Pharmacology

BARCELONA – Patients with type 2 diabetes who were treated with semaglutide achieved greater reductions in glycated hemoglobin (HbA_1c) levels and body weight, compared with those receiving liraglutide, according to results presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDEdge News

In the phase 3b SUSTAIN 10 trial, conducted in 11 European countries, mean glycated hemoglobin at 30 weeks decreased by 1.7% with once-weekly semaglutide and 1.0% for once-daily liraglutide, from the overall baseline level of 8.2%. The estimated treatment difference (ETD) between the two treatments was –0.69 percentage points (95% confidence interval, –0.82 to –0.56; P less than .0001).

Mean body weight decreased during the same period by 5.8 kg with semaglutide and 1.9 kg with liraglutide, from a baseline of 96.9 kg. The ETD was 3.83 kg (95% CI, –4.57 to –3.09; P less than .0001).

The doses of semaglutide and liraglutide used in the study were 1.0 mg and 1.2 mg, respectively, the latter being the dose that is used most commonly in clinical practice, study investigator Matthew Capehorn, MB, CAB, explained in an interview at the meeting.

“We know that at a dose of 1.8 mg, liraglutide is more effective than 1.2 mg, but it’s about whether it is deemed more cost effective,” said Dr. Capehorn, who is clinical manager at Rotherham (England) Institute for Obesity, Clifton Medical Centre. “Certainly, in the United Kingdom, we’re encouraged to use the 1.2-mg dose” according to guidance from the National Institute for Heath and Care Excellence, and “other European countries are the same.”

Dr. Capehorn noted that studies are being done with a higher dose of semaglutide to see if it has potential as a weight loss drug in its own right in patients who do not have type 2 diabetes. “I care as much about obesity and cardiovascular disease as I do about chasing the HbA_1c level and getting that reduced, so I would rather pick an agent that covers all three [components], than just looking at the HbA_1c,” he said.

In SUSTAIN 10,577 adults with type 2 diabetes and an HbA_1c level of between 7.0% and 11.0% who were on stable doses of one to three oral antidiabetic drugs were randomized to receive semaglutide (n = 290) or liraglutide (n = 287) for 30 weeks.

The primary endpoint was the change in HbA1c from baseline to week 30, and the secondary confirmatory endpoint was change in body weight over the same period.

In presenting the findings, which were simultaneously published in Diabetes & Metabolism, Dr. Capehorn noted that the efficacy results were consistent with those of other SUSTAIN trials that compared semaglutide with other glucagonlike peptide–1 receptor antagonists, notably SUSTAIN 3 (with exenatide extended release) and SUSTAIN 7 (with dulaglutide).

Other efficacy findings from SUSTAIN 10 were that semaglutide produced greater mean changes than did liraglutide in both fasting plasma glucose and in a 7-point, self-monitoring of blood glucose profile.

A greater percentage of people treated with semaglutide, compared with liraglutide, also achieved their glycemic targets of less than 7.0% (80% vs. 46%, respectively) and of 6.5% or less (58% vs. 25%), and their weight loss targets of 5% or more (56% vs. 18%) and 10% or more (19% vs. 4%).

In addition, more semaglutide- than liraglutide-treated patients achieved an HbA_1c target of less than 7.0% without severe or blood glucose–confirmed symptomatic hypoglycemia, with or without weight gain (76% vs. 37%; P less than .0001). There were also more semaglutide patients who achieved an HbA_1c reduction of 1% or more and a weight loss reduction of 10% or more (17% vs. 4% for liraglutide, P less than .0001).

The safety profiles were similar for semaglutide and liraglutide, Dr. Capehorn noted, but gastrointestinal adverse events were more prevalent in patients receiving semaglutide, compared with liraglutide (43.9% vs. 38.3%), and more patients receiving semaglutide discontinued treatment prematurely because of those adverse events (11.4% vs. 6.6% for liraglutide).

Novo Nordisk sponsored the study. Dr. Capehorn reported receiving research funding from, providing advisory board support to, and speaker fees from Novo Nordisk and from several other companies.
 

SOURCE: Capehorn M et al. EASD 2019, Oral Presentation 53; Capehorn M et al. Diabetes Metab. 2019 Sep 17. doi: 10.1016/j.diabet.2019.101117.

BARCELONA – Patients with type 2 diabetes who were treated with semaglutide achieved greater reductions in glycated hemoglobin (HbA_1c) levels and body weight, compared with those receiving liraglutide, according to results presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDEdge News

In the phase 3b SUSTAIN 10 trial, conducted in 11 European countries, mean glycated hemoglobin at 30 weeks decreased by 1.7% with once-weekly semaglutide and 1.0% for once-daily liraglutide, from the overall baseline level of 8.2%. The estimated treatment difference (ETD) between the two treatments was –0.69 percentage points (95% confidence interval, –0.82 to –0.56; P less than .0001).

Mean body weight decreased during the same period by 5.8 kg with semaglutide and 1.9 kg with liraglutide, from a baseline of 96.9 kg. The ETD was 3.83 kg (95% CI, –4.57 to –3.09; P less than .0001).

The doses of semaglutide and liraglutide used in the study were 1.0 mg and 1.2 mg, respectively, the latter being the dose that is used most commonly in clinical practice, study investigator Matthew Capehorn, MB, CAB, explained in an interview at the meeting.

“We know that at a dose of 1.8 mg, liraglutide is more effective than 1.2 mg, but it’s about whether it is deemed more cost effective,” said Dr. Capehorn, who is clinical manager at Rotherham (England) Institute for Obesity, Clifton Medical Centre. “Certainly, in the United Kingdom, we’re encouraged to use the 1.2-mg dose” according to guidance from the National Institute for Heath and Care Excellence, and “other European countries are the same.”

Dr. Capehorn noted that studies are being done with a higher dose of semaglutide to see if it has potential as a weight loss drug in its own right in patients who do not have type 2 diabetes. “I care as much about obesity and cardiovascular disease as I do about chasing the HbA_1c level and getting that reduced, so I would rather pick an agent that covers all three [components], than just looking at the HbA_1c,” he said.

In SUSTAIN 10,577 adults with type 2 diabetes and an HbA_1c level of between 7.0% and 11.0% who were on stable doses of one to three oral antidiabetic drugs were randomized to receive semaglutide (n = 290) or liraglutide (n = 287) for 30 weeks.

The primary endpoint was the change in HbA1c from baseline to week 30, and the secondary confirmatory endpoint was change in body weight over the same period.

In presenting the findings, which were simultaneously published in Diabetes & Metabolism, Dr. Capehorn noted that the efficacy results were consistent with those of other SUSTAIN trials that compared semaglutide with other glucagonlike peptide–1 receptor antagonists, notably SUSTAIN 3 (with exenatide extended release) and SUSTAIN 7 (with dulaglutide).

Other efficacy findings from SUSTAIN 10 were that semaglutide produced greater mean changes than did liraglutide in both fasting plasma glucose and in a 7-point, self-monitoring of blood glucose profile.

A greater percentage of people treated with semaglutide, compared with liraglutide, also achieved their glycemic targets of less than 7.0% (80% vs. 46%, respectively) and of 6.5% or less (58% vs. 25%), and their weight loss targets of 5% or more (56% vs. 18%) and 10% or more (19% vs. 4%).

In addition, more semaglutide- than liraglutide-treated patients achieved an HbA_1c target of less than 7.0% without severe or blood glucose–confirmed symptomatic hypoglycemia, with or without weight gain (76% vs. 37%; P less than .0001). There were also more semaglutide patients who achieved an HbA_1c reduction of 1% or more and a weight loss reduction of 10% or more (17% vs. 4% for liraglutide, P less than .0001).

The safety profiles were similar for semaglutide and liraglutide, Dr. Capehorn noted, but gastrointestinal adverse events were more prevalent in patients receiving semaglutide, compared with liraglutide (43.9% vs. 38.3%), and more patients receiving semaglutide discontinued treatment prematurely because of those adverse events (11.4% vs. 6.6% for liraglutide).

Novo Nordisk sponsored the study. Dr. Capehorn reported receiving research funding from, providing advisory board support to, and speaker fees from Novo Nordisk and from several other companies.
 

SOURCE: Capehorn M et al. EASD 2019, Oral Presentation 53; Capehorn M et al. Diabetes Metab. 2019 Sep 17. doi: 10.1016/j.diabet.2019.101117.

BARCELONA – Patients with type 2 diabetes who were treated with semaglutide achieved greater reductions in glycated hemoglobin (HbA_1c) levels and body weight, compared with those receiving liraglutide, according to results presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDEdge News

In the phase 3b SUSTAIN 10 trial, conducted in 11 European countries, mean glycated hemoglobin at 30 weeks decreased by 1.7% with once-weekly semaglutide and 1.0% for once-daily liraglutide, from the overall baseline level of 8.2%. The estimated treatment difference (ETD) between the two treatments was –0.69 percentage points (95% confidence interval, –0.82 to –0.56; P less than .0001).

Mean body weight decreased during the same period by 5.8 kg with semaglutide and 1.9 kg with liraglutide, from a baseline of 96.9 kg. The ETD was 3.83 kg (95% CI, –4.57 to –3.09; P less than .0001).

The doses of semaglutide and liraglutide used in the study were 1.0 mg and 1.2 mg, respectively, the latter being the dose that is used most commonly in clinical practice, study investigator Matthew Capehorn, MB, CAB, explained in an interview at the meeting.

“We know that at a dose of 1.8 mg, liraglutide is more effective than 1.2 mg, but it’s about whether it is deemed more cost effective,” said Dr. Capehorn, who is clinical manager at Rotherham (England) Institute for Obesity, Clifton Medical Centre. “Certainly, in the United Kingdom, we’re encouraged to use the 1.2-mg dose” according to guidance from the National Institute for Heath and Care Excellence, and “other European countries are the same.”

Dr. Capehorn noted that studies are being done with a higher dose of semaglutide to see if it has potential as a weight loss drug in its own right in patients who do not have type 2 diabetes. “I care as much about obesity and cardiovascular disease as I do about chasing the HbA_1c level and getting that reduced, so I would rather pick an agent that covers all three [components], than just looking at the HbA_1c,” he said.

In SUSTAIN 10,577 adults with type 2 diabetes and an HbA_1c level of between 7.0% and 11.0% who were on stable doses of one to three oral antidiabetic drugs were randomized to receive semaglutide (n = 290) or liraglutide (n = 287) for 30 weeks.

The primary endpoint was the change in HbA1c from baseline to week 30, and the secondary confirmatory endpoint was change in body weight over the same period.

In presenting the findings, which were simultaneously published in Diabetes & Metabolism, Dr. Capehorn noted that the efficacy results were consistent with those of other SUSTAIN trials that compared semaglutide with other glucagonlike peptide–1 receptor antagonists, notably SUSTAIN 3 (with exenatide extended release) and SUSTAIN 7 (with dulaglutide).

Other efficacy findings from SUSTAIN 10 were that semaglutide produced greater mean changes than did liraglutide in both fasting plasma glucose and in a 7-point, self-monitoring of blood glucose profile.

A greater percentage of people treated with semaglutide, compared with liraglutide, also achieved their glycemic targets of less than 7.0% (80% vs. 46%, respectively) and of 6.5% or less (58% vs. 25%), and their weight loss targets of 5% or more (56% vs. 18%) and 10% or more (19% vs. 4%).

In addition, more semaglutide- than liraglutide-treated patients achieved an HbA_1c target of less than 7.0% without severe or blood glucose–confirmed symptomatic hypoglycemia, with or without weight gain (76% vs. 37%; P less than .0001). There were also more semaglutide patients who achieved an HbA_1c reduction of 1% or more and a weight loss reduction of 10% or more (17% vs. 4% for liraglutide, P less than .0001).

The safety profiles were similar for semaglutide and liraglutide, Dr. Capehorn noted, but gastrointestinal adverse events were more prevalent in patients receiving semaglutide, compared with liraglutide (43.9% vs. 38.3%), and more patients receiving semaglutide discontinued treatment prematurely because of those adverse events (11.4% vs. 6.6% for liraglutide).

Novo Nordisk sponsored the study. Dr. Capehorn reported receiving research funding from, providing advisory board support to, and speaker fees from Novo Nordisk and from several other companies.
 

SOURCE: Capehorn M et al. EASD 2019, Oral Presentation 53; Capehorn M et al. Diabetes Metab. 2019 Sep 17. doi: 10.1016/j.diabet.2019.101117.

The House Ways and Means Committee is the latest to pass H.R. 3, a bill aimed at driving the price of prescription drugs down.

©Mathier/thinkstockphotos.com

During an Oct. 22, 2019, markup of the bill, Republican members criticized committee leadership for abandoning bipartisan efforts to reign in drug prices in favor of a partisan bill that so far gained no support from the minority party. H.R. 3 was passed by the Ways and Means Committee on a 24-17 party line vote.

Both “Democrats and Republicans support lowering drug prices, cracking down on overpriced drugs, giving patients more power to choose affordable medicines, and removing the wrong incentives in federal health programs that reward bad actors for raising prices,” Committee Ranking Member Kevin Brady (R-Tex.) said in his opening statement. In fact, at the request of Committee Chairman Richard Neal (D-Mass.), “both parties in this committee were working together toward that important goal. At least until Speaker Nancy Pelosi (D-Calif.) trashed the bipartisan work and forced through a secretly written, deeply controversial, and highly partisan drug bill to cure political illnesses rather than real ones.”

H.R. 3, recently renamed the Elijah E. Cummings Lower Drug Costs Now Act of 2019, would give the secretary of the Department of Health & Human Services the ability to negotiate drug prices for Medicare Part D (something explicitly banned under current law), implement an excise tax on drugs that see price hikes above the rate of inflation, cap out-of-pocket expenditures annually for Medicare Part D beneficiaries at $2,000, and use an international pricing index to help bring prices for drugs sold in the United States more in line with the lower prices in foreign countries.

But panel Democrats praised the bill as a step forward in helping to lower the cost of prescription drugs.

“H.R. 3 levels the playing field for U.S. consumers who, on average, pay four times more than patients in other countries for the exact same drugs,” Chairman Neal said in a statement following the passage.

He highlighted specifically the provision that caps out-of-pocket expenses in Part D and the HHS’ negotiating power, noting that “more people will be able to afford the drugs they need that they may have previously forgone due to high costs. With more Americans taking the medicines they’re prescribed, families will be healthier, and premiums will go down.”

Republican committee members argued that these same provisions would stifle innovation and ultimately would reduce access to medicine. Most attempts at altering the provisions through amendments were met with strict party line rejection.

[email protected]

The House Ways and Means Committee is the latest to pass H.R. 3, a bill aimed at driving the price of prescription drugs down.

©Mathier/thinkstockphotos.com

During an Oct. 22, 2019, markup of the bill, Republican members criticized committee leadership for abandoning bipartisan efforts to reign in drug prices in favor of a partisan bill that so far gained no support from the minority party. H.R. 3 was passed by the Ways and Means Committee on a 24-17 party line vote.

Both “Democrats and Republicans support lowering drug prices, cracking down on overpriced drugs, giving patients more power to choose affordable medicines, and removing the wrong incentives in federal health programs that reward bad actors for raising prices,” Committee Ranking Member Kevin Brady (R-Tex.) said in his opening statement. In fact, at the request of Committee Chairman Richard Neal (D-Mass.), “both parties in this committee were working together toward that important goal. At least until Speaker Nancy Pelosi (D-Calif.) trashed the bipartisan work and forced through a secretly written, deeply controversial, and highly partisan drug bill to cure political illnesses rather than real ones.”

H.R. 3, recently renamed the Elijah E. Cummings Lower Drug Costs Now Act of 2019, would give the secretary of the Department of Health & Human Services the ability to negotiate drug prices for Medicare Part D (something explicitly banned under current law), implement an excise tax on drugs that see price hikes above the rate of inflation, cap out-of-pocket expenditures annually for Medicare Part D beneficiaries at $2,000, and use an international pricing index to help bring prices for drugs sold in the United States more in line with the lower prices in foreign countries.

But panel Democrats praised the bill as a step forward in helping to lower the cost of prescription drugs.

“H.R. 3 levels the playing field for U.S. consumers who, on average, pay four times more than patients in other countries for the exact same drugs,” Chairman Neal said in a statement following the passage.

He highlighted specifically the provision that caps out-of-pocket expenses in Part D and the HHS’ negotiating power, noting that “more people will be able to afford the drugs they need that they may have previously forgone due to high costs. With more Americans taking the medicines they’re prescribed, families will be healthier, and premiums will go down.”

Republican committee members argued that these same provisions would stifle innovation and ultimately would reduce access to medicine. Most attempts at altering the provisions through amendments were met with strict party line rejection.

[email protected]

The House Ways and Means Committee is the latest to pass H.R. 3, a bill aimed at driving the price of prescription drugs down.

©Mathier/thinkstockphotos.com

During an Oct. 22, 2019, markup of the bill, Republican members criticized committee leadership for abandoning bipartisan efforts to reign in drug prices in favor of a partisan bill that so far gained no support from the minority party. H.R. 3 was passed by the Ways and Means Committee on a 24-17 party line vote.

Both “Democrats and Republicans support lowering drug prices, cracking down on overpriced drugs, giving patients more power to choose affordable medicines, and removing the wrong incentives in federal health programs that reward bad actors for raising prices,” Committee Ranking Member Kevin Brady (R-Tex.) said in his opening statement. In fact, at the request of Committee Chairman Richard Neal (D-Mass.), “both parties in this committee were working together toward that important goal. At least until Speaker Nancy Pelosi (D-Calif.) trashed the bipartisan work and forced through a secretly written, deeply controversial, and highly partisan drug bill to cure political illnesses rather than real ones.”

H.R. 3, recently renamed the Elijah E. Cummings Lower Drug Costs Now Act of 2019, would give the secretary of the Department of Health & Human Services the ability to negotiate drug prices for Medicare Part D (something explicitly banned under current law), implement an excise tax on drugs that see price hikes above the rate of inflation, cap out-of-pocket expenditures annually for Medicare Part D beneficiaries at $2,000, and use an international pricing index to help bring prices for drugs sold in the United States more in line with the lower prices in foreign countries.

But panel Democrats praised the bill as a step forward in helping to lower the cost of prescription drugs.

“H.R. 3 levels the playing field for U.S. consumers who, on average, pay four times more than patients in other countries for the exact same drugs,” Chairman Neal said in a statement following the passage.

He highlighted specifically the provision that caps out-of-pocket expenses in Part D and the HHS’ negotiating power, noting that “more people will be able to afford the drugs they need that they may have previously forgone due to high costs. With more Americans taking the medicines they’re prescribed, families will be healthier, and premiums will go down.”

Republican committee members argued that these same provisions would stifle innovation and ultimately would reduce access to medicine. Most attempts at altering the provisions through amendments were met with strict party line rejection.

[email protected]

The novel drug bremelanotide shows promise in acquired female hypoactive sexual desire disorder, according to the results of two randomized, controlled trials and a 52-week open-label extension study published online in Obstetrics & Gynecology.

Bremelanotide, which received Food and Drug Administration approval for this indication in June 2019, is an analog of the endogenous neuropeptide alpha-melanocyte-stimulating hormone.

Two separate, identically designed phase 3 studies (RECONNECT) were performed by Sheryl Kingsburg, MD, of the Cleveland Medical Center, and associates. Combined, 1,267 premenopausal women in monogamous relationships with acquired hypoactive sexual desire disorder were randomized to bremelanotide or placebo. Women in the treatment arm had significant improvement in female sexual function index–desire domain (FSFI-D) scores from baseline to week 24 (integrated studies: 0.35; P less than .001; effect size, 0.39), compared with placebo. They also experienced significant improvement in the FSFI-desire/arousal/orgasm (FSFI-DAO) domain (integrated studies: –0.33; P less than .001; effect size, 0.27).

The most common adverse events were nausea (integrated: 40% versus 1% in placebo), flushing (20% versus 0.3%), and headache (11% versus 2%). Overall, 77% in the treatment group reported a treatment-emergent adverse event, compared with 58% in the placebo group.

The open-label follow-up study was led by James Simon, MD, of George Washington University and IntimMedicine Specialists, Washington. Of the 684 participants who opted to enter the extension study, 40% completed it. In those who received bremelanotide during the randomized trial, the change in FSFI-D scores from baseline to the end of the open-label study ranged from 1.25 to 1.30, while the change in FSFI-DAO ranged from –1.4 to –1.7. In patients originally on placebo, the changes were 0.70-0.77 and –0.9, respectively.

Both groups surpassed the minimally clinically important difference for the FSFI-D score, which is considered to be 0.6.

“Patients switching from placebo experienced a higher incidence of adverse events than those continuing on bremelanotide during the open-label extension (79% versus 63%, respectively),” Dr. Simon and associates said.

The treatment is subcutaneous and can be self-administered up to about 45 minutes before a sexual event, no more than once during a 24-hour period, and no more than 8 doses per month, according to an FDA press release. The drug is contraindicated for women with cardiovascular disease or uncontrolled hypertension due to observations of transiently, slightly increased blood pressure.

The trials were funded by Palatin Technologies and AMAG Pharmaceuticals. The authors and coauthors have extensive financial relationships with pharmaceutical companies. Dr. Carson reported no financial conflicts.

SOURCE: Obstet Gynecol. 2019 Oct 8. doi: 10.1097/AOG.0000000000003500; Obstet Gynecol. 2019 Oct 8. doi: 10.1097/AOG.0000000000003514.

The novel drug bremelanotide shows promise in acquired female hypoactive sexual desire disorder, according to the results of two randomized, controlled trials and a 52-week open-label extension study published online in Obstetrics & Gynecology.

Bremelanotide, which received Food and Drug Administration approval for this indication in June 2019, is an analog of the endogenous neuropeptide alpha-melanocyte-stimulating hormone.

Two separate, identically designed phase 3 studies (RECONNECT) were performed by Sheryl Kingsburg, MD, of the Cleveland Medical Center, and associates. Combined, 1,267 premenopausal women in monogamous relationships with acquired hypoactive sexual desire disorder were randomized to bremelanotide or placebo. Women in the treatment arm had significant improvement in female sexual function index–desire domain (FSFI-D) scores from baseline to week 24 (integrated studies: 0.35; P less than .001; effect size, 0.39), compared with placebo. They also experienced significant improvement in the FSFI-desire/arousal/orgasm (FSFI-DAO) domain (integrated studies: –0.33; P less than .001; effect size, 0.27).

The most common adverse events were nausea (integrated: 40% versus 1% in placebo), flushing (20% versus 0.3%), and headache (11% versus 2%). Overall, 77% in the treatment group reported a treatment-emergent adverse event, compared with 58% in the placebo group.

The open-label follow-up study was led by James Simon, MD, of George Washington University and IntimMedicine Specialists, Washington. Of the 684 participants who opted to enter the extension study, 40% completed it. In those who received bremelanotide during the randomized trial, the change in FSFI-D scores from baseline to the end of the open-label study ranged from 1.25 to 1.30, while the change in FSFI-DAO ranged from –1.4 to –1.7. In patients originally on placebo, the changes were 0.70-0.77 and –0.9, respectively.

Both groups surpassed the minimally clinically important difference for the FSFI-D score, which is considered to be 0.6.

“Patients switching from placebo experienced a higher incidence of adverse events than those continuing on bremelanotide during the open-label extension (79% versus 63%, respectively),” Dr. Simon and associates said.

The treatment is subcutaneous and can be self-administered up to about 45 minutes before a sexual event, no more than once during a 24-hour period, and no more than 8 doses per month, according to an FDA press release. The drug is contraindicated for women with cardiovascular disease or uncontrolled hypertension due to observations of transiently, slightly increased blood pressure.

The trials were funded by Palatin Technologies and AMAG Pharmaceuticals. The authors and coauthors have extensive financial relationships with pharmaceutical companies. Dr. Carson reported no financial conflicts.

SOURCE: Obstet Gynecol. 2019 Oct 8. doi: 10.1097/AOG.0000000000003500; Obstet Gynecol. 2019 Oct 8. doi: 10.1097/AOG.0000000000003514.

The novel drug bremelanotide shows promise in acquired female hypoactive sexual desire disorder, according to the results of two randomized, controlled trials and a 52-week open-label extension study published online in Obstetrics & Gynecology.

Bremelanotide, which received Food and Drug Administration approval for this indication in June 2019, is an analog of the endogenous neuropeptide alpha-melanocyte-stimulating hormone.

Two separate, identically designed phase 3 studies (RECONNECT) were performed by Sheryl Kingsburg, MD, of the Cleveland Medical Center, and associates. Combined, 1,267 premenopausal women in monogamous relationships with acquired hypoactive sexual desire disorder were randomized to bremelanotide or placebo. Women in the treatment arm had significant improvement in female sexual function index–desire domain (FSFI-D) scores from baseline to week 24 (integrated studies: 0.35; P less than .001; effect size, 0.39), compared with placebo. They also experienced significant improvement in the FSFI-desire/arousal/orgasm (FSFI-DAO) domain (integrated studies: –0.33; P less than .001; effect size, 0.27).

The most common adverse events were nausea (integrated: 40% versus 1% in placebo), flushing (20% versus 0.3%), and headache (11% versus 2%). Overall, 77% in the treatment group reported a treatment-emergent adverse event, compared with 58% in the placebo group.

The open-label follow-up study was led by James Simon, MD, of George Washington University and IntimMedicine Specialists, Washington. Of the 684 participants who opted to enter the extension study, 40% completed it. In those who received bremelanotide during the randomized trial, the change in FSFI-D scores from baseline to the end of the open-label study ranged from 1.25 to 1.30, while the change in FSFI-DAO ranged from –1.4 to –1.7. In patients originally on placebo, the changes were 0.70-0.77 and –0.9, respectively.

Both groups surpassed the minimally clinically important difference for the FSFI-D score, which is considered to be 0.6.

“Patients switching from placebo experienced a higher incidence of adverse events than those continuing on bremelanotide during the open-label extension (79% versus 63%, respectively),” Dr. Simon and associates said.

The treatment is subcutaneous and can be self-administered up to about 45 minutes before a sexual event, no more than once during a 24-hour period, and no more than 8 doses per month, according to an FDA press release. The drug is contraindicated for women with cardiovascular disease or uncontrolled hypertension due to observations of transiently, slightly increased blood pressure.

The trials were funded by Palatin Technologies and AMAG Pharmaceuticals. The authors and coauthors have extensive financial relationships with pharmaceutical companies. Dr. Carson reported no financial conflicts.

SOURCE: Obstet Gynecol. 2019 Oct 8. doi: 10.1097/AOG.0000000000003500; Obstet Gynecol. 2019 Oct 8. doi: 10.1097/AOG.0000000000003514.

Among patients with human epidermal growth factor receptor 2–positive (HER2+) breast cancer, adding trastuzumab to adjuvant chemotherapy reduces risk of recurrence for at least 10 years, according to investigators.

The benefit of trastuzumab was greater among patients with hormone receptor–positive (HR+) disease than those with HR– disease until the 5-year timepoint, after which HR status had no significant impact on recurrence rates, reported lead author Saranya Chumsri, MD, of the Mayo Clinic in Jacksonville, Fla., and colleagues. This finding echoes a pattern similar to that of HER2– breast cancer, in which patients with HR+ disease have relatively consistent risk of recurrence over time, whereas patients with HR– disease have an early risk of recurrence that decreases after 5 years.

“To the best of our knowledge, this analysis is the first to address the risk of late relapses in subsets of HER2+ breast cancer patients who were treated with adjuvant trastuzumab,” the investigators wrote. Their report is in Journal of Clinical Oncology.

They drew data from 3,177 patients with HER2+ breast cancer who were involved in two phase 3 studies: the North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 trials. Patients involved in the analysis received either standard adjuvant chemotherapy with cyclophosphamide and doxorubicin followed by weekly paclitaxel or the same chemotherapy regimen plus concurrent trastuzumab. The primary outcome was recurrence-free survival, which was defined as time from randomization until local, regional, or distant recurrence of breast cancer or breast cancer–related death. Kaplan-Meier estimates were performed to determine recurrence-free survival, while Cox proportional hazards regression models were used to determine factors that predicted relapse.

Including a median follow-up of 8 years across all patients, the analysis showed that those with HR+ breast cancer had a significantly higher estimated rate of recurrence-free survival than that of those with HR– disease after 5 years (81.49% vs. 74.65%) and 10 years (73.84% vs. 69.22%). Overall, a comparable level of benefit was derived from adding trastuzumab regardless of HR status (interaction P = .87). However, during the first 5 years, HR positivity predicted greater benefit from adding trastuzumab, as patients with HR+ disease had a 40% lower risk of relapse than that of those with HR– disease (hazard ratio, 0.60; P less than .001). Between years 5 and 10, the statistical significance of HR status faded (P = .12), suggesting that HR status is not a predictor of long-term recurrence.

“Given concerning adverse effects and potentially smaller benefit of extended adjuvant endocrine therapy, particularly in patients with N0 or N1 disease, our findings highlight the need to develop better risk prediction models and biomarkers to identify which patients have sufficient risk for late relapse to warrant the use of extended endocrine therapy in HER2+ breast cancer,” the investigators concluded.

The study was funded by the National Institutes of Health, the Breast Cancer Research Foundation, Bankhead-Coley Research Program, the DONNA Foundation, and Genentech. Dr. Chumsri disclosed a financial relationship with Merck. Coauthors disclosed ties with Merck, Novartis, Genentech, and NanoString Technologies.

SOURCE: Chumsri et al. J Clin Oncol. 2019 Oct 17. doi: 10.1200/JCO.19.00443.

Among patients with human epidermal growth factor receptor 2–positive (HER2+) breast cancer, adding trastuzumab to adjuvant chemotherapy reduces risk of recurrence for at least 10 years, according to investigators.

The benefit of trastuzumab was greater among patients with hormone receptor–positive (HR+) disease than those with HR– disease until the 5-year timepoint, after which HR status had no significant impact on recurrence rates, reported lead author Saranya Chumsri, MD, of the Mayo Clinic in Jacksonville, Fla., and colleagues. This finding echoes a pattern similar to that of HER2– breast cancer, in which patients with HR+ disease have relatively consistent risk of recurrence over time, whereas patients with HR– disease have an early risk of recurrence that decreases after 5 years.

“To the best of our knowledge, this analysis is the first to address the risk of late relapses in subsets of HER2+ breast cancer patients who were treated with adjuvant trastuzumab,” the investigators wrote. Their report is in Journal of Clinical Oncology.

They drew data from 3,177 patients with HER2+ breast cancer who were involved in two phase 3 studies: the North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 trials. Patients involved in the analysis received either standard adjuvant chemotherapy with cyclophosphamide and doxorubicin followed by weekly paclitaxel or the same chemotherapy regimen plus concurrent trastuzumab. The primary outcome was recurrence-free survival, which was defined as time from randomization until local, regional, or distant recurrence of breast cancer or breast cancer–related death. Kaplan-Meier estimates were performed to determine recurrence-free survival, while Cox proportional hazards regression models were used to determine factors that predicted relapse.

Including a median follow-up of 8 years across all patients, the analysis showed that those with HR+ breast cancer had a significantly higher estimated rate of recurrence-free survival than that of those with HR– disease after 5 years (81.49% vs. 74.65%) and 10 years (73.84% vs. 69.22%). Overall, a comparable level of benefit was derived from adding trastuzumab regardless of HR status (interaction P = .87). However, during the first 5 years, HR positivity predicted greater benefit from adding trastuzumab, as patients with HR+ disease had a 40% lower risk of relapse than that of those with HR– disease (hazard ratio, 0.60; P less than .001). Between years 5 and 10, the statistical significance of HR status faded (P = .12), suggesting that HR status is not a predictor of long-term recurrence.

“Given concerning adverse effects and potentially smaller benefit of extended adjuvant endocrine therapy, particularly in patients with N0 or N1 disease, our findings highlight the need to develop better risk prediction models and biomarkers to identify which patients have sufficient risk for late relapse to warrant the use of extended endocrine therapy in HER2+ breast cancer,” the investigators concluded.

The study was funded by the National Institutes of Health, the Breast Cancer Research Foundation, Bankhead-Coley Research Program, the DONNA Foundation, and Genentech. Dr. Chumsri disclosed a financial relationship with Merck. Coauthors disclosed ties with Merck, Novartis, Genentech, and NanoString Technologies.

SOURCE: Chumsri et al. J Clin Oncol. 2019 Oct 17. doi: 10.1200/JCO.19.00443.

Among patients with human epidermal growth factor receptor 2–positive (HER2+) breast cancer, adding trastuzumab to adjuvant chemotherapy reduces risk of recurrence for at least 10 years, according to investigators.

The benefit of trastuzumab was greater among patients with hormone receptor–positive (HR+) disease than those with HR– disease until the 5-year timepoint, after which HR status had no significant impact on recurrence rates, reported lead author Saranya Chumsri, MD, of the Mayo Clinic in Jacksonville, Fla., and colleagues. This finding echoes a pattern similar to that of HER2– breast cancer, in which patients with HR+ disease have relatively consistent risk of recurrence over time, whereas patients with HR– disease have an early risk of recurrence that decreases after 5 years.

“To the best of our knowledge, this analysis is the first to address the risk of late relapses in subsets of HER2+ breast cancer patients who were treated with adjuvant trastuzumab,” the investigators wrote. Their report is in Journal of Clinical Oncology.

They drew data from 3,177 patients with HER2+ breast cancer who were involved in two phase 3 studies: the North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 trials. Patients involved in the analysis received either standard adjuvant chemotherapy with cyclophosphamide and doxorubicin followed by weekly paclitaxel or the same chemotherapy regimen plus concurrent trastuzumab. The primary outcome was recurrence-free survival, which was defined as time from randomization until local, regional, or distant recurrence of breast cancer or breast cancer–related death. Kaplan-Meier estimates were performed to determine recurrence-free survival, while Cox proportional hazards regression models were used to determine factors that predicted relapse.

Including a median follow-up of 8 years across all patients, the analysis showed that those with HR+ breast cancer had a significantly higher estimated rate of recurrence-free survival than that of those with HR– disease after 5 years (81.49% vs. 74.65%) and 10 years (73.84% vs. 69.22%). Overall, a comparable level of benefit was derived from adding trastuzumab regardless of HR status (interaction P = .87). However, during the first 5 years, HR positivity predicted greater benefit from adding trastuzumab, as patients with HR+ disease had a 40% lower risk of relapse than that of those with HR– disease (hazard ratio, 0.60; P less than .001). Between years 5 and 10, the statistical significance of HR status faded (P = .12), suggesting that HR status is not a predictor of long-term recurrence.

“Given concerning adverse effects and potentially smaller benefit of extended adjuvant endocrine therapy, particularly in patients with N0 or N1 disease, our findings highlight the need to develop better risk prediction models and biomarkers to identify which patients have sufficient risk for late relapse to warrant the use of extended endocrine therapy in HER2+ breast cancer,” the investigators concluded.

The study was funded by the National Institutes of Health, the Breast Cancer Research Foundation, Bankhead-Coley Research Program, the DONNA Foundation, and Genentech. Dr. Chumsri disclosed a financial relationship with Merck. Coauthors disclosed ties with Merck, Novartis, Genentech, and NanoString Technologies.

SOURCE: Chumsri et al. J Clin Oncol. 2019 Oct 17. doi: 10.1200/JCO.19.00443.

Back in 1980, the American Psychiatric Association dropped the word “neurosis” from the DSM-III, so that if you had been neurotic, after 1980, you were neurotic no longer.

ClaudioVentrella/Thinkstock

At the time, I discussed this on my daily radio show. For those folks who were nervous, worried, fearful, and full of anxieties about themselves, their families, welfare, health, and the environment around them, a new set of labels was introduced to more specifically describe one or more problems related to anxiety.

For codification, and at times, a clearer understanding of a specific problem, the change was made to be helpful. Certainly, for insurers and pharmacologic treatments, it worked. However, it’s interesting that the word and concept, neurosis, which still is used by some psychiatrists and psychologists – although not scientific – does offer a clear overall picture of a suffering, anxiety-ridden person who might have a combination of an anxiety disorder, panic attacks, somatic symptoms, and endless worry. This overlapping picture often is seen in clinical practice more than the multiple one-dimensional labels that are currently used. So be it.

This all leads me to what I’ve recently learned about the Neuroscience-based Nomenclature (NbN) Project. According to a recent article in the APA’s Psychiatric News, the group’s board of trustees has endorsed a proposal that would change or revise the names of psychiatric medications so that the names reflect their mechanism of action – a move seemingly focused on a pure biological model.

For example, according to the article, the medication perphenazine would be renamed a “D2 receptor antagonist” rather than an antipsychotic. For depression, we might have a serotonergic reuptake inhibitor, according to the report, and of course, the list of changes would go on – based on current knowledge of biological activity. It’s true that in general medicine, there are examples where mode of action is discussed. For example, in cardiology we have beta-blockers and alpha-blockers, which are descriptive of their actions. As doctors who have trained for years and know the mechanism of action of various medications, we will understand all this. But in patient care, both doctors and their patients often understand and feel comfortable using descriptive terms indicating the treatment modality, such as antibiotics, antivirals, antifungals, anti-inflammatory medications, as well as anti-itching, antiaging, and antispasmodic drugs.

So, I am concerned about these proposed changes. In an era focused on patient-centered care, where we seek to make it simpler for the patient/health care consumer, we might make it harder for the patient to grasp what’s going on.

It’s very important to keep in mind that we as physicians know the ins and outs of medications, and that even the most educated and bright patients who are not in medicine do not know what our education has taught us. For example, regardless of specialty, we all know the difference between left-sided and right-sided heart failure. Those outside of medicine, however, rarely know the difference. They understand heart disease as a rule. People in general might understand some general concepts, such as RBC, WBC, and platelets. A patient will speak of taking a blood thinner but rarely know or understand the differences between antiplatelets and anticoagulants. And why should they know this? How many of us know how or understand how to prepare a legal document or determine what type of steel is used in bridge construction?

The point here is that I believe good patient care is keeping it simple and taking the time to explain what’s being treated, aiming to inform patients using down-to-earth, accessible language rather than the language of biochemistry.

It’s true that in psychiatry, wider use of certain medications than originally indicated has grown tremendously as well as off-label use. In light of that, the NbN idea is laudable. However, it would seem more practical to leave the traditional modes of action in place and expand our discussions with patients as to why we are using a specific medication. I have found a very simple and even rewarding way to explain to patients, for example, that yes, this is an antiseizure medication but it is now used in psychiatry as a mood stabilizer.

Another important point is the question of whether using nomenclature that describes the exact location of the problem is all that accurate. Currently, we know we still have a lot to learn about brain chemistry and neuronal transmission in mental disorders, just as in many medical disorders, there are gaps in our understanding of many illnesses and subsequent molecular changes.

Just as the DSM-III left behind the all-encompassing and descriptive word neurosis and the APA has changed labels in the DSM-IV and DSM-5, so the NbN project would change the nomenclature of current psychotropic medications. The intentions are good, but the idea that those changes will foster better patient understanding defies common sense. A better idea might be to continue use of both scientific names and names of commonly used actions of the medications, leaving both in place and letting clinicians decide what nomenclature best suits each patient.

It will be a sad day when psychiatrists become so medically and “scientifically” driven that we cannot explain to a patient, “I’m prescribing this antidepressant because it’s now used to treat anxiety,” or “Yes, this medicine is labeled ‘antipsychotic,’ but you’re not psychotic. It may help your mood swings and may even help you sleep better.” Now, is that hard? Is talking to a person and explaining the treatment no longer part of care? The take-home messages from the recent APA/Institute of Psychiatric Services meeting I attended seemed to suggest that human attention and care have great value. My father, a surgeon, always said that you learn a lot by simply talking to patients – and they learn from you.

Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019).

Back in 1980, the American Psychiatric Association dropped the word “neurosis” from the DSM-III, so that if you had been neurotic, after 1980, you were neurotic no longer.

ClaudioVentrella/Thinkstock

At the time, I discussed this on my daily radio show. For those folks who were nervous, worried, fearful, and full of anxieties about themselves, their families, welfare, health, and the environment around them, a new set of labels was introduced to more specifically describe one or more problems related to anxiety.

For codification, and at times, a clearer understanding of a specific problem, the change was made to be helpful. Certainly, for insurers and pharmacologic treatments, it worked. However, it’s interesting that the word and concept, neurosis, which still is used by some psychiatrists and psychologists – although not scientific – does offer a clear overall picture of a suffering, anxiety-ridden person who might have a combination of an anxiety disorder, panic attacks, somatic symptoms, and endless worry. This overlapping picture often is seen in clinical practice more than the multiple one-dimensional labels that are currently used. So be it.

This all leads me to what I’ve recently learned about the Neuroscience-based Nomenclature (NbN) Project. According to a recent article in the APA’s Psychiatric News, the group’s board of trustees has endorsed a proposal that would change or revise the names of psychiatric medications so that the names reflect their mechanism of action – a move seemingly focused on a pure biological model.

For example, according to the article, the medication perphenazine would be renamed a “D2 receptor antagonist” rather than an antipsychotic. For depression, we might have a serotonergic reuptake inhibitor, according to the report, and of course, the list of changes would go on – based on current knowledge of biological activity. It’s true that in general medicine, there are examples where mode of action is discussed. For example, in cardiology we have beta-blockers and alpha-blockers, which are descriptive of their actions. As doctors who have trained for years and know the mechanism of action of various medications, we will understand all this. But in patient care, both doctors and their patients often understand and feel comfortable using descriptive terms indicating the treatment modality, such as antibiotics, antivirals, antifungals, anti-inflammatory medications, as well as anti-itching, antiaging, and antispasmodic drugs.

So, I am concerned about these proposed changes. In an era focused on patient-centered care, where we seek to make it simpler for the patient/health care consumer, we might make it harder for the patient to grasp what’s going on.

It’s very important to keep in mind that we as physicians know the ins and outs of medications, and that even the most educated and bright patients who are not in medicine do not know what our education has taught us. For example, regardless of specialty, we all know the difference between left-sided and right-sided heart failure. Those outside of medicine, however, rarely know the difference. They understand heart disease as a rule. People in general might understand some general concepts, such as RBC, WBC, and platelets. A patient will speak of taking a blood thinner but rarely know or understand the differences between antiplatelets and anticoagulants. And why should they know this? How many of us know how or understand how to prepare a legal document or determine what type of steel is used in bridge construction?

The point here is that I believe good patient care is keeping it simple and taking the time to explain what’s being treated, aiming to inform patients using down-to-earth, accessible language rather than the language of biochemistry.

It’s true that in psychiatry, wider use of certain medications than originally indicated has grown tremendously as well as off-label use. In light of that, the NbN idea is laudable. However, it would seem more practical to leave the traditional modes of action in place and expand our discussions with patients as to why we are using a specific medication. I have found a very simple and even rewarding way to explain to patients, for example, that yes, this is an antiseizure medication but it is now used in psychiatry as a mood stabilizer.

Another important point is the question of whether using nomenclature that describes the exact location of the problem is all that accurate. Currently, we know we still have a lot to learn about brain chemistry and neuronal transmission in mental disorders, just as in many medical disorders, there are gaps in our understanding of many illnesses and subsequent molecular changes.

Just as the DSM-III left behind the all-encompassing and descriptive word neurosis and the APA has changed labels in the DSM-IV and DSM-5, so the NbN project would change the nomenclature of current psychotropic medications. The intentions are good, but the idea that those changes will foster better patient understanding defies common sense. A better idea might be to continue use of both scientific names and names of commonly used actions of the medications, leaving both in place and letting clinicians decide what nomenclature best suits each patient.

It will be a sad day when psychiatrists become so medically and “scientifically” driven that we cannot explain to a patient, “I’m prescribing this antidepressant because it’s now used to treat anxiety,” or “Yes, this medicine is labeled ‘antipsychotic,’ but you’re not psychotic. It may help your mood swings and may even help you sleep better.” Now, is that hard? Is talking to a person and explaining the treatment no longer part of care? The take-home messages from the recent APA/Institute of Psychiatric Services meeting I attended seemed to suggest that human attention and care have great value. My father, a surgeon, always said that you learn a lot by simply talking to patients – and they learn from you.

Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019).

Back in 1980, the American Psychiatric Association dropped the word “neurosis” from the DSM-III, so that if you had been neurotic, after 1980, you were neurotic no longer.

ClaudioVentrella/Thinkstock

At the time, I discussed this on my daily radio show. For those folks who were nervous, worried, fearful, and full of anxieties about themselves, their families, welfare, health, and the environment around them, a new set of labels was introduced to more specifically describe one or more problems related to anxiety.

For codification, and at times, a clearer understanding of a specific problem, the change was made to be helpful. Certainly, for insurers and pharmacologic treatments, it worked. However, it’s interesting that the word and concept, neurosis, which still is used by some psychiatrists and psychologists – although not scientific – does offer a clear overall picture of a suffering, anxiety-ridden person who might have a combination of an anxiety disorder, panic attacks, somatic symptoms, and endless worry. This overlapping picture often is seen in clinical practice more than the multiple one-dimensional labels that are currently used. So be it.

This all leads me to what I’ve recently learned about the Neuroscience-based Nomenclature (NbN) Project. According to a recent article in the APA’s Psychiatric News, the group’s board of trustees has endorsed a proposal that would change or revise the names of psychiatric medications so that the names reflect their mechanism of action – a move seemingly focused on a pure biological model.

For example, according to the article, the medication perphenazine would be renamed a “D2 receptor antagonist” rather than an antipsychotic. For depression, we might have a serotonergic reuptake inhibitor, according to the report, and of course, the list of changes would go on – based on current knowledge of biological activity. It’s true that in general medicine, there are examples where mode of action is discussed. For example, in cardiology we have beta-blockers and alpha-blockers, which are descriptive of their actions. As doctors who have trained for years and know the mechanism of action of various medications, we will understand all this. But in patient care, both doctors and their patients often understand and feel comfortable using descriptive terms indicating the treatment modality, such as antibiotics, antivirals, antifungals, anti-inflammatory medications, as well as anti-itching, antiaging, and antispasmodic drugs.

So, I am concerned about these proposed changes. In an era focused on patient-centered care, where we seek to make it simpler for the patient/health care consumer, we might make it harder for the patient to grasp what’s going on.

It’s very important to keep in mind that we as physicians know the ins and outs of medications, and that even the most educated and bright patients who are not in medicine do not know what our education has taught us. For example, regardless of specialty, we all know the difference between left-sided and right-sided heart failure. Those outside of medicine, however, rarely know the difference. They understand heart disease as a rule. People in general might understand some general concepts, such as RBC, WBC, and platelets. A patient will speak of taking a blood thinner but rarely know or understand the differences between antiplatelets and anticoagulants. And why should they know this? How many of us know how or understand how to prepare a legal document or determine what type of steel is used in bridge construction?

The point here is that I believe good patient care is keeping it simple and taking the time to explain what’s being treated, aiming to inform patients using down-to-earth, accessible language rather than the language of biochemistry.

It’s true that in psychiatry, wider use of certain medications than originally indicated has grown tremendously as well as off-label use. In light of that, the NbN idea is laudable. However, it would seem more practical to leave the traditional modes of action in place and expand our discussions with patients as to why we are using a specific medication. I have found a very simple and even rewarding way to explain to patients, for example, that yes, this is an antiseizure medication but it is now used in psychiatry as a mood stabilizer.

Another important point is the question of whether using nomenclature that describes the exact location of the problem is all that accurate. Currently, we know we still have a lot to learn about brain chemistry and neuronal transmission in mental disorders, just as in many medical disorders, there are gaps in our understanding of many illnesses and subsequent molecular changes.

Just as the DSM-III left behind the all-encompassing and descriptive word neurosis and the APA has changed labels in the DSM-IV and DSM-5, so the NbN project would change the nomenclature of current psychotropic medications. The intentions are good, but the idea that those changes will foster better patient understanding defies common sense. A better idea might be to continue use of both scientific names and names of commonly used actions of the medications, leaving both in place and letting clinicians decide what nomenclature best suits each patient.

It will be a sad day when psychiatrists become so medically and “scientifically” driven that we cannot explain to a patient, “I’m prescribing this antidepressant because it’s now used to treat anxiety,” or “Yes, this medicine is labeled ‘antipsychotic,’ but you’re not psychotic. It may help your mood swings and may even help you sleep better.” Now, is that hard? Is talking to a person and explaining the treatment no longer part of care? The take-home messages from the recent APA/Institute of Psychiatric Services meeting I attended seemed to suggest that human attention and care have great value. My father, a surgeon, always said that you learn a lot by simply talking to patients – and they learn from you.

Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019).

The Food And Drug Administration has approved the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) for reducing the risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors, according to a statement from AstraZeneca.

The approval was based on results from the DECLARE-TIMI 58 cardiovascular outcomes trial, which evaluated dapagliflozin in more than 17,000 patients with type 2 diabetes and cardiovascular risk factors or cardiovascular disease. They showed that dapagliflozin significantly reduced the risk of the primary composite endpoint of hospitalization for heart failure by 27%, compared with placebo (2.5% vs. 3.3%; HR, 0.73; 95% confidence interval, 0.61-0.88).

The drug is an oral, once-daily SGLT2 inhibitor initially approved as a monotherapy or combination therapy for glycemic control in adults with type 2 diabetes. It has additional benefits of weight loss and reduction in blood pressure in concert with diet and exercise in the same population.

“[Dapagliflozin] is the first SGLT2 inhibitor approved in the US to reduce the risk of hospitalization for heart failure in patients with type 2 diabetes with established cardiovascular disease or multiple cardiovascular risk factors,” Ruud Dobber, PhD, executive vice president of the company’s biopharmaceuticals business unit, said in the statement. “This is promising news for the 30 million people living with type 2 diabetes in the U.S., as heart failure is one of the earliest cardiovascular complications for them, before heart attack or stroke. [Dapagliflozin] now offers the opportunity for physicians to act sooner and reduce the risk of hospitalization for heart failure.”


In September, the agency granted dapagliflozin a Fast Track designation to reduce the risk of cardiovascular death, or the worsening of heart failure in adults with heart failure with reduced ejection fraction or preserved ejection fraction, based on the phase 3 DAPA-HF and DELIVER trials. It also gave the drug Fast Track designation to delay the progression of renal failure and prevent CV and renal death in patients with chronic kidney disease based on the phase 3 DAPA-CKD trial, the statement noted.

[email protected]

The Food And Drug Administration has approved the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) for reducing the risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors, according to a statement from AstraZeneca.

The approval was based on results from the DECLARE-TIMI 58 cardiovascular outcomes trial, which evaluated dapagliflozin in more than 17,000 patients with type 2 diabetes and cardiovascular risk factors or cardiovascular disease. They showed that dapagliflozin significantly reduced the risk of the primary composite endpoint of hospitalization for heart failure by 27%, compared with placebo (2.5% vs. 3.3%; HR, 0.73; 95% confidence interval, 0.61-0.88).

The drug is an oral, once-daily SGLT2 inhibitor initially approved as a monotherapy or combination therapy for glycemic control in adults with type 2 diabetes. It has additional benefits of weight loss and reduction in blood pressure in concert with diet and exercise in the same population.

“[Dapagliflozin] is the first SGLT2 inhibitor approved in the US to reduce the risk of hospitalization for heart failure in patients with type 2 diabetes with established cardiovascular disease or multiple cardiovascular risk factors,” Ruud Dobber, PhD, executive vice president of the company’s biopharmaceuticals business unit, said in the statement. “This is promising news for the 30 million people living with type 2 diabetes in the U.S., as heart failure is one of the earliest cardiovascular complications for them, before heart attack or stroke. [Dapagliflozin] now offers the opportunity for physicians to act sooner and reduce the risk of hospitalization for heart failure.”


In September, the agency granted dapagliflozin a Fast Track designation to reduce the risk of cardiovascular death, or the worsening of heart failure in adults with heart failure with reduced ejection fraction or preserved ejection fraction, based on the phase 3 DAPA-HF and DELIVER trials. It also gave the drug Fast Track designation to delay the progression of renal failure and prevent CV and renal death in patients with chronic kidney disease based on the phase 3 DAPA-CKD trial, the statement noted.

[email protected]

The Food And Drug Administration has approved the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) for reducing the risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors, according to a statement from AstraZeneca.

The approval was based on results from the DECLARE-TIMI 58 cardiovascular outcomes trial, which evaluated dapagliflozin in more than 17,000 patients with type 2 diabetes and cardiovascular risk factors or cardiovascular disease. They showed that dapagliflozin significantly reduced the risk of the primary composite endpoint of hospitalization for heart failure by 27%, compared with placebo (2.5% vs. 3.3%; HR, 0.73; 95% confidence interval, 0.61-0.88).

The drug is an oral, once-daily SGLT2 inhibitor initially approved as a monotherapy or combination therapy for glycemic control in adults with type 2 diabetes. It has additional benefits of weight loss and reduction in blood pressure in concert with diet and exercise in the same population.

“[Dapagliflozin] is the first SGLT2 inhibitor approved in the US to reduce the risk of hospitalization for heart failure in patients with type 2 diabetes with established cardiovascular disease or multiple cardiovascular risk factors,” Ruud Dobber, PhD, executive vice president of the company’s biopharmaceuticals business unit, said in the statement. “This is promising news for the 30 million people living with type 2 diabetes in the U.S., as heart failure is one of the earliest cardiovascular complications for them, before heart attack or stroke. [Dapagliflozin] now offers the opportunity for physicians to act sooner and reduce the risk of hospitalization for heart failure.”


In September, the agency granted dapagliflozin a Fast Track designation to reduce the risk of cardiovascular death, or the worsening of heart failure in adults with heart failure with reduced ejection fraction or preserved ejection fraction, based on the phase 3 DAPA-HF and DELIVER trials. It also gave the drug Fast Track designation to delay the progression of renal failure and prevent CV and renal death in patients with chronic kidney disease based on the phase 3 DAPA-CKD trial, the statement noted.

[email protected]

COPENHAGEN – Selected antidiabetes medications appear to blunt the increased risk of dementia associated with type 2 diabetes, according to a Danish national case control registry study.

Boarding1Now/Thinkstock

This benefit applies to the newer antidiabetic agents – specifically, the dipeptidyl peptidase 4 (DPP4) inhibitors, the glucagon-like peptide 1 (GLP1) analogs, and the sodium-glucose transport protein 2 (SGLT2) inhibitors – and metformin as well, Merete Osler, MD, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

In contrast, neither insulin nor the sulfonylureas showed any signal of a protective effect against development of dementia. In fact, the use of sulfonylureas was associated with a small but statistically significant 7% increased risk, added Dr. Osler, of the University of Copenhagen.

Elsewhere at the meeting, investigators tapped a Swedish national registry to demonstrate that individuals with type 1 diabetes have a sharply reduced risk of developing schizophrenia.
 

Type 2 diabetes medications and dementia

Dr. Osler and colleagues are among several groups of investigators who have previously shown that patients with type 2 diabetes have an increased risk of dementia.

“This has raised the question of the role of dysregulated glucose metabolism in the development of this neurodegenerative disorder, and the possible effect of antidiabetic medications,” she noted.

To further explore this issue, which links two great ongoing global epidemics, Dr. Osler and coinvestigators conducted a nested case-control study including all 176,250 patients with type 2 diabetes in the comprehensive Danish National Diabetes Register for 1995-2012. The 11,619 patients with type 2 diabetes who received a dementia diagnosis were matched with 46,476 type 2 diabetes patients without dementia. The objective was to determine associations between dementia and ever-use and cumulative dose of antidiabetes drugs, alone and in combination, in logistic regression analyses adjusted for demographics, comorbid conditions, marital status, diabetic complications, and year of dementia diagnosis.

Patients who had ever used metformin had an adjusted 6% reduction in the likelihood of dementia compared with metformin nonusers, a modest but statistically significant difference. Those on a DPP4 inhibitor had a 20% reduction in risk. The GLP1 analogs were associated with a 42% decrease in risk. So were the SGLT2 inhibitors. A dose-response relationship was evident: The higher the cumulative exposure to these agents, the lower the odds of dementia.

Combination therapy is common in type 2 diabetes, so the investigators scrutinized the impact of a variety of multidrug combinations. The clear winner in terms of the magnitude of associated reduction in dementia risk were the combinations including an SGLT2 inhibitor, with a 62% relative risk reduction. Combinations including a DPP4 inhibitor or GLP1 analog were also associated with significantly reduced dementia risk.

Records of glycemic control in the form of hemoglobin A_1c values were available on only 1,446 type 2 diabetic dementia patients and 4,003 matched controls. An analysis that incorporated this variable showed that the observed anti-dementia effect of selected diabetes drugs was independent of glycemic control, according to Dr. Osler.

The protective effect appeared to extend to both Alzheimer’s disease and vascular dementias, although firm conclusions can’t be drawn on this score because the study was insufficiently powered to address that issue.

Dr. Osler noted that the Danish study confirms a recent Taiwanese study showing an apparent protective effect against dementia for metformin in patients with type 2 diabetes (Aging Dis. 2019 Feb 1;10(1):37-48).

“Ours is the first study on the newer diabetic drugs, so our results need to be confirmed,” she pointed out.

If confirmed, however, it would warrant exploration of these drugs more generally as potential interventions to prevent dementia. That could open a whole new chapter in the remarkable story of the SGLT2 inhibitors, a class of drugs originally developed for treatment of type 2 diabetes but which in major randomized clinical trials later proved to be so effective in the treatment of heart failure that they are now considered cardiology drugs first.

Asked if she thinks these antidiabetes agents have a general neuroprotective effect or, instead, that the observed reduced risk of dementia is a function of patients being treated better early on with modern drugs, the psychiatrist replied, “I think it might be a combination of both, especially because we find different risk estimates between the drugs.”

Dr. Osler reported having no financial conflicts of interest regarding the study, which was funded by the Danish Diabetes Foundation, the Danish Medical Association, and several other foundations.

The full study details were published online shortly before her presentation at ECNP 2019 (Eur J Endocrinol. 2019 Aug 1. pii: EJE-19-0259.R1. doi: 10.1530/EJE-19-0259).

Type 1 diabetes and schizophrenia risk

Kristina Melkersson, MD, PhD, presented a cohort study that utilized Swedish national registries to examine the relationship between type 1 diabetes and schizophrenia. The study comprised 1,745,977 individuals, of whom 10,117 had type 1 diabetes, who were followed for a median of 9.7 and maximum of 18 years from their 13th birthday. During follow-up, 1,280 individuals were diagnosed with schizophrenia and 649 others with schizoaffective disorder. The adjusted risk of schizophrenia was 70% lower in patients with type 1 diabetes. However, there was no difference in the risk of schizoaffective disorder in the type 1 diabetic versus nondiabetic subjects.

The Swedish data confirm the findings of an earlier Finnish national study showing that the risk of schizophrenia is reduced in patients with type 1 diabetes (Arch Gen Psychiatry. 2007 Aug;64(8):894-9). These findings raise the intriguing possibility that autoimmunity somehow figures into the etiology of the psychiatric disorder. Other investigators have previously reported a reduced prevalence of rheumatoid arthritis in patients with schizophrenia, noted Dr. Melkersson of the Karolinska Institute in Stockholm.

She reported having no financial conflicts regarding her study.

[email protected]

SOURCE: Osler M. ECNP Abstract P180. Melkersson K. Abstract 81.

COPENHAGEN – Selected antidiabetes medications appear to blunt the increased risk of dementia associated with type 2 diabetes, according to a Danish national case control registry study.

Boarding1Now/Thinkstock

This benefit applies to the newer antidiabetic agents – specifically, the dipeptidyl peptidase 4 (DPP4) inhibitors, the glucagon-like peptide 1 (GLP1) analogs, and the sodium-glucose transport protein 2 (SGLT2) inhibitors – and metformin as well, Merete Osler, MD, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

In contrast, neither insulin nor the sulfonylureas showed any signal of a protective effect against development of dementia. In fact, the use of sulfonylureas was associated with a small but statistically significant 7% increased risk, added Dr. Osler, of the University of Copenhagen.

Elsewhere at the meeting, investigators tapped a Swedish national registry to demonstrate that individuals with type 1 diabetes have a sharply reduced risk of developing schizophrenia.
 

Type 2 diabetes medications and dementia

Dr. Osler and colleagues are among several groups of investigators who have previously shown that patients with type 2 diabetes have an increased risk of dementia.

“This has raised the question of the role of dysregulated glucose metabolism in the development of this neurodegenerative disorder, and the possible effect of antidiabetic medications,” she noted.

To further explore this issue, which links two great ongoing global epidemics, Dr. Osler and coinvestigators conducted a nested case-control study including all 176,250 patients with type 2 diabetes in the comprehensive Danish National Diabetes Register for 1995-2012. The 11,619 patients with type 2 diabetes who received a dementia diagnosis were matched with 46,476 type 2 diabetes patients without dementia. The objective was to determine associations between dementia and ever-use and cumulative dose of antidiabetes drugs, alone and in combination, in logistic regression analyses adjusted for demographics, comorbid conditions, marital status, diabetic complications, and year of dementia diagnosis.

Patients who had ever used metformin had an adjusted 6% reduction in the likelihood of dementia compared with metformin nonusers, a modest but statistically significant difference. Those on a DPP4 inhibitor had a 20% reduction in risk. The GLP1 analogs were associated with a 42% decrease in risk. So were the SGLT2 inhibitors. A dose-response relationship was evident: The higher the cumulative exposure to these agents, the lower the odds of dementia.

Combination therapy is common in type 2 diabetes, so the investigators scrutinized the impact of a variety of multidrug combinations. The clear winner in terms of the magnitude of associated reduction in dementia risk were the combinations including an SGLT2 inhibitor, with a 62% relative risk reduction. Combinations including a DPP4 inhibitor or GLP1 analog were also associated with significantly reduced dementia risk.

Records of glycemic control in the form of hemoglobin A_1c values were available on only 1,446 type 2 diabetic dementia patients and 4,003 matched controls. An analysis that incorporated this variable showed that the observed anti-dementia effect of selected diabetes drugs was independent of glycemic control, according to Dr. Osler.

The protective effect appeared to extend to both Alzheimer’s disease and vascular dementias, although firm conclusions can’t be drawn on this score because the study was insufficiently powered to address that issue.

Dr. Osler noted that the Danish study confirms a recent Taiwanese study showing an apparent protective effect against dementia for metformin in patients with type 2 diabetes (Aging Dis. 2019 Feb 1;10(1):37-48).

“Ours is the first study on the newer diabetic drugs, so our results need to be confirmed,” she pointed out.

If confirmed, however, it would warrant exploration of these drugs more generally as potential interventions to prevent dementia. That could open a whole new chapter in the remarkable story of the SGLT2 inhibitors, a class of drugs originally developed for treatment of type 2 diabetes but which in major randomized clinical trials later proved to be so effective in the treatment of heart failure that they are now considered cardiology drugs first.

Asked if she thinks these antidiabetes agents have a general neuroprotective effect or, instead, that the observed reduced risk of dementia is a function of patients being treated better early on with modern drugs, the psychiatrist replied, “I think it might be a combination of both, especially because we find different risk estimates between the drugs.”

Dr. Osler reported having no financial conflicts of interest regarding the study, which was funded by the Danish Diabetes Foundation, the Danish Medical Association, and several other foundations.

The full study details were published online shortly before her presentation at ECNP 2019 (Eur J Endocrinol. 2019 Aug 1. pii: EJE-19-0259.R1. doi: 10.1530/EJE-19-0259).

Type 1 diabetes and schizophrenia risk

Kristina Melkersson, MD, PhD, presented a cohort study that utilized Swedish national registries to examine the relationship between type 1 diabetes and schizophrenia. The study comprised 1,745,977 individuals, of whom 10,117 had type 1 diabetes, who were followed for a median of 9.7 and maximum of 18 years from their 13th birthday. During follow-up, 1,280 individuals were diagnosed with schizophrenia and 649 others with schizoaffective disorder. The adjusted risk of schizophrenia was 70% lower in patients with type 1 diabetes. However, there was no difference in the risk of schizoaffective disorder in the type 1 diabetic versus nondiabetic subjects.

The Swedish data confirm the findings of an earlier Finnish national study showing that the risk of schizophrenia is reduced in patients with type 1 diabetes (Arch Gen Psychiatry. 2007 Aug;64(8):894-9). These findings raise the intriguing possibility that autoimmunity somehow figures into the etiology of the psychiatric disorder. Other investigators have previously reported a reduced prevalence of rheumatoid arthritis in patients with schizophrenia, noted Dr. Melkersson of the Karolinska Institute in Stockholm.

She reported having no financial conflicts regarding her study.

[email protected]

SOURCE: Osler M. ECNP Abstract P180. Melkersson K. Abstract 81.

COPENHAGEN – Selected antidiabetes medications appear to blunt the increased risk of dementia associated with type 2 diabetes, according to a Danish national case control registry study.

Boarding1Now/Thinkstock

This benefit applies to the newer antidiabetic agents – specifically, the dipeptidyl peptidase 4 (DPP4) inhibitors, the glucagon-like peptide 1 (GLP1) analogs, and the sodium-glucose transport protein 2 (SGLT2) inhibitors – and metformin as well, Merete Osler, MD, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

In contrast, neither insulin nor the sulfonylureas showed any signal of a protective effect against development of dementia. In fact, the use of sulfonylureas was associated with a small but statistically significant 7% increased risk, added Dr. Osler, of the University of Copenhagen.

Elsewhere at the meeting, investigators tapped a Swedish national registry to demonstrate that individuals with type 1 diabetes have a sharply reduced risk of developing schizophrenia.
 

Type 2 diabetes medications and dementia

Dr. Osler and colleagues are among several groups of investigators who have previously shown that patients with type 2 diabetes have an increased risk of dementia.

“This has raised the question of the role of dysregulated glucose metabolism in the development of this neurodegenerative disorder, and the possible effect of antidiabetic medications,” she noted.

To further explore this issue, which links two great ongoing global epidemics, Dr. Osler and coinvestigators conducted a nested case-control study including all 176,250 patients with type 2 diabetes in the comprehensive Danish National Diabetes Register for 1995-2012. The 11,619 patients with type 2 diabetes who received a dementia diagnosis were matched with 46,476 type 2 diabetes patients without dementia. The objective was to determine associations between dementia and ever-use and cumulative dose of antidiabetes drugs, alone and in combination, in logistic regression analyses adjusted for demographics, comorbid conditions, marital status, diabetic complications, and year of dementia diagnosis.

Patients who had ever used metformin had an adjusted 6% reduction in the likelihood of dementia compared with metformin nonusers, a modest but statistically significant difference. Those on a DPP4 inhibitor had a 20% reduction in risk. The GLP1 analogs were associated with a 42% decrease in risk. So were the SGLT2 inhibitors. A dose-response relationship was evident: The higher the cumulative exposure to these agents, the lower the odds of dementia.

Combination therapy is common in type 2 diabetes, so the investigators scrutinized the impact of a variety of multidrug combinations. The clear winner in terms of the magnitude of associated reduction in dementia risk were the combinations including an SGLT2 inhibitor, with a 62% relative risk reduction. Combinations including a DPP4 inhibitor or GLP1 analog were also associated with significantly reduced dementia risk.

Records of glycemic control in the form of hemoglobin A_1c values were available on only 1,446 type 2 diabetic dementia patients and 4,003 matched controls. An analysis that incorporated this variable showed that the observed anti-dementia effect of selected diabetes drugs was independent of glycemic control, according to Dr. Osler.

The protective effect appeared to extend to both Alzheimer’s disease and vascular dementias, although firm conclusions can’t be drawn on this score because the study was insufficiently powered to address that issue.

Dr. Osler noted that the Danish study confirms a recent Taiwanese study showing an apparent protective effect against dementia for metformin in patients with type 2 diabetes (Aging Dis. 2019 Feb 1;10(1):37-48).

“Ours is the first study on the newer diabetic drugs, so our results need to be confirmed,” she pointed out.

If confirmed, however, it would warrant exploration of these drugs more generally as potential interventions to prevent dementia. That could open a whole new chapter in the remarkable story of the SGLT2 inhibitors, a class of drugs originally developed for treatment of type 2 diabetes but which in major randomized clinical trials later proved to be so effective in the treatment of heart failure that they are now considered cardiology drugs first.

Asked if she thinks these antidiabetes agents have a general neuroprotective effect or, instead, that the observed reduced risk of dementia is a function of patients being treated better early on with modern drugs, the psychiatrist replied, “I think it might be a combination of both, especially because we find different risk estimates between the drugs.”

Dr. Osler reported having no financial conflicts of interest regarding the study, which was funded by the Danish Diabetes Foundation, the Danish Medical Association, and several other foundations.

The full study details were published online shortly before her presentation at ECNP 2019 (Eur J Endocrinol. 2019 Aug 1. pii: EJE-19-0259.R1. doi: 10.1530/EJE-19-0259).

Type 1 diabetes and schizophrenia risk

Kristina Melkersson, MD, PhD, presented a cohort study that utilized Swedish national registries to examine the relationship between type 1 diabetes and schizophrenia. The study comprised 1,745,977 individuals, of whom 10,117 had type 1 diabetes, who were followed for a median of 9.7 and maximum of 18 years from their 13th birthday. During follow-up, 1,280 individuals were diagnosed with schizophrenia and 649 others with schizoaffective disorder. The adjusted risk of schizophrenia was 70% lower in patients with type 1 diabetes. However, there was no difference in the risk of schizoaffective disorder in the type 1 diabetic versus nondiabetic subjects.

The Swedish data confirm the findings of an earlier Finnish national study showing that the risk of schizophrenia is reduced in patients with type 1 diabetes (Arch Gen Psychiatry. 2007 Aug;64(8):894-9). These findings raise the intriguing possibility that autoimmunity somehow figures into the etiology of the psychiatric disorder. Other investigators have previously reported a reduced prevalence of rheumatoid arthritis in patients with schizophrenia, noted Dr. Melkersson of the Karolinska Institute in Stockholm.

She reported having no financial conflicts regarding her study.

[email protected]

SOURCE: Osler M. ECNP Abstract P180. Melkersson K. Abstract 81.

An investigation into a potential biomarker for response to methotrexate found that changes in DNA methylation at 4 weeks were associated with improvements in rheumatoid arthritis (RA) patients at 6 months.

Zffoto/Thinkstock

“The findings in the current study are promising and appear to identify methylation patterns that are predictive of improvement of SJC [swollen joint count] and CRP [C-reactive protein],” wrote Nisha Nair, PhD, of the University of Manchester (England) and her coauthors. The study was published in Rheumatology.

The investigators analyzed DNA samples taken from patients recruited into the Rheumatoid Arthritis Medication Study (RAMS) who had RA or inflammatory polyarthritis and were beginning methotrexate for the first time. The samples were collected at baseline and at 4 weeks from patients who were classified as having good (n = 34) or poor (n = 34) responses to methotrexate after 6 months according to European League Against Rheumatism response criteria, in which good response was defined as having a 28-joint disease activity score (DAS28) of 3.2 or less and a 1.2-point improvement in DAS28 at 6 months, and poor response was defined as having DAS28 higher than 5.1 and improvement of 0.6 points or less at 6 months.

After analysis, two differentially methylated positions that differed between good and poor responders were identified in samples taken at the 4-week mark (P less than 1 × 10^–6). Four CpG (cytosine-phosphate-guanine) sites also predicted improvements in RA patients at 6 months: Two sites associated increased methylation in good responders at 4 weeks with long-term SJC improvement, while two others associated increased methylation at baseline and in good responders at 4 weeks with improvement of CRP levels.

The authors acknowledged their study’s limitations, including the fact that the relapsing nature of RA could have contributed to natural variance in DAS28. In addition, the study’s lack of a control group does not allow for separating prognostic from theranostic biomarkers, although they added that “in terms of selecting treatments that will be effective, that may not necessarily matter in the clinical setting.”

The study was funded by the Medical Research Council and Versus Arthritis. The authors reported no conflicts of interest.
 

SOURCE: Nair N et al. Rheumatology. 2019 Oct 10. doi: 10.1093/rheumatology/kez411

An investigation into a potential biomarker for response to methotrexate found that changes in DNA methylation at 4 weeks were associated with improvements in rheumatoid arthritis (RA) patients at 6 months.

Zffoto/Thinkstock

“The findings in the current study are promising and appear to identify methylation patterns that are predictive of improvement of SJC [swollen joint count] and CRP [C-reactive protein],” wrote Nisha Nair, PhD, of the University of Manchester (England) and her coauthors. The study was published in Rheumatology.

The investigators analyzed DNA samples taken from patients recruited into the Rheumatoid Arthritis Medication Study (RAMS) who had RA or inflammatory polyarthritis and were beginning methotrexate for the first time. The samples were collected at baseline and at 4 weeks from patients who were classified as having good (n = 34) or poor (n = 34) responses to methotrexate after 6 months according to European League Against Rheumatism response criteria, in which good response was defined as having a 28-joint disease activity score (DAS28) of 3.2 or less and a 1.2-point improvement in DAS28 at 6 months, and poor response was defined as having DAS28 higher than 5.1 and improvement of 0.6 points or less at 6 months.

After analysis, two differentially methylated positions that differed between good and poor responders were identified in samples taken at the 4-week mark (P less than 1 × 10^–6). Four CpG (cytosine-phosphate-guanine) sites also predicted improvements in RA patients at 6 months: Two sites associated increased methylation in good responders at 4 weeks with long-term SJC improvement, while two others associated increased methylation at baseline and in good responders at 4 weeks with improvement of CRP levels.

The authors acknowledged their study’s limitations, including the fact that the relapsing nature of RA could have contributed to natural variance in DAS28. In addition, the study’s lack of a control group does not allow for separating prognostic from theranostic biomarkers, although they added that “in terms of selecting treatments that will be effective, that may not necessarily matter in the clinical setting.”

The study was funded by the Medical Research Council and Versus Arthritis. The authors reported no conflicts of interest.
 

SOURCE: Nair N et al. Rheumatology. 2019 Oct 10. doi: 10.1093/rheumatology/kez411

An investigation into a potential biomarker for response to methotrexate found that changes in DNA methylation at 4 weeks were associated with improvements in rheumatoid arthritis (RA) patients at 6 months.

Zffoto/Thinkstock

“The findings in the current study are promising and appear to identify methylation patterns that are predictive of improvement of SJC [swollen joint count] and CRP [C-reactive protein],” wrote Nisha Nair, PhD, of the University of Manchester (England) and her coauthors. The study was published in Rheumatology.

The investigators analyzed DNA samples taken from patients recruited into the Rheumatoid Arthritis Medication Study (RAMS) who had RA or inflammatory polyarthritis and were beginning methotrexate for the first time. The samples were collected at baseline and at 4 weeks from patients who were classified as having good (n = 34) or poor (n = 34) responses to methotrexate after 6 months according to European League Against Rheumatism response criteria, in which good response was defined as having a 28-joint disease activity score (DAS28) of 3.2 or less and a 1.2-point improvement in DAS28 at 6 months, and poor response was defined as having DAS28 higher than 5.1 and improvement of 0.6 points or less at 6 months.

After analysis, two differentially methylated positions that differed between good and poor responders were identified in samples taken at the 4-week mark (P less than 1 × 10^–6). Four CpG (cytosine-phosphate-guanine) sites also predicted improvements in RA patients at 6 months: Two sites associated increased methylation in good responders at 4 weeks with long-term SJC improvement, while two others associated increased methylation at baseline and in good responders at 4 weeks with improvement of CRP levels.

The authors acknowledged their study’s limitations, including the fact that the relapsing nature of RA could have contributed to natural variance in DAS28. In addition, the study’s lack of a control group does not allow for separating prognostic from theranostic biomarkers, although they added that “in terms of selecting treatments that will be effective, that may not necessarily matter in the clinical setting.”

The study was funded by the Medical Research Council and Versus Arthritis. The authors reported no conflicts of interest.
 

SOURCE: Nair N et al. Rheumatology. 2019 Oct 10. doi: 10.1093/rheumatology/kez411

SEATTLE – Treatment of psoriasis has been profoundly impacted by the advent of biologic therapies, but “topical therapy is not dead,” Linda Stein Gold, MD, said at the annual Coastal Dermatology Symposium.

Jim Kling/MDedge News

“We have to remember when we think back to our practice, how many topical prescriptions do we write, compared to preventive prescriptions? Probably most are topical,” said Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Hospital Center, Detroit.

Topical agents have a place when a patient is doing well on treatment with a biologic but is not responding completely, she noted. One open-label, single-arm study looked at adjunctive calcipotriene 0.005%/betamethasone dipropionate 0.064% (Enstilar) foam, applied once daily for 4 week, then twice a week on consecutive days for 12 weeks in 25 patients with psoriasis who had a mean body surface area (BSA) of less than 5% but significant remaining disease despite treatment with biologics.

At week 4, 76% achieved a BSA of 1% or less and Physician’s Global Assessment score of 1 or less at week 4, as did 68% at week 16. This was compared with 12% and 4%, respectively (J Drugs Dermatol. 2018 Aug 1;17[8]:845-50). “They found that a good potent topical on top of a biologic does really well. That can really kick up the last part of the efficacy to get the patients almost to clear,” she observed.

At the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education, Dr. Stein Gold also discussed tazarotene, a topical retinoid approved by the Food and Drug Administration for treating psoriasis and is available as a 0.1% and 0.05% cream and gel. About 10%-30% of patients experience side effects with tazarotene, such as pruritus, stinging, and burning. Topical corticosteroids can help, which prompted development of a combined product, she noted.

She referred to a phase 2 study of patients with moderate to severe plaque psoriasis, which compared the fixed combination lotion formulation of tazarotene plus halobetasol propionate to the two components alone. The investigators found almost a 9% rate of treatment success with tazarotene alone, versus about 23% with halobetasol propionate alone and about 43% with the combined product. The combined individual effect of the two drugs was about 32%, so the 43% efficacy of the combined product had an absolute synergistic effect of about 11%, Dr. Stein Gold pointed out.

Two phase 3 trials of adults with moderate to severe psoriasis supported the phase 2 results of the combined lotion formulation (halobetasol 0.01% with tazarotene 0.045%), said Dr. Stein Gold, the first author (J Am Acad Dermatol. 2018 Aug;79[2]:287-93). Treatment success was defined as at least a 2-grade Investigator’s Global Assessment score and improvement from baseline and a score of “clear” or “almost clear.” In one of the studies, 36% of those on the combination versus 7% of those on the vehicle met this endpoint at week 8, as did 45% versus 13%, respectively, in the second study (P less than .001 for both studies).

Patients also had less itching, drying, and stinging than typically seen with tazarotene alone, Dr. Stein Gold said. In the studies, contact dermatitis was the most common side effect associated with treatment, reported in 6.3%

Dr. Stein Gold has received research support from Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, and Foamix. She has been a consultant for Sol-gel, Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, Promis, Anacor, and Medimetriks. She has been on the speakers bureau of Galderma, Leo, Valeant, Novartis, Celgene, and Allergan. She has been a member of scientific advisory boards for Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, and Promius.

This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – Treatment of psoriasis has been profoundly impacted by the advent of biologic therapies, but “topical therapy is not dead,” Linda Stein Gold, MD, said at the annual Coastal Dermatology Symposium.

Jim Kling/MDedge News

“We have to remember when we think back to our practice, how many topical prescriptions do we write, compared to preventive prescriptions? Probably most are topical,” said Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Hospital Center, Detroit.

Topical agents have a place when a patient is doing well on treatment with a biologic but is not responding completely, she noted. One open-label, single-arm study looked at adjunctive calcipotriene 0.005%/betamethasone dipropionate 0.064% (Enstilar) foam, applied once daily for 4 week, then twice a week on consecutive days for 12 weeks in 25 patients with psoriasis who had a mean body surface area (BSA) of less than 5% but significant remaining disease despite treatment with biologics.

At week 4, 76% achieved a BSA of 1% or less and Physician’s Global Assessment score of 1 or less at week 4, as did 68% at week 16. This was compared with 12% and 4%, respectively (J Drugs Dermatol. 2018 Aug 1;17[8]:845-50). “They found that a good potent topical on top of a biologic does really well. That can really kick up the last part of the efficacy to get the patients almost to clear,” she observed.

At the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education, Dr. Stein Gold also discussed tazarotene, a topical retinoid approved by the Food and Drug Administration for treating psoriasis and is available as a 0.1% and 0.05% cream and gel. About 10%-30% of patients experience side effects with tazarotene, such as pruritus, stinging, and burning. Topical corticosteroids can help, which prompted development of a combined product, she noted.

She referred to a phase 2 study of patients with moderate to severe plaque psoriasis, which compared the fixed combination lotion formulation of tazarotene plus halobetasol propionate to the two components alone. The investigators found almost a 9% rate of treatment success with tazarotene alone, versus about 23% with halobetasol propionate alone and about 43% with the combined product. The combined individual effect of the two drugs was about 32%, so the 43% efficacy of the combined product had an absolute synergistic effect of about 11%, Dr. Stein Gold pointed out.

Two phase 3 trials of adults with moderate to severe psoriasis supported the phase 2 results of the combined lotion formulation (halobetasol 0.01% with tazarotene 0.045%), said Dr. Stein Gold, the first author (J Am Acad Dermatol. 2018 Aug;79[2]:287-93). Treatment success was defined as at least a 2-grade Investigator’s Global Assessment score and improvement from baseline and a score of “clear” or “almost clear.” In one of the studies, 36% of those on the combination versus 7% of those on the vehicle met this endpoint at week 8, as did 45% versus 13%, respectively, in the second study (P less than .001 for both studies).

Patients also had less itching, drying, and stinging than typically seen with tazarotene alone, Dr. Stein Gold said. In the studies, contact dermatitis was the most common side effect associated with treatment, reported in 6.3%

Dr. Stein Gold has received research support from Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, and Foamix. She has been a consultant for Sol-gel, Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, Promis, Anacor, and Medimetriks. She has been on the speakers bureau of Galderma, Leo, Valeant, Novartis, Celgene, and Allergan. She has been a member of scientific advisory boards for Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, and Promius.

This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – Treatment of psoriasis has been profoundly impacted by the advent of biologic therapies, but “topical therapy is not dead,” Linda Stein Gold, MD, said at the annual Coastal Dermatology Symposium.

Jim Kling/MDedge News

“We have to remember when we think back to our practice, how many topical prescriptions do we write, compared to preventive prescriptions? Probably most are topical,” said Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Hospital Center, Detroit.

Topical agents have a place when a patient is doing well on treatment with a biologic but is not responding completely, she noted. One open-label, single-arm study looked at adjunctive calcipotriene 0.005%/betamethasone dipropionate 0.064% (Enstilar) foam, applied once daily for 4 week, then twice a week on consecutive days for 12 weeks in 25 patients with psoriasis who had a mean body surface area (BSA) of less than 5% but significant remaining disease despite treatment with biologics.

At week 4, 76% achieved a BSA of 1% or less and Physician’s Global Assessment score of 1 or less at week 4, as did 68% at week 16. This was compared with 12% and 4%, respectively (J Drugs Dermatol. 2018 Aug 1;17[8]:845-50). “They found that a good potent topical on top of a biologic does really well. That can really kick up the last part of the efficacy to get the patients almost to clear,” she observed.

At the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education, Dr. Stein Gold also discussed tazarotene, a topical retinoid approved by the Food and Drug Administration for treating psoriasis and is available as a 0.1% and 0.05% cream and gel. About 10%-30% of patients experience side effects with tazarotene, such as pruritus, stinging, and burning. Topical corticosteroids can help, which prompted development of a combined product, she noted.

She referred to a phase 2 study of patients with moderate to severe plaque psoriasis, which compared the fixed combination lotion formulation of tazarotene plus halobetasol propionate to the two components alone. The investigators found almost a 9% rate of treatment success with tazarotene alone, versus about 23% with halobetasol propionate alone and about 43% with the combined product. The combined individual effect of the two drugs was about 32%, so the 43% efficacy of the combined product had an absolute synergistic effect of about 11%, Dr. Stein Gold pointed out.

Two phase 3 trials of adults with moderate to severe psoriasis supported the phase 2 results of the combined lotion formulation (halobetasol 0.01% with tazarotene 0.045%), said Dr. Stein Gold, the first author (J Am Acad Dermatol. 2018 Aug;79[2]:287-93). Treatment success was defined as at least a 2-grade Investigator’s Global Assessment score and improvement from baseline and a score of “clear” or “almost clear.” In one of the studies, 36% of those on the combination versus 7% of those on the vehicle met this endpoint at week 8, as did 45% versus 13%, respectively, in the second study (P less than .001 for both studies).

Patients also had less itching, drying, and stinging than typically seen with tazarotene alone, Dr. Stein Gold said. In the studies, contact dermatitis was the most common side effect associated with treatment, reported in 6.3%

Dr. Stein Gold has received research support from Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, and Foamix. She has been a consultant for Sol-gel, Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, Promis, Anacor, and Medimetriks. She has been on the speakers bureau of Galderma, Leo, Valeant, Novartis, Celgene, and Allergan. She has been a member of scientific advisory boards for Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, and Promius.

This publication and Global Academy for Medical Education are owned by the same parent company.

MADRID – In adults with severe chronic rhinosinusitus with nasal polyps (CRSwNP), the monoclonal antibody dupilumab is effective for shrinking the polyps, improving symptoms, and reducing the need for systemic corticosteroids and surgery, according to results of two phase 3 studies reported together at the annual congress of the European Respiratory Society.

“Dupilumab improved all of the disease components, and the improvement was observed in most of them at the first assessment,” reported Jorge F. Máspero, MD, research director, Fundacion Cidea, Buenos Aires.

The data were drawn from multicenter phase 3 trials called LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52. Both included stratifications for asthma and for NSAID-exacerbated respiratory disease (ERD), which are common comorbidities. Findings of the two studies were published together just prior to Dr. Máspero’s presentation at the ERS (Lancet. 2019 Sep 26. doi: 10.1016/S0140-6736(19)31881-1).

For the coprimary end point of endoscopic nasal polyp score (NSP), the reductions were 2.06 and 1.8 at 24 weeks from baseline (both P less than .0001) in SINUS-24 and SINUS-52, respectively. For the nasal congestion or obstruction score, another primary end point, the reductions were 0.89 and 0.87, respectively (both P less than .0001).

There were also major improvements at week 24 on secondary end points, including the Lund-McKay CT score for staging of CRSwNP (P less than .0001), total symptom score (P less than .0001), the UPSIT test for smell (P less than .0001), and SNOT-22 (P less than .0001), a quality of life instrument specific for nasal and sinus diseases.

When these outcomes were graphed, curves for the dupilumab and placebo arms had already separated by 4 weeks, “and then we see the dupilumab patients keep getting better over the course of follow-up, and the effect was seen regardless of comorbidities,” said Dr. Máspero, referring to concomitant asthma or ERD.

The SINUS-24 trial randomly assigned 276 CRSwNP patients to 300 mg dupilumab or placebo, each given subcutaneously every 2 weeks. The SINUS-52 trial, which randomized 448 patients, included the same two arms plus a third arm in which patients also received 300 mg dupilumab every 2 weeks for 24 weeks and then 300 mg every month for an additional 26 weeks.

In a pooled analysis of these trials, patients randomized to dupilumab had a 78% reduction in likelihood of receiving systemic corticosteroids and a 79% reduction in being referred for surgery relative to placebo, Dr. Máspero reported.

Dupilumab, a monoclonal antibody that inhibits the activity of interleukin-4, IL-5, and IL-13, was well tolerated. Among the most common adverse events, there were lower rates of headache (9% vs. 7%), epistaxis (7% vs. 6%), and injection-site erythema (8% vs. 6%) in the dupilumab and placebo arms, respectively, but the rate of serious adverse events (6% vs. 3%) and adverse events leading to treatment discontinuation (5% vs. 3%) were only slightly higher in the active treatment group.

Both trials, which required a bilateral baseline NPS score of 5.0 for entry, recruited a population with relatively severe CRSwNP, according to Dr. Máspero. Of the 724 patients, 204 had ERD.

A restored sense of smell was one of the contributors to an improvement in quality of life.

“The sense of smell improves very quickly after starting dupilumab. Patients reported results within 2 weeks, and there was an almost complete lack of improvement in the placebo group,” Dr. Máspero reported.

Dupilumab is already indicated for the treatment of CRSwNP, but this study confirms a major effect on polyp size, sinus congestion, and symptoms irrespective of the presence of common comorbidities affecting the airways, Dr. Máspero said.

Dr. Maspero reports no potential conflicts of interest.

SOURCE: (Bachert C et al. Lancet. 2019 Sep 26. doi: 10.1016/S0140-6736(19)31881-1.

MADRID – In adults with severe chronic rhinosinusitus with nasal polyps (CRSwNP), the monoclonal antibody dupilumab is effective for shrinking the polyps, improving symptoms, and reducing the need for systemic corticosteroids and surgery, according to results of two phase 3 studies reported together at the annual congress of the European Respiratory Society.

“Dupilumab improved all of the disease components, and the improvement was observed in most of them at the first assessment,” reported Jorge F. Máspero, MD, research director, Fundacion Cidea, Buenos Aires.

The data were drawn from multicenter phase 3 trials called LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52. Both included stratifications for asthma and for NSAID-exacerbated respiratory disease (ERD), which are common comorbidities. Findings of the two studies were published together just prior to Dr. Máspero’s presentation at the ERS (Lancet. 2019 Sep 26. doi: 10.1016/S0140-6736(19)31881-1).

For the coprimary end point of endoscopic nasal polyp score (NSP), the reductions were 2.06 and 1.8 at 24 weeks from baseline (both P less than .0001) in SINUS-24 and SINUS-52, respectively. For the nasal congestion or obstruction score, another primary end point, the reductions were 0.89 and 0.87, respectively (both P less than .0001).

There were also major improvements at week 24 on secondary end points, including the Lund-McKay CT score for staging of CRSwNP (P less than .0001), total symptom score (P less than .0001), the UPSIT test for smell (P less than .0001), and SNOT-22 (P less than .0001), a quality of life instrument specific for nasal and sinus diseases.

When these outcomes were graphed, curves for the dupilumab and placebo arms had already separated by 4 weeks, “and then we see the dupilumab patients keep getting better over the course of follow-up, and the effect was seen regardless of comorbidities,” said Dr. Máspero, referring to concomitant asthma or ERD.

The SINUS-24 trial randomly assigned 276 CRSwNP patients to 300 mg dupilumab or placebo, each given subcutaneously every 2 weeks. The SINUS-52 trial, which randomized 448 patients, included the same two arms plus a third arm in which patients also received 300 mg dupilumab every 2 weeks for 24 weeks and then 300 mg every month for an additional 26 weeks.

In a pooled analysis of these trials, patients randomized to dupilumab had a 78% reduction in likelihood of receiving systemic corticosteroids and a 79% reduction in being referred for surgery relative to placebo, Dr. Máspero reported.

Dupilumab, a monoclonal antibody that inhibits the activity of interleukin-4, IL-5, and IL-13, was well tolerated. Among the most common adverse events, there were lower rates of headache (9% vs. 7%), epistaxis (7% vs. 6%), and injection-site erythema (8% vs. 6%) in the dupilumab and placebo arms, respectively, but the rate of serious adverse events (6% vs. 3%) and adverse events leading to treatment discontinuation (5% vs. 3%) were only slightly higher in the active treatment group.

Both trials, which required a bilateral baseline NPS score of 5.0 for entry, recruited a population with relatively severe CRSwNP, according to Dr. Máspero. Of the 724 patients, 204 had ERD.

A restored sense of smell was one of the contributors to an improvement in quality of life.

“The sense of smell improves very quickly after starting dupilumab. Patients reported results within 2 weeks, and there was an almost complete lack of improvement in the placebo group,” Dr. Máspero reported.

Dupilumab is already indicated for the treatment of CRSwNP, but this study confirms a major effect on polyp size, sinus congestion, and symptoms irrespective of the presence of common comorbidities affecting the airways, Dr. Máspero said.

Dr. Maspero reports no potential conflicts of interest.

SOURCE: (Bachert C et al. Lancet. 2019 Sep 26. doi: 10.1016/S0140-6736(19)31881-1.

MADRID – In adults with severe chronic rhinosinusitus with nasal polyps (CRSwNP), the monoclonal antibody dupilumab is effective for shrinking the polyps, improving symptoms, and reducing the need for systemic corticosteroids and surgery, according to results of two phase 3 studies reported together at the annual congress of the European Respiratory Society.

“Dupilumab improved all of the disease components, and the improvement was observed in most of them at the first assessment,” reported Jorge F. Máspero, MD, research director, Fundacion Cidea, Buenos Aires.

The data were drawn from multicenter phase 3 trials called LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52. Both included stratifications for asthma and for NSAID-exacerbated respiratory disease (ERD), which are common comorbidities. Findings of the two studies were published together just prior to Dr. Máspero’s presentation at the ERS (Lancet. 2019 Sep 26. doi: 10.1016/S0140-6736(19)31881-1).

For the coprimary end point of endoscopic nasal polyp score (NSP), the reductions were 2.06 and 1.8 at 24 weeks from baseline (both P less than .0001) in SINUS-24 and SINUS-52, respectively. For the nasal congestion or obstruction score, another primary end point, the reductions were 0.89 and 0.87, respectively (both P less than .0001).

There were also major improvements at week 24 on secondary end points, including the Lund-McKay CT score for staging of CRSwNP (P less than .0001), total symptom score (P less than .0001), the UPSIT test for smell (P less than .0001), and SNOT-22 (P less than .0001), a quality of life instrument specific for nasal and sinus diseases.

When these outcomes were graphed, curves for the dupilumab and placebo arms had already separated by 4 weeks, “and then we see the dupilumab patients keep getting better over the course of follow-up, and the effect was seen regardless of comorbidities,” said Dr. Máspero, referring to concomitant asthma or ERD.

The SINUS-24 trial randomly assigned 276 CRSwNP patients to 300 mg dupilumab or placebo, each given subcutaneously every 2 weeks. The SINUS-52 trial, which randomized 448 patients, included the same two arms plus a third arm in which patients also received 300 mg dupilumab every 2 weeks for 24 weeks and then 300 mg every month for an additional 26 weeks.

In a pooled analysis of these trials, patients randomized to dupilumab had a 78% reduction in likelihood of receiving systemic corticosteroids and a 79% reduction in being referred for surgery relative to placebo, Dr. Máspero reported.

Dupilumab, a monoclonal antibody that inhibits the activity of interleukin-4, IL-5, and IL-13, was well tolerated. Among the most common adverse events, there were lower rates of headache (9% vs. 7%), epistaxis (7% vs. 6%), and injection-site erythema (8% vs. 6%) in the dupilumab and placebo arms, respectively, but the rate of serious adverse events (6% vs. 3%) and adverse events leading to treatment discontinuation (5% vs. 3%) were only slightly higher in the active treatment group.

Both trials, which required a bilateral baseline NPS score of 5.0 for entry, recruited a population with relatively severe CRSwNP, according to Dr. Máspero. Of the 724 patients, 204 had ERD.

A restored sense of smell was one of the contributors to an improvement in quality of life.

“The sense of smell improves very quickly after starting dupilumab. Patients reported results within 2 weeks, and there was an almost complete lack of improvement in the placebo group,” Dr. Máspero reported.

Dupilumab is already indicated for the treatment of CRSwNP, but this study confirms a major effect on polyp size, sinus congestion, and symptoms irrespective of the presence of common comorbidities affecting the airways, Dr. Máspero said.

Dr. Maspero reports no potential conflicts of interest.

SOURCE: (Bachert C et al. Lancet. 2019 Sep 26. doi: 10.1016/S0140-6736(19)31881-1.