MIAMI – Women distressed by a low desire for sex could have a novel pharmaceutical intervention soon.

Phase III results from the two Reconnect studies of 1,247 premenopausal women with hypoactive sexual desire disorder in stable relationships showed that bremelanotide was associated with statistically significant improvements in sexual desire and levels of distress about hyposexuality, compared with placebo. The phase III results confirm a phase IIb randomized, double-blind, multicenter trial showing that the drug boosts sexual arousal and desire in this population.

In addition to meeting the studies’ primary endpoints, bremelanotide also was associated with significant improvements in other patient-reported outcomes such as increased levels of arousal, lubrication, and orgasm, with an overall increase in the number of satisfying sexual events, reported lead investigator Anita H. Clayton, MD, who chairs the department of psychiatry and neurobehavioral sciences department at the University of Virginia, Charlottesville.

The phase III data were presented in a poster and during a session dedicated to new drugs in the pipeline at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Bremelanotide, administered subcutaneously, is a novel cyclic 7-amino acid melanocortin-receptor agonist with a high affinity for the type-4 receptor. The mechanism of action is thought to be analogous to a peptide alpha-melanocyte–stimulating hormone that is thought to enhance dopamine and norepinephrine, said Dr. Clayton, the David C. Wilson Professor of Psychiatry and Neurobehavioral Sciences, and professor of clinical obstetrics and gynecology at UVA.

Women in the modified, intent-to-treat study were all given a 1-month, no-drug qualification month, followed by a 1-month single-blind placebo treatment, before they were randomly assigned to 24 weeks of either placebo or 1.75 mg bremelanotide. They could choose to use the drug at their discretion, whenever they anticipated that they would like to have sex.

“Women, on average, had sex about four times a month and used the product three times a month,” Dr. Clayton said in an interview. “We don’t have the answer for [why], but the likelihood is that they used it, and then, when they did, they had more desire and so didn’t need to [use it every time]. But, they could have used it every day of the month if they wanted.”

Changes in Female Sexual Function Index (FSFI) scores from baseline to study’s end were 0.24 in the 316 placebo group, compared with 0.54 in the 314 women in the study drug arm of the first study (P less than .0002). In the second study, the 290 women given placebo had a 0.21 improvement in FSFI scores, compared with a 0.63 improvement in the 282 study drug arm (P less than .0001). The FSFI is a validated, 19-item measure of female sexual function across several domains, including arousal and desire, from the past 30 days. Higher scores indicate better sexual function.

Reductions in distress levels as measured by the Female Sexual Distress Scale: Desire, Arousal, Orgasm (FSDS:DAO), item #13, were –0.35 in the placebo group of the first study, compared with –0.74 in the drug arm (P less than .0001). In the second study, the placebo arm had a –0.42 shift in scores from baseline, compared with –0.71 in the study drug arm (P less than .0057). The FSDS:DAO is a validated, 15-item Likert scale that measures aspects of distress surrounding aspects of sexual functioning in the past 30 days.

Across several secondary patient-reported outcomes study wide, when compared with placebo, the women who had been given bremelanotide reported higher levels of perceived benefit for having been in the study and higher levels of overall satisfaction with their sexual relations while taking the intervention. Changes in pain levels experienced during sex and differences from placebo in the number of satisfying sexual events, as defined by the individual woman, were not statistically significant. However, across the combined study arms, the reported number of satisfying sexual events was numerically better than placebo.

“That just means that ‘satisfying sexual events’ is not a very specific measure in studies of HSDD,” Dr. Clayton said, noting that the Food and Drug Administration no longer requires it as a primary endpoint in the most recent guidance on female sexual dysfunction. “[It’s] nonspecific. Some women think, ‘Yeah, I had a satisfying event because I had an orgasm. Others think it’s because they actually wanted to participate in sex, and that was so much better for them than going along with it but thinking, ‘Just get it over with.’ ”

Mild to moderate treatment-emergent adverse events led 18% of women in the combined drug study groups to either discontinue or interrupt treatment, mostly because of nausea, vomiting, flushing, or headaches. This was in comparison to discontinuation or interruption in 2% of the women in the combined placebo arms.

Because all study participants, whose average age was 39 years, were screened for depression and relationship problems, Dr. Clayton said the causes of HSDD in the study cohort were “biologically based” but that hypoactive sexual desire disorder is a biopsychosocial condition.

“These were women who were in a relationship for at least 6 months and had previously had at least 2 years of what they considered adequate or satisfactory sexual desire and function,” Dr. Clayton said. “My experience with these patients is that they are in love with their partners, they agree on their values, they communicate. But, what’s happened is they biologically and physiologically don’t desire sex anymore.”

In 2015, the FDA approved flibanserin (Addyi) a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist, as the first treatment for hypoactive sexual desire disorder in premenopausal women. Flibanserin, a central acting medication that is taken as 100 mg daily, is marketed by Valeant.*

The bremelanotide studies were sponsored by Palatin Technologies, now with a licensing agreement with AMAG Pharmaceuticals. Dr. Clayton reported numerous financial disclosures, including ties with Palatin, Valeant, and S1 Biopharma. She also receives royalties from Guilford Publications and for her role in developing the Changes in Sexual Functioning Questionnaire.

 

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

* Clarification, 6/21/2017: An earlier version of this story misstated the name of the company marketing Addyi and one of Dr. Clayton’s disclosures. The name of that company is Valeant.

 

MIAMI – Women distressed by a low desire for sex could have a novel pharmaceutical intervention soon.

Phase III results from the two Reconnect studies of 1,247 premenopausal women with hypoactive sexual desire disorder in stable relationships showed that bremelanotide was associated with statistically significant improvements in sexual desire and levels of distress about hyposexuality, compared with placebo. The phase III results confirm a phase IIb randomized, double-blind, multicenter trial showing that the drug boosts sexual arousal and desire in this population.

In addition to meeting the studies’ primary endpoints, bremelanotide also was associated with significant improvements in other patient-reported outcomes such as increased levels of arousal, lubrication, and orgasm, with an overall increase in the number of satisfying sexual events, reported lead investigator Anita H. Clayton, MD, who chairs the department of psychiatry and neurobehavioral sciences department at the University of Virginia, Charlottesville.

The phase III data were presented in a poster and during a session dedicated to new drugs in the pipeline at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Bremelanotide, administered subcutaneously, is a novel cyclic 7-amino acid melanocortin-receptor agonist with a high affinity for the type-4 receptor. The mechanism of action is thought to be analogous to a peptide alpha-melanocyte–stimulating hormone that is thought to enhance dopamine and norepinephrine, said Dr. Clayton, the David C. Wilson Professor of Psychiatry and Neurobehavioral Sciences, and professor of clinical obstetrics and gynecology at UVA.

Women in the modified, intent-to-treat study were all given a 1-month, no-drug qualification month, followed by a 1-month single-blind placebo treatment, before they were randomly assigned to 24 weeks of either placebo or 1.75 mg bremelanotide. They could choose to use the drug at their discretion, whenever they anticipated that they would like to have sex.

“Women, on average, had sex about four times a month and used the product three times a month,” Dr. Clayton said in an interview. “We don’t have the answer for [why], but the likelihood is that they used it, and then, when they did, they had more desire and so didn’t need to [use it every time]. But, they could have used it every day of the month if they wanted.”

Changes in Female Sexual Function Index (FSFI) scores from baseline to study’s end were 0.24 in the 316 placebo group, compared with 0.54 in the 314 women in the study drug arm of the first study (P less than .0002). In the second study, the 290 women given placebo had a 0.21 improvement in FSFI scores, compared with a 0.63 improvement in the 282 study drug arm (P less than .0001). The FSFI is a validated, 19-item measure of female sexual function across several domains, including arousal and desire, from the past 30 days. Higher scores indicate better sexual function.

Reductions in distress levels as measured by the Female Sexual Distress Scale: Desire, Arousal, Orgasm (FSDS:DAO), item #13, were –0.35 in the placebo group of the first study, compared with –0.74 in the drug arm (P less than .0001). In the second study, the placebo arm had a –0.42 shift in scores from baseline, compared with –0.71 in the study drug arm (P less than .0057). The FSDS:DAO is a validated, 15-item Likert scale that measures aspects of distress surrounding aspects of sexual functioning in the past 30 days.

Across several secondary patient-reported outcomes study wide, when compared with placebo, the women who had been given bremelanotide reported higher levels of perceived benefit for having been in the study and higher levels of overall satisfaction with their sexual relations while taking the intervention. Changes in pain levels experienced during sex and differences from placebo in the number of satisfying sexual events, as defined by the individual woman, were not statistically significant. However, across the combined study arms, the reported number of satisfying sexual events was numerically better than placebo.

“That just means that ‘satisfying sexual events’ is not a very specific measure in studies of HSDD,” Dr. Clayton said, noting that the Food and Drug Administration no longer requires it as a primary endpoint in the most recent guidance on female sexual dysfunction. “[It’s] nonspecific. Some women think, ‘Yeah, I had a satisfying event because I had an orgasm. Others think it’s because they actually wanted to participate in sex, and that was so much better for them than going along with it but thinking, ‘Just get it over with.’ ”

Mild to moderate treatment-emergent adverse events led 18% of women in the combined drug study groups to either discontinue or interrupt treatment, mostly because of nausea, vomiting, flushing, or headaches. This was in comparison to discontinuation or interruption in 2% of the women in the combined placebo arms.

Because all study participants, whose average age was 39 years, were screened for depression and relationship problems, Dr. Clayton said the causes of HSDD in the study cohort were “biologically based” but that hypoactive sexual desire disorder is a biopsychosocial condition.

“These were women who were in a relationship for at least 6 months and had previously had at least 2 years of what they considered adequate or satisfactory sexual desire and function,” Dr. Clayton said. “My experience with these patients is that they are in love with their partners, they agree on their values, they communicate. But, what’s happened is they biologically and physiologically don’t desire sex anymore.”

In 2015, the FDA approved flibanserin (Addyi) a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist, as the first treatment for hypoactive sexual desire disorder in premenopausal women. Flibanserin, a central acting medication that is taken as 100 mg daily, is marketed by Valeant.*

The bremelanotide studies were sponsored by Palatin Technologies, now with a licensing agreement with AMAG Pharmaceuticals. Dr. Clayton reported numerous financial disclosures, including ties with Palatin, Valeant, and S1 Biopharma. She also receives royalties from Guilford Publications and for her role in developing the Changes in Sexual Functioning Questionnaire.

 

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

* Clarification, 6/21/2017: An earlier version of this story misstated the name of the company marketing Addyi and one of Dr. Clayton’s disclosures. The name of that company is Valeant.

 

MIAMI – Women distressed by a low desire for sex could have a novel pharmaceutical intervention soon.

Phase III results from the two Reconnect studies of 1,247 premenopausal women with hypoactive sexual desire disorder in stable relationships showed that bremelanotide was associated with statistically significant improvements in sexual desire and levels of distress about hyposexuality, compared with placebo. The phase III results confirm a phase IIb randomized, double-blind, multicenter trial showing that the drug boosts sexual arousal and desire in this population.

In addition to meeting the studies’ primary endpoints, bremelanotide also was associated with significant improvements in other patient-reported outcomes such as increased levels of arousal, lubrication, and orgasm, with an overall increase in the number of satisfying sexual events, reported lead investigator Anita H. Clayton, MD, who chairs the department of psychiatry and neurobehavioral sciences department at the University of Virginia, Charlottesville.

The phase III data were presented in a poster and during a session dedicated to new drugs in the pipeline at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Bremelanotide, administered subcutaneously, is a novel cyclic 7-amino acid melanocortin-receptor agonist with a high affinity for the type-4 receptor. The mechanism of action is thought to be analogous to a peptide alpha-melanocyte–stimulating hormone that is thought to enhance dopamine and norepinephrine, said Dr. Clayton, the David C. Wilson Professor of Psychiatry and Neurobehavioral Sciences, and professor of clinical obstetrics and gynecology at UVA.

Women in the modified, intent-to-treat study were all given a 1-month, no-drug qualification month, followed by a 1-month single-blind placebo treatment, before they were randomly assigned to 24 weeks of either placebo or 1.75 mg bremelanotide. They could choose to use the drug at their discretion, whenever they anticipated that they would like to have sex.

“Women, on average, had sex about four times a month and used the product three times a month,” Dr. Clayton said in an interview. “We don’t have the answer for [why], but the likelihood is that they used it, and then, when they did, they had more desire and so didn’t need to [use it every time]. But, they could have used it every day of the month if they wanted.”

Changes in Female Sexual Function Index (FSFI) scores from baseline to study’s end were 0.24 in the 316 placebo group, compared with 0.54 in the 314 women in the study drug arm of the first study (P less than .0002). In the second study, the 290 women given placebo had a 0.21 improvement in FSFI scores, compared with a 0.63 improvement in the 282 study drug arm (P less than .0001). The FSFI is a validated, 19-item measure of female sexual function across several domains, including arousal and desire, from the past 30 days. Higher scores indicate better sexual function.

Reductions in distress levels as measured by the Female Sexual Distress Scale: Desire, Arousal, Orgasm (FSDS:DAO), item #13, were –0.35 in the placebo group of the first study, compared with –0.74 in the drug arm (P less than .0001). In the second study, the placebo arm had a –0.42 shift in scores from baseline, compared with –0.71 in the study drug arm (P less than .0057). The FSDS:DAO is a validated, 15-item Likert scale that measures aspects of distress surrounding aspects of sexual functioning in the past 30 days.

Across several secondary patient-reported outcomes study wide, when compared with placebo, the women who had been given bremelanotide reported higher levels of perceived benefit for having been in the study and higher levels of overall satisfaction with their sexual relations while taking the intervention. Changes in pain levels experienced during sex and differences from placebo in the number of satisfying sexual events, as defined by the individual woman, were not statistically significant. However, across the combined study arms, the reported number of satisfying sexual events was numerically better than placebo.

“That just means that ‘satisfying sexual events’ is not a very specific measure in studies of HSDD,” Dr. Clayton said, noting that the Food and Drug Administration no longer requires it as a primary endpoint in the most recent guidance on female sexual dysfunction. “[It’s] nonspecific. Some women think, ‘Yeah, I had a satisfying event because I had an orgasm. Others think it’s because they actually wanted to participate in sex, and that was so much better for them than going along with it but thinking, ‘Just get it over with.’ ”

Mild to moderate treatment-emergent adverse events led 18% of women in the combined drug study groups to either discontinue or interrupt treatment, mostly because of nausea, vomiting, flushing, or headaches. This was in comparison to discontinuation or interruption in 2% of the women in the combined placebo arms.

Because all study participants, whose average age was 39 years, were screened for depression and relationship problems, Dr. Clayton said the causes of HSDD in the study cohort were “biologically based” but that hypoactive sexual desire disorder is a biopsychosocial condition.

“These were women who were in a relationship for at least 6 months and had previously had at least 2 years of what they considered adequate or satisfactory sexual desire and function,” Dr. Clayton said. “My experience with these patients is that they are in love with their partners, they agree on their values, they communicate. But, what’s happened is they biologically and physiologically don’t desire sex anymore.”

In 2015, the FDA approved flibanserin (Addyi) a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist, as the first treatment for hypoactive sexual desire disorder in premenopausal women. Flibanserin, a central acting medication that is taken as 100 mg daily, is marketed by Valeant.*

The bremelanotide studies were sponsored by Palatin Technologies, now with a licensing agreement with AMAG Pharmaceuticals. Dr. Clayton reported numerous financial disclosures, including ties with Palatin, Valeant, and S1 Biopharma. She also receives royalties from Guilford Publications and for her role in developing the Changes in Sexual Functioning Questionnaire.

 

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

* Clarification, 6/21/2017: An earlier version of this story misstated the name of the company marketing Addyi and one of Dr. Clayton’s disclosures. The name of that company is Valeant.

 

I had just done an ED&C, scraping the friable tumor gently from her tissue paper–thin skin. “Yes,” I replied more loudly than our close proximity would warrant. “This is probably another basal cell carcinoma. When I get the pathology back, I’ll call you.” As my medical assistant was putting on the Band-Aid, my patient exclaimed, “Oh, no! “Don’t call me! Just send me an email, honey.”

At the time of the biopsy, she was 84 years old. My 84-year-old patient just chastised me for not using her preferred method of communication. She didn’t want a follow-up visit or a phone call. She wanted an email.

This reminded me of a recent study in the American Journal of Managed Care. The authors found that 83% of patients wanted to receive laboratory results online regardless of whether if the result was normal or abnormal (Am J Manag Care. 2017;23[4]:e113-e119). Their findings were skewed toward digital, which contrasts with a JAMA Dermatology study from 2015 that found more patients (67%) preferred a phone call to learn their skin biopsy results (JAMA Dermatol. 2015;151[5]:513-521). Pathology results might be different than lab results in patients’ views.

A certain trend is that patients want speed and convenience. Patients, like all humans, hate to wait. They hate to wait for an appointment. They hate to wait in waiting rooms. They hate to wait for answers. They also hate phone tag and long lines at the TSA (the latter will not be covered in this column).

For most of my biopsy results, I send a secure message – essentially an email – to my patients. I do this for benign results, as well as for treated cancerous growths. For serious diagnoses such as melanoma, I call them and sometimes arrange for a follow-up appointment.

Securely emailing results saves my patients, and me, bags of time. In fact, I not only send them the diagnosis, I include the pathology report. This might seem risky: What will patients make of “atypical melanocytic hyperplasia” or “cannot rule out invasive carcinoma” in their result? I can tell you, not much. After thousands of such emails, I’ve learned that follow-up replies are rare. And I cannot recall any follow-up question that was unhelpful. I’ve even had one correct our report (“Doc, it was on the left arm, not the right”) and at least one that led to a great discussion of different treatments based on my patient’s research.

If nothing else, I hope sending path reports directly to patients will eradicate the unhelpful past medical history of “skin cancer of unknown type or stage.” One biopsy result at a time, thousands of results later, each of my patients has his or her own copy to print and share with their next dermatologist, who might just be you.

“Yes, ma’am, I’ll email the result as soon as it’s back,” I replied, trying to save face. “Great!” she said, showing me her new iPhone, which was one generation advanced from my own. “I’ll get it right here!”

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.

 

I had just done an ED&C, scraping the friable tumor gently from her tissue paper–thin skin. “Yes,” I replied more loudly than our close proximity would warrant. “This is probably another basal cell carcinoma. When I get the pathology back, I’ll call you.” As my medical assistant was putting on the Band-Aid, my patient exclaimed, “Oh, no! “Don’t call me! Just send me an email, honey.”

At the time of the biopsy, she was 84 years old. My 84-year-old patient just chastised me for not using her preferred method of communication. She didn’t want a follow-up visit or a phone call. She wanted an email.

This reminded me of a recent study in the American Journal of Managed Care. The authors found that 83% of patients wanted to receive laboratory results online regardless of whether if the result was normal or abnormal (Am J Manag Care. 2017;23[4]:e113-e119). Their findings were skewed toward digital, which contrasts with a JAMA Dermatology study from 2015 that found more patients (67%) preferred a phone call to learn their skin biopsy results (JAMA Dermatol. 2015;151[5]:513-521). Pathology results might be different than lab results in patients’ views.

A certain trend is that patients want speed and convenience. Patients, like all humans, hate to wait. They hate to wait for an appointment. They hate to wait in waiting rooms. They hate to wait for answers. They also hate phone tag and long lines at the TSA (the latter will not be covered in this column).

For most of my biopsy results, I send a secure message – essentially an email – to my patients. I do this for benign results, as well as for treated cancerous growths. For serious diagnoses such as melanoma, I call them and sometimes arrange for a follow-up appointment.

Securely emailing results saves my patients, and me, bags of time. In fact, I not only send them the diagnosis, I include the pathology report. This might seem risky: What will patients make of “atypical melanocytic hyperplasia” or “cannot rule out invasive carcinoma” in their result? I can tell you, not much. After thousands of such emails, I’ve learned that follow-up replies are rare. And I cannot recall any follow-up question that was unhelpful. I’ve even had one correct our report (“Doc, it was on the left arm, not the right”) and at least one that led to a great discussion of different treatments based on my patient’s research.

If nothing else, I hope sending path reports directly to patients will eradicate the unhelpful past medical history of “skin cancer of unknown type or stage.” One biopsy result at a time, thousands of results later, each of my patients has his or her own copy to print and share with their next dermatologist, who might just be you.

“Yes, ma’am, I’ll email the result as soon as it’s back,” I replied, trying to save face. “Great!” she said, showing me her new iPhone, which was one generation advanced from my own. “I’ll get it right here!”

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.

 

I had just done an ED&C, scraping the friable tumor gently from her tissue paper–thin skin. “Yes,” I replied more loudly than our close proximity would warrant. “This is probably another basal cell carcinoma. When I get the pathology back, I’ll call you.” As my medical assistant was putting on the Band-Aid, my patient exclaimed, “Oh, no! “Don’t call me! Just send me an email, honey.”

At the time of the biopsy, she was 84 years old. My 84-year-old patient just chastised me for not using her preferred method of communication. She didn’t want a follow-up visit or a phone call. She wanted an email.

This reminded me of a recent study in the American Journal of Managed Care. The authors found that 83% of patients wanted to receive laboratory results online regardless of whether if the result was normal or abnormal (Am J Manag Care. 2017;23[4]:e113-e119). Their findings were skewed toward digital, which contrasts with a JAMA Dermatology study from 2015 that found more patients (67%) preferred a phone call to learn their skin biopsy results (JAMA Dermatol. 2015;151[5]:513-521). Pathology results might be different than lab results in patients’ views.

A certain trend is that patients want speed and convenience. Patients, like all humans, hate to wait. They hate to wait for an appointment. They hate to wait in waiting rooms. They hate to wait for answers. They also hate phone tag and long lines at the TSA (the latter will not be covered in this column).

For most of my biopsy results, I send a secure message – essentially an email – to my patients. I do this for benign results, as well as for treated cancerous growths. For serious diagnoses such as melanoma, I call them and sometimes arrange for a follow-up appointment.

Securely emailing results saves my patients, and me, bags of time. In fact, I not only send them the diagnosis, I include the pathology report. This might seem risky: What will patients make of “atypical melanocytic hyperplasia” or “cannot rule out invasive carcinoma” in their result? I can tell you, not much. After thousands of such emails, I’ve learned that follow-up replies are rare. And I cannot recall any follow-up question that was unhelpful. I’ve even had one correct our report (“Doc, it was on the left arm, not the right”) and at least one that led to a great discussion of different treatments based on my patient’s research.

If nothing else, I hope sending path reports directly to patients will eradicate the unhelpful past medical history of “skin cancer of unknown type or stage.” One biopsy result at a time, thousands of results later, each of my patients has his or her own copy to print and share with their next dermatologist, who might just be you.

“Yes, ma’am, I’ll email the result as soon as it’s back,” I replied, trying to save face. “Great!” she said, showing me her new iPhone, which was one generation advanced from my own. “I’ll get it right here!”

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.

 

WASHINGTON – Bronchiectasis patients with three or more exacerbations per year had twice the mortality during 5-year follow-up as patients with no recent exacerbations, in a prospective registry of nearly 2,600 European bronchiectasis patients.

A multivariate analysis showed this statistically significant doubled death rate after adjustment for baseline demographic and clinical differences between patients with no exacerbations during the year before they entered the registry, James D. Chalmers, MD, said at an international conference of the American Thoracic Society.

Having had frequent exacerbations at a rate of three or more annually prior to enrollment was common, with 37% of the 2,596 bronchiectasis patients in the registry having this history, said Dr. Chalmers, a pulmonologist at the University of Dundee, Scotland.

This 37% prevalence contrasted with a 19% U.S. prevalence of bronchiectasis patients having two or more exacerbations per year among 2,114 patients enrolled in a 13-center U.S. registry that was reported during the same session by Timothy R. Aksamit, MD, a pulmonologist at the Mayo Clinic in Rochester, Minn. During his talk, Dr. Aksamit suggested that the European cohort might include more patients with asthma, chronic obstructive pulmonary disease, or other complications in addition to bronchiectasis. Dr. Aksamit contended that the U.S. registry tried to exclusively enroll patients with bronchiectasis and no other disorder, possibly explaining the prevalence difference between Europe and the United States.

The European registry included patients with bronchiectasis seen in 10 centers in seven European countries and Israel. They averaged 67 years of age. While more than a third had a history of at least three exacerbations a year, one-quarter had no exacerbations during the year before they entered the study.

The prospective study also showed that, among patients with three or more exacerbations annually, the risk for a subsequent exacerbation was five times higher than among patients with no recent exacerbations, Dr. Chalmers reported.

The U.S. registry reported by Dr. Aksamit had 2-year follow-up data for 1,049 of the enrolled patients, a subgroup that closely matched the entire population initially enrolled. The 2-year follow-up showed an overall average exacerbation rate of 0.75 episodes per year, but this was driven largely by the subgroup of patients who entered the registry with a history of two or more exacerbations per year, who then averaged about 2.6 exacerbations during follow-up. In contrast, patients who entered the registry with a history of fewer than two exacerbations per year averaged fewer than a third of an exacerbation per year during follow-up, Dr. Aksamit reported.

The European bronchiectasis registry was partially funded by Bayer. Dr. Chalmers has been a consultant to Bayer and to AstraZeneca, Basilea, Grifols, Napp, and Raptor and has received research funding from Aradigm, AstraZeneca, Bayer, GlaxoSmithKline, and Pfizer. Dr. Aksamit had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

 

WASHINGTON – Bronchiectasis patients with three or more exacerbations per year had twice the mortality during 5-year follow-up as patients with no recent exacerbations, in a prospective registry of nearly 2,600 European bronchiectasis patients.

A multivariate analysis showed this statistically significant doubled death rate after adjustment for baseline demographic and clinical differences between patients with no exacerbations during the year before they entered the registry, James D. Chalmers, MD, said at an international conference of the American Thoracic Society.

Having had frequent exacerbations at a rate of three or more annually prior to enrollment was common, with 37% of the 2,596 bronchiectasis patients in the registry having this history, said Dr. Chalmers, a pulmonologist at the University of Dundee, Scotland.

This 37% prevalence contrasted with a 19% U.S. prevalence of bronchiectasis patients having two or more exacerbations per year among 2,114 patients enrolled in a 13-center U.S. registry that was reported during the same session by Timothy R. Aksamit, MD, a pulmonologist at the Mayo Clinic in Rochester, Minn. During his talk, Dr. Aksamit suggested that the European cohort might include more patients with asthma, chronic obstructive pulmonary disease, or other complications in addition to bronchiectasis. Dr. Aksamit contended that the U.S. registry tried to exclusively enroll patients with bronchiectasis and no other disorder, possibly explaining the prevalence difference between Europe and the United States.

The European registry included patients with bronchiectasis seen in 10 centers in seven European countries and Israel. They averaged 67 years of age. While more than a third had a history of at least three exacerbations a year, one-quarter had no exacerbations during the year before they entered the study.

The prospective study also showed that, among patients with three or more exacerbations annually, the risk for a subsequent exacerbation was five times higher than among patients with no recent exacerbations, Dr. Chalmers reported.

The U.S. registry reported by Dr. Aksamit had 2-year follow-up data for 1,049 of the enrolled patients, a subgroup that closely matched the entire population initially enrolled. The 2-year follow-up showed an overall average exacerbation rate of 0.75 episodes per year, but this was driven largely by the subgroup of patients who entered the registry with a history of two or more exacerbations per year, who then averaged about 2.6 exacerbations during follow-up. In contrast, patients who entered the registry with a history of fewer than two exacerbations per year averaged fewer than a third of an exacerbation per year during follow-up, Dr. Aksamit reported.

The European bronchiectasis registry was partially funded by Bayer. Dr. Chalmers has been a consultant to Bayer and to AstraZeneca, Basilea, Grifols, Napp, and Raptor and has received research funding from Aradigm, AstraZeneca, Bayer, GlaxoSmithKline, and Pfizer. Dr. Aksamit had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

 

WASHINGTON – Bronchiectasis patients with three or more exacerbations per year had twice the mortality during 5-year follow-up as patients with no recent exacerbations, in a prospective registry of nearly 2,600 European bronchiectasis patients.

A multivariate analysis showed this statistically significant doubled death rate after adjustment for baseline demographic and clinical differences between patients with no exacerbations during the year before they entered the registry, James D. Chalmers, MD, said at an international conference of the American Thoracic Society.

Having had frequent exacerbations at a rate of three or more annually prior to enrollment was common, with 37% of the 2,596 bronchiectasis patients in the registry having this history, said Dr. Chalmers, a pulmonologist at the University of Dundee, Scotland.

This 37% prevalence contrasted with a 19% U.S. prevalence of bronchiectasis patients having two or more exacerbations per year among 2,114 patients enrolled in a 13-center U.S. registry that was reported during the same session by Timothy R. Aksamit, MD, a pulmonologist at the Mayo Clinic in Rochester, Minn. During his talk, Dr. Aksamit suggested that the European cohort might include more patients with asthma, chronic obstructive pulmonary disease, or other complications in addition to bronchiectasis. Dr. Aksamit contended that the U.S. registry tried to exclusively enroll patients with bronchiectasis and no other disorder, possibly explaining the prevalence difference between Europe and the United States.

The European registry included patients with bronchiectasis seen in 10 centers in seven European countries and Israel. They averaged 67 years of age. While more than a third had a history of at least three exacerbations a year, one-quarter had no exacerbations during the year before they entered the study.

The prospective study also showed that, among patients with three or more exacerbations annually, the risk for a subsequent exacerbation was five times higher than among patients with no recent exacerbations, Dr. Chalmers reported.

The U.S. registry reported by Dr. Aksamit had 2-year follow-up data for 1,049 of the enrolled patients, a subgroup that closely matched the entire population initially enrolled. The 2-year follow-up showed an overall average exacerbation rate of 0.75 episodes per year, but this was driven largely by the subgroup of patients who entered the registry with a history of two or more exacerbations per year, who then averaged about 2.6 exacerbations during follow-up. In contrast, patients who entered the registry with a history of fewer than two exacerbations per year averaged fewer than a third of an exacerbation per year during follow-up, Dr. Aksamit reported.

The European bronchiectasis registry was partially funded by Bayer. Dr. Chalmers has been a consultant to Bayer and to AstraZeneca, Basilea, Grifols, Napp, and Raptor and has received research funding from Aradigm, AstraZeneca, Bayer, GlaxoSmithKline, and Pfizer. Dr. Aksamit had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

 

NEW YORK – While bioprosthetic valves have become the predominant choice for cardiothoracic surgeons performing heart valve replacement, situations exist in which a mechanical valve may be a better choice. Young and middle-aged adults are the ideal candidates for mechanical valves, but achieving long-term success with mechanical valves also depends on a patient’s circumstances, according to an expert panel at the American Association for Thoracic Surgery Mitral Conclave 2017 here.

“I think we should put in more mechanical valves,” said panel chair Thoralf M. Sundt III, MD, of Massachusetts General Hospital, Boston and former AATS president. “I think mechanical valves have gotten a bad rap. If patients have a supportive, stable social structure and they can manage their anticoagulation, I don’t think there’s anything wrong with a mechanical valve. I think the pendulum has swung too far.”

Socioeconomic factors can play a role too, Dr. Sundt said. “It depends a lot on what the risk and practicality of a reoperation are like,” he said. “There are environments where a reoperation just isn’t an economic possibility. If you’re in a country where a family has to sell the farm in order to get the first operation, there’s not going to be a second operation.”

Anelechi C. Anyanwu, MD, of Mount Sinai Health System, New York, acknowledged another patient factor that would enter his calculus for recommending a mechanical mitral valve. “We would consider a mechanical valve in the patient who is compliant [and] well informed and understands well the requirements and implications of long-term anticoagulation,” he said. In another scenario – “the patient who’s had multiple reoperations – we may consider a mechanical valve.” Particularly, the patient who has had a reoperation for a bioprosthetic valve resulting from early degeneration will merit consideration of a mechanical prosthesis, Dr. Anyanwu said.

Michael A. Borger, MD, of Columbia University Medical Center, New York, agreed that the younger patient who has had a series of operations is a good candidate for a mechanical mitral valve. “In addition, the mechanical valve does have some hemodynamic advantages over bioprosthetic valves,” Dr. Borger said. “If a surgeon implants a 25-mm tissue valve with a plan for the patient to undergo a series of valve-in-valve operations in the future, mitral stenosis will definitely become a factor at some point.”

Small children are another population in which mechanical valves may be considered, but the long-term success rate has been discouraging, said Rudiger Lange, MD, of the German Heart Center, Munich.

Pedro J. del Nido, MD, a pediatric cardiac surgeon at Children’s Hospital, Boston, expanded on that point. “We very, very rarely use mechanical valves in young patients,” Dr. del Nido said. “In very young patients, the reoperation rates for mechanical or biological valves are not much different. We still have to reoperate on both sets of patients. But, the reoperation itself for a mechanical valve is more difficult, and there is the need for full anticoagulation.”

Instead, Dr. del Nido has used the bovine Melody valve (Medtronic) in the mitral position for these patients because it accommodates some growth. Typically, the only time Dr. del Nido considers a mechanical valve in these young patients is for an aortic valve replacement.

Another younger patient that may be a good candidate for a mechanical valve is the 25-year-old male with rheumatic mitral stenosis. “I would err on the side of the mechanical valve in this patient if I were to make a choice, but I would present the patient with informed data on the outcomes of both mechanical valve and bioprosthesis,” according to Dr. Anyanwu

However, Dr. Lange would still opt for a biological valve in that 25-year-old. “The patient’s preference is important,” he said. “I would rather put in a biological valve in this patient – maybe put two more transcatheter valves transeptally in the future and do one reoperation.”

For even younger patients, Dr. del Nido bases his valve choice on their activity level. “I have a lot of young teenagers, and my decision is entirely based on what their background is like – what their regular life is like,” he said. “If they have a support structure than can help them manage anticoagulation, absolutely the mechanical valve is probably the best thing.”

However, there are exceptions because the couching of the device can change over time. “Eventually that 12-year-old [or] that 15-year-old is going to decide he can still snowboard or ride a motorcycle, and that’s when he’s going to get into trouble,” Dr. del Nido said. “If a reoperation is not problematic, I would still say it’s a tossup between the mechanical and biological valve. I would still offer the possibility of a bioprosthesis knowing that they’ll be back in 6, 8, or 10 years.”

Bleeding risk is another factor that can influence valve choice, as mechanical valve recipients must stay on anticoagulation. “The bleeding complication rates are very low when patients are younger, in their 40s or 50s, but the bleeding rates increase exponentially with warfarin for patients in their 80s and 90s,” Dr. Borger said. “The older you are, the more difficult it is to manage anticoagulation. In addition, the ability to stop anticoagulants because of bleeding is different for the two types of prostheses. If a patient develops bleeding during anticoagulation for leaflet immobility after a tissue valve-in-valve procedure, the physician can simply stop the warfarin. But, if you have a mechanical mitral valve in place that’s not an option.”

That’s not necessarily a bad problem to have, Dr. Sundt said, quoting Steven Bolling, MD, of the University of Michigan. “If you’re 25 and you’ve had your valve replaced and you’re worried about bleeding at the age of 80, I call that a success.”

Dr. Borger disclosed he is a speaker for and consultant to Edwards Lifesciences, Medtronic, and CryoLife; a speaker for St. Jude; and a recipient of research support from NeoChord. Dr. Lange disclosed he is a consultant and speaker for Medtronic, St. Jude/Abbott, LivaNova and NeoChord and cofounder of HighLife. Dr. Anyanwu, Dr. del Nido, and Dr. Sundt reported no relevant financial relationships.

 

NEW YORK – While bioprosthetic valves have become the predominant choice for cardiothoracic surgeons performing heart valve replacement, situations exist in which a mechanical valve may be a better choice. Young and middle-aged adults are the ideal candidates for mechanical valves, but achieving long-term success with mechanical valves also depends on a patient’s circumstances, according to an expert panel at the American Association for Thoracic Surgery Mitral Conclave 2017 here.

“I think we should put in more mechanical valves,” said panel chair Thoralf M. Sundt III, MD, of Massachusetts General Hospital, Boston and former AATS president. “I think mechanical valves have gotten a bad rap. If patients have a supportive, stable social structure and they can manage their anticoagulation, I don’t think there’s anything wrong with a mechanical valve. I think the pendulum has swung too far.”

Socioeconomic factors can play a role too, Dr. Sundt said. “It depends a lot on what the risk and practicality of a reoperation are like,” he said. “There are environments where a reoperation just isn’t an economic possibility. If you’re in a country where a family has to sell the farm in order to get the first operation, there’s not going to be a second operation.”

Anelechi C. Anyanwu, MD, of Mount Sinai Health System, New York, acknowledged another patient factor that would enter his calculus for recommending a mechanical mitral valve. “We would consider a mechanical valve in the patient who is compliant [and] well informed and understands well the requirements and implications of long-term anticoagulation,” he said. In another scenario – “the patient who’s had multiple reoperations – we may consider a mechanical valve.” Particularly, the patient who has had a reoperation for a bioprosthetic valve resulting from early degeneration will merit consideration of a mechanical prosthesis, Dr. Anyanwu said.

Michael A. Borger, MD, of Columbia University Medical Center, New York, agreed that the younger patient who has had a series of operations is a good candidate for a mechanical mitral valve. “In addition, the mechanical valve does have some hemodynamic advantages over bioprosthetic valves,” Dr. Borger said. “If a surgeon implants a 25-mm tissue valve with a plan for the patient to undergo a series of valve-in-valve operations in the future, mitral stenosis will definitely become a factor at some point.”

Small children are another population in which mechanical valves may be considered, but the long-term success rate has been discouraging, said Rudiger Lange, MD, of the German Heart Center, Munich.

Pedro J. del Nido, MD, a pediatric cardiac surgeon at Children’s Hospital, Boston, expanded on that point. “We very, very rarely use mechanical valves in young patients,” Dr. del Nido said. “In very young patients, the reoperation rates for mechanical or biological valves are not much different. We still have to reoperate on both sets of patients. But, the reoperation itself for a mechanical valve is more difficult, and there is the need for full anticoagulation.”

Instead, Dr. del Nido has used the bovine Melody valve (Medtronic) in the mitral position for these patients because it accommodates some growth. Typically, the only time Dr. del Nido considers a mechanical valve in these young patients is for an aortic valve replacement.

Another younger patient that may be a good candidate for a mechanical valve is the 25-year-old male with rheumatic mitral stenosis. “I would err on the side of the mechanical valve in this patient if I were to make a choice, but I would present the patient with informed data on the outcomes of both mechanical valve and bioprosthesis,” according to Dr. Anyanwu

However, Dr. Lange would still opt for a biological valve in that 25-year-old. “The patient’s preference is important,” he said. “I would rather put in a biological valve in this patient – maybe put two more transcatheter valves transeptally in the future and do one reoperation.”

For even younger patients, Dr. del Nido bases his valve choice on their activity level. “I have a lot of young teenagers, and my decision is entirely based on what their background is like – what their regular life is like,” he said. “If they have a support structure than can help them manage anticoagulation, absolutely the mechanical valve is probably the best thing.”

However, there are exceptions because the couching of the device can change over time. “Eventually that 12-year-old [or] that 15-year-old is going to decide he can still snowboard or ride a motorcycle, and that’s when he’s going to get into trouble,” Dr. del Nido said. “If a reoperation is not problematic, I would still say it’s a tossup between the mechanical and biological valve. I would still offer the possibility of a bioprosthesis knowing that they’ll be back in 6, 8, or 10 years.”

Bleeding risk is another factor that can influence valve choice, as mechanical valve recipients must stay on anticoagulation. “The bleeding complication rates are very low when patients are younger, in their 40s or 50s, but the bleeding rates increase exponentially with warfarin for patients in their 80s and 90s,” Dr. Borger said. “The older you are, the more difficult it is to manage anticoagulation. In addition, the ability to stop anticoagulants because of bleeding is different for the two types of prostheses. If a patient develops bleeding during anticoagulation for leaflet immobility after a tissue valve-in-valve procedure, the physician can simply stop the warfarin. But, if you have a mechanical mitral valve in place that’s not an option.”

That’s not necessarily a bad problem to have, Dr. Sundt said, quoting Steven Bolling, MD, of the University of Michigan. “If you’re 25 and you’ve had your valve replaced and you’re worried about bleeding at the age of 80, I call that a success.”

Dr. Borger disclosed he is a speaker for and consultant to Edwards Lifesciences, Medtronic, and CryoLife; a speaker for St. Jude; and a recipient of research support from NeoChord. Dr. Lange disclosed he is a consultant and speaker for Medtronic, St. Jude/Abbott, LivaNova and NeoChord and cofounder of HighLife. Dr. Anyanwu, Dr. del Nido, and Dr. Sundt reported no relevant financial relationships.

 

NEW YORK – While bioprosthetic valves have become the predominant choice for cardiothoracic surgeons performing heart valve replacement, situations exist in which a mechanical valve may be a better choice. Young and middle-aged adults are the ideal candidates for mechanical valves, but achieving long-term success with mechanical valves also depends on a patient’s circumstances, according to an expert panel at the American Association for Thoracic Surgery Mitral Conclave 2017 here.

“I think we should put in more mechanical valves,” said panel chair Thoralf M. Sundt III, MD, of Massachusetts General Hospital, Boston and former AATS president. “I think mechanical valves have gotten a bad rap. If patients have a supportive, stable social structure and they can manage their anticoagulation, I don’t think there’s anything wrong with a mechanical valve. I think the pendulum has swung too far.”

Socioeconomic factors can play a role too, Dr. Sundt said. “It depends a lot on what the risk and practicality of a reoperation are like,” he said. “There are environments where a reoperation just isn’t an economic possibility. If you’re in a country where a family has to sell the farm in order to get the first operation, there’s not going to be a second operation.”

Anelechi C. Anyanwu, MD, of Mount Sinai Health System, New York, acknowledged another patient factor that would enter his calculus for recommending a mechanical mitral valve. “We would consider a mechanical valve in the patient who is compliant [and] well informed and understands well the requirements and implications of long-term anticoagulation,” he said. In another scenario – “the patient who’s had multiple reoperations – we may consider a mechanical valve.” Particularly, the patient who has had a reoperation for a bioprosthetic valve resulting from early degeneration will merit consideration of a mechanical prosthesis, Dr. Anyanwu said.

Michael A. Borger, MD, of Columbia University Medical Center, New York, agreed that the younger patient who has had a series of operations is a good candidate for a mechanical mitral valve. “In addition, the mechanical valve does have some hemodynamic advantages over bioprosthetic valves,” Dr. Borger said. “If a surgeon implants a 25-mm tissue valve with a plan for the patient to undergo a series of valve-in-valve operations in the future, mitral stenosis will definitely become a factor at some point.”

Small children are another population in which mechanical valves may be considered, but the long-term success rate has been discouraging, said Rudiger Lange, MD, of the German Heart Center, Munich.

Pedro J. del Nido, MD, a pediatric cardiac surgeon at Children’s Hospital, Boston, expanded on that point. “We very, very rarely use mechanical valves in young patients,” Dr. del Nido said. “In very young patients, the reoperation rates for mechanical or biological valves are not much different. We still have to reoperate on both sets of patients. But, the reoperation itself for a mechanical valve is more difficult, and there is the need for full anticoagulation.”

Instead, Dr. del Nido has used the bovine Melody valve (Medtronic) in the mitral position for these patients because it accommodates some growth. Typically, the only time Dr. del Nido considers a mechanical valve in these young patients is for an aortic valve replacement.

Another younger patient that may be a good candidate for a mechanical valve is the 25-year-old male with rheumatic mitral stenosis. “I would err on the side of the mechanical valve in this patient if I were to make a choice, but I would present the patient with informed data on the outcomes of both mechanical valve and bioprosthesis,” according to Dr. Anyanwu

However, Dr. Lange would still opt for a biological valve in that 25-year-old. “The patient’s preference is important,” he said. “I would rather put in a biological valve in this patient – maybe put two more transcatheter valves transeptally in the future and do one reoperation.”

For even younger patients, Dr. del Nido bases his valve choice on their activity level. “I have a lot of young teenagers, and my decision is entirely based on what their background is like – what their regular life is like,” he said. “If they have a support structure than can help them manage anticoagulation, absolutely the mechanical valve is probably the best thing.”

However, there are exceptions because the couching of the device can change over time. “Eventually that 12-year-old [or] that 15-year-old is going to decide he can still snowboard or ride a motorcycle, and that’s when he’s going to get into trouble,” Dr. del Nido said. “If a reoperation is not problematic, I would still say it’s a tossup between the mechanical and biological valve. I would still offer the possibility of a bioprosthesis knowing that they’ll be back in 6, 8, or 10 years.”

Bleeding risk is another factor that can influence valve choice, as mechanical valve recipients must stay on anticoagulation. “The bleeding complication rates are very low when patients are younger, in their 40s or 50s, but the bleeding rates increase exponentially with warfarin for patients in their 80s and 90s,” Dr. Borger said. “The older you are, the more difficult it is to manage anticoagulation. In addition, the ability to stop anticoagulants because of bleeding is different for the two types of prostheses. If a patient develops bleeding during anticoagulation for leaflet immobility after a tissue valve-in-valve procedure, the physician can simply stop the warfarin. But, if you have a mechanical mitral valve in place that’s not an option.”

That’s not necessarily a bad problem to have, Dr. Sundt said, quoting Steven Bolling, MD, of the University of Michigan. “If you’re 25 and you’ve had your valve replaced and you’re worried about bleeding at the age of 80, I call that a success.”

Dr. Borger disclosed he is a speaker for and consultant to Edwards Lifesciences, Medtronic, and CryoLife; a speaker for St. Jude; and a recipient of research support from NeoChord. Dr. Lange disclosed he is a consultant and speaker for Medtronic, St. Jude/Abbott, LivaNova and NeoChord and cofounder of HighLife. Dr. Anyanwu, Dr. del Nido, and Dr. Sundt reported no relevant financial relationships.

 

SAN DIEGO – When basal insulin alone does not achieve glucose targets in type 2 diabetes, a single fixed-dose injection of insulin degludec and liraglutide (IDegLira) is as effective as multiple insulin injections and has a significantly lower risk of hypoglycemia, according to a randomized, multicenter, open-label, industry-sponsored trial.

After 26 weeks of treatment, average hemoglobin A1c levels dropped similarly with once-daily IDegLira (1.48%) as with basal insulin glargine U100 plus mealtime injections of short-acting insulin aspart (1.46%; P less than .0001 for noninferiority), reported Liana K. Billings, MD, at the annual scientific sessions of the American Diabetes Association.

Importantly, just 20% of IDegLira patients had at least one confirmed event of hypoglycemia, compared with 53% of those on basal-bolus insulin (rate ratio, 0.11; 95% confidence interval, 0.08-0.17; P less than .0001), reported Dr. Billings of Northshore University Health System in Skokie, Ill. That translated to seven fewer hypoglycemic events per year in the IDegLira arm, she said. “Now, take this in context – this is comparing one injection a day with four injections a day,” she added.

Patients also needed significantly less insulin and lost significantly more weight on IDegLira, compared with the basal-bolus regimen. “This is some of the most robust, most impressive data I’ve seen in years,” Julio Rosenstock, MD, director of the Dallas Diabetes and Endocrine Center in Texas, commented from the audience. Dr. Rosenstock was not involved in the trial and has studied other combination regimens for type 2 diabetes.

The advent of new insulins and adjunct therapies gives clinicians many potential algorithms for treating type 2 diabetes patients. The ADA recommends that health care professionals consider dual or triple therapy if patients do not meet glycemic targets with lifestyle changes and metformin alone. However, weight gain, hypoglycemia, and complex treatment regimens can make it difficult to intensify treatment in the real world, Dr. Billings said.

Insulin degludec is an ultra–long-acting basal insulin analogue, while liraglutide is a GLP-1 receptor agonist. The open-label, phase III DUAL VII study compared once-daily IDegLira injection (Xultophy, Novo Nordisk) with once-daily basal insulin glargine (Lantus, Sanofi) U100 plus bolus insulin aspart (NovoLog, Novo Nordisk) at mealtimes in 506 adults with type 2 diabetes. All patients were on metformin and glargine (typically 34 U) at baseline. Most were in their late 50s and obese, with an average 13-year duration of type 2 diabetes and HbA1c levels of 8.2% despite treatment. The IDegLira group started at 16 U and titrated by 2 U twice weekly to reach a fasting glucose target of 72-90 mg/dL. Basal-bolus patients maintained their baseline glargine dose and added 4 U mealtime bolus insulin aspart, titrating to target by 1 U twice weekly. The primary endpoint was change in HbA1c levels after 26 weeks. More than 98% of patients completed the trial. Approximately two-thirds of patients in both arms achieved an HbA1c level below 7%, but IDegLira recipients were significantly more likely to do so without gaining weight or experiencing hypoglycemia during the last 12 weeks of treatment (odds ratio, 10.39; 95% CI, 5.76-18.75). The IDegLira arm received significantly less daily insulin than the basal-bolus arm (40 U versus 84 U; P less than .0001), and IDegLira patients lost an average of 0.93 kg, while the comparison group gained 2.64 kg. Rates of serious adverse events were low and similar between arms. The cumulative rate of nausea was higher with IDegLira (11.1%) than with basal-bolus therapy (1.6%), Dr. Billings said. There were no deaths or unexpected adverse events.

Novo Nordisk makes Xultophy and funded the trial. Dr. Billings reported having served on advisory panels and speaker bureaus for Novo Nordisk.

cenews@frontlinemedcom.com

 

SAN DIEGO – When basal insulin alone does not achieve glucose targets in type 2 diabetes, a single fixed-dose injection of insulin degludec and liraglutide (IDegLira) is as effective as multiple insulin injections and has a significantly lower risk of hypoglycemia, according to a randomized, multicenter, open-label, industry-sponsored trial.

After 26 weeks of treatment, average hemoglobin A1c levels dropped similarly with once-daily IDegLira (1.48%) as with basal insulin glargine U100 plus mealtime injections of short-acting insulin aspart (1.46%; P less than .0001 for noninferiority), reported Liana K. Billings, MD, at the annual scientific sessions of the American Diabetes Association.

Importantly, just 20% of IDegLira patients had at least one confirmed event of hypoglycemia, compared with 53% of those on basal-bolus insulin (rate ratio, 0.11; 95% confidence interval, 0.08-0.17; P less than .0001), reported Dr. Billings of Northshore University Health System in Skokie, Ill. That translated to seven fewer hypoglycemic events per year in the IDegLira arm, she said. “Now, take this in context – this is comparing one injection a day with four injections a day,” she added.

Patients also needed significantly less insulin and lost significantly more weight on IDegLira, compared with the basal-bolus regimen. “This is some of the most robust, most impressive data I’ve seen in years,” Julio Rosenstock, MD, director of the Dallas Diabetes and Endocrine Center in Texas, commented from the audience. Dr. Rosenstock was not involved in the trial and has studied other combination regimens for type 2 diabetes.

The advent of new insulins and adjunct therapies gives clinicians many potential algorithms for treating type 2 diabetes patients. The ADA recommends that health care professionals consider dual or triple therapy if patients do not meet glycemic targets with lifestyle changes and metformin alone. However, weight gain, hypoglycemia, and complex treatment regimens can make it difficult to intensify treatment in the real world, Dr. Billings said.

Insulin degludec is an ultra–long-acting basal insulin analogue, while liraglutide is a GLP-1 receptor agonist. The open-label, phase III DUAL VII study compared once-daily IDegLira injection (Xultophy, Novo Nordisk) with once-daily basal insulin glargine (Lantus, Sanofi) U100 plus bolus insulin aspart (NovoLog, Novo Nordisk) at mealtimes in 506 adults with type 2 diabetes. All patients were on metformin and glargine (typically 34 U) at baseline. Most were in their late 50s and obese, with an average 13-year duration of type 2 diabetes and HbA1c levels of 8.2% despite treatment. The IDegLira group started at 16 U and titrated by 2 U twice weekly to reach a fasting glucose target of 72-90 mg/dL. Basal-bolus patients maintained their baseline glargine dose and added 4 U mealtime bolus insulin aspart, titrating to target by 1 U twice weekly. The primary endpoint was change in HbA1c levels after 26 weeks. More than 98% of patients completed the trial. Approximately two-thirds of patients in both arms achieved an HbA1c level below 7%, but IDegLira recipients were significantly more likely to do so without gaining weight or experiencing hypoglycemia during the last 12 weeks of treatment (odds ratio, 10.39; 95% CI, 5.76-18.75). The IDegLira arm received significantly less daily insulin than the basal-bolus arm (40 U versus 84 U; P less than .0001), and IDegLira patients lost an average of 0.93 kg, while the comparison group gained 2.64 kg. Rates of serious adverse events were low and similar between arms. The cumulative rate of nausea was higher with IDegLira (11.1%) than with basal-bolus therapy (1.6%), Dr. Billings said. There were no deaths or unexpected adverse events.

Novo Nordisk makes Xultophy and funded the trial. Dr. Billings reported having served on advisory panels and speaker bureaus for Novo Nordisk.

cenews@frontlinemedcom.com

 

SAN DIEGO – When basal insulin alone does not achieve glucose targets in type 2 diabetes, a single fixed-dose injection of insulin degludec and liraglutide (IDegLira) is as effective as multiple insulin injections and has a significantly lower risk of hypoglycemia, according to a randomized, multicenter, open-label, industry-sponsored trial.

After 26 weeks of treatment, average hemoglobin A1c levels dropped similarly with once-daily IDegLira (1.48%) as with basal insulin glargine U100 plus mealtime injections of short-acting insulin aspart (1.46%; P less than .0001 for noninferiority), reported Liana K. Billings, MD, at the annual scientific sessions of the American Diabetes Association.

Importantly, just 20% of IDegLira patients had at least one confirmed event of hypoglycemia, compared with 53% of those on basal-bolus insulin (rate ratio, 0.11; 95% confidence interval, 0.08-0.17; P less than .0001), reported Dr. Billings of Northshore University Health System in Skokie, Ill. That translated to seven fewer hypoglycemic events per year in the IDegLira arm, she said. “Now, take this in context – this is comparing one injection a day with four injections a day,” she added.

Patients also needed significantly less insulin and lost significantly more weight on IDegLira, compared with the basal-bolus regimen. “This is some of the most robust, most impressive data I’ve seen in years,” Julio Rosenstock, MD, director of the Dallas Diabetes and Endocrine Center in Texas, commented from the audience. Dr. Rosenstock was not involved in the trial and has studied other combination regimens for type 2 diabetes.

The advent of new insulins and adjunct therapies gives clinicians many potential algorithms for treating type 2 diabetes patients. The ADA recommends that health care professionals consider dual or triple therapy if patients do not meet glycemic targets with lifestyle changes and metformin alone. However, weight gain, hypoglycemia, and complex treatment regimens can make it difficult to intensify treatment in the real world, Dr. Billings said.

Insulin degludec is an ultra–long-acting basal insulin analogue, while liraglutide is a GLP-1 receptor agonist. The open-label, phase III DUAL VII study compared once-daily IDegLira injection (Xultophy, Novo Nordisk) with once-daily basal insulin glargine (Lantus, Sanofi) U100 plus bolus insulin aspart (NovoLog, Novo Nordisk) at mealtimes in 506 adults with type 2 diabetes. All patients were on metformin and glargine (typically 34 U) at baseline. Most were in their late 50s and obese, with an average 13-year duration of type 2 diabetes and HbA1c levels of 8.2% despite treatment. The IDegLira group started at 16 U and titrated by 2 U twice weekly to reach a fasting glucose target of 72-90 mg/dL. Basal-bolus patients maintained their baseline glargine dose and added 4 U mealtime bolus insulin aspart, titrating to target by 1 U twice weekly. The primary endpoint was change in HbA1c levels after 26 weeks. More than 98% of patients completed the trial. Approximately two-thirds of patients in both arms achieved an HbA1c level below 7%, but IDegLira recipients were significantly more likely to do so without gaining weight or experiencing hypoglycemia during the last 12 weeks of treatment (odds ratio, 10.39; 95% CI, 5.76-18.75). The IDegLira arm received significantly less daily insulin than the basal-bolus arm (40 U versus 84 U; P less than .0001), and IDegLira patients lost an average of 0.93 kg, while the comparison group gained 2.64 kg. Rates of serious adverse events were low and similar between arms. The cumulative rate of nausea was higher with IDegLira (11.1%) than with basal-bolus therapy (1.6%), Dr. Billings said. There were no deaths or unexpected adverse events.

Novo Nordisk makes Xultophy and funded the trial. Dr. Billings reported having served on advisory panels and speaker bureaus for Novo Nordisk.

cenews@frontlinemedcom.com

 

BOSTON – Remote monitoring of continuous positive airway pressure (CPAP) use with feedback messaging to patients improves adherence but only when patients opt to receive continual feedback on their usage, according to a study.

Dennis Hwang, MD, medical director of Kaiser Permanent Fontana Medical Center in California and his colleagues designed the four-arm Tele-OSA study to evaluate the impact of two automated telemedicine interventions: an obstructive sleep apnea (OSA) education program (provided by Emmi Solutions) and a CPAP remote monitoring system with automated patient feedback (U-Sleep, ResMed). Dr. Hwang, who is also cochair of sleep medicine at Southern California Permanente Medical Group, presented his findings at the annual meeting of the Associated Professional Sleep Societies.

Debra L. Beck/Frontline Medical News

A total of 1,455 patients with OSA were randomized to usual care, usual care + tele-education, usual care + telemonitoring, or usual care and both tele-education and telemonitoring. The tele-education provided OSA and CPAP web-based education, offered patients a personalized invitation via email, was interactive, allowed for repeat viewing, and tracked patient viewing status. The telemonitoring system used automated algorithms to process the uploaded CPAP data. If the patient met certain thresholds, such as no CPAP-data for 2 consecutive days or CPAP usage greater than 4 hours for 3 consecutive nights, a message was automatically sent either by text, email, or phone to the patient.

CPAP adherence was compared at 3 months and 1 year for patients in all four groups. Dr. Hwang reported findings from 556 patients who completed one-year follow-up.

At 90 days, patients assigned to either of the telemonitoring arms had significantly higher CPAP usage than those who did not receive telemonitoring.

However, at 3 months when the study protocol called for the automated messaging to be turned off, CPAP adherence dropped off. By 8 months, adherence in patients using the telemonitoring system was no different from that in those who never received the automated messaging. That would have been the end of the story, except that there was a glitch in the system.

“Perhaps serendipitously, we had a group of patients, about one-third, for whom we inadvertently did not turn off the messaging,” explained Dr. Hwang. “In these patients who continued to receive feedback, CPAP usage remained elevated throughout the course of the year and, at 12 months, was significantly higher than in the patients who were not receiving any kind of messaging.”

Dr. Hwang added that the telemonitoring required no additional provider intervention, “suggesting that this could be a cost-effective strategy.”

Only one-third of patients (66.7%) assigned to one of the tele-education groups viewed the video. Additionally, the researchers found that, whether patients used the tele-education alone or in combination with the telemonitoring, tele-education use had no impact on 90-day compliance with CPAP.

Dr. Hwang received support from the American Sleep Medicine Foundation and ResMed Science.

 

BOSTON – Remote monitoring of continuous positive airway pressure (CPAP) use with feedback messaging to patients improves adherence but only when patients opt to receive continual feedback on their usage, according to a study.

Dennis Hwang, MD, medical director of Kaiser Permanent Fontana Medical Center in California and his colleagues designed the four-arm Tele-OSA study to evaluate the impact of two automated telemedicine interventions: an obstructive sleep apnea (OSA) education program (provided by Emmi Solutions) and a CPAP remote monitoring system with automated patient feedback (U-Sleep, ResMed). Dr. Hwang, who is also cochair of sleep medicine at Southern California Permanente Medical Group, presented his findings at the annual meeting of the Associated Professional Sleep Societies.

Debra L. Beck/Frontline Medical News

A total of 1,455 patients with OSA were randomized to usual care, usual care + tele-education, usual care + telemonitoring, or usual care and both tele-education and telemonitoring. The tele-education provided OSA and CPAP web-based education, offered patients a personalized invitation via email, was interactive, allowed for repeat viewing, and tracked patient viewing status. The telemonitoring system used automated algorithms to process the uploaded CPAP data. If the patient met certain thresholds, such as no CPAP-data for 2 consecutive days or CPAP usage greater than 4 hours for 3 consecutive nights, a message was automatically sent either by text, email, or phone to the patient.

CPAP adherence was compared at 3 months and 1 year for patients in all four groups. Dr. Hwang reported findings from 556 patients who completed one-year follow-up.

At 90 days, patients assigned to either of the telemonitoring arms had significantly higher CPAP usage than those who did not receive telemonitoring.

However, at 3 months when the study protocol called for the automated messaging to be turned off, CPAP adherence dropped off. By 8 months, adherence in patients using the telemonitoring system was no different from that in those who never received the automated messaging. That would have been the end of the story, except that there was a glitch in the system.

“Perhaps serendipitously, we had a group of patients, about one-third, for whom we inadvertently did not turn off the messaging,” explained Dr. Hwang. “In these patients who continued to receive feedback, CPAP usage remained elevated throughout the course of the year and, at 12 months, was significantly higher than in the patients who were not receiving any kind of messaging.”

Dr. Hwang added that the telemonitoring required no additional provider intervention, “suggesting that this could be a cost-effective strategy.”

Only one-third of patients (66.7%) assigned to one of the tele-education groups viewed the video. Additionally, the researchers found that, whether patients used the tele-education alone or in combination with the telemonitoring, tele-education use had no impact on 90-day compliance with CPAP.

Dr. Hwang received support from the American Sleep Medicine Foundation and ResMed Science.

 

BOSTON – Remote monitoring of continuous positive airway pressure (CPAP) use with feedback messaging to patients improves adherence but only when patients opt to receive continual feedback on their usage, according to a study.

Dennis Hwang, MD, medical director of Kaiser Permanent Fontana Medical Center in California and his colleagues designed the four-arm Tele-OSA study to evaluate the impact of two automated telemedicine interventions: an obstructive sleep apnea (OSA) education program (provided by Emmi Solutions) and a CPAP remote monitoring system with automated patient feedback (U-Sleep, ResMed). Dr. Hwang, who is also cochair of sleep medicine at Southern California Permanente Medical Group, presented his findings at the annual meeting of the Associated Professional Sleep Societies.

Debra L. Beck/Frontline Medical News

A total of 1,455 patients with OSA were randomized to usual care, usual care + tele-education, usual care + telemonitoring, or usual care and both tele-education and telemonitoring. The tele-education provided OSA and CPAP web-based education, offered patients a personalized invitation via email, was interactive, allowed for repeat viewing, and tracked patient viewing status. The telemonitoring system used automated algorithms to process the uploaded CPAP data. If the patient met certain thresholds, such as no CPAP-data for 2 consecutive days or CPAP usage greater than 4 hours for 3 consecutive nights, a message was automatically sent either by text, email, or phone to the patient.

CPAP adherence was compared at 3 months and 1 year for patients in all four groups. Dr. Hwang reported findings from 556 patients who completed one-year follow-up.

At 90 days, patients assigned to either of the telemonitoring arms had significantly higher CPAP usage than those who did not receive telemonitoring.

However, at 3 months when the study protocol called for the automated messaging to be turned off, CPAP adherence dropped off. By 8 months, adherence in patients using the telemonitoring system was no different from that in those who never received the automated messaging. That would have been the end of the story, except that there was a glitch in the system.

“Perhaps serendipitously, we had a group of patients, about one-third, for whom we inadvertently did not turn off the messaging,” explained Dr. Hwang. “In these patients who continued to receive feedback, CPAP usage remained elevated throughout the course of the year and, at 12 months, was significantly higher than in the patients who were not receiving any kind of messaging.”

Dr. Hwang added that the telemonitoring required no additional provider intervention, “suggesting that this could be a cost-effective strategy.”

Only one-third of patients (66.7%) assigned to one of the tele-education groups viewed the video. Additionally, the researchers found that, whether patients used the tele-education alone or in combination with the telemonitoring, tele-education use had no impact on 90-day compliance with CPAP.

Dr. Hwang received support from the American Sleep Medicine Foundation and ResMed Science.

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has approved daratumumab (Darzalex®) in combination with pomalidomide (POM) and dexamethasone (dex) for the treatment of multiple myeloma (MM) in patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor (PI).

The FDA previously approved daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with MM who had at least 1 prior therapy.

Daratumumab is also approved by the FDA as monotherapy in MM patients who had at least 3 prior lines of therapy, including a PI and an immunomodulatory (IMiD) agent, or who are double refractory to a PI and an IMiD.

The latest indication is based on the results of the phase 1b MMY1001 EQUULEUS study, which demonstrated that daratumumab produced an overall response (OR) rate of 59% in combination with pomalidomide and dexamethasone, and a very good partial response (VGPR) in 28% of patients.

EQUULEUS study

The daratumumab-POM-Dex arm of the phase 1 open-label EQUULEUS study included 103 MM patients who had received prior treatment with a PI and an immunomodulatory agent.

Patients were a median age of 64 years, and 8% were older than 75.

They had received a median of 4 prior lines of therapy, and 74% had received prior autologous stem cell transplant.

Most (89%) were refractory to lenalidomide and 71% were refractory to bortezomib. Almost two thirds (64%) were refractory to bortezomib and lenalidomide.

Patients were treated with 16 mg/kg of daratumumab in combination with POM and Dex, and 6% achieved a complete response (CR) and 8% achieved a stringent CR.

The median time to response was 1 month (range, 0.9 to 2.8), and the median duration of response was 13.6 months (range, 0.9+ to 14.6+ months).

The most frequent adverse events (AEs) reported in more than 20% of patients were infusion reactions, fatigue, and upper respiratory tract infections (50% each), cough (43%), diarrhea (38%), dyspnea (33%), nausea (30%), muscle spasms (26%), pyrexia (25%), and vomiting (21%).

The overall incidence of serious adverse reactions was 49%.

Grade 3/4 serious AEs reported in 5% of patients or more included pneumonia (7%).

The most common treatment-emergent hematologic laboratory abnormalities included lymphopenia (94%), neutropenia (95%), thrombocytopenia (75%), and anemia (57%).

And the most common grade 3/4 treatment-emergent hematology laboratory abnormalities were neutropenia (82%), lymphopenia (71%), anemia (30%), and thrombocytopenia (20%).

Daratumumab is being developed by Janssen Biotech, Inc., under an exclusive worldwide license to develop, manufacture, and commercialize daratumumab from Genmab.

See the package insert for full prescribing information. 

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has approved daratumumab (Darzalex®) in combination with pomalidomide (POM) and dexamethasone (dex) for the treatment of multiple myeloma (MM) in patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor (PI).

The FDA previously approved daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with MM who had at least 1 prior therapy.

Daratumumab is also approved by the FDA as monotherapy in MM patients who had at least 3 prior lines of therapy, including a PI and an immunomodulatory (IMiD) agent, or who are double refractory to a PI and an IMiD.

The latest indication is based on the results of the phase 1b MMY1001 EQUULEUS study, which demonstrated that daratumumab produced an overall response (OR) rate of 59% in combination with pomalidomide and dexamethasone, and a very good partial response (VGPR) in 28% of patients.

EQUULEUS study

The daratumumab-POM-Dex arm of the phase 1 open-label EQUULEUS study included 103 MM patients who had received prior treatment with a PI and an immunomodulatory agent.

Patients were a median age of 64 years, and 8% were older than 75.

They had received a median of 4 prior lines of therapy, and 74% had received prior autologous stem cell transplant.

Most (89%) were refractory to lenalidomide and 71% were refractory to bortezomib. Almost two thirds (64%) were refractory to bortezomib and lenalidomide.

Patients were treated with 16 mg/kg of daratumumab in combination with POM and Dex, and 6% achieved a complete response (CR) and 8% achieved a stringent CR.

The median time to response was 1 month (range, 0.9 to 2.8), and the median duration of response was 13.6 months (range, 0.9+ to 14.6+ months).

The most frequent adverse events (AEs) reported in more than 20% of patients were infusion reactions, fatigue, and upper respiratory tract infections (50% each), cough (43%), diarrhea (38%), dyspnea (33%), nausea (30%), muscle spasms (26%), pyrexia (25%), and vomiting (21%).

The overall incidence of serious adverse reactions was 49%.

Grade 3/4 serious AEs reported in 5% of patients or more included pneumonia (7%).

The most common treatment-emergent hematologic laboratory abnormalities included lymphopenia (94%), neutropenia (95%), thrombocytopenia (75%), and anemia (57%).

And the most common grade 3/4 treatment-emergent hematology laboratory abnormalities were neutropenia (82%), lymphopenia (71%), anemia (30%), and thrombocytopenia (20%).

Daratumumab is being developed by Janssen Biotech, Inc., under an exclusive worldwide license to develop, manufacture, and commercialize daratumumab from Genmab.

See the package insert for full prescribing information. 

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has approved daratumumab (Darzalex®) in combination with pomalidomide (POM) and dexamethasone (dex) for the treatment of multiple myeloma (MM) in patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor (PI).

The FDA previously approved daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with MM who had at least 1 prior therapy.

Daratumumab is also approved by the FDA as monotherapy in MM patients who had at least 3 prior lines of therapy, including a PI and an immunomodulatory (IMiD) agent, or who are double refractory to a PI and an IMiD.

The latest indication is based on the results of the phase 1b MMY1001 EQUULEUS study, which demonstrated that daratumumab produced an overall response (OR) rate of 59% in combination with pomalidomide and dexamethasone, and a very good partial response (VGPR) in 28% of patients.

EQUULEUS study

The daratumumab-POM-Dex arm of the phase 1 open-label EQUULEUS study included 103 MM patients who had received prior treatment with a PI and an immunomodulatory agent.

Patients were a median age of 64 years, and 8% were older than 75.

They had received a median of 4 prior lines of therapy, and 74% had received prior autologous stem cell transplant.

Most (89%) were refractory to lenalidomide and 71% were refractory to bortezomib. Almost two thirds (64%) were refractory to bortezomib and lenalidomide.

Patients were treated with 16 mg/kg of daratumumab in combination with POM and Dex, and 6% achieved a complete response (CR) and 8% achieved a stringent CR.

The median time to response was 1 month (range, 0.9 to 2.8), and the median duration of response was 13.6 months (range, 0.9+ to 14.6+ months).

The most frequent adverse events (AEs) reported in more than 20% of patients were infusion reactions, fatigue, and upper respiratory tract infections (50% each), cough (43%), diarrhea (38%), dyspnea (33%), nausea (30%), muscle spasms (26%), pyrexia (25%), and vomiting (21%).

The overall incidence of serious adverse reactions was 49%.

Grade 3/4 serious AEs reported in 5% of patients or more included pneumonia (7%).

The most common treatment-emergent hematologic laboratory abnormalities included lymphopenia (94%), neutropenia (95%), thrombocytopenia (75%), and anemia (57%).

And the most common grade 3/4 treatment-emergent hematology laboratory abnormalities were neutropenia (82%), lymphopenia (71%), anemia (30%), and thrombocytopenia (20%).

Daratumumab is being developed by Janssen Biotech, Inc., under an exclusive worldwide license to develop, manufacture, and commercialize daratumumab from Genmab.

See the package insert for full prescribing information. 

Photo © ASCO/Scott Morgan 2017

CHICAGO—The largest international multiple myeloma (MM) trial ever conducted, according to the trial sponsor, met its primary endpoint, demonstrating that denosumab is non-inferior to zoledronic acid (ZA) in delaying the time to first on-study skeletal-related event (SRE) in patients with MM.

In addition to bone-specific benefits, denosumab-treated patients had significantly fewer renal adverse events and possible prolongation of progression-free survival.

Denosumab “may in fact be a new standard of care for multiple myeloma-related bone disease,” according to one of the investigators.

“The other important thing to note,” Noopur S. Raje, MD, said during her presentation at the ASCO 2017 Annual Meeting, “is denosumab can be administered despite renal function in patients with myeloma.” It does not need to be dose-adjusted, unlike bisphosphonates.

Dr Raje, of the Massachusetts General Hospital Cancer Center in Boston, Massachusetts, presented the study results as abstract 8005.

Study design

The international, phase 3, randomized, double-blind study is evaluating the safety of denosumab compared with ZA in newly diagnosed MM patients.

Investigators enrolled 1718 patients from 259 sites and 29 countries.

They randomized 859 patients to receive denosumab 120 mg subcutaneously every 4 weeks plus intravenous placebo every 4 weeks, and 859 patients to the standard ZA dose of 4 mg intravenously plus subcutaneous placebo every 4 weeks.

Patients were stratified by whether they were on novel-based anti-myeloma therapy, whether they planned to have an autologous peripheral blood stem cell (PBSC) transplant, disease stage, and previous SRE.

“We were looking for 676 on-study SREs, and if we saw a benefit, patients would be offered open-label denosumab for up to 2 years after this,” Dr Raje said.

“Patients had to have radiographic evidence of bone disease, and this is different from some of the other bone disease studies that you’ve seen in the recent past,” she added.

In addition to documented evidence of MM, patients had to be 18 years or older, be ECOG status of 2 or better, have adequate organ function, and plan to receive or be receiving primary frontline anti-myeloma therapy.

Patients were excluded if they had nonsecretory MM, more than 30 days of previous treatment with anti-myeloma therapy prior to screening, prior use of denosumab, use of oral bisphosphonates with a cumulative dose of more than 1 year, more than 1 previous dose of intravenous bisphosphonate, or prior history or current evidence of osteonecrosis/osteomyelitis of the jaw.

The primary endpoint was time to first on-study SRE, “and the idea here was to look for non-inferiority,” Dr Raje explained.

Secondary endpoints included time to the first on-study SRE (superiority), time to the first-and-subsequent on-study SRE (superiority), and overall survival.

Investigators also included the exploratory objective of progression-free survival (PFS).

Patient demographics

Patients were well balanced across the 2 arms, Dr Raje noted, and the breakdown of myeloma disease stage at diagnosis was comparable between the ZA and denosumab arms.

About 32% of patients were stage I, 37% stage II, and 29% stage III. Stage was not available for 49 patients.

A little more than half (54%) were male, mean age was 63 years, and 82% were white.

Two thirds had prior SRE history, and 54% of patients intended to undergo autologous PBSC transplant.

Enrollment began May 2012 and continued through the end of March 2016. The primary analysis cutoff was July 19, 2016.

Results

The primary endpoint for non-inferiority for time to first on-study SRE was met by denosumab (HR=0.98, 95%CI: 0.85, 1.14; P=0.01).

 

“When we looked at the secondary endpoints for superiority, we were not able to confirm superiority in this analysis, either for time to first SRE or time to first-and subsequent SRE on this study,” Dr Raje said.

The investigators also did not observe a survival difference between denosumab and ZA, with a hazard ratio (HR) (95% CI) of 0.90 (0.70, 1.16), P=0.41.

“Importantly, we had an exploratory endpoint where we looked at progression-free survival in this newly diagnosed patient population,” she added, “and we saw an interestingly increased or prolonged progression-free survival in patients getting denosumab.”

“And that survival difference was more than 10 months between denosumab and zoledronic acid, favoring the denosumab arm,” she affirmed. The HR was 0.82, 95% CI: 0.68, 0.99, P=0.036 (descriptive).

Safety

“[I]f you look at all treatment-emergent adverse events between denosumab and zoledronic acid, we really could not find a big difference in either of these 2 groups of patients,” Dr Raje said.

“We saw that in general both denosumab and zoledronic acid were extremely well tolerated between the 2 groups of patients.”

The investigators “drilled down” on certain toxicity issues of interest and examined events such as atypical stress fractures, hypersensitivity reactions, musculoskeletal pain, infections and infestations, new primary malignancies, and acute phase reactions.

They observed no atypical femur fractures on the study, nor did they see any big differences with respect to hypersensitivity or acute phase reactions.

The investigators examined closely any renal issues because dosing of ZA specifically is impacted by renal function.

The data showed that treatment-emergent adverse event (TEAE) renal toxicity was significantly higher in the ZA group compared to the denosumab group, 17% and 10%, respectively (P<0.001).

“When you look at patients who had a creatinine clearance less than 60 mL per minute,” Dr Raje emphasized, “we saw an almost doubling of renal toxicity in the zoledronic acid arm (26.4%) compared to the denosumab arm (12.9%).”

Patients with a creatinine level greater than 2 mg/dL had a significant increase in creatinine in the ZA arm (P=0.010), which was also significantly increased if their creatinine clearance was less than 60 mL/minute (P=0.054).

“There was a doubling of creatinine from baseline, more so in the zoledronic acid arm compared to the patients with denosumab,” Dr Raje said. “And this was again more pronounced if you had a creatinine clearance of less than 60.”

Hypocalcemia was “not surprisingly” more common in the denosumab arm than the ZA arm (P=0.009) for all patients, and osteonecrosis of the jaw was equal in both arms (P=0.147), although numerically slightly higher with denosumab treatment.

Dr Raje summarized that there was no difference in overall survival at the time of this analysis, “but I will say that the follow-up for a newly diagnosed patient population is fairly short right now.”

“Progression-free survival, which we saw [cut] off 10.7 months, was actually quite striking when denosumab was compared to zoledronic acid, and this was statistically highly significant.”

“The bone-specific benefits in combination with significantly fewer renal adverse events and possible prolongation of PFS with denosumab therapy we do think is very promising,” she said, “and may in fact be a new standard of care for multiple myeloma-related bone disease.”

The study was funded by Amgen Inc.

Denosumab (XGEVA^®) is indicated by the US Food and Drug Administration for the prevention of fractures and other SREs in patients with bone metastases from solid tumors. It is currently not indicated for the prevention of SREs in patients with MM. 

Photo © ASCO/Scott Morgan 2017

CHICAGO—The largest international multiple myeloma (MM) trial ever conducted, according to the trial sponsor, met its primary endpoint, demonstrating that denosumab is non-inferior to zoledronic acid (ZA) in delaying the time to first on-study skeletal-related event (SRE) in patients with MM.

In addition to bone-specific benefits, denosumab-treated patients had significantly fewer renal adverse events and possible prolongation of progression-free survival.

Denosumab “may in fact be a new standard of care for multiple myeloma-related bone disease,” according to one of the investigators.

“The other important thing to note,” Noopur S. Raje, MD, said during her presentation at the ASCO 2017 Annual Meeting, “is denosumab can be administered despite renal function in patients with myeloma.” It does not need to be dose-adjusted, unlike bisphosphonates.

Dr Raje, of the Massachusetts General Hospital Cancer Center in Boston, Massachusetts, presented the study results as abstract 8005.

Study design

The international, phase 3, randomized, double-blind study is evaluating the safety of denosumab compared with ZA in newly diagnosed MM patients.

Investigators enrolled 1718 patients from 259 sites and 29 countries.

They randomized 859 patients to receive denosumab 120 mg subcutaneously every 4 weeks plus intravenous placebo every 4 weeks, and 859 patients to the standard ZA dose of 4 mg intravenously plus subcutaneous placebo every 4 weeks.

Patients were stratified by whether they were on novel-based anti-myeloma therapy, whether they planned to have an autologous peripheral blood stem cell (PBSC) transplant, disease stage, and previous SRE.

“We were looking for 676 on-study SREs, and if we saw a benefit, patients would be offered open-label denosumab for up to 2 years after this,” Dr Raje said.

“Patients had to have radiographic evidence of bone disease, and this is different from some of the other bone disease studies that you’ve seen in the recent past,” she added.

In addition to documented evidence of MM, patients had to be 18 years or older, be ECOG status of 2 or better, have adequate organ function, and plan to receive or be receiving primary frontline anti-myeloma therapy.

Patients were excluded if they had nonsecretory MM, more than 30 days of previous treatment with anti-myeloma therapy prior to screening, prior use of denosumab, use of oral bisphosphonates with a cumulative dose of more than 1 year, more than 1 previous dose of intravenous bisphosphonate, or prior history or current evidence of osteonecrosis/osteomyelitis of the jaw.

The primary endpoint was time to first on-study SRE, “and the idea here was to look for non-inferiority,” Dr Raje explained.

Secondary endpoints included time to the first on-study SRE (superiority), time to the first-and-subsequent on-study SRE (superiority), and overall survival.

Investigators also included the exploratory objective of progression-free survival (PFS).

Patient demographics

Patients were well balanced across the 2 arms, Dr Raje noted, and the breakdown of myeloma disease stage at diagnosis was comparable between the ZA and denosumab arms.

About 32% of patients were stage I, 37% stage II, and 29% stage III. Stage was not available for 49 patients.

A little more than half (54%) were male, mean age was 63 years, and 82% were white.

Two thirds had prior SRE history, and 54% of patients intended to undergo autologous PBSC transplant.

Enrollment began May 2012 and continued through the end of March 2016. The primary analysis cutoff was July 19, 2016.

Results

The primary endpoint for non-inferiority for time to first on-study SRE was met by denosumab (HR=0.98, 95%CI: 0.85, 1.14; P=0.01).

 

“When we looked at the secondary endpoints for superiority, we were not able to confirm superiority in this analysis, either for time to first SRE or time to first-and subsequent SRE on this study,” Dr Raje said.

The investigators also did not observe a survival difference between denosumab and ZA, with a hazard ratio (HR) (95% CI) of 0.90 (0.70, 1.16), P=0.41.

“Importantly, we had an exploratory endpoint where we looked at progression-free survival in this newly diagnosed patient population,” she added, “and we saw an interestingly increased or prolonged progression-free survival in patients getting denosumab.”

“And that survival difference was more than 10 months between denosumab and zoledronic acid, favoring the denosumab arm,” she affirmed. The HR was 0.82, 95% CI: 0.68, 0.99, P=0.036 (descriptive).

Safety

“[I]f you look at all treatment-emergent adverse events between denosumab and zoledronic acid, we really could not find a big difference in either of these 2 groups of patients,” Dr Raje said.

“We saw that in general both denosumab and zoledronic acid were extremely well tolerated between the 2 groups of patients.”

The investigators “drilled down” on certain toxicity issues of interest and examined events such as atypical stress fractures, hypersensitivity reactions, musculoskeletal pain, infections and infestations, new primary malignancies, and acute phase reactions.

They observed no atypical femur fractures on the study, nor did they see any big differences with respect to hypersensitivity or acute phase reactions.

The investigators examined closely any renal issues because dosing of ZA specifically is impacted by renal function.

The data showed that treatment-emergent adverse event (TEAE) renal toxicity was significantly higher in the ZA group compared to the denosumab group, 17% and 10%, respectively (P<0.001).

“When you look at patients who had a creatinine clearance less than 60 mL per minute,” Dr Raje emphasized, “we saw an almost doubling of renal toxicity in the zoledronic acid arm (26.4%) compared to the denosumab arm (12.9%).”

Patients with a creatinine level greater than 2 mg/dL had a significant increase in creatinine in the ZA arm (P=0.010), which was also significantly increased if their creatinine clearance was less than 60 mL/minute (P=0.054).

“There was a doubling of creatinine from baseline, more so in the zoledronic acid arm compared to the patients with denosumab,” Dr Raje said. “And this was again more pronounced if you had a creatinine clearance of less than 60.”

Hypocalcemia was “not surprisingly” more common in the denosumab arm than the ZA arm (P=0.009) for all patients, and osteonecrosis of the jaw was equal in both arms (P=0.147), although numerically slightly higher with denosumab treatment.

Dr Raje summarized that there was no difference in overall survival at the time of this analysis, “but I will say that the follow-up for a newly diagnosed patient population is fairly short right now.”

“Progression-free survival, which we saw [cut] off 10.7 months, was actually quite striking when denosumab was compared to zoledronic acid, and this was statistically highly significant.”

“The bone-specific benefits in combination with significantly fewer renal adverse events and possible prolongation of PFS with denosumab therapy we do think is very promising,” she said, “and may in fact be a new standard of care for multiple myeloma-related bone disease.”

The study was funded by Amgen Inc.

Denosumab (XGEVA^®) is indicated by the US Food and Drug Administration for the prevention of fractures and other SREs in patients with bone metastases from solid tumors. It is currently not indicated for the prevention of SREs in patients with MM. 

Photo © ASCO/Scott Morgan 2017

CHICAGO—The largest international multiple myeloma (MM) trial ever conducted, according to the trial sponsor, met its primary endpoint, demonstrating that denosumab is non-inferior to zoledronic acid (ZA) in delaying the time to first on-study skeletal-related event (SRE) in patients with MM.

In addition to bone-specific benefits, denosumab-treated patients had significantly fewer renal adverse events and possible prolongation of progression-free survival.

Denosumab “may in fact be a new standard of care for multiple myeloma-related bone disease,” according to one of the investigators.

“The other important thing to note,” Noopur S. Raje, MD, said during her presentation at the ASCO 2017 Annual Meeting, “is denosumab can be administered despite renal function in patients with myeloma.” It does not need to be dose-adjusted, unlike bisphosphonates.

Dr Raje, of the Massachusetts General Hospital Cancer Center in Boston, Massachusetts, presented the study results as abstract 8005.

Study design

The international, phase 3, randomized, double-blind study is evaluating the safety of denosumab compared with ZA in newly diagnosed MM patients.

Investigators enrolled 1718 patients from 259 sites and 29 countries.

They randomized 859 patients to receive denosumab 120 mg subcutaneously every 4 weeks plus intravenous placebo every 4 weeks, and 859 patients to the standard ZA dose of 4 mg intravenously plus subcutaneous placebo every 4 weeks.

Patients were stratified by whether they were on novel-based anti-myeloma therapy, whether they planned to have an autologous peripheral blood stem cell (PBSC) transplant, disease stage, and previous SRE.

“We were looking for 676 on-study SREs, and if we saw a benefit, patients would be offered open-label denosumab for up to 2 years after this,” Dr Raje said.

“Patients had to have radiographic evidence of bone disease, and this is different from some of the other bone disease studies that you’ve seen in the recent past,” she added.

In addition to documented evidence of MM, patients had to be 18 years or older, be ECOG status of 2 or better, have adequate organ function, and plan to receive or be receiving primary frontline anti-myeloma therapy.

Patients were excluded if they had nonsecretory MM, more than 30 days of previous treatment with anti-myeloma therapy prior to screening, prior use of denosumab, use of oral bisphosphonates with a cumulative dose of more than 1 year, more than 1 previous dose of intravenous bisphosphonate, or prior history or current evidence of osteonecrosis/osteomyelitis of the jaw.

The primary endpoint was time to first on-study SRE, “and the idea here was to look for non-inferiority,” Dr Raje explained.

Secondary endpoints included time to the first on-study SRE (superiority), time to the first-and-subsequent on-study SRE (superiority), and overall survival.

Investigators also included the exploratory objective of progression-free survival (PFS).

Patient demographics

Patients were well balanced across the 2 arms, Dr Raje noted, and the breakdown of myeloma disease stage at diagnosis was comparable between the ZA and denosumab arms.

About 32% of patients were stage I, 37% stage II, and 29% stage III. Stage was not available for 49 patients.

A little more than half (54%) were male, mean age was 63 years, and 82% were white.

Two thirds had prior SRE history, and 54% of patients intended to undergo autologous PBSC transplant.

Enrollment began May 2012 and continued through the end of March 2016. The primary analysis cutoff was July 19, 2016.

Results

The primary endpoint for non-inferiority for time to first on-study SRE was met by denosumab (HR=0.98, 95%CI: 0.85, 1.14; P=0.01).

 

“When we looked at the secondary endpoints for superiority, we were not able to confirm superiority in this analysis, either for time to first SRE or time to first-and subsequent SRE on this study,” Dr Raje said.

The investigators also did not observe a survival difference between denosumab and ZA, with a hazard ratio (HR) (95% CI) of 0.90 (0.70, 1.16), P=0.41.

“Importantly, we had an exploratory endpoint where we looked at progression-free survival in this newly diagnosed patient population,” she added, “and we saw an interestingly increased or prolonged progression-free survival in patients getting denosumab.”

“And that survival difference was more than 10 months between denosumab and zoledronic acid, favoring the denosumab arm,” she affirmed. The HR was 0.82, 95% CI: 0.68, 0.99, P=0.036 (descriptive).

Safety

“[I]f you look at all treatment-emergent adverse events between denosumab and zoledronic acid, we really could not find a big difference in either of these 2 groups of patients,” Dr Raje said.

“We saw that in general both denosumab and zoledronic acid were extremely well tolerated between the 2 groups of patients.”

The investigators “drilled down” on certain toxicity issues of interest and examined events such as atypical stress fractures, hypersensitivity reactions, musculoskeletal pain, infections and infestations, new primary malignancies, and acute phase reactions.

They observed no atypical femur fractures on the study, nor did they see any big differences with respect to hypersensitivity or acute phase reactions.

The investigators examined closely any renal issues because dosing of ZA specifically is impacted by renal function.

The data showed that treatment-emergent adverse event (TEAE) renal toxicity was significantly higher in the ZA group compared to the denosumab group, 17% and 10%, respectively (P<0.001).

“When you look at patients who had a creatinine clearance less than 60 mL per minute,” Dr Raje emphasized, “we saw an almost doubling of renal toxicity in the zoledronic acid arm (26.4%) compared to the denosumab arm (12.9%).”

Patients with a creatinine level greater than 2 mg/dL had a significant increase in creatinine in the ZA arm (P=0.010), which was also significantly increased if their creatinine clearance was less than 60 mL/minute (P=0.054).

“There was a doubling of creatinine from baseline, more so in the zoledronic acid arm compared to the patients with denosumab,” Dr Raje said. “And this was again more pronounced if you had a creatinine clearance of less than 60.”

Hypocalcemia was “not surprisingly” more common in the denosumab arm than the ZA arm (P=0.009) for all patients, and osteonecrosis of the jaw was equal in both arms (P=0.147), although numerically slightly higher with denosumab treatment.

Dr Raje summarized that there was no difference in overall survival at the time of this analysis, “but I will say that the follow-up for a newly diagnosed patient population is fairly short right now.”

“Progression-free survival, which we saw [cut] off 10.7 months, was actually quite striking when denosumab was compared to zoledronic acid, and this was statistically highly significant.”

“The bone-specific benefits in combination with significantly fewer renal adverse events and possible prolongation of PFS with denosumab therapy we do think is very promising,” she said, “and may in fact be a new standard of care for multiple myeloma-related bone disease.”

The study was funded by Amgen Inc.

Denosumab (XGEVA^®) is indicated by the US Food and Drug Administration for the prevention of fractures and other SREs in patients with bone metastases from solid tumors. It is currently not indicated for the prevention of SREs in patients with MM. 

 

Boys, older children, and minorities are disproportionately affected when it comes to firearm injuries and deaths in U.S. children and adolescents, and child firearm suicide rates are at the highest they have been in more than a decade, new study results revealed.

Around 19 children are either medically treated for a gunshot wound or killed by one every day in the United States. “The majority of these children are boys 13-17 years old, African American in the case of firearm homicide, and white and American Indian in the case of firearm suicide. Pediatric firearm injuries and deaths are an important public health problem in the United States, contributing substantially each year to premature death, illness, and disability of children,” said Katherine A. Fowler, PhD, of the National Center for Injury Prevention and Control, Atlanta, and her associates. “Finding ways to prevent such injuries and ensure that all children have safe, stable, nurturing relationships and environments remains one of our most important priorities” (Pediatrics. 2017;140(1):e20163486).

Kateywhat/ThinkStock

National data on fatal firearm injuries in 2011-2014 for this study were derived from death certificate data from the Centers for Disease Control and Prevention’s National Vital Statistics System, obtained via the CDC’s Web-based Injury Statistics Query and Reporting System. Data on nonfatal firearm injuries for 2011-2014 were obtained from the National Electronic Injury Surveillance System.

“From 2012 to 2014, the average annual case fatality rate was 74% for firearm-related self-harm, 14% for firearm-related assaults, and 6% for unintentional firearm injuries,” the investigators reported.

Boys accounted for 82% of all child firearm deaths from 2012 to 2014. In this time period, the annual rate of firearm death for boys was 4.5 times higher than the annual rate for girls (2.8 vs. 0.6 per 100,000). This difference was even more pronounced by age, with the rate for 13- to 17-year-old boys being six times higher than the rate for same-aged girls. Similarly, boys suffer the majority of nonfatal firearm injuries treated in U.S. emergency departments, accounting for 84% of all nonfatal firearm injuries medically treated each year from 2012 to 2014. The average annual rate of nonfatal firearm injuries for boys was five times the rate for girls at 13 vs. 3 per 100,000.

The annual rate of firearm homicide was 10 times higher among 13- to 17-year-olds versus 0- to 12-year-olds (3 vs. 0.3 per 100,000). Unintentional firearm death rates were approximately twice as high when comparing these two groups (0.2 vs. 0.1 per 100,000).

Dr. Fowler and her associates wrote, “Our findings indicate that most children who died of unintentional firearm injuries were shot by another child in their own age range and most often in the context of playing with a gun or showing it to others. More than one-third of the deaths of older children occurred in incidents in which the shooter thought that the gun was unloaded or thought that the safety was engaged.”

“Child firearm suicide rates showed a significant upward trend between 2007 and 2014, increasing 60% from 1.0 to 1.6 (P less than .05) to the highest rate seen over the period examined,” Dr. Fowler and her associates said.

Firearm suicide rates were 11 times higher among 13- to 17-year-olds vs. 10- to 12-year-olds (2 vs. 0.2 per 100,000). Older children also accounted for 88% of all nonfatal firearm injuries treated in an ED. The overall average annual rate of nonfatal firearm injuries for older children was 19 times that of younger children (24 vs. 1 per 100,000).

The annual firearm homicide rate for African American children was nearly 10 times higher than the rate for white children (4 vs. 0.4 per 100,000). However, the annual rate of firearm suicide among white children was nearly four times higher than the rate for African American children (2. vs. 0.6 per 100,000).

Awareness of the availability of firearms during times of crisis is crucial because suicides are often impulsive in young people, Dr. Fowler and her associates said, “with previous findings indicating that many who attempt suicide spend 10 minutes or less deliberating.‍ Safe storage practices (i.e., unloading and locking all firearms and ammunition) can potentially be lifesaving in these instances,” as the results of previous studies in this age group attest.

Firearm deaths are the third leading cause of death overall among children in the United States aged 1-17 years, beating pediatric congenital anomalies, heart disease, influenza/pneumonia, chronic lower respiratory disease, and cerebrovascular causes. Understanding the nature, scale, and impact of firearm violence against children is an important first step, concluded Dr. Fowler and her associates.

Dr. Fowler and her associates said they had no relevant financial disclosures.

 

mkalaycio@frontlinemedcom.com

 

Boys, older children, and minorities are disproportionately affected when it comes to firearm injuries and deaths in U.S. children and adolescents, and child firearm suicide rates are at the highest they have been in more than a decade, new study results revealed.

Around 19 children are either medically treated for a gunshot wound or killed by one every day in the United States. “The majority of these children are boys 13-17 years old, African American in the case of firearm homicide, and white and American Indian in the case of firearm suicide. Pediatric firearm injuries and deaths are an important public health problem in the United States, contributing substantially each year to premature death, illness, and disability of children,” said Katherine A. Fowler, PhD, of the National Center for Injury Prevention and Control, Atlanta, and her associates. “Finding ways to prevent such injuries and ensure that all children have safe, stable, nurturing relationships and environments remains one of our most important priorities” (Pediatrics. 2017;140(1):e20163486).

Kateywhat/ThinkStock

National data on fatal firearm injuries in 2011-2014 for this study were derived from death certificate data from the Centers for Disease Control and Prevention’s National Vital Statistics System, obtained via the CDC’s Web-based Injury Statistics Query and Reporting System. Data on nonfatal firearm injuries for 2011-2014 were obtained from the National Electronic Injury Surveillance System.

“From 2012 to 2014, the average annual case fatality rate was 74% for firearm-related self-harm, 14% for firearm-related assaults, and 6% for unintentional firearm injuries,” the investigators reported.

Boys accounted for 82% of all child firearm deaths from 2012 to 2014. In this time period, the annual rate of firearm death for boys was 4.5 times higher than the annual rate for girls (2.8 vs. 0.6 per 100,000). This difference was even more pronounced by age, with the rate for 13- to 17-year-old boys being six times higher than the rate for same-aged girls. Similarly, boys suffer the majority of nonfatal firearm injuries treated in U.S. emergency departments, accounting for 84% of all nonfatal firearm injuries medically treated each year from 2012 to 2014. The average annual rate of nonfatal firearm injuries for boys was five times the rate for girls at 13 vs. 3 per 100,000.

The annual rate of firearm homicide was 10 times higher among 13- to 17-year-olds versus 0- to 12-year-olds (3 vs. 0.3 per 100,000). Unintentional firearm death rates were approximately twice as high when comparing these two groups (0.2 vs. 0.1 per 100,000).

Dr. Fowler and her associates wrote, “Our findings indicate that most children who died of unintentional firearm injuries were shot by another child in their own age range and most often in the context of playing with a gun or showing it to others. More than one-third of the deaths of older children occurred in incidents in which the shooter thought that the gun was unloaded or thought that the safety was engaged.”

“Child firearm suicide rates showed a significant upward trend between 2007 and 2014, increasing 60% from 1.0 to 1.6 (P less than .05) to the highest rate seen over the period examined,” Dr. Fowler and her associates said.

Firearm suicide rates were 11 times higher among 13- to 17-year-olds vs. 10- to 12-year-olds (2 vs. 0.2 per 100,000). Older children also accounted for 88% of all nonfatal firearm injuries treated in an ED. The overall average annual rate of nonfatal firearm injuries for older children was 19 times that of younger children (24 vs. 1 per 100,000).

The annual firearm homicide rate for African American children was nearly 10 times higher than the rate for white children (4 vs. 0.4 per 100,000). However, the annual rate of firearm suicide among white children was nearly four times higher than the rate for African American children (2. vs. 0.6 per 100,000).

Awareness of the availability of firearms during times of crisis is crucial because suicides are often impulsive in young people, Dr. Fowler and her associates said, “with previous findings indicating that many who attempt suicide spend 10 minutes or less deliberating.‍ Safe storage practices (i.e., unloading and locking all firearms and ammunition) can potentially be lifesaving in these instances,” as the results of previous studies in this age group attest.

Firearm deaths are the third leading cause of death overall among children in the United States aged 1-17 years, beating pediatric congenital anomalies, heart disease, influenza/pneumonia, chronic lower respiratory disease, and cerebrovascular causes. Understanding the nature, scale, and impact of firearm violence against children is an important first step, concluded Dr. Fowler and her associates.

Dr. Fowler and her associates said they had no relevant financial disclosures.

 

mkalaycio@frontlinemedcom.com

 

Boys, older children, and minorities are disproportionately affected when it comes to firearm injuries and deaths in U.S. children and adolescents, and child firearm suicide rates are at the highest they have been in more than a decade, new study results revealed.

Around 19 children are either medically treated for a gunshot wound or killed by one every day in the United States. “The majority of these children are boys 13-17 years old, African American in the case of firearm homicide, and white and American Indian in the case of firearm suicide. Pediatric firearm injuries and deaths are an important public health problem in the United States, contributing substantially each year to premature death, illness, and disability of children,” said Katherine A. Fowler, PhD, of the National Center for Injury Prevention and Control, Atlanta, and her associates. “Finding ways to prevent such injuries and ensure that all children have safe, stable, nurturing relationships and environments remains one of our most important priorities” (Pediatrics. 2017;140(1):e20163486).

Kateywhat/ThinkStock

National data on fatal firearm injuries in 2011-2014 for this study were derived from death certificate data from the Centers for Disease Control and Prevention’s National Vital Statistics System, obtained via the CDC’s Web-based Injury Statistics Query and Reporting System. Data on nonfatal firearm injuries for 2011-2014 were obtained from the National Electronic Injury Surveillance System.

“From 2012 to 2014, the average annual case fatality rate was 74% for firearm-related self-harm, 14% for firearm-related assaults, and 6% for unintentional firearm injuries,” the investigators reported.

Boys accounted for 82% of all child firearm deaths from 2012 to 2014. In this time period, the annual rate of firearm death for boys was 4.5 times higher than the annual rate for girls (2.8 vs. 0.6 per 100,000). This difference was even more pronounced by age, with the rate for 13- to 17-year-old boys being six times higher than the rate for same-aged girls. Similarly, boys suffer the majority of nonfatal firearm injuries treated in U.S. emergency departments, accounting for 84% of all nonfatal firearm injuries medically treated each year from 2012 to 2014. The average annual rate of nonfatal firearm injuries for boys was five times the rate for girls at 13 vs. 3 per 100,000.

The annual rate of firearm homicide was 10 times higher among 13- to 17-year-olds versus 0- to 12-year-olds (3 vs. 0.3 per 100,000). Unintentional firearm death rates were approximately twice as high when comparing these two groups (0.2 vs. 0.1 per 100,000).

Dr. Fowler and her associates wrote, “Our findings indicate that most children who died of unintentional firearm injuries were shot by another child in their own age range and most often in the context of playing with a gun or showing it to others. More than one-third of the deaths of older children occurred in incidents in which the shooter thought that the gun was unloaded or thought that the safety was engaged.”

“Child firearm suicide rates showed a significant upward trend between 2007 and 2014, increasing 60% from 1.0 to 1.6 (P less than .05) to the highest rate seen over the period examined,” Dr. Fowler and her associates said.

Firearm suicide rates were 11 times higher among 13- to 17-year-olds vs. 10- to 12-year-olds (2 vs. 0.2 per 100,000). Older children also accounted for 88% of all nonfatal firearm injuries treated in an ED. The overall average annual rate of nonfatal firearm injuries for older children was 19 times that of younger children (24 vs. 1 per 100,000).

The annual firearm homicide rate for African American children was nearly 10 times higher than the rate for white children (4 vs. 0.4 per 100,000). However, the annual rate of firearm suicide among white children was nearly four times higher than the rate for African American children (2. vs. 0.6 per 100,000).

Awareness of the availability of firearms during times of crisis is crucial because suicides are often impulsive in young people, Dr. Fowler and her associates said, “with previous findings indicating that many who attempt suicide spend 10 minutes or less deliberating.‍ Safe storage practices (i.e., unloading and locking all firearms and ammunition) can potentially be lifesaving in these instances,” as the results of previous studies in this age group attest.

Firearm deaths are the third leading cause of death overall among children in the United States aged 1-17 years, beating pediatric congenital anomalies, heart disease, influenza/pneumonia, chronic lower respiratory disease, and cerebrovascular causes. Understanding the nature, scale, and impact of firearm violence against children is an important first step, concluded Dr. Fowler and her associates.

Dr. Fowler and her associates said they had no relevant financial disclosures.

 

mkalaycio@frontlinemedcom.com

1. This patient is concerned about the numerous long-standing “moles” on her face. Only occasionally pruritic, they are otherwise asymptomatic. Nevertheless, the patient wants them investigated and removed.

Diagnosis: Dermatosis papulosa nigra (DPN) is a benign condition that presents as multiple brown to dark-brown 1- to 5-mm papules on the face, neck, and trunk. The lesions are a sign of aging in darker skinned patients and do not require treatment. They can, however, be safely, easily, and effectively removed. Both electrodesiccation and KTP (532 nm) laser have comparable efficacy in the removal of DPN, according to a  2009 study published in the American Journal of Dermatologic Surgery. Without use of anesthetics, the KTP laser is preferred for patient comfort.

For more information, see “Skin of Color: Dermatosis Papulosa Nigra Removal.” Dermatology News. February 1, 2012.

 

2. A 17-year-old African-American boy likes to keep his face clean-shaven, but his skin becomes irritated every time he shaves. He states that his father also has this problem, but doesn’t have a solution.

Diagnosis: Pseudofolliculitis is a common skin condition affecting hair-bearing areas of the body that are shaved. It develops when the free end of a tightly coiled hair reenters the skin after shaving, causing a foreign-body–like inflammatory reaction. Tightly curled hair has a greater tendency to pierce the follicle and the surface of the skin, explaining the relative predominance of pseudofolliculitis in patients of African descent; at least half of black men who shave develop the condition.

For more information, see “Bumps in beard area.” J Fam Pract. 2015 November;64(11).

 

3. A 15-year-old African-American boy presents with a two-month history of hair loss and pruritic papules on the back of his head that developed after a barber shaved the area. There are two dozen 1- to 2-mm papules on his posterior neck and occipital scalp with areas of focal crusting. The patient had a similar episode a year ago after shaving the same area, but those papules cleared after one month of applying rubbing alcohol.

Diagnosis: This patient’s diagnosis is acne keloidalis nuchae (AKN), a chronic folliculitis characterized by smooth, dome-shaped papules on the posterior scalp and neck that become confluent and form firm papules and hairless, keloid-like plaques. Seen almost exclusively in young, postpubescent African-American males, the condition is often asymptomatic, although some patients complain of itching in the affected area.

For more information, see “Scalp papules in a teenage boy.” J Fam Pract. 2017 March;66(3).

 

4. Several years after a motorcycle accident and resulting road rash, this 23-year-old Hispanic woman is left with complex scars. She experiences pruritus, pain, and hypersensitivity and is seeking relief.

Diagnosis: Often confused with hypertrophic scars, keloids are benign overgrowths of scar tissue that can occur months to years after skin trauma. They are most common in those ages 10 to 30, with a higher incidence among blacks, Hispanics, and Asians. Although the exact etiology of keloids is unknown, they are related to aberrant collagen production and breakdown in wound healing.

For more information, see “Laser treatment of scars and keloids.” Cosmet Dermatol. 2012;25:318-325.

1. This patient is concerned about the numerous long-standing “moles” on her face. Only occasionally pruritic, they are otherwise asymptomatic. Nevertheless, the patient wants them investigated and removed.

Diagnosis: Dermatosis papulosa nigra (DPN) is a benign condition that presents as multiple brown to dark-brown 1- to 5-mm papules on the face, neck, and trunk. The lesions are a sign of aging in darker skinned patients and do not require treatment. They can, however, be safely, easily, and effectively removed. Both electrodesiccation and KTP (532 nm) laser have comparable efficacy in the removal of DPN, according to a  2009 study published in the American Journal of Dermatologic Surgery. Without use of anesthetics, the KTP laser is preferred for patient comfort.

For more information, see “Skin of Color: Dermatosis Papulosa Nigra Removal.” Dermatology News. February 1, 2012.

 

2. A 17-year-old African-American boy likes to keep his face clean-shaven, but his skin becomes irritated every time he shaves. He states that his father also has this problem, but doesn’t have a solution.

Diagnosis: Pseudofolliculitis is a common skin condition affecting hair-bearing areas of the body that are shaved. It develops when the free end of a tightly coiled hair reenters the skin after shaving, causing a foreign-body–like inflammatory reaction. Tightly curled hair has a greater tendency to pierce the follicle and the surface of the skin, explaining the relative predominance of pseudofolliculitis in patients of African descent; at least half of black men who shave develop the condition.

For more information, see “Bumps in beard area.” J Fam Pract. 2015 November;64(11).

 

3. A 15-year-old African-American boy presents with a two-month history of hair loss and pruritic papules on the back of his head that developed after a barber shaved the area. There are two dozen 1- to 2-mm papules on his posterior neck and occipital scalp with areas of focal crusting. The patient had a similar episode a year ago after shaving the same area, but those papules cleared after one month of applying rubbing alcohol.

Diagnosis: This patient’s diagnosis is acne keloidalis nuchae (AKN), a chronic folliculitis characterized by smooth, dome-shaped papules on the posterior scalp and neck that become confluent and form firm papules and hairless, keloid-like plaques. Seen almost exclusively in young, postpubescent African-American males, the condition is often asymptomatic, although some patients complain of itching in the affected area.

For more information, see “Scalp papules in a teenage boy.” J Fam Pract. 2017 March;66(3).

 

4. Several years after a motorcycle accident and resulting road rash, this 23-year-old Hispanic woman is left with complex scars. She experiences pruritus, pain, and hypersensitivity and is seeking relief.

Diagnosis: Often confused with hypertrophic scars, keloids are benign overgrowths of scar tissue that can occur months to years after skin trauma. They are most common in those ages 10 to 30, with a higher incidence among blacks, Hispanics, and Asians. Although the exact etiology of keloids is unknown, they are related to aberrant collagen production and breakdown in wound healing.

For more information, see “Laser treatment of scars and keloids.” Cosmet Dermatol. 2012;25:318-325.

1. This patient is concerned about the numerous long-standing “moles” on her face. Only occasionally pruritic, they are otherwise asymptomatic. Nevertheless, the patient wants them investigated and removed.

Diagnosis: Dermatosis papulosa nigra (DPN) is a benign condition that presents as multiple brown to dark-brown 1- to 5-mm papules on the face, neck, and trunk. The lesions are a sign of aging in darker skinned patients and do not require treatment. They can, however, be safely, easily, and effectively removed. Both electrodesiccation and KTP (532 nm) laser have comparable efficacy in the removal of DPN, according to a  2009 study published in the American Journal of Dermatologic Surgery. Without use of anesthetics, the KTP laser is preferred for patient comfort.

For more information, see “Skin of Color: Dermatosis Papulosa Nigra Removal.” Dermatology News. February 1, 2012.

 

2. A 17-year-old African-American boy likes to keep his face clean-shaven, but his skin becomes irritated every time he shaves. He states that his father also has this problem, but doesn’t have a solution.

Diagnosis: Pseudofolliculitis is a common skin condition affecting hair-bearing areas of the body that are shaved. It develops when the free end of a tightly coiled hair reenters the skin after shaving, causing a foreign-body–like inflammatory reaction. Tightly curled hair has a greater tendency to pierce the follicle and the surface of the skin, explaining the relative predominance of pseudofolliculitis in patients of African descent; at least half of black men who shave develop the condition.

For more information, see “Bumps in beard area.” J Fam Pract. 2015 November;64(11).

 

3. A 15-year-old African-American boy presents with a two-month history of hair loss and pruritic papules on the back of his head that developed after a barber shaved the area. There are two dozen 1- to 2-mm papules on his posterior neck and occipital scalp with areas of focal crusting. The patient had a similar episode a year ago after shaving the same area, but those papules cleared after one month of applying rubbing alcohol.

Diagnosis: This patient’s diagnosis is acne keloidalis nuchae (AKN), a chronic folliculitis characterized by smooth, dome-shaped papules on the posterior scalp and neck that become confluent and form firm papules and hairless, keloid-like plaques. Seen almost exclusively in young, postpubescent African-American males, the condition is often asymptomatic, although some patients complain of itching in the affected area.

For more information, see “Scalp papules in a teenage boy.” J Fam Pract. 2017 March;66(3).

 

4. Several years after a motorcycle accident and resulting road rash, this 23-year-old Hispanic woman is left with complex scars. She experiences pruritus, pain, and hypersensitivity and is seeking relief.

Diagnosis: Often confused with hypertrophic scars, keloids are benign overgrowths of scar tissue that can occur months to years after skin trauma. They are most common in those ages 10 to 30, with a higher incidence among blacks, Hispanics, and Asians. Although the exact etiology of keloids is unknown, they are related to aberrant collagen production and breakdown in wound healing.

For more information, see “Laser treatment of scars and keloids.” Cosmet Dermatol. 2012;25:318-325.