High plasma levels of tumor necrosis factor (TNF)–alpha and adiponectin can be used to differentiate patients with psoriasis and psoriatic arthritis, according to Wen-Qing Li, PhD, of Brown University, Providence, R.I., and his associates.

In a research letter published in the British Journal of Dermatology, the investigators detailed an analysis of 180 patients with psoriasis only and 143 patients with psoriatic arthritis (PsA) from the Psoriatic Arthritis and Psoriasis Follow-up Study. Patients in both groups had a mean age of 51 years. Plasma levels of interleukin-6, C-reactive protein, TNF-alpha, leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin were assessed as potential biomarkers by ultrasensitive enzyme-linked immunosorbent assay or immunoturbidimetric assay.

Median TNF-alpha plasma levels were higher in patients with PsA, compared with those with psoriasis (3.27 vs. 1.32 pg/mL^–1), while total and HMW adiponectin levels were lower in patients with PsA, compared with those with psoriasis (4.66 vs. 5.36 mcg/mL^–1; 2.58 vs. 3.01 mcg/mL^–1). After logistic regression, TNF-alpha (adjusted odds ratio, 2.25; 95% confidence interval, 1.41-3.61) and total adiponectin (aOR, 0.61; 95% CI, 0.39-0.96) remained significantly associated as biomarkers. HMW adiponectin maintained marginal significance (aOR, 0.64; 95% CI, 0.41-1.01).

“Further large-scale investigation in a prospective setting of patients with PsO [psoriasis] would be warranted, if a clinically useful screening test is to be developed for risk prediction of PsA based on circulating biomarkers,” the investigators concluded.

Two study authors reported consulting with or advising numerous pharmaceutical companies.

lfranki@mdedge.com

SOURCE: Li W-Q et al. Br J Dermatol. 2019 Jan 29. doi: 10.1111/bjd.17700.

High plasma levels of tumor necrosis factor (TNF)–alpha and adiponectin can be used to differentiate patients with psoriasis and psoriatic arthritis, according to Wen-Qing Li, PhD, of Brown University, Providence, R.I., and his associates.

In a research letter published in the British Journal of Dermatology, the investigators detailed an analysis of 180 patients with psoriasis only and 143 patients with psoriatic arthritis (PsA) from the Psoriatic Arthritis and Psoriasis Follow-up Study. Patients in both groups had a mean age of 51 years. Plasma levels of interleukin-6, C-reactive protein, TNF-alpha, leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin were assessed as potential biomarkers by ultrasensitive enzyme-linked immunosorbent assay or immunoturbidimetric assay.

Median TNF-alpha plasma levels were higher in patients with PsA, compared with those with psoriasis (3.27 vs. 1.32 pg/mL^–1), while total and HMW adiponectin levels were lower in patients with PsA, compared with those with psoriasis (4.66 vs. 5.36 mcg/mL^–1; 2.58 vs. 3.01 mcg/mL^–1). After logistic regression, TNF-alpha (adjusted odds ratio, 2.25; 95% confidence interval, 1.41-3.61) and total adiponectin (aOR, 0.61; 95% CI, 0.39-0.96) remained significantly associated as biomarkers. HMW adiponectin maintained marginal significance (aOR, 0.64; 95% CI, 0.41-1.01).

“Further large-scale investigation in a prospective setting of patients with PsO [psoriasis] would be warranted, if a clinically useful screening test is to be developed for risk prediction of PsA based on circulating biomarkers,” the investigators concluded.

Two study authors reported consulting with or advising numerous pharmaceutical companies.

lfranki@mdedge.com

SOURCE: Li W-Q et al. Br J Dermatol. 2019 Jan 29. doi: 10.1111/bjd.17700.

High plasma levels of tumor necrosis factor (TNF)–alpha and adiponectin can be used to differentiate patients with psoriasis and psoriatic arthritis, according to Wen-Qing Li, PhD, of Brown University, Providence, R.I., and his associates.

In a research letter published in the British Journal of Dermatology, the investigators detailed an analysis of 180 patients with psoriasis only and 143 patients with psoriatic arthritis (PsA) from the Psoriatic Arthritis and Psoriasis Follow-up Study. Patients in both groups had a mean age of 51 years. Plasma levels of interleukin-6, C-reactive protein, TNF-alpha, leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin were assessed as potential biomarkers by ultrasensitive enzyme-linked immunosorbent assay or immunoturbidimetric assay.

Median TNF-alpha plasma levels were higher in patients with PsA, compared with those with psoriasis (3.27 vs. 1.32 pg/mL^–1), while total and HMW adiponectin levels were lower in patients with PsA, compared with those with psoriasis (4.66 vs. 5.36 mcg/mL^–1; 2.58 vs. 3.01 mcg/mL^–1). After logistic regression, TNF-alpha (adjusted odds ratio, 2.25; 95% confidence interval, 1.41-3.61) and total adiponectin (aOR, 0.61; 95% CI, 0.39-0.96) remained significantly associated as biomarkers. HMW adiponectin maintained marginal significance (aOR, 0.64; 95% CI, 0.41-1.01).

“Further large-scale investigation in a prospective setting of patients with PsO [psoriasis] would be warranted, if a clinically useful screening test is to be developed for risk prediction of PsA based on circulating biomarkers,” the investigators concluded.

Two study authors reported consulting with or advising numerous pharmaceutical companies.

lfranki@mdedge.com

SOURCE: Li W-Q et al. Br J Dermatol. 2019 Jan 29. doi: 10.1111/bjd.17700.

PHILADELPHIA – Medical marijuana research to date provides some support for its use in neuropathic pain, nausea and vomiting, and spasticity, some insights into adverse effects, and “a lot of the Wild West,” Ellie Grossman, MD, MPH, said here at the annual meeting of the American College of Physicians.

Andrew Bowser/MDedge News

The opioid-sparing effects of medical marijuana have been highlighted in recent reports suggesting that cannabis users may use less opioids, and that states with medical marijuana laws have seen drops in opioid overdose mortality, Dr. Grossman said.

“That’s kind of a story on pain and cannabinoids, and that’s really the biggest story there is in terms of medical evidence and effectiveness for this agent,” said Dr. Grossman, an instructor at Harvard Medical School and Primary Care Lead for Behavioral Health Integration, Cambridge Health Alliance, Somerville, Mass.

However, being the top story in medical marijuana may not be a very high bar in 2019, given current issues with research in this area, including inconsistencies in medical marijuana formulations, relatively small numbers of patients enrolled in studies, and meta-analyses that have produced equivocal results.

“Unfortunately, this is an area where there’s a lot of, shall I say, ‘squishiness’ in the data, through no fault of the researchers involved – it’s just an area that’s really hard to study,” Dr. Goodman said in her update on medical marijuana use at the meeting.

Most studies of cannabinoids for chronic pain have compared these agents to placebo, rather than the long list of other medications that might be used to treat pain, Dr. Grossman said.

There are several meta-analyses available, including a recently published Cochrane review in which authors concluded that, for neuropathic pain, the potential benefits of cannabis-based medicines may outweigh their potential harms.

“The upshot here is that there may be some evidence for neuropathic pain, but the evidence is generally of poor quality and kind of mixed,” said Dr. Grossman.

State-level medical cannabis laws were linked to significantly lower opioid overdose mortality rates in a 2014 study (JAMA Intern Med. 2014;174[10]:1668-73). In more recent studies, states with medical cannabis laws were found to have lower Medicare Part D opioid-prescribing rates, and in another study, legalization of medical marijuana was linked to lower rates of chronic and high-risk opioid use.

“It certainly seems like maybe we as prescribers are prescribing [fewer] opioids if there’s medical cannabis around,” Dr. Grossman said. “What this means for our patients in the short term and long term, we don’t totally know. But clearly, fewer opioid overdoses is a way better thing than more, so there could be something here.”

The cannabinoids approved by the Food and Drug Administration include nabilone (Cesamet) and dronabinol (Marinol), both synthetic cannabinoids indicated for cancer chemotherapy–related nausea and vomiting, along with cannabidiol (Epidiolex), just approved in June 2018 for treatment of some rare pediatric refractory epilepsy syndromes, Dr. Grossman said.

For chemotherapy-induced nausea and vomiting, evidence suggests oral cannabinoids are more effective than placebo, but there’s mixed evidence as to whether they are better than other antiemetics, Dr. Grossman said, while in terms of spasticity related to multiple sclerosis, research has shown small improvements in patient-reported symptoms.

Long-term adverse event data specific to medical marijuana are scant, with much of the evidence coming from studies of recreational marijuana users, Dr. Grossman said.

Those long-term effects include increased risk of pulmonary effects such as cough, wheeze, and phlegm that improve with discontinuation; case reports of unintentional pediatric ingestions; and lower neonatal birth weight, which should be discussed with women of reproductive age who are using or considering medical marijuana, Dr. Grossman said.

Motor vehicle accidents, development of psychiatric symptoms, and psychosis relapse also have been linked to use, she said.

Some real-world adverse event data specific to medical marijuana data are available through the Minnesota medical cannabis program. They found 16% of surveyed users reported an adverse event within the first 4 months, including dry mouth, fatigue, mental clouding, and drowsiness, Dr. Grossman told attendees.

Dr. Grossman reported that she has no relationship with entities producing, marketing, reselling, or distributing health care goods or services consumed by, or used on, patients.

SOURCE: Grossman E. ACP 2019, Presentation MTP 010.

PHILADELPHIA – Medical marijuana research to date provides some support for its use in neuropathic pain, nausea and vomiting, and spasticity, some insights into adverse effects, and “a lot of the Wild West,” Ellie Grossman, MD, MPH, said here at the annual meeting of the American College of Physicians.

Andrew Bowser/MDedge News

The opioid-sparing effects of medical marijuana have been highlighted in recent reports suggesting that cannabis users may use less opioids, and that states with medical marijuana laws have seen drops in opioid overdose mortality, Dr. Grossman said.

“That’s kind of a story on pain and cannabinoids, and that’s really the biggest story there is in terms of medical evidence and effectiveness for this agent,” said Dr. Grossman, an instructor at Harvard Medical School and Primary Care Lead for Behavioral Health Integration, Cambridge Health Alliance, Somerville, Mass.

However, being the top story in medical marijuana may not be a very high bar in 2019, given current issues with research in this area, including inconsistencies in medical marijuana formulations, relatively small numbers of patients enrolled in studies, and meta-analyses that have produced equivocal results.

“Unfortunately, this is an area where there’s a lot of, shall I say, ‘squishiness’ in the data, through no fault of the researchers involved – it’s just an area that’s really hard to study,” Dr. Goodman said in her update on medical marijuana use at the meeting.

Most studies of cannabinoids for chronic pain have compared these agents to placebo, rather than the long list of other medications that might be used to treat pain, Dr. Grossman said.

There are several meta-analyses available, including a recently published Cochrane review in which authors concluded that, for neuropathic pain, the potential benefits of cannabis-based medicines may outweigh their potential harms.

“The upshot here is that there may be some evidence for neuropathic pain, but the evidence is generally of poor quality and kind of mixed,” said Dr. Grossman.

State-level medical cannabis laws were linked to significantly lower opioid overdose mortality rates in a 2014 study (JAMA Intern Med. 2014;174[10]:1668-73). In more recent studies, states with medical cannabis laws were found to have lower Medicare Part D opioid-prescribing rates, and in another study, legalization of medical marijuana was linked to lower rates of chronic and high-risk opioid use.

“It certainly seems like maybe we as prescribers are prescribing [fewer] opioids if there’s medical cannabis around,” Dr. Grossman said. “What this means for our patients in the short term and long term, we don’t totally know. But clearly, fewer opioid overdoses is a way better thing than more, so there could be something here.”

The cannabinoids approved by the Food and Drug Administration include nabilone (Cesamet) and dronabinol (Marinol), both synthetic cannabinoids indicated for cancer chemotherapy–related nausea and vomiting, along with cannabidiol (Epidiolex), just approved in June 2018 for treatment of some rare pediatric refractory epilepsy syndromes, Dr. Grossman said.

For chemotherapy-induced nausea and vomiting, evidence suggests oral cannabinoids are more effective than placebo, but there’s mixed evidence as to whether they are better than other antiemetics, Dr. Grossman said, while in terms of spasticity related to multiple sclerosis, research has shown small improvements in patient-reported symptoms.

Long-term adverse event data specific to medical marijuana are scant, with much of the evidence coming from studies of recreational marijuana users, Dr. Grossman said.

Those long-term effects include increased risk of pulmonary effects such as cough, wheeze, and phlegm that improve with discontinuation; case reports of unintentional pediatric ingestions; and lower neonatal birth weight, which should be discussed with women of reproductive age who are using or considering medical marijuana, Dr. Grossman said.

Motor vehicle accidents, development of psychiatric symptoms, and psychosis relapse also have been linked to use, she said.

Some real-world adverse event data specific to medical marijuana data are available through the Minnesota medical cannabis program. They found 16% of surveyed users reported an adverse event within the first 4 months, including dry mouth, fatigue, mental clouding, and drowsiness, Dr. Grossman told attendees.

Dr. Grossman reported that she has no relationship with entities producing, marketing, reselling, or distributing health care goods or services consumed by, or used on, patients.

SOURCE: Grossman E. ACP 2019, Presentation MTP 010.

PHILADELPHIA – Medical marijuana research to date provides some support for its use in neuropathic pain, nausea and vomiting, and spasticity, some insights into adverse effects, and “a lot of the Wild West,” Ellie Grossman, MD, MPH, said here at the annual meeting of the American College of Physicians.

Andrew Bowser/MDedge News

The opioid-sparing effects of medical marijuana have been highlighted in recent reports suggesting that cannabis users may use less opioids, and that states with medical marijuana laws have seen drops in opioid overdose mortality, Dr. Grossman said.

“That’s kind of a story on pain and cannabinoids, and that’s really the biggest story there is in terms of medical evidence and effectiveness for this agent,” said Dr. Grossman, an instructor at Harvard Medical School and Primary Care Lead for Behavioral Health Integration, Cambridge Health Alliance, Somerville, Mass.

However, being the top story in medical marijuana may not be a very high bar in 2019, given current issues with research in this area, including inconsistencies in medical marijuana formulations, relatively small numbers of patients enrolled in studies, and meta-analyses that have produced equivocal results.

“Unfortunately, this is an area where there’s a lot of, shall I say, ‘squishiness’ in the data, through no fault of the researchers involved – it’s just an area that’s really hard to study,” Dr. Goodman said in her update on medical marijuana use at the meeting.

Most studies of cannabinoids for chronic pain have compared these agents to placebo, rather than the long list of other medications that might be used to treat pain, Dr. Grossman said.

There are several meta-analyses available, including a recently published Cochrane review in which authors concluded that, for neuropathic pain, the potential benefits of cannabis-based medicines may outweigh their potential harms.

“The upshot here is that there may be some evidence for neuropathic pain, but the evidence is generally of poor quality and kind of mixed,” said Dr. Grossman.

State-level medical cannabis laws were linked to significantly lower opioid overdose mortality rates in a 2014 study (JAMA Intern Med. 2014;174[10]:1668-73). In more recent studies, states with medical cannabis laws were found to have lower Medicare Part D opioid-prescribing rates, and in another study, legalization of medical marijuana was linked to lower rates of chronic and high-risk opioid use.

“It certainly seems like maybe we as prescribers are prescribing [fewer] opioids if there’s medical cannabis around,” Dr. Grossman said. “What this means for our patients in the short term and long term, we don’t totally know. But clearly, fewer opioid overdoses is a way better thing than more, so there could be something here.”

The cannabinoids approved by the Food and Drug Administration include nabilone (Cesamet) and dronabinol (Marinol), both synthetic cannabinoids indicated for cancer chemotherapy–related nausea and vomiting, along with cannabidiol (Epidiolex), just approved in June 2018 for treatment of some rare pediatric refractory epilepsy syndromes, Dr. Grossman said.

For chemotherapy-induced nausea and vomiting, evidence suggests oral cannabinoids are more effective than placebo, but there’s mixed evidence as to whether they are better than other antiemetics, Dr. Grossman said, while in terms of spasticity related to multiple sclerosis, research has shown small improvements in patient-reported symptoms.

Long-term adverse event data specific to medical marijuana are scant, with much of the evidence coming from studies of recreational marijuana users, Dr. Grossman said.

Those long-term effects include increased risk of pulmonary effects such as cough, wheeze, and phlegm that improve with discontinuation; case reports of unintentional pediatric ingestions; and lower neonatal birth weight, which should be discussed with women of reproductive age who are using or considering medical marijuana, Dr. Grossman said.

Motor vehicle accidents, development of psychiatric symptoms, and psychosis relapse also have been linked to use, she said.

Some real-world adverse event data specific to medical marijuana data are available through the Minnesota medical cannabis program. They found 16% of surveyed users reported an adverse event within the first 4 months, including dry mouth, fatigue, mental clouding, and drowsiness, Dr. Grossman told attendees.

Dr. Grossman reported that she has no relationship with entities producing, marketing, reselling, or distributing health care goods or services consumed by, or used on, patients.

SOURCE: Grossman E. ACP 2019, Presentation MTP 010.

NEW ORLEANS – Waiting a few months after a patient has been hospitalized for acute decompensated heart failure before launching a switch from enalapril to sacubitril/valsartan imposes a steep price in terms of extra major cardiovascular events, compared with starting the angiotensin-neprilysin inhibitor during the initial hospitalization, according to the open-label extension of the PIONEER-HF trial.

Bruce Jancin/MDedge News

“We think these data have important clinical implications: While sacubitril/valsartan decreases NT-proBNP compared with enalapril regardless of when it is initiated, the early improvement in postdischarge outcomes supports the in-hospital initiation of sacubitril/valsartan in stabilized patients with acute decompensated heart failure,” Adam D. DeVore, MD, declared in presenting the PIONEER-HF Extension results at the annual meeting of the American College of Cardiology.

PIONEER-HF was a landmark, practice-changing, double-blind clinical trial in which 881 patients were randomized to initiation of sacubitril/valsartan (Entresto) or enalapril during hospitalization for acute decompensated heart failure. In the previously reported main outcome, 8 weeks after discharge the sacubitril/valsartan group had a 29% greater reduction in NT-proBNP (the N-terminal prohormone of brain natriuretic peptide) and a 42% lower rate of the composite clinical endpoint of cardiovascular death or heart failure rehospitalization than the enalapril group (N Engl J Med. 2019 Feb 7;380[6]:539-48).

The 4-week open-label extension of PIONEER-HF began at week 8, when participants initially randomized to enalapril during the double-blind phase were switched to sacubitril/valsartan, while those assigned to in-hospital initiation of the angiotensin-neprilysin inhibitor (ARNI) stayed the course.

At week 12, after 4 weeks of open-label treatment, patients on sacubitril/valsartan from the start experienced an additional 18.5% drop in NT-proBNP from their week-8 baseline of 1,218 pg/mL. Meanwhile, the NT-proBNP level in the switch group plunged by 35.8% from a week-8 baseline of 1,630 pg/mL. As a result, both groups ended up at the same much-improved biomarker level at week 12, observed Dr. DeVore, a cardiologist at Duke University in Durham, N.C.

Clinical event rates, however, were another story altogether. The clinical event gap between the two study arms documented at week 8 in the double-blind phase of the trial didn’t close significantly in the 4 weeks after the enalapril group crossed over to open-label sacubitril/valsartan. Indeed, the relative risk of the composite endpoint of cardiovascular death, heart failure rehospitalization, or left ventricular assist device implantation during the 4-week extension phase was 33% lower in the continuous sacubitril/valsartan group than in the switchers. The absolute risk reduction was 5.6%, with a favorable number needed to treat of 18.

This difference was driven mainly by less rehospitalization for heart failure. Few cardiovascular deaths or LVAD implantations occurred during the relatively brief 4-week extension phase of the trial.

“But this is an important thing as we think about what we’re trying to accomplish in heart failure: trying to find tools that improve rehospitalization rates after people leave the hospital is extremely important,” Dr. DeVore said. “We do know that the really vulnerable period for rehospitalization is early on, so my sus```picion – though I can’t prove it – is that’s the important part. That’s when we need to have patients on the best therapy.”

He was asked how practical it is to initiate sacubitril/valsartan during hospitalization for acute decompensated heart failure in real-world clinical practice, given that it can be done only after patients achieve hemodynamic stability.

“I think the definition of hemodynamic stability we used in the trial was a fairly straightforward one, very clinical, and one we can translate to the bedside,” Dr. DeVore replied. “Patients had to have a systolic blood pressure of 100 mm Hg or greater for 6 hours, which is easily documented in the hospital, no changes in IV diuretics or IV vasodilators for 6 hours, and no IV inotropes for the last 24 hours. That’s how we defined hemodynamic stability. I think we should be able to find these patients.”

Average length of stay in the index hospitalization in PIONEER-HF was just over 5 days, but the study protocol actually resulted in longer-than-needed hospitalization because it required that patients had to receive three double-blind doses of their study medication before discharge. In routine practice, it’s unlikely that in-hospital initiation of sacubitril/valsartan will result in a length of stay greater than the national average of about 4.5 days, according the cardiologist.

Current ACC/American Heart Association/Heart Failure Society of American guidelines on management of heart failure include a Class Ia recommendation to switch patients from an ACE inhibitor or angiotensin inhibitor to sacubitril/valsartan (Circulation. 2017 Aug 8;136[6]:e137-61).

However, heart failure specialists are concerned by national data showing that sacubitril/valsartan remains widely underprescribed.

Dr. DeVore reported serving as a consultant to Novartis and receiving research grants from a half dozen pharmaceutical companies as well as the American Heart Association, National Heart, Lung, and Blood Institute, and the Patient-Centered Outcomes Research Institute .

bjancin@mdedge.com

NEW ORLEANS – Waiting a few months after a patient has been hospitalized for acute decompensated heart failure before launching a switch from enalapril to sacubitril/valsartan imposes a steep price in terms of extra major cardiovascular events, compared with starting the angiotensin-neprilysin inhibitor during the initial hospitalization, according to the open-label extension of the PIONEER-HF trial.

Bruce Jancin/MDedge News

“We think these data have important clinical implications: While sacubitril/valsartan decreases NT-proBNP compared with enalapril regardless of when it is initiated, the early improvement in postdischarge outcomes supports the in-hospital initiation of sacubitril/valsartan in stabilized patients with acute decompensated heart failure,” Adam D. DeVore, MD, declared in presenting the PIONEER-HF Extension results at the annual meeting of the American College of Cardiology.

PIONEER-HF was a landmark, practice-changing, double-blind clinical trial in which 881 patients were randomized to initiation of sacubitril/valsartan (Entresto) or enalapril during hospitalization for acute decompensated heart failure. In the previously reported main outcome, 8 weeks after discharge the sacubitril/valsartan group had a 29% greater reduction in NT-proBNP (the N-terminal prohormone of brain natriuretic peptide) and a 42% lower rate of the composite clinical endpoint of cardiovascular death or heart failure rehospitalization than the enalapril group (N Engl J Med. 2019 Feb 7;380[6]:539-48).

The 4-week open-label extension of PIONEER-HF began at week 8, when participants initially randomized to enalapril during the double-blind phase were switched to sacubitril/valsartan, while those assigned to in-hospital initiation of the angiotensin-neprilysin inhibitor (ARNI) stayed the course.

At week 12, after 4 weeks of open-label treatment, patients on sacubitril/valsartan from the start experienced an additional 18.5% drop in NT-proBNP from their week-8 baseline of 1,218 pg/mL. Meanwhile, the NT-proBNP level in the switch group plunged by 35.8% from a week-8 baseline of 1,630 pg/mL. As a result, both groups ended up at the same much-improved biomarker level at week 12, observed Dr. DeVore, a cardiologist at Duke University in Durham, N.C.

Clinical event rates, however, were another story altogether. The clinical event gap between the two study arms documented at week 8 in the double-blind phase of the trial didn’t close significantly in the 4 weeks after the enalapril group crossed over to open-label sacubitril/valsartan. Indeed, the relative risk of the composite endpoint of cardiovascular death, heart failure rehospitalization, or left ventricular assist device implantation during the 4-week extension phase was 33% lower in the continuous sacubitril/valsartan group than in the switchers. The absolute risk reduction was 5.6%, with a favorable number needed to treat of 18.

This difference was driven mainly by less rehospitalization for heart failure. Few cardiovascular deaths or LVAD implantations occurred during the relatively brief 4-week extension phase of the trial.

“But this is an important thing as we think about what we’re trying to accomplish in heart failure: trying to find tools that improve rehospitalization rates after people leave the hospital is extremely important,” Dr. DeVore said. “We do know that the really vulnerable period for rehospitalization is early on, so my sus```picion – though I can’t prove it – is that’s the important part. That’s when we need to have patients on the best therapy.”

He was asked how practical it is to initiate sacubitril/valsartan during hospitalization for acute decompensated heart failure in real-world clinical practice, given that it can be done only after patients achieve hemodynamic stability.

“I think the definition of hemodynamic stability we used in the trial was a fairly straightforward one, very clinical, and one we can translate to the bedside,” Dr. DeVore replied. “Patients had to have a systolic blood pressure of 100 mm Hg or greater for 6 hours, which is easily documented in the hospital, no changes in IV diuretics or IV vasodilators for 6 hours, and no IV inotropes for the last 24 hours. That’s how we defined hemodynamic stability. I think we should be able to find these patients.”

Average length of stay in the index hospitalization in PIONEER-HF was just over 5 days, but the study protocol actually resulted in longer-than-needed hospitalization because it required that patients had to receive three double-blind doses of their study medication before discharge. In routine practice, it’s unlikely that in-hospital initiation of sacubitril/valsartan will result in a length of stay greater than the national average of about 4.5 days, according the cardiologist.

Current ACC/American Heart Association/Heart Failure Society of American guidelines on management of heart failure include a Class Ia recommendation to switch patients from an ACE inhibitor or angiotensin inhibitor to sacubitril/valsartan (Circulation. 2017 Aug 8;136[6]:e137-61).

However, heart failure specialists are concerned by national data showing that sacubitril/valsartan remains widely underprescribed.

Dr. DeVore reported serving as a consultant to Novartis and receiving research grants from a half dozen pharmaceutical companies as well as the American Heart Association, National Heart, Lung, and Blood Institute, and the Patient-Centered Outcomes Research Institute .

bjancin@mdedge.com

NEW ORLEANS – Waiting a few months after a patient has been hospitalized for acute decompensated heart failure before launching a switch from enalapril to sacubitril/valsartan imposes a steep price in terms of extra major cardiovascular events, compared with starting the angiotensin-neprilysin inhibitor during the initial hospitalization, according to the open-label extension of the PIONEER-HF trial.

Bruce Jancin/MDedge News

“We think these data have important clinical implications: While sacubitril/valsartan decreases NT-proBNP compared with enalapril regardless of when it is initiated, the early improvement in postdischarge outcomes supports the in-hospital initiation of sacubitril/valsartan in stabilized patients with acute decompensated heart failure,” Adam D. DeVore, MD, declared in presenting the PIONEER-HF Extension results at the annual meeting of the American College of Cardiology.

PIONEER-HF was a landmark, practice-changing, double-blind clinical trial in which 881 patients were randomized to initiation of sacubitril/valsartan (Entresto) or enalapril during hospitalization for acute decompensated heart failure. In the previously reported main outcome, 8 weeks after discharge the sacubitril/valsartan group had a 29% greater reduction in NT-proBNP (the N-terminal prohormone of brain natriuretic peptide) and a 42% lower rate of the composite clinical endpoint of cardiovascular death or heart failure rehospitalization than the enalapril group (N Engl J Med. 2019 Feb 7;380[6]:539-48).

The 4-week open-label extension of PIONEER-HF began at week 8, when participants initially randomized to enalapril during the double-blind phase were switched to sacubitril/valsartan, while those assigned to in-hospital initiation of the angiotensin-neprilysin inhibitor (ARNI) stayed the course.

At week 12, after 4 weeks of open-label treatment, patients on sacubitril/valsartan from the start experienced an additional 18.5% drop in NT-proBNP from their week-8 baseline of 1,218 pg/mL. Meanwhile, the NT-proBNP level in the switch group plunged by 35.8% from a week-8 baseline of 1,630 pg/mL. As a result, both groups ended up at the same much-improved biomarker level at week 12, observed Dr. DeVore, a cardiologist at Duke University in Durham, N.C.

Clinical event rates, however, were another story altogether. The clinical event gap between the two study arms documented at week 8 in the double-blind phase of the trial didn’t close significantly in the 4 weeks after the enalapril group crossed over to open-label sacubitril/valsartan. Indeed, the relative risk of the composite endpoint of cardiovascular death, heart failure rehospitalization, or left ventricular assist device implantation during the 4-week extension phase was 33% lower in the continuous sacubitril/valsartan group than in the switchers. The absolute risk reduction was 5.6%, with a favorable number needed to treat of 18.

This difference was driven mainly by less rehospitalization for heart failure. Few cardiovascular deaths or LVAD implantations occurred during the relatively brief 4-week extension phase of the trial.

“But this is an important thing as we think about what we’re trying to accomplish in heart failure: trying to find tools that improve rehospitalization rates after people leave the hospital is extremely important,” Dr. DeVore said. “We do know that the really vulnerable period for rehospitalization is early on, so my sus```picion – though I can’t prove it – is that’s the important part. That’s when we need to have patients on the best therapy.”

He was asked how practical it is to initiate sacubitril/valsartan during hospitalization for acute decompensated heart failure in real-world clinical practice, given that it can be done only after patients achieve hemodynamic stability.

“I think the definition of hemodynamic stability we used in the trial was a fairly straightforward one, very clinical, and one we can translate to the bedside,” Dr. DeVore replied. “Patients had to have a systolic blood pressure of 100 mm Hg or greater for 6 hours, which is easily documented in the hospital, no changes in IV diuretics or IV vasodilators for 6 hours, and no IV inotropes for the last 24 hours. That’s how we defined hemodynamic stability. I think we should be able to find these patients.”

Average length of stay in the index hospitalization in PIONEER-HF was just over 5 days, but the study protocol actually resulted in longer-than-needed hospitalization because it required that patients had to receive three double-blind doses of their study medication before discharge. In routine practice, it’s unlikely that in-hospital initiation of sacubitril/valsartan will result in a length of stay greater than the national average of about 4.5 days, according the cardiologist.

Current ACC/American Heart Association/Heart Failure Society of American guidelines on management of heart failure include a Class Ia recommendation to switch patients from an ACE inhibitor or angiotensin inhibitor to sacubitril/valsartan (Circulation. 2017 Aug 8;136[6]:e137-61).

However, heart failure specialists are concerned by national data showing that sacubitril/valsartan remains widely underprescribed.

Dr. DeVore reported serving as a consultant to Novartis and receiving research grants from a half dozen pharmaceutical companies as well as the American Heart Association, National Heart, Lung, and Blood Institute, and the Patient-Centered Outcomes Research Institute .

bjancin@mdedge.com

The Food and Drug Administration has announced a potential temporary shortage of a type of Bivona tracheostomy tube manufactured by Smiths Medical caused by the closure of a large ethylene oxide sterilization facilities in Willowbrook, Ill., and the future planned closure of a similar facility.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The shortage may affect pediatric use because, although tubes are used for both adults and children, there are fewer alternative products on the market for pediatric patients. Parents and caregivers of children who use the Bivona tube are encouraged to check with Smiths Medical about available inventory and with their health care providers about alternative products.

Jeff Shuren, MD, director of the Center for Devices and Radiological Health, wrote in a press release, “I want to assure you that the FDA is working closely with the company to quickly resolve their sterilization challenges and bring these critical devices to the patients who need them as quickly as possible, which we anticipate will be made available again beginning the week of April 22.”

For patients currently using the Bivona tubes, Dr. Shuren noted, “The closure of the Willowbrook facility does not impact tubes already in use by patients at home or in health care settings. The company is communicating with patients about the tubes and how patients and caregivers can mitigate any potential impact, including reusing and cleaning tubes in accordance with the manufacturer’s instructions for use.”

Read the entire announcement at the FDA website.

tborden@mdedge.com

The Food and Drug Administration has announced a potential temporary shortage of a type of Bivona tracheostomy tube manufactured by Smiths Medical caused by the closure of a large ethylene oxide sterilization facilities in Willowbrook, Ill., and the future planned closure of a similar facility.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The shortage may affect pediatric use because, although tubes are used for both adults and children, there are fewer alternative products on the market for pediatric patients. Parents and caregivers of children who use the Bivona tube are encouraged to check with Smiths Medical about available inventory and with their health care providers about alternative products.

Jeff Shuren, MD, director of the Center for Devices and Radiological Health, wrote in a press release, “I want to assure you that the FDA is working closely with the company to quickly resolve their sterilization challenges and bring these critical devices to the patients who need them as quickly as possible, which we anticipate will be made available again beginning the week of April 22.”

For patients currently using the Bivona tubes, Dr. Shuren noted, “The closure of the Willowbrook facility does not impact tubes already in use by patients at home or in health care settings. The company is communicating with patients about the tubes and how patients and caregivers can mitigate any potential impact, including reusing and cleaning tubes in accordance with the manufacturer’s instructions for use.”

Read the entire announcement at the FDA website.

tborden@mdedge.com

The Food and Drug Administration has announced a potential temporary shortage of a type of Bivona tracheostomy tube manufactured by Smiths Medical caused by the closure of a large ethylene oxide sterilization facilities in Willowbrook, Ill., and the future planned closure of a similar facility.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The shortage may affect pediatric use because, although tubes are used for both adults and children, there are fewer alternative products on the market for pediatric patients. Parents and caregivers of children who use the Bivona tube are encouraged to check with Smiths Medical about available inventory and with their health care providers about alternative products.

Jeff Shuren, MD, director of the Center for Devices and Radiological Health, wrote in a press release, “I want to assure you that the FDA is working closely with the company to quickly resolve their sterilization challenges and bring these critical devices to the patients who need them as quickly as possible, which we anticipate will be made available again beginning the week of April 22.”

For patients currently using the Bivona tubes, Dr. Shuren noted, “The closure of the Willowbrook facility does not impact tubes already in use by patients at home or in health care settings. The company is communicating with patients about the tubes and how patients and caregivers can mitigate any potential impact, including reusing and cleaning tubes in accordance with the manufacturer’s instructions for use.”

Read the entire announcement at the FDA website.

tborden@mdedge.com

PHILADELPHIA – Opening the door to transformational change can be as simple as opening a door.

Gregory Twachtman/MDedge News

At least one physician can attest to this.

Priya Radhakrishnan, MD, chief academic officer at HonorHealth Medical Group, Phoenix, described one of her earliest successes in working on the Transforming Clinical Practice Initiative as her literal and figurative opening of the door between a behavioral health office and a physician health office.

In her example, which she presented in a panel on transformational change at the annual meeting of the American College of Physicians, both the behavioral health office and the physician office coordinated to have the same Medicaid patients. Because of that, when the behavioral health specialist learned of a physical condition, a “warm hand-off” was made simply by walking the patient into the doctor’s office, she said.

Transformational changes in the delivery of health care can come from events and opportunities within your medical practice. And your practice data can be the tools that guide you to make the change happen, noted Dr. Radhakrishnan and her copanelists, during the April 12 session. The panelists focused their presentation on lessons learned from the ongoing Transforming Clinical Practice Initiative, a test project of the Centers for Medicare & Medicaid Services’ Center for Medicare and Medicaid Innovation. The project is providing assistance to physicians and practices looking to transform their organizations into using value-based care delivery models.

“I think most of us don’t realize how much power we hold over the ability to change health care within our neighborhood,” said Thomas Spain, MD, of Vanderbilt University Medical Center, Nashville, Tenn., during his presentation. “[We] have been lulled into this idea that health care will change ... when someone in Washington, D.C., finally makes a change.”

Actually, specific events in a single practice typically drive changes, he said. Most physicians who made these changes “really had very little interest in [practice changes]; then something would happen. It was a patient experience that they had, a family experience, a new program that came along” that made them realize there is an opportunity here for a physician to take the lead and make a change.

And, invariably, those physicians discovered “new satisfaction in their work through the process ... [their] practices looked very different at the end of the project,” Dr. Spain noted.

The other component to the success was looking differently at data to assure continuous data-driven quality improvement, said copanelist M. Carol Greenlee, MD, an endocrinologist and chair and counsel of subspecialty societies at ACP.

Data aren’t just about “being judged [and] not getting penalized,” she said. Data need to be viewed as a tool to really help understand the needs of the patient and the population.

Change makers “had to [ask], ‘For my population, how do I reduce admissions, what are the unnecessary tests my patients are getting, what are the unnecessary procedures?’ ” she said. Through the Transforming Clinical Practice Initiative, “we are teaching [participants] how to use data to show their value to payers ... and to find their voice in sharing their value.”

Some of the aims of the program included building solutions that were scalable, reducing unnecessary hospital admissions, generating $1 billion to $4 billion in savings, and transitioning 75% of practices completing the program to alternative payment models.

Dr. Spain noted that something as simple as moving the “if this is a medical emergency” disclaimer to the end of the outbound message at the physician office could help reduce trips to the emergency department. This could instead bring the patient to the office.

“Start small,” Dr. Radhakrishnan advised. “Value and quality freaks all of us out.”

Target small successes that can be built upon.

“Care delivery is the final mile,” Dr. Greenlee added. “We have all this medical knowledge, all the science and clinical research, and we know what to do with our guidelines, but if we don’t have care delivery, that final mile of [improving] ... the health of our patients, all of this is for naught.”

gtwachtman@mdedge.com

PHILADELPHIA – Opening the door to transformational change can be as simple as opening a door.

Gregory Twachtman/MDedge News

At least one physician can attest to this.

Priya Radhakrishnan, MD, chief academic officer at HonorHealth Medical Group, Phoenix, described one of her earliest successes in working on the Transforming Clinical Practice Initiative as her literal and figurative opening of the door between a behavioral health office and a physician health office.

In her example, which she presented in a panel on transformational change at the annual meeting of the American College of Physicians, both the behavioral health office and the physician office coordinated to have the same Medicaid patients. Because of that, when the behavioral health specialist learned of a physical condition, a “warm hand-off” was made simply by walking the patient into the doctor’s office, she said.

Transformational changes in the delivery of health care can come from events and opportunities within your medical practice. And your practice data can be the tools that guide you to make the change happen, noted Dr. Radhakrishnan and her copanelists, during the April 12 session. The panelists focused their presentation on lessons learned from the ongoing Transforming Clinical Practice Initiative, a test project of the Centers for Medicare & Medicaid Services’ Center for Medicare and Medicaid Innovation. The project is providing assistance to physicians and practices looking to transform their organizations into using value-based care delivery models.

“I think most of us don’t realize how much power we hold over the ability to change health care within our neighborhood,” said Thomas Spain, MD, of Vanderbilt University Medical Center, Nashville, Tenn., during his presentation. “[We] have been lulled into this idea that health care will change ... when someone in Washington, D.C., finally makes a change.”

Actually, specific events in a single practice typically drive changes, he said. Most physicians who made these changes “really had very little interest in [practice changes]; then something would happen. It was a patient experience that they had, a family experience, a new program that came along” that made them realize there is an opportunity here for a physician to take the lead and make a change.

And, invariably, those physicians discovered “new satisfaction in their work through the process ... [their] practices looked very different at the end of the project,” Dr. Spain noted.

The other component to the success was looking differently at data to assure continuous data-driven quality improvement, said copanelist M. Carol Greenlee, MD, an endocrinologist and chair and counsel of subspecialty societies at ACP.

Data aren’t just about “being judged [and] not getting penalized,” she said. Data need to be viewed as a tool to really help understand the needs of the patient and the population.

Change makers “had to [ask], ‘For my population, how do I reduce admissions, what are the unnecessary tests my patients are getting, what are the unnecessary procedures?’ ” she said. Through the Transforming Clinical Practice Initiative, “we are teaching [participants] how to use data to show their value to payers ... and to find their voice in sharing their value.”

Some of the aims of the program included building solutions that were scalable, reducing unnecessary hospital admissions, generating $1 billion to $4 billion in savings, and transitioning 75% of practices completing the program to alternative payment models.

Dr. Spain noted that something as simple as moving the “if this is a medical emergency” disclaimer to the end of the outbound message at the physician office could help reduce trips to the emergency department. This could instead bring the patient to the office.

“Start small,” Dr. Radhakrishnan advised. “Value and quality freaks all of us out.”

Target small successes that can be built upon.

“Care delivery is the final mile,” Dr. Greenlee added. “We have all this medical knowledge, all the science and clinical research, and we know what to do with our guidelines, but if we don’t have care delivery, that final mile of [improving] ... the health of our patients, all of this is for naught.”

gtwachtman@mdedge.com

PHILADELPHIA – Opening the door to transformational change can be as simple as opening a door.

Gregory Twachtman/MDedge News

At least one physician can attest to this.

Priya Radhakrishnan, MD, chief academic officer at HonorHealth Medical Group, Phoenix, described one of her earliest successes in working on the Transforming Clinical Practice Initiative as her literal and figurative opening of the door between a behavioral health office and a physician health office.

In her example, which she presented in a panel on transformational change at the annual meeting of the American College of Physicians, both the behavioral health office and the physician office coordinated to have the same Medicaid patients. Because of that, when the behavioral health specialist learned of a physical condition, a “warm hand-off” was made simply by walking the patient into the doctor’s office, she said.

Transformational changes in the delivery of health care can come from events and opportunities within your medical practice. And your practice data can be the tools that guide you to make the change happen, noted Dr. Radhakrishnan and her copanelists, during the April 12 session. The panelists focused their presentation on lessons learned from the ongoing Transforming Clinical Practice Initiative, a test project of the Centers for Medicare & Medicaid Services’ Center for Medicare and Medicaid Innovation. The project is providing assistance to physicians and practices looking to transform their organizations into using value-based care delivery models.

“I think most of us don’t realize how much power we hold over the ability to change health care within our neighborhood,” said Thomas Spain, MD, of Vanderbilt University Medical Center, Nashville, Tenn., during his presentation. “[We] have been lulled into this idea that health care will change ... when someone in Washington, D.C., finally makes a change.”

Actually, specific events in a single practice typically drive changes, he said. Most physicians who made these changes “really had very little interest in [practice changes]; then something would happen. It was a patient experience that they had, a family experience, a new program that came along” that made them realize there is an opportunity here for a physician to take the lead and make a change.

And, invariably, those physicians discovered “new satisfaction in their work through the process ... [their] practices looked very different at the end of the project,” Dr. Spain noted.

The other component to the success was looking differently at data to assure continuous data-driven quality improvement, said copanelist M. Carol Greenlee, MD, an endocrinologist and chair and counsel of subspecialty societies at ACP.

Data aren’t just about “being judged [and] not getting penalized,” she said. Data need to be viewed as a tool to really help understand the needs of the patient and the population.

Change makers “had to [ask], ‘For my population, how do I reduce admissions, what are the unnecessary tests my patients are getting, what are the unnecessary procedures?’ ” she said. Through the Transforming Clinical Practice Initiative, “we are teaching [participants] how to use data to show their value to payers ... and to find their voice in sharing their value.”

Some of the aims of the program included building solutions that were scalable, reducing unnecessary hospital admissions, generating $1 billion to $4 billion in savings, and transitioning 75% of practices completing the program to alternative payment models.

Dr. Spain noted that something as simple as moving the “if this is a medical emergency” disclaimer to the end of the outbound message at the physician office could help reduce trips to the emergency department. This could instead bring the patient to the office.

“Start small,” Dr. Radhakrishnan advised. “Value and quality freaks all of us out.”

Target small successes that can be built upon.

“Care delivery is the final mile,” Dr. Greenlee added. “We have all this medical knowledge, all the science and clinical research, and we know what to do with our guidelines, but if we don’t have care delivery, that final mile of [improving] ... the health of our patients, all of this is for naught.”

gtwachtman@mdedge.com

The use of energy-based devices for vaginal rejuvenation, a practice that sparked a recent safety communication from the Food and Drug Administration, was implicated in nearly four dozen adverse event reports found in the agency’s medical device adverse event reporting database, researchers report.

The 45 unique event reports, submitted to the FDA during October 2015–January 2019, described 46 patients in total, of whom 33 reported long-term effects including pain, numbness, and burning, said the researchers, led by Jusleen Ahluwalia, MD, of the department of dermatology at the University of California, San Diego, and her coauthors. They included 31 that were reported by the patients, 8 reported by the manufacturer; 4 reported by the distributor, and 2 not specified.

These findings emphasize the need for clinical trials to evaluate the safety and efficacy of the lasers and radiofrequency devices that have been marketed and used for so-called vaginal rejuvenation procedures, they wrote in Lasers in Surgery and Medicine. The coauthors are Arisa Ortiz, MD, also with the University of California, San Diego, and Mathew M. Avram, MD, director of the Massachusetts General Hospital Dermatology Laser & Cosmetic Center, Boston. “Randomized studies are necessary to compare these therapies with standard modalities and to establish the safety of these devices,” they wrote.

In July 2018, the FDA issued a safety communication alerting patients and health care providers that the safety and effectiveness of energy-based devices has not been established for procedures described as “vaginal rejuvenation.” Scott Gottlieb, MD, FDA commissioner at the time, issued a statement decrying “deceptive health claims and significant risks” related to devices marketed for those medical procedures. In a November 2018 update, the FDA said they contacted some device manufacturers to express concerns that the devices were being marketed inappropriately and that manufacturers they had contacted so far “responded with adequate corrections.”

In their report, Dr. Ahluwalia and her associates noted that “vaginal rejuvenation” is an ill-defined term that may encompass a variety of procedures related to tightening; dyspareunia; dysuria; urinary incontinence; vulvar issues including irritation, dryness, and atrophy; and orgasmic dysfunction.

They found a total of 58 records in their review of the Manufacturer and User Facility Device Experience database, of which 25 were reported prior to the FDA’s July 2018 statement. Of 45 unique event descriptions found in those records, 39 were categorized as patient-related injuries, while 2 were operator-related injuries, 2 were device malfunctions, and 2 were not specified.

Pain was the most commonly adverse event, accounting for 19 reports in their analysis, while 11 patients reported numbness or burning.

Among the laser- and energy-based devices specifically described in the 39 patient-report injuries, the MonaLisa Touch had the highest number of adverse event reports (16), the data show. “However, this may be reflective of length of time bias as it is one of the first devices utilized to promote vaginal rejuvenation,” the authors pointed out.

In light of these findings, the authors advised clinicians to ask patients about their reasons for seeking vaginal rejuvenation procedures. “Normal variety of female genital appearances should also be reviewed when patients express cosmetic concerns,” they added. Concerns about related to genitourinary syndrome of menopause “or optimizing sexual function may be alleviated by exploring nonprocedural, conservative approaches, such as hormonal creams, if not contraindicated, and/or counseling,” they noted.

The authors provided conflict of interest disclosures related to Zalea, Inmode, Cytrellis, Zeltiq Aesthetics, Soliton, Sciton, Allergan, and Sienna Biopharmaceuticals, among others.

Adverse events related to devices and drugs can be reported to the FDA’s Medwatch program.

SOURCE: Ahluwalia J et al. Lasers Surg Med. 2019 Mar 29. doi: 10.1002/lsm.23084.

The use of energy-based devices for vaginal rejuvenation, a practice that sparked a recent safety communication from the Food and Drug Administration, was implicated in nearly four dozen adverse event reports found in the agency’s medical device adverse event reporting database, researchers report.

The 45 unique event reports, submitted to the FDA during October 2015–January 2019, described 46 patients in total, of whom 33 reported long-term effects including pain, numbness, and burning, said the researchers, led by Jusleen Ahluwalia, MD, of the department of dermatology at the University of California, San Diego, and her coauthors. They included 31 that were reported by the patients, 8 reported by the manufacturer; 4 reported by the distributor, and 2 not specified.

These findings emphasize the need for clinical trials to evaluate the safety and efficacy of the lasers and radiofrequency devices that have been marketed and used for so-called vaginal rejuvenation procedures, they wrote in Lasers in Surgery and Medicine. The coauthors are Arisa Ortiz, MD, also with the University of California, San Diego, and Mathew M. Avram, MD, director of the Massachusetts General Hospital Dermatology Laser & Cosmetic Center, Boston. “Randomized studies are necessary to compare these therapies with standard modalities and to establish the safety of these devices,” they wrote.

In July 2018, the FDA issued a safety communication alerting patients and health care providers that the safety and effectiveness of energy-based devices has not been established for procedures described as “vaginal rejuvenation.” Scott Gottlieb, MD, FDA commissioner at the time, issued a statement decrying “deceptive health claims and significant risks” related to devices marketed for those medical procedures. In a November 2018 update, the FDA said they contacted some device manufacturers to express concerns that the devices were being marketed inappropriately and that manufacturers they had contacted so far “responded with adequate corrections.”

In their report, Dr. Ahluwalia and her associates noted that “vaginal rejuvenation” is an ill-defined term that may encompass a variety of procedures related to tightening; dyspareunia; dysuria; urinary incontinence; vulvar issues including irritation, dryness, and atrophy; and orgasmic dysfunction.

They found a total of 58 records in their review of the Manufacturer and User Facility Device Experience database, of which 25 were reported prior to the FDA’s July 2018 statement. Of 45 unique event descriptions found in those records, 39 were categorized as patient-related injuries, while 2 were operator-related injuries, 2 were device malfunctions, and 2 were not specified.

Pain was the most commonly adverse event, accounting for 19 reports in their analysis, while 11 patients reported numbness or burning.

Among the laser- and energy-based devices specifically described in the 39 patient-report injuries, the MonaLisa Touch had the highest number of adverse event reports (16), the data show. “However, this may be reflective of length of time bias as it is one of the first devices utilized to promote vaginal rejuvenation,” the authors pointed out.

In light of these findings, the authors advised clinicians to ask patients about their reasons for seeking vaginal rejuvenation procedures. “Normal variety of female genital appearances should also be reviewed when patients express cosmetic concerns,” they added. Concerns about related to genitourinary syndrome of menopause “or optimizing sexual function may be alleviated by exploring nonprocedural, conservative approaches, such as hormonal creams, if not contraindicated, and/or counseling,” they noted.

The authors provided conflict of interest disclosures related to Zalea, Inmode, Cytrellis, Zeltiq Aesthetics, Soliton, Sciton, Allergan, and Sienna Biopharmaceuticals, among others.

Adverse events related to devices and drugs can be reported to the FDA’s Medwatch program.

SOURCE: Ahluwalia J et al. Lasers Surg Med. 2019 Mar 29. doi: 10.1002/lsm.23084.

The use of energy-based devices for vaginal rejuvenation, a practice that sparked a recent safety communication from the Food and Drug Administration, was implicated in nearly four dozen adverse event reports found in the agency’s medical device adverse event reporting database, researchers report.

The 45 unique event reports, submitted to the FDA during October 2015–January 2019, described 46 patients in total, of whom 33 reported long-term effects including pain, numbness, and burning, said the researchers, led by Jusleen Ahluwalia, MD, of the department of dermatology at the University of California, San Diego, and her coauthors. They included 31 that were reported by the patients, 8 reported by the manufacturer; 4 reported by the distributor, and 2 not specified.

These findings emphasize the need for clinical trials to evaluate the safety and efficacy of the lasers and radiofrequency devices that have been marketed and used for so-called vaginal rejuvenation procedures, they wrote in Lasers in Surgery and Medicine. The coauthors are Arisa Ortiz, MD, also with the University of California, San Diego, and Mathew M. Avram, MD, director of the Massachusetts General Hospital Dermatology Laser & Cosmetic Center, Boston. “Randomized studies are necessary to compare these therapies with standard modalities and to establish the safety of these devices,” they wrote.

In July 2018, the FDA issued a safety communication alerting patients and health care providers that the safety and effectiveness of energy-based devices has not been established for procedures described as “vaginal rejuvenation.” Scott Gottlieb, MD, FDA commissioner at the time, issued a statement decrying “deceptive health claims and significant risks” related to devices marketed for those medical procedures. In a November 2018 update, the FDA said they contacted some device manufacturers to express concerns that the devices were being marketed inappropriately and that manufacturers they had contacted so far “responded with adequate corrections.”

In their report, Dr. Ahluwalia and her associates noted that “vaginal rejuvenation” is an ill-defined term that may encompass a variety of procedures related to tightening; dyspareunia; dysuria; urinary incontinence; vulvar issues including irritation, dryness, and atrophy; and orgasmic dysfunction.

They found a total of 58 records in their review of the Manufacturer and User Facility Device Experience database, of which 25 were reported prior to the FDA’s July 2018 statement. Of 45 unique event descriptions found in those records, 39 were categorized as patient-related injuries, while 2 were operator-related injuries, 2 were device malfunctions, and 2 were not specified.

Pain was the most commonly adverse event, accounting for 19 reports in their analysis, while 11 patients reported numbness or burning.

Among the laser- and energy-based devices specifically described in the 39 patient-report injuries, the MonaLisa Touch had the highest number of adverse event reports (16), the data show. “However, this may be reflective of length of time bias as it is one of the first devices utilized to promote vaginal rejuvenation,” the authors pointed out.

In light of these findings, the authors advised clinicians to ask patients about their reasons for seeking vaginal rejuvenation procedures. “Normal variety of female genital appearances should also be reviewed when patients express cosmetic concerns,” they added. Concerns about related to genitourinary syndrome of menopause “or optimizing sexual function may be alleviated by exploring nonprocedural, conservative approaches, such as hormonal creams, if not contraindicated, and/or counseling,” they noted.

The authors provided conflict of interest disclosures related to Zalea, Inmode, Cytrellis, Zeltiq Aesthetics, Soliton, Sciton, Allergan, and Sienna Biopharmaceuticals, among others.

Adverse events related to devices and drugs can be reported to the FDA’s Medwatch program.

SOURCE: Ahluwalia J et al. Lasers Surg Med. 2019 Mar 29. doi: 10.1002/lsm.23084.

NEW ORLEANS – The 2015 American Thyroid Association risk stratification system for patients with differentiated thyroid cancer performed well in a real-world cohort with a high proportion of high-risk patients, according to a study presented at the annual meeting of the Endocrine Society.

“The 2015 ATA Risk Stratification System is an excellent predictor of both persisting disease and survival,” wrote Evert F.S. van Velsen, MD, and his colleagues at Erasmus Medical Center, Rotterdam, the Netherlands, in a poster accompanying the presentation.

Among a group of 236 patients with differentiated thyroid cancer (DTC), Dr. van Velsen and his coauthors looked at how the ATA high-risk criteria influenced patient response to therapy. By the end of the 14-year study period, initial gross extrathyroidal disease extension meant patients were much less likely to have an excellent response (odds ratio, 0.26; P less than .001), and much more likely to have persistent disease (OR, 2.57; P = .001).

Odds of having an excellent response were reduced by having high postoperative thyroglobulin levels (OR, 0.21; P less than .001), and persistent disease was more likely (OR, 2.39; P = .002).

Other high-risk criteria associated with significantly lower odds of excellent response included distant metastases (OR, 0.36), incomplete resection (OR, 0.51), and having follicular thyroid carcinoma (FTC) with extensive vascular invasion (OR, 0.27). All these risk factors also were associated with higher odds of persistent disease.

“Recurrence after no evidence of disease occurred in 14%” of the study population, said Dr. van Velsen and his coauthors, adding, “Clinicians should be aware of the relatively high recurrence risk, even after an excellent response to therapy.”

The study aimed to evaluate the 2015 ATA risk stratification system’s prognostic value in a population that included a relatively large proportion of high-risk DTC patients, to include many FTC patients. This work, they noted, augments previous assessments of the risk stratification system in lower-risk populations.

The authors noted that, in addition to predicting disease recurrence, the risk stratification system also worked as a predictor of disease-specific survival. Patients with structural incomplete response fared the worst, with a survival probability below 0.5 at 200 months on a Kaplan-Meier curve of disease-specific survival. Survival probability remained at 1.0 for patients with excellent response after first therapy and was intermediate for those with indeterminate response and biochemical incomplete response.

Overall mortality was higher in FTC patients. Over the study period, 31 of the 76 FTC patients (41%) died, compared with 39 of the PTC patients (24%; P = .010). In all, 28% of the FTC patients and 18% of the PTC patients died of thyroid cancer, but this difference didn’t reach statistical significance.

The retrospective study included adults with DTC meeting the 2015 ATA high-risk criteria who were diagnosed and/or treated at Erasmus Medical Center over a 13-year span ending in December 2015.

Overall, the investigators found 236 patients meeting inclusion criteria; 160 had papillary thyroid cancer (PTC), and the remaining 76 had FTC. The latter group were significantly older at baseline than PTC patients (64 versus 53 years), and were significantly less likely to undergo neck dissection (22% versus 55%).

In the full cohort, 96 patients (41%) had one high-risk factor, and an additional 74 (31%) had two risk factors. The remaining patients had three or more risk factors.

There was no between-group difference in the likelihood of receiving radioactive iodine treatment, but those with FTC had a lower cumulative radiation dose (195 versus 298 mCi; P less than .001).

More than half of patients (58%) had persistent disease after completing their first therapy. Of these, 51% had structural incomplete response and 7% had biochemical incomplete response. The response was indeterminate for about a quarter of the cohort, and the remaining 17% had an excellent initial response.

By the end of the study period, 55% of patients had persistent disease, and 51% had structural incomplete response (a more likely result for those with FTC than PTC). Just 4% had a biochemical incomplete response, and the response was indeterminate for 16%. Response was judged excellent for 29% of patients.

Dr. van Velsen and his coauthors reported that they had no relevant disclosures.

koakes@mdedge.com

SOURCE: van Velsen EFS et al. ENDO 2019, Abstract MON-549.

NEW ORLEANS – The 2015 American Thyroid Association risk stratification system for patients with differentiated thyroid cancer performed well in a real-world cohort with a high proportion of high-risk patients, according to a study presented at the annual meeting of the Endocrine Society.

“The 2015 ATA Risk Stratification System is an excellent predictor of both persisting disease and survival,” wrote Evert F.S. van Velsen, MD, and his colleagues at Erasmus Medical Center, Rotterdam, the Netherlands, in a poster accompanying the presentation.

Among a group of 236 patients with differentiated thyroid cancer (DTC), Dr. van Velsen and his coauthors looked at how the ATA high-risk criteria influenced patient response to therapy. By the end of the 14-year study period, initial gross extrathyroidal disease extension meant patients were much less likely to have an excellent response (odds ratio, 0.26; P less than .001), and much more likely to have persistent disease (OR, 2.57; P = .001).

Odds of having an excellent response were reduced by having high postoperative thyroglobulin levels (OR, 0.21; P less than .001), and persistent disease was more likely (OR, 2.39; P = .002).

Other high-risk criteria associated with significantly lower odds of excellent response included distant metastases (OR, 0.36), incomplete resection (OR, 0.51), and having follicular thyroid carcinoma (FTC) with extensive vascular invasion (OR, 0.27). All these risk factors also were associated with higher odds of persistent disease.

“Recurrence after no evidence of disease occurred in 14%” of the study population, said Dr. van Velsen and his coauthors, adding, “Clinicians should be aware of the relatively high recurrence risk, even after an excellent response to therapy.”

The study aimed to evaluate the 2015 ATA risk stratification system’s prognostic value in a population that included a relatively large proportion of high-risk DTC patients, to include many FTC patients. This work, they noted, augments previous assessments of the risk stratification system in lower-risk populations.

The authors noted that, in addition to predicting disease recurrence, the risk stratification system also worked as a predictor of disease-specific survival. Patients with structural incomplete response fared the worst, with a survival probability below 0.5 at 200 months on a Kaplan-Meier curve of disease-specific survival. Survival probability remained at 1.0 for patients with excellent response after first therapy and was intermediate for those with indeterminate response and biochemical incomplete response.

Overall mortality was higher in FTC patients. Over the study period, 31 of the 76 FTC patients (41%) died, compared with 39 of the PTC patients (24%; P = .010). In all, 28% of the FTC patients and 18% of the PTC patients died of thyroid cancer, but this difference didn’t reach statistical significance.

The retrospective study included adults with DTC meeting the 2015 ATA high-risk criteria who were diagnosed and/or treated at Erasmus Medical Center over a 13-year span ending in December 2015.

Overall, the investigators found 236 patients meeting inclusion criteria; 160 had papillary thyroid cancer (PTC), and the remaining 76 had FTC. The latter group were significantly older at baseline than PTC patients (64 versus 53 years), and were significantly less likely to undergo neck dissection (22% versus 55%).

In the full cohort, 96 patients (41%) had one high-risk factor, and an additional 74 (31%) had two risk factors. The remaining patients had three or more risk factors.

There was no between-group difference in the likelihood of receiving radioactive iodine treatment, but those with FTC had a lower cumulative radiation dose (195 versus 298 mCi; P less than .001).

More than half of patients (58%) had persistent disease after completing their first therapy. Of these, 51% had structural incomplete response and 7% had biochemical incomplete response. The response was indeterminate for about a quarter of the cohort, and the remaining 17% had an excellent initial response.

By the end of the study period, 55% of patients had persistent disease, and 51% had structural incomplete response (a more likely result for those with FTC than PTC). Just 4% had a biochemical incomplete response, and the response was indeterminate for 16%. Response was judged excellent for 29% of patients.

Dr. van Velsen and his coauthors reported that they had no relevant disclosures.

koakes@mdedge.com

SOURCE: van Velsen EFS et al. ENDO 2019, Abstract MON-549.

NEW ORLEANS – The 2015 American Thyroid Association risk stratification system for patients with differentiated thyroid cancer performed well in a real-world cohort with a high proportion of high-risk patients, according to a study presented at the annual meeting of the Endocrine Society.

“The 2015 ATA Risk Stratification System is an excellent predictor of both persisting disease and survival,” wrote Evert F.S. van Velsen, MD, and his colleagues at Erasmus Medical Center, Rotterdam, the Netherlands, in a poster accompanying the presentation.

Among a group of 236 patients with differentiated thyroid cancer (DTC), Dr. van Velsen and his coauthors looked at how the ATA high-risk criteria influenced patient response to therapy. By the end of the 14-year study period, initial gross extrathyroidal disease extension meant patients were much less likely to have an excellent response (odds ratio, 0.26; P less than .001), and much more likely to have persistent disease (OR, 2.57; P = .001).

Odds of having an excellent response were reduced by having high postoperative thyroglobulin levels (OR, 0.21; P less than .001), and persistent disease was more likely (OR, 2.39; P = .002).

Other high-risk criteria associated with significantly lower odds of excellent response included distant metastases (OR, 0.36), incomplete resection (OR, 0.51), and having follicular thyroid carcinoma (FTC) with extensive vascular invasion (OR, 0.27). All these risk factors also were associated with higher odds of persistent disease.

“Recurrence after no evidence of disease occurred in 14%” of the study population, said Dr. van Velsen and his coauthors, adding, “Clinicians should be aware of the relatively high recurrence risk, even after an excellent response to therapy.”

The study aimed to evaluate the 2015 ATA risk stratification system’s prognostic value in a population that included a relatively large proportion of high-risk DTC patients, to include many FTC patients. This work, they noted, augments previous assessments of the risk stratification system in lower-risk populations.

The authors noted that, in addition to predicting disease recurrence, the risk stratification system also worked as a predictor of disease-specific survival. Patients with structural incomplete response fared the worst, with a survival probability below 0.5 at 200 months on a Kaplan-Meier curve of disease-specific survival. Survival probability remained at 1.0 for patients with excellent response after first therapy and was intermediate for those with indeterminate response and biochemical incomplete response.

Overall mortality was higher in FTC patients. Over the study period, 31 of the 76 FTC patients (41%) died, compared with 39 of the PTC patients (24%; P = .010). In all, 28% of the FTC patients and 18% of the PTC patients died of thyroid cancer, but this difference didn’t reach statistical significance.

The retrospective study included adults with DTC meeting the 2015 ATA high-risk criteria who were diagnosed and/or treated at Erasmus Medical Center over a 13-year span ending in December 2015.

Overall, the investigators found 236 patients meeting inclusion criteria; 160 had papillary thyroid cancer (PTC), and the remaining 76 had FTC. The latter group were significantly older at baseline than PTC patients (64 versus 53 years), and were significantly less likely to undergo neck dissection (22% versus 55%).

In the full cohort, 96 patients (41%) had one high-risk factor, and an additional 74 (31%) had two risk factors. The remaining patients had three or more risk factors.

There was no between-group difference in the likelihood of receiving radioactive iodine treatment, but those with FTC had a lower cumulative radiation dose (195 versus 298 mCi; P less than .001).

More than half of patients (58%) had persistent disease after completing their first therapy. Of these, 51% had structural incomplete response and 7% had biochemical incomplete response. The response was indeterminate for about a quarter of the cohort, and the remaining 17% had an excellent initial response.

By the end of the study period, 55% of patients had persistent disease, and 51% had structural incomplete response (a more likely result for those with FTC than PTC). Just 4% had a biochemical incomplete response, and the response was indeterminate for 16%. Response was judged excellent for 29% of patients.

Dr. van Velsen and his coauthors reported that they had no relevant disclosures.

koakes@mdedge.com

SOURCE: van Velsen EFS et al. ENDO 2019, Abstract MON-549.

DENVER – Oral low-dose isotretinoin in combination with pulsed dye laser achieves high percentage of papulopustular rosacea clearance with a low risk of side effects, results from a single-center study found.

“Rosacea has been classically treated with topical and oral antibiotics, retinoids or ivermectin, and it is really important to enhance laser contribution for rosacea clearance,” lead study author Natalia Jiménez Gómez, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “Our work points to the high efficacy of a scarcely published combination treatment: low-dose oral isotretinoin and pulsed dye laser. Moreover, this combined treatment is employed in papulopustular rosacea, a clinical form that is usually treated without employing physical methods.”

For the study, Dr. Gómez and her colleagues retrospectively analyzed 40 patients with moderate or severe papulopustular rosacea who underwent concomitant treatment of pulsed dye laser and low-dose oral isotretinoin (5-10 mg/day). Pulsed dye laser sessions were performed with a 10-mm spot size at a pulse duration of 0.5 milliseconds delivered at a fluence of 8 J/cm² every 3-4 weeks in combination with low-dose oral isotretinoin during 4- to 6-month periods. The treatment endpoint was purpura. Five patients were withdrawn from the analysis because of loss to follow-up or to a lack of clinical images.

All 35 patients achieved a complete clearance of papulopustular lesions of rosacea within 7-10 days, said Dr. Gómez, who practices at the Madrid-based Hospital Universitario Ramón y Cajal. The researchers did not observe any permanent adverse events such as scarring, hyperpigmentation, or hypopigmentation.

“The most surprising finding was the high percentage of rosacea clearance obtained with the combined treatment, considering that all the patients were previously nonresponsive to oral low-dose isotretinoin monotherapy,” Dr. Gómez said. “This finding highlights the important role of pulsed dye laser.”

She acknowledged certain limitations of the study, including its retrospective design and small sample size. “It would also be interesting to compare pulsed dye laser with intense pulsed light, so that we can conclude if one of them is more effective than the other when we combine it with low dose oral isotretinoin,” she said.

Dr. Gómez reported having no financial disclosures.

dbrunk@mdedge.com

DENVER – Oral low-dose isotretinoin in combination with pulsed dye laser achieves high percentage of papulopustular rosacea clearance with a low risk of side effects, results from a single-center study found.

“Rosacea has been classically treated with topical and oral antibiotics, retinoids or ivermectin, and it is really important to enhance laser contribution for rosacea clearance,” lead study author Natalia Jiménez Gómez, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “Our work points to the high efficacy of a scarcely published combination treatment: low-dose oral isotretinoin and pulsed dye laser. Moreover, this combined treatment is employed in papulopustular rosacea, a clinical form that is usually treated without employing physical methods.”

For the study, Dr. Gómez and her colleagues retrospectively analyzed 40 patients with moderate or severe papulopustular rosacea who underwent concomitant treatment of pulsed dye laser and low-dose oral isotretinoin (5-10 mg/day). Pulsed dye laser sessions were performed with a 10-mm spot size at a pulse duration of 0.5 milliseconds delivered at a fluence of 8 J/cm² every 3-4 weeks in combination with low-dose oral isotretinoin during 4- to 6-month periods. The treatment endpoint was purpura. Five patients were withdrawn from the analysis because of loss to follow-up or to a lack of clinical images.

All 35 patients achieved a complete clearance of papulopustular lesions of rosacea within 7-10 days, said Dr. Gómez, who practices at the Madrid-based Hospital Universitario Ramón y Cajal. The researchers did not observe any permanent adverse events such as scarring, hyperpigmentation, or hypopigmentation.

“The most surprising finding was the high percentage of rosacea clearance obtained with the combined treatment, considering that all the patients were previously nonresponsive to oral low-dose isotretinoin monotherapy,” Dr. Gómez said. “This finding highlights the important role of pulsed dye laser.”

She acknowledged certain limitations of the study, including its retrospective design and small sample size. “It would also be interesting to compare pulsed dye laser with intense pulsed light, so that we can conclude if one of them is more effective than the other when we combine it with low dose oral isotretinoin,” she said.

Dr. Gómez reported having no financial disclosures.

dbrunk@mdedge.com

DENVER – Oral low-dose isotretinoin in combination with pulsed dye laser achieves high percentage of papulopustular rosacea clearance with a low risk of side effects, results from a single-center study found.

“Rosacea has been classically treated with topical and oral antibiotics, retinoids or ivermectin, and it is really important to enhance laser contribution for rosacea clearance,” lead study author Natalia Jiménez Gómez, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “Our work points to the high efficacy of a scarcely published combination treatment: low-dose oral isotretinoin and pulsed dye laser. Moreover, this combined treatment is employed in papulopustular rosacea, a clinical form that is usually treated without employing physical methods.”

For the study, Dr. Gómez and her colleagues retrospectively analyzed 40 patients with moderate or severe papulopustular rosacea who underwent concomitant treatment of pulsed dye laser and low-dose oral isotretinoin (5-10 mg/day). Pulsed dye laser sessions were performed with a 10-mm spot size at a pulse duration of 0.5 milliseconds delivered at a fluence of 8 J/cm² every 3-4 weeks in combination with low-dose oral isotretinoin during 4- to 6-month periods. The treatment endpoint was purpura. Five patients were withdrawn from the analysis because of loss to follow-up or to a lack of clinical images.

All 35 patients achieved a complete clearance of papulopustular lesions of rosacea within 7-10 days, said Dr. Gómez, who practices at the Madrid-based Hospital Universitario Ramón y Cajal. The researchers did not observe any permanent adverse events such as scarring, hyperpigmentation, or hypopigmentation.

“The most surprising finding was the high percentage of rosacea clearance obtained with the combined treatment, considering that all the patients were previously nonresponsive to oral low-dose isotretinoin monotherapy,” Dr. Gómez said. “This finding highlights the important role of pulsed dye laser.”

She acknowledged certain limitations of the study, including its retrospective design and small sample size. “It would also be interesting to compare pulsed dye laser with intense pulsed light, so that we can conclude if one of them is more effective than the other when we combine it with low dose oral isotretinoin,” she said.

Dr. Gómez reported having no financial disclosures.

dbrunk@mdedge.com

SAN FRANCISCO – The announcement of a first-ever multicenter randomized trial of ACE inhibitors for the treatment of cognitive impairment in systemic lupus erythematosus patients generated some of the biggest buzz at LUPUS 2019.

Bruce Jancin/MDedge News

“The time has come to implement clinical trials in lupus to see if we can address what is one of the most distressing aspects of the disease to patients,” Betty Diamond, MD, said in announcing the planned trial at an international congress on systemic lupus erythematosus (SLE).

Neuropsychiatric lupus, characterized most often by cognitive impairment, affects 40%-90% of SLE patients, according to various epidemiologic studies. This confusion and memory loss has been shown to be independent of systemic disease activity.

“Cognitive impairment is a very common problem and a very insidious problem in lupus patients,” emphasized Dr. Diamond, professor and head of the Center for Autoimmune Musculoskeletal and Hematopoietic Diseases at the Feinstein Institute for Medical Research in Manhasset, New York.

Dr. Diamond was the recipient of the 2018 Lupus Insight Prize awarded by the Lupus Research Alliance, which is funding the multicenter randomized trial. For the study, roughly 70 SLE patients with cognitive impairment not associated with a focal brain lesion will be randomized to receive a centrally acting ACE inhibitor – captopril was the one she and her coinvestigators have used in their mouse model and preliminary clinical studies – or to a non–centrally acting ACE inhibitor, such as enalapril.

“The clinical trial compares an ACE inhibitor that crosses the blood-brain barrier with one that doesn’t. They both have the same renal protection and systemic anti-inflammatory effects,” explained Dr. Diamond, who is also professor of molecular medicine and of medicine at the Zucker School of Medicine at Hofstra/Northwell, East Garden City, N.Y.

In a recent publication (J Exp Med. 2018 Oct 1;215[10]:2554-66), Dr. Diamond and her coinvestigators presented much of the background work that underpins the upcoming randomized trial. Sixteen years ago, they discovered two anti-DNA antibodies that cross-react with the N-methyl-D-aspartate receptor (NMDAR) and enhance NMDAR signaling. They showed that while the NMDARs are critical in learning and memory, their prolonged stimulation results in a high degree of calcium influx, causing neuronal death. These anti-DNA/anti-NMDAR antibodies, known as DNRAbs, are present at elevated titers in 30%-40% of SLE patients, and in a higher proportion of those with neuropsychiatric lupus.

“Most importantly, DNRAbs are present in the cerebrospinal fluid of patients who have nonfocal CNS manifestations of lupus,” Dr. Diamond said.

She and her coworkers developed a mouse model of cognitive impairment in lupus and utilized it to identify a two-stage model of the pathogenesis of DNRAb-mediated neuropsychiatric lupus. First, a traumatic event such as an infection causes a temporary opening in the blood-brain barrier, allowing the DNRAbs to reach the brain. This results in acute excitotoxic neuronal death. This is followed by a second stage, which entails activation of microglia – known as the macrophages of the CNS – with resultant loss of neuronal dendritic arborization and complexity. In the mouse model, this causes a selective impairment in spatial memory that corresponds well to the spatial memory deficit the investigators documented in DNRAb-positive SLE patients, compared with healthy controls and DNRAb-negative lupus patients.

A key finding in this project, Dr. Diamond continued, was that activated microglia turn out to be critical for dendritic loss. If the microglia are deactivated, regrowth of the dendritic processes occurs. This raises a possibility that attendees at LUPUS 2019 found thrilling: Perhaps the cognitive impairment of neuropsychiatric SLE can be prevented and even reversed by suppressing microglial activation.

Promising work in the field of Alzheimer’s disease suggests that centrally acting ACE inhibitors can indeed suppress microglial activation and actually improve cognition. Dr. Diamond and her colleagues showed this also was the case in their mouse model. Moreover, in a small clinical study they used PET brain imaging to show that captopril reduced the increased glucose uptake and hippocampal hypermetabolism associated with DNRAb-positive neuropsychiatric lupus, an effect maintained through 18 months of follow-up.

“We think DNRAbs contribute to cognitive impairment in SLE patients, but we certainly wouldn’t say that antibodies are the only mechanism. Other investigators have shown that interferon can also do this, and that, like the antibodies, interferon acts through microglial activation. We think that this microglial activation is going to be a general paradigm in cognitive impairment in lupus and in other diseases, so microglia are a very good therapeutic target,” Dr. Diamond said.

The primary outcomes in the forthcoming randomized trial involve PET neuronal imaging. They investigators are hoping to see reduced hippocampal hypermetabolism and suppression of activated microglial cells.

“We’ll see if we’re actually hitting our target. We’re doing neuropsychologic testing, too, but we’re really concentrating on imaging outcomes, because those are objective and have many fewer variables to confound them,” according to Dr. Diamond.

Microglial activation is a current topic of intense research interest within the pharmaceutical industry, she added. If the imaging study is positive, she anticipates drug companies will quickly ramp up and conduct large clinical trials powered to show significant results in terms of neuropsychologic test scores and clinical outcomes.

Dr. Diamond reported having no financial conflicts regarding her work, which has been supported largely by the National Institutes of Health.

bjancin@mdedge.com

SAN FRANCISCO – The announcement of a first-ever multicenter randomized trial of ACE inhibitors for the treatment of cognitive impairment in systemic lupus erythematosus patients generated some of the biggest buzz at LUPUS 2019.

Bruce Jancin/MDedge News

“The time has come to implement clinical trials in lupus to see if we can address what is one of the most distressing aspects of the disease to patients,” Betty Diamond, MD, said in announcing the planned trial at an international congress on systemic lupus erythematosus (SLE).

Neuropsychiatric lupus, characterized most often by cognitive impairment, affects 40%-90% of SLE patients, according to various epidemiologic studies. This confusion and memory loss has been shown to be independent of systemic disease activity.

“Cognitive impairment is a very common problem and a very insidious problem in lupus patients,” emphasized Dr. Diamond, professor and head of the Center for Autoimmune Musculoskeletal and Hematopoietic Diseases at the Feinstein Institute for Medical Research in Manhasset, New York.

Dr. Diamond was the recipient of the 2018 Lupus Insight Prize awarded by the Lupus Research Alliance, which is funding the multicenter randomized trial. For the study, roughly 70 SLE patients with cognitive impairment not associated with a focal brain lesion will be randomized to receive a centrally acting ACE inhibitor – captopril was the one she and her coinvestigators have used in their mouse model and preliminary clinical studies – or to a non–centrally acting ACE inhibitor, such as enalapril.

“The clinical trial compares an ACE inhibitor that crosses the blood-brain barrier with one that doesn’t. They both have the same renal protection and systemic anti-inflammatory effects,” explained Dr. Diamond, who is also professor of molecular medicine and of medicine at the Zucker School of Medicine at Hofstra/Northwell, East Garden City, N.Y.

In a recent publication (J Exp Med. 2018 Oct 1;215[10]:2554-66), Dr. Diamond and her coinvestigators presented much of the background work that underpins the upcoming randomized trial. Sixteen years ago, they discovered two anti-DNA antibodies that cross-react with the N-methyl-D-aspartate receptor (NMDAR) and enhance NMDAR signaling. They showed that while the NMDARs are critical in learning and memory, their prolonged stimulation results in a high degree of calcium influx, causing neuronal death. These anti-DNA/anti-NMDAR antibodies, known as DNRAbs, are present at elevated titers in 30%-40% of SLE patients, and in a higher proportion of those with neuropsychiatric lupus.

“Most importantly, DNRAbs are present in the cerebrospinal fluid of patients who have nonfocal CNS manifestations of lupus,” Dr. Diamond said.

She and her coworkers developed a mouse model of cognitive impairment in lupus and utilized it to identify a two-stage model of the pathogenesis of DNRAb-mediated neuropsychiatric lupus. First, a traumatic event such as an infection causes a temporary opening in the blood-brain barrier, allowing the DNRAbs to reach the brain. This results in acute excitotoxic neuronal death. This is followed by a second stage, which entails activation of microglia – known as the macrophages of the CNS – with resultant loss of neuronal dendritic arborization and complexity. In the mouse model, this causes a selective impairment in spatial memory that corresponds well to the spatial memory deficit the investigators documented in DNRAb-positive SLE patients, compared with healthy controls and DNRAb-negative lupus patients.

A key finding in this project, Dr. Diamond continued, was that activated microglia turn out to be critical for dendritic loss. If the microglia are deactivated, regrowth of the dendritic processes occurs. This raises a possibility that attendees at LUPUS 2019 found thrilling: Perhaps the cognitive impairment of neuropsychiatric SLE can be prevented and even reversed by suppressing microglial activation.

Promising work in the field of Alzheimer’s disease suggests that centrally acting ACE inhibitors can indeed suppress microglial activation and actually improve cognition. Dr. Diamond and her colleagues showed this also was the case in their mouse model. Moreover, in a small clinical study they used PET brain imaging to show that captopril reduced the increased glucose uptake and hippocampal hypermetabolism associated with DNRAb-positive neuropsychiatric lupus, an effect maintained through 18 months of follow-up.

“We think DNRAbs contribute to cognitive impairment in SLE patients, but we certainly wouldn’t say that antibodies are the only mechanism. Other investigators have shown that interferon can also do this, and that, like the antibodies, interferon acts through microglial activation. We think that this microglial activation is going to be a general paradigm in cognitive impairment in lupus and in other diseases, so microglia are a very good therapeutic target,” Dr. Diamond said.

The primary outcomes in the forthcoming randomized trial involve PET neuronal imaging. They investigators are hoping to see reduced hippocampal hypermetabolism and suppression of activated microglial cells.

“We’ll see if we’re actually hitting our target. We’re doing neuropsychologic testing, too, but we’re really concentrating on imaging outcomes, because those are objective and have many fewer variables to confound them,” according to Dr. Diamond.

Microglial activation is a current topic of intense research interest within the pharmaceutical industry, she added. If the imaging study is positive, she anticipates drug companies will quickly ramp up and conduct large clinical trials powered to show significant results in terms of neuropsychologic test scores and clinical outcomes.

Dr. Diamond reported having no financial conflicts regarding her work, which has been supported largely by the National Institutes of Health.

bjancin@mdedge.com

SAN FRANCISCO – The announcement of a first-ever multicenter randomized trial of ACE inhibitors for the treatment of cognitive impairment in systemic lupus erythematosus patients generated some of the biggest buzz at LUPUS 2019.

Bruce Jancin/MDedge News

“The time has come to implement clinical trials in lupus to see if we can address what is one of the most distressing aspects of the disease to patients,” Betty Diamond, MD, said in announcing the planned trial at an international congress on systemic lupus erythematosus (SLE).

Neuropsychiatric lupus, characterized most often by cognitive impairment, affects 40%-90% of SLE patients, according to various epidemiologic studies. This confusion and memory loss has been shown to be independent of systemic disease activity.

“Cognitive impairment is a very common problem and a very insidious problem in lupus patients,” emphasized Dr. Diamond, professor and head of the Center for Autoimmune Musculoskeletal and Hematopoietic Diseases at the Feinstein Institute for Medical Research in Manhasset, New York.

Dr. Diamond was the recipient of the 2018 Lupus Insight Prize awarded by the Lupus Research Alliance, which is funding the multicenter randomized trial. For the study, roughly 70 SLE patients with cognitive impairment not associated with a focal brain lesion will be randomized to receive a centrally acting ACE inhibitor – captopril was the one she and her coinvestigators have used in their mouse model and preliminary clinical studies – or to a non–centrally acting ACE inhibitor, such as enalapril.

“The clinical trial compares an ACE inhibitor that crosses the blood-brain barrier with one that doesn’t. They both have the same renal protection and systemic anti-inflammatory effects,” explained Dr. Diamond, who is also professor of molecular medicine and of medicine at the Zucker School of Medicine at Hofstra/Northwell, East Garden City, N.Y.

In a recent publication (J Exp Med. 2018 Oct 1;215[10]:2554-66), Dr. Diamond and her coinvestigators presented much of the background work that underpins the upcoming randomized trial. Sixteen years ago, they discovered two anti-DNA antibodies that cross-react with the N-methyl-D-aspartate receptor (NMDAR) and enhance NMDAR signaling. They showed that while the NMDARs are critical in learning and memory, their prolonged stimulation results in a high degree of calcium influx, causing neuronal death. These anti-DNA/anti-NMDAR antibodies, known as DNRAbs, are present at elevated titers in 30%-40% of SLE patients, and in a higher proportion of those with neuropsychiatric lupus.

“Most importantly, DNRAbs are present in the cerebrospinal fluid of patients who have nonfocal CNS manifestations of lupus,” Dr. Diamond said.

She and her coworkers developed a mouse model of cognitive impairment in lupus and utilized it to identify a two-stage model of the pathogenesis of DNRAb-mediated neuropsychiatric lupus. First, a traumatic event such as an infection causes a temporary opening in the blood-brain barrier, allowing the DNRAbs to reach the brain. This results in acute excitotoxic neuronal death. This is followed by a second stage, which entails activation of microglia – known as the macrophages of the CNS – with resultant loss of neuronal dendritic arborization and complexity. In the mouse model, this causes a selective impairment in spatial memory that corresponds well to the spatial memory deficit the investigators documented in DNRAb-positive SLE patients, compared with healthy controls and DNRAb-negative lupus patients.

A key finding in this project, Dr. Diamond continued, was that activated microglia turn out to be critical for dendritic loss. If the microglia are deactivated, regrowth of the dendritic processes occurs. This raises a possibility that attendees at LUPUS 2019 found thrilling: Perhaps the cognitive impairment of neuropsychiatric SLE can be prevented and even reversed by suppressing microglial activation.

Promising work in the field of Alzheimer’s disease suggests that centrally acting ACE inhibitors can indeed suppress microglial activation and actually improve cognition. Dr. Diamond and her colleagues showed this also was the case in their mouse model. Moreover, in a small clinical study they used PET brain imaging to show that captopril reduced the increased glucose uptake and hippocampal hypermetabolism associated with DNRAb-positive neuropsychiatric lupus, an effect maintained through 18 months of follow-up.

“We think DNRAbs contribute to cognitive impairment in SLE patients, but we certainly wouldn’t say that antibodies are the only mechanism. Other investigators have shown that interferon can also do this, and that, like the antibodies, interferon acts through microglial activation. We think that this microglial activation is going to be a general paradigm in cognitive impairment in lupus and in other diseases, so microglia are a very good therapeutic target,” Dr. Diamond said.

The primary outcomes in the forthcoming randomized trial involve PET neuronal imaging. They investigators are hoping to see reduced hippocampal hypermetabolism and suppression of activated microglial cells.

“We’ll see if we’re actually hitting our target. We’re doing neuropsychologic testing, too, but we’re really concentrating on imaging outcomes, because those are objective and have many fewer variables to confound them,” according to Dr. Diamond.

Microglial activation is a current topic of intense research interest within the pharmaceutical industry, she added. If the imaging study is positive, she anticipates drug companies will quickly ramp up and conduct large clinical trials powered to show significant results in terms of neuropsychologic test scores and clinical outcomes.

Dr. Diamond reported having no financial conflicts regarding her work, which has been supported largely by the National Institutes of Health.

bjancin@mdedge.com

PHILADELPHIA – Nearly 7%-10% of the general population experiences neuropathic pain, but studies on treatments have not found a clear winner for reducing this “burning or electriclike pain,” explained Raymond Price, MD, during a presentation.

Andrew Bowser/MDedge News

“It isn’t that exciting,” said Dr. Price, associate professor of neurology at the University of Pennsylvania, Philadelphia, in reference to his review of level 1-2 evidence for treatment of neuropathic pain that was presented in a study published in JAMA (2015 Nov 24;314[20]:2172-81). a few years ago. “On a scale of 1 to 10, you can reduce their pain scale by 1-2 points more than placebo,” he told his audience at the annual meeting of the American College of Physicians.

“In general, you can use any of these medicines [for neuropathic pain]. There are very limited head-to-head data as to which one is actually better,” he explained.

Given the absence of robust head-to-head trial data, Dr. Price tends to start a lot of patients on old, cheap medications like nortriptyline.

While there aren’t many head-to-head trials to guide treatment choice, the results of one prospective, randomized, open-label study of 333 patients with cryptogenic sensory polyneuropathy was presented by Barohn and colleagues at the 2018 annual meeting of the American Academy of Neurology, he said. In that study, somewhat higher efficacy rates were seen with duloxetine, a serotonin-noradrenaline reuptake inhibitor, and nortriptyline, a tricyclic antidepressant, compared with pregabalin, Dr. Price noted. Duloxetine and nortriptyline also had slightly better tolerability, as evidenced by a lower quit rate, compared with pregabalin, he added.

There was also a systematic review and meta-analysis (Lancet Neurol. 2015 Feb; 14[2]:162-73) conducted that determined the number needed to treat for neuropathic pain treatments, Dr. Price noted. In that paper, tricyclic antidepressants had a number needed to treat of 3.6, comparing favorably to 7.7 for pregabalin, 7.2 for gabapentin, and 6.4 for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine, said Dr. Price.

Regardless of the cause of neuropathic pain, the same general approach to treatment is taken, though most of the evidence comes from studies of patients with painful diabetic peripheral neuropathy or postherpetic neuralgia, he added.

For these patients, an adequate trial of a neuropathic pain treatment should be 6-12 weeks, reflecting the length of the intervention needed to demonstrate the efficacy of these agents, he said.

If that first drug doesn’t work, another can be tried, or multiple drugs can be tried together to see if the patient’s condition improves, he said.

Dr. Price reported no conflicts of interest.
 

SOURCE: Price R Internal Medicine 2019, Presentation MSFM 002.

PHILADELPHIA – Nearly 7%-10% of the general population experiences neuropathic pain, but studies on treatments have not found a clear winner for reducing this “burning or electriclike pain,” explained Raymond Price, MD, during a presentation.

Andrew Bowser/MDedge News

“It isn’t that exciting,” said Dr. Price, associate professor of neurology at the University of Pennsylvania, Philadelphia, in reference to his review of level 1-2 evidence for treatment of neuropathic pain that was presented in a study published in JAMA (2015 Nov 24;314[20]:2172-81). a few years ago. “On a scale of 1 to 10, you can reduce their pain scale by 1-2 points more than placebo,” he told his audience at the annual meeting of the American College of Physicians.

“In general, you can use any of these medicines [for neuropathic pain]. There are very limited head-to-head data as to which one is actually better,” he explained.

Given the absence of robust head-to-head trial data, Dr. Price tends to start a lot of patients on old, cheap medications like nortriptyline.

While there aren’t many head-to-head trials to guide treatment choice, the results of one prospective, randomized, open-label study of 333 patients with cryptogenic sensory polyneuropathy was presented by Barohn and colleagues at the 2018 annual meeting of the American Academy of Neurology, he said. In that study, somewhat higher efficacy rates were seen with duloxetine, a serotonin-noradrenaline reuptake inhibitor, and nortriptyline, a tricyclic antidepressant, compared with pregabalin, Dr. Price noted. Duloxetine and nortriptyline also had slightly better tolerability, as evidenced by a lower quit rate, compared with pregabalin, he added.

There was also a systematic review and meta-analysis (Lancet Neurol. 2015 Feb; 14[2]:162-73) conducted that determined the number needed to treat for neuropathic pain treatments, Dr. Price noted. In that paper, tricyclic antidepressants had a number needed to treat of 3.6, comparing favorably to 7.7 for pregabalin, 7.2 for gabapentin, and 6.4 for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine, said Dr. Price.

Regardless of the cause of neuropathic pain, the same general approach to treatment is taken, though most of the evidence comes from studies of patients with painful diabetic peripheral neuropathy or postherpetic neuralgia, he added.

For these patients, an adequate trial of a neuropathic pain treatment should be 6-12 weeks, reflecting the length of the intervention needed to demonstrate the efficacy of these agents, he said.

If that first drug doesn’t work, another can be tried, or multiple drugs can be tried together to see if the patient’s condition improves, he said.

Dr. Price reported no conflicts of interest.
 

SOURCE: Price R Internal Medicine 2019, Presentation MSFM 002.

PHILADELPHIA – Nearly 7%-10% of the general population experiences neuropathic pain, but studies on treatments have not found a clear winner for reducing this “burning or electriclike pain,” explained Raymond Price, MD, during a presentation.

Andrew Bowser/MDedge News

“It isn’t that exciting,” said Dr. Price, associate professor of neurology at the University of Pennsylvania, Philadelphia, in reference to his review of level 1-2 evidence for treatment of neuropathic pain that was presented in a study published in JAMA (2015 Nov 24;314[20]:2172-81). a few years ago. “On a scale of 1 to 10, you can reduce their pain scale by 1-2 points more than placebo,” he told his audience at the annual meeting of the American College of Physicians.

“In general, you can use any of these medicines [for neuropathic pain]. There are very limited head-to-head data as to which one is actually better,” he explained.

Given the absence of robust head-to-head trial data, Dr. Price tends to start a lot of patients on old, cheap medications like nortriptyline.

While there aren’t many head-to-head trials to guide treatment choice, the results of one prospective, randomized, open-label study of 333 patients with cryptogenic sensory polyneuropathy was presented by Barohn and colleagues at the 2018 annual meeting of the American Academy of Neurology, he said. In that study, somewhat higher efficacy rates were seen with duloxetine, a serotonin-noradrenaline reuptake inhibitor, and nortriptyline, a tricyclic antidepressant, compared with pregabalin, Dr. Price noted. Duloxetine and nortriptyline also had slightly better tolerability, as evidenced by a lower quit rate, compared with pregabalin, he added.

There was also a systematic review and meta-analysis (Lancet Neurol. 2015 Feb; 14[2]:162-73) conducted that determined the number needed to treat for neuropathic pain treatments, Dr. Price noted. In that paper, tricyclic antidepressants had a number needed to treat of 3.6, comparing favorably to 7.7 for pregabalin, 7.2 for gabapentin, and 6.4 for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine, said Dr. Price.

Regardless of the cause of neuropathic pain, the same general approach to treatment is taken, though most of the evidence comes from studies of patients with painful diabetic peripheral neuropathy or postherpetic neuralgia, he added.

For these patients, an adequate trial of a neuropathic pain treatment should be 6-12 weeks, reflecting the length of the intervention needed to demonstrate the efficacy of these agents, he said.

If that first drug doesn’t work, another can be tried, or multiple drugs can be tried together to see if the patient’s condition improves, he said.

Dr. Price reported no conflicts of interest.
 

SOURCE: Price R Internal Medicine 2019, Presentation MSFM 002.