Use of a robotics platform provides a surgeon with more information so they can make better decisions, especially in challenging situations of primary and revisional bariatric surgery, according to Cheguevara Afaneh, MD, of New York–Presbyterian Hospital and Weill Cornell Medical Center, New York.

“The value of modern technology is to be able to do the most difficult cases in a much simpler format,” he said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium by Global Academy for Medical Education.

Dr. Afaneh shared examples of how robotic assistance can help surgeons address challenges in bariatric surgery clinical practice, including managing super- and super-super-obese patients, dealing with gastroesophageal reflux disease (GERD), and negating the impact of surgical assistant experience.

“Super-obese patients pose more of a challenge interoperatively for both the surgeon and the assistant,” Dr. Afaneh noted. He and colleagues conducted a study of perioperative outcomes and found no significant differences between morbidly obese and super-obese patients in perioperative morbidity or operating time when a robotic platform was used.

The benefits to the surgeon when using robotic assistance in super-obese patients include effortless navigation of the abdominal wall, the ability to execute complex maneuvers in a challenging environment, and the security of a stable platform with no assistant fatigue, Dr. Afaneh emphasized. “When you are using the robotic platform, you are negating a lot of the patient factors” and fatigue factors that make bariatric surgery in super-obese and super-super-obese patients especially difficult, he said.

For example, in a patient who weighed nearly 500 pounds, pulling up on the stomach to get behind the actual stomach is easier because assistant fatigue is not a factor, so the surgeon can take more time and prevent a more difficult dissection, he said. In addition, Dr. Afaneh’s research showed no difference in operative time, and that the robot assistance outcomes were reproducible across a range of body mass index categories.

Robotic assistance also allows for comparable outcomes in surgeons with less experience, notably in revisional surgery, said Dr. Afaneh. He reviewed data from his first year of experience in revisional procedures using robotic assistance to his partners’ more than 20 years of laparoscopic experience. He found no significant differences in operative time, complications, or conversions to open procedures.

However, the more important message from the study was that less experienced surgeons were able to safely perform some of the most difficult revisional procedures without increasing morbidity, compared with more experienced surgeons. The data suggest that, with robotic assistance, surgeons early in their career can take on some of the bigger cases and expect outcomes similar to those of more experienced surgeons, Dr. Afaneh said.

Robotics has demonstrated improved outcomes in managing patients with GERD, which has become a common problem after bariatric surgery, noted Dr. Afaneh. When he and his colleagues reviewed data from their center on robotic-assisted approaches to GERD after bariatric surgery, they found that, even in primary magnetic sphincter operations, “robotics maintains comparable outcomes in revisional sleeve gastrectomy fields,” he said.

Another notable benefit of robotics in bariatric surgery is the negation of the “assistant effect,” said Dr. Afaneh. Often, less experienced surgeons are matched with less experienced assistants. “We took a look at the use of the robotic in cases of complex GI surgeries,” he said. They compared laparoscopic and robotic cases and stratified them by third-year assistant or fellow. “If you had a fellow, the operative time dropped by half an hour for laparoscopic cases, but the time was no different in robotics cases,” regardless of the use of fellow or third-year assistant, he said.

“The robotic platform allows you to assist yourself,” and allows for full surgeon autonomy, Dr. Afaneh emphasized. “You are the best person at predicting your next step.” The robotics platform also serves as a teaching tool. “For those who teach, there is no added morbidity based on the assistance of the trainee,” he said. In addition, the improved visualization of robotics “allows for better appreciation of scarred tissue planes and more precise suturing,” he noted.

Overall, “one of the values of the robotic platform is shortening the learning curve,” Dr. Afaneh said. He reviewed data from his fellows and himself, and found no difference in operative times. “My mentee was able to achieve operative times as good as my third year in practice. The robotic platform shaved off several years of learning experience,” he said. Dr. Afaneh’s operative times also decreased with robotics, which shows how experienced surgeons learn from this technology, he said.

Dr. Afaneh disclosed serving as a consultant for Intuitive Surgical.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Use of a robotics platform provides a surgeon with more information so they can make better decisions, especially in challenging situations of primary and revisional bariatric surgery, according to Cheguevara Afaneh, MD, of New York–Presbyterian Hospital and Weill Cornell Medical Center, New York.

“The value of modern technology is to be able to do the most difficult cases in a much simpler format,” he said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium by Global Academy for Medical Education.

Dr. Afaneh shared examples of how robotic assistance can help surgeons address challenges in bariatric surgery clinical practice, including managing super- and super-super-obese patients, dealing with gastroesophageal reflux disease (GERD), and negating the impact of surgical assistant experience.

“Super-obese patients pose more of a challenge interoperatively for both the surgeon and the assistant,” Dr. Afaneh noted. He and colleagues conducted a study of perioperative outcomes and found no significant differences between morbidly obese and super-obese patients in perioperative morbidity or operating time when a robotic platform was used.

The benefits to the surgeon when using robotic assistance in super-obese patients include effortless navigation of the abdominal wall, the ability to execute complex maneuvers in a challenging environment, and the security of a stable platform with no assistant fatigue, Dr. Afaneh emphasized. “When you are using the robotic platform, you are negating a lot of the patient factors” and fatigue factors that make bariatric surgery in super-obese and super-super-obese patients especially difficult, he said.

For example, in a patient who weighed nearly 500 pounds, pulling up on the stomach to get behind the actual stomach is easier because assistant fatigue is not a factor, so the surgeon can take more time and prevent a more difficult dissection, he said. In addition, Dr. Afaneh’s research showed no difference in operative time, and that the robot assistance outcomes were reproducible across a range of body mass index categories.

Robotic assistance also allows for comparable outcomes in surgeons with less experience, notably in revisional surgery, said Dr. Afaneh. He reviewed data from his first year of experience in revisional procedures using robotic assistance to his partners’ more than 20 years of laparoscopic experience. He found no significant differences in operative time, complications, or conversions to open procedures.

However, the more important message from the study was that less experienced surgeons were able to safely perform some of the most difficult revisional procedures without increasing morbidity, compared with more experienced surgeons. The data suggest that, with robotic assistance, surgeons early in their career can take on some of the bigger cases and expect outcomes similar to those of more experienced surgeons, Dr. Afaneh said.

Robotics has demonstrated improved outcomes in managing patients with GERD, which has become a common problem after bariatric surgery, noted Dr. Afaneh. When he and his colleagues reviewed data from their center on robotic-assisted approaches to GERD after bariatric surgery, they found that, even in primary magnetic sphincter operations, “robotics maintains comparable outcomes in revisional sleeve gastrectomy fields,” he said.

Another notable benefit of robotics in bariatric surgery is the negation of the “assistant effect,” said Dr. Afaneh. Often, less experienced surgeons are matched with less experienced assistants. “We took a look at the use of the robotic in cases of complex GI surgeries,” he said. They compared laparoscopic and robotic cases and stratified them by third-year assistant or fellow. “If you had a fellow, the operative time dropped by half an hour for laparoscopic cases, but the time was no different in robotics cases,” regardless of the use of fellow or third-year assistant, he said.

“The robotic platform allows you to assist yourself,” and allows for full surgeon autonomy, Dr. Afaneh emphasized. “You are the best person at predicting your next step.” The robotics platform also serves as a teaching tool. “For those who teach, there is no added morbidity based on the assistance of the trainee,” he said. In addition, the improved visualization of robotics “allows for better appreciation of scarred tissue planes and more precise suturing,” he noted.

Overall, “one of the values of the robotic platform is shortening the learning curve,” Dr. Afaneh said. He reviewed data from his fellows and himself, and found no difference in operative times. “My mentee was able to achieve operative times as good as my third year in practice. The robotic platform shaved off several years of learning experience,” he said. Dr. Afaneh’s operative times also decreased with robotics, which shows how experienced surgeons learn from this technology, he said.

Dr. Afaneh disclosed serving as a consultant for Intuitive Surgical.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Use of a robotics platform provides a surgeon with more information so they can make better decisions, especially in challenging situations of primary and revisional bariatric surgery, according to Cheguevara Afaneh, MD, of New York–Presbyterian Hospital and Weill Cornell Medical Center, New York.

“The value of modern technology is to be able to do the most difficult cases in a much simpler format,” he said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium by Global Academy for Medical Education.

Dr. Afaneh shared examples of how robotic assistance can help surgeons address challenges in bariatric surgery clinical practice, including managing super- and super-super-obese patients, dealing with gastroesophageal reflux disease (GERD), and negating the impact of surgical assistant experience.

“Super-obese patients pose more of a challenge interoperatively for both the surgeon and the assistant,” Dr. Afaneh noted. He and colleagues conducted a study of perioperative outcomes and found no significant differences between morbidly obese and super-obese patients in perioperative morbidity or operating time when a robotic platform was used.

The benefits to the surgeon when using robotic assistance in super-obese patients include effortless navigation of the abdominal wall, the ability to execute complex maneuvers in a challenging environment, and the security of a stable platform with no assistant fatigue, Dr. Afaneh emphasized. “When you are using the robotic platform, you are negating a lot of the patient factors” and fatigue factors that make bariatric surgery in super-obese and super-super-obese patients especially difficult, he said.

For example, in a patient who weighed nearly 500 pounds, pulling up on the stomach to get behind the actual stomach is easier because assistant fatigue is not a factor, so the surgeon can take more time and prevent a more difficult dissection, he said. In addition, Dr. Afaneh’s research showed no difference in operative time, and that the robot assistance outcomes were reproducible across a range of body mass index categories.

Robotic assistance also allows for comparable outcomes in surgeons with less experience, notably in revisional surgery, said Dr. Afaneh. He reviewed data from his first year of experience in revisional procedures using robotic assistance to his partners’ more than 20 years of laparoscopic experience. He found no significant differences in operative time, complications, or conversions to open procedures.

However, the more important message from the study was that less experienced surgeons were able to safely perform some of the most difficult revisional procedures without increasing morbidity, compared with more experienced surgeons. The data suggest that, with robotic assistance, surgeons early in their career can take on some of the bigger cases and expect outcomes similar to those of more experienced surgeons, Dr. Afaneh said.

Robotics has demonstrated improved outcomes in managing patients with GERD, which has become a common problem after bariatric surgery, noted Dr. Afaneh. When he and his colleagues reviewed data from their center on robotic-assisted approaches to GERD after bariatric surgery, they found that, even in primary magnetic sphincter operations, “robotics maintains comparable outcomes in revisional sleeve gastrectomy fields,” he said.

Another notable benefit of robotics in bariatric surgery is the negation of the “assistant effect,” said Dr. Afaneh. Often, less experienced surgeons are matched with less experienced assistants. “We took a look at the use of the robotic in cases of complex GI surgeries,” he said. They compared laparoscopic and robotic cases and stratified them by third-year assistant or fellow. “If you had a fellow, the operative time dropped by half an hour for laparoscopic cases, but the time was no different in robotics cases,” regardless of the use of fellow or third-year assistant, he said.

“The robotic platform allows you to assist yourself,” and allows for full surgeon autonomy, Dr. Afaneh emphasized. “You are the best person at predicting your next step.” The robotics platform also serves as a teaching tool. “For those who teach, there is no added morbidity based on the assistance of the trainee,” he said. In addition, the improved visualization of robotics “allows for better appreciation of scarred tissue planes and more precise suturing,” he noted.

Overall, “one of the values of the robotic platform is shortening the learning curve,” Dr. Afaneh said. He reviewed data from his fellows and himself, and found no difference in operative times. “My mentee was able to achieve operative times as good as my third year in practice. The robotic platform shaved off several years of learning experience,” he said. Dr. Afaneh’s operative times also decreased with robotics, which shows how experienced surgeons learn from this technology, he said.

Dr. Afaneh disclosed serving as a consultant for Intuitive Surgical.

Global Academy for Medical Education and this news organization are owned by the same parent company.

COVID-19 patients with an underlying condition are 6 times as likely to be hospitalized and 12 times as likely to die, compared with those who have no such condition, according to the Centers for Disease Control and Prevention.

Among those with underlying conditions such as cardiovascular disease or diabetes, 45.4% of patients with COVID-19 were hospitalized, versus 7.6% of patients without an underlying condition, said Erin K. Stokes, MPH, and associates of the CDC COVID-19 Emergency Response team.

The difference in deaths was even greater over the study period of Jan. 22–May 30, 2020: 19.5% of COVID-19 patients with underlying conditions died, compared with 1.6% of those with no underlying condition. The gap narrowed, however, for ICU admissions, with corresponding rates of 8.5% and 1.5%, the investigators reported June 15 in the Morbidity and Mortality Weekly Report.

“The COVID-19 pandemic continues to be severe, particularly in certain population groups,” they said.

The cumulative incidence of laboratory-confirmed cases up to May 30, for instance, was nearly twice as high for those aged 80 years and over (902 per 100,000 population) than for those aged 70-79 years (464.2 per 100,000). Those aged 50-59 years had the second-highest incidence, 550.5 per 100,000, Ms. Stokes and associates said.

“Among cases with known race and ethnicity, 33% of persons were Hispanic, 22% were black, and 1.3% were [American Indian/Alaska Native]. These findings suggest that persons in these groups, who account for 18%, 13%, and 0.7% of the U.S. population, respectively, are disproportionately affected by the COVID-19 pandemic,” they wrote.

Another source of disparity: “Incidence among males and females was similar overall, [but] severe outcomes were more commonly reported among males,” the investigators noted. Cumulative incidence was 401.1 per 100,000 for males and 406.0 for females, but 6.0% of male patients died, compared with 4.8% of females.

As of May 30, a total of 1,761,503 cases and 103,700 deaths had been reported to the CDC. Of those cases, approximately 1.3 million were included in the analysis, with data on individual underlying health conditions available for 287,320 (22%). The split on those cases was 198,879 with health conditions and 88,411 without, the CDC data show.

The most frequently reported underlying conditions were cardiovascular disease (32%), diabetes (30%), chronic lung disease (18%), and renal disease (7.6%), and there were no significant differences between males and females, Ms. Stokes and associates said.

The pandemic “is an ongoing public health crisis in the United States that continues to affect all populations and result in severe outcomes including death,” they said, emphasizing “the continued need for community mitigation strategies, especially for vulnerable populations, to slow COVID-19 transmission.”

[email protected]

SOURCE: Stokes EK et al. MMWR. 2020 Jun 15;69(early release):1-7.

COVID-19 patients with an underlying condition are 6 times as likely to be hospitalized and 12 times as likely to die, compared with those who have no such condition, according to the Centers for Disease Control and Prevention.

Among those with underlying conditions such as cardiovascular disease or diabetes, 45.4% of patients with COVID-19 were hospitalized, versus 7.6% of patients without an underlying condition, said Erin K. Stokes, MPH, and associates of the CDC COVID-19 Emergency Response team.

The difference in deaths was even greater over the study period of Jan. 22–May 30, 2020: 19.5% of COVID-19 patients with underlying conditions died, compared with 1.6% of those with no underlying condition. The gap narrowed, however, for ICU admissions, with corresponding rates of 8.5% and 1.5%, the investigators reported June 15 in the Morbidity and Mortality Weekly Report.

“The COVID-19 pandemic continues to be severe, particularly in certain population groups,” they said.

The cumulative incidence of laboratory-confirmed cases up to May 30, for instance, was nearly twice as high for those aged 80 years and over (902 per 100,000 population) than for those aged 70-79 years (464.2 per 100,000). Those aged 50-59 years had the second-highest incidence, 550.5 per 100,000, Ms. Stokes and associates said.

“Among cases with known race and ethnicity, 33% of persons were Hispanic, 22% were black, and 1.3% were [American Indian/Alaska Native]. These findings suggest that persons in these groups, who account for 18%, 13%, and 0.7% of the U.S. population, respectively, are disproportionately affected by the COVID-19 pandemic,” they wrote.

Another source of disparity: “Incidence among males and females was similar overall, [but] severe outcomes were more commonly reported among males,” the investigators noted. Cumulative incidence was 401.1 per 100,000 for males and 406.0 for females, but 6.0% of male patients died, compared with 4.8% of females.

As of May 30, a total of 1,761,503 cases and 103,700 deaths had been reported to the CDC. Of those cases, approximately 1.3 million were included in the analysis, with data on individual underlying health conditions available for 287,320 (22%). The split on those cases was 198,879 with health conditions and 88,411 without, the CDC data show.

The most frequently reported underlying conditions were cardiovascular disease (32%), diabetes (30%), chronic lung disease (18%), and renal disease (7.6%), and there were no significant differences between males and females, Ms. Stokes and associates said.

The pandemic “is an ongoing public health crisis in the United States that continues to affect all populations and result in severe outcomes including death,” they said, emphasizing “the continued need for community mitigation strategies, especially for vulnerable populations, to slow COVID-19 transmission.”

[email protected]

SOURCE: Stokes EK et al. MMWR. 2020 Jun 15;69(early release):1-7.

COVID-19 patients with an underlying condition are 6 times as likely to be hospitalized and 12 times as likely to die, compared with those who have no such condition, according to the Centers for Disease Control and Prevention.

Among those with underlying conditions such as cardiovascular disease or diabetes, 45.4% of patients with COVID-19 were hospitalized, versus 7.6% of patients without an underlying condition, said Erin K. Stokes, MPH, and associates of the CDC COVID-19 Emergency Response team.

The difference in deaths was even greater over the study period of Jan. 22–May 30, 2020: 19.5% of COVID-19 patients with underlying conditions died, compared with 1.6% of those with no underlying condition. The gap narrowed, however, for ICU admissions, with corresponding rates of 8.5% and 1.5%, the investigators reported June 15 in the Morbidity and Mortality Weekly Report.

“The COVID-19 pandemic continues to be severe, particularly in certain population groups,” they said.

The cumulative incidence of laboratory-confirmed cases up to May 30, for instance, was nearly twice as high for those aged 80 years and over (902 per 100,000 population) than for those aged 70-79 years (464.2 per 100,000). Those aged 50-59 years had the second-highest incidence, 550.5 per 100,000, Ms. Stokes and associates said.

“Among cases with known race and ethnicity, 33% of persons were Hispanic, 22% were black, and 1.3% were [American Indian/Alaska Native]. These findings suggest that persons in these groups, who account for 18%, 13%, and 0.7% of the U.S. population, respectively, are disproportionately affected by the COVID-19 pandemic,” they wrote.

Another source of disparity: “Incidence among males and females was similar overall, [but] severe outcomes were more commonly reported among males,” the investigators noted. Cumulative incidence was 401.1 per 100,000 for males and 406.0 for females, but 6.0% of male patients died, compared with 4.8% of females.

As of May 30, a total of 1,761,503 cases and 103,700 deaths had been reported to the CDC. Of those cases, approximately 1.3 million were included in the analysis, with data on individual underlying health conditions available for 287,320 (22%). The split on those cases was 198,879 with health conditions and 88,411 without, the CDC data show.

The most frequently reported underlying conditions were cardiovascular disease (32%), diabetes (30%), chronic lung disease (18%), and renal disease (7.6%), and there were no significant differences between males and females, Ms. Stokes and associates said.

The pandemic “is an ongoing public health crisis in the United States that continues to affect all populations and result in severe outcomes including death,” they said, emphasizing “the continued need for community mitigation strategies, especially for vulnerable populations, to slow COVID-19 transmission.”

[email protected]

SOURCE: Stokes EK et al. MMWR. 2020 Jun 15;69(early release):1-7.

Patients who underwent conversion to a laparoscopic sleeve gastrectomy after a previous laparoscopic adjustable gastric banding procedure experienced similar weight loss with either a one- or two-step procedure, a study of 78 patients showed.

“Laparoscopic adjustable gastric banding (LAGB) has largely fallen out of favor, likely related to variable efficacy in weight reduction coupled with poor effectiveness in reducing obesity related comorbidities like type 2 diabetes and hypercholesterolemia,” Vasu Chirumamilla, MD, of Westchester Medical Center, Valhalla, N.Y., and colleagues wrote in a poster presented at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

LAGB also can cause complications including, slippage, erosion, and gastric pouch dilation; subsequently many patients undergo conversion to laparoscopic sleeve gastrectomy (LSG). However, the impact of a one-step vs. two-step conversion procedure on patient weight loss remains unclear, the researchers said.

To compare weight loss after the two types of procedures, the researchers reviewed data from 78 patients (71 women) aged 15-74 years treated between 2013 and 2018 at a multi-surgeon, private practice bariatric surgery center. All patients had a history of LAGB; 31 underwent conversion to LSG in one stage, and 47 underwent conversion in two stages. Weight loss, defined as the percentage excess weight loss, was the primary endpoint.

The average excess weight loss was 44% for patients in both the one-stage and two-stage groups, and body mass index decreased by 8.9 points and 8.8 points, respectively, in the two groups, the researchers wrote.

Patients in the two-stage group experienced a significant increase in body mass index (P = .008) during the time between band removal to sleeve gastrectomy, which was an average of 207 days, they said.

The findings were limited in part by the small sample size and retrospective design, and more data are needed to compare complication rates in one-stage and two-stage procedures, the researchers noted. However, the results showed “no difference in excess weight loss in patients converted from laparoscopic adjustable gastric band to sleeve gastrectomy in one-stage versus a two-stage procedure,” they concluded.

“LAGB used to be a very popular weight loss procedure – bands were placed in a great deal of patients,” Dr. Chirumamilla said in an interview. “Now those patients are presenting with increasing frequency to bariatric surgeons with band complications or weight regain. The volume for LSG is increasing and results in percentage excess weight loss of approximately 65% versus approximately 42% for LAGB,” he said. A goal of the study was to provide patients and the surgeons with a more informed approach to performing and consenting to the particular operation, he added.

“The results have not surprised us, because as long as done by experienced surgeons on compliant patients the weight loss outcomes from the day of surgery onward should be equivalent,” Dr. Chirumamilla explained. “We were also not surprised to find that patients undergoing a two-stage conversion gained weight before their second-stage sleeve gastrectomy.”

The bottom line for clinicians is that “patients getting a conversion from band to sleeve in one-stage versus two-stages experience the same percentage excess body weight loss from time of surgery,” although two-stage patients do gain weight while awaiting their second-stage sleeve gastrectomy, Dr. Chirumamilla said.

“More research is needed to compare short- and long-term complications rates between one-stage and two-stage conversions. The ideal research situation would be a randomized, multicenter, large volume study to reduce bias,” he noted.

Dr. Chirumamilla’s collaborators included Akia Caine MD, Zachary Ballinger, Rebecca Castro, Thomas Cerabona MD, and Ashutosh Kaul MD, of the surgical group Advanced Surgeons at nygetfit.com.

Global Academy for Medical Education and this news organization are owned by the same parent company. The study received no outside funding. The researchers had no financial conflicts to disclose.
 

SOURCE: Chirumamilla V et al. MISS 2020. Poster PA-14.

Patients who underwent conversion to a laparoscopic sleeve gastrectomy after a previous laparoscopic adjustable gastric banding procedure experienced similar weight loss with either a one- or two-step procedure, a study of 78 patients showed.

“Laparoscopic adjustable gastric banding (LAGB) has largely fallen out of favor, likely related to variable efficacy in weight reduction coupled with poor effectiveness in reducing obesity related comorbidities like type 2 diabetes and hypercholesterolemia,” Vasu Chirumamilla, MD, of Westchester Medical Center, Valhalla, N.Y., and colleagues wrote in a poster presented at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

LAGB also can cause complications including, slippage, erosion, and gastric pouch dilation; subsequently many patients undergo conversion to laparoscopic sleeve gastrectomy (LSG). However, the impact of a one-step vs. two-step conversion procedure on patient weight loss remains unclear, the researchers said.

To compare weight loss after the two types of procedures, the researchers reviewed data from 78 patients (71 women) aged 15-74 years treated between 2013 and 2018 at a multi-surgeon, private practice bariatric surgery center. All patients had a history of LAGB; 31 underwent conversion to LSG in one stage, and 47 underwent conversion in two stages. Weight loss, defined as the percentage excess weight loss, was the primary endpoint.

The average excess weight loss was 44% for patients in both the one-stage and two-stage groups, and body mass index decreased by 8.9 points and 8.8 points, respectively, in the two groups, the researchers wrote.

Patients in the two-stage group experienced a significant increase in body mass index (P = .008) during the time between band removal to sleeve gastrectomy, which was an average of 207 days, they said.

The findings were limited in part by the small sample size and retrospective design, and more data are needed to compare complication rates in one-stage and two-stage procedures, the researchers noted. However, the results showed “no difference in excess weight loss in patients converted from laparoscopic adjustable gastric band to sleeve gastrectomy in one-stage versus a two-stage procedure,” they concluded.

“LAGB used to be a very popular weight loss procedure – bands were placed in a great deal of patients,” Dr. Chirumamilla said in an interview. “Now those patients are presenting with increasing frequency to bariatric surgeons with band complications or weight regain. The volume for LSG is increasing and results in percentage excess weight loss of approximately 65% versus approximately 42% for LAGB,” he said. A goal of the study was to provide patients and the surgeons with a more informed approach to performing and consenting to the particular operation, he added.

“The results have not surprised us, because as long as done by experienced surgeons on compliant patients the weight loss outcomes from the day of surgery onward should be equivalent,” Dr. Chirumamilla explained. “We were also not surprised to find that patients undergoing a two-stage conversion gained weight before their second-stage sleeve gastrectomy.”

The bottom line for clinicians is that “patients getting a conversion from band to sleeve in one-stage versus two-stages experience the same percentage excess body weight loss from time of surgery,” although two-stage patients do gain weight while awaiting their second-stage sleeve gastrectomy, Dr. Chirumamilla said.

“More research is needed to compare short- and long-term complications rates between one-stage and two-stage conversions. The ideal research situation would be a randomized, multicenter, large volume study to reduce bias,” he noted.

Dr. Chirumamilla’s collaborators included Akia Caine MD, Zachary Ballinger, Rebecca Castro, Thomas Cerabona MD, and Ashutosh Kaul MD, of the surgical group Advanced Surgeons at nygetfit.com.

Global Academy for Medical Education and this news organization are owned by the same parent company. The study received no outside funding. The researchers had no financial conflicts to disclose.
 

SOURCE: Chirumamilla V et al. MISS 2020. Poster PA-14.

Patients who underwent conversion to a laparoscopic sleeve gastrectomy after a previous laparoscopic adjustable gastric banding procedure experienced similar weight loss with either a one- or two-step procedure, a study of 78 patients showed.

“Laparoscopic adjustable gastric banding (LAGB) has largely fallen out of favor, likely related to variable efficacy in weight reduction coupled with poor effectiveness in reducing obesity related comorbidities like type 2 diabetes and hypercholesterolemia,” Vasu Chirumamilla, MD, of Westchester Medical Center, Valhalla, N.Y., and colleagues wrote in a poster presented at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

LAGB also can cause complications including, slippage, erosion, and gastric pouch dilation; subsequently many patients undergo conversion to laparoscopic sleeve gastrectomy (LSG). However, the impact of a one-step vs. two-step conversion procedure on patient weight loss remains unclear, the researchers said.

To compare weight loss after the two types of procedures, the researchers reviewed data from 78 patients (71 women) aged 15-74 years treated between 2013 and 2018 at a multi-surgeon, private practice bariatric surgery center. All patients had a history of LAGB; 31 underwent conversion to LSG in one stage, and 47 underwent conversion in two stages. Weight loss, defined as the percentage excess weight loss, was the primary endpoint.

The average excess weight loss was 44% for patients in both the one-stage and two-stage groups, and body mass index decreased by 8.9 points and 8.8 points, respectively, in the two groups, the researchers wrote.

Patients in the two-stage group experienced a significant increase in body mass index (P = .008) during the time between band removal to sleeve gastrectomy, which was an average of 207 days, they said.

The findings were limited in part by the small sample size and retrospective design, and more data are needed to compare complication rates in one-stage and two-stage procedures, the researchers noted. However, the results showed “no difference in excess weight loss in patients converted from laparoscopic adjustable gastric band to sleeve gastrectomy in one-stage versus a two-stage procedure,” they concluded.

“LAGB used to be a very popular weight loss procedure – bands were placed in a great deal of patients,” Dr. Chirumamilla said in an interview. “Now those patients are presenting with increasing frequency to bariatric surgeons with band complications or weight regain. The volume for LSG is increasing and results in percentage excess weight loss of approximately 65% versus approximately 42% for LAGB,” he said. A goal of the study was to provide patients and the surgeons with a more informed approach to performing and consenting to the particular operation, he added.

“The results have not surprised us, because as long as done by experienced surgeons on compliant patients the weight loss outcomes from the day of surgery onward should be equivalent,” Dr. Chirumamilla explained. “We were also not surprised to find that patients undergoing a two-stage conversion gained weight before their second-stage sleeve gastrectomy.”

The bottom line for clinicians is that “patients getting a conversion from band to sleeve in one-stage versus two-stages experience the same percentage excess body weight loss from time of surgery,” although two-stage patients do gain weight while awaiting their second-stage sleeve gastrectomy, Dr. Chirumamilla said.

“More research is needed to compare short- and long-term complications rates between one-stage and two-stage conversions. The ideal research situation would be a randomized, multicenter, large volume study to reduce bias,” he noted.

Dr. Chirumamilla’s collaborators included Akia Caine MD, Zachary Ballinger, Rebecca Castro, Thomas Cerabona MD, and Ashutosh Kaul MD, of the surgical group Advanced Surgeons at nygetfit.com.

Global Academy for Medical Education and this news organization are owned by the same parent company. The study received no outside funding. The researchers had no financial conflicts to disclose.
 

SOURCE: Chirumamilla V et al. MISS 2020. Poster PA-14.

Preliminary results from a population-based cohort study support previous reports that migraine is a midlife risk factor for dementia later in life, but further determined that migraine with aura and frequent hospital contacts significantly increased dementia risk after age 60 years, according to results from a Danish registry presented at the virtual annual meeting of the American Headache Society.

“The findings of this study emphasize the need for studies in the migraine-dementia pathophysiology, in particular in migraine cases with aura,” said Sabrina Islamoska, MSc, PhD, a postdoctoral researcher in the department of public health at the University of Copenhagen. “This study highlights the importance of monitoring severe migraine to potentially prevent dementia.”
 

A national register-based study

The study used Danish national register–based data from 1988 to 2017 of 1.66 million individuals born between 1935 and 1956, retrieving exposure information until age 59 years and following individuals for dementia after age 60. The matched analysis included 18,135 people registered with migraine before age 59 and 1.38 million without migraine. The matched study population was 62,578.

A diagnosis of dementia or use of dementia medications after age 60 years was the main outcome. Covariates included socioeconomic factors, psychiatric comorbidities and other headache diagnoses.

“To the best of our knowledge, no previous national register–based studies have investigated the risk of dementia among individuals who suffer from migraine with aura,” Dr. Islamoska said.

The preliminary findings revealed that the median age at diagnosis was 49 years and about 70% of the migraine population were women. “There was a 50% higher dementia rate in individuals who had any migraine diagnosis,” Dr. Islamoska said.

“We also found a 20% higher but nonsignificant dementia rate in individuals who had migraine without aura,” she said. However, when the migraine-with-aura population was evaluated, it was found to have a dementia rate two times higher than people with no migraine. “The dementia rate was higher if individuals had more frequent hospital contacts with migraine.”

The findings support the hypothesis that migraine is a midlife risk factor for dementia later in life, she said.

“The findings underline the value of investigating the effect of migraine medications in dementia risk to assess the impact of mild to moderate migraines,” Dr. Islamoska said. “Therefore, the next step is to investigate the risk of dementia among users of migraine medications who are not diagnosed with migraines at hospitals.”

Strengths of the study, Dr. Islamoska noted, were its size and national nature of its population, that it included all migraine diagnoses at hospitals over a 29-year period, that it made adjustments for confounding of well-established dementia risk factors, and that it validated dementia diagnoses after age 60 years.

One limitation was that the study only included hospital-based diagnoses of dementia while 60% of cases in Denmark are undiagnosed, “thus our results only apply to migraine that is severe enough to require a hospital contact,” Dr. Islamoska said, while most migraine cases are treated in the primary care setting.

Also, the young study population may have a lower dementia risk. “We also know that age of migraine registration may not corresponded with the actual onset, since migraine is a complex disorder with individual variation in patient’s burden and course of disease,” Dr. Islamoska said.

“Future studies are needed to understand the pathological mechanisms underlying the relationship between migraine and dementia and to investigate whether proper prophylactic treatment of migraine can potentially prevent dementia,” Dr. Islamoska said. “In addition, when investigating the association between these two prevalent neurological disorders, the timing of migraine diagnosis and dementia onset is important to ensure temporality. We took this into account in our study to strengthen the validity of our results.”
 

‘Surprising’ findings

Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles, said the Danish study makes an important contribution to the literature on dementia risk factors. “Vanishingly small amounts of attention have been paid to migraine as a potential risk factor,” he said. However, he called the results “surprising” based on his own clinical experience. “I actually had a sense that migraine was somehow protective against Alzheimer’s or other kinds of dementias.”

He questioned if the migraine-dementia link could be a “reporting artifact” of migraine sufferers merely going to the neurologist, raising the likelihood of a positive migraine diagnosis. Nonetheless, the results are “intriguing” and raise important questions about migraine therapy and dementia risk.

“If it holds up, it really is something that behooves us to understand whether intervening in terms of therapy for migraine has even more consequences beyond just the immediate relief of symptoms,” Dr. Charles said. “It’s something we should be thinking about in terms of preventing longer-term consequences of this disorder.”

Dr. Islamoska disclosed that Veluxfondent funded the study as part of her PhD project. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.

SOURCE: Islamoska S et al. AHS 2020, Submission 846214.

Preliminary results from a population-based cohort study support previous reports that migraine is a midlife risk factor for dementia later in life, but further determined that migraine with aura and frequent hospital contacts significantly increased dementia risk after age 60 years, according to results from a Danish registry presented at the virtual annual meeting of the American Headache Society.

“The findings of this study emphasize the need for studies in the migraine-dementia pathophysiology, in particular in migraine cases with aura,” said Sabrina Islamoska, MSc, PhD, a postdoctoral researcher in the department of public health at the University of Copenhagen. “This study highlights the importance of monitoring severe migraine to potentially prevent dementia.”
 

A national register-based study

The study used Danish national register–based data from 1988 to 2017 of 1.66 million individuals born between 1935 and 1956, retrieving exposure information until age 59 years and following individuals for dementia after age 60. The matched analysis included 18,135 people registered with migraine before age 59 and 1.38 million without migraine. The matched study population was 62,578.

A diagnosis of dementia or use of dementia medications after age 60 years was the main outcome. Covariates included socioeconomic factors, psychiatric comorbidities and other headache diagnoses.

“To the best of our knowledge, no previous national register–based studies have investigated the risk of dementia among individuals who suffer from migraine with aura,” Dr. Islamoska said.

The preliminary findings revealed that the median age at diagnosis was 49 years and about 70% of the migraine population were women. “There was a 50% higher dementia rate in individuals who had any migraine diagnosis,” Dr. Islamoska said.

“We also found a 20% higher but nonsignificant dementia rate in individuals who had migraine without aura,” she said. However, when the migraine-with-aura population was evaluated, it was found to have a dementia rate two times higher than people with no migraine. “The dementia rate was higher if individuals had more frequent hospital contacts with migraine.”

The findings support the hypothesis that migraine is a midlife risk factor for dementia later in life, she said.

“The findings underline the value of investigating the effect of migraine medications in dementia risk to assess the impact of mild to moderate migraines,” Dr. Islamoska said. “Therefore, the next step is to investigate the risk of dementia among users of migraine medications who are not diagnosed with migraines at hospitals.”

Strengths of the study, Dr. Islamoska noted, were its size and national nature of its population, that it included all migraine diagnoses at hospitals over a 29-year period, that it made adjustments for confounding of well-established dementia risk factors, and that it validated dementia diagnoses after age 60 years.

One limitation was that the study only included hospital-based diagnoses of dementia while 60% of cases in Denmark are undiagnosed, “thus our results only apply to migraine that is severe enough to require a hospital contact,” Dr. Islamoska said, while most migraine cases are treated in the primary care setting.

Also, the young study population may have a lower dementia risk. “We also know that age of migraine registration may not corresponded with the actual onset, since migraine is a complex disorder with individual variation in patient’s burden and course of disease,” Dr. Islamoska said.

“Future studies are needed to understand the pathological mechanisms underlying the relationship between migraine and dementia and to investigate whether proper prophylactic treatment of migraine can potentially prevent dementia,” Dr. Islamoska said. “In addition, when investigating the association between these two prevalent neurological disorders, the timing of migraine diagnosis and dementia onset is important to ensure temporality. We took this into account in our study to strengthen the validity of our results.”
 

‘Surprising’ findings

Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles, said the Danish study makes an important contribution to the literature on dementia risk factors. “Vanishingly small amounts of attention have been paid to migraine as a potential risk factor,” he said. However, he called the results “surprising” based on his own clinical experience. “I actually had a sense that migraine was somehow protective against Alzheimer’s or other kinds of dementias.”

He questioned if the migraine-dementia link could be a “reporting artifact” of migraine sufferers merely going to the neurologist, raising the likelihood of a positive migraine diagnosis. Nonetheless, the results are “intriguing” and raise important questions about migraine therapy and dementia risk.

“If it holds up, it really is something that behooves us to understand whether intervening in terms of therapy for migraine has even more consequences beyond just the immediate relief of symptoms,” Dr. Charles said. “It’s something we should be thinking about in terms of preventing longer-term consequences of this disorder.”

Dr. Islamoska disclosed that Veluxfondent funded the study as part of her PhD project. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.

SOURCE: Islamoska S et al. AHS 2020, Submission 846214.

Preliminary results from a population-based cohort study support previous reports that migraine is a midlife risk factor for dementia later in life, but further determined that migraine with aura and frequent hospital contacts significantly increased dementia risk after age 60 years, according to results from a Danish registry presented at the virtual annual meeting of the American Headache Society.

“The findings of this study emphasize the need for studies in the migraine-dementia pathophysiology, in particular in migraine cases with aura,” said Sabrina Islamoska, MSc, PhD, a postdoctoral researcher in the department of public health at the University of Copenhagen. “This study highlights the importance of monitoring severe migraine to potentially prevent dementia.”
 

A national register-based study

The study used Danish national register–based data from 1988 to 2017 of 1.66 million individuals born between 1935 and 1956, retrieving exposure information until age 59 years and following individuals for dementia after age 60. The matched analysis included 18,135 people registered with migraine before age 59 and 1.38 million without migraine. The matched study population was 62,578.

A diagnosis of dementia or use of dementia medications after age 60 years was the main outcome. Covariates included socioeconomic factors, psychiatric comorbidities and other headache diagnoses.

“To the best of our knowledge, no previous national register–based studies have investigated the risk of dementia among individuals who suffer from migraine with aura,” Dr. Islamoska said.

The preliminary findings revealed that the median age at diagnosis was 49 years and about 70% of the migraine population were women. “There was a 50% higher dementia rate in individuals who had any migraine diagnosis,” Dr. Islamoska said.

“We also found a 20% higher but nonsignificant dementia rate in individuals who had migraine without aura,” she said. However, when the migraine-with-aura population was evaluated, it was found to have a dementia rate two times higher than people with no migraine. “The dementia rate was higher if individuals had more frequent hospital contacts with migraine.”

The findings support the hypothesis that migraine is a midlife risk factor for dementia later in life, she said.

“The findings underline the value of investigating the effect of migraine medications in dementia risk to assess the impact of mild to moderate migraines,” Dr. Islamoska said. “Therefore, the next step is to investigate the risk of dementia among users of migraine medications who are not diagnosed with migraines at hospitals.”

Strengths of the study, Dr. Islamoska noted, were its size and national nature of its population, that it included all migraine diagnoses at hospitals over a 29-year period, that it made adjustments for confounding of well-established dementia risk factors, and that it validated dementia diagnoses after age 60 years.

One limitation was that the study only included hospital-based diagnoses of dementia while 60% of cases in Denmark are undiagnosed, “thus our results only apply to migraine that is severe enough to require a hospital contact,” Dr. Islamoska said, while most migraine cases are treated in the primary care setting.

Also, the young study population may have a lower dementia risk. “We also know that age of migraine registration may not corresponded with the actual onset, since migraine is a complex disorder with individual variation in patient’s burden and course of disease,” Dr. Islamoska said.

“Future studies are needed to understand the pathological mechanisms underlying the relationship between migraine and dementia and to investigate whether proper prophylactic treatment of migraine can potentially prevent dementia,” Dr. Islamoska said. “In addition, when investigating the association between these two prevalent neurological disorders, the timing of migraine diagnosis and dementia onset is important to ensure temporality. We took this into account in our study to strengthen the validity of our results.”
 

‘Surprising’ findings

Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles, said the Danish study makes an important contribution to the literature on dementia risk factors. “Vanishingly small amounts of attention have been paid to migraine as a potential risk factor,” he said. However, he called the results “surprising” based on his own clinical experience. “I actually had a sense that migraine was somehow protective against Alzheimer’s or other kinds of dementias.”

He questioned if the migraine-dementia link could be a “reporting artifact” of migraine sufferers merely going to the neurologist, raising the likelihood of a positive migraine diagnosis. Nonetheless, the results are “intriguing” and raise important questions about migraine therapy and dementia risk.

“If it holds up, it really is something that behooves us to understand whether intervening in terms of therapy for migraine has even more consequences beyond just the immediate relief of symptoms,” Dr. Charles said. “It’s something we should be thinking about in terms of preventing longer-term consequences of this disorder.”

Dr. Islamoska disclosed that Veluxfondent funded the study as part of her PhD project. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.

SOURCE: Islamoska S et al. AHS 2020, Submission 846214.

Hematopoietic stem cell transplantation (HSCT) may offer the chance of a cure for patients with leukemia and other blood cancers, but the process of preparing the body to receive such a transplant can be brutal, involving whole body irradiation as well as chemotherapy conditioning. New results show that both steps are needed: a trial that omitted whole body irradiation in young patients with acute lymphoblastic leukemia (ALL) was stopped early because of significantly poorer outcomes.

The multicenter, global FORUM (For Omitting Radiation Under Majority Age) trial involved 75 centers in 17 countries between 2013 and 2018.

“Our study shows significantly better outcomes for total body irradiation compared to myeloablative chemo-conditioning arms, with no differences between the [two] chemo-conditioning groups,” concluded Christina Peters, MD, professor of pediatrics in the department of stem cell transplantation at St Anna Children’s Hospital in Vienna.

The findings in favor of total body irradiation were pronounced enough that the study was halted early by a safety committee, she added.

Dr. Peters presented the findings as part of the virtual annual congress of the European Hematology Association.

Describing the results as “sobering,” session comoderator Shai Izraeli, MD, director of the department of hematology-oncology at Schneider Children’s Medical Center, in Petah Tikva, Israel, said an online comment from the virtual meeting audience reflected the reaction to these unwelcome results: “So we are still stuck with total body irradiation?”

Dr. Peters said the good news is that the number of patients needing to undergo stem cell transplants is low, and with research advances, may hopefully drop even further.

“Only 10% of patients under the age of 18 nowadays undergo allogeneic HSCT, and perhaps in the future that will become even less if we are able to rescue some of the groups with other immunological measures such as CAR-T cells and antibodies,” she said.

“I think it is very important to better identify those who really need total body irradiation in the future,” she added.

In an interview, Dr. Izraeli agreed.

“The prognosis of children after bone marrow transplantation is excellent – the majority are cured from their leukemia,” he said. “And we have to remember that those who undergo bone marrow transplant have the worst leukemias.”

He pointed out that, in fact, contemporary chemotherapy alone is effective in the treatment of more than 90% of patients with ALL younger than aged 18.

For the 10% of patients who do not respond to chemotherapy alone and undergo allogeneic HSCT, about 50%-80% of pediatric patients who have resistant leukemia are cured. However, the total body irradiation used to prepare the body to receive the transplant is linked to potentially serious consequences later in life, including sterility, lung problems, growth retardation, and secondary cancer.

To determine if the irradiation component could be safely replaced with a chemotherapy-based conditioning approach, Dr. Peters and colleagues conducted the FORUM trial.

In total 413 patients undergoing HSCT were enrolled and randomized to pretransplant conditioning with total body irradiation and etoposide (n = 202) or a chemotherapy-only approach with fludarabine/thiotepa/busulfan (flu/thio/bu; n = 99) or fludarabine/thiotepa/treosulfan (treo; n = 93).

Most patients (72%) had B-cell precursor ALL and 23% had T-cell ALL. Just over half (54%) were transplanted in first complete remission (CR1), 40% in CR2, and 4% in CR3.

The source of stem cells was bone marrow for most patients (82%); peripheral blood stem cell for 12%, and cord blood for 4%.
 

Study stopped early

The aim of the study was to demonstrate noninferiority with the chemotherapy approach.

However, the significantly inferior outcome observed in the chemotherapy-only group led to randomization being halted in March 2019.

The 2-year overall survival in the intent-to-treat (ITT) analysis, with a mean observation time of 2.1 years, was 0.75 ± 0.04 for chemo-conditioning versus 0.91 ± 0.02 for total body irradiation/etoposide (ITT P < .001).

The ITT analysis showed relapses were significantly higher in the chemo-conditioning group (2-year cumulative incidence of relapse [CIR], 0.33) compared with the total body irradiation group (CIR, 0.12; P < .001).

The 2-year event-free survival (EFS) rate was also significantly higher in the total body irradiation group (0.86 vs 0.58; P < .001), and transplant-related mortality over 2 years was lower with total body irradiation (0.02 vs 0.09; P = .02).

A per-protocol analysis showed the 2-year overall survival to be the same in the two chemotherapy groups (both 0.77 ± 0.05) compared with 0.91 ± 0.02 in the total body irradiation group (P = .003).

“In this cohort [the 91% overall survival rate] may even be lower than contemporary intensive frontline therapy results that are achieved nowadays,” Dr. Peters said.

In looking at subgroups, there were no significant differences according to age group or cancer phenotype, while MLL rearrangement was associated with higher relapse incidence.

Remission status was found to notably influence EFS, dropping from 0.91 in CR1 patients with total body irradiation to 0.76 in CR2 patients. However, total body irradiation remained significantly higher compared with the chemo-conditioning groups in CR1 (P = .004) and CR2 (P < .001).

Transplant-related mortality was not significantly different between the total body irradiation and chemo-conditioning groups in the CR1 or CR2 groups (P = .09 and P = .18, respectively), despite the significant difference when remission status was not included.

Overall, “we tried to identify subgroups in which total body irradiation might be eliminated, however in all analyses, total body irradiation was better than chemo-conditioning in all arms,” Dr. Peters said.

Meanwhile, the findings underscore that even when patients cannot receive total body irradiation, the alternative chemo-conditioning therapy in fact shows favorable efficacy on its own, Dr. Izraeli said.

“The prognosis of the chemotherapy group is also quite remarkably good, although less than the total body irradiation arm. This means that if for some reason total body irradiation cannot be given, the chemotherapy is a very reasonable alternative.”

Dr. Peters has reported relationships with Amgen, Novartis, Pfizer, Medac, Jazz, and Neovii. Dr. Izraeli has reported no relevant financial relationships.

SOURCE: EHA Congress. Abstract S102.

A version of this article originally appeared on Medscape.com.

Hematopoietic stem cell transplantation (HSCT) may offer the chance of a cure for patients with leukemia and other blood cancers, but the process of preparing the body to receive such a transplant can be brutal, involving whole body irradiation as well as chemotherapy conditioning. New results show that both steps are needed: a trial that omitted whole body irradiation in young patients with acute lymphoblastic leukemia (ALL) was stopped early because of significantly poorer outcomes.

The multicenter, global FORUM (For Omitting Radiation Under Majority Age) trial involved 75 centers in 17 countries between 2013 and 2018.

“Our study shows significantly better outcomes for total body irradiation compared to myeloablative chemo-conditioning arms, with no differences between the [two] chemo-conditioning groups,” concluded Christina Peters, MD, professor of pediatrics in the department of stem cell transplantation at St Anna Children’s Hospital in Vienna.

The findings in favor of total body irradiation were pronounced enough that the study was halted early by a safety committee, she added.

Dr. Peters presented the findings as part of the virtual annual congress of the European Hematology Association.

Describing the results as “sobering,” session comoderator Shai Izraeli, MD, director of the department of hematology-oncology at Schneider Children’s Medical Center, in Petah Tikva, Israel, said an online comment from the virtual meeting audience reflected the reaction to these unwelcome results: “So we are still stuck with total body irradiation?”

Dr. Peters said the good news is that the number of patients needing to undergo stem cell transplants is low, and with research advances, may hopefully drop even further.

“Only 10% of patients under the age of 18 nowadays undergo allogeneic HSCT, and perhaps in the future that will become even less if we are able to rescue some of the groups with other immunological measures such as CAR-T cells and antibodies,” she said.

“I think it is very important to better identify those who really need total body irradiation in the future,” she added.

In an interview, Dr. Izraeli agreed.

“The prognosis of children after bone marrow transplantation is excellent – the majority are cured from their leukemia,” he said. “And we have to remember that those who undergo bone marrow transplant have the worst leukemias.”

He pointed out that, in fact, contemporary chemotherapy alone is effective in the treatment of more than 90% of patients with ALL younger than aged 18.

For the 10% of patients who do not respond to chemotherapy alone and undergo allogeneic HSCT, about 50%-80% of pediatric patients who have resistant leukemia are cured. However, the total body irradiation used to prepare the body to receive the transplant is linked to potentially serious consequences later in life, including sterility, lung problems, growth retardation, and secondary cancer.

To determine if the irradiation component could be safely replaced with a chemotherapy-based conditioning approach, Dr. Peters and colleagues conducted the FORUM trial.

In total 413 patients undergoing HSCT were enrolled and randomized to pretransplant conditioning with total body irradiation and etoposide (n = 202) or a chemotherapy-only approach with fludarabine/thiotepa/busulfan (flu/thio/bu; n = 99) or fludarabine/thiotepa/treosulfan (treo; n = 93).

Most patients (72%) had B-cell precursor ALL and 23% had T-cell ALL. Just over half (54%) were transplanted in first complete remission (CR1), 40% in CR2, and 4% in CR3.

The source of stem cells was bone marrow for most patients (82%); peripheral blood stem cell for 12%, and cord blood for 4%.
 

Study stopped early

The aim of the study was to demonstrate noninferiority with the chemotherapy approach.

However, the significantly inferior outcome observed in the chemotherapy-only group led to randomization being halted in March 2019.

The 2-year overall survival in the intent-to-treat (ITT) analysis, with a mean observation time of 2.1 years, was 0.75 ± 0.04 for chemo-conditioning versus 0.91 ± 0.02 for total body irradiation/etoposide (ITT P < .001).

The ITT analysis showed relapses were significantly higher in the chemo-conditioning group (2-year cumulative incidence of relapse [CIR], 0.33) compared with the total body irradiation group (CIR, 0.12; P < .001).

The 2-year event-free survival (EFS) rate was also significantly higher in the total body irradiation group (0.86 vs 0.58; P < .001), and transplant-related mortality over 2 years was lower with total body irradiation (0.02 vs 0.09; P = .02).

A per-protocol analysis showed the 2-year overall survival to be the same in the two chemotherapy groups (both 0.77 ± 0.05) compared with 0.91 ± 0.02 in the total body irradiation group (P = .003).

“In this cohort [the 91% overall survival rate] may even be lower than contemporary intensive frontline therapy results that are achieved nowadays,” Dr. Peters said.

In looking at subgroups, there were no significant differences according to age group or cancer phenotype, while MLL rearrangement was associated with higher relapse incidence.

Remission status was found to notably influence EFS, dropping from 0.91 in CR1 patients with total body irradiation to 0.76 in CR2 patients. However, total body irradiation remained significantly higher compared with the chemo-conditioning groups in CR1 (P = .004) and CR2 (P < .001).

Transplant-related mortality was not significantly different between the total body irradiation and chemo-conditioning groups in the CR1 or CR2 groups (P = .09 and P = .18, respectively), despite the significant difference when remission status was not included.

Overall, “we tried to identify subgroups in which total body irradiation might be eliminated, however in all analyses, total body irradiation was better than chemo-conditioning in all arms,” Dr. Peters said.

Meanwhile, the findings underscore that even when patients cannot receive total body irradiation, the alternative chemo-conditioning therapy in fact shows favorable efficacy on its own, Dr. Izraeli said.

“The prognosis of the chemotherapy group is also quite remarkably good, although less than the total body irradiation arm. This means that if for some reason total body irradiation cannot be given, the chemotherapy is a very reasonable alternative.”

Dr. Peters has reported relationships with Amgen, Novartis, Pfizer, Medac, Jazz, and Neovii. Dr. Izraeli has reported no relevant financial relationships.

SOURCE: EHA Congress. Abstract S102.

A version of this article originally appeared on Medscape.com.

Hematopoietic stem cell transplantation (HSCT) may offer the chance of a cure for patients with leukemia and other blood cancers, but the process of preparing the body to receive such a transplant can be brutal, involving whole body irradiation as well as chemotherapy conditioning. New results show that both steps are needed: a trial that omitted whole body irradiation in young patients with acute lymphoblastic leukemia (ALL) was stopped early because of significantly poorer outcomes.

The multicenter, global FORUM (For Omitting Radiation Under Majority Age) trial involved 75 centers in 17 countries between 2013 and 2018.

“Our study shows significantly better outcomes for total body irradiation compared to myeloablative chemo-conditioning arms, with no differences between the [two] chemo-conditioning groups,” concluded Christina Peters, MD, professor of pediatrics in the department of stem cell transplantation at St Anna Children’s Hospital in Vienna.

The findings in favor of total body irradiation were pronounced enough that the study was halted early by a safety committee, she added.

Dr. Peters presented the findings as part of the virtual annual congress of the European Hematology Association.

Describing the results as “sobering,” session comoderator Shai Izraeli, MD, director of the department of hematology-oncology at Schneider Children’s Medical Center, in Petah Tikva, Israel, said an online comment from the virtual meeting audience reflected the reaction to these unwelcome results: “So we are still stuck with total body irradiation?”

Dr. Peters said the good news is that the number of patients needing to undergo stem cell transplants is low, and with research advances, may hopefully drop even further.

“Only 10% of patients under the age of 18 nowadays undergo allogeneic HSCT, and perhaps in the future that will become even less if we are able to rescue some of the groups with other immunological measures such as CAR-T cells and antibodies,” she said.

“I think it is very important to better identify those who really need total body irradiation in the future,” she added.

In an interview, Dr. Izraeli agreed.

“The prognosis of children after bone marrow transplantation is excellent – the majority are cured from their leukemia,” he said. “And we have to remember that those who undergo bone marrow transplant have the worst leukemias.”

He pointed out that, in fact, contemporary chemotherapy alone is effective in the treatment of more than 90% of patients with ALL younger than aged 18.

For the 10% of patients who do not respond to chemotherapy alone and undergo allogeneic HSCT, about 50%-80% of pediatric patients who have resistant leukemia are cured. However, the total body irradiation used to prepare the body to receive the transplant is linked to potentially serious consequences later in life, including sterility, lung problems, growth retardation, and secondary cancer.

To determine if the irradiation component could be safely replaced with a chemotherapy-based conditioning approach, Dr. Peters and colleagues conducted the FORUM trial.

In total 413 patients undergoing HSCT were enrolled and randomized to pretransplant conditioning with total body irradiation and etoposide (n = 202) or a chemotherapy-only approach with fludarabine/thiotepa/busulfan (flu/thio/bu; n = 99) or fludarabine/thiotepa/treosulfan (treo; n = 93).

Most patients (72%) had B-cell precursor ALL and 23% had T-cell ALL. Just over half (54%) were transplanted in first complete remission (CR1), 40% in CR2, and 4% in CR3.

The source of stem cells was bone marrow for most patients (82%); peripheral blood stem cell for 12%, and cord blood for 4%.
 

Study stopped early

The aim of the study was to demonstrate noninferiority with the chemotherapy approach.

However, the significantly inferior outcome observed in the chemotherapy-only group led to randomization being halted in March 2019.

The 2-year overall survival in the intent-to-treat (ITT) analysis, with a mean observation time of 2.1 years, was 0.75 ± 0.04 for chemo-conditioning versus 0.91 ± 0.02 for total body irradiation/etoposide (ITT P < .001).

The ITT analysis showed relapses were significantly higher in the chemo-conditioning group (2-year cumulative incidence of relapse [CIR], 0.33) compared with the total body irradiation group (CIR, 0.12; P < .001).

The 2-year event-free survival (EFS) rate was also significantly higher in the total body irradiation group (0.86 vs 0.58; P < .001), and transplant-related mortality over 2 years was lower with total body irradiation (0.02 vs 0.09; P = .02).

A per-protocol analysis showed the 2-year overall survival to be the same in the two chemotherapy groups (both 0.77 ± 0.05) compared with 0.91 ± 0.02 in the total body irradiation group (P = .003).

“In this cohort [the 91% overall survival rate] may even be lower than contemporary intensive frontline therapy results that are achieved nowadays,” Dr. Peters said.

In looking at subgroups, there were no significant differences according to age group or cancer phenotype, while MLL rearrangement was associated with higher relapse incidence.

Remission status was found to notably influence EFS, dropping from 0.91 in CR1 patients with total body irradiation to 0.76 in CR2 patients. However, total body irradiation remained significantly higher compared with the chemo-conditioning groups in CR1 (P = .004) and CR2 (P < .001).

Transplant-related mortality was not significantly different between the total body irradiation and chemo-conditioning groups in the CR1 or CR2 groups (P = .09 and P = .18, respectively), despite the significant difference when remission status was not included.

Overall, “we tried to identify subgroups in which total body irradiation might be eliminated, however in all analyses, total body irradiation was better than chemo-conditioning in all arms,” Dr. Peters said.

Meanwhile, the findings underscore that even when patients cannot receive total body irradiation, the alternative chemo-conditioning therapy in fact shows favorable efficacy on its own, Dr. Izraeli said.

“The prognosis of the chemotherapy group is also quite remarkably good, although less than the total body irradiation arm. This means that if for some reason total body irradiation cannot be given, the chemotherapy is a very reasonable alternative.”

Dr. Peters has reported relationships with Amgen, Novartis, Pfizer, Medac, Jazz, and Neovii. Dr. Izraeli has reported no relevant financial relationships.

SOURCE: EHA Congress. Abstract S102.

A version of this article originally appeared on Medscape.com.

The results from a pair of clinical trials should help to take the guesswork out of starting and stopping the tumor necrosis factor inhibitor etanercept (Enbrel) in patients with nonradiographic axial spondyloarthritis (nr-axSpA). The trials were reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

Optimal use of etanercept in this disease is still being defined, according to the investigators. Its effects, if any, when given very early in the disease course is unclear, and guidance is conflicting when it comes to stopping the drug after inactive disease is achieved.

In the Dutch randomized controlled PrevAS trial of 80 patients with suspected very early nr-axSpA, initiating etanercept instead of placebo did not significantly improve the odds of achieving a 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) response criteria at week 16.

And in the multinational, open-label, phase 4 RE-EMBARK trial, three-quarters of the 119 patients with nr-axSpA who achieved inactive disease on etanercept and stopped the drug experienced a flare within 40 weeks. However, the majority were able to regain disease inactivity after restarting the drug.
 

Findings in context

“We all have some patients like this [PrevAS population] where we strongly believe they have axial spondyloarthritis but do not fully qualify,” Nigil Haroon MD, PhD, said in an interview. “From a clinical decision-making process, we may diagnose these patients with axial spondyloarthritis, but due to restrictions in access to medications, we have difficulty accessing biologic medications for them. Hence, this study has practical implications.”

“It has already been shown in other, much larger studies that, even in patients who satisfy the criteria of axial spondyloarthritis, those who are MRI and CRP [C-reactive protein] negative are unlikely to respond, so the results are not surprising,” commented Dr. Haroon, who is codirector of the spondylitis program at the University Health Network and associate professor of medicine and rheumatology at the University of Toronto.

Although intended to be a population with suspected very early disease, several of the PrevAS patients would have met ASAS criteria for the disease at baseline, Dr. Haroon cautioned. In addition, the small sample size precluded subgroup analyses.

“The overall conclusion should be, this is a negative study, rather than state there was a trend to better improvement on etanercept. Although there are practical implications, as mentioned, I don’t think this study, with the numbers and the results presented, will change clinical practice,” he said.

The question of stopping biologics in nr-axSpA was previously addressed in the ABILITY-3 randomized trial of adalimumab (Humira), which found that flares were significantly more common with stopping versus continuing the drug and only about half of patients were able to get back in remission by restarting the drug, according to Dr. Haroon.

However, the RE-EMBARK and ABILITY-3 studies differed in both design and patient population, he noted. For example, the mean disease duration was only about 2 years in the former study, compared with 7 years in the latter.

The initial 59% rate of attaining inactive disease on etanercept in RE-EMBARK was “impressive,” Dr. Haroon said, “but as this was an open-label study, higher values are expected.”

“The message in both studies is that stopping biologics completely is not a good idea as the majority of patients, 70%-75%, will relapse within a short period,” he concluded. “However, it should be kept in mind that these [RE-EMBARK] patients received biologic only for a short 24-week period. This study does not answer the question of whether nonradiographic axial spondyloarthritis patients with sustained inactive disease can be taken off biologics abruptly without a taper over time.”

Details of the studies

In the PrevAS trial, Tamara Rusman, a PhD candidate in Rheumatology at the VU University Medical Center Amsterdam and coinvestigators studied patients meeting Calin criteria for inflammatory back pain who had high disease activity plus either HLA-B27 positivity with at least one feature of axial spondyloarthritis or HLA-B27 negativity with two features.

This population is of interest because “most studies have included only patients with nonradiographic axial spondyloarthritis with a positive MRI of the sacroiliac joints and/or an elevated C-reactive protein level,” she noted.

Results showed that, during 16 weeks of treatment, etanercept users had a nonsignficantly higher rate of achieving an ASAS 20 response with etanercept versus placebo users (17% vs. 11%; hazard ratio, 2.1; P = .2). The etanercept group also had a somewhat higher rate of response as defined by the Ankylosing Spondylitis Disease Activity Score CRP (ASDAS-CRP) criterion (25% vs. 13%; hazard ratio, 1.1; P = .8).

“Based on these data, early treatment in inflammatory back pain patients prone to develop axial spondyloarthritis seems not to be useful,” Ms. Rusman concluded. “However, monitoring of these patients should be continued since they remain a risk group for developing axial spondyloarthritis.”

In the RE-EMBARK trial, investigators led by Filip Van den Bosch, MD, PhD, Rheumatology Head-of-Clinic at Ghent (Belgium) University Hospital, started with a cohort of 208 patients with nr-axSpA who were given etanercept and background NSAIDs for 24 weeks.

“Current guidelines do not agree on whether a TNF-blocking agent or another biological DMARD should be tapered once a status of low disease activity or remission is achieved,” he noted.

Overall, 59% of the patients achieved inactive disease (defined as an ASDAS-CRP < 1.3) and discontinued etanercept.

During the next 40 weeks, 24% of these patients maintained inactive disease with only the background NSAID therapy. Among the 75% who experienced a flare, defined as an ASDAS with erythrocyte sedimentation rate (ASDAS-ESR) score of 2.1 or greater, the median time to flare was 16.1 weeks. Fully 62% of this group were able to regain disease inactivity within 12 weeks of restarting etanercept.

In a comparative analysis, relative to the RE-EMBARK patients discontinuing etanercept, similar patients who continued etanercept on the companion EMBARK trial had a longer time to flare (P < .0001) and an 85% lower risk of this outcome.

“There were no new safety signals identified, and as expected, the number of treatment-emergent adverse events dropped during the drug-free period and, interestingly, remained stable over retreatment,” Dr. Van den Bosch noted.

“Temporarily discontinuing etanercept may be an option for some patients with stable inactive nonradiographic axial spondyloarthritis,” he concluded.

The PrevAS trial was financially supported by Pfizer and ReumaNederland. Ms. Rusman declared no relevant conflicts of interest; four coauthors reported financial relationship(s) with Pfizer and other pharmaceutical companies. The RE-EMBARK trial was sponsored by Pfizer. Dr. Van den Bosch disclosed receiving grant/research support from AbbVie, Merck, and UCB, and consulting fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. Four coauthors reported financial ties to Pfizer and other pharmaceutical companies, and five coauthors were employees and shareholders of Pfizer.

SOURCES: Rusman T et al. Ann Rheum Dis. 2020;79[suppl 1]:72-3; and Van den Bosch F et al. Ann Rheum Dis. 2020;79[suppl 1]:70.

The results from a pair of clinical trials should help to take the guesswork out of starting and stopping the tumor necrosis factor inhibitor etanercept (Enbrel) in patients with nonradiographic axial spondyloarthritis (nr-axSpA). The trials were reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

Optimal use of etanercept in this disease is still being defined, according to the investigators. Its effects, if any, when given very early in the disease course is unclear, and guidance is conflicting when it comes to stopping the drug after inactive disease is achieved.

In the Dutch randomized controlled PrevAS trial of 80 patients with suspected very early nr-axSpA, initiating etanercept instead of placebo did not significantly improve the odds of achieving a 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) response criteria at week 16.

And in the multinational, open-label, phase 4 RE-EMBARK trial, three-quarters of the 119 patients with nr-axSpA who achieved inactive disease on etanercept and stopped the drug experienced a flare within 40 weeks. However, the majority were able to regain disease inactivity after restarting the drug.
 

Findings in context

“We all have some patients like this [PrevAS population] where we strongly believe they have axial spondyloarthritis but do not fully qualify,” Nigil Haroon MD, PhD, said in an interview. “From a clinical decision-making process, we may diagnose these patients with axial spondyloarthritis, but due to restrictions in access to medications, we have difficulty accessing biologic medications for them. Hence, this study has practical implications.”

“It has already been shown in other, much larger studies that, even in patients who satisfy the criteria of axial spondyloarthritis, those who are MRI and CRP [C-reactive protein] negative are unlikely to respond, so the results are not surprising,” commented Dr. Haroon, who is codirector of the spondylitis program at the University Health Network and associate professor of medicine and rheumatology at the University of Toronto.

Although intended to be a population with suspected very early disease, several of the PrevAS patients would have met ASAS criteria for the disease at baseline, Dr. Haroon cautioned. In addition, the small sample size precluded subgroup analyses.

“The overall conclusion should be, this is a negative study, rather than state there was a trend to better improvement on etanercept. Although there are practical implications, as mentioned, I don’t think this study, with the numbers and the results presented, will change clinical practice,” he said.

The question of stopping biologics in nr-axSpA was previously addressed in the ABILITY-3 randomized trial of adalimumab (Humira), which found that flares were significantly more common with stopping versus continuing the drug and only about half of patients were able to get back in remission by restarting the drug, according to Dr. Haroon.

However, the RE-EMBARK and ABILITY-3 studies differed in both design and patient population, he noted. For example, the mean disease duration was only about 2 years in the former study, compared with 7 years in the latter.

The initial 59% rate of attaining inactive disease on etanercept in RE-EMBARK was “impressive,” Dr. Haroon said, “but as this was an open-label study, higher values are expected.”

“The message in both studies is that stopping biologics completely is not a good idea as the majority of patients, 70%-75%, will relapse within a short period,” he concluded. “However, it should be kept in mind that these [RE-EMBARK] patients received biologic only for a short 24-week period. This study does not answer the question of whether nonradiographic axial spondyloarthritis patients with sustained inactive disease can be taken off biologics abruptly without a taper over time.”

Details of the studies

In the PrevAS trial, Tamara Rusman, a PhD candidate in Rheumatology at the VU University Medical Center Amsterdam and coinvestigators studied patients meeting Calin criteria for inflammatory back pain who had high disease activity plus either HLA-B27 positivity with at least one feature of axial spondyloarthritis or HLA-B27 negativity with two features.

This population is of interest because “most studies have included only patients with nonradiographic axial spondyloarthritis with a positive MRI of the sacroiliac joints and/or an elevated C-reactive protein level,” she noted.

Results showed that, during 16 weeks of treatment, etanercept users had a nonsignficantly higher rate of achieving an ASAS 20 response with etanercept versus placebo users (17% vs. 11%; hazard ratio, 2.1; P = .2). The etanercept group also had a somewhat higher rate of response as defined by the Ankylosing Spondylitis Disease Activity Score CRP (ASDAS-CRP) criterion (25% vs. 13%; hazard ratio, 1.1; P = .8).

“Based on these data, early treatment in inflammatory back pain patients prone to develop axial spondyloarthritis seems not to be useful,” Ms. Rusman concluded. “However, monitoring of these patients should be continued since they remain a risk group for developing axial spondyloarthritis.”

In the RE-EMBARK trial, investigators led by Filip Van den Bosch, MD, PhD, Rheumatology Head-of-Clinic at Ghent (Belgium) University Hospital, started with a cohort of 208 patients with nr-axSpA who were given etanercept and background NSAIDs for 24 weeks.

“Current guidelines do not agree on whether a TNF-blocking agent or another biological DMARD should be tapered once a status of low disease activity or remission is achieved,” he noted.

Overall, 59% of the patients achieved inactive disease (defined as an ASDAS-CRP < 1.3) and discontinued etanercept.

During the next 40 weeks, 24% of these patients maintained inactive disease with only the background NSAID therapy. Among the 75% who experienced a flare, defined as an ASDAS with erythrocyte sedimentation rate (ASDAS-ESR) score of 2.1 or greater, the median time to flare was 16.1 weeks. Fully 62% of this group were able to regain disease inactivity within 12 weeks of restarting etanercept.

In a comparative analysis, relative to the RE-EMBARK patients discontinuing etanercept, similar patients who continued etanercept on the companion EMBARK trial had a longer time to flare (P < .0001) and an 85% lower risk of this outcome.

“There were no new safety signals identified, and as expected, the number of treatment-emergent adverse events dropped during the drug-free period and, interestingly, remained stable over retreatment,” Dr. Van den Bosch noted.

“Temporarily discontinuing etanercept may be an option for some patients with stable inactive nonradiographic axial spondyloarthritis,” he concluded.

The PrevAS trial was financially supported by Pfizer and ReumaNederland. Ms. Rusman declared no relevant conflicts of interest; four coauthors reported financial relationship(s) with Pfizer and other pharmaceutical companies. The RE-EMBARK trial was sponsored by Pfizer. Dr. Van den Bosch disclosed receiving grant/research support from AbbVie, Merck, and UCB, and consulting fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. Four coauthors reported financial ties to Pfizer and other pharmaceutical companies, and five coauthors were employees and shareholders of Pfizer.

SOURCES: Rusman T et al. Ann Rheum Dis. 2020;79[suppl 1]:72-3; and Van den Bosch F et al. Ann Rheum Dis. 2020;79[suppl 1]:70.

The results from a pair of clinical trials should help to take the guesswork out of starting and stopping the tumor necrosis factor inhibitor etanercept (Enbrel) in patients with nonradiographic axial spondyloarthritis (nr-axSpA). The trials were reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

Optimal use of etanercept in this disease is still being defined, according to the investigators. Its effects, if any, when given very early in the disease course is unclear, and guidance is conflicting when it comes to stopping the drug after inactive disease is achieved.

In the Dutch randomized controlled PrevAS trial of 80 patients with suspected very early nr-axSpA, initiating etanercept instead of placebo did not significantly improve the odds of achieving a 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) response criteria at week 16.

And in the multinational, open-label, phase 4 RE-EMBARK trial, three-quarters of the 119 patients with nr-axSpA who achieved inactive disease on etanercept and stopped the drug experienced a flare within 40 weeks. However, the majority were able to regain disease inactivity after restarting the drug.
 

Findings in context

“We all have some patients like this [PrevAS population] where we strongly believe they have axial spondyloarthritis but do not fully qualify,” Nigil Haroon MD, PhD, said in an interview. “From a clinical decision-making process, we may diagnose these patients with axial spondyloarthritis, but due to restrictions in access to medications, we have difficulty accessing biologic medications for them. Hence, this study has practical implications.”

“It has already been shown in other, much larger studies that, even in patients who satisfy the criteria of axial spondyloarthritis, those who are MRI and CRP [C-reactive protein] negative are unlikely to respond, so the results are not surprising,” commented Dr. Haroon, who is codirector of the spondylitis program at the University Health Network and associate professor of medicine and rheumatology at the University of Toronto.

Although intended to be a population with suspected very early disease, several of the PrevAS patients would have met ASAS criteria for the disease at baseline, Dr. Haroon cautioned. In addition, the small sample size precluded subgroup analyses.

“The overall conclusion should be, this is a negative study, rather than state there was a trend to better improvement on etanercept. Although there are practical implications, as mentioned, I don’t think this study, with the numbers and the results presented, will change clinical practice,” he said.

The question of stopping biologics in nr-axSpA was previously addressed in the ABILITY-3 randomized trial of adalimumab (Humira), which found that flares were significantly more common with stopping versus continuing the drug and only about half of patients were able to get back in remission by restarting the drug, according to Dr. Haroon.

However, the RE-EMBARK and ABILITY-3 studies differed in both design and patient population, he noted. For example, the mean disease duration was only about 2 years in the former study, compared with 7 years in the latter.

The initial 59% rate of attaining inactive disease on etanercept in RE-EMBARK was “impressive,” Dr. Haroon said, “but as this was an open-label study, higher values are expected.”

“The message in both studies is that stopping biologics completely is not a good idea as the majority of patients, 70%-75%, will relapse within a short period,” he concluded. “However, it should be kept in mind that these [RE-EMBARK] patients received biologic only for a short 24-week period. This study does not answer the question of whether nonradiographic axial spondyloarthritis patients with sustained inactive disease can be taken off biologics abruptly without a taper over time.”

Details of the studies

In the PrevAS trial, Tamara Rusman, a PhD candidate in Rheumatology at the VU University Medical Center Amsterdam and coinvestigators studied patients meeting Calin criteria for inflammatory back pain who had high disease activity plus either HLA-B27 positivity with at least one feature of axial spondyloarthritis or HLA-B27 negativity with two features.

This population is of interest because “most studies have included only patients with nonradiographic axial spondyloarthritis with a positive MRI of the sacroiliac joints and/or an elevated C-reactive protein level,” she noted.

Results showed that, during 16 weeks of treatment, etanercept users had a nonsignficantly higher rate of achieving an ASAS 20 response with etanercept versus placebo users (17% vs. 11%; hazard ratio, 2.1; P = .2). The etanercept group also had a somewhat higher rate of response as defined by the Ankylosing Spondylitis Disease Activity Score CRP (ASDAS-CRP) criterion (25% vs. 13%; hazard ratio, 1.1; P = .8).

“Based on these data, early treatment in inflammatory back pain patients prone to develop axial spondyloarthritis seems not to be useful,” Ms. Rusman concluded. “However, monitoring of these patients should be continued since they remain a risk group for developing axial spondyloarthritis.”

In the RE-EMBARK trial, investigators led by Filip Van den Bosch, MD, PhD, Rheumatology Head-of-Clinic at Ghent (Belgium) University Hospital, started with a cohort of 208 patients with nr-axSpA who were given etanercept and background NSAIDs for 24 weeks.

“Current guidelines do not agree on whether a TNF-blocking agent or another biological DMARD should be tapered once a status of low disease activity or remission is achieved,” he noted.

Overall, 59% of the patients achieved inactive disease (defined as an ASDAS-CRP < 1.3) and discontinued etanercept.

During the next 40 weeks, 24% of these patients maintained inactive disease with only the background NSAID therapy. Among the 75% who experienced a flare, defined as an ASDAS with erythrocyte sedimentation rate (ASDAS-ESR) score of 2.1 or greater, the median time to flare was 16.1 weeks. Fully 62% of this group were able to regain disease inactivity within 12 weeks of restarting etanercept.

In a comparative analysis, relative to the RE-EMBARK patients discontinuing etanercept, similar patients who continued etanercept on the companion EMBARK trial had a longer time to flare (P < .0001) and an 85% lower risk of this outcome.

“There were no new safety signals identified, and as expected, the number of treatment-emergent adverse events dropped during the drug-free period and, interestingly, remained stable over retreatment,” Dr. Van den Bosch noted.

“Temporarily discontinuing etanercept may be an option for some patients with stable inactive nonradiographic axial spondyloarthritis,” he concluded.

The PrevAS trial was financially supported by Pfizer and ReumaNederland. Ms. Rusman declared no relevant conflicts of interest; four coauthors reported financial relationship(s) with Pfizer and other pharmaceutical companies. The RE-EMBARK trial was sponsored by Pfizer. Dr. Van den Bosch disclosed receiving grant/research support from AbbVie, Merck, and UCB, and consulting fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. Four coauthors reported financial ties to Pfizer and other pharmaceutical companies, and five coauthors were employees and shareholders of Pfizer.

SOURCES: Rusman T et al. Ann Rheum Dis. 2020;79[suppl 1]:72-3; and Van den Bosch F et al. Ann Rheum Dis. 2020;79[suppl 1]:70.

Patients with metastatic small-cell lung cancer (SCLC) whose disease has progressed after or during treatment with platinum-based chemotherapy now have a new option to try — lurbinectedin (Zepzelca, Jazz Pharma/PharmaMar).

The drug was granted accelerated approval by the US Food and Drug Administration (FDA) based on response data. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, the FDA notes.

“Small-cell lung cancer is a disease with limited treatment options,” said Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals. “While patients may initially respond to traditional chemotherapy, they often experience an aggressive recurrence that is historically resistant to treatment.”

“Seeing first-hand the aggressive nature of SCLC and knowing that the large majority of those diagnosed will experience relapse, I am excited to see an effective new treatment demonstrating durable responses,” Jeff Petty, MD, oncology specialist, Wake Forest Baptist Health, Winston-Salem, North Carolina, commented in the company press release. This new drug “is an important and much-needed addition to the treatment landscape for relapsing SCLC,” he added.
 

Approval based on monotherapy trial

The approval is based on a monotherapy clinical trial in 105 patients, which was published in May in Lancet Oncology, with first author José Trigo, MD, from the Hospital Universitario Virgen de la Victoria in Malaga, Spain.  

These were adult patients with both platinum-sensitive and platinum-resistant SCLC who had disease progression after treatment with platinum-based chemotherapy. They were treated at 26 hospitals across six European countries and the US. All patients received lurbinectedin at 3.2 mg/m² by intravenous infusion over 1 hour. Median follow-up was 17.1 months.

Overall response by investigator assessment was seen in 37 (35.2%) of the 105 patients. The response was greater (at 45%) among the patients with platinum-sensitive disease and smaller (22.2%) among those with platinum-resistant disease.

Lurbinectedin demonstrated a median duration of response of 5.3 months as measured by investigator assessment.

In a post-hoc analysis, among the 37 patients who had an initial objective response, the median overall survival was just over 1 year (12.6 months). It was even longer among patients who had platinum-sensitive disease (15.8 months), although it was shorter in patients with resistant disease (10.9 months).

These data are “particularly encouraging,” comment the authors of an accompanying editorial, led by Oscar Arrieta, MD, from the Thoracic Oncology Unit at the Instituto Nacional de Cancerología in Mexico City, Mexico. These response rates “outperform all previous results achieved with topotecan and other less established treatment schemes including cyclophosphamide, doxorubicin, and vincristine, or platinum re-challenge, in this setting.”

“Lurbinectedin represents an innovative approach to conventional anti-cancer drugs, with an elegant mechanism of action based on the inhibition of transcription-dependent replication stress and genome instability of tumor cells,” the editorialists comment. “The drug binds to specific DNA triplets commonly found in transcription sites and triggers cellular apoptosis.”

“At present, the only evidence-based second-line treatment approved for SCLC is topotecan, a topoisomerase 1 inhibitor with moderate activity in patients with sensitive disease, although its effect is much less evident in patients with resistant SCLC,” they continue.

“Overall, the study by Trigo and colleagues presents novel data for a very challenging disease for which few treatment options exist, and the data on response and survival do seem to outperform data from historical controls,” Arrieta and colleagues write.

The editorialists also note that, in this trial, a few patients had received immunotherapy as part of their first-line treatment, and some of these patients (5 of 8 patients, 68%) had “an outstanding rate of durable response to lurbinectedin.” This raises the possibility of a synergistic effect between immunotherapy and lurbinectedin, as the combination seems to enhance immune memory and impair subsequent tumor growth, they add. Further trials will need to explore sequencing of therapy, they suggest.

A large phase 3 study known as ATLANTIS is currently underway.  

The most common grade 3-4 adverse events in the present trial were hematologic abnormalities: anemia (9% of patients), leukopenia (29%), neutropenia (46%), and thrombocytopenia (7%). Serious treatment-related adverse events occurred in 10% of patients, of which neutropenia and febrile neutropenia were the most common (5% each). No treatment-related deaths were reported.

The study was funded by PharmaMar. Trigo and coauthors, and Arrieta and fellow editorialists, all report relationships with pharmaceutical companies, as detailed in the published articles.

This article first appeared on Medscape.com.

Patients with metastatic small-cell lung cancer (SCLC) whose disease has progressed after or during treatment with platinum-based chemotherapy now have a new option to try — lurbinectedin (Zepzelca, Jazz Pharma/PharmaMar).

The drug was granted accelerated approval by the US Food and Drug Administration (FDA) based on response data. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, the FDA notes.

“Small-cell lung cancer is a disease with limited treatment options,” said Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals. “While patients may initially respond to traditional chemotherapy, they often experience an aggressive recurrence that is historically resistant to treatment.”

“Seeing first-hand the aggressive nature of SCLC and knowing that the large majority of those diagnosed will experience relapse, I am excited to see an effective new treatment demonstrating durable responses,” Jeff Petty, MD, oncology specialist, Wake Forest Baptist Health, Winston-Salem, North Carolina, commented in the company press release. This new drug “is an important and much-needed addition to the treatment landscape for relapsing SCLC,” he added.
 

Approval based on monotherapy trial

The approval is based on a monotherapy clinical trial in 105 patients, which was published in May in Lancet Oncology, with first author José Trigo, MD, from the Hospital Universitario Virgen de la Victoria in Malaga, Spain.  

These were adult patients with both platinum-sensitive and platinum-resistant SCLC who had disease progression after treatment with platinum-based chemotherapy. They were treated at 26 hospitals across six European countries and the US. All patients received lurbinectedin at 3.2 mg/m² by intravenous infusion over 1 hour. Median follow-up was 17.1 months.

Overall response by investigator assessment was seen in 37 (35.2%) of the 105 patients. The response was greater (at 45%) among the patients with platinum-sensitive disease and smaller (22.2%) among those with platinum-resistant disease.

Lurbinectedin demonstrated a median duration of response of 5.3 months as measured by investigator assessment.

In a post-hoc analysis, among the 37 patients who had an initial objective response, the median overall survival was just over 1 year (12.6 months). It was even longer among patients who had platinum-sensitive disease (15.8 months), although it was shorter in patients with resistant disease (10.9 months).

These data are “particularly encouraging,” comment the authors of an accompanying editorial, led by Oscar Arrieta, MD, from the Thoracic Oncology Unit at the Instituto Nacional de Cancerología in Mexico City, Mexico. These response rates “outperform all previous results achieved with topotecan and other less established treatment schemes including cyclophosphamide, doxorubicin, and vincristine, or platinum re-challenge, in this setting.”

“Lurbinectedin represents an innovative approach to conventional anti-cancer drugs, with an elegant mechanism of action based on the inhibition of transcription-dependent replication stress and genome instability of tumor cells,” the editorialists comment. “The drug binds to specific DNA triplets commonly found in transcription sites and triggers cellular apoptosis.”

“At present, the only evidence-based second-line treatment approved for SCLC is topotecan, a topoisomerase 1 inhibitor with moderate activity in patients with sensitive disease, although its effect is much less evident in patients with resistant SCLC,” they continue.

“Overall, the study by Trigo and colleagues presents novel data for a very challenging disease for which few treatment options exist, and the data on response and survival do seem to outperform data from historical controls,” Arrieta and colleagues write.

The editorialists also note that, in this trial, a few patients had received immunotherapy as part of their first-line treatment, and some of these patients (5 of 8 patients, 68%) had “an outstanding rate of durable response to lurbinectedin.” This raises the possibility of a synergistic effect between immunotherapy and lurbinectedin, as the combination seems to enhance immune memory and impair subsequent tumor growth, they add. Further trials will need to explore sequencing of therapy, they suggest.

A large phase 3 study known as ATLANTIS is currently underway.  

The most common grade 3-4 adverse events in the present trial were hematologic abnormalities: anemia (9% of patients), leukopenia (29%), neutropenia (46%), and thrombocytopenia (7%). Serious treatment-related adverse events occurred in 10% of patients, of which neutropenia and febrile neutropenia were the most common (5% each). No treatment-related deaths were reported.

The study was funded by PharmaMar. Trigo and coauthors, and Arrieta and fellow editorialists, all report relationships with pharmaceutical companies, as detailed in the published articles.

This article first appeared on Medscape.com.

Patients with metastatic small-cell lung cancer (SCLC) whose disease has progressed after or during treatment with platinum-based chemotherapy now have a new option to try — lurbinectedin (Zepzelca, Jazz Pharma/PharmaMar).

The drug was granted accelerated approval by the US Food and Drug Administration (FDA) based on response data. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, the FDA notes.

“Small-cell lung cancer is a disease with limited treatment options,” said Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals. “While patients may initially respond to traditional chemotherapy, they often experience an aggressive recurrence that is historically resistant to treatment.”

“Seeing first-hand the aggressive nature of SCLC and knowing that the large majority of those diagnosed will experience relapse, I am excited to see an effective new treatment demonstrating durable responses,” Jeff Petty, MD, oncology specialist, Wake Forest Baptist Health, Winston-Salem, North Carolina, commented in the company press release. This new drug “is an important and much-needed addition to the treatment landscape for relapsing SCLC,” he added.
 

Approval based on monotherapy trial

The approval is based on a monotherapy clinical trial in 105 patients, which was published in May in Lancet Oncology, with first author José Trigo, MD, from the Hospital Universitario Virgen de la Victoria in Malaga, Spain.  

These were adult patients with both platinum-sensitive and platinum-resistant SCLC who had disease progression after treatment with platinum-based chemotherapy. They were treated at 26 hospitals across six European countries and the US. All patients received lurbinectedin at 3.2 mg/m² by intravenous infusion over 1 hour. Median follow-up was 17.1 months.

Overall response by investigator assessment was seen in 37 (35.2%) of the 105 patients. The response was greater (at 45%) among the patients with platinum-sensitive disease and smaller (22.2%) among those with platinum-resistant disease.

Lurbinectedin demonstrated a median duration of response of 5.3 months as measured by investigator assessment.

In a post-hoc analysis, among the 37 patients who had an initial objective response, the median overall survival was just over 1 year (12.6 months). It was even longer among patients who had platinum-sensitive disease (15.8 months), although it was shorter in patients with resistant disease (10.9 months).

These data are “particularly encouraging,” comment the authors of an accompanying editorial, led by Oscar Arrieta, MD, from the Thoracic Oncology Unit at the Instituto Nacional de Cancerología in Mexico City, Mexico. These response rates “outperform all previous results achieved with topotecan and other less established treatment schemes including cyclophosphamide, doxorubicin, and vincristine, or platinum re-challenge, in this setting.”

“Lurbinectedin represents an innovative approach to conventional anti-cancer drugs, with an elegant mechanism of action based on the inhibition of transcription-dependent replication stress and genome instability of tumor cells,” the editorialists comment. “The drug binds to specific DNA triplets commonly found in transcription sites and triggers cellular apoptosis.”

“At present, the only evidence-based second-line treatment approved for SCLC is topotecan, a topoisomerase 1 inhibitor with moderate activity in patients with sensitive disease, although its effect is much less evident in patients with resistant SCLC,” they continue.

“Overall, the study by Trigo and colleagues presents novel data for a very challenging disease for which few treatment options exist, and the data on response and survival do seem to outperform data from historical controls,” Arrieta and colleagues write.

The editorialists also note that, in this trial, a few patients had received immunotherapy as part of their first-line treatment, and some of these patients (5 of 8 patients, 68%) had “an outstanding rate of durable response to lurbinectedin.” This raises the possibility of a synergistic effect between immunotherapy and lurbinectedin, as the combination seems to enhance immune memory and impair subsequent tumor growth, they add. Further trials will need to explore sequencing of therapy, they suggest.

A large phase 3 study known as ATLANTIS is currently underway.  

The most common grade 3-4 adverse events in the present trial were hematologic abnormalities: anemia (9% of patients), leukopenia (29%), neutropenia (46%), and thrombocytopenia (7%). Serious treatment-related adverse events occurred in 10% of patients, of which neutropenia and febrile neutropenia were the most common (5% each). No treatment-related deaths were reported.

The study was funded by PharmaMar. Trigo and coauthors, and Arrieta and fellow editorialists, all report relationships with pharmaceutical companies, as detailed in the published articles.

This article first appeared on Medscape.com.

The investigational once-weekly basal insulin analog icodec (Novo Nordisk) was comparable in efficacy and safety with once-daily insulin glargine U100, new research suggests.

Julio Rosenstock, MD, of the University of Texas, Dallas, presented the data from the phase 2 pivotal study of icodec on June 14 during the virtual American Diabetes Association 80th Scientific Sessions.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour half-life. A once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

“Many people with type 2 diabetes are reluctant to start on insulin therapy due to the need for daily injections. ... I’m truly excited about the potential of such innovative treatments which could reduce the number of basal insulin injections for my patients with diabetes,” Dr. Rosenstock commented in a Novo Nordisk statement.

During his presentation, he added that the product “has the potential to be a major player in the management of type 2 diabetes if eventually approved.”

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said that “it’s a phase 2 study. Obviously we need to see the phase 3 data, but it’s very encouraging.”

Dr. Alexander, who was global medical director for diabetes in medical affairs at Merck from 2008 to 2015, observed that “the theory is that you have better adherence to once-weekly, compared to daily [dosing], but when you actually do the studies it’s very difficult to prove that.

“I think the big advantage is that the company can develop a coformulation of [the glucagonlike peptide–1 receptor agonist] semaglutide and icodec in the same pen or vial. ... There is a convenience factor of once weekly over daily.”

In fact, he noted, Novo Nordisk is already in phase 1 trials with that product, called icosema.

“Potential to be transformational”

The phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial included 247 insulin-naive patients with type 2 diabetes with hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with about half also taking a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). All participants took seven injections per week with a vial and syringe plus one injection per week with a pen injector. Doses were titrated up or down to achieve blood glucose levels 70-108 mg/dL, with glargine dose adjustments of 2 or 4 units and icodec units of 14 or 28 units.

Participants were a mean age of 59.6 years, had a diabetes duration of 9.7 years, and 56.3% were men. Baseline A1c was 8.0% overall and fasting blood glucose was 181 mg/dL, and both were similar between the two groups.

The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, which was not significantly different (P = .08). Estimated mean A1c levels were 6.7% for icodec and 6.9% for glargine.

The icodec result, Dr. Rosenstock said, “is a very impressive final A1c.”

The proportions of patients achieving A1c <7% by week 26 for icodec versus glargine were 72% versus 68%, and for A1c ≤6.5% were 49% and 39%, respectively. Those differences weren’t statistically significant because of lack of power, Dr. Rosenstock observed.

Fasting plasma glucose levels were nearly identical at 26 weeks, with drops of 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

However, there was a significant difference in favor of icodec in the 9-point self-monitoring of blood glucose profile, with a difference in mean change from baseline to week 26 of –7.9 mg/dL (P = .01).

Lower postbreakfast and postlunch glucose peaks at 90 minutes accounted for most of the difference, Dr. Rosenstock noted. 

Total insulin doses during the last 2 weeks of treatment with icodec versus glargine were 229 versus 284 units/week (P = .01); those translate to approximate daily doses of 33 versus 41 units/day, respectively.

Both groups gained a small amount of weight, 1.5 kg with icodec and 1.6 kg with glargine by week 26 (P = .88).

Hypoglycemia was more common with icodec than glargine, including mild (53.6% vs. 37.7%), moderate or clinically significant (16.0% vs. 9.8%), and severe (1 [0.8%] vs. 0 participants). Corresponding event rates were 508.9 versus 210.8 per 100 patient-years (mild hypoglycemia), 52.5 versus 45.6 per 100 patient-years (moderate or clinically significant), and 1.4 versus 0 per 100 patient-years (severe) for icodec versus glargine.

The difference between the two groups in moderate or clinically significant hypoglycemia wasn’t statistically significant (P = .85), and the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between groups.

“Based on the robustness of these data, further evidence on the role of weekly basal insulin icodec will be pursued in a comprehensive phase 3 clinical development program,” Dr. Rosenstock explained. If those data confirm the phase 2 results, “I believe personally that a weekly basal insulin has the potential to be transformational in the management of people with type 2 diabetes needing insulin therapy.”

Dr. Rosenstock has reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander has reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The investigational once-weekly basal insulin analog icodec (Novo Nordisk) was comparable in efficacy and safety with once-daily insulin glargine U100, new research suggests.

Julio Rosenstock, MD, of the University of Texas, Dallas, presented the data from the phase 2 pivotal study of icodec on June 14 during the virtual American Diabetes Association 80th Scientific Sessions.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour half-life. A once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

“Many people with type 2 diabetes are reluctant to start on insulin therapy due to the need for daily injections. ... I’m truly excited about the potential of such innovative treatments which could reduce the number of basal insulin injections for my patients with diabetes,” Dr. Rosenstock commented in a Novo Nordisk statement.

During his presentation, he added that the product “has the potential to be a major player in the management of type 2 diabetes if eventually approved.”

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said that “it’s a phase 2 study. Obviously we need to see the phase 3 data, but it’s very encouraging.”

Dr. Alexander, who was global medical director for diabetes in medical affairs at Merck from 2008 to 2015, observed that “the theory is that you have better adherence to once-weekly, compared to daily [dosing], but when you actually do the studies it’s very difficult to prove that.

“I think the big advantage is that the company can develop a coformulation of [the glucagonlike peptide–1 receptor agonist] semaglutide and icodec in the same pen or vial. ... There is a convenience factor of once weekly over daily.”

In fact, he noted, Novo Nordisk is already in phase 1 trials with that product, called icosema.

“Potential to be transformational”

The phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial included 247 insulin-naive patients with type 2 diabetes with hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with about half also taking a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). All participants took seven injections per week with a vial and syringe plus one injection per week with a pen injector. Doses were titrated up or down to achieve blood glucose levels 70-108 mg/dL, with glargine dose adjustments of 2 or 4 units and icodec units of 14 or 28 units.

Participants were a mean age of 59.6 years, had a diabetes duration of 9.7 years, and 56.3% were men. Baseline A1c was 8.0% overall and fasting blood glucose was 181 mg/dL, and both were similar between the two groups.

The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, which was not significantly different (P = .08). Estimated mean A1c levels were 6.7% for icodec and 6.9% for glargine.

The icodec result, Dr. Rosenstock said, “is a very impressive final A1c.”

The proportions of patients achieving A1c <7% by week 26 for icodec versus glargine were 72% versus 68%, and for A1c ≤6.5% were 49% and 39%, respectively. Those differences weren’t statistically significant because of lack of power, Dr. Rosenstock observed.

Fasting plasma glucose levels were nearly identical at 26 weeks, with drops of 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

However, there was a significant difference in favor of icodec in the 9-point self-monitoring of blood glucose profile, with a difference in mean change from baseline to week 26 of –7.9 mg/dL (P = .01).

Lower postbreakfast and postlunch glucose peaks at 90 minutes accounted for most of the difference, Dr. Rosenstock noted. 

Total insulin doses during the last 2 weeks of treatment with icodec versus glargine were 229 versus 284 units/week (P = .01); those translate to approximate daily doses of 33 versus 41 units/day, respectively.

Both groups gained a small amount of weight, 1.5 kg with icodec and 1.6 kg with glargine by week 26 (P = .88).

Hypoglycemia was more common with icodec than glargine, including mild (53.6% vs. 37.7%), moderate or clinically significant (16.0% vs. 9.8%), and severe (1 [0.8%] vs. 0 participants). Corresponding event rates were 508.9 versus 210.8 per 100 patient-years (mild hypoglycemia), 52.5 versus 45.6 per 100 patient-years (moderate or clinically significant), and 1.4 versus 0 per 100 patient-years (severe) for icodec versus glargine.

The difference between the two groups in moderate or clinically significant hypoglycemia wasn’t statistically significant (P = .85), and the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between groups.

“Based on the robustness of these data, further evidence on the role of weekly basal insulin icodec will be pursued in a comprehensive phase 3 clinical development program,” Dr. Rosenstock explained. If those data confirm the phase 2 results, “I believe personally that a weekly basal insulin has the potential to be transformational in the management of people with type 2 diabetes needing insulin therapy.”

Dr. Rosenstock has reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander has reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The investigational once-weekly basal insulin analog icodec (Novo Nordisk) was comparable in efficacy and safety with once-daily insulin glargine U100, new research suggests.

Julio Rosenstock, MD, of the University of Texas, Dallas, presented the data from the phase 2 pivotal study of icodec on June 14 during the virtual American Diabetes Association 80th Scientific Sessions.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour half-life. A once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

“Many people with type 2 diabetes are reluctant to start on insulin therapy due to the need for daily injections. ... I’m truly excited about the potential of such innovative treatments which could reduce the number of basal insulin injections for my patients with diabetes,” Dr. Rosenstock commented in a Novo Nordisk statement.

During his presentation, he added that the product “has the potential to be a major player in the management of type 2 diabetes if eventually approved.”

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said that “it’s a phase 2 study. Obviously we need to see the phase 3 data, but it’s very encouraging.”

Dr. Alexander, who was global medical director for diabetes in medical affairs at Merck from 2008 to 2015, observed that “the theory is that you have better adherence to once-weekly, compared to daily [dosing], but when you actually do the studies it’s very difficult to prove that.

“I think the big advantage is that the company can develop a coformulation of [the glucagonlike peptide–1 receptor agonist] semaglutide and icodec in the same pen or vial. ... There is a convenience factor of once weekly over daily.”

In fact, he noted, Novo Nordisk is already in phase 1 trials with that product, called icosema.

“Potential to be transformational”

The phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial included 247 insulin-naive patients with type 2 diabetes with hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with about half also taking a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). All participants took seven injections per week with a vial and syringe plus one injection per week with a pen injector. Doses were titrated up or down to achieve blood glucose levels 70-108 mg/dL, with glargine dose adjustments of 2 or 4 units and icodec units of 14 or 28 units.

Participants were a mean age of 59.6 years, had a diabetes duration of 9.7 years, and 56.3% were men. Baseline A1c was 8.0% overall and fasting blood glucose was 181 mg/dL, and both were similar between the two groups.

The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, which was not significantly different (P = .08). Estimated mean A1c levels were 6.7% for icodec and 6.9% for glargine.

The icodec result, Dr. Rosenstock said, “is a very impressive final A1c.”

The proportions of patients achieving A1c <7% by week 26 for icodec versus glargine were 72% versus 68%, and for A1c ≤6.5% were 49% and 39%, respectively. Those differences weren’t statistically significant because of lack of power, Dr. Rosenstock observed.

Fasting plasma glucose levels were nearly identical at 26 weeks, with drops of 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

However, there was a significant difference in favor of icodec in the 9-point self-monitoring of blood glucose profile, with a difference in mean change from baseline to week 26 of –7.9 mg/dL (P = .01).

Lower postbreakfast and postlunch glucose peaks at 90 minutes accounted for most of the difference, Dr. Rosenstock noted. 

Total insulin doses during the last 2 weeks of treatment with icodec versus glargine were 229 versus 284 units/week (P = .01); those translate to approximate daily doses of 33 versus 41 units/day, respectively.

Both groups gained a small amount of weight, 1.5 kg with icodec and 1.6 kg with glargine by week 26 (P = .88).

Hypoglycemia was more common with icodec than glargine, including mild (53.6% vs. 37.7%), moderate or clinically significant (16.0% vs. 9.8%), and severe (1 [0.8%] vs. 0 participants). Corresponding event rates were 508.9 versus 210.8 per 100 patient-years (mild hypoglycemia), 52.5 versus 45.6 per 100 patient-years (moderate or clinically significant), and 1.4 versus 0 per 100 patient-years (severe) for icodec versus glargine.

The difference between the two groups in moderate or clinically significant hypoglycemia wasn’t statistically significant (P = .85), and the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between groups.

“Based on the robustness of these data, further evidence on the role of weekly basal insulin icodec will be pursued in a comprehensive phase 3 clinical development program,” Dr. Rosenstock explained. If those data confirm the phase 2 results, “I believe personally that a weekly basal insulin has the potential to be transformational in the management of people with type 2 diabetes needing insulin therapy.”

Dr. Rosenstock has reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander has reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

With new daily coronavirus cases rising in at least two dozen states, an explosion of new infections in Arizona is stretching some hospitals and alarming public health experts who link the surge in cases to the state’s lifting of a stay-at-home order a month ago.

Arizona has emerged as one of the country’s newest coronavirus hot spots, with the weekly average of daily cases more than doubling from 2 weeks ago. The total number of people hospitalized is climbing, too.

Over the past week, Arizona has seen an average of more than 1,300 new COVID-19 cases each day.

After the state’s largest hospital system warned about a shortage of ICU beds, Arizona Gov. Doug Ducey, a Republican, pushed back on claims that the health care system could soon be overwhelmed.

“The entire time we’ve been focused on a possible worst-case scenario with surge capacity for hospital beds, ICU beds and ventilators,” Ducey told reporters on Thursday. “Those are not needed or necessary right now.”

While he acknowledged a spike in positive cases, Ducey said a second stay-at-home order was “not under discussion.”

“We put the stay-at-home order there so we could prepare for what we are going through,” he said.

Some states have reopened more slowly with a set of specific benchmarks for different regions, but Arizona took a more aggressive approach.

The state began easing restrictions on businesses in early May and lifted its statewide lockdown order after May 15. Under Arizona’s reopening plan, businesses are advised to follow federal guidance on social distancing.

There is also no requirement for everyone to wear masks in public.

Public health experts agree: The timing of this spike reflects the state’s reopening.

“Perhaps, Arizona will be a warning sign to other areas,” said Katherine Ellingson, an epidemiologist at the University of Arizona. “We never had that consistent downward trend that would signal it’s time to reopen and we have everything in place to do it safely.”

Before Arizona lifted its stay-at-home order, only about 5% of COVID-19 tests registered as positive. On Monday, that number was around 16%.

A slower reopening gives public health agencies time to identify whether cases are rising and then respond with contact tracing and isolating those who are infected.

“With a fast, rapid reopening, we don’t have the time to mobilize those resources,” said Ellingson.

Maricopa County, home to about 60% of the state’s population, has ramped up contact tracing in recent weeks, but it may not have enough capacity if the surge in cases continues.

Dr. Peter Hotez said the spike in Arizona, as well as in parts of Texas such as Houston, Dallas and Austin, is the consequence of removing restrictions too quickly and without a public health system that can keep pace.

“It was just ‘open it up’ and then more or less business as usual, with a little bit of window dressing,” said Hotez, the dean for the National School of Tropical Medicine at Baylor College of Medicine in Houston. “This is not an abstract number of cases. We’re seeing people pile into intensive care units.”

Arizona’s governor has also faced criticism from the mayors of Arizona’s two biggest cities for not putting in place more stringent requirements.

“There is a pandemic and it’s spreading uncontrollably,” said Tucson Mayor Regina Romero, a Democrat. Ducey, she said, “is just putting up his hands and saying ‘the spread is happening and we just have to go about our business.’”

And the governor’s executive order forbids local governments from implementing their own extra measures, which adds to Romero’s frustration. Texas has a similar measure.

“What he did was pretty much tie the hands of mayors and public health officials,” Romero said.

Arizona’s hospital industry has tried to tamp down fears that it’s on the verge of a crisis. Hospitals are still performing elective surgeries.

“It’s very unfortunate because hospitals right now in Arizona are quite busy with elective procedures,” said Saskia Popescu, a Phoenix-based epidemiologist with George Mason University. “You throw in increasing cases of COVID, and that’s going to very much stress your hospital systems.”

Phoenix’s triple-digit summer temperatures actually may fuel the spread of the virus. People forgo outdoor activities and retreat to air-conditioned indoor spaces, where the risk of transmitting the virus goes up significantly.

“My concern is we’re going to see a lot more people in close quarters for prolonged periods of time,” Popescu said.

Since the stay-at-home order was lifted, Popescu and others say they’ve seen people returning to a pre-pandemic mindset, neglecting to wear masks or maintain social distance. Videos of crowded bars have only propelled these fears.

On Thursday, however, Arizona’s top doctor stressed there were also dangers to keeping the state on lockdown, including the mental health effects of loneliness and isolation.

“We know that it’s in the community. We are not going to be able to stop the spread. And so we can’t stop living as well,” said Dr. Cara Christ, health director for the Arizona Department of Health Services.

But Dr. Quinn Snyder, an emergency medicine physician in Mesa, Arizona, said there needs to be more consistent messaging on public health measures like wearing masks.

“Frankly, I just think a wholesale reevaluation of where we’re at is critical right now, but I can tell you that we’re not doing nearly enough,” said Snyder, who has seen the uptick in seriously ill COVID-19 patients firsthand.

“If we continue to head down this path, the virus will press our health care facilities beyond capacity, where we’re going to have to be making tough decisions like who gets a ventilator and who doesn’t.”

A version of this article originally appeared on Kaiser Health News, which is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

With new daily coronavirus cases rising in at least two dozen states, an explosion of new infections in Arizona is stretching some hospitals and alarming public health experts who link the surge in cases to the state’s lifting of a stay-at-home order a month ago.

Arizona has emerged as one of the country’s newest coronavirus hot spots, with the weekly average of daily cases more than doubling from 2 weeks ago. The total number of people hospitalized is climbing, too.

Over the past week, Arizona has seen an average of more than 1,300 new COVID-19 cases each day.

After the state’s largest hospital system warned about a shortage of ICU beds, Arizona Gov. Doug Ducey, a Republican, pushed back on claims that the health care system could soon be overwhelmed.

“The entire time we’ve been focused on a possible worst-case scenario with surge capacity for hospital beds, ICU beds and ventilators,” Ducey told reporters on Thursday. “Those are not needed or necessary right now.”

While he acknowledged a spike in positive cases, Ducey said a second stay-at-home order was “not under discussion.”

“We put the stay-at-home order there so we could prepare for what we are going through,” he said.

Some states have reopened more slowly with a set of specific benchmarks for different regions, but Arizona took a more aggressive approach.

The state began easing restrictions on businesses in early May and lifted its statewide lockdown order after May 15. Under Arizona’s reopening plan, businesses are advised to follow federal guidance on social distancing.

There is also no requirement for everyone to wear masks in public.

Public health experts agree: The timing of this spike reflects the state’s reopening.

“Perhaps, Arizona will be a warning sign to other areas,” said Katherine Ellingson, an epidemiologist at the University of Arizona. “We never had that consistent downward trend that would signal it’s time to reopen and we have everything in place to do it safely.”

Before Arizona lifted its stay-at-home order, only about 5% of COVID-19 tests registered as positive. On Monday, that number was around 16%.

A slower reopening gives public health agencies time to identify whether cases are rising and then respond with contact tracing and isolating those who are infected.

“With a fast, rapid reopening, we don’t have the time to mobilize those resources,” said Ellingson.

Maricopa County, home to about 60% of the state’s population, has ramped up contact tracing in recent weeks, but it may not have enough capacity if the surge in cases continues.

Dr. Peter Hotez said the spike in Arizona, as well as in parts of Texas such as Houston, Dallas and Austin, is the consequence of removing restrictions too quickly and without a public health system that can keep pace.

“It was just ‘open it up’ and then more or less business as usual, with a little bit of window dressing,” said Hotez, the dean for the National School of Tropical Medicine at Baylor College of Medicine in Houston. “This is not an abstract number of cases. We’re seeing people pile into intensive care units.”

Arizona’s governor has also faced criticism from the mayors of Arizona’s two biggest cities for not putting in place more stringent requirements.

“There is a pandemic and it’s spreading uncontrollably,” said Tucson Mayor Regina Romero, a Democrat. Ducey, she said, “is just putting up his hands and saying ‘the spread is happening and we just have to go about our business.’”

And the governor’s executive order forbids local governments from implementing their own extra measures, which adds to Romero’s frustration. Texas has a similar measure.

“What he did was pretty much tie the hands of mayors and public health officials,” Romero said.

Arizona’s hospital industry has tried to tamp down fears that it’s on the verge of a crisis. Hospitals are still performing elective surgeries.

“It’s very unfortunate because hospitals right now in Arizona are quite busy with elective procedures,” said Saskia Popescu, a Phoenix-based epidemiologist with George Mason University. “You throw in increasing cases of COVID, and that’s going to very much stress your hospital systems.”

Phoenix’s triple-digit summer temperatures actually may fuel the spread of the virus. People forgo outdoor activities and retreat to air-conditioned indoor spaces, where the risk of transmitting the virus goes up significantly.

“My concern is we’re going to see a lot more people in close quarters for prolonged periods of time,” Popescu said.

Since the stay-at-home order was lifted, Popescu and others say they’ve seen people returning to a pre-pandemic mindset, neglecting to wear masks or maintain social distance. Videos of crowded bars have only propelled these fears.

On Thursday, however, Arizona’s top doctor stressed there were also dangers to keeping the state on lockdown, including the mental health effects of loneliness and isolation.

“We know that it’s in the community. We are not going to be able to stop the spread. And so we can’t stop living as well,” said Dr. Cara Christ, health director for the Arizona Department of Health Services.

But Dr. Quinn Snyder, an emergency medicine physician in Mesa, Arizona, said there needs to be more consistent messaging on public health measures like wearing masks.

“Frankly, I just think a wholesale reevaluation of where we’re at is critical right now, but I can tell you that we’re not doing nearly enough,” said Snyder, who has seen the uptick in seriously ill COVID-19 patients firsthand.

“If we continue to head down this path, the virus will press our health care facilities beyond capacity, where we’re going to have to be making tough decisions like who gets a ventilator and who doesn’t.”

A version of this article originally appeared on Kaiser Health News, which is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

With new daily coronavirus cases rising in at least two dozen states, an explosion of new infections in Arizona is stretching some hospitals and alarming public health experts who link the surge in cases to the state’s lifting of a stay-at-home order a month ago.

Arizona has emerged as one of the country’s newest coronavirus hot spots, with the weekly average of daily cases more than doubling from 2 weeks ago. The total number of people hospitalized is climbing, too.

Over the past week, Arizona has seen an average of more than 1,300 new COVID-19 cases each day.

After the state’s largest hospital system warned about a shortage of ICU beds, Arizona Gov. Doug Ducey, a Republican, pushed back on claims that the health care system could soon be overwhelmed.

“The entire time we’ve been focused on a possible worst-case scenario with surge capacity for hospital beds, ICU beds and ventilators,” Ducey told reporters on Thursday. “Those are not needed or necessary right now.”

While he acknowledged a spike in positive cases, Ducey said a second stay-at-home order was “not under discussion.”

“We put the stay-at-home order there so we could prepare for what we are going through,” he said.

Some states have reopened more slowly with a set of specific benchmarks for different regions, but Arizona took a more aggressive approach.

The state began easing restrictions on businesses in early May and lifted its statewide lockdown order after May 15. Under Arizona’s reopening plan, businesses are advised to follow federal guidance on social distancing.

There is also no requirement for everyone to wear masks in public.

Public health experts agree: The timing of this spike reflects the state’s reopening.

“Perhaps, Arizona will be a warning sign to other areas,” said Katherine Ellingson, an epidemiologist at the University of Arizona. “We never had that consistent downward trend that would signal it’s time to reopen and we have everything in place to do it safely.”

Before Arizona lifted its stay-at-home order, only about 5% of COVID-19 tests registered as positive. On Monday, that number was around 16%.

A slower reopening gives public health agencies time to identify whether cases are rising and then respond with contact tracing and isolating those who are infected.

“With a fast, rapid reopening, we don’t have the time to mobilize those resources,” said Ellingson.

Maricopa County, home to about 60% of the state’s population, has ramped up contact tracing in recent weeks, but it may not have enough capacity if the surge in cases continues.

Dr. Peter Hotez said the spike in Arizona, as well as in parts of Texas such as Houston, Dallas and Austin, is the consequence of removing restrictions too quickly and without a public health system that can keep pace.

“It was just ‘open it up’ and then more or less business as usual, with a little bit of window dressing,” said Hotez, the dean for the National School of Tropical Medicine at Baylor College of Medicine in Houston. “This is not an abstract number of cases. We’re seeing people pile into intensive care units.”

Arizona’s governor has also faced criticism from the mayors of Arizona’s two biggest cities for not putting in place more stringent requirements.

“There is a pandemic and it’s spreading uncontrollably,” said Tucson Mayor Regina Romero, a Democrat. Ducey, she said, “is just putting up his hands and saying ‘the spread is happening and we just have to go about our business.’”

And the governor’s executive order forbids local governments from implementing their own extra measures, which adds to Romero’s frustration. Texas has a similar measure.

“What he did was pretty much tie the hands of mayors and public health officials,” Romero said.

Arizona’s hospital industry has tried to tamp down fears that it’s on the verge of a crisis. Hospitals are still performing elective surgeries.

“It’s very unfortunate because hospitals right now in Arizona are quite busy with elective procedures,” said Saskia Popescu, a Phoenix-based epidemiologist with George Mason University. “You throw in increasing cases of COVID, and that’s going to very much stress your hospital systems.”

Phoenix’s triple-digit summer temperatures actually may fuel the spread of the virus. People forgo outdoor activities and retreat to air-conditioned indoor spaces, where the risk of transmitting the virus goes up significantly.

“My concern is we’re going to see a lot more people in close quarters for prolonged periods of time,” Popescu said.

Since the stay-at-home order was lifted, Popescu and others say they’ve seen people returning to a pre-pandemic mindset, neglecting to wear masks or maintain social distance. Videos of crowded bars have only propelled these fears.

On Thursday, however, Arizona’s top doctor stressed there were also dangers to keeping the state on lockdown, including the mental health effects of loneliness and isolation.

“We know that it’s in the community. We are not going to be able to stop the spread. And so we can’t stop living as well,” said Dr. Cara Christ, health director for the Arizona Department of Health Services.

But Dr. Quinn Snyder, an emergency medicine physician in Mesa, Arizona, said there needs to be more consistent messaging on public health measures like wearing masks.

“Frankly, I just think a wholesale reevaluation of where we’re at is critical right now, but I can tell you that we’re not doing nearly enough,” said Snyder, who has seen the uptick in seriously ill COVID-19 patients firsthand.

“If we continue to head down this path, the virus will press our health care facilities beyond capacity, where we’re going to have to be making tough decisions like who gets a ventilator and who doesn’t.”

A version of this article originally appeared on Kaiser Health News, which is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Tralokinumab, an investigational biologic agent for the treatment of moderate to severe atopic dermatitis (AD), hit all primary and secondary endpoints in three pivotal phase 3 clinical trials presented at the virtual annual meeting of the American Academy of Dermatology.

Tralokinumab is a fully human monoclonal antibody which binds specifically to interleukin-13 and thereby prevents downstream IL-13 signaling. In contrast, dupilumab (Dupixent), at present the only approved biologic agent for AD, blocks both the IL-13 and IL-4 pathways.

Two of the pivotal phase 3 trials presented at AAD 2020 – ECZTRA 1 and ECZTRA 2 – were identically designed, randomized, double-blind, placebo-controlled, 52-week, multinational monotherapy studies including a collective 1,596 adults with moderate to severe AD. In contrast, ECZTRA 3 was a 380-patient, double-blind, randomized, 32-week study of tralokinumab in combination with a topical corticosteroid versus placebo injections plus a topical corticosteroid.

“I would say the take-home point of these trials is they are proof of principle that blocking just IL-13 can be an effective approach. The studies help us understand that IL-13 is an important driver cytokine for the disease,” Eric Simpson, MD, lead clinical investigator for ECZTRA 2, said in an interview.

In all three phase 3 trials, the primary endpoint was achievement of a clinical response as defined by an Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) plus at least a 75% improvement in the Eczema Area and Severity Index score (EASI-75) at week 16. In ECZTRA 1 and 2, this was accomplished in 16% and 22% of patients on 300 mg of tralokinumab administered subcutaneously every 2 weeks, compared with 7% and 11% of placebo-treated controls.

Patients with a clinical response at week 16 were then rerandomized to tralokinumab either every other week or every 4 weeks or to placebo for an additional 36 weeks. At 52 weeks, 51% and 59% of patients in ECZTRA 1 and 2, respectively, who had a clinical response at week 16 maintained an IGA 0/1 response while on tralokinumab every 2 weeks, as did 39% and 45% of those switched to treatment every 4 weeks. Similarly, 60% and 56% of clinical responders at week 16 maintained an EASI-75 response at week 52 with tralokinumab every 2 weeks, as did 49% and 51% of those rerandomized to treatment every 4 weeks.

The safety profile of tralokinumab in the two monotherapy trials was comparable with placebo.

In the ECZTRA studies, tralokinumab achieved significant improvement at week 16 in secondary endpoints including itch, health-related quality of life, and severity and extent of skin lesions.

How does tralokinumab, with its narrower focus targeting a single cytokine, stack up against dupilumab, the dual IL-13/IL-4 inhibitor that’s transformed the treatment of patients with moderate or severe AD?

Dr. Simpson, who was also principal investigator in a pivotal phase 3 trial for dupilumab, emphasized that no firm conclusions can be drawn because there have been no head-to-head comparative trials and the tralokinumab and dupilumab trials had different patient populations, geographic locations, and washout periods. With those caveats, however, he commented that, “just on the surface, numerically, for the monotherapy studies, dupilumab hit some higher targets than tralokinumab in terms of the percentage of patients clear or almost clear.”

In terms of safety, it appears that the risk of conjunctivitis may be lower with tralokinumab than dupilumab, with rates of 7% and 3% through 52 weeks in ECZTRA 1 and 2, respectively, versus 2% with placebo, although again this is “a caveated conclusion,” said Dr. Simpson, professor of dermatology at Oregon Health and Science University, Portland.

Tralokinumab combination therapy in ECZTRA 3

At 16 weeks, 39% of patients treated with tralokinumab plus topical corticosteroids had an IGA of 0/1 and 56% had an EASI-75 response, compared with 26% and 36% of patients on topical corticosteroids plus biweekly placebo injections. More than 90% of patients with a good clinical response at week 16 maintained that response at week 32 while on tralokinumab biweekly plus topical steroids. Among good responders at week 16 who were rerandomized to 300 mg of tralokinumab every 4 weeks plus topical steroids, 78% still had an IGA of 0/1 at week 32, and 91% had an EASI-75, reported Jonathan I. Silverberg, MD, PhD, director of clinical research and contact dermatitis at George Washington University, Washington.

A randomized, placebo-controlled combination therapy study such as this provides information that’s especially useful in clinical practice, Dr. Simpson observed.

“When I’m talking to patients about any biologics or oral therapies, I usually quote the figures from the combination therapy studies because the vast majority of our patients are using topical therapy in addition to systemics,” he said in the interview.

Asked how he envisions tralokinumab’s role in clinical practice, should the drug receive regulatory approval, Dr. Simpson said that he welcomes the prospect of having an additional treatment option to discuss with patients. Tralokinumab could be considered either as first-line therapy in patients who are failing on topical therapy or for patients who don’t respond adequately to or experience limiting side effects on dupilumab.

“There isn’t any established, published treatment algorithm in atopic dermatitis, probably for good reason, since we don’t have data to tell us you should start here and then move there. Those are long, difficult studies to perform,” Dr. Simpson said.

LEO Pharma has announced that it has applied for marketing approval for tralokinumab to the European Medicines Agency and plans to do so with the Food and Drug Administration by year’s end.

Dr. Simpson reported receiving research grants from and serving as a consultant to LEO Pharma, sponsor of the ECZTRA trials. He has similar financial relationships with close to a dozen other pharmaceutical companies.

[email protected]

Tralokinumab, an investigational biologic agent for the treatment of moderate to severe atopic dermatitis (AD), hit all primary and secondary endpoints in three pivotal phase 3 clinical trials presented at the virtual annual meeting of the American Academy of Dermatology.

Tralokinumab is a fully human monoclonal antibody which binds specifically to interleukin-13 and thereby prevents downstream IL-13 signaling. In contrast, dupilumab (Dupixent), at present the only approved biologic agent for AD, blocks both the IL-13 and IL-4 pathways.

Two of the pivotal phase 3 trials presented at AAD 2020 – ECZTRA 1 and ECZTRA 2 – were identically designed, randomized, double-blind, placebo-controlled, 52-week, multinational monotherapy studies including a collective 1,596 adults with moderate to severe AD. In contrast, ECZTRA 3 was a 380-patient, double-blind, randomized, 32-week study of tralokinumab in combination with a topical corticosteroid versus placebo injections plus a topical corticosteroid.

“I would say the take-home point of these trials is they are proof of principle that blocking just IL-13 can be an effective approach. The studies help us understand that IL-13 is an important driver cytokine for the disease,” Eric Simpson, MD, lead clinical investigator for ECZTRA 2, said in an interview.

In all three phase 3 trials, the primary endpoint was achievement of a clinical response as defined by an Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) plus at least a 75% improvement in the Eczema Area and Severity Index score (EASI-75) at week 16. In ECZTRA 1 and 2, this was accomplished in 16% and 22% of patients on 300 mg of tralokinumab administered subcutaneously every 2 weeks, compared with 7% and 11% of placebo-treated controls.

Patients with a clinical response at week 16 were then rerandomized to tralokinumab either every other week or every 4 weeks or to placebo for an additional 36 weeks. At 52 weeks, 51% and 59% of patients in ECZTRA 1 and 2, respectively, who had a clinical response at week 16 maintained an IGA 0/1 response while on tralokinumab every 2 weeks, as did 39% and 45% of those switched to treatment every 4 weeks. Similarly, 60% and 56% of clinical responders at week 16 maintained an EASI-75 response at week 52 with tralokinumab every 2 weeks, as did 49% and 51% of those rerandomized to treatment every 4 weeks.

The safety profile of tralokinumab in the two monotherapy trials was comparable with placebo.

In the ECZTRA studies, tralokinumab achieved significant improvement at week 16 in secondary endpoints including itch, health-related quality of life, and severity and extent of skin lesions.

How does tralokinumab, with its narrower focus targeting a single cytokine, stack up against dupilumab, the dual IL-13/IL-4 inhibitor that’s transformed the treatment of patients with moderate or severe AD?

Dr. Simpson, who was also principal investigator in a pivotal phase 3 trial for dupilumab, emphasized that no firm conclusions can be drawn because there have been no head-to-head comparative trials and the tralokinumab and dupilumab trials had different patient populations, geographic locations, and washout periods. With those caveats, however, he commented that, “just on the surface, numerically, for the monotherapy studies, dupilumab hit some higher targets than tralokinumab in terms of the percentage of patients clear or almost clear.”

In terms of safety, it appears that the risk of conjunctivitis may be lower with tralokinumab than dupilumab, with rates of 7% and 3% through 52 weeks in ECZTRA 1 and 2, respectively, versus 2% with placebo, although again this is “a caveated conclusion,” said Dr. Simpson, professor of dermatology at Oregon Health and Science University, Portland.

Tralokinumab combination therapy in ECZTRA 3

At 16 weeks, 39% of patients treated with tralokinumab plus topical corticosteroids had an IGA of 0/1 and 56% had an EASI-75 response, compared with 26% and 36% of patients on topical corticosteroids plus biweekly placebo injections. More than 90% of patients with a good clinical response at week 16 maintained that response at week 32 while on tralokinumab biweekly plus topical steroids. Among good responders at week 16 who were rerandomized to 300 mg of tralokinumab every 4 weeks plus topical steroids, 78% still had an IGA of 0/1 at week 32, and 91% had an EASI-75, reported Jonathan I. Silverberg, MD, PhD, director of clinical research and contact dermatitis at George Washington University, Washington.

A randomized, placebo-controlled combination therapy study such as this provides information that’s especially useful in clinical practice, Dr. Simpson observed.

“When I’m talking to patients about any biologics or oral therapies, I usually quote the figures from the combination therapy studies because the vast majority of our patients are using topical therapy in addition to systemics,” he said in the interview.

Asked how he envisions tralokinumab’s role in clinical practice, should the drug receive regulatory approval, Dr. Simpson said that he welcomes the prospect of having an additional treatment option to discuss with patients. Tralokinumab could be considered either as first-line therapy in patients who are failing on topical therapy or for patients who don’t respond adequately to or experience limiting side effects on dupilumab.

“There isn’t any established, published treatment algorithm in atopic dermatitis, probably for good reason, since we don’t have data to tell us you should start here and then move there. Those are long, difficult studies to perform,” Dr. Simpson said.

LEO Pharma has announced that it has applied for marketing approval for tralokinumab to the European Medicines Agency and plans to do so with the Food and Drug Administration by year’s end.

Dr. Simpson reported receiving research grants from and serving as a consultant to LEO Pharma, sponsor of the ECZTRA trials. He has similar financial relationships with close to a dozen other pharmaceutical companies.

[email protected]

Tralokinumab, an investigational biologic agent for the treatment of moderate to severe atopic dermatitis (AD), hit all primary and secondary endpoints in three pivotal phase 3 clinical trials presented at the virtual annual meeting of the American Academy of Dermatology.

Tralokinumab is a fully human monoclonal antibody which binds specifically to interleukin-13 and thereby prevents downstream IL-13 signaling. In contrast, dupilumab (Dupixent), at present the only approved biologic agent for AD, blocks both the IL-13 and IL-4 pathways.

Two of the pivotal phase 3 trials presented at AAD 2020 – ECZTRA 1 and ECZTRA 2 – were identically designed, randomized, double-blind, placebo-controlled, 52-week, multinational monotherapy studies including a collective 1,596 adults with moderate to severe AD. In contrast, ECZTRA 3 was a 380-patient, double-blind, randomized, 32-week study of tralokinumab in combination with a topical corticosteroid versus placebo injections plus a topical corticosteroid.

“I would say the take-home point of these trials is they are proof of principle that blocking just IL-13 can be an effective approach. The studies help us understand that IL-13 is an important driver cytokine for the disease,” Eric Simpson, MD, lead clinical investigator for ECZTRA 2, said in an interview.

In all three phase 3 trials, the primary endpoint was achievement of a clinical response as defined by an Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) plus at least a 75% improvement in the Eczema Area and Severity Index score (EASI-75) at week 16. In ECZTRA 1 and 2, this was accomplished in 16% and 22% of patients on 300 mg of tralokinumab administered subcutaneously every 2 weeks, compared with 7% and 11% of placebo-treated controls.

Patients with a clinical response at week 16 were then rerandomized to tralokinumab either every other week or every 4 weeks or to placebo for an additional 36 weeks. At 52 weeks, 51% and 59% of patients in ECZTRA 1 and 2, respectively, who had a clinical response at week 16 maintained an IGA 0/1 response while on tralokinumab every 2 weeks, as did 39% and 45% of those switched to treatment every 4 weeks. Similarly, 60% and 56% of clinical responders at week 16 maintained an EASI-75 response at week 52 with tralokinumab every 2 weeks, as did 49% and 51% of those rerandomized to treatment every 4 weeks.

The safety profile of tralokinumab in the two monotherapy trials was comparable with placebo.

In the ECZTRA studies, tralokinumab achieved significant improvement at week 16 in secondary endpoints including itch, health-related quality of life, and severity and extent of skin lesions.

How does tralokinumab, with its narrower focus targeting a single cytokine, stack up against dupilumab, the dual IL-13/IL-4 inhibitor that’s transformed the treatment of patients with moderate or severe AD?

Dr. Simpson, who was also principal investigator in a pivotal phase 3 trial for dupilumab, emphasized that no firm conclusions can be drawn because there have been no head-to-head comparative trials and the tralokinumab and dupilumab trials had different patient populations, geographic locations, and washout periods. With those caveats, however, he commented that, “just on the surface, numerically, for the monotherapy studies, dupilumab hit some higher targets than tralokinumab in terms of the percentage of patients clear or almost clear.”

In terms of safety, it appears that the risk of conjunctivitis may be lower with tralokinumab than dupilumab, with rates of 7% and 3% through 52 weeks in ECZTRA 1 and 2, respectively, versus 2% with placebo, although again this is “a caveated conclusion,” said Dr. Simpson, professor of dermatology at Oregon Health and Science University, Portland.

Tralokinumab combination therapy in ECZTRA 3

At 16 weeks, 39% of patients treated with tralokinumab plus topical corticosteroids had an IGA of 0/1 and 56% had an EASI-75 response, compared with 26% and 36% of patients on topical corticosteroids plus biweekly placebo injections. More than 90% of patients with a good clinical response at week 16 maintained that response at week 32 while on tralokinumab biweekly plus topical steroids. Among good responders at week 16 who were rerandomized to 300 mg of tralokinumab every 4 weeks plus topical steroids, 78% still had an IGA of 0/1 at week 32, and 91% had an EASI-75, reported Jonathan I. Silverberg, MD, PhD, director of clinical research and contact dermatitis at George Washington University, Washington.

A randomized, placebo-controlled combination therapy study such as this provides information that’s especially useful in clinical practice, Dr. Simpson observed.

“When I’m talking to patients about any biologics or oral therapies, I usually quote the figures from the combination therapy studies because the vast majority of our patients are using topical therapy in addition to systemics,” he said in the interview.

Asked how he envisions tralokinumab’s role in clinical practice, should the drug receive regulatory approval, Dr. Simpson said that he welcomes the prospect of having an additional treatment option to discuss with patients. Tralokinumab could be considered either as first-line therapy in patients who are failing on topical therapy or for patients who don’t respond adequately to or experience limiting side effects on dupilumab.

“There isn’t any established, published treatment algorithm in atopic dermatitis, probably for good reason, since we don’t have data to tell us you should start here and then move there. Those are long, difficult studies to perform,” Dr. Simpson said.

LEO Pharma has announced that it has applied for marketing approval for tralokinumab to the European Medicines Agency and plans to do so with the Food and Drug Administration by year’s end.

Dr. Simpson reported receiving research grants from and serving as a consultant to LEO Pharma, sponsor of the ECZTRA trials. He has similar financial relationships with close to a dozen other pharmaceutical companies.

[email protected]