For patients with hypothyroidism who underwent treatment with desiccated thyroid, there were no significant differences in the time spent in normal ranges of thyroid stimulating hormone (TSH) over 3 years, compared with patients who received the standard therapy of synthetic levothyroxine (T4), new research shows.

The findings are “unanticipated ... given concerns for variability between batches of desiccated thyroid cited by national guidelines,” wrote the authors of the study, which was published this month in the Annals of Family Medicine.

In the trial, patients who had been treated for hypothyroidism at Kaiser Permanente Colorado were matched retrospectively into groups of 450 patients each according to whether they were treated with desiccated thyroid or synthetic levothyroxine.

After a follow-up of 3 years, TSH values within normal ranges (0.320-5.500 uIU/mL) were seen at approximately the same rate among those treated with desiccated thyroid and those who received levothyroxine (79.1% vs. 79.3%; P = .905).

“This study showed that after 3 years TSH values in both groups remained within reference ranges approximately 80% of the time,” said Rolake Kuye, PharmD, and colleagues with Kaiser Permanente, in Denver, Colorado.

In an accompanying editorial, Jill Schneiderhan, MD, and Suzanna Zick, ND, MPH, of the University of Michigan, Ann Arbor, say the overall results indicate that the continued use of desiccated thyroid is warranted in some cases.

“Keeping desiccated thyroid medications as an option in our tool kit will allow for improved shared decision-making, while allowing for patient preference, and offer an option for those patients who remain symptomatic on levothyroxine monotherapy,” they advised.
 

Some variability still seen with desiccated thyroid

Desiccated thyroid (dehydrated porcine thyroid), which was long the standard of care, is still commonly used in the treatment of hypothyroidism, despite having been replaced beginning in the 1970s by synthetic levothyroxine in light of evidence that the former was associated with more variability in thyroid hormone levels.

Desiccated thyroid is still sold legally by prescription in the United States under the names Nature Thyroid, Thyroid USP, and Armour Thyroid and is currently used by up to 30% of patients with hypothyroidism, according to recent estimates.

Consistent with concerns about variability in thyroid hormone levels, the new study did show greater variability in TSH levels with desiccated thyroid when assessed on a visit-to-visit basis.

Dr. Kuye and coauthors therefore recommended that, “[f]or providers targeting a tighter TSH goal in certain patients, the decreased TSH variability with levothyroxine could be clinically meaningful.”
 

This long-term investigation is “much needed”

This new study adds important new insight to the ongoing debate over hypothyroidism treatment, said Dr. Schneiderhan and Dr. Zick in their editorial.

“[The study authors] begin a much-needed investigation into whether patients prescribed synthetic levothyroxine compared with desiccated thyroid had differences in TSH stability over the course of 3 years.

“Further prospective studies are needed to confirm these results and to explore differences in more diverse patient populations, such as Hashimoto’s thyroiditis, as well as on quality of life and other important patient-reported outcomes such as fatigue and weight gain,” the editorialists added.

“This study does, however, provide helpful information that desiccated thyroid products are a reasonable choice for treating some hypothyroid patients.”
 

For 60% of patients in both groups, TSH levels were within reference range for whole study

In the study, Dr. Kuye and colleagues matched patients (average age, 63 years; 90% women) in terms of characteristics such as race, comorbidities, and cholesterol levels.

Patients were excluded if they had been prescribed more than one agent for the treatment of hypothyroidism or if they had comorbid conditions, including a history of thyroid cancer or other related comorbidities, as well as pregnancy.

With respect to visit-to-visit TSH level variability, the lower rate among patients prescribed levothyroxine in comparison with patients prescribed desiccated thyroid was statistically significant (1.25 vs. 1.44; P = .015). Among 60% of patients in both groups, all TSH values measured during the study period were within reference ranges, however (P = .951).

The median number of TSH laboratory studies obtained during the study was four in the synthetic levothyroxine group and three for patients prescribed desiccated thyroid (P = .578).

There were some notable differences between the groups. Patients in the desiccated thyroid group had lower body mass index (P = .032), hemoglobin A1c levels (P = .041), and lower baseline TSH values (2.4 vs. 3.4 uIU/mL; P = .001). compared with those prescribed levothyroxine.

Limitations include the fact that the authors could not account for potentially important variables such as rates of adherence, differences in prescriber practice between agents, or the concurrent use of other medications.
 

Subjective outcomes not assessed: “One-size-fits-all approach doesn’t work”

The authors note they were not able to assess subjective outcomes, which, as noted by the editorialists, are particularly important in hypothyroidism.

“Emerging evidence shows that for many patients, symptoms persist despite normal TSH values,” Dr. Schneiderhan and Dr. Zick write.

They cite as an example a large study that found significant impairment in psychological well-being among patients treated with thyroxine replacement, despite their achieving normal TSH levels.

In addition, synthetic levothyroxine is associated with other uncertainties, such as complexities in the conversion of T4 to triiodothyronine (T3) that may disrupt thyroid metabolism in some patients.

In addition, there are differences in the amounts of thyroid replacement needed by certain groups, such as patients who have undergone thyroidectomies.

“The one-size-fits-all approach for treating hypothyroidism does not work ... for all patients,” they concluded.

The study authors and editorialists have disclosed no relevant financial relationships.
 

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

For patients with hypothyroidism who underwent treatment with desiccated thyroid, there were no significant differences in the time spent in normal ranges of thyroid stimulating hormone (TSH) over 3 years, compared with patients who received the standard therapy of synthetic levothyroxine (T4), new research shows.

The findings are “unanticipated ... given concerns for variability between batches of desiccated thyroid cited by national guidelines,” wrote the authors of the study, which was published this month in the Annals of Family Medicine.

In the trial, patients who had been treated for hypothyroidism at Kaiser Permanente Colorado were matched retrospectively into groups of 450 patients each according to whether they were treated with desiccated thyroid or synthetic levothyroxine.

After a follow-up of 3 years, TSH values within normal ranges (0.320-5.500 uIU/mL) were seen at approximately the same rate among those treated with desiccated thyroid and those who received levothyroxine (79.1% vs. 79.3%; P = .905).

“This study showed that after 3 years TSH values in both groups remained within reference ranges approximately 80% of the time,” said Rolake Kuye, PharmD, and colleagues with Kaiser Permanente, in Denver, Colorado.

In an accompanying editorial, Jill Schneiderhan, MD, and Suzanna Zick, ND, MPH, of the University of Michigan, Ann Arbor, say the overall results indicate that the continued use of desiccated thyroid is warranted in some cases.

“Keeping desiccated thyroid medications as an option in our tool kit will allow for improved shared decision-making, while allowing for patient preference, and offer an option for those patients who remain symptomatic on levothyroxine monotherapy,” they advised.
 

Some variability still seen with desiccated thyroid

Desiccated thyroid (dehydrated porcine thyroid), which was long the standard of care, is still commonly used in the treatment of hypothyroidism, despite having been replaced beginning in the 1970s by synthetic levothyroxine in light of evidence that the former was associated with more variability in thyroid hormone levels.

Desiccated thyroid is still sold legally by prescription in the United States under the names Nature Thyroid, Thyroid USP, and Armour Thyroid and is currently used by up to 30% of patients with hypothyroidism, according to recent estimates.

Consistent with concerns about variability in thyroid hormone levels, the new study did show greater variability in TSH levels with desiccated thyroid when assessed on a visit-to-visit basis.

Dr. Kuye and coauthors therefore recommended that, “[f]or providers targeting a tighter TSH goal in certain patients, the decreased TSH variability with levothyroxine could be clinically meaningful.”
 

This long-term investigation is “much needed”

This new study adds important new insight to the ongoing debate over hypothyroidism treatment, said Dr. Schneiderhan and Dr. Zick in their editorial.

“[The study authors] begin a much-needed investigation into whether patients prescribed synthetic levothyroxine compared with desiccated thyroid had differences in TSH stability over the course of 3 years.

“Further prospective studies are needed to confirm these results and to explore differences in more diverse patient populations, such as Hashimoto’s thyroiditis, as well as on quality of life and other important patient-reported outcomes such as fatigue and weight gain,” the editorialists added.

“This study does, however, provide helpful information that desiccated thyroid products are a reasonable choice for treating some hypothyroid patients.”
 

For 60% of patients in both groups, TSH levels were within reference range for whole study

In the study, Dr. Kuye and colleagues matched patients (average age, 63 years; 90% women) in terms of characteristics such as race, comorbidities, and cholesterol levels.

Patients were excluded if they had been prescribed more than one agent for the treatment of hypothyroidism or if they had comorbid conditions, including a history of thyroid cancer or other related comorbidities, as well as pregnancy.

With respect to visit-to-visit TSH level variability, the lower rate among patients prescribed levothyroxine in comparison with patients prescribed desiccated thyroid was statistically significant (1.25 vs. 1.44; P = .015). Among 60% of patients in both groups, all TSH values measured during the study period were within reference ranges, however (P = .951).

The median number of TSH laboratory studies obtained during the study was four in the synthetic levothyroxine group and three for patients prescribed desiccated thyroid (P = .578).

There were some notable differences between the groups. Patients in the desiccated thyroid group had lower body mass index (P = .032), hemoglobin A1c levels (P = .041), and lower baseline TSH values (2.4 vs. 3.4 uIU/mL; P = .001). compared with those prescribed levothyroxine.

Limitations include the fact that the authors could not account for potentially important variables such as rates of adherence, differences in prescriber practice between agents, or the concurrent use of other medications.
 

Subjective outcomes not assessed: “One-size-fits-all approach doesn’t work”

The authors note they were not able to assess subjective outcomes, which, as noted by the editorialists, are particularly important in hypothyroidism.

“Emerging evidence shows that for many patients, symptoms persist despite normal TSH values,” Dr. Schneiderhan and Dr. Zick write.

They cite as an example a large study that found significant impairment in psychological well-being among patients treated with thyroxine replacement, despite their achieving normal TSH levels.

In addition, synthetic levothyroxine is associated with other uncertainties, such as complexities in the conversion of T4 to triiodothyronine (T3) that may disrupt thyroid metabolism in some patients.

In addition, there are differences in the amounts of thyroid replacement needed by certain groups, such as patients who have undergone thyroidectomies.

“The one-size-fits-all approach for treating hypothyroidism does not work ... for all patients,” they concluded.

The study authors and editorialists have disclosed no relevant financial relationships.
 

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

For patients with hypothyroidism who underwent treatment with desiccated thyroid, there were no significant differences in the time spent in normal ranges of thyroid stimulating hormone (TSH) over 3 years, compared with patients who received the standard therapy of synthetic levothyroxine (T4), new research shows.

The findings are “unanticipated ... given concerns for variability between batches of desiccated thyroid cited by national guidelines,” wrote the authors of the study, which was published this month in the Annals of Family Medicine.

In the trial, patients who had been treated for hypothyroidism at Kaiser Permanente Colorado were matched retrospectively into groups of 450 patients each according to whether they were treated with desiccated thyroid or synthetic levothyroxine.

After a follow-up of 3 years, TSH values within normal ranges (0.320-5.500 uIU/mL) were seen at approximately the same rate among those treated with desiccated thyroid and those who received levothyroxine (79.1% vs. 79.3%; P = .905).

“This study showed that after 3 years TSH values in both groups remained within reference ranges approximately 80% of the time,” said Rolake Kuye, PharmD, and colleagues with Kaiser Permanente, in Denver, Colorado.

In an accompanying editorial, Jill Schneiderhan, MD, and Suzanna Zick, ND, MPH, of the University of Michigan, Ann Arbor, say the overall results indicate that the continued use of desiccated thyroid is warranted in some cases.

“Keeping desiccated thyroid medications as an option in our tool kit will allow for improved shared decision-making, while allowing for patient preference, and offer an option for those patients who remain symptomatic on levothyroxine monotherapy,” they advised.
 

Some variability still seen with desiccated thyroid

Desiccated thyroid (dehydrated porcine thyroid), which was long the standard of care, is still commonly used in the treatment of hypothyroidism, despite having been replaced beginning in the 1970s by synthetic levothyroxine in light of evidence that the former was associated with more variability in thyroid hormone levels.

Desiccated thyroid is still sold legally by prescription in the United States under the names Nature Thyroid, Thyroid USP, and Armour Thyroid and is currently used by up to 30% of patients with hypothyroidism, according to recent estimates.

Consistent with concerns about variability in thyroid hormone levels, the new study did show greater variability in TSH levels with desiccated thyroid when assessed on a visit-to-visit basis.

Dr. Kuye and coauthors therefore recommended that, “[f]or providers targeting a tighter TSH goal in certain patients, the decreased TSH variability with levothyroxine could be clinically meaningful.”
 

This long-term investigation is “much needed”

This new study adds important new insight to the ongoing debate over hypothyroidism treatment, said Dr. Schneiderhan and Dr. Zick in their editorial.

“[The study authors] begin a much-needed investigation into whether patients prescribed synthetic levothyroxine compared with desiccated thyroid had differences in TSH stability over the course of 3 years.

“Further prospective studies are needed to confirm these results and to explore differences in more diverse patient populations, such as Hashimoto’s thyroiditis, as well as on quality of life and other important patient-reported outcomes such as fatigue and weight gain,” the editorialists added.

“This study does, however, provide helpful information that desiccated thyroid products are a reasonable choice for treating some hypothyroid patients.”
 

For 60% of patients in both groups, TSH levels were within reference range for whole study

In the study, Dr. Kuye and colleagues matched patients (average age, 63 years; 90% women) in terms of characteristics such as race, comorbidities, and cholesterol levels.

Patients were excluded if they had been prescribed more than one agent for the treatment of hypothyroidism or if they had comorbid conditions, including a history of thyroid cancer or other related comorbidities, as well as pregnancy.

With respect to visit-to-visit TSH level variability, the lower rate among patients prescribed levothyroxine in comparison with patients prescribed desiccated thyroid was statistically significant (1.25 vs. 1.44; P = .015). Among 60% of patients in both groups, all TSH values measured during the study period were within reference ranges, however (P = .951).

The median number of TSH laboratory studies obtained during the study was four in the synthetic levothyroxine group and three for patients prescribed desiccated thyroid (P = .578).

There were some notable differences between the groups. Patients in the desiccated thyroid group had lower body mass index (P = .032), hemoglobin A1c levels (P = .041), and lower baseline TSH values (2.4 vs. 3.4 uIU/mL; P = .001). compared with those prescribed levothyroxine.

Limitations include the fact that the authors could not account for potentially important variables such as rates of adherence, differences in prescriber practice between agents, or the concurrent use of other medications.
 

Subjective outcomes not assessed: “One-size-fits-all approach doesn’t work”

The authors note they were not able to assess subjective outcomes, which, as noted by the editorialists, are particularly important in hypothyroidism.

“Emerging evidence shows that for many patients, symptoms persist despite normal TSH values,” Dr. Schneiderhan and Dr. Zick write.

They cite as an example a large study that found significant impairment in psychological well-being among patients treated with thyroxine replacement, despite their achieving normal TSH levels.

In addition, synthetic levothyroxine is associated with other uncertainties, such as complexities in the conversion of T4 to triiodothyronine (T3) that may disrupt thyroid metabolism in some patients.

In addition, there are differences in the amounts of thyroid replacement needed by certain groups, such as patients who have undergone thyroidectomies.

“The one-size-fits-all approach for treating hypothyroidism does not work ... for all patients,” they concluded.

The study authors and editorialists have disclosed no relevant financial relationships.
 

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

Phase 2 data for the investigational, once-weekly basal insulin analog icodec (Novo Nordisk) showing comparable efficacy and safety to once-daily insulin glargine U100 have been published in the New England Journal of Medicine.

“Insulin icodec could potentially improve acceptance and likely would facilitate management in type 2 diabetes patients needing basal insulin, and I think it will be transformational in the way we manage people with type 2 diabetes requiring insulin,” said lead author Julio Rosenstock, MD, University of Texas Southwestern Medical Center, Dallas, who also presented the data at the virtual annual meeting of the European Association for the Study of Diabetes.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour (8.1 days) half-life, so the once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week, with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

In the 26-week, randomized, phase 2 trial involving 247 insulin-naive patients with type 2 diabetes, once-weekly icodec’s glucose-lowering and safety profiles were similar to those of once-daily insulin glargine U100. These results were previously presented by Dr. Rosenstock in June at the virtual American Diabetes Association conference, as reported by Medscape Medical News.

In addition, new data in a poster at EASD 2020 showed that switching to icodec from other basal insulins is efficacious without causing significant hypoglycemia, as reported by Harpreet Bajaj, MD, MPH, director of the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto.

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said in an interview that “some patients will find once-weekly basal insulin an attractive option, while other patients will be indifferent to its availability.”

Dr. Alexander also pointed out that “payers are not going to be very interested in paying for a once-weekly basal insulin when daily basal insulins have been available for many years, unless the cost is the same or less. Resource-constrained health plans will wait until the price is [similar].”
 

The phase 2 study: Once weekly is just as good as daily

In the phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial, the patients had baseline hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with or without a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, down to 6.7% and 6.9%, respectively. The difference wasn’t significant (P = .08). Fasting plasma glucose levels dropped by 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

Time in range (70-140 mg/dL or 3.9-7.8 mmol/L) as assessed by flash glucose monitoring (FreeStyle Libre Pro) was greater with Icodec, by 5.4 percentage points, corresponding to an extra 78 minutes per day in range.

Mild hypoglycemia was more common with icodec than glargine (509 vs. 211 events per 100 patient-years, but rates of moderate/clinically significant hypoglycemia (52.5 vs. 46 per 100 patient-years, respectively) and severe hypoglycemia (1.4 vs. 0 per 100 patient-years) did not differ significantly (P = .85).

And the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between the groups.

Use of a once-weekly basal insulin could reduce the number of annual insulin injections from 365 to just 52, the authors noted in their paper.
 

New data: Switching to icodec is effective, safe

The new data on switching came from a 16-week, open-label, phase 2 trial of 154 patients with type 2 diabetes with insufficient glycemic control (mean A1c 7.9%) while taking oral medication and basal insulin. They were randomized to once-weekly icodec with or without an initial loading dose, or once-daily glargine U100.

Insulin doses were titrated weekly based on blood glucose levels as measured by continuous glucose monitoring (Dexcom G6).

The primary endpoint, time in range (70-180 mg/dL or 3.9-10.0 mmol/L) during weeks 15-16 was significantly better for icodec plus loading dose, compared with glargine U100 (72.9% vs 65.0%, P = .01) and similar between icodec and glargine U100 (66.0% vs 65.0%, P = .75).

Estimated mean percentage point reductions in A1c were 0.77 for icodec plus loading dose, 0.47 for icodec without the loading dose, and 0.54 for glargine U100.

Rates of moderate to severe hypoglycemia were similar between icodec plus loading dose and glargine U100 (78.0 and 79.4 events per 100 patient-years, respectively), and lower for icodec without the loading dose (14.8/100 patient-years).

There were no unexpected safety findings.

Novo Nordisk’s phase 3 trial for icodec is set to begin in late November.

The company is also developing a coformulation of icodec with its glucagonlike peptide–1 receptor agonist semaglutide, currently in phase 1 testing. Meanwhile, Eli Lilly is also developing a once-weekly basal analog, LY3209590, currently in phase 2 trials.

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

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

Phase 2 data for the investigational, once-weekly basal insulin analog icodec (Novo Nordisk) showing comparable efficacy and safety to once-daily insulin glargine U100 have been published in the New England Journal of Medicine.

“Insulin icodec could potentially improve acceptance and likely would facilitate management in type 2 diabetes patients needing basal insulin, and I think it will be transformational in the way we manage people with type 2 diabetes requiring insulin,” said lead author Julio Rosenstock, MD, University of Texas Southwestern Medical Center, Dallas, who also presented the data at the virtual annual meeting of the European Association for the Study of Diabetes.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour (8.1 days) half-life, so the once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week, with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

In the 26-week, randomized, phase 2 trial involving 247 insulin-naive patients with type 2 diabetes, once-weekly icodec’s glucose-lowering and safety profiles were similar to those of once-daily insulin glargine U100. These results were previously presented by Dr. Rosenstock in June at the virtual American Diabetes Association conference, as reported by Medscape Medical News.

In addition, new data in a poster at EASD 2020 showed that switching to icodec from other basal insulins is efficacious without causing significant hypoglycemia, as reported by Harpreet Bajaj, MD, MPH, director of the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto.

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said in an interview that “some patients will find once-weekly basal insulin an attractive option, while other patients will be indifferent to its availability.”

Dr. Alexander also pointed out that “payers are not going to be very interested in paying for a once-weekly basal insulin when daily basal insulins have been available for many years, unless the cost is the same or less. Resource-constrained health plans will wait until the price is [similar].”
 

The phase 2 study: Once weekly is just as good as daily

In the phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial, the patients had baseline hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with or without a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, down to 6.7% and 6.9%, respectively. The difference wasn’t significant (P = .08). Fasting plasma glucose levels dropped by 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

Time in range (70-140 mg/dL or 3.9-7.8 mmol/L) as assessed by flash glucose monitoring (FreeStyle Libre Pro) was greater with Icodec, by 5.4 percentage points, corresponding to an extra 78 minutes per day in range.

Mild hypoglycemia was more common with icodec than glargine (509 vs. 211 events per 100 patient-years, but rates of moderate/clinically significant hypoglycemia (52.5 vs. 46 per 100 patient-years, respectively) and severe hypoglycemia (1.4 vs. 0 per 100 patient-years) did not differ significantly (P = .85).

And the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between the groups.

Use of a once-weekly basal insulin could reduce the number of annual insulin injections from 365 to just 52, the authors noted in their paper.
 

New data: Switching to icodec is effective, safe

The new data on switching came from a 16-week, open-label, phase 2 trial of 154 patients with type 2 diabetes with insufficient glycemic control (mean A1c 7.9%) while taking oral medication and basal insulin. They were randomized to once-weekly icodec with or without an initial loading dose, or once-daily glargine U100.

Insulin doses were titrated weekly based on blood glucose levels as measured by continuous glucose monitoring (Dexcom G6).

The primary endpoint, time in range (70-180 mg/dL or 3.9-10.0 mmol/L) during weeks 15-16 was significantly better for icodec plus loading dose, compared with glargine U100 (72.9% vs 65.0%, P = .01) and similar between icodec and glargine U100 (66.0% vs 65.0%, P = .75).

Estimated mean percentage point reductions in A1c were 0.77 for icodec plus loading dose, 0.47 for icodec without the loading dose, and 0.54 for glargine U100.

Rates of moderate to severe hypoglycemia were similar between icodec plus loading dose and glargine U100 (78.0 and 79.4 events per 100 patient-years, respectively), and lower for icodec without the loading dose (14.8/100 patient-years).

There were no unexpected safety findings.

Novo Nordisk’s phase 3 trial for icodec is set to begin in late November.

The company is also developing a coformulation of icodec with its glucagonlike peptide–1 receptor agonist semaglutide, currently in phase 1 testing. Meanwhile, Eli Lilly is also developing a once-weekly basal analog, LY3209590, currently in phase 2 trials.

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

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

Phase 2 data for the investigational, once-weekly basal insulin analog icodec (Novo Nordisk) showing comparable efficacy and safety to once-daily insulin glargine U100 have been published in the New England Journal of Medicine.

“Insulin icodec could potentially improve acceptance and likely would facilitate management in type 2 diabetes patients needing basal insulin, and I think it will be transformational in the way we manage people with type 2 diabetes requiring insulin,” said lead author Julio Rosenstock, MD, University of Texas Southwestern Medical Center, Dallas, who also presented the data at the virtual annual meeting of the European Association for the Study of Diabetes.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour (8.1 days) half-life, so the once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week, with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

In the 26-week, randomized, phase 2 trial involving 247 insulin-naive patients with type 2 diabetes, once-weekly icodec’s glucose-lowering and safety profiles were similar to those of once-daily insulin glargine U100. These results were previously presented by Dr. Rosenstock in June at the virtual American Diabetes Association conference, as reported by Medscape Medical News.

In addition, new data in a poster at EASD 2020 showed that switching to icodec from other basal insulins is efficacious without causing significant hypoglycemia, as reported by Harpreet Bajaj, MD, MPH, director of the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto.

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said in an interview that “some patients will find once-weekly basal insulin an attractive option, while other patients will be indifferent to its availability.”

Dr. Alexander also pointed out that “payers are not going to be very interested in paying for a once-weekly basal insulin when daily basal insulins have been available for many years, unless the cost is the same or less. Resource-constrained health plans will wait until the price is [similar].”
 

The phase 2 study: Once weekly is just as good as daily

In the phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial, the patients had baseline hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with or without a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, down to 6.7% and 6.9%, respectively. The difference wasn’t significant (P = .08). Fasting plasma glucose levels dropped by 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

Time in range (70-140 mg/dL or 3.9-7.8 mmol/L) as assessed by flash glucose monitoring (FreeStyle Libre Pro) was greater with Icodec, by 5.4 percentage points, corresponding to an extra 78 minutes per day in range.

Mild hypoglycemia was more common with icodec than glargine (509 vs. 211 events per 100 patient-years, but rates of moderate/clinically significant hypoglycemia (52.5 vs. 46 per 100 patient-years, respectively) and severe hypoglycemia (1.4 vs. 0 per 100 patient-years) did not differ significantly (P = .85).

And the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between the groups.

Use of a once-weekly basal insulin could reduce the number of annual insulin injections from 365 to just 52, the authors noted in their paper.
 

New data: Switching to icodec is effective, safe

The new data on switching came from a 16-week, open-label, phase 2 trial of 154 patients with type 2 diabetes with insufficient glycemic control (mean A1c 7.9%) while taking oral medication and basal insulin. They were randomized to once-weekly icodec with or without an initial loading dose, or once-daily glargine U100.

Insulin doses were titrated weekly based on blood glucose levels as measured by continuous glucose monitoring (Dexcom G6).

The primary endpoint, time in range (70-180 mg/dL or 3.9-10.0 mmol/L) during weeks 15-16 was significantly better for icodec plus loading dose, compared with glargine U100 (72.9% vs 65.0%, P = .01) and similar between icodec and glargine U100 (66.0% vs 65.0%, P = .75).

Estimated mean percentage point reductions in A1c were 0.77 for icodec plus loading dose, 0.47 for icodec without the loading dose, and 0.54 for glargine U100.

Rates of moderate to severe hypoglycemia were similar between icodec plus loading dose and glargine U100 (78.0 and 79.4 events per 100 patient-years, respectively), and lower for icodec without the loading dose (14.8/100 patient-years).

There were no unexpected safety findings.

Novo Nordisk’s phase 3 trial for icodec is set to begin in late November.

The company is also developing a coformulation of icodec with its glucagonlike peptide–1 receptor agonist semaglutide, currently in phase 1 testing. Meanwhile, Eli Lilly is also developing a once-weekly basal analog, LY3209590, currently in phase 2 trials.

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

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

As may be expected, lifestyle risk factors, including physical activity and diet, are found to be more influential in determining type 2 diabetes risk within a married couple than physiologic factors such as glucose tolerance or insulin sensitivity, researchers have shown.

“Essentially, these data suggest that couple-based interventions targeting spouses’ similarities might be [an] efficient way of delivering lifestyle interventions,” said study lead Omar Silverman-Retana, MD, PhD.

“We identified that spousal concordance was strongest for behavioral risk factors, in particular physical activity and diet,” he told Medscape Medical News in an interview.

Silverman-Retana, of Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark, reported the findings in a poster at this year’s annual meeting of the European Association for the Study of Diabetes (EASD), held online because of the coronavirus pandemic.

Effectively, concordance was found to be weaker in the pathophysiologic markers because these are more biologically determined compared with lifestyle factors.

Janice Kiecolt-Glaser, PhD, is a marital biobehavioral researcher who is interested in spousal concordance for many chronic health conditions.

This “research is part of a growing body of evidence that carries a clear message: Be careful whom you marry, your life may depend on it!” she explained.

“Your partner’s behavior definitely influences your own, and in the case of diabetes, the researchers have found clear behavioral links, and those make sense,” she told Medscape Medical News.

“In addition, data from our lab and others show that the gut microbiomes of cohabiting couples are more similar than those of unrelated pairs,” noted Kiecolt-Glaser, who is professor of psychiatry and behavioral Health at Ohio State University College of Medicine in Columbus.

“Diet and exercise both have substantial influences on the gut microbiome, and there is growing evidence that the gut microbiome contributes to risk for diabetes. This research fits with, and extends, what we know.”
 

A comprehensive picture of mechanisms leading to diabetes

The research led by Silverman-Retana and colleagues comprised a cross-sectional analysis of couples who participated in The Maastricht Study, an extensive phenotyping trial that focuses on the causes of type 2 diabetes, its classic complications, and its emerging comorbidities.

The researchers measured a comprehensive list of lifestyle and physiologic indicators, and using the social network aspect of the study, identified 172 couples with complete information for the final analysis.

Spousal concordance in lifestyle factors and pathophysiologic mechanisms of type 2 diabetes, including beta cell function and insulin sensitivity, were determined using regression analysis. Risk factors included waist circumference, percentage body fat, physical activity, sedentary time, the Dutch Healthy Diet Index (DHDI), and total energy consumption.

In addition, the researchers assessed glucose metabolism status using fasting and 2-hour plasma glucose, as well as HbA1c, and they also derived beta cell function indices using a seven-time point glucose tolerance test, and insulin sensitivity.

“Most importantly, we measured risk factors and pathophysiologic factors in the same study, and to the same level of detail in both partners, providing a more comprehensive picture of the mechanisms that lead to type 2 diabetes,” Silverman-Retana highlighted.

There have been previous studies addressing disease risk and couples’ concordance. A prior study, also by Silverman-Retana and colleagues at Aarhus University, found a link between the weight of one spouse and the chances of a diagnosis of type 2 diabetes in the other spouse.

Another study, reported by Medscape Medical News  in 2018, showed that when one spouse tried to lose weight with a weight management program, the other ‘untreated’ spouse was also likely to drop some weight.

Silverman-Retana noted that other research examining the similarities and differences within couples has investigated physical activity using self-reported questionnaires, but the current study used accelerometer data.  “These provide a more precise measure of physical activity,” he said, in pointing out one way in which the new study differs from previous ones. 

The findings suggest that for men, the strongest spousal concordance was for the Dutch Healthy Diet Index (DHDI), meaning that a one unit increase in wives’ DHDI was associated with a 0.53 unit difference in the men’s DHDI.

For women, the strongest concordance was for the time spent in high intensity physical activity, such that a one unit increase in husbands’ time spent in high intensity physical activity was associated with a 0.36 unit difference in women’s time spent in high intensity physical activity.

“If we compare the concordance, it weakens as we move downstream to the immediate causal risk factors of type 2 diabetes,” explained Silverman-Retana. “The weakest concordance was found in beta cell function indices and glucose metabolism indicators because these are more biologically determined.”

Concordance is mainly explained by the fact that we tend to choose a partner who has similar characteristics to our own, in terms of social class and/or educational level, smoking status, exercise habits and diet, explained the researcher.

“It would be interesting to know how behavioral similarity depends on the length of marriage or time as a couple. Future studies will need to look into this,” he concluded.   

Silverman-Retana and Kiecolt-Glaser have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

As may be expected, lifestyle risk factors, including physical activity and diet, are found to be more influential in determining type 2 diabetes risk within a married couple than physiologic factors such as glucose tolerance or insulin sensitivity, researchers have shown.

“Essentially, these data suggest that couple-based interventions targeting spouses’ similarities might be [an] efficient way of delivering lifestyle interventions,” said study lead Omar Silverman-Retana, MD, PhD.

“We identified that spousal concordance was strongest for behavioral risk factors, in particular physical activity and diet,” he told Medscape Medical News in an interview.

Silverman-Retana, of Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark, reported the findings in a poster at this year’s annual meeting of the European Association for the Study of Diabetes (EASD), held online because of the coronavirus pandemic.

Effectively, concordance was found to be weaker in the pathophysiologic markers because these are more biologically determined compared with lifestyle factors.

Janice Kiecolt-Glaser, PhD, is a marital biobehavioral researcher who is interested in spousal concordance for many chronic health conditions.

This “research is part of a growing body of evidence that carries a clear message: Be careful whom you marry, your life may depend on it!” she explained.

“Your partner’s behavior definitely influences your own, and in the case of diabetes, the researchers have found clear behavioral links, and those make sense,” she told Medscape Medical News.

“In addition, data from our lab and others show that the gut microbiomes of cohabiting couples are more similar than those of unrelated pairs,” noted Kiecolt-Glaser, who is professor of psychiatry and behavioral Health at Ohio State University College of Medicine in Columbus.

“Diet and exercise both have substantial influences on the gut microbiome, and there is growing evidence that the gut microbiome contributes to risk for diabetes. This research fits with, and extends, what we know.”
 

A comprehensive picture of mechanisms leading to diabetes

The research led by Silverman-Retana and colleagues comprised a cross-sectional analysis of couples who participated in The Maastricht Study, an extensive phenotyping trial that focuses on the causes of type 2 diabetes, its classic complications, and its emerging comorbidities.

The researchers measured a comprehensive list of lifestyle and physiologic indicators, and using the social network aspect of the study, identified 172 couples with complete information for the final analysis.

Spousal concordance in lifestyle factors and pathophysiologic mechanisms of type 2 diabetes, including beta cell function and insulin sensitivity, were determined using regression analysis. Risk factors included waist circumference, percentage body fat, physical activity, sedentary time, the Dutch Healthy Diet Index (DHDI), and total energy consumption.

In addition, the researchers assessed glucose metabolism status using fasting and 2-hour plasma glucose, as well as HbA1c, and they also derived beta cell function indices using a seven-time point glucose tolerance test, and insulin sensitivity.

“Most importantly, we measured risk factors and pathophysiologic factors in the same study, and to the same level of detail in both partners, providing a more comprehensive picture of the mechanisms that lead to type 2 diabetes,” Silverman-Retana highlighted.

There have been previous studies addressing disease risk and couples’ concordance. A prior study, also by Silverman-Retana and colleagues at Aarhus University, found a link between the weight of one spouse and the chances of a diagnosis of type 2 diabetes in the other spouse.

Another study, reported by Medscape Medical News  in 2018, showed that when one spouse tried to lose weight with a weight management program, the other ‘untreated’ spouse was also likely to drop some weight.

Silverman-Retana noted that other research examining the similarities and differences within couples has investigated physical activity using self-reported questionnaires, but the current study used accelerometer data.  “These provide a more precise measure of physical activity,” he said, in pointing out one way in which the new study differs from previous ones. 

The findings suggest that for men, the strongest spousal concordance was for the Dutch Healthy Diet Index (DHDI), meaning that a one unit increase in wives’ DHDI was associated with a 0.53 unit difference in the men’s DHDI.

For women, the strongest concordance was for the time spent in high intensity physical activity, such that a one unit increase in husbands’ time spent in high intensity physical activity was associated with a 0.36 unit difference in women’s time spent in high intensity physical activity.

“If we compare the concordance, it weakens as we move downstream to the immediate causal risk factors of type 2 diabetes,” explained Silverman-Retana. “The weakest concordance was found in beta cell function indices and glucose metabolism indicators because these are more biologically determined.”

Concordance is mainly explained by the fact that we tend to choose a partner who has similar characteristics to our own, in terms of social class and/or educational level, smoking status, exercise habits and diet, explained the researcher.

“It would be interesting to know how behavioral similarity depends on the length of marriage or time as a couple. Future studies will need to look into this,” he concluded.   

Silverman-Retana and Kiecolt-Glaser have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

As may be expected, lifestyle risk factors, including physical activity and diet, are found to be more influential in determining type 2 diabetes risk within a married couple than physiologic factors such as glucose tolerance or insulin sensitivity, researchers have shown.

“Essentially, these data suggest that couple-based interventions targeting spouses’ similarities might be [an] efficient way of delivering lifestyle interventions,” said study lead Omar Silverman-Retana, MD, PhD.

“We identified that spousal concordance was strongest for behavioral risk factors, in particular physical activity and diet,” he told Medscape Medical News in an interview.

Silverman-Retana, of Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark, reported the findings in a poster at this year’s annual meeting of the European Association for the Study of Diabetes (EASD), held online because of the coronavirus pandemic.

Effectively, concordance was found to be weaker in the pathophysiologic markers because these are more biologically determined compared with lifestyle factors.

Janice Kiecolt-Glaser, PhD, is a marital biobehavioral researcher who is interested in spousal concordance for many chronic health conditions.

This “research is part of a growing body of evidence that carries a clear message: Be careful whom you marry, your life may depend on it!” she explained.

“Your partner’s behavior definitely influences your own, and in the case of diabetes, the researchers have found clear behavioral links, and those make sense,” she told Medscape Medical News.

“In addition, data from our lab and others show that the gut microbiomes of cohabiting couples are more similar than those of unrelated pairs,” noted Kiecolt-Glaser, who is professor of psychiatry and behavioral Health at Ohio State University College of Medicine in Columbus.

“Diet and exercise both have substantial influences on the gut microbiome, and there is growing evidence that the gut microbiome contributes to risk for diabetes. This research fits with, and extends, what we know.”
 

A comprehensive picture of mechanisms leading to diabetes

The research led by Silverman-Retana and colleagues comprised a cross-sectional analysis of couples who participated in The Maastricht Study, an extensive phenotyping trial that focuses on the causes of type 2 diabetes, its classic complications, and its emerging comorbidities.

The researchers measured a comprehensive list of lifestyle and physiologic indicators, and using the social network aspect of the study, identified 172 couples with complete information for the final analysis.

Spousal concordance in lifestyle factors and pathophysiologic mechanisms of type 2 diabetes, including beta cell function and insulin sensitivity, were determined using regression analysis. Risk factors included waist circumference, percentage body fat, physical activity, sedentary time, the Dutch Healthy Diet Index (DHDI), and total energy consumption.

In addition, the researchers assessed glucose metabolism status using fasting and 2-hour plasma glucose, as well as HbA1c, and they also derived beta cell function indices using a seven-time point glucose tolerance test, and insulin sensitivity.

“Most importantly, we measured risk factors and pathophysiologic factors in the same study, and to the same level of detail in both partners, providing a more comprehensive picture of the mechanisms that lead to type 2 diabetes,” Silverman-Retana highlighted.

There have been previous studies addressing disease risk and couples’ concordance. A prior study, also by Silverman-Retana and colleagues at Aarhus University, found a link between the weight of one spouse and the chances of a diagnosis of type 2 diabetes in the other spouse.

Another study, reported by Medscape Medical News  in 2018, showed that when one spouse tried to lose weight with a weight management program, the other ‘untreated’ spouse was also likely to drop some weight.

Silverman-Retana noted that other research examining the similarities and differences within couples has investigated physical activity using self-reported questionnaires, but the current study used accelerometer data.  “These provide a more precise measure of physical activity,” he said, in pointing out one way in which the new study differs from previous ones. 

The findings suggest that for men, the strongest spousal concordance was for the Dutch Healthy Diet Index (DHDI), meaning that a one unit increase in wives’ DHDI was associated with a 0.53 unit difference in the men’s DHDI.

For women, the strongest concordance was for the time spent in high intensity physical activity, such that a one unit increase in husbands’ time spent in high intensity physical activity was associated with a 0.36 unit difference in women’s time spent in high intensity physical activity.

“If we compare the concordance, it weakens as we move downstream to the immediate causal risk factors of type 2 diabetes,” explained Silverman-Retana. “The weakest concordance was found in beta cell function indices and glucose metabolism indicators because these are more biologically determined.”

Concordance is mainly explained by the fact that we tend to choose a partner who has similar characteristics to our own, in terms of social class and/or educational level, smoking status, exercise habits and diet, explained the researcher.

“It would be interesting to know how behavioral similarity depends on the length of marriage or time as a couple. Future studies will need to look into this,” he concluded.   

Silverman-Retana and Kiecolt-Glaser have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Cosmetic laser procedures in darker skin types are associated with higher risks of pigmentary alterations and scarring, but can be performed safely with special considerations, according to Andrew F. Alexis, MD, MPH.

“With the devices and approaches we have today, we can achieve safe and favorable outcomes, as long as we keep in mind that there is no one-size-fits all approach,” Dr. Alexis, chair of the department of dermatology at Mount Sinai Morningside and Mount Sinai West, New York, said during the virtual annual Masters of Aesthetics Symposium. “Conservative parameters are key.”

According to 2018 data from the American Society for Aesthetic Plastic Surgery, 30% of all aesthetic procedures in the United States are being performed on self-identified non-White racial ethnic groups. “This is projected to continue to increase given demographic changes as well as changes in our technologies and approaches to aesthetic procedures that allow for safer outcomes across a more diverse range of patients,” said Dr. Alexis, professor of dermatology at Icahn School of Medicine at Mount Sinai, New York. “That being said, even though we have many safe and effective options for all skin types today, we still have to consider that on the whole, there are higher risks of pigmentary and scarring complications when we perform most of our aesthetic procedures in darker skin types. The concept of limiting the degree of injury associated with a procedure remains paramount. Even when we pick the correct device for a give patient’s skin type, if our parameters aren’t optimal, or if our technique isn’t optimal, we can still end up with pigmentary and scarring complications.”

He offered key principles for maximining safety and optimal outcomes:

Know your device. Understand the range of parameters that are safe and effective for the given skin types that you see in your practice. “Don’t just rely on what the manufacturer provides in the manual, because you could have safe parameters as directed by the manual but undertreat some patients because the settings are too conservative,” Dr. Alexis said. “On the other hand, there might be scenarios where following recommended settings for a specific skin type might still wind up with a complication. Doing test spots is key in order to master the device that you are using.”

Know your patient. Don’t assume that you know a patient’s skin phototype or ancestry when that person first presents. “When we do that, we can arrive at erroneous conclusions with respect to phototype and with respect to ancestral background, and with respect to risk of pigmentary and scarring complications,” he said. “Treat your patient as an individual; no cookie-cutter responses, no assumptions.” He makes it a point to ask patients about their ancestry and about how their skin responds to sunlight in terms of tanning ability and to injury and inflammation such as insect bites, acne, and minor abrasions. “What happens to their skin when those things happen?” Dr. Alexis said. “Do they have a tendency to hyperpigment or not? You can easily ask for that or look for evidence of that on their skin. Similarly, asking about a personal or family history of keloids or hypertrophic scars is helpful in determining an overall risk assessment for a patient before you proceed with a given procedure.”

Recognize differences in preferred treatment options and parameters. Often, less is more. For example, he said, with laser hair removal, strive for longer wavelengths, lower fluences, longer pulse durations, and increased epidermal cooling. A study from 2002 in the Journal of the American Academy of Dermatology showed that the maximum tolerated fluence of type VI skin with the 1064 Nd: YAG laser was 50 J/cm².

According to Dr. Alexis, nonablative fractional resurfacing “set the stage for being able to have safe outcomes for all skin types,” he said. “That being said, the higher the skin phototype, the higher the incidence of postinflammatory hyperpigmentation. How can we reduce this? The most important parameter is the treatment density, even though in a retrospective review from my center, high energies were associated with higher PIH rates too. Using conservative treatment densities lowers the risk of hyperpigmentation.”

Prophylactic use of hydroquinone prior to resurfacing with fractional lasers is another way to minimize the risk of postinflammatory hyperpigmentation. With this approach, Dr. Alexis asks patients to apply hydroquinone two weeks before treatment and for at least 4 weeks after. “Sun protection is key,” he said. “But when taking all of this into account, using conservative treatment densities in the range of 11%-20% coverage with a 1,550-nm Erbium-doped fractional laser, you can get favorable outcomes across skin types. But sometimes you can wind up with complications even if you do the right things.” He recalled a patient he treated for acne scarring and atrophic scars. After three treatments with the nonablative fractional 1,550-nm Erbium-doped laser set at level 4 (11% coverage), the patient developed hyperpigmentation of the treatment area. Dr. Alexis chose to continue treatment “with a few tweaks to reduce the risk of further hyperpigmentation,” he said. “I reduced the treatment density and the number of passes by half, so that the total energy delivered was halved. I also increased the concentration of hydroquinone from 4% to 6%. With that, the postinflammatory hyperpigmentation resolved.”

Another tool for resurfacing is the microsecond 1,064-nm Nd:YAG laser. “No anesthesia is required, there’s minimal down time, and you can treat all skin types,” Dr. Alexis said. “No pre- or posttreatment prophylaxis with bleaching agents are necessary, but multiple laser treatment sessions are required in order to achieve clinically meaningful results.” His approach to treating types V and VI skin involves a 1,064-nm Nd:YAG laser with a 5-mm spot size, a 0.3-microsecond pulse duration, a fluence of 12-14 J/cm², a repetition rate of 5-8 Hz, 1,000-2,000 pulses per cosmetic unit, and avoidance of pulse stacking. He generally performs 4-6 treatment sessions 2-6 weeks apart.

An additional option for resurfacing is the 650-microsecond 1,064-nm Nd:YAG laser. The recommend fluence in skin of color is 14-21 J/cm^2. A recent review article in the Journal of Drugs in Dermatology described clinical experience using this device for a wide range of conditions in darker skin types, including acne, hyperpigmentation, and melasma.

A more recent approach is using fractional radiofrequency devices, especially those that feature coated pin tips. These tips “protect the epidermis from heat injury and deliver heat to the deeper dermis where we want it, and minimize the risk to the epidermis,” Dr. Alexis said. In a 2018 study in the Journal of Drugs in Dermatology of 35 patients with skin type VI, participants received three sessions of facial treatments, 4 weeks apart using a fractional RF device with 24-pin coated tip. The researchers found that the regimen was safe and effective, and that it resulted in improved wrinkles, acne scars, and overall skin appearance.

Dr. Alexis disclosed that he has served as an adviser to or has received consulting fees from Leo, Novartis, Menlo, Galderma, Pfizer, Sanofi-Regeneron, Dermavant, Unilever, Celgene, Beiersdorf, Valeant, L’Oreal, BMS, Scientis, Bausch Health, UCB, Foamix, and Cassiopea.

[email protected]

Cosmetic laser procedures in darker skin types are associated with higher risks of pigmentary alterations and scarring, but can be performed safely with special considerations, according to Andrew F. Alexis, MD, MPH.

“With the devices and approaches we have today, we can achieve safe and favorable outcomes, as long as we keep in mind that there is no one-size-fits all approach,” Dr. Alexis, chair of the department of dermatology at Mount Sinai Morningside and Mount Sinai West, New York, said during the virtual annual Masters of Aesthetics Symposium. “Conservative parameters are key.”

According to 2018 data from the American Society for Aesthetic Plastic Surgery, 30% of all aesthetic procedures in the United States are being performed on self-identified non-White racial ethnic groups. “This is projected to continue to increase given demographic changes as well as changes in our technologies and approaches to aesthetic procedures that allow for safer outcomes across a more diverse range of patients,” said Dr. Alexis, professor of dermatology at Icahn School of Medicine at Mount Sinai, New York. “That being said, even though we have many safe and effective options for all skin types today, we still have to consider that on the whole, there are higher risks of pigmentary and scarring complications when we perform most of our aesthetic procedures in darker skin types. The concept of limiting the degree of injury associated with a procedure remains paramount. Even when we pick the correct device for a give patient’s skin type, if our parameters aren’t optimal, or if our technique isn’t optimal, we can still end up with pigmentary and scarring complications.”

He offered key principles for maximining safety and optimal outcomes:

Know your device. Understand the range of parameters that are safe and effective for the given skin types that you see in your practice. “Don’t just rely on what the manufacturer provides in the manual, because you could have safe parameters as directed by the manual but undertreat some patients because the settings are too conservative,” Dr. Alexis said. “On the other hand, there might be scenarios where following recommended settings for a specific skin type might still wind up with a complication. Doing test spots is key in order to master the device that you are using.”

Know your patient. Don’t assume that you know a patient’s skin phototype or ancestry when that person first presents. “When we do that, we can arrive at erroneous conclusions with respect to phototype and with respect to ancestral background, and with respect to risk of pigmentary and scarring complications,” he said. “Treat your patient as an individual; no cookie-cutter responses, no assumptions.” He makes it a point to ask patients about their ancestry and about how their skin responds to sunlight in terms of tanning ability and to injury and inflammation such as insect bites, acne, and minor abrasions. “What happens to their skin when those things happen?” Dr. Alexis said. “Do they have a tendency to hyperpigment or not? You can easily ask for that or look for evidence of that on their skin. Similarly, asking about a personal or family history of keloids or hypertrophic scars is helpful in determining an overall risk assessment for a patient before you proceed with a given procedure.”

Recognize differences in preferred treatment options and parameters. Often, less is more. For example, he said, with laser hair removal, strive for longer wavelengths, lower fluences, longer pulse durations, and increased epidermal cooling. A study from 2002 in the Journal of the American Academy of Dermatology showed that the maximum tolerated fluence of type VI skin with the 1064 Nd: YAG laser was 50 J/cm².

According to Dr. Alexis, nonablative fractional resurfacing “set the stage for being able to have safe outcomes for all skin types,” he said. “That being said, the higher the skin phototype, the higher the incidence of postinflammatory hyperpigmentation. How can we reduce this? The most important parameter is the treatment density, even though in a retrospective review from my center, high energies were associated with higher PIH rates too. Using conservative treatment densities lowers the risk of hyperpigmentation.”

Prophylactic use of hydroquinone prior to resurfacing with fractional lasers is another way to minimize the risk of postinflammatory hyperpigmentation. With this approach, Dr. Alexis asks patients to apply hydroquinone two weeks before treatment and for at least 4 weeks after. “Sun protection is key,” he said. “But when taking all of this into account, using conservative treatment densities in the range of 11%-20% coverage with a 1,550-nm Erbium-doped fractional laser, you can get favorable outcomes across skin types. But sometimes you can wind up with complications even if you do the right things.” He recalled a patient he treated for acne scarring and atrophic scars. After three treatments with the nonablative fractional 1,550-nm Erbium-doped laser set at level 4 (11% coverage), the patient developed hyperpigmentation of the treatment area. Dr. Alexis chose to continue treatment “with a few tweaks to reduce the risk of further hyperpigmentation,” he said. “I reduced the treatment density and the number of passes by half, so that the total energy delivered was halved. I also increased the concentration of hydroquinone from 4% to 6%. With that, the postinflammatory hyperpigmentation resolved.”

Another tool for resurfacing is the microsecond 1,064-nm Nd:YAG laser. “No anesthesia is required, there’s minimal down time, and you can treat all skin types,” Dr. Alexis said. “No pre- or posttreatment prophylaxis with bleaching agents are necessary, but multiple laser treatment sessions are required in order to achieve clinically meaningful results.” His approach to treating types V and VI skin involves a 1,064-nm Nd:YAG laser with a 5-mm spot size, a 0.3-microsecond pulse duration, a fluence of 12-14 J/cm², a repetition rate of 5-8 Hz, 1,000-2,000 pulses per cosmetic unit, and avoidance of pulse stacking. He generally performs 4-6 treatment sessions 2-6 weeks apart.

An additional option for resurfacing is the 650-microsecond 1,064-nm Nd:YAG laser. The recommend fluence in skin of color is 14-21 J/cm^2. A recent review article in the Journal of Drugs in Dermatology described clinical experience using this device for a wide range of conditions in darker skin types, including acne, hyperpigmentation, and melasma.

A more recent approach is using fractional radiofrequency devices, especially those that feature coated pin tips. These tips “protect the epidermis from heat injury and deliver heat to the deeper dermis where we want it, and minimize the risk to the epidermis,” Dr. Alexis said. In a 2018 study in the Journal of Drugs in Dermatology of 35 patients with skin type VI, participants received three sessions of facial treatments, 4 weeks apart using a fractional RF device with 24-pin coated tip. The researchers found that the regimen was safe and effective, and that it resulted in improved wrinkles, acne scars, and overall skin appearance.

Dr. Alexis disclosed that he has served as an adviser to or has received consulting fees from Leo, Novartis, Menlo, Galderma, Pfizer, Sanofi-Regeneron, Dermavant, Unilever, Celgene, Beiersdorf, Valeant, L’Oreal, BMS, Scientis, Bausch Health, UCB, Foamix, and Cassiopea.

[email protected]

Cosmetic laser procedures in darker skin types are associated with higher risks of pigmentary alterations and scarring, but can be performed safely with special considerations, according to Andrew F. Alexis, MD, MPH.

“With the devices and approaches we have today, we can achieve safe and favorable outcomes, as long as we keep in mind that there is no one-size-fits all approach,” Dr. Alexis, chair of the department of dermatology at Mount Sinai Morningside and Mount Sinai West, New York, said during the virtual annual Masters of Aesthetics Symposium. “Conservative parameters are key.”

According to 2018 data from the American Society for Aesthetic Plastic Surgery, 30% of all aesthetic procedures in the United States are being performed on self-identified non-White racial ethnic groups. “This is projected to continue to increase given demographic changes as well as changes in our technologies and approaches to aesthetic procedures that allow for safer outcomes across a more diverse range of patients,” said Dr. Alexis, professor of dermatology at Icahn School of Medicine at Mount Sinai, New York. “That being said, even though we have many safe and effective options for all skin types today, we still have to consider that on the whole, there are higher risks of pigmentary and scarring complications when we perform most of our aesthetic procedures in darker skin types. The concept of limiting the degree of injury associated with a procedure remains paramount. Even when we pick the correct device for a give patient’s skin type, if our parameters aren’t optimal, or if our technique isn’t optimal, we can still end up with pigmentary and scarring complications.”

He offered key principles for maximining safety and optimal outcomes:

Know your device. Understand the range of parameters that are safe and effective for the given skin types that you see in your practice. “Don’t just rely on what the manufacturer provides in the manual, because you could have safe parameters as directed by the manual but undertreat some patients because the settings are too conservative,” Dr. Alexis said. “On the other hand, there might be scenarios where following recommended settings for a specific skin type might still wind up with a complication. Doing test spots is key in order to master the device that you are using.”

Know your patient. Don’t assume that you know a patient’s skin phototype or ancestry when that person first presents. “When we do that, we can arrive at erroneous conclusions with respect to phototype and with respect to ancestral background, and with respect to risk of pigmentary and scarring complications,” he said. “Treat your patient as an individual; no cookie-cutter responses, no assumptions.” He makes it a point to ask patients about their ancestry and about how their skin responds to sunlight in terms of tanning ability and to injury and inflammation such as insect bites, acne, and minor abrasions. “What happens to their skin when those things happen?” Dr. Alexis said. “Do they have a tendency to hyperpigment or not? You can easily ask for that or look for evidence of that on their skin. Similarly, asking about a personal or family history of keloids or hypertrophic scars is helpful in determining an overall risk assessment for a patient before you proceed with a given procedure.”

Recognize differences in preferred treatment options and parameters. Often, less is more. For example, he said, with laser hair removal, strive for longer wavelengths, lower fluences, longer pulse durations, and increased epidermal cooling. A study from 2002 in the Journal of the American Academy of Dermatology showed that the maximum tolerated fluence of type VI skin with the 1064 Nd: YAG laser was 50 J/cm².

According to Dr. Alexis, nonablative fractional resurfacing “set the stage for being able to have safe outcomes for all skin types,” he said. “That being said, the higher the skin phototype, the higher the incidence of postinflammatory hyperpigmentation. How can we reduce this? The most important parameter is the treatment density, even though in a retrospective review from my center, high energies were associated with higher PIH rates too. Using conservative treatment densities lowers the risk of hyperpigmentation.”

Prophylactic use of hydroquinone prior to resurfacing with fractional lasers is another way to minimize the risk of postinflammatory hyperpigmentation. With this approach, Dr. Alexis asks patients to apply hydroquinone two weeks before treatment and for at least 4 weeks after. “Sun protection is key,” he said. “But when taking all of this into account, using conservative treatment densities in the range of 11%-20% coverage with a 1,550-nm Erbium-doped fractional laser, you can get favorable outcomes across skin types. But sometimes you can wind up with complications even if you do the right things.” He recalled a patient he treated for acne scarring and atrophic scars. After three treatments with the nonablative fractional 1,550-nm Erbium-doped laser set at level 4 (11% coverage), the patient developed hyperpigmentation of the treatment area. Dr. Alexis chose to continue treatment “with a few tweaks to reduce the risk of further hyperpigmentation,” he said. “I reduced the treatment density and the number of passes by half, so that the total energy delivered was halved. I also increased the concentration of hydroquinone from 4% to 6%. With that, the postinflammatory hyperpigmentation resolved.”

Another tool for resurfacing is the microsecond 1,064-nm Nd:YAG laser. “No anesthesia is required, there’s minimal down time, and you can treat all skin types,” Dr. Alexis said. “No pre- or posttreatment prophylaxis with bleaching agents are necessary, but multiple laser treatment sessions are required in order to achieve clinically meaningful results.” His approach to treating types V and VI skin involves a 1,064-nm Nd:YAG laser with a 5-mm spot size, a 0.3-microsecond pulse duration, a fluence of 12-14 J/cm², a repetition rate of 5-8 Hz, 1,000-2,000 pulses per cosmetic unit, and avoidance of pulse stacking. He generally performs 4-6 treatment sessions 2-6 weeks apart.

An additional option for resurfacing is the 650-microsecond 1,064-nm Nd:YAG laser. The recommend fluence in skin of color is 14-21 J/cm^2. A recent review article in the Journal of Drugs in Dermatology described clinical experience using this device for a wide range of conditions in darker skin types, including acne, hyperpigmentation, and melasma.

A more recent approach is using fractional radiofrequency devices, especially those that feature coated pin tips. These tips “protect the epidermis from heat injury and deliver heat to the deeper dermis where we want it, and minimize the risk to the epidermis,” Dr. Alexis said. In a 2018 study in the Journal of Drugs in Dermatology of 35 patients with skin type VI, participants received three sessions of facial treatments, 4 weeks apart using a fractional RF device with 24-pin coated tip. The researchers found that the regimen was safe and effective, and that it resulted in improved wrinkles, acne scars, and overall skin appearance.

Dr. Alexis disclosed that he has served as an adviser to or has received consulting fees from Leo, Novartis, Menlo, Galderma, Pfizer, Sanofi-Regeneron, Dermavant, Unilever, Celgene, Beiersdorf, Valeant, L’Oreal, BMS, Scientis, Bausch Health, UCB, Foamix, and Cassiopea.

[email protected]

Patients with advanced melanoma who have progressed on anti–programmed death 1/PD-ligand 1 (PD-L1) immunotherapy could substantially extend their overall survival (OS) with a combination of the tyrosine kinase inhibitor lenvatinib (Lenvima) and pembrolizumab (Keytruda), suggests an open-label, single arm study.

The research was presented Sept. 19 at the European Society for Medical Oncology Virtual Congress 2020.

In LEAP-004 trial, over 100 patients with stage 3 or 4 melanoma who had progressed after immunotherapy were given lenvatinib plus pembrolizumab, which yielded a median progression-free survival (PFS) of more than 4 months and a median OS of more than a year. Median follow-up was 12 months.

Presenting the findings, Ana Maria Arance Fernandez, MD, PhD, Hospital Clínic de Barcelona, Spain, said lenvatinib plus pembrolizumab has “promising” antitumor activity in patients with advanced melanoma with confirmed progression on a PD-1 inhibitor given alone or in combination. “These results are encouraging given the stringent definition of progression on prior anti-PD-1 therapy and the enrollment of poor-risk patients.”

Dr. Arance Fernandez added that “these data support lenvatinib plus pembrolizumab as a potential treatment regimen for this population of high unmet medical need.”

Bartosz Chmielowski, MD, PhD, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, who was not involved in the study, discussed the findings.

He highlighted that the patients were not randomly assigned in LEAP-004, with all of them receiving the same therapy.

Nevertheless, the response rate was “quite impressive for this patient population.”

He also drew comparison with previous data with nivolumab (Opdivo) alone or in combination with ipilimumab (Yervoy) in a similar population, noting that the overall survival was less than half that seen in the current trial, “which makes these results even more important.”

“It tells us that this combination might be an option with disease progression on anti-PD-1,” Dr. Chmielowski noted.

Dr. Arance Fernandez pointed out that patients with advanced melanoma who progress on standard-of-care treatment with anti-PD-1 therapy or a cytotoxic T-lymphocyte–associated protein 4 (CTLA4) inhibitor plus anti-PD-1 “have very limited therapeutic options available and there is no approved regimen in this indication.”
 

Response rate, PFS, and OS

Previous studies have indicated that adding an anti-PD-1 drug to lenvatinib achieves superior antitumor activity than either treatment alone, with promising results in phase 1/2b data in pretreated metastatic melanoma.

LEAP-004 therefore enrolled patients with unresectable stage 3 or 4 melanoma, who had disease progression within 12 weeks of their last dose of anti-PD-(L)1 therapy either alone or with a CTLA4 inhibitor. There was no limit on the number of prior treatments.

The patients received pembrolizumab 200 mg IV for up to 35 cycles plus lenvatinib 20 mg daily until progression, unacceptable toxicity, or patient or physician decision.

They were imaged at baseline and every 9 weeks through to week 54, then every 12 weeks until week 102, and then every 24 weeks.

From February to September 2019, 103 patients were enrolled, all of whom received at least one dose of lenvatinib plus pembrolizumab. The median age of the patients was 63 years, and 53.4% were male.

Dr. Arance Fernandez pointed out that this was a high-risk population, with 20.4% having a lactate dehydrogenase level twice the upper limit of normal and 14.6% having brain metastasis, while the median sum of target lesions was 100 mm.

A BRAFv600 mutation was identified in 36.9% of patients, and 64.1% were PD-L1 positive.

Nearly one third (28.2%) had received a prior anti-CTLA4 plus anti-PD-(L)1 combination, and 19.5% had undergone four or more prior lines of therapy.

The overall response rate to lenvatinib plus pembrolizumab was 21.4%, with 1.9% having a complete response and 19.4% a partial response. This was seen across subgroups, including by age and disease stage.

Dr. Arance Fernandez said the overall response rate was even higher in patients who had previously been treated with an anti-CTLA4 plus anti-PD-(L)1 combination, at 31%.

However, Dr. Chmielowski warned that “we must interpret this result with caution since only 29 patients were in this subpopulation.”

The median duration of response (per blinded independent committee review) across the study population was 6.3 months, with 72.6% still responding at 6 months.

The median PFS was 4.2 months with the combination therapy, with 41.7% of patients progression free at 6 months, and 26.2% at 9 months.

Median overall survival was 13.9 months, with 77.3% of patients still alive at 6 months and 65.4% alive at 9 months.

Although 96.1% of patients experienced at least one treatment-related adverse event of any grade, only 44.7% had grade 3 or higher events, and only in 7.8% of cases did that lead to treatment discontinuation.

The most common adverse events were hypertension (56.3%), diarrhea (35.9%), nausea (34%), and hypothyroidism (33%), although, in the vast majority of cases, these events were grade 1 or 2.
 

LEAP presents challenges

Dr. Chmielowski would like to see treatment in this setting individualized somehow.

“It will be also important to come up with personalized immunotherapy so that, based on the mechanism of resistance in patient populations, we would be able to choose the subsequent treatments,” he commented.

Dr. Arance Fernandez explained that lenvatinib inhibits multiple tyrosine kinases involved in angiogenesis, cell proliferation, and immune modulation, and has demonstrated immunomodulatory activity in the tumor microenvironment.

However, Dr. Arance Fernandez noted that, as resistance to immunotherapy is “multifactorial,” it may be that a combination treatment will be more effective in these patients.

The study was funded by Merck. Dr. Arance Fernandez has financial ties to Merck and multiple other drug companies. Dr. Chmielowski has financial ties to Merck Serono and multiple other companies.  

This article first appeared on Medscape.com.

Patients with advanced melanoma who have progressed on anti–programmed death 1/PD-ligand 1 (PD-L1) immunotherapy could substantially extend their overall survival (OS) with a combination of the tyrosine kinase inhibitor lenvatinib (Lenvima) and pembrolizumab (Keytruda), suggests an open-label, single arm study.

The research was presented Sept. 19 at the European Society for Medical Oncology Virtual Congress 2020.

In LEAP-004 trial, over 100 patients with stage 3 or 4 melanoma who had progressed after immunotherapy were given lenvatinib plus pembrolizumab, which yielded a median progression-free survival (PFS) of more than 4 months and a median OS of more than a year. Median follow-up was 12 months.

Presenting the findings, Ana Maria Arance Fernandez, MD, PhD, Hospital Clínic de Barcelona, Spain, said lenvatinib plus pembrolizumab has “promising” antitumor activity in patients with advanced melanoma with confirmed progression on a PD-1 inhibitor given alone or in combination. “These results are encouraging given the stringent definition of progression on prior anti-PD-1 therapy and the enrollment of poor-risk patients.”

Dr. Arance Fernandez added that “these data support lenvatinib plus pembrolizumab as a potential treatment regimen for this population of high unmet medical need.”

Bartosz Chmielowski, MD, PhD, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, who was not involved in the study, discussed the findings.

He highlighted that the patients were not randomly assigned in LEAP-004, with all of them receiving the same therapy.

Nevertheless, the response rate was “quite impressive for this patient population.”

He also drew comparison with previous data with nivolumab (Opdivo) alone or in combination with ipilimumab (Yervoy) in a similar population, noting that the overall survival was less than half that seen in the current trial, “which makes these results even more important.”

“It tells us that this combination might be an option with disease progression on anti-PD-1,” Dr. Chmielowski noted.

Dr. Arance Fernandez pointed out that patients with advanced melanoma who progress on standard-of-care treatment with anti-PD-1 therapy or a cytotoxic T-lymphocyte–associated protein 4 (CTLA4) inhibitor plus anti-PD-1 “have very limited therapeutic options available and there is no approved regimen in this indication.”
 

Response rate, PFS, and OS

Previous studies have indicated that adding an anti-PD-1 drug to lenvatinib achieves superior antitumor activity than either treatment alone, with promising results in phase 1/2b data in pretreated metastatic melanoma.

LEAP-004 therefore enrolled patients with unresectable stage 3 or 4 melanoma, who had disease progression within 12 weeks of their last dose of anti-PD-(L)1 therapy either alone or with a CTLA4 inhibitor. There was no limit on the number of prior treatments.

The patients received pembrolizumab 200 mg IV for up to 35 cycles plus lenvatinib 20 mg daily until progression, unacceptable toxicity, or patient or physician decision.

They were imaged at baseline and every 9 weeks through to week 54, then every 12 weeks until week 102, and then every 24 weeks.

From February to September 2019, 103 patients were enrolled, all of whom received at least one dose of lenvatinib plus pembrolizumab. The median age of the patients was 63 years, and 53.4% were male.

Dr. Arance Fernandez pointed out that this was a high-risk population, with 20.4% having a lactate dehydrogenase level twice the upper limit of normal and 14.6% having brain metastasis, while the median sum of target lesions was 100 mm.

A BRAFv600 mutation was identified in 36.9% of patients, and 64.1% were PD-L1 positive.

Nearly one third (28.2%) had received a prior anti-CTLA4 plus anti-PD-(L)1 combination, and 19.5% had undergone four or more prior lines of therapy.

The overall response rate to lenvatinib plus pembrolizumab was 21.4%, with 1.9% having a complete response and 19.4% a partial response. This was seen across subgroups, including by age and disease stage.

Dr. Arance Fernandez said the overall response rate was even higher in patients who had previously been treated with an anti-CTLA4 plus anti-PD-(L)1 combination, at 31%.

However, Dr. Chmielowski warned that “we must interpret this result with caution since only 29 patients were in this subpopulation.”

The median duration of response (per blinded independent committee review) across the study population was 6.3 months, with 72.6% still responding at 6 months.

The median PFS was 4.2 months with the combination therapy, with 41.7% of patients progression free at 6 months, and 26.2% at 9 months.

Median overall survival was 13.9 months, with 77.3% of patients still alive at 6 months and 65.4% alive at 9 months.

Although 96.1% of patients experienced at least one treatment-related adverse event of any grade, only 44.7% had grade 3 or higher events, and only in 7.8% of cases did that lead to treatment discontinuation.

The most common adverse events were hypertension (56.3%), diarrhea (35.9%), nausea (34%), and hypothyroidism (33%), although, in the vast majority of cases, these events were grade 1 or 2.
 

LEAP presents challenges

Dr. Chmielowski would like to see treatment in this setting individualized somehow.

“It will be also important to come up with personalized immunotherapy so that, based on the mechanism of resistance in patient populations, we would be able to choose the subsequent treatments,” he commented.

Dr. Arance Fernandez explained that lenvatinib inhibits multiple tyrosine kinases involved in angiogenesis, cell proliferation, and immune modulation, and has demonstrated immunomodulatory activity in the tumor microenvironment.

However, Dr. Arance Fernandez noted that, as resistance to immunotherapy is “multifactorial,” it may be that a combination treatment will be more effective in these patients.

The study was funded by Merck. Dr. Arance Fernandez has financial ties to Merck and multiple other drug companies. Dr. Chmielowski has financial ties to Merck Serono and multiple other companies.  

This article first appeared on Medscape.com.

Patients with advanced melanoma who have progressed on anti–programmed death 1/PD-ligand 1 (PD-L1) immunotherapy could substantially extend their overall survival (OS) with a combination of the tyrosine kinase inhibitor lenvatinib (Lenvima) and pembrolizumab (Keytruda), suggests an open-label, single arm study.

The research was presented Sept. 19 at the European Society for Medical Oncology Virtual Congress 2020.

In LEAP-004 trial, over 100 patients with stage 3 or 4 melanoma who had progressed after immunotherapy were given lenvatinib plus pembrolizumab, which yielded a median progression-free survival (PFS) of more than 4 months and a median OS of more than a year. Median follow-up was 12 months.

Presenting the findings, Ana Maria Arance Fernandez, MD, PhD, Hospital Clínic de Barcelona, Spain, said lenvatinib plus pembrolizumab has “promising” antitumor activity in patients with advanced melanoma with confirmed progression on a PD-1 inhibitor given alone or in combination. “These results are encouraging given the stringent definition of progression on prior anti-PD-1 therapy and the enrollment of poor-risk patients.”

Dr. Arance Fernandez added that “these data support lenvatinib plus pembrolizumab as a potential treatment regimen for this population of high unmet medical need.”

Bartosz Chmielowski, MD, PhD, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, who was not involved in the study, discussed the findings.

He highlighted that the patients were not randomly assigned in LEAP-004, with all of them receiving the same therapy.

Nevertheless, the response rate was “quite impressive for this patient population.”

He also drew comparison with previous data with nivolumab (Opdivo) alone or in combination with ipilimumab (Yervoy) in a similar population, noting that the overall survival was less than half that seen in the current trial, “which makes these results even more important.”

“It tells us that this combination might be an option with disease progression on anti-PD-1,” Dr. Chmielowski noted.

Dr. Arance Fernandez pointed out that patients with advanced melanoma who progress on standard-of-care treatment with anti-PD-1 therapy or a cytotoxic T-lymphocyte–associated protein 4 (CTLA4) inhibitor plus anti-PD-1 “have very limited therapeutic options available and there is no approved regimen in this indication.”
 

Response rate, PFS, and OS

Previous studies have indicated that adding an anti-PD-1 drug to lenvatinib achieves superior antitumor activity than either treatment alone, with promising results in phase 1/2b data in pretreated metastatic melanoma.

LEAP-004 therefore enrolled patients with unresectable stage 3 or 4 melanoma, who had disease progression within 12 weeks of their last dose of anti-PD-(L)1 therapy either alone or with a CTLA4 inhibitor. There was no limit on the number of prior treatments.

The patients received pembrolizumab 200 mg IV for up to 35 cycles plus lenvatinib 20 mg daily until progression, unacceptable toxicity, or patient or physician decision.

They were imaged at baseline and every 9 weeks through to week 54, then every 12 weeks until week 102, and then every 24 weeks.

From February to September 2019, 103 patients were enrolled, all of whom received at least one dose of lenvatinib plus pembrolizumab. The median age of the patients was 63 years, and 53.4% were male.

Dr. Arance Fernandez pointed out that this was a high-risk population, with 20.4% having a lactate dehydrogenase level twice the upper limit of normal and 14.6% having brain metastasis, while the median sum of target lesions was 100 mm.

A BRAFv600 mutation was identified in 36.9% of patients, and 64.1% were PD-L1 positive.

Nearly one third (28.2%) had received a prior anti-CTLA4 plus anti-PD-(L)1 combination, and 19.5% had undergone four or more prior lines of therapy.

The overall response rate to lenvatinib plus pembrolizumab was 21.4%, with 1.9% having a complete response and 19.4% a partial response. This was seen across subgroups, including by age and disease stage.

Dr. Arance Fernandez said the overall response rate was even higher in patients who had previously been treated with an anti-CTLA4 plus anti-PD-(L)1 combination, at 31%.

However, Dr. Chmielowski warned that “we must interpret this result with caution since only 29 patients were in this subpopulation.”

The median duration of response (per blinded independent committee review) across the study population was 6.3 months, with 72.6% still responding at 6 months.

The median PFS was 4.2 months with the combination therapy, with 41.7% of patients progression free at 6 months, and 26.2% at 9 months.

Median overall survival was 13.9 months, with 77.3% of patients still alive at 6 months and 65.4% alive at 9 months.

Although 96.1% of patients experienced at least one treatment-related adverse event of any grade, only 44.7% had grade 3 or higher events, and only in 7.8% of cases did that lead to treatment discontinuation.

The most common adverse events were hypertension (56.3%), diarrhea (35.9%), nausea (34%), and hypothyroidism (33%), although, in the vast majority of cases, these events were grade 1 or 2.
 

LEAP presents challenges

Dr. Chmielowski would like to see treatment in this setting individualized somehow.

“It will be also important to come up with personalized immunotherapy so that, based on the mechanism of resistance in patient populations, we would be able to choose the subsequent treatments,” he commented.

Dr. Arance Fernandez explained that lenvatinib inhibits multiple tyrosine kinases involved in angiogenesis, cell proliferation, and immune modulation, and has demonstrated immunomodulatory activity in the tumor microenvironment.

However, Dr. Arance Fernandez noted that, as resistance to immunotherapy is “multifactorial,” it may be that a combination treatment will be more effective in these patients.

The study was funded by Merck. Dr. Arance Fernandez has financial ties to Merck and multiple other drug companies. Dr. Chmielowski has financial ties to Merck Serono and multiple other companies.  

This article first appeared on Medscape.com.

The companies behind three major COVID-19 vaccines in development released the protocols of their trials, outlining their expectations for participant enrollment, benchmarks for vaccine efficacy, and more details about the makeup of each product.

Typically, manufacturers guard the specifics of preclinical vaccine trials. This rare move follows calls for greater transparency. For example, the American Medical Association wrote a letter in late August asking the Food and Drug Administration to keep physicians informed of their COVID-19 vaccine review process.

On September 17, ModernaTx released the phase 3 trial protocol for its mRNA-1273 SARS-CoV-2 vaccine. In short order, on September 19, Pfizer/BioNTech shared their phase 1/2/3 trial vaccine protocol. AstraZeneca, which is developing a vaccine along with Oxford University, also released its protocol.

The AstraZeneca vaccine trial made headlines recently for having to be temporarily halted because of unexpected illnesses that arose in two participants, according to the New York Times and other sources.

“I applaud the release of the clinical trial protocols by the companies. The public trust in any COVID-19 vaccine is paramount, especially given the fast timeline and perceived political pressures of these candidates,” Robert Kruse, MD, PhD, told Medscape Medical News when asked to comment.
 

AstraZeneca takes a shot at transparency

The three primary objectives of the AstraZeneca AZD1222 trial outlined in the 110-page protocol include estimating the efficacy, safety, tolerability, and reactogenicity associated with two intramuscular doses of the vaccine in comparison with placebo in adults.

The projected enrollment is 30,000 participants, and the estimated primary completion date is Dec. 2, 2020, according to information on clinicaltrials.gov.

“Given the unprecedented global impact of the coronavirus pandemic and the need for public information, AstraZeneca has published the detailed protocol and design of our AZD1222 clinical trial,” the company said in a statement. “As with most clinical development, protocols are not typically shared publicly due to the importance of maintaining confidentiality and integrity of trials.

“AstraZeneca continues to work with industry peers to ensure a consistent approach to sharing timely clinical trial information,” the company added.
 

Moderna methodology

The ModernaTX 135-page protocol outlines the primary trial objectives of evaluating efficacy, safety, and reactogenicity of two injections of the vaccine administered 28 days apart. Researchers also plan to randomly assign 30,000 adults to receive either vaccine or placebo. The estimated primary completion date is Oct. 27, 2022.

A statement that was requested from ModernaTX was not received by press time.
 

Pfizer protocol

In the Pfizer/BioNTech vaccine trial, researchers plan to evaluate different doses in different age groups in a multistep protocol. The trial features 20 primary safety objectives, which include reporting adverse events and serious adverse events, including any local or systemic events.

Efficacy endpoints are secondary objectives. The estimated enrollment is 29,481 adults; the estimated primary completion date is April 19, 2021.

“Pfizer and BioNTech recognize that the COVID-19 pandemic is a unique circumstance, and the need for transparency is clear,” Pfizer spokesperson Sharon Castillo told Medscape Medical News. By making the full protocol available, “we believe this will reinforce our long-standing commitment to scientific and regulatory rigor that benefits patients,” she said.

“Based on current infection rates, Pfizer and BioNTech continue to expect that a conclusive read-out on efficacy is likely by the end of October. Neither Pfizer nor the FDA can move faster than the data we are generating through our clinical trial,” Castillo said.

If clinical work and regulatory approval or authorization proceed as planned, Pfizer and BioNTech expect to supply up to 100 million doses worldwide by the end of 2020 and approximately 1.3 billion doses worldwide by the end of 2021.

Pfizer is not willing to sacrifice safety and efficacy in the name of expediency, Castillo said. “We will not cut corners in this pursuit. Patient safety is our highest priority, and Pfizer will not bring a vaccine to market without adequate evidence of safety and efficacy.”
 

A positive move

“COVID-19 vaccines will only be useful if many people are willing to receive them,” said Kruse, a postgraduate year 3 resident in the Department of Pathology at Johns Hopkins Medicine in Baltimore, Maryland.

“By giving the general public along with other scientists and physicians the opportunity to critique the protocols, everyone can understand what the metrics would be for an early look at efficacy,” Kruse said. He noted that information could help inform a potential FDA emergency use authorization.

Kruse has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The companies behind three major COVID-19 vaccines in development released the protocols of their trials, outlining their expectations for participant enrollment, benchmarks for vaccine efficacy, and more details about the makeup of each product.

Typically, manufacturers guard the specifics of preclinical vaccine trials. This rare move follows calls for greater transparency. For example, the American Medical Association wrote a letter in late August asking the Food and Drug Administration to keep physicians informed of their COVID-19 vaccine review process.

On September 17, ModernaTx released the phase 3 trial protocol for its mRNA-1273 SARS-CoV-2 vaccine. In short order, on September 19, Pfizer/BioNTech shared their phase 1/2/3 trial vaccine protocol. AstraZeneca, which is developing a vaccine along with Oxford University, also released its protocol.

The AstraZeneca vaccine trial made headlines recently for having to be temporarily halted because of unexpected illnesses that arose in two participants, according to the New York Times and other sources.

“I applaud the release of the clinical trial protocols by the companies. The public trust in any COVID-19 vaccine is paramount, especially given the fast timeline and perceived political pressures of these candidates,” Robert Kruse, MD, PhD, told Medscape Medical News when asked to comment.
 

AstraZeneca takes a shot at transparency

The three primary objectives of the AstraZeneca AZD1222 trial outlined in the 110-page protocol include estimating the efficacy, safety, tolerability, and reactogenicity associated with two intramuscular doses of the vaccine in comparison with placebo in adults.

The projected enrollment is 30,000 participants, and the estimated primary completion date is Dec. 2, 2020, according to information on clinicaltrials.gov.

“Given the unprecedented global impact of the coronavirus pandemic and the need for public information, AstraZeneca has published the detailed protocol and design of our AZD1222 clinical trial,” the company said in a statement. “As with most clinical development, protocols are not typically shared publicly due to the importance of maintaining confidentiality and integrity of trials.

“AstraZeneca continues to work with industry peers to ensure a consistent approach to sharing timely clinical trial information,” the company added.
 

Moderna methodology

The ModernaTX 135-page protocol outlines the primary trial objectives of evaluating efficacy, safety, and reactogenicity of two injections of the vaccine administered 28 days apart. Researchers also plan to randomly assign 30,000 adults to receive either vaccine or placebo. The estimated primary completion date is Oct. 27, 2022.

A statement that was requested from ModernaTX was not received by press time.
 

Pfizer protocol

In the Pfizer/BioNTech vaccine trial, researchers plan to evaluate different doses in different age groups in a multistep protocol. The trial features 20 primary safety objectives, which include reporting adverse events and serious adverse events, including any local or systemic events.

Efficacy endpoints are secondary objectives. The estimated enrollment is 29,481 adults; the estimated primary completion date is April 19, 2021.

“Pfizer and BioNTech recognize that the COVID-19 pandemic is a unique circumstance, and the need for transparency is clear,” Pfizer spokesperson Sharon Castillo told Medscape Medical News. By making the full protocol available, “we believe this will reinforce our long-standing commitment to scientific and regulatory rigor that benefits patients,” she said.

“Based on current infection rates, Pfizer and BioNTech continue to expect that a conclusive read-out on efficacy is likely by the end of October. Neither Pfizer nor the FDA can move faster than the data we are generating through our clinical trial,” Castillo said.

If clinical work and regulatory approval or authorization proceed as planned, Pfizer and BioNTech expect to supply up to 100 million doses worldwide by the end of 2020 and approximately 1.3 billion doses worldwide by the end of 2021.

Pfizer is not willing to sacrifice safety and efficacy in the name of expediency, Castillo said. “We will not cut corners in this pursuit. Patient safety is our highest priority, and Pfizer will not bring a vaccine to market without adequate evidence of safety and efficacy.”
 

A positive move

“COVID-19 vaccines will only be useful if many people are willing to receive them,” said Kruse, a postgraduate year 3 resident in the Department of Pathology at Johns Hopkins Medicine in Baltimore, Maryland.

“By giving the general public along with other scientists and physicians the opportunity to critique the protocols, everyone can understand what the metrics would be for an early look at efficacy,” Kruse said. He noted that information could help inform a potential FDA emergency use authorization.

Kruse has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The companies behind three major COVID-19 vaccines in development released the protocols of their trials, outlining their expectations for participant enrollment, benchmarks for vaccine efficacy, and more details about the makeup of each product.

Typically, manufacturers guard the specifics of preclinical vaccine trials. This rare move follows calls for greater transparency. For example, the American Medical Association wrote a letter in late August asking the Food and Drug Administration to keep physicians informed of their COVID-19 vaccine review process.

On September 17, ModernaTx released the phase 3 trial protocol for its mRNA-1273 SARS-CoV-2 vaccine. In short order, on September 19, Pfizer/BioNTech shared their phase 1/2/3 trial vaccine protocol. AstraZeneca, which is developing a vaccine along with Oxford University, also released its protocol.

The AstraZeneca vaccine trial made headlines recently for having to be temporarily halted because of unexpected illnesses that arose in two participants, according to the New York Times and other sources.

“I applaud the release of the clinical trial protocols by the companies. The public trust in any COVID-19 vaccine is paramount, especially given the fast timeline and perceived political pressures of these candidates,” Robert Kruse, MD, PhD, told Medscape Medical News when asked to comment.
 

AstraZeneca takes a shot at transparency

The three primary objectives of the AstraZeneca AZD1222 trial outlined in the 110-page protocol include estimating the efficacy, safety, tolerability, and reactogenicity associated with two intramuscular doses of the vaccine in comparison with placebo in adults.

The projected enrollment is 30,000 participants, and the estimated primary completion date is Dec. 2, 2020, according to information on clinicaltrials.gov.

“Given the unprecedented global impact of the coronavirus pandemic and the need for public information, AstraZeneca has published the detailed protocol and design of our AZD1222 clinical trial,” the company said in a statement. “As with most clinical development, protocols are not typically shared publicly due to the importance of maintaining confidentiality and integrity of trials.

“AstraZeneca continues to work with industry peers to ensure a consistent approach to sharing timely clinical trial information,” the company added.
 

Moderna methodology

The ModernaTX 135-page protocol outlines the primary trial objectives of evaluating efficacy, safety, and reactogenicity of two injections of the vaccine administered 28 days apart. Researchers also plan to randomly assign 30,000 adults to receive either vaccine or placebo. The estimated primary completion date is Oct. 27, 2022.

A statement that was requested from ModernaTX was not received by press time.
 

Pfizer protocol

In the Pfizer/BioNTech vaccine trial, researchers plan to evaluate different doses in different age groups in a multistep protocol. The trial features 20 primary safety objectives, which include reporting adverse events and serious adverse events, including any local or systemic events.

Efficacy endpoints are secondary objectives. The estimated enrollment is 29,481 adults; the estimated primary completion date is April 19, 2021.

“Pfizer and BioNTech recognize that the COVID-19 pandemic is a unique circumstance, and the need for transparency is clear,” Pfizer spokesperson Sharon Castillo told Medscape Medical News. By making the full protocol available, “we believe this will reinforce our long-standing commitment to scientific and regulatory rigor that benefits patients,” she said.

“Based on current infection rates, Pfizer and BioNTech continue to expect that a conclusive read-out on efficacy is likely by the end of October. Neither Pfizer nor the FDA can move faster than the data we are generating through our clinical trial,” Castillo said.

If clinical work and regulatory approval or authorization proceed as planned, Pfizer and BioNTech expect to supply up to 100 million doses worldwide by the end of 2020 and approximately 1.3 billion doses worldwide by the end of 2021.

Pfizer is not willing to sacrifice safety and efficacy in the name of expediency, Castillo said. “We will not cut corners in this pursuit. Patient safety is our highest priority, and Pfizer will not bring a vaccine to market without adequate evidence of safety and efficacy.”
 

A positive move

“COVID-19 vaccines will only be useful if many people are willing to receive them,” said Kruse, a postgraduate year 3 resident in the Department of Pathology at Johns Hopkins Medicine in Baltimore, Maryland.

“By giving the general public along with other scientists and physicians the opportunity to critique the protocols, everyone can understand what the metrics would be for an early look at efficacy,” Kruse said. He noted that information could help inform a potential FDA emergency use authorization.

Kruse has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Hurricane Sally recently crossed the Gulf of Mexico and landed with torrential rainfalls along the Alabama coast. A little rainfall is important for crops; too much leads to devastation. As physicians, we need data in order to help manage patients’ illnesses and to help to keep them healthy. Our fear though is that too much data provided too quickly may have the opposite effect.

Personal monitoring devices

When I bought my first Fitbit 7 years ago, I was enamored with the technology. The Fitbit was little more than a step tracker, yet I proudly wore its black rubber strap on my wrist. It was my first foray into wearable technology, and it felt quite empowering to have an objective way to track my fitness beyond just using my bathroom scale. Now less than a decade later, that Fitbit looks archaic in comparison with the wrist-top technology currently available.

As I write this, the world’s largest technology company is in the process of releasing its sixth-generation Apple Watch. In addition to acting as a smartphone, this new device, which is barely larger than a postage stamp, offers GPS-based movement tracking, the ability to detect falls, continuous heart rate monitoring, a built-in EKG capable of diagnosing atrial fibrillation, and an oxygen saturation sensor. These features weren’t added thoughtlessly. Apple is marketing this as a health-focused device, with their primary advertising campaign claiming that “the future of health is on your wrist,” and they aren’t the only company making this play.

Along with Apple, Samsung, Withings, Fitbit, and other companies continue to bring products to market that monitor our activity and provide new insights into our health. Typically linked to smartphone-based apps, these devices record all of their measurements for later review, while software helps interpret the findings to make them actionable. From heart rate tracking to sleep analysis, these options now provide access to volumes of data that promise to improve our wellness and change our lives. Of course, those promises will only be fulfilled if our behavior is altered as a consequence of having more detailed information. Whether that will happen remains to be seen.
 

Health system–linked devices

Major advancements in medical monitoring technology are now enabling physicians to get much deeper insight into their patients’ health status. Internet-connected scales, blood pressure cuffs, and exercise equipment offer the ability to upload information into patient portals and integrate that information into EHRs. New devices provide access to information that previously was impossible to obtain. For example, wearable continuous blood glucose monitors, such as the FreeStyle Libre or DexCom’s G6, allow patients and physicians to follow blood sugar readings 24 hours a day. This provides unprecedented awareness of diabetes control and relieves the pain and inconvenience of finger sticks and blood draws. It also aids with compliance because patients don’t need to remember to check their sugar levels on a schedule.

Other compliance-boosting breakthroughs, such as Bluetooth-enabled asthma inhalers and cellular-connected continuous positive airway pressure machines, assist patients with managing chronic respiratory conditions. Many companies are developing technologies to manage acute conditions as well. One such company, an on-demand telemedicine provider called TytoCare, has developed a $299 suite of instruments that includes a digital stethoscope, thermometer, and camera-based otoscope. In concert with a virtual visit, their providers can remotely use these tools to examine and assess sick individuals. This virtual “laying on of hands” may have sounded like science fiction and likely would have been rejected by patients just a few years ago. Now it is becoming commonplace and will soon be an expectation of many seeking care.

We as clinicians need to learn how best to adapt to the new world and integrate these new sources of health data into our practices. But if we are to be successful, everyone must acknowledge that this revolution in health care brings many challenges along with it. One of those is the deluge of data that connected devices provide.
 

Information overload

There is such a thing as “too much of a good thing.” Described by journalist David Shenk as “data smog” in his 1997 book of the same name, the idea is clear: There is only so much information we can assimilate.

Even after years of using EHRs and with government-implemented incentives that promote “meaningful use,” physicians are still struggling with EHRs. Additionally, many have expressed frustration with the connectedness that EHRs provide and lament their inability to ever really “leave the office.” As more and more data become available to physicians, the challenge of how to assimilate and act on those data will continue to grow. The addition of patient-provided health statistics will only make information overload worse, with clinicians will feeling an ever-growing burden to know, understand, and act on this information.

Unless we develop systems to sort, filter, and prioritize the flow of information, there is potential for liability from not acting on the amount of virtual information doctors receive. This new risk for already fatigued and overburdened physicians combined with an increase in the amount of virtual information at doctors’ fingertips may lead to the value of patient data being lost.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

Hurricane Sally recently crossed the Gulf of Mexico and landed with torrential rainfalls along the Alabama coast. A little rainfall is important for crops; too much leads to devastation. As physicians, we need data in order to help manage patients’ illnesses and to help to keep them healthy. Our fear though is that too much data provided too quickly may have the opposite effect.

Personal monitoring devices

When I bought my first Fitbit 7 years ago, I was enamored with the technology. The Fitbit was little more than a step tracker, yet I proudly wore its black rubber strap on my wrist. It was my first foray into wearable technology, and it felt quite empowering to have an objective way to track my fitness beyond just using my bathroom scale. Now less than a decade later, that Fitbit looks archaic in comparison with the wrist-top technology currently available.

As I write this, the world’s largest technology company is in the process of releasing its sixth-generation Apple Watch. In addition to acting as a smartphone, this new device, which is barely larger than a postage stamp, offers GPS-based movement tracking, the ability to detect falls, continuous heart rate monitoring, a built-in EKG capable of diagnosing atrial fibrillation, and an oxygen saturation sensor. These features weren’t added thoughtlessly. Apple is marketing this as a health-focused device, with their primary advertising campaign claiming that “the future of health is on your wrist,” and they aren’t the only company making this play.

Along with Apple, Samsung, Withings, Fitbit, and other companies continue to bring products to market that monitor our activity and provide new insights into our health. Typically linked to smartphone-based apps, these devices record all of their measurements for later review, while software helps interpret the findings to make them actionable. From heart rate tracking to sleep analysis, these options now provide access to volumes of data that promise to improve our wellness and change our lives. Of course, those promises will only be fulfilled if our behavior is altered as a consequence of having more detailed information. Whether that will happen remains to be seen.
 

Health system–linked devices

Major advancements in medical monitoring technology are now enabling physicians to get much deeper insight into their patients’ health status. Internet-connected scales, blood pressure cuffs, and exercise equipment offer the ability to upload information into patient portals and integrate that information into EHRs. New devices provide access to information that previously was impossible to obtain. For example, wearable continuous blood glucose monitors, such as the FreeStyle Libre or DexCom’s G6, allow patients and physicians to follow blood sugar readings 24 hours a day. This provides unprecedented awareness of diabetes control and relieves the pain and inconvenience of finger sticks and blood draws. It also aids with compliance because patients don’t need to remember to check their sugar levels on a schedule.

Other compliance-boosting breakthroughs, such as Bluetooth-enabled asthma inhalers and cellular-connected continuous positive airway pressure machines, assist patients with managing chronic respiratory conditions. Many companies are developing technologies to manage acute conditions as well. One such company, an on-demand telemedicine provider called TytoCare, has developed a $299 suite of instruments that includes a digital stethoscope, thermometer, and camera-based otoscope. In concert with a virtual visit, their providers can remotely use these tools to examine and assess sick individuals. This virtual “laying on of hands” may have sounded like science fiction and likely would have been rejected by patients just a few years ago. Now it is becoming commonplace and will soon be an expectation of many seeking care.

We as clinicians need to learn how best to adapt to the new world and integrate these new sources of health data into our practices. But if we are to be successful, everyone must acknowledge that this revolution in health care brings many challenges along with it. One of those is the deluge of data that connected devices provide.
 

Information overload

There is such a thing as “too much of a good thing.” Described by journalist David Shenk as “data smog” in his 1997 book of the same name, the idea is clear: There is only so much information we can assimilate.

Even after years of using EHRs and with government-implemented incentives that promote “meaningful use,” physicians are still struggling with EHRs. Additionally, many have expressed frustration with the connectedness that EHRs provide and lament their inability to ever really “leave the office.” As more and more data become available to physicians, the challenge of how to assimilate and act on those data will continue to grow. The addition of patient-provided health statistics will only make information overload worse, with clinicians will feeling an ever-growing burden to know, understand, and act on this information.

Unless we develop systems to sort, filter, and prioritize the flow of information, there is potential for liability from not acting on the amount of virtual information doctors receive. This new risk for already fatigued and overburdened physicians combined with an increase in the amount of virtual information at doctors’ fingertips may lead to the value of patient data being lost.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

Hurricane Sally recently crossed the Gulf of Mexico and landed with torrential rainfalls along the Alabama coast. A little rainfall is important for crops; too much leads to devastation. As physicians, we need data in order to help manage patients’ illnesses and to help to keep them healthy. Our fear though is that too much data provided too quickly may have the opposite effect.

Personal monitoring devices

When I bought my first Fitbit 7 years ago, I was enamored with the technology. The Fitbit was little more than a step tracker, yet I proudly wore its black rubber strap on my wrist. It was my first foray into wearable technology, and it felt quite empowering to have an objective way to track my fitness beyond just using my bathroom scale. Now less than a decade later, that Fitbit looks archaic in comparison with the wrist-top technology currently available.

As I write this, the world’s largest technology company is in the process of releasing its sixth-generation Apple Watch. In addition to acting as a smartphone, this new device, which is barely larger than a postage stamp, offers GPS-based movement tracking, the ability to detect falls, continuous heart rate monitoring, a built-in EKG capable of diagnosing atrial fibrillation, and an oxygen saturation sensor. These features weren’t added thoughtlessly. Apple is marketing this as a health-focused device, with their primary advertising campaign claiming that “the future of health is on your wrist,” and they aren’t the only company making this play.

Along with Apple, Samsung, Withings, Fitbit, and other companies continue to bring products to market that monitor our activity and provide new insights into our health. Typically linked to smartphone-based apps, these devices record all of their measurements for later review, while software helps interpret the findings to make them actionable. From heart rate tracking to sleep analysis, these options now provide access to volumes of data that promise to improve our wellness and change our lives. Of course, those promises will only be fulfilled if our behavior is altered as a consequence of having more detailed information. Whether that will happen remains to be seen.
 

Health system–linked devices

Major advancements in medical monitoring technology are now enabling physicians to get much deeper insight into their patients’ health status. Internet-connected scales, blood pressure cuffs, and exercise equipment offer the ability to upload information into patient portals and integrate that information into EHRs. New devices provide access to information that previously was impossible to obtain. For example, wearable continuous blood glucose monitors, such as the FreeStyle Libre or DexCom’s G6, allow patients and physicians to follow blood sugar readings 24 hours a day. This provides unprecedented awareness of diabetes control and relieves the pain and inconvenience of finger sticks and blood draws. It also aids with compliance because patients don’t need to remember to check their sugar levels on a schedule.

Other compliance-boosting breakthroughs, such as Bluetooth-enabled asthma inhalers and cellular-connected continuous positive airway pressure machines, assist patients with managing chronic respiratory conditions. Many companies are developing technologies to manage acute conditions as well. One such company, an on-demand telemedicine provider called TytoCare, has developed a $299 suite of instruments that includes a digital stethoscope, thermometer, and camera-based otoscope. In concert with a virtual visit, their providers can remotely use these tools to examine and assess sick individuals. This virtual “laying on of hands” may have sounded like science fiction and likely would have been rejected by patients just a few years ago. Now it is becoming commonplace and will soon be an expectation of many seeking care.

We as clinicians need to learn how best to adapt to the new world and integrate these new sources of health data into our practices. But if we are to be successful, everyone must acknowledge that this revolution in health care brings many challenges along with it. One of those is the deluge of data that connected devices provide.
 

Information overload

There is such a thing as “too much of a good thing.” Described by journalist David Shenk as “data smog” in his 1997 book of the same name, the idea is clear: There is only so much information we can assimilate.

Even after years of using EHRs and with government-implemented incentives that promote “meaningful use,” physicians are still struggling with EHRs. Additionally, many have expressed frustration with the connectedness that EHRs provide and lament their inability to ever really “leave the office.” As more and more data become available to physicians, the challenge of how to assimilate and act on those data will continue to grow. The addition of patient-provided health statistics will only make information overload worse, with clinicians will feeling an ever-growing burden to know, understand, and act on this information.

Unless we develop systems to sort, filter, and prioritize the flow of information, there is potential for liability from not acting on the amount of virtual information doctors receive. This new risk for already fatigued and overburdened physicians combined with an increase in the amount of virtual information at doctors’ fingertips may lead to the value of patient data being lost.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of baricitinib tablets for adults with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

Baricitinib (Olumiant) is already approved in the European Union and the United States to treat moderate to severe active rheumatoid arthritis.

If approved in Europe, it will be the first Janus kinase (JAK) inhibitor and first oral medication indicated to treat patients with AD.

The CHMP’s positive opinion on baricitinib for AD was based on three phase 3, randomized, double-blind, placebo-controlled studies where the JAK inhibitor was used alone or in combination with topical treatments in adults with moderate to severe AD for whom topical treatments were insufficient or not tolerated. In all three studies, baricitinib was shown to be more effective than placebo in achieving skin that is “clear” or “almost clear” at 16 weeks.

“Patients living with AD face difficulties on a daily basis, and this CHMP opinion marks an important milestone in providing adult AD patients with a new potential treatment option,” Thomas Bieber, MD, PhD, professor of dermatology and allergy, University of Bonn (Germany), said in a company news release.

The most common side effects with baricitinib in clinical trials include increased LDL cholesterol, upper respiratory tract infections, and headache.

Patients receiving baricitinib, particularly in combination with immunosuppressants, are at risk of developing serious infections that may lead to hospitalization or death. If a serious infection develops, baricitinib should be stopped until the infection is controlled.

The CHMP’s positive opinion will be sent to the European Commission, which will adopt a final decision regarding an European Union–wide marketing authorization. Once granted, each member state will make decisions about price and reimbursement, taking into account the potential role/use of baricitinib in the context of that country’s national health system.

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

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of baricitinib tablets for adults with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

Baricitinib (Olumiant) is already approved in the European Union and the United States to treat moderate to severe active rheumatoid arthritis.

If approved in Europe, it will be the first Janus kinase (JAK) inhibitor and first oral medication indicated to treat patients with AD.

The CHMP’s positive opinion on baricitinib for AD was based on three phase 3, randomized, double-blind, placebo-controlled studies where the JAK inhibitor was used alone or in combination with topical treatments in adults with moderate to severe AD for whom topical treatments were insufficient or not tolerated. In all three studies, baricitinib was shown to be more effective than placebo in achieving skin that is “clear” or “almost clear” at 16 weeks.

“Patients living with AD face difficulties on a daily basis, and this CHMP opinion marks an important milestone in providing adult AD patients with a new potential treatment option,” Thomas Bieber, MD, PhD, professor of dermatology and allergy, University of Bonn (Germany), said in a company news release.

The most common side effects with baricitinib in clinical trials include increased LDL cholesterol, upper respiratory tract infections, and headache.

Patients receiving baricitinib, particularly in combination with immunosuppressants, are at risk of developing serious infections that may lead to hospitalization or death. If a serious infection develops, baricitinib should be stopped until the infection is controlled.

The CHMP’s positive opinion will be sent to the European Commission, which will adopt a final decision regarding an European Union–wide marketing authorization. Once granted, each member state will make decisions about price and reimbursement, taking into account the potential role/use of baricitinib in the context of that country’s national health system.

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

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of baricitinib tablets for adults with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

Baricitinib (Olumiant) is already approved in the European Union and the United States to treat moderate to severe active rheumatoid arthritis.

If approved in Europe, it will be the first Janus kinase (JAK) inhibitor and first oral medication indicated to treat patients with AD.

The CHMP’s positive opinion on baricitinib for AD was based on three phase 3, randomized, double-blind, placebo-controlled studies where the JAK inhibitor was used alone or in combination with topical treatments in adults with moderate to severe AD for whom topical treatments were insufficient or not tolerated. In all three studies, baricitinib was shown to be more effective than placebo in achieving skin that is “clear” or “almost clear” at 16 weeks.

“Patients living with AD face difficulties on a daily basis, and this CHMP opinion marks an important milestone in providing adult AD patients with a new potential treatment option,” Thomas Bieber, MD, PhD, professor of dermatology and allergy, University of Bonn (Germany), said in a company news release.

The most common side effects with baricitinib in clinical trials include increased LDL cholesterol, upper respiratory tract infections, and headache.

Patients receiving baricitinib, particularly in combination with immunosuppressants, are at risk of developing serious infections that may lead to hospitalization or death. If a serious infection develops, baricitinib should be stopped until the infection is controlled.

The CHMP’s positive opinion will be sent to the European Commission, which will adopt a final decision regarding an European Union–wide marketing authorization. Once granted, each member state will make decisions about price and reimbursement, taking into account the potential role/use of baricitinib in the context of that country’s national health system.

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

Adding palbociclib to letrozole significantly prolonged progression-free survival (PFS) in a phase 2 trial of patients with advanced or recurrent estrogen receptor (ER)–positive endometrial cancer.

This was the first randomized trial to evaluate the efficacy of a CDK4/6 inhibitor in combination with an aromatase inhibitor in patients with advanced or recurrent ER-positive endometrial cancer, noted study investigator Mansoor Raza Mirza, MD, PhD, of Rigshospitalet Copenhagen University Hospital.

Dr. Mirza presented results from this study, ENGOT-EN3-NSGO/PALEO, at the European Society for Medical Oncology Virtual Congress 2020.

Palbociclib is a selective inhibitor of CDK4/, both of which are involved in cell-cycle transitions, Dr. Mirza explained. He observed that endometrial endometrioid adenocarcinomas are hormone dependent, and endocrine treatment with an aromatase inhibitor is well established. Palbociclib has been shown to be superior, when combined with letrozole, to letrozole alone in ER-positive breast cancer.

For the ENGOT-EN3-NSGO/PALEO study, investigators enrolled 77 patients with ER-positive advanced/recurrent endometrial cancer. Patients had received at least one prior systemic therapy, no prior endocrine therapy (except medroxyprogesterone acetate and megestrol acetate), and no prior CDK inhibitor.

Patients were randomized 1:1 to receive oral letrozole (2.5 mg on days 1-28) and either palbociclib (125 mg on days 1-21) or placebo (125 mg on days 1-21) in a 28-day cycle until progression. Baseline characteristics were similar between the treatment arms.
 

Efficacy

Of the 77 patients enrolled, 73 were evaluable. The primary endpoint was PFS.

The median PFS in the intention-to-treat population was 3.0 months in the placebo arm and 8.3 months in the palbociclib arm (hazard ratio, 0.56; 95% confidence interval, 0.32-0.98; P = .0376).

Looking at stratification factors, PFS was higher in the palbociclib arm among the large majority (about 85%) of patients who had received no prior medroxyprogesterone acetate or megestrol acetate (HR, 0.55; 95% CI, 0.29-01.04; P = .0615) and among patients with relapsed disease (HR, 0.61; 95% CI, 0.34-1.09; P = .0916).

The disease control rate at 24 weeks, a secondary endpoint, was 63.6% in the palbociclib arm and 37.8% in the placebo arm.
 

Safety

Adverse events were more frequent in the palbociclib arm, with neutropenia being the most common.

Rates of adverse event–related dose reduction (to 100 mg or 75 mg) were 36% in the palbociclib arm and 3% in the placebo arm.

Adverse event–related discontinuation rates were 25% and 19% for palbociclib and letrozole, respectively, in the palbociclib arm and 14% and 11% for placebo and letrozole, respectively, in the placebo arm.

“The toxicity of palbociclib plus letrozole combination therapy was manageable, with most patients remaining on treatment until disease progression,” Dr. Mirza said.

He noted that an analysis of patient-reported outcomes revealed no detrimental effect on quality of life with the combination therapy.
 

Next steps

“Compared with placebo plus letrozole, the combination of palbociclib plus letrozole demonstrated clinically meaningful improvement in PFS,” Dr. Mirza said. “These results merit a phase 3 validation trial.”

“There is a huge rationale for using this drug in endometrial cancer,” commented study discussant Domenica Lorusso, MD, PhD, of Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Catholic University of Sacred Hearth in Rome.

Dr. Lorusso said hormone receptor expression, which has been identified as a strong predictor of CDK4/6 inhibitor activity, is present in up to 90% of patients with type 1 and in about 65% of patients with type 2 endometrial cancer.

Response rates, in experience with aromatase inhibitors, have been “quite disappointing, in the 10%-20% range,” Dr. Lorusso said, with “dismal prognosis” and guidelines stating that “no standard second-line treatment has been identified.”

This research was sponsored by investigators, but Pfizer provided a study grant. Dr. Mirza disclosed relationships with Pfizer, AstraZeneca, Biocad, Clovis Oncology, Genmab, Karyopharm Therapeutics, Merck, Oncology Adventure, Roche, Seattle Genetics, Sera Prognostics, Sotio, GlaxoSmithKline, Zai Lab, and Boehringer Ingelheim. Dr. Lorusso disclosed relationships with AstraZeneca, Biocad, Clovis Oncology, Genmab, Merck, Roche, Tesaro, Amgen, Immunogen, and Pharma Mar.

SOURCE: Mirza MR et al. ESMO 2020, Abstract LBA28.

Adding palbociclib to letrozole significantly prolonged progression-free survival (PFS) in a phase 2 trial of patients with advanced or recurrent estrogen receptor (ER)–positive endometrial cancer.

This was the first randomized trial to evaluate the efficacy of a CDK4/6 inhibitor in combination with an aromatase inhibitor in patients with advanced or recurrent ER-positive endometrial cancer, noted study investigator Mansoor Raza Mirza, MD, PhD, of Rigshospitalet Copenhagen University Hospital.

Dr. Mirza presented results from this study, ENGOT-EN3-NSGO/PALEO, at the European Society for Medical Oncology Virtual Congress 2020.

Palbociclib is a selective inhibitor of CDK4/, both of which are involved in cell-cycle transitions, Dr. Mirza explained. He observed that endometrial endometrioid adenocarcinomas are hormone dependent, and endocrine treatment with an aromatase inhibitor is well established. Palbociclib has been shown to be superior, when combined with letrozole, to letrozole alone in ER-positive breast cancer.

For the ENGOT-EN3-NSGO/PALEO study, investigators enrolled 77 patients with ER-positive advanced/recurrent endometrial cancer. Patients had received at least one prior systemic therapy, no prior endocrine therapy (except medroxyprogesterone acetate and megestrol acetate), and no prior CDK inhibitor.

Patients were randomized 1:1 to receive oral letrozole (2.5 mg on days 1-28) and either palbociclib (125 mg on days 1-21) or placebo (125 mg on days 1-21) in a 28-day cycle until progression. Baseline characteristics were similar between the treatment arms.
 

Efficacy

Of the 77 patients enrolled, 73 were evaluable. The primary endpoint was PFS.

The median PFS in the intention-to-treat population was 3.0 months in the placebo arm and 8.3 months in the palbociclib arm (hazard ratio, 0.56; 95% confidence interval, 0.32-0.98; P = .0376).

Looking at stratification factors, PFS was higher in the palbociclib arm among the large majority (about 85%) of patients who had received no prior medroxyprogesterone acetate or megestrol acetate (HR, 0.55; 95% CI, 0.29-01.04; P = .0615) and among patients with relapsed disease (HR, 0.61; 95% CI, 0.34-1.09; P = .0916).

The disease control rate at 24 weeks, a secondary endpoint, was 63.6% in the palbociclib arm and 37.8% in the placebo arm.
 

Safety

Adverse events were more frequent in the palbociclib arm, with neutropenia being the most common.

Rates of adverse event–related dose reduction (to 100 mg or 75 mg) were 36% in the palbociclib arm and 3% in the placebo arm.

Adverse event–related discontinuation rates were 25% and 19% for palbociclib and letrozole, respectively, in the palbociclib arm and 14% and 11% for placebo and letrozole, respectively, in the placebo arm.

“The toxicity of palbociclib plus letrozole combination therapy was manageable, with most patients remaining on treatment until disease progression,” Dr. Mirza said.

He noted that an analysis of patient-reported outcomes revealed no detrimental effect on quality of life with the combination therapy.
 

Next steps

“Compared with placebo plus letrozole, the combination of palbociclib plus letrozole demonstrated clinically meaningful improvement in PFS,” Dr. Mirza said. “These results merit a phase 3 validation trial.”

“There is a huge rationale for using this drug in endometrial cancer,” commented study discussant Domenica Lorusso, MD, PhD, of Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Catholic University of Sacred Hearth in Rome.

Dr. Lorusso said hormone receptor expression, which has been identified as a strong predictor of CDK4/6 inhibitor activity, is present in up to 90% of patients with type 1 and in about 65% of patients with type 2 endometrial cancer.

Response rates, in experience with aromatase inhibitors, have been “quite disappointing, in the 10%-20% range,” Dr. Lorusso said, with “dismal prognosis” and guidelines stating that “no standard second-line treatment has been identified.”

This research was sponsored by investigators, but Pfizer provided a study grant. Dr. Mirza disclosed relationships with Pfizer, AstraZeneca, Biocad, Clovis Oncology, Genmab, Karyopharm Therapeutics, Merck, Oncology Adventure, Roche, Seattle Genetics, Sera Prognostics, Sotio, GlaxoSmithKline, Zai Lab, and Boehringer Ingelheim. Dr. Lorusso disclosed relationships with AstraZeneca, Biocad, Clovis Oncology, Genmab, Merck, Roche, Tesaro, Amgen, Immunogen, and Pharma Mar.

SOURCE: Mirza MR et al. ESMO 2020, Abstract LBA28.

Adding palbociclib to letrozole significantly prolonged progression-free survival (PFS) in a phase 2 trial of patients with advanced or recurrent estrogen receptor (ER)–positive endometrial cancer.

This was the first randomized trial to evaluate the efficacy of a CDK4/6 inhibitor in combination with an aromatase inhibitor in patients with advanced or recurrent ER-positive endometrial cancer, noted study investigator Mansoor Raza Mirza, MD, PhD, of Rigshospitalet Copenhagen University Hospital.

Dr. Mirza presented results from this study, ENGOT-EN3-NSGO/PALEO, at the European Society for Medical Oncology Virtual Congress 2020.

Palbociclib is a selective inhibitor of CDK4/, both of which are involved in cell-cycle transitions, Dr. Mirza explained. He observed that endometrial endometrioid adenocarcinomas are hormone dependent, and endocrine treatment with an aromatase inhibitor is well established. Palbociclib has been shown to be superior, when combined with letrozole, to letrozole alone in ER-positive breast cancer.

For the ENGOT-EN3-NSGO/PALEO study, investigators enrolled 77 patients with ER-positive advanced/recurrent endometrial cancer. Patients had received at least one prior systemic therapy, no prior endocrine therapy (except medroxyprogesterone acetate and megestrol acetate), and no prior CDK inhibitor.

Patients were randomized 1:1 to receive oral letrozole (2.5 mg on days 1-28) and either palbociclib (125 mg on days 1-21) or placebo (125 mg on days 1-21) in a 28-day cycle until progression. Baseline characteristics were similar between the treatment arms.
 

Efficacy

Of the 77 patients enrolled, 73 were evaluable. The primary endpoint was PFS.

The median PFS in the intention-to-treat population was 3.0 months in the placebo arm and 8.3 months in the palbociclib arm (hazard ratio, 0.56; 95% confidence interval, 0.32-0.98; P = .0376).

Looking at stratification factors, PFS was higher in the palbociclib arm among the large majority (about 85%) of patients who had received no prior medroxyprogesterone acetate or megestrol acetate (HR, 0.55; 95% CI, 0.29-01.04; P = .0615) and among patients with relapsed disease (HR, 0.61; 95% CI, 0.34-1.09; P = .0916).

The disease control rate at 24 weeks, a secondary endpoint, was 63.6% in the palbociclib arm and 37.8% in the placebo arm.
 

Safety

Adverse events were more frequent in the palbociclib arm, with neutropenia being the most common.

Rates of adverse event–related dose reduction (to 100 mg or 75 mg) were 36% in the palbociclib arm and 3% in the placebo arm.

Adverse event–related discontinuation rates were 25% and 19% for palbociclib and letrozole, respectively, in the palbociclib arm and 14% and 11% for placebo and letrozole, respectively, in the placebo arm.

“The toxicity of palbociclib plus letrozole combination therapy was manageable, with most patients remaining on treatment until disease progression,” Dr. Mirza said.

He noted that an analysis of patient-reported outcomes revealed no detrimental effect on quality of life with the combination therapy.
 

Next steps

“Compared with placebo plus letrozole, the combination of palbociclib plus letrozole demonstrated clinically meaningful improvement in PFS,” Dr. Mirza said. “These results merit a phase 3 validation trial.”

“There is a huge rationale for using this drug in endometrial cancer,” commented study discussant Domenica Lorusso, MD, PhD, of Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Catholic University of Sacred Hearth in Rome.

Dr. Lorusso said hormone receptor expression, which has been identified as a strong predictor of CDK4/6 inhibitor activity, is present in up to 90% of patients with type 1 and in about 65% of patients with type 2 endometrial cancer.

Response rates, in experience with aromatase inhibitors, have been “quite disappointing, in the 10%-20% range,” Dr. Lorusso said, with “dismal prognosis” and guidelines stating that “no standard second-line treatment has been identified.”

This research was sponsored by investigators, but Pfizer provided a study grant. Dr. Mirza disclosed relationships with Pfizer, AstraZeneca, Biocad, Clovis Oncology, Genmab, Karyopharm Therapeutics, Merck, Oncology Adventure, Roche, Seattle Genetics, Sera Prognostics, Sotio, GlaxoSmithKline, Zai Lab, and Boehringer Ingelheim. Dr. Lorusso disclosed relationships with AstraZeneca, Biocad, Clovis Oncology, Genmab, Merck, Roche, Tesaro, Amgen, Immunogen, and Pharma Mar.

SOURCE: Mirza MR et al. ESMO 2020, Abstract LBA28.

Persons with type 2 diabetes may be at heightened risk for developing vascular dementia than other types of dementia, a team of international researchers has found.

Compared with a nondiabetic control population, those with type 2 diabetes had a statistically significant 35% increased chance of having vascular dementia in a large observational study.

By comparison, the risk for nonvascular dementia was increased by a “more modest” 8%, said the researchers from the University of Glasgow and the University of Gothenburg (Sweden), while the risk for Alzheimer’s dementia appeared to be reduced by 8%.

The link between type 2 diabetes and dementia is not new, observed Carlos Celis-Morales, PhD, who presented the study’s findings at the virtual annual meeting of the European Association for the Study of Diabetes. With people living longer thanks to improved preventative strategies and treatments, there is a risk for developing other chronic conditions, such as dementia.

“A third of all dementia cases may be attributable to modifiable risk factors, among them type 2 diabetes, which accounts for 3.2% of all dementia cases,” said Dr. Celis-Morales, a research fellow at the University of Glasgow’s Institute of Cardiovascular and Medical Sciences.

“Although we know that diabetes is linked to dementia, what we don’t know really well is how much of this association between diabetes and dementia outcomes are explained by modifiable and nonmodifiable risk factors,” Dr. Celis-Morales added.

“Diabetes and dementia share certain risk factors,” commented coinvestigator Naveed Sattar, MD, in a press release issued by the EASD. These include obesity, smoking, and lack of physical activity and might explain part of the association between the two conditions.

Dr. Sattar said that the heightened vascular dementia risk found in the study was “in itself an argument for preventive measures such as healthier lifestyle,” adding that “the importance of prevention is underscored by the fact that, for the majority of dementia diseases, there is no good treatment.”

Using data from the Swedish National Diabetes Register, the research team set out to determine the extent to which type 2 diabetes was associated with dementia and the incidence of different subtypes of dementia. They also looked to see if there were any associations with blood glucose control and what risk factors may be involved.

In total, data on 378,299 individuals with type 2 diabetes were compared with data on 1,886,022 similarly aged (average, 64 years) and gender-matched controls from the general population.

After a mean 7 years of follow-up, 10,143 people with and 46,479 people without type 2 diabetes developed dementia. Nonvascular dementia was the most common type of dementia recorded, followed by Alzheimer’s disease and then vascular dementia.

“Within type 2 diabetes individuals, poor glycemic [control] increased the risk of dementia especially for vascular dementia and nonvascular dementia. However, these associations were not as evident for Alzheimer’s disease,” Dr. Celis-Morales reported.

Comparing those with hemoglobin bA1c of less than 52 mmol/mol (7%) with those whose A1c was above 87 mmol/mol (10.1%), there was 93% increase in the risk for vascular dementia, a 67% increase in the risk for nonvascular dementia, and a 34% higher risk for Alzheimer’s disease–associated dementia.

“We have focused on high levels of HbA1c, but what happens if you have really low limits? It’s something we’re working on right now,” Dr. Celis-Morales said.

Importantly, cardiovascular-related risk factors – some of which, like systolic blood pressure and body weight, were potentially modifiable – accounted for more than 40% of the risk for dementia in type 2 diabetes. This suggests that a large percentage of the dementia risk could perhaps be addressed by identifying high-risk individuals and tailoring interventions accordingly.

“These are observational findings, so we need to be careful before we translate to any sort of recommendation,” Dr. Celis-Morales said.

The study was financed by the Swedish state under the agreement between the government and the county councils, the ALF agreement, as well as grant from the Novo Nordisk Foundation and the Swedish Association of Local Authorities and Regions. Dr. Celis-Morales and Dr. Sattar had no conflicts of interest.
 

SOURCE: Celis-Morales C et al. EASD 2020, Oral presentation 06.

Persons with type 2 diabetes may be at heightened risk for developing vascular dementia than other types of dementia, a team of international researchers has found.

Compared with a nondiabetic control population, those with type 2 diabetes had a statistically significant 35% increased chance of having vascular dementia in a large observational study.

By comparison, the risk for nonvascular dementia was increased by a “more modest” 8%, said the researchers from the University of Glasgow and the University of Gothenburg (Sweden), while the risk for Alzheimer’s dementia appeared to be reduced by 8%.

The link between type 2 diabetes and dementia is not new, observed Carlos Celis-Morales, PhD, who presented the study’s findings at the virtual annual meeting of the European Association for the Study of Diabetes. With people living longer thanks to improved preventative strategies and treatments, there is a risk for developing other chronic conditions, such as dementia.

“A third of all dementia cases may be attributable to modifiable risk factors, among them type 2 diabetes, which accounts for 3.2% of all dementia cases,” said Dr. Celis-Morales, a research fellow at the University of Glasgow’s Institute of Cardiovascular and Medical Sciences.

“Although we know that diabetes is linked to dementia, what we don’t know really well is how much of this association between diabetes and dementia outcomes are explained by modifiable and nonmodifiable risk factors,” Dr. Celis-Morales added.

“Diabetes and dementia share certain risk factors,” commented coinvestigator Naveed Sattar, MD, in a press release issued by the EASD. These include obesity, smoking, and lack of physical activity and might explain part of the association between the two conditions.

Dr. Sattar said that the heightened vascular dementia risk found in the study was “in itself an argument for preventive measures such as healthier lifestyle,” adding that “the importance of prevention is underscored by the fact that, for the majority of dementia diseases, there is no good treatment.”

Using data from the Swedish National Diabetes Register, the research team set out to determine the extent to which type 2 diabetes was associated with dementia and the incidence of different subtypes of dementia. They also looked to see if there were any associations with blood glucose control and what risk factors may be involved.

In total, data on 378,299 individuals with type 2 diabetes were compared with data on 1,886,022 similarly aged (average, 64 years) and gender-matched controls from the general population.

After a mean 7 years of follow-up, 10,143 people with and 46,479 people without type 2 diabetes developed dementia. Nonvascular dementia was the most common type of dementia recorded, followed by Alzheimer’s disease and then vascular dementia.

“Within type 2 diabetes individuals, poor glycemic [control] increased the risk of dementia especially for vascular dementia and nonvascular dementia. However, these associations were not as evident for Alzheimer’s disease,” Dr. Celis-Morales reported.

Comparing those with hemoglobin bA1c of less than 52 mmol/mol (7%) with those whose A1c was above 87 mmol/mol (10.1%), there was 93% increase in the risk for vascular dementia, a 67% increase in the risk for nonvascular dementia, and a 34% higher risk for Alzheimer’s disease–associated dementia.

“We have focused on high levels of HbA1c, but what happens if you have really low limits? It’s something we’re working on right now,” Dr. Celis-Morales said.

Importantly, cardiovascular-related risk factors – some of which, like systolic blood pressure and body weight, were potentially modifiable – accounted for more than 40% of the risk for dementia in type 2 diabetes. This suggests that a large percentage of the dementia risk could perhaps be addressed by identifying high-risk individuals and tailoring interventions accordingly.

“These are observational findings, so we need to be careful before we translate to any sort of recommendation,” Dr. Celis-Morales said.

The study was financed by the Swedish state under the agreement between the government and the county councils, the ALF agreement, as well as grant from the Novo Nordisk Foundation and the Swedish Association of Local Authorities and Regions. Dr. Celis-Morales and Dr. Sattar had no conflicts of interest.
 

SOURCE: Celis-Morales C et al. EASD 2020, Oral presentation 06.

Persons with type 2 diabetes may be at heightened risk for developing vascular dementia than other types of dementia, a team of international researchers has found.

Compared with a nondiabetic control population, those with type 2 diabetes had a statistically significant 35% increased chance of having vascular dementia in a large observational study.

By comparison, the risk for nonvascular dementia was increased by a “more modest” 8%, said the researchers from the University of Glasgow and the University of Gothenburg (Sweden), while the risk for Alzheimer’s dementia appeared to be reduced by 8%.

The link between type 2 diabetes and dementia is not new, observed Carlos Celis-Morales, PhD, who presented the study’s findings at the virtual annual meeting of the European Association for the Study of Diabetes. With people living longer thanks to improved preventative strategies and treatments, there is a risk for developing other chronic conditions, such as dementia.

“A third of all dementia cases may be attributable to modifiable risk factors, among them type 2 diabetes, which accounts for 3.2% of all dementia cases,” said Dr. Celis-Morales, a research fellow at the University of Glasgow’s Institute of Cardiovascular and Medical Sciences.

“Although we know that diabetes is linked to dementia, what we don’t know really well is how much of this association between diabetes and dementia outcomes are explained by modifiable and nonmodifiable risk factors,” Dr. Celis-Morales added.

“Diabetes and dementia share certain risk factors,” commented coinvestigator Naveed Sattar, MD, in a press release issued by the EASD. These include obesity, smoking, and lack of physical activity and might explain part of the association between the two conditions.

Dr. Sattar said that the heightened vascular dementia risk found in the study was “in itself an argument for preventive measures such as healthier lifestyle,” adding that “the importance of prevention is underscored by the fact that, for the majority of dementia diseases, there is no good treatment.”

Using data from the Swedish National Diabetes Register, the research team set out to determine the extent to which type 2 diabetes was associated with dementia and the incidence of different subtypes of dementia. They also looked to see if there were any associations with blood glucose control and what risk factors may be involved.

In total, data on 378,299 individuals with type 2 diabetes were compared with data on 1,886,022 similarly aged (average, 64 years) and gender-matched controls from the general population.

After a mean 7 years of follow-up, 10,143 people with and 46,479 people without type 2 diabetes developed dementia. Nonvascular dementia was the most common type of dementia recorded, followed by Alzheimer’s disease and then vascular dementia.

“Within type 2 diabetes individuals, poor glycemic [control] increased the risk of dementia especially for vascular dementia and nonvascular dementia. However, these associations were not as evident for Alzheimer’s disease,” Dr. Celis-Morales reported.

Comparing those with hemoglobin bA1c of less than 52 mmol/mol (7%) with those whose A1c was above 87 mmol/mol (10.1%), there was 93% increase in the risk for vascular dementia, a 67% increase in the risk for nonvascular dementia, and a 34% higher risk for Alzheimer’s disease–associated dementia.

“We have focused on high levels of HbA1c, but what happens if you have really low limits? It’s something we’re working on right now,” Dr. Celis-Morales said.

Importantly, cardiovascular-related risk factors – some of which, like systolic blood pressure and body weight, were potentially modifiable – accounted for more than 40% of the risk for dementia in type 2 diabetes. This suggests that a large percentage of the dementia risk could perhaps be addressed by identifying high-risk individuals and tailoring interventions accordingly.

“These are observational findings, so we need to be careful before we translate to any sort of recommendation,” Dr. Celis-Morales said.

The study was financed by the Swedish state under the agreement between the government and the county councils, the ALF agreement, as well as grant from the Novo Nordisk Foundation and the Swedish Association of Local Authorities and Regions. Dr. Celis-Morales and Dr. Sattar had no conflicts of interest.
 

SOURCE: Celis-Morales C et al. EASD 2020, Oral presentation 06.