PHM 2021 session

Let’s Go Virtual! Developing, Implementing, and Evaluating Telehealth Models of Care for Pediatric Hospital Medicine

Presenters

Brooke Geyer, DO; Christina Olson, MD; and Amy Willis, MD, FAAP

Session summary

Dr. Geyer, Dr. Olson, and Dr. Willis of the University of Colorado presented and facilitated a workshop discussing the role of telehealth in pediatric hospital medicine. Participants were given a brief introduction to the basics of telehealth practices before breaking up into small groups to explore the process of developing, implementing, and evaluating a telehealth model in a pediatric hospital. For each of these topics, the presenters led the breakout groups through a discussion of Colorado’s successful telehealth models, including virtual nocturnists, health system resource optimization, and virtual transitions of care, as well as addressed the participants’ questions unique to their telehealth experiences. The session emphasized the emerging role of telehealth in pediatric hospital medicine and that “telehealth is here to stay, and we have an opportunity to redesign health care forever.”

Key takeaways

• Telehealth is more than just synchronous virtual patient care, it encompasses asynchronous care, remote patient monitoring, education, policy, and more.
• Telehealth standards of care are the same as in-person care.
• Development and implementation of a telehealth model in pediatric hospital medicine is feasible with appropriate planning and conversations with key stakeholders.
• Evaluation and refinement of telehealth models is an iterative process that will take time, much like Plan-Do-Study-Act cycles in quality improvement work.

Dr. Scott is a second-year pediatric hospital medicine fellow at New York–Presbyterian Columbia/Cornell. Her academic interests are in curriculum development and evaluation in medical education with a focus on telemedicine.

PHM 2021 session

Let’s Go Virtual! Developing, Implementing, and Evaluating Telehealth Models of Care for Pediatric Hospital Medicine

Presenters

Brooke Geyer, DO; Christina Olson, MD; and Amy Willis, MD, FAAP

Session summary

Dr. Geyer, Dr. Olson, and Dr. Willis of the University of Colorado presented and facilitated a workshop discussing the role of telehealth in pediatric hospital medicine. Participants were given a brief introduction to the basics of telehealth practices before breaking up into small groups to explore the process of developing, implementing, and evaluating a telehealth model in a pediatric hospital. For each of these topics, the presenters led the breakout groups through a discussion of Colorado’s successful telehealth models, including virtual nocturnists, health system resource optimization, and virtual transitions of care, as well as addressed the participants’ questions unique to their telehealth experiences. The session emphasized the emerging role of telehealth in pediatric hospital medicine and that “telehealth is here to stay, and we have an opportunity to redesign health care forever.”

Key takeaways

• Telehealth is more than just synchronous virtual patient care, it encompasses asynchronous care, remote patient monitoring, education, policy, and more.
• Telehealth standards of care are the same as in-person care.
• Development and implementation of a telehealth model in pediatric hospital medicine is feasible with appropriate planning and conversations with key stakeholders.
• Evaluation and refinement of telehealth models is an iterative process that will take time, much like Plan-Do-Study-Act cycles in quality improvement work.

Dr. Scott is a second-year pediatric hospital medicine fellow at New York–Presbyterian Columbia/Cornell. Her academic interests are in curriculum development and evaluation in medical education with a focus on telemedicine.

PHM 2021 session

Let’s Go Virtual! Developing, Implementing, and Evaluating Telehealth Models of Care for Pediatric Hospital Medicine

Presenters

Brooke Geyer, DO; Christina Olson, MD; and Amy Willis, MD, FAAP

Session summary

Dr. Geyer, Dr. Olson, and Dr. Willis of the University of Colorado presented and facilitated a workshop discussing the role of telehealth in pediatric hospital medicine. Participants were given a brief introduction to the basics of telehealth practices before breaking up into small groups to explore the process of developing, implementing, and evaluating a telehealth model in a pediatric hospital. For each of these topics, the presenters led the breakout groups through a discussion of Colorado’s successful telehealth models, including virtual nocturnists, health system resource optimization, and virtual transitions of care, as well as addressed the participants’ questions unique to their telehealth experiences. The session emphasized the emerging role of telehealth in pediatric hospital medicine and that “telehealth is here to stay, and we have an opportunity to redesign health care forever.”

Key takeaways

• Telehealth is more than just synchronous virtual patient care, it encompasses asynchronous care, remote patient monitoring, education, policy, and more.
• Telehealth standards of care are the same as in-person care.
• Development and implementation of a telehealth model in pediatric hospital medicine is feasible with appropriate planning and conversations with key stakeholders.
• Evaluation and refinement of telehealth models is an iterative process that will take time, much like Plan-Do-Study-Act cycles in quality improvement work.

Dr. Scott is a second-year pediatric hospital medicine fellow at New York–Presbyterian Columbia/Cornell. Her academic interests are in curriculum development and evaluation in medical education with a focus on telemedicine.

The U.S. Preventive Services Task Force continues to recommend that pregnant women at risk of developing preeclampsia take low-dose aspirin daily, and has expanded the criteria for those at risk.

“I think that this issue has been one that people have talked about and thought about for a long time, but it hasn’t kind of leapt into the front for all practitioners,” Aaron B. Caughey, MD, MPH, PhD, a USPSTF member, said in an interview. “We think it’s really important that all providers and all pregnant persons are aware that folks at an increased risk for preeclampsia can receive a reduction in the risk of preeclampsia from receiving baby aspirin starting after 12 weeks of gestation.”

The task force concluded with moderate certainty that a daily dose of 81 milligrams of aspirin after 12 weeks of pregnancy could reduce the risk for preeclampsia, preterm birth, and stillbirths in pregnant persons at high risk for preeclampsia. The recommendations, which were published in JAMA, are identical to the panel’s 2014 recommendations.

However, the new draft includes a suggestion that expands the list of pregnant patients at risk of developing preeclampsia. In 2014, the USPSTF recommended that clinicians prescribe low-dose daily aspirin to those who had at least two moderate-risk factors related to disparity – first pregnancy, obesity, family history of preeclampsia, lower income, age of 35 years or older, of African descent, and previous adverse pregnancy outcomes. The recent update suggests clinicians consider prescribing low-dose aspirin to patients with just one of the moderate risk factors. The task force also added “in vitro fertilization” as a moderate risk factor.

Dr. Caughey said the motivation for this addition was out of concern for disparities in outcomes for people who have less access to care and to help curb the racial disparity in the prevalence of preeclampsia in Black women and other disadvantaged groups. “[In an effort] to prevent the development of preeclampsia in such individuals that have historically had worse health outcomes, we wanted to emphasize that should at least be considered by clinicians,” Dr. Caughey said.

This change is a “major one,” according to Victor Klein, MD, MBA, CPHRM, a specialist in high-risk pregnancy.

“That’s probably three-quarters of my patients. The majority of my patients will now be candidates [to receive a low-dose aspirin prescription to prevent preeclampsia],” Dr. Klein, vice chairman of obstetrics and gynecology at North Shore University Hospital, Manhasset, N.Y., said in an interview. “[This] may increase the amount of people who will be getting the aspirin and therefore decrease the chance of preeclampsia or developing preeclampsia.”

Preeclampsia is a condition characterized by high blood pressure and signs of problems with the kidneys, liver, and other organs during pregnancy, according to the Centers for Disease Control and Prevention. The condition occurs in about 1 in 25 pregnancies in the United States and can cause serious and fatal complications for both the mother and child.

Although the update reaffirms that aspirin is safe and effective in preventing preeclampsia, Dr. Klein believes the dosage they are recommending is too low, as he has had patients develop preeclampsia while taking 81 mg of aspirin daily. Dr. Klein says he prescribes two daily doses of 81 mg aspirin to some of his patients.

“The majority of us in the field of high-risk pregnancies feel that 81 milligrams is not enough,” Dr. Klein said. “So I am disappointed that [they] didn’t talk about consideration for higher doses. I have patients taking two baby aspirins who developed preeclampsia.”

However, the systematic review that the USPSTF’s recommendation was based on did not “really find evidence to suggest that a higher dose was necessarily better than the lower dose,” Dr. Caughey said. However, this may be something they look at again in the near future.

“I know of clinicians that are asking if we should be using a higher dose,” Dr. Caughey explained. “If more evidence accumulates then absolutely we will look at that issue again.”

In their draft, the task force said there’s limited evidence on the side effects of low-dose aspirin on long-term child developmental outcomes and said the evidence report found no physical or developmental differences in infants at age 12 and 18 months.

USPSTF said comparative effectiveness trials are needed to identify “specific aspirin protocols” and evaluate which dosage, timing, and time of day will have the greatest benefit. The task force also said more research is needed to improve identification of those at an increased risk of developing preeclampsia.

Dr. Caughey and Dr. Klein disclosed no conflicts of interest.

The U.S. Preventive Services Task Force continues to recommend that pregnant women at risk of developing preeclampsia take low-dose aspirin daily, and has expanded the criteria for those at risk.

“I think that this issue has been one that people have talked about and thought about for a long time, but it hasn’t kind of leapt into the front for all practitioners,” Aaron B. Caughey, MD, MPH, PhD, a USPSTF member, said in an interview. “We think it’s really important that all providers and all pregnant persons are aware that folks at an increased risk for preeclampsia can receive a reduction in the risk of preeclampsia from receiving baby aspirin starting after 12 weeks of gestation.”

The task force concluded with moderate certainty that a daily dose of 81 milligrams of aspirin after 12 weeks of pregnancy could reduce the risk for preeclampsia, preterm birth, and stillbirths in pregnant persons at high risk for preeclampsia. The recommendations, which were published in JAMA, are identical to the panel’s 2014 recommendations.

However, the new draft includes a suggestion that expands the list of pregnant patients at risk of developing preeclampsia. In 2014, the USPSTF recommended that clinicians prescribe low-dose daily aspirin to those who had at least two moderate-risk factors related to disparity – first pregnancy, obesity, family history of preeclampsia, lower income, age of 35 years or older, of African descent, and previous adverse pregnancy outcomes. The recent update suggests clinicians consider prescribing low-dose aspirin to patients with just one of the moderate risk factors. The task force also added “in vitro fertilization” as a moderate risk factor.

Dr. Caughey said the motivation for this addition was out of concern for disparities in outcomes for people who have less access to care and to help curb the racial disparity in the prevalence of preeclampsia in Black women and other disadvantaged groups. “[In an effort] to prevent the development of preeclampsia in such individuals that have historically had worse health outcomes, we wanted to emphasize that should at least be considered by clinicians,” Dr. Caughey said.

This change is a “major one,” according to Victor Klein, MD, MBA, CPHRM, a specialist in high-risk pregnancy.

“That’s probably three-quarters of my patients. The majority of my patients will now be candidates [to receive a low-dose aspirin prescription to prevent preeclampsia],” Dr. Klein, vice chairman of obstetrics and gynecology at North Shore University Hospital, Manhasset, N.Y., said in an interview. “[This] may increase the amount of people who will be getting the aspirin and therefore decrease the chance of preeclampsia or developing preeclampsia.”

Preeclampsia is a condition characterized by high blood pressure and signs of problems with the kidneys, liver, and other organs during pregnancy, according to the Centers for Disease Control and Prevention. The condition occurs in about 1 in 25 pregnancies in the United States and can cause serious and fatal complications for both the mother and child.

Although the update reaffirms that aspirin is safe and effective in preventing preeclampsia, Dr. Klein believes the dosage they are recommending is too low, as he has had patients develop preeclampsia while taking 81 mg of aspirin daily. Dr. Klein says he prescribes two daily doses of 81 mg aspirin to some of his patients.

“The majority of us in the field of high-risk pregnancies feel that 81 milligrams is not enough,” Dr. Klein said. “So I am disappointed that [they] didn’t talk about consideration for higher doses. I have patients taking two baby aspirins who developed preeclampsia.”

However, the systematic review that the USPSTF’s recommendation was based on did not “really find evidence to suggest that a higher dose was necessarily better than the lower dose,” Dr. Caughey said. However, this may be something they look at again in the near future.

“I know of clinicians that are asking if we should be using a higher dose,” Dr. Caughey explained. “If more evidence accumulates then absolutely we will look at that issue again.”

In their draft, the task force said there’s limited evidence on the side effects of low-dose aspirin on long-term child developmental outcomes and said the evidence report found no physical or developmental differences in infants at age 12 and 18 months.

USPSTF said comparative effectiveness trials are needed to identify “specific aspirin protocols” and evaluate which dosage, timing, and time of day will have the greatest benefit. The task force also said more research is needed to improve identification of those at an increased risk of developing preeclampsia.

Dr. Caughey and Dr. Klein disclosed no conflicts of interest.

The U.S. Preventive Services Task Force continues to recommend that pregnant women at risk of developing preeclampsia take low-dose aspirin daily, and has expanded the criteria for those at risk.

“I think that this issue has been one that people have talked about and thought about for a long time, but it hasn’t kind of leapt into the front for all practitioners,” Aaron B. Caughey, MD, MPH, PhD, a USPSTF member, said in an interview. “We think it’s really important that all providers and all pregnant persons are aware that folks at an increased risk for preeclampsia can receive a reduction in the risk of preeclampsia from receiving baby aspirin starting after 12 weeks of gestation.”

The task force concluded with moderate certainty that a daily dose of 81 milligrams of aspirin after 12 weeks of pregnancy could reduce the risk for preeclampsia, preterm birth, and stillbirths in pregnant persons at high risk for preeclampsia. The recommendations, which were published in JAMA, are identical to the panel’s 2014 recommendations.

However, the new draft includes a suggestion that expands the list of pregnant patients at risk of developing preeclampsia. In 2014, the USPSTF recommended that clinicians prescribe low-dose daily aspirin to those who had at least two moderate-risk factors related to disparity – first pregnancy, obesity, family history of preeclampsia, lower income, age of 35 years or older, of African descent, and previous adverse pregnancy outcomes. The recent update suggests clinicians consider prescribing low-dose aspirin to patients with just one of the moderate risk factors. The task force also added “in vitro fertilization” as a moderate risk factor.

Dr. Caughey said the motivation for this addition was out of concern for disparities in outcomes for people who have less access to care and to help curb the racial disparity in the prevalence of preeclampsia in Black women and other disadvantaged groups. “[In an effort] to prevent the development of preeclampsia in such individuals that have historically had worse health outcomes, we wanted to emphasize that should at least be considered by clinicians,” Dr. Caughey said.

This change is a “major one,” according to Victor Klein, MD, MBA, CPHRM, a specialist in high-risk pregnancy.

“That’s probably three-quarters of my patients. The majority of my patients will now be candidates [to receive a low-dose aspirin prescription to prevent preeclampsia],” Dr. Klein, vice chairman of obstetrics and gynecology at North Shore University Hospital, Manhasset, N.Y., said in an interview. “[This] may increase the amount of people who will be getting the aspirin and therefore decrease the chance of preeclampsia or developing preeclampsia.”

Preeclampsia is a condition characterized by high blood pressure and signs of problems with the kidneys, liver, and other organs during pregnancy, according to the Centers for Disease Control and Prevention. The condition occurs in about 1 in 25 pregnancies in the United States and can cause serious and fatal complications for both the mother and child.

Although the update reaffirms that aspirin is safe and effective in preventing preeclampsia, Dr. Klein believes the dosage they are recommending is too low, as he has had patients develop preeclampsia while taking 81 mg of aspirin daily. Dr. Klein says he prescribes two daily doses of 81 mg aspirin to some of his patients.

“The majority of us in the field of high-risk pregnancies feel that 81 milligrams is not enough,” Dr. Klein said. “So I am disappointed that [they] didn’t talk about consideration for higher doses. I have patients taking two baby aspirins who developed preeclampsia.”

However, the systematic review that the USPSTF’s recommendation was based on did not “really find evidence to suggest that a higher dose was necessarily better than the lower dose,” Dr. Caughey said. However, this may be something they look at again in the near future.

“I know of clinicians that are asking if we should be using a higher dose,” Dr. Caughey explained. “If more evidence accumulates then absolutely we will look at that issue again.”

In their draft, the task force said there’s limited evidence on the side effects of low-dose aspirin on long-term child developmental outcomes and said the evidence report found no physical or developmental differences in infants at age 12 and 18 months.

USPSTF said comparative effectiveness trials are needed to identify “specific aspirin protocols” and evaluate which dosage, timing, and time of day will have the greatest benefit. The task force also said more research is needed to improve identification of those at an increased risk of developing preeclampsia.

Dr. Caughey and Dr. Klein disclosed no conflicts of interest.

Checkpoint inhibition for consolidation after chemoradiotherapy (CRT) showed promising survival benefit in patients with unresectable stage III non–small cell lung cancer (NSCLC) in two recent studies, including one looking at the investigational agent sugemalimab and one assessing durvalumab in a real-world setting.

Statistically significant and clinically meaningful improvement in progression-free survival (PFS) was observed with sugemalimab versus placebo in the randomized, phase 3 GEMSTONE-301 study, and consolidation durvalumab showed effectiveness in a real-world cohort in the PACIFIC-R study.

Findings from both studies were presented at the 2021 European Society for Medical Oncology Congress.
 

GEMSTONE-301

Median progression-free survival among 381 patients randomized 2:1 to receive 1,200 mg of sugemalimab or placebo every 3 weeks after either concurrent or sequential chemoradiotherapy was 9.0 versus 5.8 months, in the treatment arms, respectively (hazard ratio, 0.64) (Abstract LBA43), reported Yi-Long Wu, MD, of Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.

Patients were recruited from 50 sites, and one-third had received sequential CRT. Progression-free survival was assessed at median follow up of 14 months.

“The 12- and 18-month PFS rates were 45% vs. 26% and 39% vs. 23%, respectively,” Dr. Wu said.

Of note, the PFS benefit was observed both for patients who underwent sequential CRT (median PFS, 8.1 vs. 4.1 months with sugemalimab vs. placebo; hazard ratio, 0.59) and for those who received concurrent CRT (median PFS, 10.5 vs. 6.4 months; HR, 0.66).

Overall survival (OS) data were not mature at the time of the presentation, but a trend favoring sugemalimab was observed (HR, 0.44) he noted.

Sugemalimab, an investigational anti–programmed death-ligand 1 (PD-L1 )monoclonal antibody, was well tolerated; grade 3 or higher treatment-emergent adverse events (AEs) occurred in 24.3% of patients in the sugemalimab group and in 23.8% in the placebo group.

Concurrent chemoradiotherapy followed by immunotherapy is the standard of care for patients with unresectable stage III NSCLC, but nearly half undergo sequential CRT because they can’t tolerate concurrent treatment, Dr. Wu explained, describing the rationale for the study – the first phase 3 trial looking at both concurrent and sequential CRT in this patient population.

The results provide evidence for sugemalimab as a consolidation treatment for those who did not progress following either approach to CRT, he concluded.
 

PACIFIC-R study

The large, international, observational PACIFIC-R study also looked at consolidation in a real-world setting, and confirmed a PFS benefit with durvalumab in stage III NSCLC patients who had completed concurrent or sequential platinum-based CRT within the previous 12 weeks without evidence of disease progression (Abstract 1171MO).

“The median real-world PFS in this cohort was 21.7 months, which is higher than that in the durvalumab arm in the PACIFIC trial, which was 16.9 months,” reported Nicolas Girard, MD, a professor at Institut Curie, Paris.

The PACIFIC trial set the standard for durvalumab-based consolidation after CRT, and ongoing survival benefit was confirmed by 5-year follow-up data, he noted.

The PACIFIC-R trial included 1,399 patients from 11 countries who were treated as part of an expanded-access program following the PACIFIC trial.

Median time to durvalumab initiation after the end of radiotherapy in the cohort was 56 days. Overall median durvalumab treatment duration was 11 months, and the median number of infusions was 22, Dr. Girard said.

Pneumonitis was the most common adverse event leading to discontinuation: 214 (18.5%) patients experienced any-grade pneumonitis and/or interstitial lung disease, and 9.5 discontinued the study as a result. Most cases were mild or moderate, he said.

Subgroup analyses showed that real-world PFS was higher among patients with stage IIIa disease and those with PD-L1–positive tumors, those with nonsquamous disease histology, and those who received concurrent CRT.

“For example, in those with stage IIIa disease, the median real-world PFS was 23.7 months versus 19.2 months in patients with stage IIIb and c disease,” he said.

“PACIFIC-R demonstrated the efficacy of durvalumab consolidation in patients with unresectable stage III non–small cell lung cancer after completion of chemoradiotherapy,” said Dr. Girard. “The effectiveness of durvalumab was consistent among key subgroups, as was safety, when comparing the data with that of PACIFIC.

“The future read-outs of OS will further provide insight into the effectiveness of this regimen.”

Session chair Lizza E. Hendriks, MD, PhD, of Maastricht (the Netherlands) University, applauded the inclusion of patients undergoing sequential CRT in the GEMSTONE-301 and PACIFIC-R studies, noting that it is “very important to have data in sequential radiochemotherapy populations” given the substantial number of patients who require a sequential approach because of poor performance status, difficulty tolerating concurrent CRT, or logistical reasons, such as an inability to travel to receive concurrent CRT.

The GEMSTONE-301 study was funded by CStone Pharmaceuticals. Dr. Wu reported having no disclosures. The PACIFIC-R study was funded by AstraZeneca. Dr. Girard reported financial relationships with AstraZeneca, Bristol Myers Squibb, and Merck Sharp & Dohme. Dr. Hendriks reported financial relationships with numerous companies.

[email protected]

Checkpoint inhibition for consolidation after chemoradiotherapy (CRT) showed promising survival benefit in patients with unresectable stage III non–small cell lung cancer (NSCLC) in two recent studies, including one looking at the investigational agent sugemalimab and one assessing durvalumab in a real-world setting.

Statistically significant and clinically meaningful improvement in progression-free survival (PFS) was observed with sugemalimab versus placebo in the randomized, phase 3 GEMSTONE-301 study, and consolidation durvalumab showed effectiveness in a real-world cohort in the PACIFIC-R study.

Findings from both studies were presented at the 2021 European Society for Medical Oncology Congress.
 

GEMSTONE-301

Median progression-free survival among 381 patients randomized 2:1 to receive 1,200 mg of sugemalimab or placebo every 3 weeks after either concurrent or sequential chemoradiotherapy was 9.0 versus 5.8 months, in the treatment arms, respectively (hazard ratio, 0.64) (Abstract LBA43), reported Yi-Long Wu, MD, of Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.

Patients were recruited from 50 sites, and one-third had received sequential CRT. Progression-free survival was assessed at median follow up of 14 months.

“The 12- and 18-month PFS rates were 45% vs. 26% and 39% vs. 23%, respectively,” Dr. Wu said.

Of note, the PFS benefit was observed both for patients who underwent sequential CRT (median PFS, 8.1 vs. 4.1 months with sugemalimab vs. placebo; hazard ratio, 0.59) and for those who received concurrent CRT (median PFS, 10.5 vs. 6.4 months; HR, 0.66).

Overall survival (OS) data were not mature at the time of the presentation, but a trend favoring sugemalimab was observed (HR, 0.44) he noted.

Sugemalimab, an investigational anti–programmed death-ligand 1 (PD-L1 )monoclonal antibody, was well tolerated; grade 3 or higher treatment-emergent adverse events (AEs) occurred in 24.3% of patients in the sugemalimab group and in 23.8% in the placebo group.

Concurrent chemoradiotherapy followed by immunotherapy is the standard of care for patients with unresectable stage III NSCLC, but nearly half undergo sequential CRT because they can’t tolerate concurrent treatment, Dr. Wu explained, describing the rationale for the study – the first phase 3 trial looking at both concurrent and sequential CRT in this patient population.

The results provide evidence for sugemalimab as a consolidation treatment for those who did not progress following either approach to CRT, he concluded.
 

PACIFIC-R study

The large, international, observational PACIFIC-R study also looked at consolidation in a real-world setting, and confirmed a PFS benefit with durvalumab in stage III NSCLC patients who had completed concurrent or sequential platinum-based CRT within the previous 12 weeks without evidence of disease progression (Abstract 1171MO).

“The median real-world PFS in this cohort was 21.7 months, which is higher than that in the durvalumab arm in the PACIFIC trial, which was 16.9 months,” reported Nicolas Girard, MD, a professor at Institut Curie, Paris.

The PACIFIC trial set the standard for durvalumab-based consolidation after CRT, and ongoing survival benefit was confirmed by 5-year follow-up data, he noted.

The PACIFIC-R trial included 1,399 patients from 11 countries who were treated as part of an expanded-access program following the PACIFIC trial.

Median time to durvalumab initiation after the end of radiotherapy in the cohort was 56 days. Overall median durvalumab treatment duration was 11 months, and the median number of infusions was 22, Dr. Girard said.

Pneumonitis was the most common adverse event leading to discontinuation: 214 (18.5%) patients experienced any-grade pneumonitis and/or interstitial lung disease, and 9.5 discontinued the study as a result. Most cases were mild or moderate, he said.

Subgroup analyses showed that real-world PFS was higher among patients with stage IIIa disease and those with PD-L1–positive tumors, those with nonsquamous disease histology, and those who received concurrent CRT.

“For example, in those with stage IIIa disease, the median real-world PFS was 23.7 months versus 19.2 months in patients with stage IIIb and c disease,” he said.

“PACIFIC-R demonstrated the efficacy of durvalumab consolidation in patients with unresectable stage III non–small cell lung cancer after completion of chemoradiotherapy,” said Dr. Girard. “The effectiveness of durvalumab was consistent among key subgroups, as was safety, when comparing the data with that of PACIFIC.

“The future read-outs of OS will further provide insight into the effectiveness of this regimen.”

Session chair Lizza E. Hendriks, MD, PhD, of Maastricht (the Netherlands) University, applauded the inclusion of patients undergoing sequential CRT in the GEMSTONE-301 and PACIFIC-R studies, noting that it is “very important to have data in sequential radiochemotherapy populations” given the substantial number of patients who require a sequential approach because of poor performance status, difficulty tolerating concurrent CRT, or logistical reasons, such as an inability to travel to receive concurrent CRT.

The GEMSTONE-301 study was funded by CStone Pharmaceuticals. Dr. Wu reported having no disclosures. The PACIFIC-R study was funded by AstraZeneca. Dr. Girard reported financial relationships with AstraZeneca, Bristol Myers Squibb, and Merck Sharp & Dohme. Dr. Hendriks reported financial relationships with numerous companies.

[email protected]

Checkpoint inhibition for consolidation after chemoradiotherapy (CRT) showed promising survival benefit in patients with unresectable stage III non–small cell lung cancer (NSCLC) in two recent studies, including one looking at the investigational agent sugemalimab and one assessing durvalumab in a real-world setting.

Statistically significant and clinically meaningful improvement in progression-free survival (PFS) was observed with sugemalimab versus placebo in the randomized, phase 3 GEMSTONE-301 study, and consolidation durvalumab showed effectiveness in a real-world cohort in the PACIFIC-R study.

Findings from both studies were presented at the 2021 European Society for Medical Oncology Congress.
 

GEMSTONE-301

Median progression-free survival among 381 patients randomized 2:1 to receive 1,200 mg of sugemalimab or placebo every 3 weeks after either concurrent or sequential chemoradiotherapy was 9.0 versus 5.8 months, in the treatment arms, respectively (hazard ratio, 0.64) (Abstract LBA43), reported Yi-Long Wu, MD, of Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.

Patients were recruited from 50 sites, and one-third had received sequential CRT. Progression-free survival was assessed at median follow up of 14 months.

“The 12- and 18-month PFS rates were 45% vs. 26% and 39% vs. 23%, respectively,” Dr. Wu said.

Of note, the PFS benefit was observed both for patients who underwent sequential CRT (median PFS, 8.1 vs. 4.1 months with sugemalimab vs. placebo; hazard ratio, 0.59) and for those who received concurrent CRT (median PFS, 10.5 vs. 6.4 months; HR, 0.66).

Overall survival (OS) data were not mature at the time of the presentation, but a trend favoring sugemalimab was observed (HR, 0.44) he noted.

Sugemalimab, an investigational anti–programmed death-ligand 1 (PD-L1 )monoclonal antibody, was well tolerated; grade 3 or higher treatment-emergent adverse events (AEs) occurred in 24.3% of patients in the sugemalimab group and in 23.8% in the placebo group.

Concurrent chemoradiotherapy followed by immunotherapy is the standard of care for patients with unresectable stage III NSCLC, but nearly half undergo sequential CRT because they can’t tolerate concurrent treatment, Dr. Wu explained, describing the rationale for the study – the first phase 3 trial looking at both concurrent and sequential CRT in this patient population.

The results provide evidence for sugemalimab as a consolidation treatment for those who did not progress following either approach to CRT, he concluded.
 

PACIFIC-R study

The large, international, observational PACIFIC-R study also looked at consolidation in a real-world setting, and confirmed a PFS benefit with durvalumab in stage III NSCLC patients who had completed concurrent or sequential platinum-based CRT within the previous 12 weeks without evidence of disease progression (Abstract 1171MO).

“The median real-world PFS in this cohort was 21.7 months, which is higher than that in the durvalumab arm in the PACIFIC trial, which was 16.9 months,” reported Nicolas Girard, MD, a professor at Institut Curie, Paris.

The PACIFIC trial set the standard for durvalumab-based consolidation after CRT, and ongoing survival benefit was confirmed by 5-year follow-up data, he noted.

The PACIFIC-R trial included 1,399 patients from 11 countries who were treated as part of an expanded-access program following the PACIFIC trial.

Median time to durvalumab initiation after the end of radiotherapy in the cohort was 56 days. Overall median durvalumab treatment duration was 11 months, and the median number of infusions was 22, Dr. Girard said.

Pneumonitis was the most common adverse event leading to discontinuation: 214 (18.5%) patients experienced any-grade pneumonitis and/or interstitial lung disease, and 9.5 discontinued the study as a result. Most cases were mild or moderate, he said.

Subgroup analyses showed that real-world PFS was higher among patients with stage IIIa disease and those with PD-L1–positive tumors, those with nonsquamous disease histology, and those who received concurrent CRT.

“For example, in those with stage IIIa disease, the median real-world PFS was 23.7 months versus 19.2 months in patients with stage IIIb and c disease,” he said.

“PACIFIC-R demonstrated the efficacy of durvalumab consolidation in patients with unresectable stage III non–small cell lung cancer after completion of chemoradiotherapy,” said Dr. Girard. “The effectiveness of durvalumab was consistent among key subgroups, as was safety, when comparing the data with that of PACIFIC.

“The future read-outs of OS will further provide insight into the effectiveness of this regimen.”

Session chair Lizza E. Hendriks, MD, PhD, of Maastricht (the Netherlands) University, applauded the inclusion of patients undergoing sequential CRT in the GEMSTONE-301 and PACIFIC-R studies, noting that it is “very important to have data in sequential radiochemotherapy populations” given the substantial number of patients who require a sequential approach because of poor performance status, difficulty tolerating concurrent CRT, or logistical reasons, such as an inability to travel to receive concurrent CRT.

The GEMSTONE-301 study was funded by CStone Pharmaceuticals. Dr. Wu reported having no disclosures. The PACIFIC-R study was funded by AstraZeneca. Dr. Girard reported financial relationships with AstraZeneca, Bristol Myers Squibb, and Merck Sharp & Dohme. Dr. Hendriks reported financial relationships with numerous companies.

[email protected]

In almost 80% of cases, cutaneous psoriasis predates the onset of arthritic psoriasis. Therefore, identifying risk factors for the development of psoriatic arthritis (PsA) in patients with skin psoriasis is of significant clinical and research interest. One such risk factor that has previous been described is the severity of psoriasis. In a prospective population-based cohort study performed within The Health Improvement Network in the UK, Ogdie et al demonstrated that in a cohort of 8881 patients aged 25–60 years with a code for psoriasis randomly selected between 2008 and 2011, the extent of psoriasis as measured by the body surface area affected (BSA) was a strong predictor of developing PsA. Comorbidities, such as obesity and depression, were additive risk factors. In this cohort, after a mean follow-up time of 4.2 years (SD 2.1), the incidence of PsA was 5.4 cases per 1000 person-years. After adjusting for age and sex, BSA > 10% [hazard ratio (HR) 2.01, 95% CI 1.29, 3.13], BSA 3–10% (HR 1.44, 95% CI 1.02, 2.03), obesity (HR 1.64, 95% CI 1.19, 2.26) and depression (HR 1.68, 95% CI 1.21, 2.33) were associated with incident PsA. Thus, patients with these risk factors should be carefully evaluated at each visit for signs of PsA.

One important question is whether treatment of psoriasis with targeted therapies reduces the risk of incident PsA. In a retrospective cohort study using the electronic medical records of the Maccabi Healthcare Services in Israel, Rosenthal et al, using propensity score matching compared patients who had received biological treatment for psoriasis and were not diagnosed with PsA before or at the time of biologic treatment initiation to controls not on such treatment. Patients were matched by age at diagnosis, gender, time until treatment initiation, maximum body mass index (BMI), and smoking. Multivariable Cox regression analysis showed that the control group had a significantly higher risk for PsA compared to patients treated with biologics (adjusted HR 1.39; 95%CI 1.03-1.87). Thus, there is increasing evidence that biologic therapy may decrease the risk of developing PsA.

Management of comorbidities remain an ongoing challenge in the management of psoriatic disease. In a cross-sectional multi-center study conducted by the Turkish League Against Rheumatism involving 1033 patients with PsA, 383 (37.1%) of whom were obese, Gok et al report that obesity was significantly associated with higher disease activity, lower quality of life scores, anxiety, depression, and fatigue. Comorbidities including obesity must be addressed for holistic management of PsA.

But counseling about modifiable risk factors remains low. Taylor et al reported that counseling or education for modifiable lifestyle risk factors were rare during psoriatic disease outpatient visits. Using data from the National Ambulatory Medical Care Survey (2002-2016) and the National Hospital Ambulatory Medical Care Survey (2002-2011) conducted in the United States, they demonstrate low rates of counseling for any modifiable lifestyle risk factor (11.1%; 95% CI 7.9%-15.3%), tobacco (4.8%; 95% CI 2.8%-8.0%), and obesity (2.8%; 95% CI 1.7%-4.5%). Thus, in addition to counseling about medications, an effort must be made to counsel about modifiable risk factors and comorbidities to improve quality of life of patients with psoriatic disease.

References

Ogdie A, Shin DB, Love TJ, Gelfand JM. Body surface area affected by psoriasis and the risk for psoriatic arthritis: a prospective population-based cohort study. Rheumatology (Oxf). 2021:Sep 11:keab622 (in press). doi: 10.1093/rheumatology/keab622 PMID: 34508558.

Shalev Rosenthal Y, Schwartz N, Sagy I, Pavlovsky L. Psoriatic arthritis incidence among patients receiving biologic medications for psoriasis: A nested case control study. Arthritis Rheumatol. 2021:Aug 23. doi: 10.1002/art.41946. Epub ahead of print. PMID: 34423909.

Shalev Rosenthal Y, Schwartz N, Sagy I, Pavlovsky L. Psoriatic arthritis incidence among patients receiving biologic medications for psoriasis: A nested case control study. Arthritis Rheumatol. 2021:Aug 23. doi: 10.1002/art.41946. Epub ahead of print. PMID: 34423909.

Gok K, Nas K, Tekeoglu I, Sunar I, Keskin Y, Kilic E, Sargin B, Acer Kasman S, Alkan H, Sahin N, Cengiz G, Cuzdan N, Albayrak Gezer İ, Keskin D, Mulkoglu C, Resorlu H, Bal A, Duruoz MT, Kucukakkas O, Yurdakul OV, Alkan Melikoglu M, Aydin Y, Ayhan FF, Bodur H, Calis M, Capkin E, Devrimsel G, Ecesoy H, Hizmetli S, Kamanli A, Kutluk O, Sen N, Sendur OF, Tolu S, Toprak M, Tuncer T. Impact of obesity on quality of life, psychological status, and disease activity in psoriatic arthritis: a multi‑center study. Rheumatol Int. 2021:Aug 28. doi: 10.1007/s00296-021-04971-8. Epub ahead of print. PMID: 34453579.

Taylor MT, Keller M, Barbieri JS. Lifestyle risk factor counseling at visits for psoriasis and psoriatic arthritis in the United States. J Am Acad Dermatol. 2021:Aug 25:S0190-9622(21)02376-8. doi: 10.1016/j.jaad.2021.08.034. Epub ahead of print. PMID: 34450204

In almost 80% of cases, cutaneous psoriasis predates the onset of arthritic psoriasis. Therefore, identifying risk factors for the development of psoriatic arthritis (PsA) in patients with skin psoriasis is of significant clinical and research interest. One such risk factor that has previous been described is the severity of psoriasis. In a prospective population-based cohort study performed within The Health Improvement Network in the UK, Ogdie et al demonstrated that in a cohort of 8881 patients aged 25–60 years with a code for psoriasis randomly selected between 2008 and 2011, the extent of psoriasis as measured by the body surface area affected (BSA) was a strong predictor of developing PsA. Comorbidities, such as obesity and depression, were additive risk factors. In this cohort, after a mean follow-up time of 4.2 years (SD 2.1), the incidence of PsA was 5.4 cases per 1000 person-years. After adjusting for age and sex, BSA > 10% [hazard ratio (HR) 2.01, 95% CI 1.29, 3.13], BSA 3–10% (HR 1.44, 95% CI 1.02, 2.03), obesity (HR 1.64, 95% CI 1.19, 2.26) and depression (HR 1.68, 95% CI 1.21, 2.33) were associated with incident PsA. Thus, patients with these risk factors should be carefully evaluated at each visit for signs of PsA.

One important question is whether treatment of psoriasis with targeted therapies reduces the risk of incident PsA. In a retrospective cohort study using the electronic medical records of the Maccabi Healthcare Services in Israel, Rosenthal et al, using propensity score matching compared patients who had received biological treatment for psoriasis and were not diagnosed with PsA before or at the time of biologic treatment initiation to controls not on such treatment. Patients were matched by age at diagnosis, gender, time until treatment initiation, maximum body mass index (BMI), and smoking. Multivariable Cox regression analysis showed that the control group had a significantly higher risk for PsA compared to patients treated with biologics (adjusted HR 1.39; 95%CI 1.03-1.87). Thus, there is increasing evidence that biologic therapy may decrease the risk of developing PsA.

Management of comorbidities remain an ongoing challenge in the management of psoriatic disease. In a cross-sectional multi-center study conducted by the Turkish League Against Rheumatism involving 1033 patients with PsA, 383 (37.1%) of whom were obese, Gok et al report that obesity was significantly associated with higher disease activity, lower quality of life scores, anxiety, depression, and fatigue. Comorbidities including obesity must be addressed for holistic management of PsA.

But counseling about modifiable risk factors remains low. Taylor et al reported that counseling or education for modifiable lifestyle risk factors were rare during psoriatic disease outpatient visits. Using data from the National Ambulatory Medical Care Survey (2002-2016) and the National Hospital Ambulatory Medical Care Survey (2002-2011) conducted in the United States, they demonstrate low rates of counseling for any modifiable lifestyle risk factor (11.1%; 95% CI 7.9%-15.3%), tobacco (4.8%; 95% CI 2.8%-8.0%), and obesity (2.8%; 95% CI 1.7%-4.5%). Thus, in addition to counseling about medications, an effort must be made to counsel about modifiable risk factors and comorbidities to improve quality of life of patients with psoriatic disease.

References

Ogdie A, Shin DB, Love TJ, Gelfand JM. Body surface area affected by psoriasis and the risk for psoriatic arthritis: a prospective population-based cohort study. Rheumatology (Oxf). 2021:Sep 11:keab622 (in press). doi: 10.1093/rheumatology/keab622 PMID: 34508558.

Shalev Rosenthal Y, Schwartz N, Sagy I, Pavlovsky L. Psoriatic arthritis incidence among patients receiving biologic medications for psoriasis: A nested case control study. Arthritis Rheumatol. 2021:Aug 23. doi: 10.1002/art.41946. Epub ahead of print. PMID: 34423909.

Shalev Rosenthal Y, Schwartz N, Sagy I, Pavlovsky L. Psoriatic arthritis incidence among patients receiving biologic medications for psoriasis: A nested case control study. Arthritis Rheumatol. 2021:Aug 23. doi: 10.1002/art.41946. Epub ahead of print. PMID: 34423909.

Gok K, Nas K, Tekeoglu I, Sunar I, Keskin Y, Kilic E, Sargin B, Acer Kasman S, Alkan H, Sahin N, Cengiz G, Cuzdan N, Albayrak Gezer İ, Keskin D, Mulkoglu C, Resorlu H, Bal A, Duruoz MT, Kucukakkas O, Yurdakul OV, Alkan Melikoglu M, Aydin Y, Ayhan FF, Bodur H, Calis M, Capkin E, Devrimsel G, Ecesoy H, Hizmetli S, Kamanli A, Kutluk O, Sen N, Sendur OF, Tolu S, Toprak M, Tuncer T. Impact of obesity on quality of life, psychological status, and disease activity in psoriatic arthritis: a multi‑center study. Rheumatol Int. 2021:Aug 28. doi: 10.1007/s00296-021-04971-8. Epub ahead of print. PMID: 34453579.

Taylor MT, Keller M, Barbieri JS. Lifestyle risk factor counseling at visits for psoriasis and psoriatic arthritis in the United States. J Am Acad Dermatol. 2021:Aug 25:S0190-9622(21)02376-8. doi: 10.1016/j.jaad.2021.08.034. Epub ahead of print. PMID: 34450204

In almost 80% of cases, cutaneous psoriasis predates the onset of arthritic psoriasis. Therefore, identifying risk factors for the development of psoriatic arthritis (PsA) in patients with skin psoriasis is of significant clinical and research interest. One such risk factor that has previous been described is the severity of psoriasis. In a prospective population-based cohort study performed within The Health Improvement Network in the UK, Ogdie et al demonstrated that in a cohort of 8881 patients aged 25–60 years with a code for psoriasis randomly selected between 2008 and 2011, the extent of psoriasis as measured by the body surface area affected (BSA) was a strong predictor of developing PsA. Comorbidities, such as obesity and depression, were additive risk factors. In this cohort, after a mean follow-up time of 4.2 years (SD 2.1), the incidence of PsA was 5.4 cases per 1000 person-years. After adjusting for age and sex, BSA > 10% [hazard ratio (HR) 2.01, 95% CI 1.29, 3.13], BSA 3–10% (HR 1.44, 95% CI 1.02, 2.03), obesity (HR 1.64, 95% CI 1.19, 2.26) and depression (HR 1.68, 95% CI 1.21, 2.33) were associated with incident PsA. Thus, patients with these risk factors should be carefully evaluated at each visit for signs of PsA.

One important question is whether treatment of psoriasis with targeted therapies reduces the risk of incident PsA. In a retrospective cohort study using the electronic medical records of the Maccabi Healthcare Services in Israel, Rosenthal et al, using propensity score matching compared patients who had received biological treatment for psoriasis and were not diagnosed with PsA before or at the time of biologic treatment initiation to controls not on such treatment. Patients were matched by age at diagnosis, gender, time until treatment initiation, maximum body mass index (BMI), and smoking. Multivariable Cox regression analysis showed that the control group had a significantly higher risk for PsA compared to patients treated with biologics (adjusted HR 1.39; 95%CI 1.03-1.87). Thus, there is increasing evidence that biologic therapy may decrease the risk of developing PsA.

Management of comorbidities remain an ongoing challenge in the management of psoriatic disease. In a cross-sectional multi-center study conducted by the Turkish League Against Rheumatism involving 1033 patients with PsA, 383 (37.1%) of whom were obese, Gok et al report that obesity was significantly associated with higher disease activity, lower quality of life scores, anxiety, depression, and fatigue. Comorbidities including obesity must be addressed for holistic management of PsA.

But counseling about modifiable risk factors remains low. Taylor et al reported that counseling or education for modifiable lifestyle risk factors were rare during psoriatic disease outpatient visits. Using data from the National Ambulatory Medical Care Survey (2002-2016) and the National Hospital Ambulatory Medical Care Survey (2002-2011) conducted in the United States, they demonstrate low rates of counseling for any modifiable lifestyle risk factor (11.1%; 95% CI 7.9%-15.3%), tobacco (4.8%; 95% CI 2.8%-8.0%), and obesity (2.8%; 95% CI 1.7%-4.5%). Thus, in addition to counseling about medications, an effort must be made to counsel about modifiable risk factors and comorbidities to improve quality of life of patients with psoriatic disease.

References

Ogdie A, Shin DB, Love TJ, Gelfand JM. Body surface area affected by psoriasis and the risk for psoriatic arthritis: a prospective population-based cohort study. Rheumatology (Oxf). 2021:Sep 11:keab622 (in press). doi: 10.1093/rheumatology/keab622 PMID: 34508558.

Shalev Rosenthal Y, Schwartz N, Sagy I, Pavlovsky L. Psoriatic arthritis incidence among patients receiving biologic medications for psoriasis: A nested case control study. Arthritis Rheumatol. 2021:Aug 23. doi: 10.1002/art.41946. Epub ahead of print. PMID: 34423909.

Shalev Rosenthal Y, Schwartz N, Sagy I, Pavlovsky L. Psoriatic arthritis incidence among patients receiving biologic medications for psoriasis: A nested case control study. Arthritis Rheumatol. 2021:Aug 23. doi: 10.1002/art.41946. Epub ahead of print. PMID: 34423909.

Gok K, Nas K, Tekeoglu I, Sunar I, Keskin Y, Kilic E, Sargin B, Acer Kasman S, Alkan H, Sahin N, Cengiz G, Cuzdan N, Albayrak Gezer İ, Keskin D, Mulkoglu C, Resorlu H, Bal A, Duruoz MT, Kucukakkas O, Yurdakul OV, Alkan Melikoglu M, Aydin Y, Ayhan FF, Bodur H, Calis M, Capkin E, Devrimsel G, Ecesoy H, Hizmetli S, Kamanli A, Kutluk O, Sen N, Sendur OF, Tolu S, Toprak M, Tuncer T. Impact of obesity on quality of life, psychological status, and disease activity in psoriatic arthritis: a multi‑center study. Rheumatol Int. 2021:Aug 28. doi: 10.1007/s00296-021-04971-8. Epub ahead of print. PMID: 34453579.

Taylor MT, Keller M, Barbieri JS. Lifestyle risk factor counseling at visits for psoriasis and psoriatic arthritis in the United States. J Am Acad Dermatol. 2021:Aug 25:S0190-9622(21)02376-8. doi: 10.1016/j.jaad.2021.08.034. Epub ahead of print. PMID: 34450204

This month’s journal scan of articles in exocrine pancreatic insufficiency explores the connection between the two functions of the pancreas, both exocrine and endocrine–and demonstrates somewhat differing findings which are worth exploration.

The first paper is from Uysal and Argun out of Istanbul, Turkey which explores the connection between insulin resistance and the development of exocrine pancreatic insufficiency (EPI). Researchers enrolled 65 patients with obesity and ages 16-69. The homeostasis model of assessment (HOMA) was used for the diagnosis of insulin resistance, and EPI was diagnosed with a fecal elastase-1 (FE-1) < 200 µg/g (via enzyme-linked immunosorbent assay). The study looked at both mean FE-1 levels as well as the distribution of EPI amongst patients with and without insulin resistance.

The study reported FE-1 levels (430.27 ± 207.63 vs. 508.64 ± 188.77 µg/g; P = .119) and the rate of EPI (FE-1 < 200 µg/g; 25.7% vs. 10.0%; P = .104) were not significantly different in patients with or without insulin resistance. The authors note that prior studies have suggested a link between EPI and diabetes mellitus (DM); however this study shows the correlation may not be strong in the pre-diabetic insulin resistance, or pre-DM period.

Further along the diabetes spectrum, researchers in China aimed to assess the prevalence of EPI amongst the type 2 DM (T2DM) Chinese population, and to further identify factors associated with the development of EPI. This study was a cross-sectional analysis of 85 adult inpatients with T2DM without known exocrine pancreatic disorders or digestive system diseases. Fecal samples were used to measure FE-1 levels, and blood samples were collected to investigate pancreatic endocrine function and metabolic biomarkers in all participants. Multiple logistic regression analysis was used to evaluate the influencing factors of pancreatic exocrine insufficiency in patients with T2DM.

Ultimately, the prevalence of EPI (FE-1 < 200 µg/g) amongst this patient population was 18.8%. There was a highly significant positive association between FE-1 levels and fasting C-peptide (FCP) levels (correlation coefficient 0.451; P < .001). Logistic regression analysis demonstrated that FCP was independently associated with EPI (odds ratio 0.204; P = .024), and receiver operating characteristic (ROC) analysis demonstrated good predictive value for EPI as well.

In summary, the authors infer a mechanistic conclusion that likely merits further investigation, “the reduced quantity and quality of β-cell lead to insufficient insulin secretion and subsequently results in hyperglycemia and DM. Further, as the trophic function from β-cells on pancreatic acinar cells weaken, the development into exocrine dysfunction in patients with DM is likely.”

Bibliography

1. Uysal BB, Argun D. Assessment of the impact of insulin resistance on pancreatic exocrine functions in obese patients. Med-Science. 2021;10(3):998-1001.
2. Lv Y, Wei Q, Yuan X, et al. Two sides of the pancreas: Exocrine insufficiency is correlated with endocrine dysfunction in type 2 diabetes. Clin Chim Acta. 2021(Sep 14);523:81-86. doi: 10.1016/j.cca.2021.09.008.

This month’s journal scan of articles in exocrine pancreatic insufficiency explores the connection between the two functions of the pancreas, both exocrine and endocrine–and demonstrates somewhat differing findings which are worth exploration.

The first paper is from Uysal and Argun out of Istanbul, Turkey which explores the connection between insulin resistance and the development of exocrine pancreatic insufficiency (EPI). Researchers enrolled 65 patients with obesity and ages 16-69. The homeostasis model of assessment (HOMA) was used for the diagnosis of insulin resistance, and EPI was diagnosed with a fecal elastase-1 (FE-1) < 200 µg/g (via enzyme-linked immunosorbent assay). The study looked at both mean FE-1 levels as well as the distribution of EPI amongst patients with and without insulin resistance.

The study reported FE-1 levels (430.27 ± 207.63 vs. 508.64 ± 188.77 µg/g; P = .119) and the rate of EPI (FE-1 < 200 µg/g; 25.7% vs. 10.0%; P = .104) were not significantly different in patients with or without insulin resistance. The authors note that prior studies have suggested a link between EPI and diabetes mellitus (DM); however this study shows the correlation may not be strong in the pre-diabetic insulin resistance, or pre-DM period.

Further along the diabetes spectrum, researchers in China aimed to assess the prevalence of EPI amongst the type 2 DM (T2DM) Chinese population, and to further identify factors associated with the development of EPI. This study was a cross-sectional analysis of 85 adult inpatients with T2DM without known exocrine pancreatic disorders or digestive system diseases. Fecal samples were used to measure FE-1 levels, and blood samples were collected to investigate pancreatic endocrine function and metabolic biomarkers in all participants. Multiple logistic regression analysis was used to evaluate the influencing factors of pancreatic exocrine insufficiency in patients with T2DM.

Ultimately, the prevalence of EPI (FE-1 < 200 µg/g) amongst this patient population was 18.8%. There was a highly significant positive association between FE-1 levels and fasting C-peptide (FCP) levels (correlation coefficient 0.451; P < .001). Logistic regression analysis demonstrated that FCP was independently associated with EPI (odds ratio 0.204; P = .024), and receiver operating characteristic (ROC) analysis demonstrated good predictive value for EPI as well.

In summary, the authors infer a mechanistic conclusion that likely merits further investigation, “the reduced quantity and quality of β-cell lead to insufficient insulin secretion and subsequently results in hyperglycemia and DM. Further, as the trophic function from β-cells on pancreatic acinar cells weaken, the development into exocrine dysfunction in patients with DM is likely.”

Bibliography

1. Uysal BB, Argun D. Assessment of the impact of insulin resistance on pancreatic exocrine functions in obese patients. Med-Science. 2021;10(3):998-1001.
2. Lv Y, Wei Q, Yuan X, et al. Two sides of the pancreas: Exocrine insufficiency is correlated with endocrine dysfunction in type 2 diabetes. Clin Chim Acta. 2021(Sep 14);523:81-86. doi: 10.1016/j.cca.2021.09.008.

This month’s journal scan of articles in exocrine pancreatic insufficiency explores the connection between the two functions of the pancreas, both exocrine and endocrine–and demonstrates somewhat differing findings which are worth exploration.

The first paper is from Uysal and Argun out of Istanbul, Turkey which explores the connection between insulin resistance and the development of exocrine pancreatic insufficiency (EPI). Researchers enrolled 65 patients with obesity and ages 16-69. The homeostasis model of assessment (HOMA) was used for the diagnosis of insulin resistance, and EPI was diagnosed with a fecal elastase-1 (FE-1) < 200 µg/g (via enzyme-linked immunosorbent assay). The study looked at both mean FE-1 levels as well as the distribution of EPI amongst patients with and without insulin resistance.

The study reported FE-1 levels (430.27 ± 207.63 vs. 508.64 ± 188.77 µg/g; P = .119) and the rate of EPI (FE-1 < 200 µg/g; 25.7% vs. 10.0%; P = .104) were not significantly different in patients with or without insulin resistance. The authors note that prior studies have suggested a link between EPI and diabetes mellitus (DM); however this study shows the correlation may not be strong in the pre-diabetic insulin resistance, or pre-DM period.

Further along the diabetes spectrum, researchers in China aimed to assess the prevalence of EPI amongst the type 2 DM (T2DM) Chinese population, and to further identify factors associated with the development of EPI. This study was a cross-sectional analysis of 85 adult inpatients with T2DM without known exocrine pancreatic disorders or digestive system diseases. Fecal samples were used to measure FE-1 levels, and blood samples were collected to investigate pancreatic endocrine function and metabolic biomarkers in all participants. Multiple logistic regression analysis was used to evaluate the influencing factors of pancreatic exocrine insufficiency in patients with T2DM.

Ultimately, the prevalence of EPI (FE-1 < 200 µg/g) amongst this patient population was 18.8%. There was a highly significant positive association between FE-1 levels and fasting C-peptide (FCP) levels (correlation coefficient 0.451; P < .001). Logistic regression analysis demonstrated that FCP was independently associated with EPI (odds ratio 0.204; P = .024), and receiver operating characteristic (ROC) analysis demonstrated good predictive value for EPI as well.

In summary, the authors infer a mechanistic conclusion that likely merits further investigation, “the reduced quantity and quality of β-cell lead to insufficient insulin secretion and subsequently results in hyperglycemia and DM. Further, as the trophic function from β-cells on pancreatic acinar cells weaken, the development into exocrine dysfunction in patients with DM is likely.”

Bibliography

1. Uysal BB, Argun D. Assessment of the impact of insulin resistance on pancreatic exocrine functions in obese patients. Med-Science. 2021;10(3):998-1001.
2. Lv Y, Wei Q, Yuan X, et al. Two sides of the pancreas: Exocrine insufficiency is correlated with endocrine dysfunction in type 2 diabetes. Clin Chim Acta. 2021(Sep 14);523:81-86. doi: 10.1016/j.cca.2021.09.008.

Contraception prescription patterns vary by specialty and geography

Access to contraceptive services is dependent on both the local availability of healthcare providers as well as the types of contraception services offered by those providers. Little is known about the national US contraception workforce, which includes any type of provider that offers contraceptive care. In this observational study, three national data sources were combined to construct a comprehensive database of the contraception provider workforce to evaluate Medicaid participation and variation in the supply, distribution, and types of contraceptive services offered. The study found that 73.1% of obstetric and gynecologic medical physicians (OBGYN), 72.6% of nurse-midwives, 51.4% of family medicine physicians, 32.4% of pediatricians, 25.2% of advanced practice nurses, 19.8% of internal medicine physicians, and 19.4% of physician assistants prescribed the contraceptive pill, patch, or ring. Approximately half of OBGYNs and family medicine physicians (50.2% and 52.2%, respectively) provided injectable contraception, compared to 34.7% of internal medicine physicians and 34.1% of pediatricians. Intrauterine devices (IUD) were provided by 92.8% of OBGYNs compared with 16.4% of family physicians, 2.6% of internal medicine physicians, and 0.6% of pediatricians. Contraceptive implants were provided by 56.2% of OBGYNs, compared with 13.7% of family medicine physicians, 1.8% of internal medicine physicians, and 4.0% of pediatricians. The contraception workforce also varied by geography, both in the density and types of providers that different communities depend upon. States ranged from provider-to-population ratios of 27.9 to 74.2 providers per 10,000 women of reproductive age. The availability of different specialties and professions also varied between counties, with 675 of the 1,411 counties lacking either OBGYNs or nurse-midwives prescribing contraception. This study also found variation across states and provider types in the proportion of contraceptive providers who accept Medicaid, with rates of Medicaid acceptance highest amongst OBGYNs and lowest amongst internal medicine physicians. This report highlights that the distribution of the contraception workforce and Medicaid acceptance varies widely by location and specialty and documents large gaps in the provision of highly effective contraceptive services including IUDs and implants. Increasing the number and types of providers that can provide family planning is central to providing comprehensive reproductive healthcare and reducing unintended pregnancies.

US Healthcare provider practices related to Emergency Contraception

Emergency contraception (EC) can prevent pregnancy after sexual encounters in which contraception was not used or used incorrectly. The US Selected Practice Recommendations for Contraceptive Use (US SPR) was initially released in 2013 and includes recommendations for healthcare providers on the initiation of EC, increasing access to EC through advance provision of EC pills, and initiation of regular contraception in conjunction with provision of EC pills. The objective of this study was to assess the percentage of healthcare providers reporting frequent provision of select EC practices around the time of and after the release of the US SPR. Two cross-sectional mailed surveys were conducted using different nationwide samples of office-based physicians and public-sector providers around the time of (2013-2014) and after (2019) the initial US SPR release. Providers were asked to indicate how often in the past year they had: 1) provided an advance prescription of EC pills to a woman not specifically seeking EC; 2) provided an advanced supply of EC pills to a woman not specifically seeking EC; 3) provided or prescribed a contraceptive at the same time as EC pills were provided; and 4) provided a copper IUD as EC. Data was pooled from both surveys, resulting in an overall sample size of 3,480 providers (n = 2,060 for the 2013-2014 survey and n = 1,420 for the 2019 survey). In the 2019 nationwide sample, 16% of respondents frequently provided an advance prescription of EC pills, 7% provided an advanced supply of EC pills, 8% provided the copper IUD as EC, and 41% cfrequently provided regular contraception at the time of EC pills. Overall, there were no significant changes in prevalence of frequently providing or prescribing an advance supply of EC pills between 2013-2014 and 2019, which may reflect changes in provider practices based on availability of over-the-counter levonogestrel EC pills in 2013. An increase in the proportion of providers who frequently provided regular contraception at the same time as EC pills and who provided a copper IUD for EC between 2013-2014 and 2019 was observed. In 2019, providers who reported using the US SPR were more likely to provide contraception at the same time as EC pills and provide the copper IUD for EC compared with those who did not use the US SPR. Wider implementation of the US SPR recommendations and an improved understanding of the barriers faced by providers in implementing these practices may improve access to EC. A recent report found that the levonorgestrel 52 IUD provides EC with efficacy similar to that of the copper IUD and may lead to more widespread placement of IUDs for EC (Turok).  


Progestogen-only pill shows promise as a potential non-prescription contraception option for both breastfeeding and non-breastfeeding women

An initiative is currently underway to apply for US Food and Drug Administration (FDA) approval for over-the-counter sales of a progestogen-only contraceptive pill (POP) containing 75 mg/day norgestrel. Although 75 mg/day norgestrel is approved by the FDA for prescription use, this formulation is not currently available in the US as marketing of this product was discontinued in 2005 for reasons not related to safety or effectiveness. The failure rate of the POP is presently reported to be the same as that of combined oral contraceptive pills (COC): 9% typical use and 0.3% perfect use unintended pregnancy rate. The objective of this review is to summarize and present the published data regarding the contraceptive effectiveness of 75 mg/day norgestrel amongst breastfeeding and non-breastfeeding women. A literature search was conducted in 2019 and identified 13 articles that specifically assessed the contraceptive efficacy of 75 mg/day norgestrel. Seven of the 13 studies included a total of 5,258 women who were breastfeeding and six of the 13 studies included a total 3,144 non-breastfeeding women. Taken together, the six studies of 3,144 non-breastfeeding women provide data on 35,319 months of use with a range of overall 12-month failure rates from 0-2.4/hundred woman-years from 75 mg/day norgestrel during typical use with a calculated aggregate Pearl Index of 2.2. Among breastfeeding women, the 12-month life table cumulative pregnancy rates for 75 mg/day norgestrel ranged from 0-3.4. This review concluded that the data support that 75 mg/day norgestrel is highly effective in clinical use, with similar estimates of failure in breastfeeding and non-breastfeeding women, providing support to the case for FDA approval of over-the-counter use of 75 mg/day norgestrel. Most contraindications to use of combination estrogen-progestin contraceptives relate to the estrogen component. Over the counter availability of the norgestrel POP could enhance women’s access to hormonal contraception.  

Millions of women view YouTube videos on self-removal of long-acting contraception

This study reviewed 58 YouTube videos related to self-removal of long-acting reversible contraception (LARC)– namely intrauterine devices (IUD) and contraceptive implants. Video content was analyzed to explore demographic characteristics, method and duration of LARC use, and motivations and experiences of self-removal. There were 48 videos (83%) that featured individuals who self-removed an IUD and 10 videos (17%) that featured individuals who self-removed an implant. All videos were uploaded between 2012-2020 and had over 4 million collective views, with the median number of views being 10,473 per video. Although a much smaller proportion of videos featured the self-removal of an implant, these videos had a higher average number of views (median 23,097 vs, 9533) and comments (median 44 vs. 14) compared to videos of IUD self-removals. The video creators of 53% were identified as White, 31% as Black, and 14% as Latina. The top comments for each video were analyzed and three primary themes emerged: positive affirmations; the viewer’s consideration of or attempt at self-removal; and complaints about LARC. There were 25 videos (n = 25/58) that included a comment from a viewer who stated they had either removed their own LARC device after watching the video or intended to do so soon. Three main motivations for self-removal were identified. Roughly half the sample (n = 30/58) described a desire to remove their method at home out of personal preference or convenience (n = 28/48 IUD users and n = 2/10 implant users). Others noted the inconvenience of an in-clinic removal. A large proportion of LARC users described barriers to clinic-based removal, including cost, lack of insurance, and long waiting times for an appointment. Most individuals in the sample (n = 56/58) successfully removed their device and described their experience in positive terms related to the ease of removal. Roughly a third of all video creators encountered challenges, including difficulty grasping the strings of their IUD or challenges removing the implant (n = 17/48 IUD users and n = 3/10 implant users). Positive experiences of self-removal and high levels of viewer engagement with online videos suggest a need for provider counseling on LARC removal at the time of insertion. Providers should clearly describe any procedural or financial requirements of removal prior to LARC placement. Providers may also wish to proactively discuss the risks and best practices for safe self-removal of LARC, including a conversation about the desired length of the IUD strings, risks associated with self-removal, and available resources when the patient encounters barriers to clinic-based removal. This study provides important data about the characteristics, motivations, and experiences of a group of people that are often invisible to researchers and healthcare providers.

References:
Broussard K, Becker A. Self-removal of long-acting reversible contraception: A content analysis of YouTube videos. Contraception. 2021 Aug 13: S0010-7824(21)00346-2 (in press).

Chen C, Strasser J, Banawa R, Luo Q, Bodas M, Castruccio-Prince C, Das K, Pittman P. Who is providing contraception care in the United States? An observational study of the contraception workforce. Am J Obstet Gynecol. 2021 Aug 18:  S0002-9378(21)00883-8 (in press).

Contraception prescription patterns vary by specialty and geography

Access to contraceptive services is dependent on both the local availability of healthcare providers as well as the types of contraception services offered by those providers. Little is known about the national US contraception workforce, which includes any type of provider that offers contraceptive care. In this observational study, three national data sources were combined to construct a comprehensive database of the contraception provider workforce to evaluate Medicaid participation and variation in the supply, distribution, and types of contraceptive services offered. The study found that 73.1% of obstetric and gynecologic medical physicians (OBGYN), 72.6% of nurse-midwives, 51.4% of family medicine physicians, 32.4% of pediatricians, 25.2% of advanced practice nurses, 19.8% of internal medicine physicians, and 19.4% of physician assistants prescribed the contraceptive pill, patch, or ring. Approximately half of OBGYNs and family medicine physicians (50.2% and 52.2%, respectively) provided injectable contraception, compared to 34.7% of internal medicine physicians and 34.1% of pediatricians. Intrauterine devices (IUD) were provided by 92.8% of OBGYNs compared with 16.4% of family physicians, 2.6% of internal medicine physicians, and 0.6% of pediatricians. Contraceptive implants were provided by 56.2% of OBGYNs, compared with 13.7% of family medicine physicians, 1.8% of internal medicine physicians, and 4.0% of pediatricians. The contraception workforce also varied by geography, both in the density and types of providers that different communities depend upon. States ranged from provider-to-population ratios of 27.9 to 74.2 providers per 10,000 women of reproductive age. The availability of different specialties and professions also varied between counties, with 675 of the 1,411 counties lacking either OBGYNs or nurse-midwives prescribing contraception. This study also found variation across states and provider types in the proportion of contraceptive providers who accept Medicaid, with rates of Medicaid acceptance highest amongst OBGYNs and lowest amongst internal medicine physicians. This report highlights that the distribution of the contraception workforce and Medicaid acceptance varies widely by location and specialty and documents large gaps in the provision of highly effective contraceptive services including IUDs and implants. Increasing the number and types of providers that can provide family planning is central to providing comprehensive reproductive healthcare and reducing unintended pregnancies.

US Healthcare provider practices related to Emergency Contraception

Emergency contraception (EC) can prevent pregnancy after sexual encounters in which contraception was not used or used incorrectly. The US Selected Practice Recommendations for Contraceptive Use (US SPR) was initially released in 2013 and includes recommendations for healthcare providers on the initiation of EC, increasing access to EC through advance provision of EC pills, and initiation of regular contraception in conjunction with provision of EC pills. The objective of this study was to assess the percentage of healthcare providers reporting frequent provision of select EC practices around the time of and after the release of the US SPR. Two cross-sectional mailed surveys were conducted using different nationwide samples of office-based physicians and public-sector providers around the time of (2013-2014) and after (2019) the initial US SPR release. Providers were asked to indicate how often in the past year they had: 1) provided an advance prescription of EC pills to a woman not specifically seeking EC; 2) provided an advanced supply of EC pills to a woman not specifically seeking EC; 3) provided or prescribed a contraceptive at the same time as EC pills were provided; and 4) provided a copper IUD as EC. Data was pooled from both surveys, resulting in an overall sample size of 3,480 providers (n = 2,060 for the 2013-2014 survey and n = 1,420 for the 2019 survey). In the 2019 nationwide sample, 16% of respondents frequently provided an advance prescription of EC pills, 7% provided an advanced supply of EC pills, 8% provided the copper IUD as EC, and 41% cfrequently provided regular contraception at the time of EC pills. Overall, there were no significant changes in prevalence of frequently providing or prescribing an advance supply of EC pills between 2013-2014 and 2019, which may reflect changes in provider practices based on availability of over-the-counter levonogestrel EC pills in 2013. An increase in the proportion of providers who frequently provided regular contraception at the same time as EC pills and who provided a copper IUD for EC between 2013-2014 and 2019 was observed. In 2019, providers who reported using the US SPR were more likely to provide contraception at the same time as EC pills and provide the copper IUD for EC compared with those who did not use the US SPR. Wider implementation of the US SPR recommendations and an improved understanding of the barriers faced by providers in implementing these practices may improve access to EC. A recent report found that the levonorgestrel 52 IUD provides EC with efficacy similar to that of the copper IUD and may lead to more widespread placement of IUDs for EC (Turok).  


Progestogen-only pill shows promise as a potential non-prescription contraception option for both breastfeeding and non-breastfeeding women

An initiative is currently underway to apply for US Food and Drug Administration (FDA) approval for over-the-counter sales of a progestogen-only contraceptive pill (POP) containing 75 mg/day norgestrel. Although 75 mg/day norgestrel is approved by the FDA for prescription use, this formulation is not currently available in the US as marketing of this product was discontinued in 2005 for reasons not related to safety or effectiveness. The failure rate of the POP is presently reported to be the same as that of combined oral contraceptive pills (COC): 9% typical use and 0.3% perfect use unintended pregnancy rate. The objective of this review is to summarize and present the published data regarding the contraceptive effectiveness of 75 mg/day norgestrel amongst breastfeeding and non-breastfeeding women. A literature search was conducted in 2019 and identified 13 articles that specifically assessed the contraceptive efficacy of 75 mg/day norgestrel. Seven of the 13 studies included a total of 5,258 women who were breastfeeding and six of the 13 studies included a total 3,144 non-breastfeeding women. Taken together, the six studies of 3,144 non-breastfeeding women provide data on 35,319 months of use with a range of overall 12-month failure rates from 0-2.4/hundred woman-years from 75 mg/day norgestrel during typical use with a calculated aggregate Pearl Index of 2.2. Among breastfeeding women, the 12-month life table cumulative pregnancy rates for 75 mg/day norgestrel ranged from 0-3.4. This review concluded that the data support that 75 mg/day norgestrel is highly effective in clinical use, with similar estimates of failure in breastfeeding and non-breastfeeding women, providing support to the case for FDA approval of over-the-counter use of 75 mg/day norgestrel. Most contraindications to use of combination estrogen-progestin contraceptives relate to the estrogen component. Over the counter availability of the norgestrel POP could enhance women’s access to hormonal contraception.  

Millions of women view YouTube videos on self-removal of long-acting contraception

This study reviewed 58 YouTube videos related to self-removal of long-acting reversible contraception (LARC)– namely intrauterine devices (IUD) and contraceptive implants. Video content was analyzed to explore demographic characteristics, method and duration of LARC use, and motivations and experiences of self-removal. There were 48 videos (83%) that featured individuals who self-removed an IUD and 10 videos (17%) that featured individuals who self-removed an implant. All videos were uploaded between 2012-2020 and had over 4 million collective views, with the median number of views being 10,473 per video. Although a much smaller proportion of videos featured the self-removal of an implant, these videos had a higher average number of views (median 23,097 vs, 9533) and comments (median 44 vs. 14) compared to videos of IUD self-removals. The video creators of 53% were identified as White, 31% as Black, and 14% as Latina. The top comments for each video were analyzed and three primary themes emerged: positive affirmations; the viewer’s consideration of or attempt at self-removal; and complaints about LARC. There were 25 videos (n = 25/58) that included a comment from a viewer who stated they had either removed their own LARC device after watching the video or intended to do so soon. Three main motivations for self-removal were identified. Roughly half the sample (n = 30/58) described a desire to remove their method at home out of personal preference or convenience (n = 28/48 IUD users and n = 2/10 implant users). Others noted the inconvenience of an in-clinic removal. A large proportion of LARC users described barriers to clinic-based removal, including cost, lack of insurance, and long waiting times for an appointment. Most individuals in the sample (n = 56/58) successfully removed their device and described their experience in positive terms related to the ease of removal. Roughly a third of all video creators encountered challenges, including difficulty grasping the strings of their IUD or challenges removing the implant (n = 17/48 IUD users and n = 3/10 implant users). Positive experiences of self-removal and high levels of viewer engagement with online videos suggest a need for provider counseling on LARC removal at the time of insertion. Providers should clearly describe any procedural or financial requirements of removal prior to LARC placement. Providers may also wish to proactively discuss the risks and best practices for safe self-removal of LARC, including a conversation about the desired length of the IUD strings, risks associated with self-removal, and available resources when the patient encounters barriers to clinic-based removal. This study provides important data about the characteristics, motivations, and experiences of a group of people that are often invisible to researchers and healthcare providers.

References:
Broussard K, Becker A. Self-removal of long-acting reversible contraception: A content analysis of YouTube videos. Contraception. 2021 Aug 13: S0010-7824(21)00346-2 (in press).

Chen C, Strasser J, Banawa R, Luo Q, Bodas M, Castruccio-Prince C, Das K, Pittman P. Who is providing contraception care in the United States? An observational study of the contraception workforce. Am J Obstet Gynecol. 2021 Aug 18:  S0002-9378(21)00883-8 (in press).

Contraception prescription patterns vary by specialty and geography

Access to contraceptive services is dependent on both the local availability of healthcare providers as well as the types of contraception services offered by those providers. Little is known about the national US contraception workforce, which includes any type of provider that offers contraceptive care. In this observational study, three national data sources were combined to construct a comprehensive database of the contraception provider workforce to evaluate Medicaid participation and variation in the supply, distribution, and types of contraceptive services offered. The study found that 73.1% of obstetric and gynecologic medical physicians (OBGYN), 72.6% of nurse-midwives, 51.4% of family medicine physicians, 32.4% of pediatricians, 25.2% of advanced practice nurses, 19.8% of internal medicine physicians, and 19.4% of physician assistants prescribed the contraceptive pill, patch, or ring. Approximately half of OBGYNs and family medicine physicians (50.2% and 52.2%, respectively) provided injectable contraception, compared to 34.7% of internal medicine physicians and 34.1% of pediatricians. Intrauterine devices (IUD) were provided by 92.8% of OBGYNs compared with 16.4% of family physicians, 2.6% of internal medicine physicians, and 0.6% of pediatricians. Contraceptive implants were provided by 56.2% of OBGYNs, compared with 13.7% of family medicine physicians, 1.8% of internal medicine physicians, and 4.0% of pediatricians. The contraception workforce also varied by geography, both in the density and types of providers that different communities depend upon. States ranged from provider-to-population ratios of 27.9 to 74.2 providers per 10,000 women of reproductive age. The availability of different specialties and professions also varied between counties, with 675 of the 1,411 counties lacking either OBGYNs or nurse-midwives prescribing contraception. This study also found variation across states and provider types in the proportion of contraceptive providers who accept Medicaid, with rates of Medicaid acceptance highest amongst OBGYNs and lowest amongst internal medicine physicians. This report highlights that the distribution of the contraception workforce and Medicaid acceptance varies widely by location and specialty and documents large gaps in the provision of highly effective contraceptive services including IUDs and implants. Increasing the number and types of providers that can provide family planning is central to providing comprehensive reproductive healthcare and reducing unintended pregnancies.

US Healthcare provider practices related to Emergency Contraception

Emergency contraception (EC) can prevent pregnancy after sexual encounters in which contraception was not used or used incorrectly. The US Selected Practice Recommendations for Contraceptive Use (US SPR) was initially released in 2013 and includes recommendations for healthcare providers on the initiation of EC, increasing access to EC through advance provision of EC pills, and initiation of regular contraception in conjunction with provision of EC pills. The objective of this study was to assess the percentage of healthcare providers reporting frequent provision of select EC practices around the time of and after the release of the US SPR. Two cross-sectional mailed surveys were conducted using different nationwide samples of office-based physicians and public-sector providers around the time of (2013-2014) and after (2019) the initial US SPR release. Providers were asked to indicate how often in the past year they had: 1) provided an advance prescription of EC pills to a woman not specifically seeking EC; 2) provided an advanced supply of EC pills to a woman not specifically seeking EC; 3) provided or prescribed a contraceptive at the same time as EC pills were provided; and 4) provided a copper IUD as EC. Data was pooled from both surveys, resulting in an overall sample size of 3,480 providers (n = 2,060 for the 2013-2014 survey and n = 1,420 for the 2019 survey). In the 2019 nationwide sample, 16% of respondents frequently provided an advance prescription of EC pills, 7% provided an advanced supply of EC pills, 8% provided the copper IUD as EC, and 41% cfrequently provided regular contraception at the time of EC pills. Overall, there were no significant changes in prevalence of frequently providing or prescribing an advance supply of EC pills between 2013-2014 and 2019, which may reflect changes in provider practices based on availability of over-the-counter levonogestrel EC pills in 2013. An increase in the proportion of providers who frequently provided regular contraception at the same time as EC pills and who provided a copper IUD for EC between 2013-2014 and 2019 was observed. In 2019, providers who reported using the US SPR were more likely to provide contraception at the same time as EC pills and provide the copper IUD for EC compared with those who did not use the US SPR. Wider implementation of the US SPR recommendations and an improved understanding of the barriers faced by providers in implementing these practices may improve access to EC. A recent report found that the levonorgestrel 52 IUD provides EC with efficacy similar to that of the copper IUD and may lead to more widespread placement of IUDs for EC (Turok).  


Progestogen-only pill shows promise as a potential non-prescription contraception option for both breastfeeding and non-breastfeeding women

An initiative is currently underway to apply for US Food and Drug Administration (FDA) approval for over-the-counter sales of a progestogen-only contraceptive pill (POP) containing 75 mg/day norgestrel. Although 75 mg/day norgestrel is approved by the FDA for prescription use, this formulation is not currently available in the US as marketing of this product was discontinued in 2005 for reasons not related to safety or effectiveness. The failure rate of the POP is presently reported to be the same as that of combined oral contraceptive pills (COC): 9% typical use and 0.3% perfect use unintended pregnancy rate. The objective of this review is to summarize and present the published data regarding the contraceptive effectiveness of 75 mg/day norgestrel amongst breastfeeding and non-breastfeeding women. A literature search was conducted in 2019 and identified 13 articles that specifically assessed the contraceptive efficacy of 75 mg/day norgestrel. Seven of the 13 studies included a total of 5,258 women who were breastfeeding and six of the 13 studies included a total 3,144 non-breastfeeding women. Taken together, the six studies of 3,144 non-breastfeeding women provide data on 35,319 months of use with a range of overall 12-month failure rates from 0-2.4/hundred woman-years from 75 mg/day norgestrel during typical use with a calculated aggregate Pearl Index of 2.2. Among breastfeeding women, the 12-month life table cumulative pregnancy rates for 75 mg/day norgestrel ranged from 0-3.4. This review concluded that the data support that 75 mg/day norgestrel is highly effective in clinical use, with similar estimates of failure in breastfeeding and non-breastfeeding women, providing support to the case for FDA approval of over-the-counter use of 75 mg/day norgestrel. Most contraindications to use of combination estrogen-progestin contraceptives relate to the estrogen component. Over the counter availability of the norgestrel POP could enhance women’s access to hormonal contraception.  

Millions of women view YouTube videos on self-removal of long-acting contraception

This study reviewed 58 YouTube videos related to self-removal of long-acting reversible contraception (LARC)– namely intrauterine devices (IUD) and contraceptive implants. Video content was analyzed to explore demographic characteristics, method and duration of LARC use, and motivations and experiences of self-removal. There were 48 videos (83%) that featured individuals who self-removed an IUD and 10 videos (17%) that featured individuals who self-removed an implant. All videos were uploaded between 2012-2020 and had over 4 million collective views, with the median number of views being 10,473 per video. Although a much smaller proportion of videos featured the self-removal of an implant, these videos had a higher average number of views (median 23,097 vs, 9533) and comments (median 44 vs. 14) compared to videos of IUD self-removals. The video creators of 53% were identified as White, 31% as Black, and 14% as Latina. The top comments for each video were analyzed and three primary themes emerged: positive affirmations; the viewer’s consideration of or attempt at self-removal; and complaints about LARC. There were 25 videos (n = 25/58) that included a comment from a viewer who stated they had either removed their own LARC device after watching the video or intended to do so soon. Three main motivations for self-removal were identified. Roughly half the sample (n = 30/58) described a desire to remove their method at home out of personal preference or convenience (n = 28/48 IUD users and n = 2/10 implant users). Others noted the inconvenience of an in-clinic removal. A large proportion of LARC users described barriers to clinic-based removal, including cost, lack of insurance, and long waiting times for an appointment. Most individuals in the sample (n = 56/58) successfully removed their device and described their experience in positive terms related to the ease of removal. Roughly a third of all video creators encountered challenges, including difficulty grasping the strings of their IUD or challenges removing the implant (n = 17/48 IUD users and n = 3/10 implant users). Positive experiences of self-removal and high levels of viewer engagement with online videos suggest a need for provider counseling on LARC removal at the time of insertion. Providers should clearly describe any procedural or financial requirements of removal prior to LARC placement. Providers may also wish to proactively discuss the risks and best practices for safe self-removal of LARC, including a conversation about the desired length of the IUD strings, risks associated with self-removal, and available resources when the patient encounters barriers to clinic-based removal. This study provides important data about the characteristics, motivations, and experiences of a group of people that are often invisible to researchers and healthcare providers.

References:
Broussard K, Becker A. Self-removal of long-acting reversible contraception: A content analysis of YouTube videos. Contraception. 2021 Aug 13: S0010-7824(21)00346-2 (in press).

Chen C, Strasser J, Banawa R, Luo Q, Bodas M, Castruccio-Prince C, Das K, Pittman P. Who is providing contraception care in the United States? An observational study of the contraception workforce. Am J Obstet Gynecol. 2021 Aug 18:  S0002-9378(21)00883-8 (in press).

We’ve launched a new app designed to help AGA trainees and early career members navigate each step along their GI career path. Once users get started by setting up their professional profile, AGA Career Compass offers curated resources on topics like career planning, clinical education, and leadership skills.

The Connections Corner section hosts experienced mentors and matches them with users based on profile compatibility and shared topics of interest, such as grant writing, setting up a lab, navigating career options in academic medicine, managing burnout, and more. Download the app today to branch out from your institution or practice and receive personalized career guidance.

Now available in Apple and Google Play stores.

We’ve launched a new app designed to help AGA trainees and early career members navigate each step along their GI career path. Once users get started by setting up their professional profile, AGA Career Compass offers curated resources on topics like career planning, clinical education, and leadership skills.

The Connections Corner section hosts experienced mentors and matches them with users based on profile compatibility and shared topics of interest, such as grant writing, setting up a lab, navigating career options in academic medicine, managing burnout, and more. Download the app today to branch out from your institution or practice and receive personalized career guidance.

Now available in Apple and Google Play stores.

We’ve launched a new app designed to help AGA trainees and early career members navigate each step along their GI career path. Once users get started by setting up their professional profile, AGA Career Compass offers curated resources on topics like career planning, clinical education, and leadership skills.

The Connections Corner section hosts experienced mentors and matches them with users based on profile compatibility and shared topics of interest, such as grant writing, setting up a lab, navigating career options in academic medicine, managing burnout, and more. Download the app today to branch out from your institution or practice and receive personalized career guidance.

Now available in Apple and Google Play stores.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:  

Junaid Beig, MBBS, FRACP wrote the following in “Subtherapeutic Azathioprine metabolites despite being adherent to medication”:

“I have an Ulcerative patient (Pancolitis) on Mesalazine and Azathioprine 150mg since 2018. His levels are subtherapeutic (6TGN 159 and 6MMP 70) despite being adherent to medication. He drinks 2 liters of wine per week.

“Questions: Is there any way we can find if he has high TPMT activity (Level is normal 6.1)? Does alcohol have an impact on TPMT activity? Does he warrant alternative treatment?”

See how AGA members responded and join the discussion: https://community.gastro.org/posts/25109.
 

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:  

Junaid Beig, MBBS, FRACP wrote the following in “Subtherapeutic Azathioprine metabolites despite being adherent to medication”:

“I have an Ulcerative patient (Pancolitis) on Mesalazine and Azathioprine 150mg since 2018. His levels are subtherapeutic (6TGN 159 and 6MMP 70) despite being adherent to medication. He drinks 2 liters of wine per week.

“Questions: Is there any way we can find if he has high TPMT activity (Level is normal 6.1)? Does alcohol have an impact on TPMT activity? Does he warrant alternative treatment?”

See how AGA members responded and join the discussion: https://community.gastro.org/posts/25109.
 

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:  

Junaid Beig, MBBS, FRACP wrote the following in “Subtherapeutic Azathioprine metabolites despite being adherent to medication”:

“I have an Ulcerative patient (Pancolitis) on Mesalazine and Azathioprine 150mg since 2018. His levels are subtherapeutic (6TGN 159 and 6MMP 70) despite being adherent to medication. He drinks 2 liters of wine per week.

“Questions: Is there any way we can find if he has high TPMT activity (Level is normal 6.1)? Does alcohol have an impact on TPMT activity? Does he warrant alternative treatment?”

See how AGA members responded and join the discussion: https://community.gastro.org/posts/25109.
 

Avanos medical to pay $22 million to resolve criminal charge for fraudulent misbranding of PPE

A U.S.-based multinational medical device corporation will pay more than $22 million to resolve a criminal charge regarding fraudulent misbranding of their surgical gowns.

Avanos Medical Inc, which as its U.S. headquarters in Alpharetta, Georgia, is charged with one count of introducing misbranded surgical gowns into interstate commerce with the intent to defraud and mislead.

According to the Department of Justice, the company knowingly falsely labeled its MicroCool surgical gowns as providing AAMI Level 4 protection (the highest level) against fluid and virus penetration. Under the standards set by the American National Standards Institute (ANSI) and the Association for the Advancement of Medical Instrumentation (AAMI), the highest protection level for surgical gowns is reserved for gowns intended to be used in surgeries and other high-risk medical procedures on patients suspected of having infectious diseases.

Avanos admitted to selling hundreds of thousands of MicroCool gowns that were falsely labeled as AAMI Level 4 between late 2014 and early 2015, as well as directly lying to customers about the gowns’ protective capacities. In total, Avanos sold almost $9 million of misbranded MicroCool gowns.

“The last thing health care workers should have to worry about is whether their personal protective equipment lives up to manufacturers’ claims,” said Acting U.S. Attorney Prerak Shah for the Northern District of Texas. “Misbranded PPE can pose serious risks to medical professionals and patients alike.”
 

Company pays $38.75 million to settle allegations of knowingly selling defective devices 

Medical device manufacturers Alere and Alere San Diego (collectively, Alere) have agreed to pay almost $39 million to resolve allegations that they violated the False Claims Act by billing, and causing others to bill, the Medicare program for defective rapid point-of-care testing devices. 

From 2008 to 2016, the Department of Justice alleges, Alere knowingly sold defective INRatio blood coagulation monitors used by Medicare beneficiaries who were taking anticoagulants. The software algorithms in the monitors contained a material defect, which Alere had found in their research, to cause inaccurate readings. Blood coagulation monitoring is essential for the safety of these patients, enabling them to maintain a safe dosage of their medications. Taking too much of an anticoagulant can cause major bleeding, while taking too little can cause blood clots that lead to strokes. 

While Alere was aware that these devices were linked to over a dozen deaths and hundreds of injuries, the company continued to conceal the defect and billed Medicare for the devices.

In 2016, the product was taken off the market at the request of the FDA.
 

Mass. doctor, wife charged in international money laundering, fraud scheme

Massachusetts psychiatrist Rahim Shafa, MD, and his wife and office manager, Nahid Tormosi Shafa, are charged in connection to an international money laundering scheme involving importing illegal and misbranded drugs. 

Through Shafa’s company, Novel Psychopharmacology, the two allegedly filed false and fraudulent Medicare reimbursement claims from 2016-2019, then deposited the money in their bank accounts, according to federal officials. From 2008-2018, the couple also engaged in an international money laundering scheme to purchase naltrexone pellet implants, disulfiram pellet implants, and injections from Hong Kong that were not approved by the FDA. According to officials, they falsified shipping documents, disguising the naltrexone pellet implants as “plastic beads in plastic tubes” to receive the drugs. They then offered to sell these drugs to patients of Novel Psychopharmacology. 

Rahim Shafa was indicted on conspiracies of international money laundering, health care fraud, and defrauding the United States, as well as illegally importing merchandise and purposely delivering misbranded drugs. His wife was indicted on one count each of health care fraud conspiracy and international money laundering conspiracy.
 

Jury convicts medical equipment company owners of $27 million fraud

A federal jury in Texas convicted the owners of two durable medical equipment (DME) companies linked to a scheme to defraud Medicare.

Leah Hagen, 49, and Michael Hagen, 54, were convicted of one count of conspiracy to defraud the United States and to pay and receive health care kickbacks and one count of conspiracy to commit money laundering. The defendants owned and operated Metro DME Supply and Ortho Pain Solutions. 

Ms. Hagen and Mr. Hagen paid a fixed rate per DME item in exchange for prescriptions and paperwork completed by telemedicine doctors that were used to submit false claims to Medicare, which totaled about $59 million. They were paid $27 million, and wired millions to their personal bank accounts. The defendants paid illegal bribes and kickbacks and wired money to their co-conspirator’s call center in the Philippines that provided signed doctor’s orders for orthotic braces. 

At trial, evidence showed emails between Leah and Michael Hagen and their co-conspirators outlining a per-product pricing structure for orthotic braces, but not disclosing their agreement as one for marketing and other services.

At sentencing, the Hagens each face a maximum sentence of 25 years in prison.

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

Avanos medical to pay $22 million to resolve criminal charge for fraudulent misbranding of PPE

A U.S.-based multinational medical device corporation will pay more than $22 million to resolve a criminal charge regarding fraudulent misbranding of their surgical gowns.

Avanos Medical Inc, which as its U.S. headquarters in Alpharetta, Georgia, is charged with one count of introducing misbranded surgical gowns into interstate commerce with the intent to defraud and mislead.

According to the Department of Justice, the company knowingly falsely labeled its MicroCool surgical gowns as providing AAMI Level 4 protection (the highest level) against fluid and virus penetration. Under the standards set by the American National Standards Institute (ANSI) and the Association for the Advancement of Medical Instrumentation (AAMI), the highest protection level for surgical gowns is reserved for gowns intended to be used in surgeries and other high-risk medical procedures on patients suspected of having infectious diseases.

Avanos admitted to selling hundreds of thousands of MicroCool gowns that were falsely labeled as AAMI Level 4 between late 2014 and early 2015, as well as directly lying to customers about the gowns’ protective capacities. In total, Avanos sold almost $9 million of misbranded MicroCool gowns.

“The last thing health care workers should have to worry about is whether their personal protective equipment lives up to manufacturers’ claims,” said Acting U.S. Attorney Prerak Shah for the Northern District of Texas. “Misbranded PPE can pose serious risks to medical professionals and patients alike.”
 

Company pays $38.75 million to settle allegations of knowingly selling defective devices 

Medical device manufacturers Alere and Alere San Diego (collectively, Alere) have agreed to pay almost $39 million to resolve allegations that they violated the False Claims Act by billing, and causing others to bill, the Medicare program for defective rapid point-of-care testing devices. 

From 2008 to 2016, the Department of Justice alleges, Alere knowingly sold defective INRatio blood coagulation monitors used by Medicare beneficiaries who were taking anticoagulants. The software algorithms in the monitors contained a material defect, which Alere had found in their research, to cause inaccurate readings. Blood coagulation monitoring is essential for the safety of these patients, enabling them to maintain a safe dosage of their medications. Taking too much of an anticoagulant can cause major bleeding, while taking too little can cause blood clots that lead to strokes. 

While Alere was aware that these devices were linked to over a dozen deaths and hundreds of injuries, the company continued to conceal the defect and billed Medicare for the devices.

In 2016, the product was taken off the market at the request of the FDA.
 

Mass. doctor, wife charged in international money laundering, fraud scheme

Massachusetts psychiatrist Rahim Shafa, MD, and his wife and office manager, Nahid Tormosi Shafa, are charged in connection to an international money laundering scheme involving importing illegal and misbranded drugs. 

Through Shafa’s company, Novel Psychopharmacology, the two allegedly filed false and fraudulent Medicare reimbursement claims from 2016-2019, then deposited the money in their bank accounts, according to federal officials. From 2008-2018, the couple also engaged in an international money laundering scheme to purchase naltrexone pellet implants, disulfiram pellet implants, and injections from Hong Kong that were not approved by the FDA. According to officials, they falsified shipping documents, disguising the naltrexone pellet implants as “plastic beads in plastic tubes” to receive the drugs. They then offered to sell these drugs to patients of Novel Psychopharmacology. 

Rahim Shafa was indicted on conspiracies of international money laundering, health care fraud, and defrauding the United States, as well as illegally importing merchandise and purposely delivering misbranded drugs. His wife was indicted on one count each of health care fraud conspiracy and international money laundering conspiracy.
 

Jury convicts medical equipment company owners of $27 million fraud

A federal jury in Texas convicted the owners of two durable medical equipment (DME) companies linked to a scheme to defraud Medicare.

Leah Hagen, 49, and Michael Hagen, 54, were convicted of one count of conspiracy to defraud the United States and to pay and receive health care kickbacks and one count of conspiracy to commit money laundering. The defendants owned and operated Metro DME Supply and Ortho Pain Solutions. 

Ms. Hagen and Mr. Hagen paid a fixed rate per DME item in exchange for prescriptions and paperwork completed by telemedicine doctors that were used to submit false claims to Medicare, which totaled about $59 million. They were paid $27 million, and wired millions to their personal bank accounts. The defendants paid illegal bribes and kickbacks and wired money to their co-conspirator’s call center in the Philippines that provided signed doctor’s orders for orthotic braces. 

At trial, evidence showed emails between Leah and Michael Hagen and their co-conspirators outlining a per-product pricing structure for orthotic braces, but not disclosing their agreement as one for marketing and other services.

At sentencing, the Hagens each face a maximum sentence of 25 years in prison.

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

Avanos medical to pay $22 million to resolve criminal charge for fraudulent misbranding of PPE

A U.S.-based multinational medical device corporation will pay more than $22 million to resolve a criminal charge regarding fraudulent misbranding of their surgical gowns.

Avanos Medical Inc, which as its U.S. headquarters in Alpharetta, Georgia, is charged with one count of introducing misbranded surgical gowns into interstate commerce with the intent to defraud and mislead.

According to the Department of Justice, the company knowingly falsely labeled its MicroCool surgical gowns as providing AAMI Level 4 protection (the highest level) against fluid and virus penetration. Under the standards set by the American National Standards Institute (ANSI) and the Association for the Advancement of Medical Instrumentation (AAMI), the highest protection level for surgical gowns is reserved for gowns intended to be used in surgeries and other high-risk medical procedures on patients suspected of having infectious diseases.

Avanos admitted to selling hundreds of thousands of MicroCool gowns that were falsely labeled as AAMI Level 4 between late 2014 and early 2015, as well as directly lying to customers about the gowns’ protective capacities. In total, Avanos sold almost $9 million of misbranded MicroCool gowns.

“The last thing health care workers should have to worry about is whether their personal protective equipment lives up to manufacturers’ claims,” said Acting U.S. Attorney Prerak Shah for the Northern District of Texas. “Misbranded PPE can pose serious risks to medical professionals and patients alike.”
 

Company pays $38.75 million to settle allegations of knowingly selling defective devices 

Medical device manufacturers Alere and Alere San Diego (collectively, Alere) have agreed to pay almost $39 million to resolve allegations that they violated the False Claims Act by billing, and causing others to bill, the Medicare program for defective rapid point-of-care testing devices. 

From 2008 to 2016, the Department of Justice alleges, Alere knowingly sold defective INRatio blood coagulation monitors used by Medicare beneficiaries who were taking anticoagulants. The software algorithms in the monitors contained a material defect, which Alere had found in their research, to cause inaccurate readings. Blood coagulation monitoring is essential for the safety of these patients, enabling them to maintain a safe dosage of their medications. Taking too much of an anticoagulant can cause major bleeding, while taking too little can cause blood clots that lead to strokes. 

While Alere was aware that these devices were linked to over a dozen deaths and hundreds of injuries, the company continued to conceal the defect and billed Medicare for the devices.

In 2016, the product was taken off the market at the request of the FDA.
 

Mass. doctor, wife charged in international money laundering, fraud scheme

Massachusetts psychiatrist Rahim Shafa, MD, and his wife and office manager, Nahid Tormosi Shafa, are charged in connection to an international money laundering scheme involving importing illegal and misbranded drugs. 

Through Shafa’s company, Novel Psychopharmacology, the two allegedly filed false and fraudulent Medicare reimbursement claims from 2016-2019, then deposited the money in their bank accounts, according to federal officials. From 2008-2018, the couple also engaged in an international money laundering scheme to purchase naltrexone pellet implants, disulfiram pellet implants, and injections from Hong Kong that were not approved by the FDA. According to officials, they falsified shipping documents, disguising the naltrexone pellet implants as “plastic beads in plastic tubes” to receive the drugs. They then offered to sell these drugs to patients of Novel Psychopharmacology. 

Rahim Shafa was indicted on conspiracies of international money laundering, health care fraud, and defrauding the United States, as well as illegally importing merchandise and purposely delivering misbranded drugs. His wife was indicted on one count each of health care fraud conspiracy and international money laundering conspiracy.
 

Jury convicts medical equipment company owners of $27 million fraud

A federal jury in Texas convicted the owners of two durable medical equipment (DME) companies linked to a scheme to defraud Medicare.

Leah Hagen, 49, and Michael Hagen, 54, were convicted of one count of conspiracy to defraud the United States and to pay and receive health care kickbacks and one count of conspiracy to commit money laundering. The defendants owned and operated Metro DME Supply and Ortho Pain Solutions. 

Ms. Hagen and Mr. Hagen paid a fixed rate per DME item in exchange for prescriptions and paperwork completed by telemedicine doctors that were used to submit false claims to Medicare, which totaled about $59 million. They were paid $27 million, and wired millions to their personal bank accounts. The defendants paid illegal bribes and kickbacks and wired money to their co-conspirator’s call center in the Philippines that provided signed doctor’s orders for orthotic braces. 

At trial, evidence showed emails between Leah and Michael Hagen and their co-conspirators outlining a per-product pricing structure for orthotic braces, but not disclosing their agreement as one for marketing and other services.

At sentencing, the Hagens each face a maximum sentence of 25 years in prison.

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

Once-daily dosing of poziotinib shows clinically meaningful efficacy for patients with treatment-naive non–small cell lung cancer (NSCLC) HER2 exon 20 mutations, according to results of the ZENITH20 trial presented at the 2021 European Society for Medical Oncology Congress. Tumor reductions, stated lead author Robin Cornelissen, PhD, MD, Erasmus University, Rotterdam, the Netherlands, were seen in 88% of patients.

EGFR and HER2 exon 20 insertion mutations are rare subsets accounting for about 10% each of all mutations and 2%-4% each in NSCLC. “There is no approved therapy for either treatment-naive or previously treated NSCLC with HER2 exon 20 mutations,” Dr. Cornelissen said in a virtual oral presentation (abstract LBA46) on Sept. 18. While chemotherapy agents with or without checkpoint inhibitors and tyrosine kinase inhibitors (TKIs) are currently utilized, none are specific to exon 20 mutations, and historical response rates from mostly small uncontrolled studies vary widely from about 6.9%-35%, with median progression-free survival (PFS) ranging from 3 to 7 months. Poziotinib is a potent oral pan-HER TKI with activity in patients with EGFR or HER2 exon 20–mutated NSCLC.

Dr. Cornelissen presented preliminary safety and efficacy data from the phase 2 ZENITH20, a seven-cohort global clinical trial, specifically from cohort 4 (daily dosing) which included 48 HER2 exon 20 insertion NSCLC patients (median age, 60.5 years; female/male, 26/22) treated first-line with oral daily poziotinib (16 mg). The majority were White (75%), female (54%), and nonsmokers (69%) with an Eastern Cooperative Oncology Group performance status of 1 (65%).The primary endpoint was objective response rate evaluated centrally by an independent image review committee using RECIST 1.1 criteria.

All patients have experienced treatment-related adverse events (TRAEs) with 10% considered serious, and permanent discontinuation in 13%. About 83% of patients had dose interruptions and 76% had dose reductions. The most common adverse events were diarrhea (any grade, 83%; grade 3, 15%), rash (any grade, 69%; grade 3, 35%), stomatitis/mucosal inflammation (any grade, 81%; grade 3, 21%), and paronychia (any grade, 46%; grade 3 8%). Pneumonitis occurred in two patients (4%), with one grade 3 (2%). No grade 4/5 TRAEs were reported.

Discontinuations in 44 patients (92%), Dr. Cornelissen said, are attributed to death (5/10%), disease progression (30/63%), adverse events (1/2%), and other (8/17%), with treatment ongoing in 4 patients (8%).

The rate for the primary endpoint of ORR was 43.8% (n = 21) (95% confidence interval, 29.5%-58.8%).Tumor reductions have been observed in 42/48 patients (88%) with a median reduction of 35%. One complete response was reported (2.1%), with partial responses in 20 (41.7%), stable disease in 15 (31.3%), progressive disease in 7 (14.6%), and 5 (10.4%) not evaluable. The disease control rate was 75.0%.

Among secondary endpoints, median duration of response (DoR) was 5.4 months (range, 2.8 to >19.1), with 42% of patients having response duration greater than6 months and 24% greater than 12 months. Median PFS was 5.6 months (range, 0 to >20.2), with progression-free survival duration greater than6 months in 42% and duration greater than12 months in 26%.

Dr. Cornelissen concluded: “Poziotinib shows clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.” The toxicity profile, he added, is manageable and in line with previous poziotinib studies and other second-generation EGFR TKIs.

Noting that improved tolerability and antitumor activity have been observed in the cohort 5 (8 mg b.i.d.) interim analysis, Dr. Cornelissen said that cohort 4 is ongoing with patients enrolling at 8-mg b.i.d. dosing.

HER2 mutations represents 1.7%-2.2% of NSCLC, with high-sequence homology with EGFR mutation, observed ESMO-appointed discussant Daniel S.W. Tan, PhD, National Cancer Center in Singapore. He pointed out that, while HER2 antibody drug conjugates and TKIs have gained approval in other cancer types (e.g., breast, gastric), currently no HER2 therapies are approved in NSCLC. Reviewing ZENITH20 findings (risk ratio, 43.8%; DoR, 5.4 months; PFS, 5.6 months), Dr. Tan stated that poziotinib is an active agent in HER2 mutated NSCLC. “One concern that remains for me is the safety profile that will require further evaluation in order to determine optimal dosing,” he said.

Potential combinations, he added, need to be explored to improve the durability of response. “Until we can properly characterize this and other important aspects such as CNS activity, we need to be cautious about transitioning to a frontline setting. Also, we do need to give due consideration to strategies to improve HER2 testing rates in order to expand on clinical experience. This argues for the importance of broad upfront next generation sequencing testing in NSCLC.”

The study was funded by Spectrum Pharmaceuticals. Other authors associated with the research disclosed full or part-time employment with Spectrum.

Once-daily dosing of poziotinib shows clinically meaningful efficacy for patients with treatment-naive non–small cell lung cancer (NSCLC) HER2 exon 20 mutations, according to results of the ZENITH20 trial presented at the 2021 European Society for Medical Oncology Congress. Tumor reductions, stated lead author Robin Cornelissen, PhD, MD, Erasmus University, Rotterdam, the Netherlands, were seen in 88% of patients.

EGFR and HER2 exon 20 insertion mutations are rare subsets accounting for about 10% each of all mutations and 2%-4% each in NSCLC. “There is no approved therapy for either treatment-naive or previously treated NSCLC with HER2 exon 20 mutations,” Dr. Cornelissen said in a virtual oral presentation (abstract LBA46) on Sept. 18. While chemotherapy agents with or without checkpoint inhibitors and tyrosine kinase inhibitors (TKIs) are currently utilized, none are specific to exon 20 mutations, and historical response rates from mostly small uncontrolled studies vary widely from about 6.9%-35%, with median progression-free survival (PFS) ranging from 3 to 7 months. Poziotinib is a potent oral pan-HER TKI with activity in patients with EGFR or HER2 exon 20–mutated NSCLC.

Dr. Cornelissen presented preliminary safety and efficacy data from the phase 2 ZENITH20, a seven-cohort global clinical trial, specifically from cohort 4 (daily dosing) which included 48 HER2 exon 20 insertion NSCLC patients (median age, 60.5 years; female/male, 26/22) treated first-line with oral daily poziotinib (16 mg). The majority were White (75%), female (54%), and nonsmokers (69%) with an Eastern Cooperative Oncology Group performance status of 1 (65%).The primary endpoint was objective response rate evaluated centrally by an independent image review committee using RECIST 1.1 criteria.

All patients have experienced treatment-related adverse events (TRAEs) with 10% considered serious, and permanent discontinuation in 13%. About 83% of patients had dose interruptions and 76% had dose reductions. The most common adverse events were diarrhea (any grade, 83%; grade 3, 15%), rash (any grade, 69%; grade 3, 35%), stomatitis/mucosal inflammation (any grade, 81%; grade 3, 21%), and paronychia (any grade, 46%; grade 3 8%). Pneumonitis occurred in two patients (4%), with one grade 3 (2%). No grade 4/5 TRAEs were reported.

Discontinuations in 44 patients (92%), Dr. Cornelissen said, are attributed to death (5/10%), disease progression (30/63%), adverse events (1/2%), and other (8/17%), with treatment ongoing in 4 patients (8%).

The rate for the primary endpoint of ORR was 43.8% (n = 21) (95% confidence interval, 29.5%-58.8%).Tumor reductions have been observed in 42/48 patients (88%) with a median reduction of 35%. One complete response was reported (2.1%), with partial responses in 20 (41.7%), stable disease in 15 (31.3%), progressive disease in 7 (14.6%), and 5 (10.4%) not evaluable. The disease control rate was 75.0%.

Among secondary endpoints, median duration of response (DoR) was 5.4 months (range, 2.8 to >19.1), with 42% of patients having response duration greater than6 months and 24% greater than 12 months. Median PFS was 5.6 months (range, 0 to >20.2), with progression-free survival duration greater than6 months in 42% and duration greater than12 months in 26%.

Dr. Cornelissen concluded: “Poziotinib shows clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.” The toxicity profile, he added, is manageable and in line with previous poziotinib studies and other second-generation EGFR TKIs.

Noting that improved tolerability and antitumor activity have been observed in the cohort 5 (8 mg b.i.d.) interim analysis, Dr. Cornelissen said that cohort 4 is ongoing with patients enrolling at 8-mg b.i.d. dosing.

HER2 mutations represents 1.7%-2.2% of NSCLC, with high-sequence homology with EGFR mutation, observed ESMO-appointed discussant Daniel S.W. Tan, PhD, National Cancer Center in Singapore. He pointed out that, while HER2 antibody drug conjugates and TKIs have gained approval in other cancer types (e.g., breast, gastric), currently no HER2 therapies are approved in NSCLC. Reviewing ZENITH20 findings (risk ratio, 43.8%; DoR, 5.4 months; PFS, 5.6 months), Dr. Tan stated that poziotinib is an active agent in HER2 mutated NSCLC. “One concern that remains for me is the safety profile that will require further evaluation in order to determine optimal dosing,” he said.

Potential combinations, he added, need to be explored to improve the durability of response. “Until we can properly characterize this and other important aspects such as CNS activity, we need to be cautious about transitioning to a frontline setting. Also, we do need to give due consideration to strategies to improve HER2 testing rates in order to expand on clinical experience. This argues for the importance of broad upfront next generation sequencing testing in NSCLC.”

The study was funded by Spectrum Pharmaceuticals. Other authors associated with the research disclosed full or part-time employment with Spectrum.

Once-daily dosing of poziotinib shows clinically meaningful efficacy for patients with treatment-naive non–small cell lung cancer (NSCLC) HER2 exon 20 mutations, according to results of the ZENITH20 trial presented at the 2021 European Society for Medical Oncology Congress. Tumor reductions, stated lead author Robin Cornelissen, PhD, MD, Erasmus University, Rotterdam, the Netherlands, were seen in 88% of patients.

EGFR and HER2 exon 20 insertion mutations are rare subsets accounting for about 10% each of all mutations and 2%-4% each in NSCLC. “There is no approved therapy for either treatment-naive or previously treated NSCLC with HER2 exon 20 mutations,” Dr. Cornelissen said in a virtual oral presentation (abstract LBA46) on Sept. 18. While chemotherapy agents with or without checkpoint inhibitors and tyrosine kinase inhibitors (TKIs) are currently utilized, none are specific to exon 20 mutations, and historical response rates from mostly small uncontrolled studies vary widely from about 6.9%-35%, with median progression-free survival (PFS) ranging from 3 to 7 months. Poziotinib is a potent oral pan-HER TKI with activity in patients with EGFR or HER2 exon 20–mutated NSCLC.

Dr. Cornelissen presented preliminary safety and efficacy data from the phase 2 ZENITH20, a seven-cohort global clinical trial, specifically from cohort 4 (daily dosing) which included 48 HER2 exon 20 insertion NSCLC patients (median age, 60.5 years; female/male, 26/22) treated first-line with oral daily poziotinib (16 mg). The majority were White (75%), female (54%), and nonsmokers (69%) with an Eastern Cooperative Oncology Group performance status of 1 (65%).The primary endpoint was objective response rate evaluated centrally by an independent image review committee using RECIST 1.1 criteria.

All patients have experienced treatment-related adverse events (TRAEs) with 10% considered serious, and permanent discontinuation in 13%. About 83% of patients had dose interruptions and 76% had dose reductions. The most common adverse events were diarrhea (any grade, 83%; grade 3, 15%), rash (any grade, 69%; grade 3, 35%), stomatitis/mucosal inflammation (any grade, 81%; grade 3, 21%), and paronychia (any grade, 46%; grade 3 8%). Pneumonitis occurred in two patients (4%), with one grade 3 (2%). No grade 4/5 TRAEs were reported.

Discontinuations in 44 patients (92%), Dr. Cornelissen said, are attributed to death (5/10%), disease progression (30/63%), adverse events (1/2%), and other (8/17%), with treatment ongoing in 4 patients (8%).

The rate for the primary endpoint of ORR was 43.8% (n = 21) (95% confidence interval, 29.5%-58.8%).Tumor reductions have been observed in 42/48 patients (88%) with a median reduction of 35%. One complete response was reported (2.1%), with partial responses in 20 (41.7%), stable disease in 15 (31.3%), progressive disease in 7 (14.6%), and 5 (10.4%) not evaluable. The disease control rate was 75.0%.

Among secondary endpoints, median duration of response (DoR) was 5.4 months (range, 2.8 to >19.1), with 42% of patients having response duration greater than6 months and 24% greater than 12 months. Median PFS was 5.6 months (range, 0 to >20.2), with progression-free survival duration greater than6 months in 42% and duration greater than12 months in 26%.

Dr. Cornelissen concluded: “Poziotinib shows clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.” The toxicity profile, he added, is manageable and in line with previous poziotinib studies and other second-generation EGFR TKIs.

Noting that improved tolerability and antitumor activity have been observed in the cohort 5 (8 mg b.i.d.) interim analysis, Dr. Cornelissen said that cohort 4 is ongoing with patients enrolling at 8-mg b.i.d. dosing.

HER2 mutations represents 1.7%-2.2% of NSCLC, with high-sequence homology with EGFR mutation, observed ESMO-appointed discussant Daniel S.W. Tan, PhD, National Cancer Center in Singapore. He pointed out that, while HER2 antibody drug conjugates and TKIs have gained approval in other cancer types (e.g., breast, gastric), currently no HER2 therapies are approved in NSCLC. Reviewing ZENITH20 findings (risk ratio, 43.8%; DoR, 5.4 months; PFS, 5.6 months), Dr. Tan stated that poziotinib is an active agent in HER2 mutated NSCLC. “One concern that remains for me is the safety profile that will require further evaluation in order to determine optimal dosing,” he said.

Potential combinations, he added, need to be explored to improve the durability of response. “Until we can properly characterize this and other important aspects such as CNS activity, we need to be cautious about transitioning to a frontline setting. Also, we do need to give due consideration to strategies to improve HER2 testing rates in order to expand on clinical experience. This argues for the importance of broad upfront next generation sequencing testing in NSCLC.”

The study was funded by Spectrum Pharmaceuticals. Other authors associated with the research disclosed full or part-time employment with Spectrum.