prosthesis and orthopedic surgical devices and implants. The study was sponsored by the Canadian Population Health Research Institute, the Ontario Strategy for Patient Oriented Research Support Unit, the Ontario Ministry of Health and Long-Term Care, the Hamilton Health Sciences Foundation, Physicians’ Services Incorporated Foundation, Michael G. DeGroote Institute for Pain Research and Care, Smith & Nephew (to recruit patients in Spain), and Indiegogo Crowdfunding.

SOURCE: Borges F et al. Lancet. 2020 Feb. 9. doi: 10.1016/S0140-6736(20)30058-1.


 

An accelerated path to surgery after hip fracture did not improve mortality or major complications, according to a new international randomized trial. However, a fast track to surgery hastened mobilization, weight-bearing, and hospital discharge, and reduced the risk of urinary tract infection and delirium.

The HIP ATTACK (Hip Fracture Accelerated Surgical Treatment and Care Track) study enrolled 2,970 patients (median age, 79 years; 69% women) during March 2014-May 2019. The study excluded patients younger than 45 years, as well as those who were on nonreversible anticoagulation and who had high-energy or more complex hip fractures. In all, 1,487 patients were randomly assigned to the accelerated-surgery group, which received early medical evaluation with a goal of heading to surgery within 6 hours of a hip fracture diagnosis. The goal was achieved, with patients in the intervention arm receiving care at a median 6 hours after diagnosis. Patients in the 69 participating hospitals in 17 countries who were assigned to standard of care received surgery at a median 24 hours after diagnosis (P less than .001).

“Observational data, clinical experience, and biological rationale suggest that the longer a patient is immobile and lying in a bed, the higher the risk of poor outcomes,” wrote principal investigators Philip J. Devereaux, MD, PhD, and Mohit Bhandari, MD, PhD, of McMaster University, Hamilton, Ont., and their colleagues on the HIP ATTACK writing committee.

The study was the first large, randomized trial that directly compared accelerated surgery with standard of care, noted the authors. Previous observational studies had shown worse outcomes for those usual-care patients who waited longer for surgery.

In HIP ATTACK, there was no difference in the primary outcome measures of 90-day mortality and major complications for patients receiving surgery within 6 hours after hip fracture diagnosis, compared with those who received surgery within 24 hours. The coprimary outcome measures included serious complications, such as MI, stroke, venous thromboembolism, sepsis, pneumonia, and life-threatening or major bleeding.

In practice, the researchers found that patients in the accelerated-surgery group received medical clearance in a median time of 2 hours after a diagnosis of hip fracture, whereas the standard of care group was cleared in 4 hours.

At 90 days, 9% of patients in the accelerated-surgery group and 10% of those in the usual-care group had died, a nonsignificant difference between the two groups. In both groups, 22% of patients experienced a major complication. A post hoc analysis that looked for any site-clustering effects did not detect different outcomes, the investigators wrote.

Delirium occurred in 132 patients (9%) of the accelerated-surgery group and in 175 patients (12%) in the usual-care group (odds ratio, 0.72; 95% confidence interval, 0.58-0.92). Infection without sepsis and urinary tract infection were both less common in the accelerated-surgery group (hazard ratio, 0.80 and 0.78, respectively).

The authors noted that the potential benefits of a speedy course to surgery, including reduced immobility and less pain, could be negated if physicians had less time to optimize medical care for older patients with multiple comorbidities and who make up a significant proportion of those who sustain low-energy hip fractures. However, medical complications, such as MI and new-onset atrial fibrillation, were not seen more frequently in the accelerated-surgery group.

In an editorial accompanying the study, Alejandro Lizaur-Utrilla, MD, and Fernando Lopez-Prats, MD, of the Universidad Miguel Hernández, Alicante, Spain, observed that the 6-hour window for hip fracture surgery may be difficult to achieve given clinical practicalities and that, in some cases, the 6-hour window might be unavoidable if severe comorbidities and overall poor health make early surgery inadvisable.

They also expressed concern that, despite the lack of harm shown in the patients who underwent accelerated surgery, the surgery “might negatively affect patients’ outcomes by preventing or limiting the opportunity for optimization of patients’ medical conditions before surgery.” They called for further study to delineate how fitness for surgery affects outcomes in accelerated surgery and to further examine whether the better outcomes are associated with improved cost-effectiveness.

Multiple HIP ATTACK coinvestigators reported relationships with pharmaceutical and medical device companies, including companies that manufacture hip prosthesis and orthopedic surgical devices and implants. The study was sponsored by the Canadian Population Health Research Institute, the Ontario Strategy for Patient Oriented Research Support Unit, the Ontario Ministry of Health and Long-Term Care, the Hamilton Health Sciences Foundation, Physicians’ Services Incorporated Foundation, Michael G. DeGroote Institute for Pain Research and Care, Smith & Nephew (to recruit patients in Spain), and Indiegogo Crowdfunding.

SOURCE: Borges F et al. Lancet. 2020 Feb. 9. doi: 10.1016/S0140-6736(20)30058-1.


 

An accelerated path to surgery after hip fracture did not improve mortality or major complications, according to a new international randomized trial. However, a fast track to surgery hastened mobilization, weight-bearing, and hospital discharge, and reduced the risk of urinary tract infection and delirium.

The HIP ATTACK (Hip Fracture Accelerated Surgical Treatment and Care Track) study enrolled 2,970 patients (median age, 79 years; 69% women) during March 2014-May 2019. The study excluded patients younger than 45 years, as well as those who were on nonreversible anticoagulation and who had high-energy or more complex hip fractures. In all, 1,487 patients were randomly assigned to the accelerated-surgery group, which received early medical evaluation with a goal of heading to surgery within 6 hours of a hip fracture diagnosis. The goal was achieved, with patients in the intervention arm receiving care at a median 6 hours after diagnosis. Patients in the 69 participating hospitals in 17 countries who were assigned to standard of care received surgery at a median 24 hours after diagnosis (P less than .001).

“Observational data, clinical experience, and biological rationale suggest that the longer a patient is immobile and lying in a bed, the higher the risk of poor outcomes,” wrote principal investigators Philip J. Devereaux, MD, PhD, and Mohit Bhandari, MD, PhD, of McMaster University, Hamilton, Ont., and their colleagues on the HIP ATTACK writing committee.

The study was the first large, randomized trial that directly compared accelerated surgery with standard of care, noted the authors. Previous observational studies had shown worse outcomes for those usual-care patients who waited longer for surgery.

In HIP ATTACK, there was no difference in the primary outcome measures of 90-day mortality and major complications for patients receiving surgery within 6 hours after hip fracture diagnosis, compared with those who received surgery within 24 hours. The coprimary outcome measures included serious complications, such as MI, stroke, venous thromboembolism, sepsis, pneumonia, and life-threatening or major bleeding.

In practice, the researchers found that patients in the accelerated-surgery group received medical clearance in a median time of 2 hours after a diagnosis of hip fracture, whereas the standard of care group was cleared in 4 hours.

At 90 days, 9% of patients in the accelerated-surgery group and 10% of those in the usual-care group had died, a nonsignificant difference between the two groups. In both groups, 22% of patients experienced a major complication. A post hoc analysis that looked for any site-clustering effects did not detect different outcomes, the investigators wrote.

Delirium occurred in 132 patients (9%) of the accelerated-surgery group and in 175 patients (12%) in the usual-care group (odds ratio, 0.72; 95% confidence interval, 0.58-0.92). Infection without sepsis and urinary tract infection were both less common in the accelerated-surgery group (hazard ratio, 0.80 and 0.78, respectively).

The authors noted that the potential benefits of a speedy course to surgery, including reduced immobility and less pain, could be negated if physicians had less time to optimize medical care for older patients with multiple comorbidities and who make up a significant proportion of those who sustain low-energy hip fractures. However, medical complications, such as MI and new-onset atrial fibrillation, were not seen more frequently in the accelerated-surgery group.

In an editorial accompanying the study, Alejandro Lizaur-Utrilla, MD, and Fernando Lopez-Prats, MD, of the Universidad Miguel Hernández, Alicante, Spain, observed that the 6-hour window for hip fracture surgery may be difficult to achieve given clinical practicalities and that, in some cases, the 6-hour window might be unavoidable if severe comorbidities and overall poor health make early surgery inadvisable.

They also expressed concern that, despite the lack of harm shown in the patients who underwent accelerated surgery, the surgery “might negatively affect patients’ outcomes by preventing or limiting the opportunity for optimization of patients’ medical conditions before surgery.” They called for further study to delineate how fitness for surgery affects outcomes in accelerated surgery and to further examine whether the better outcomes are associated with improved cost-effectiveness.

Multiple HIP ATTACK coinvestigators reported relationships with pharmaceutical and medical device companies, including companies that manufacture hip prosthesis and orthopedic surgical devices and implants. The study was sponsored by the Canadian Population Health Research Institute, the Ontario Strategy for Patient Oriented Research Support Unit, the Ontario Ministry of Health and Long-Term Care, the Hamilton Health Sciences Foundation, Physicians’ Services Incorporated Foundation, Michael G. DeGroote Institute for Pain Research and Care, Smith & Nephew (to recruit patients in Spain), and Indiegogo Crowdfunding.

SOURCE: Borges F et al. Lancet. 2020 Feb. 9. doi: 10.1016/S0140-6736(20)30058-1.


 

For patients with high-risk stage II resected colorectal cancer (CRC), 3 months of adjuvant therapy with capecitabine plus oxaliplatin (CAPOX) may be significantly safer and nearly as effective as a 6-month course, based on results of the phase 3 TOSCA trial.

In contrast, a shortened duration of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) may negatively impact 5-year recurrence-free survival, reported Fausto Petrelli, MD, of ASST Bergamo Ovest in Treviglio, Italy, and colleagues.

An earlier analysis from the Italian Three or Six Colon Adjuvant (TOSCA) trial showed that 6 months of oxaliplatin-based adjuvant chemotherapy was superior to a 3-month regimen among patients with stage III CRC, the investigators wrote in JAMA Oncology.

To determine if this finding carried over to patients with less advanced disease, the investigators recruited 1,254 patients with high-risk stage II resected CRC who were treated at 130 centers in Italy. Patients were randomized in a 1:1 ratio to receive a 6-month or 3-month regimen of oxaliplatin-based chemotherapy (either FOLFOX or CAPOX). The primary outcome was a test for noninferiority between the two durations, with the null hypothesis rejected by a hazard ratio of at least 1.2.

Almost two-thirds (61.9%) of patients received FOLFOX, while the remainder (38.1%) received CAPOX. Across all of these patients, 6 months of therapy was associated with a 5-year recurrence-free survival rate of 88.2%, compared with 82.2% for the 3-month course. This translates to a hazard ratio of 1.41, which is insufficient to reject noninferiority (P = .86) and suggests a longer duration of oxaliplatin-based chemotherapy is significantly more effective.

However, when the CAPOX and FOLFOX subgroups were considered independently, distinct efficacy trends emerged. The difference in the 5-year recurrence-free survival rate between 6 months and 3 months of CAPOX was only slightly in favor of the longer course (0.76%). There was a much greater survival rate difference of 8.56% that favored the 6-month course of FOLFOX.

The investigators noted that 6 months of adjuvant therapy was associated with significantly more adverse events than a 3-month course, particularly for grade 3/4 neuropathy (8.4% vs. 1.3%; P less than .001). Taken together, the findings suggest the shortened CAPOX regimen may be a viable option.

“[E]ither 3 months of CAPOX or 6 months of FOLFOX treatment can be used whenever an oxaliplatin doublet is indicated for use in patients with stage II CRC,” the investigators wrote. At the same time, they suggested the subgroup findings be interpreted with caution, as the study was not powered for these analyses.

“[T]he utility of oxaliplatin in stage II CRC remains unclear, and the choice between 6 months of fluoropyrimidine-based chemotherapy and 3 or 6 months of oxaliplatin-based chemotherapy must be made on an individual basis,” the investigators concluded.

The study was funded by the Italian Group for the Study of Digestive Tract Cancers (GISCAD) Foundation and Agenzia Italiana del Farmaco. The investigators disclosed relationships with Servier, Merck, Bristol-Myers Squibb, and other companies.


SOURCE: Petrelli F et al. JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6486.

For patients with high-risk stage II resected colorectal cancer (CRC), 3 months of adjuvant therapy with capecitabine plus oxaliplatin (CAPOX) may be significantly safer and nearly as effective as a 6-month course, based on results of the phase 3 TOSCA trial.

In contrast, a shortened duration of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) may negatively impact 5-year recurrence-free survival, reported Fausto Petrelli, MD, of ASST Bergamo Ovest in Treviglio, Italy, and colleagues.

An earlier analysis from the Italian Three or Six Colon Adjuvant (TOSCA) trial showed that 6 months of oxaliplatin-based adjuvant chemotherapy was superior to a 3-month regimen among patients with stage III CRC, the investigators wrote in JAMA Oncology.

To determine if this finding carried over to patients with less advanced disease, the investigators recruited 1,254 patients with high-risk stage II resected CRC who were treated at 130 centers in Italy. Patients were randomized in a 1:1 ratio to receive a 6-month or 3-month regimen of oxaliplatin-based chemotherapy (either FOLFOX or CAPOX). The primary outcome was a test for noninferiority between the two durations, with the null hypothesis rejected by a hazard ratio of at least 1.2.

Almost two-thirds (61.9%) of patients received FOLFOX, while the remainder (38.1%) received CAPOX. Across all of these patients, 6 months of therapy was associated with a 5-year recurrence-free survival rate of 88.2%, compared with 82.2% for the 3-month course. This translates to a hazard ratio of 1.41, which is insufficient to reject noninferiority (P = .86) and suggests a longer duration of oxaliplatin-based chemotherapy is significantly more effective.

However, when the CAPOX and FOLFOX subgroups were considered independently, distinct efficacy trends emerged. The difference in the 5-year recurrence-free survival rate between 6 months and 3 months of CAPOX was only slightly in favor of the longer course (0.76%). There was a much greater survival rate difference of 8.56% that favored the 6-month course of FOLFOX.

The investigators noted that 6 months of adjuvant therapy was associated with significantly more adverse events than a 3-month course, particularly for grade 3/4 neuropathy (8.4% vs. 1.3%; P less than .001). Taken together, the findings suggest the shortened CAPOX regimen may be a viable option.

“[E]ither 3 months of CAPOX or 6 months of FOLFOX treatment can be used whenever an oxaliplatin doublet is indicated for use in patients with stage II CRC,” the investigators wrote. At the same time, they suggested the subgroup findings be interpreted with caution, as the study was not powered for these analyses.

“[T]he utility of oxaliplatin in stage II CRC remains unclear, and the choice between 6 months of fluoropyrimidine-based chemotherapy and 3 or 6 months of oxaliplatin-based chemotherapy must be made on an individual basis,” the investigators concluded.

The study was funded by the Italian Group for the Study of Digestive Tract Cancers (GISCAD) Foundation and Agenzia Italiana del Farmaco. The investigators disclosed relationships with Servier, Merck, Bristol-Myers Squibb, and other companies.


SOURCE: Petrelli F et al. JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6486.

For patients with high-risk stage II resected colorectal cancer (CRC), 3 months of adjuvant therapy with capecitabine plus oxaliplatin (CAPOX) may be significantly safer and nearly as effective as a 6-month course, based on results of the phase 3 TOSCA trial.

In contrast, a shortened duration of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) may negatively impact 5-year recurrence-free survival, reported Fausto Petrelli, MD, of ASST Bergamo Ovest in Treviglio, Italy, and colleagues.

An earlier analysis from the Italian Three or Six Colon Adjuvant (TOSCA) trial showed that 6 months of oxaliplatin-based adjuvant chemotherapy was superior to a 3-month regimen among patients with stage III CRC, the investigators wrote in JAMA Oncology.

To determine if this finding carried over to patients with less advanced disease, the investigators recruited 1,254 patients with high-risk stage II resected CRC who were treated at 130 centers in Italy. Patients were randomized in a 1:1 ratio to receive a 6-month or 3-month regimen of oxaliplatin-based chemotherapy (either FOLFOX or CAPOX). The primary outcome was a test for noninferiority between the two durations, with the null hypothesis rejected by a hazard ratio of at least 1.2.

Almost two-thirds (61.9%) of patients received FOLFOX, while the remainder (38.1%) received CAPOX. Across all of these patients, 6 months of therapy was associated with a 5-year recurrence-free survival rate of 88.2%, compared with 82.2% for the 3-month course. This translates to a hazard ratio of 1.41, which is insufficient to reject noninferiority (P = .86) and suggests a longer duration of oxaliplatin-based chemotherapy is significantly more effective.

However, when the CAPOX and FOLFOX subgroups were considered independently, distinct efficacy trends emerged. The difference in the 5-year recurrence-free survival rate between 6 months and 3 months of CAPOX was only slightly in favor of the longer course (0.76%). There was a much greater survival rate difference of 8.56% that favored the 6-month course of FOLFOX.

The investigators noted that 6 months of adjuvant therapy was associated with significantly more adverse events than a 3-month course, particularly for grade 3/4 neuropathy (8.4% vs. 1.3%; P less than .001). Taken together, the findings suggest the shortened CAPOX regimen may be a viable option.

“[E]ither 3 months of CAPOX or 6 months of FOLFOX treatment can be used whenever an oxaliplatin doublet is indicated for use in patients with stage II CRC,” the investigators wrote. At the same time, they suggested the subgroup findings be interpreted with caution, as the study was not powered for these analyses.

“[T]he utility of oxaliplatin in stage II CRC remains unclear, and the choice between 6 months of fluoropyrimidine-based chemotherapy and 3 or 6 months of oxaliplatin-based chemotherapy must be made on an individual basis,” the investigators concluded.

The study was funded by the Italian Group for the Study of Digestive Tract Cancers (GISCAD) Foundation and Agenzia Italiana del Farmaco. The investigators disclosed relationships with Servier, Merck, Bristol-Myers Squibb, and other companies.


SOURCE: Petrelli F et al. JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6486.

AUSTIN, TEX. – As more states legalize recreational and medical marijuana and cannabinoid products, and as evidence shows that up to 40% of patients with inflammatory bowel disease may be users, their gastroenterologists and other medical providers may be failing to even ask if they’re using, let alone talk to them about how it could impact their disease, according to a study of a hospital population in Washington, where recreational marijuana is legal.

The single-center, chart-review study at George Washington University found that providers noted they inquired about marijuana/CBD use in fewer than half of encounters with IBD patients – 47.8% to be precise – and that 4.9% of charts actually noted patients were users, according to a poster at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“This study acknowledges the growth of recreational and medical marijuana use as well as CBD products,” said poster presenter Scott Baumgartner, PA, a fourth-year medical student. “Understanding that because there’s increased legalization of both medical and recreational marijuana, our patients may be using them at increased rates. But are we asking them?”

According to the Drug Policy Alliance, recreational marijuana is legal in 11 states as well as Washington, which legalized recreational pot in 2014, and medical marijuana is legal in 33 states. The prevalence of cannabis use in patients with IBD has been reported at 15%-40% (Gastroenterol Hepatol [NY]. 2016;12:668-79).

The study consisted of a retrospective review of 381 charts of patients with IBD. Of the 19 charts that noted marijuana/CBD use, only 2 noted a prescription for medical purposes, although 4 noted IBD symptoms as the reason for use. Three charts noted recreational use and 12 gave no reason.

Mr. Baumgartner noted that it’s important gastroenterologists and other providers ask about marijuana/CBD use in their patients because of the inconclusive evidence about how it affects the disease (Dig Dis Sci. 2019;64:2696-8). “If you’re using marijuana for an IBD such as Crohn’s or ulcerative colitis because you think it’s relieving your symptoms, does it actually work in your long-term course?” he asked. “Does it relieve some symptoms but make other disease manifestations worse. We need more research in that area.”

The takeaway of the study: “We need to do a better job of asking whether or not patients are using recreational drugs,” Mr. Baumgartner said. “And if they are using recreational drugs, what recreational drugs they are using, because it could have a big impact on the outcome of their disease.”

The next steps for this research, Mr. Baumgartner said, is to focus on the specific questions providers are asking about their patients’ marijuana and recreational drug use and how they’re documenting those responses. “Once we see that, we could consider looking at a cohort of patients who are using and see if they are reporting symptom relief, or if we are seeing disease remission, or not,” Mr. Baumgartner said.

Mr. Baumgartner has no financial relationships to disclose.

SOURCE: Baumgartner S et al. Crohn’s & Colitis Congress 2020. 2020 Jan 23. Poster 011.

AUSTIN, TEX. – As more states legalize recreational and medical marijuana and cannabinoid products, and as evidence shows that up to 40% of patients with inflammatory bowel disease may be users, their gastroenterologists and other medical providers may be failing to even ask if they’re using, let alone talk to them about how it could impact their disease, according to a study of a hospital population in Washington, where recreational marijuana is legal.

The single-center, chart-review study at George Washington University found that providers noted they inquired about marijuana/CBD use in fewer than half of encounters with IBD patients – 47.8% to be precise – and that 4.9% of charts actually noted patients were users, according to a poster at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“This study acknowledges the growth of recreational and medical marijuana use as well as CBD products,” said poster presenter Scott Baumgartner, PA, a fourth-year medical student. “Understanding that because there’s increased legalization of both medical and recreational marijuana, our patients may be using them at increased rates. But are we asking them?”

According to the Drug Policy Alliance, recreational marijuana is legal in 11 states as well as Washington, which legalized recreational pot in 2014, and medical marijuana is legal in 33 states. The prevalence of cannabis use in patients with IBD has been reported at 15%-40% (Gastroenterol Hepatol [NY]. 2016;12:668-79).

The study consisted of a retrospective review of 381 charts of patients with IBD. Of the 19 charts that noted marijuana/CBD use, only 2 noted a prescription for medical purposes, although 4 noted IBD symptoms as the reason for use. Three charts noted recreational use and 12 gave no reason.

Mr. Baumgartner noted that it’s important gastroenterologists and other providers ask about marijuana/CBD use in their patients because of the inconclusive evidence about how it affects the disease (Dig Dis Sci. 2019;64:2696-8). “If you’re using marijuana for an IBD such as Crohn’s or ulcerative colitis because you think it’s relieving your symptoms, does it actually work in your long-term course?” he asked. “Does it relieve some symptoms but make other disease manifestations worse. We need more research in that area.”

The takeaway of the study: “We need to do a better job of asking whether or not patients are using recreational drugs,” Mr. Baumgartner said. “And if they are using recreational drugs, what recreational drugs they are using, because it could have a big impact on the outcome of their disease.”

The next steps for this research, Mr. Baumgartner said, is to focus on the specific questions providers are asking about their patients’ marijuana and recreational drug use and how they’re documenting those responses. “Once we see that, we could consider looking at a cohort of patients who are using and see if they are reporting symptom relief, or if we are seeing disease remission, or not,” Mr. Baumgartner said.

Mr. Baumgartner has no financial relationships to disclose.

SOURCE: Baumgartner S et al. Crohn’s & Colitis Congress 2020. 2020 Jan 23. Poster 011.

AUSTIN, TEX. – As more states legalize recreational and medical marijuana and cannabinoid products, and as evidence shows that up to 40% of patients with inflammatory bowel disease may be users, their gastroenterologists and other medical providers may be failing to even ask if they’re using, let alone talk to them about how it could impact their disease, according to a study of a hospital population in Washington, where recreational marijuana is legal.

The single-center, chart-review study at George Washington University found that providers noted they inquired about marijuana/CBD use in fewer than half of encounters with IBD patients – 47.8% to be precise – and that 4.9% of charts actually noted patients were users, according to a poster at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“This study acknowledges the growth of recreational and medical marijuana use as well as CBD products,” said poster presenter Scott Baumgartner, PA, a fourth-year medical student. “Understanding that because there’s increased legalization of both medical and recreational marijuana, our patients may be using them at increased rates. But are we asking them?”

According to the Drug Policy Alliance, recreational marijuana is legal in 11 states as well as Washington, which legalized recreational pot in 2014, and medical marijuana is legal in 33 states. The prevalence of cannabis use in patients with IBD has been reported at 15%-40% (Gastroenterol Hepatol [NY]. 2016;12:668-79).

The study consisted of a retrospective review of 381 charts of patients with IBD. Of the 19 charts that noted marijuana/CBD use, only 2 noted a prescription for medical purposes, although 4 noted IBD symptoms as the reason for use. Three charts noted recreational use and 12 gave no reason.

Mr. Baumgartner noted that it’s important gastroenterologists and other providers ask about marijuana/CBD use in their patients because of the inconclusive evidence about how it affects the disease (Dig Dis Sci. 2019;64:2696-8). “If you’re using marijuana for an IBD such as Crohn’s or ulcerative colitis because you think it’s relieving your symptoms, does it actually work in your long-term course?” he asked. “Does it relieve some symptoms but make other disease manifestations worse. We need more research in that area.”

The takeaway of the study: “We need to do a better job of asking whether or not patients are using recreational drugs,” Mr. Baumgartner said. “And if they are using recreational drugs, what recreational drugs they are using, because it could have a big impact on the outcome of their disease.”

The next steps for this research, Mr. Baumgartner said, is to focus on the specific questions providers are asking about their patients’ marijuana and recreational drug use and how they’re documenting those responses. “Once we see that, we could consider looking at a cohort of patients who are using and see if they are reporting symptom relief, or if we are seeing disease remission, or not,” Mr. Baumgartner said.

Mr. Baumgartner has no financial relationships to disclose.

SOURCE: Baumgartner S et al. Crohn’s & Colitis Congress 2020. 2020 Jan 23. Poster 011.