Ted Bosworth

When the PCSK9 inhibitor alirocumab is added to high-intensity statins soon after an acute myocardial infarction (AMI), the reduction in atheroma volume is doubled at 12 months, compared with placebo, while other key signs of plaque stabilization, such as fibrous cap thickness, are also significantly and substantially improved, according to the results of the PACMAN-AMI trial.

The study is consistent with other PCSK9 inhibitor trials, supporting the concept that “we should be seeking very low levels of LDL-C in high-risk patients,” reported Lorenz Räber, MD, PhD, of Bern (Switz.) University Hospital, at the annual scientific sessions of the American College of Cardiology.

Catherine Hackett/MDedge News

Primary outcome was atheroma volume

The primary endpoint was atheroma volume as determined by intravenous ultrasound (IVUS), but the secondary endpoints of maximum lipid core burden, as determined by near infrared spectroscopy (NIRS), and fibrous cap thickness, as determined by optical coherence tomography (OCT), were also adequately powered, according to Dr. Räber.

The imaging measures taken at baseline were repeated in exactly the same spot after 52 weeks on treatment.

For the primary outcome of atheroma volume, the mean 2.1% reduction among those randomized to alirocumab was more than double the 0.9% reduction in the placebo group (P = .001).

The mean reduction in lipid core volume based on a maximum lipid core burden index was also more than doubled (-79.42 vs. -37.60 maxLCBI­4mm; P = .006). The increase in fibrous cap thickness was not quite twofold greater but very close (62.67 vs. 33.19 mcm; P = .001).

From baseline, the relative reductions in LDL-C, which were reached about 4 weeks after starting treatment and maintained over the course of the study, were greater in the group randomized to alirocumab (-84.8% vs. -50.7%). This was expected, but the more important finding was a near linear relationship between reductions of LDL-C and each of these endpoints regardless of treatment, fully explaining the advantage of alirocumab, according to Dr. Räber.

For the addition of alirocumab, “these findings indicate incremental coronary plaque regression, lipid core reduction, and plaque stabilization, and provide a mechanistic rationale in favor of early initiation of very intensive LDL-C lower in the setting of an acute MI,” he said.

The results of the PACMAN-AMI trial were published simultaneously at the time of the ACC presentation.
 

Results consistent with earlier trials

Alirocumab was well tolerated. Injection site reactions (6.1% vs. 3.3%) and general allergic reactions (3.4% vs. 0%) were more common on alirocumab, but there were no significant differences between the arms of this study for serious adverse events. There were slightly more neurocognitive events (2.0 vs. 0%) and abnormal alanine transferase levels (0.7% vs. 0%) in the alirocumab group.

The data are generally consistent with two previously published trials with another PCSK9 inhibitor, according to Dr. Räber. In the randomized GLAGOV trial published more than 5 years ago, evolocumab also produced about a 1% absolute reduction (P < .001) in plaque volume at the end of 78 weeks of follow-up relative to placebo.

However, that trial was limited to patients with coronary artery disease without a recent cardiovascular event. The more recent HUYGENS trial, which was presented virtually at the 2021 annual meeting of the European Society of Cardiology meeting and has not yet been published, looked at one of the endpoints also evaluated in PACMAN-AMI. In that study of 161 randomized NSTEMI patients, there was also about a doubling of fibrous cap thickness (42.7 vs. 21.5 mcm) for the PCSK9 inhibitor relative to placebo.

Clinical endpoints were not compared in either the PACMAN-AMI or HUYGENS trial.
 

PACMAN-AMI confirms plaque stabilization

Nevertheless, the message of plaque stabilization is important, according to Anthony N. DeMaria, MD, Founding Director of the Sulpizio Cardiovascular Center at the University of San Diego. Although he acknowledged that a 1% absolute reduction in mean plaque volume might “make you want to yawn,” he argued that this is a misreading of important changes observed in plaque physiology.

“What we have now is evidence that very low lipid levels result in plaque remodeling. The plaques might not get a whole lot smaller, but the changes are important,” he said, noting, for example, that a thicker fibrous cap and increased plaque stability “clearly plays a role in reducing risk of subsequent events.”

“You cannot help but be impressed by the relationship of lipid lowering and the favorable effect on remodeling,” he added.

The data associating PCSK9 inhibitors with protection from cardiovascular events is already extensive, according to Michael J. Blaha, MD, Director of Clinical Research for Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, but he called PACMAN-ACS “an extremely relevant study.”

When the PCSK9 inhibitor alirocumab is added to high-intensity statins soon after an acute myocardial infarction (AMI), the reduction in atheroma volume is doubled at 12 months, compared with placebo, while other key signs of plaque stabilization, such as fibrous cap thickness, are also significantly and substantially improved, according to the results of the PACMAN-AMI trial.

The study is consistent with other PCSK9 inhibitor trials, supporting the concept that “we should be seeking very low levels of LDL-C in high-risk patients,” reported Lorenz Räber, MD, PhD, of Bern (Switz.) University Hospital, at the annual scientific sessions of the American College of Cardiology.

Catherine Hackett/MDedge News

Primary outcome was atheroma volume

The primary endpoint was atheroma volume as determined by intravenous ultrasound (IVUS), but the secondary endpoints of maximum lipid core burden, as determined by near infrared spectroscopy (NIRS), and fibrous cap thickness, as determined by optical coherence tomography (OCT), were also adequately powered, according to Dr. Räber.

The imaging measures taken at baseline were repeated in exactly the same spot after 52 weeks on treatment.

For the primary outcome of atheroma volume, the mean 2.1% reduction among those randomized to alirocumab was more than double the 0.9% reduction in the placebo group (P = .001).

The mean reduction in lipid core volume based on a maximum lipid core burden index was also more than doubled (-79.42 vs. -37.60 maxLCBI­4mm; P = .006). The increase in fibrous cap thickness was not quite twofold greater but very close (62.67 vs. 33.19 mcm; P = .001).

From baseline, the relative reductions in LDL-C, which were reached about 4 weeks after starting treatment and maintained over the course of the study, were greater in the group randomized to alirocumab (-84.8% vs. -50.7%). This was expected, but the more important finding was a near linear relationship between reductions of LDL-C and each of these endpoints regardless of treatment, fully explaining the advantage of alirocumab, according to Dr. Räber.

For the addition of alirocumab, “these findings indicate incremental coronary plaque regression, lipid core reduction, and plaque stabilization, and provide a mechanistic rationale in favor of early initiation of very intensive LDL-C lower in the setting of an acute MI,” he said.

The results of the PACMAN-AMI trial were published simultaneously at the time of the ACC presentation.
 

Results consistent with earlier trials

Alirocumab was well tolerated. Injection site reactions (6.1% vs. 3.3%) and general allergic reactions (3.4% vs. 0%) were more common on alirocumab, but there were no significant differences between the arms of this study for serious adverse events. There were slightly more neurocognitive events (2.0 vs. 0%) and abnormal alanine transferase levels (0.7% vs. 0%) in the alirocumab group.

The data are generally consistent with two previously published trials with another PCSK9 inhibitor, according to Dr. Räber. In the randomized GLAGOV trial published more than 5 years ago, evolocumab also produced about a 1% absolute reduction (P < .001) in plaque volume at the end of 78 weeks of follow-up relative to placebo.

However, that trial was limited to patients with coronary artery disease without a recent cardiovascular event. The more recent HUYGENS trial, which was presented virtually at the 2021 annual meeting of the European Society of Cardiology meeting and has not yet been published, looked at one of the endpoints also evaluated in PACMAN-AMI. In that study of 161 randomized NSTEMI patients, there was also about a doubling of fibrous cap thickness (42.7 vs. 21.5 mcm) for the PCSK9 inhibitor relative to placebo.

Clinical endpoints were not compared in either the PACMAN-AMI or HUYGENS trial.
 

PACMAN-AMI confirms plaque stabilization

Nevertheless, the message of plaque stabilization is important, according to Anthony N. DeMaria, MD, Founding Director of the Sulpizio Cardiovascular Center at the University of San Diego. Although he acknowledged that a 1% absolute reduction in mean plaque volume might “make you want to yawn,” he argued that this is a misreading of important changes observed in plaque physiology.

“What we have now is evidence that very low lipid levels result in plaque remodeling. The plaques might not get a whole lot smaller, but the changes are important,” he said, noting, for example, that a thicker fibrous cap and increased plaque stability “clearly plays a role in reducing risk of subsequent events.”

“You cannot help but be impressed by the relationship of lipid lowering and the favorable effect on remodeling,” he added.

The data associating PCSK9 inhibitors with protection from cardiovascular events is already extensive, according to Michael J. Blaha, MD, Director of Clinical Research for Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, but he called PACMAN-ACS “an extremely relevant study.”

When the PCSK9 inhibitor alirocumab is added to high-intensity statins soon after an acute myocardial infarction (AMI), the reduction in atheroma volume is doubled at 12 months, compared with placebo, while other key signs of plaque stabilization, such as fibrous cap thickness, are also significantly and substantially improved, according to the results of the PACMAN-AMI trial.

The study is consistent with other PCSK9 inhibitor trials, supporting the concept that “we should be seeking very low levels of LDL-C in high-risk patients,” reported Lorenz Räber, MD, PhD, of Bern (Switz.) University Hospital, at the annual scientific sessions of the American College of Cardiology.

Catherine Hackett/MDedge News

Primary outcome was atheroma volume

The primary endpoint was atheroma volume as determined by intravenous ultrasound (IVUS), but the secondary endpoints of maximum lipid core burden, as determined by near infrared spectroscopy (NIRS), and fibrous cap thickness, as determined by optical coherence tomography (OCT), were also adequately powered, according to Dr. Räber.

The imaging measures taken at baseline were repeated in exactly the same spot after 52 weeks on treatment.

For the primary outcome of atheroma volume, the mean 2.1% reduction among those randomized to alirocumab was more than double the 0.9% reduction in the placebo group (P = .001).

The mean reduction in lipid core volume based on a maximum lipid core burden index was also more than doubled (-79.42 vs. -37.60 maxLCBI­4mm; P = .006). The increase in fibrous cap thickness was not quite twofold greater but very close (62.67 vs. 33.19 mcm; P = .001).

From baseline, the relative reductions in LDL-C, which were reached about 4 weeks after starting treatment and maintained over the course of the study, were greater in the group randomized to alirocumab (-84.8% vs. -50.7%). This was expected, but the more important finding was a near linear relationship between reductions of LDL-C and each of these endpoints regardless of treatment, fully explaining the advantage of alirocumab, according to Dr. Räber.

For the addition of alirocumab, “these findings indicate incremental coronary plaque regression, lipid core reduction, and plaque stabilization, and provide a mechanistic rationale in favor of early initiation of very intensive LDL-C lower in the setting of an acute MI,” he said.

The results of the PACMAN-AMI trial were published simultaneously at the time of the ACC presentation.
 

Results consistent with earlier trials

Alirocumab was well tolerated. Injection site reactions (6.1% vs. 3.3%) and general allergic reactions (3.4% vs. 0%) were more common on alirocumab, but there were no significant differences between the arms of this study for serious adverse events. There were slightly more neurocognitive events (2.0 vs. 0%) and abnormal alanine transferase levels (0.7% vs. 0%) in the alirocumab group.

The data are generally consistent with two previously published trials with another PCSK9 inhibitor, according to Dr. Räber. In the randomized GLAGOV trial published more than 5 years ago, evolocumab also produced about a 1% absolute reduction (P < .001) in plaque volume at the end of 78 weeks of follow-up relative to placebo.

However, that trial was limited to patients with coronary artery disease without a recent cardiovascular event. The more recent HUYGENS trial, which was presented virtually at the 2021 annual meeting of the European Society of Cardiology meeting and has not yet been published, looked at one of the endpoints also evaluated in PACMAN-AMI. In that study of 161 randomized NSTEMI patients, there was also about a doubling of fibrous cap thickness (42.7 vs. 21.5 mcm) for the PCSK9 inhibitor relative to placebo.

Clinical endpoints were not compared in either the PACMAN-AMI or HUYGENS trial.
 

PACMAN-AMI confirms plaque stabilization

Nevertheless, the message of plaque stabilization is important, according to Anthony N. DeMaria, MD, Founding Director of the Sulpizio Cardiovascular Center at the University of San Diego. Although he acknowledged that a 1% absolute reduction in mean plaque volume might “make you want to yawn,” he argued that this is a misreading of important changes observed in plaque physiology.

“What we have now is evidence that very low lipid levels result in plaque remodeling. The plaques might not get a whole lot smaller, but the changes are important,” he said, noting, for example, that a thicker fibrous cap and increased plaque stability “clearly plays a role in reducing risk of subsequent events.”

“You cannot help but be impressed by the relationship of lipid lowering and the favorable effect on remodeling,” he added.

The data associating PCSK9 inhibitors with protection from cardiovascular events is already extensive, according to Michael J. Blaha, MD, Director of Clinical Research for Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, but he called PACMAN-ACS “an extremely relevant study.”

A new subanalysis of the FAME 3 trial, which failed to show that percutaneous intervention (PCI) guided by fractional flow reserve (FFR) is noninferior to coronary artery bypass grafting (CABG) for treating three-vessel coronary artery disease, has associated PCI with early quality of life (QOL) advantages, according to findings presented at the annual scientific sessions of the American College of Cardiology.

Despite a modestly greater risk of major adverse cardiac events (MACE) at the end of 12 months’ follow-up among those treated with FFR-guided PCI, the greater QOL early after the procedure might be relevant to patients weighing these options, according to Frederik M. Zimmerman, MD, of Catharina Hospital in Eindhoven, the Netherlands.

“FFR-guided PCI results in a faster improvement in quality of life than CABG during the first year after revascularization, and it improved working status in patients younger than 65 years of age,” Dr. Zimmermann said.

The primary results of FAME 3 were presented at the 2021 Transcatheter Cardiovascular Therapeutics annual meeting by lead author William F. Fearon, MD, of Stanford (Calif.) University and published simultaneously in the New England Journal of Medicine.

Rather than confirming the hypothesis that FFR-guided PCI is comparable with CABG for the primary composite MACE outcome death from any cause, myocardial infarction, stroke, or revascularization, the incidence of MACE at 12 months was 10.6% in those randomized to PCI and 6.9% in the group assigned to CABG.

This translated into a hazard ratio for MACE of 1.5, signifying a 50% increase in risk for FFR-guided PCI relative to CABG for the primary outcome, a difference that negated the study definition of noninferiority (P = .35).

In this new health-related subanalysis, which was published simultaneously with his ACC presentation, the groups were compared over 12 months for QOL as measured with European Quality of Life–5 dimensions (EQ-5D) scale, angina as measured with the Canadian Cardiovascular Classification (CCC) system, and employment.

Outcomes data available in >85% of patients

Of the 1,500 patients enrolled and randomized in FAME 3 (757 to FFR-guided PCI and 743 to CABG), this health outcomes subanalysis was performed with complete data at 12 months from 89% of those in the PCI group and 88% of those in the CABG group.

Ultimately, the study did not show differences in any of these measures at the end of 12 months, but there were significant differences in QOL and employment at earlier time points. In particular, the significantly different (P < .001) trajectory for QOL improvement at 1 and 6 months favored FFR-guided PCI whether evaluated with the EQ-5D instrument or an EQ visual analog scale.

Rates of angina defined by as CCC class of at least 2 were low after revascularization in both arms of the study, negating any opportunity for differences, but patients aged younger than 65 years were almost twice as likely to have returned to full- or part-time work 1 month after revascularization (60.2% vs. 33.1%), and they remained at higher odds for working at 12 months (68.1% vs. 57.4%).

In patients aged older than 65 years, return-to-work rates did not differ significantly at any time point.

These results suggest potentially clinically meaningful early advantages for FFR-guided PCI, but some experts questioned the rationale for reporting positive secondary findings from a negative trial.

“This subanalysis is curious,” said Allen Jeremias, MD, director of interventional cardiology research, Saint Francis Hospital, Roslyn, N.Y. He pointed out that reporting these data is an anomaly.
 

Subanalyses uncommon in negative trials

“CABG was found to be better, so why look at QOL,” said Dr. Jeremias, who was an ACC-invited expert to discuss the results. However, he went on to say, “this could be an exception to the rule.”

The reason, according to Dr. Jeremias, is that the absolute difference at 12 months between FFR-guided PCI and CABG for the MACE events of greatest concern – death, MI, or stroke – was only about 2% greater in the FFR-guided PCI group (7.3% vs. 5.2%). The biggest contributor to the difference in MACE in FAME 3 at 12 months was the higher rate of repeat revascularization (5.9% vs. 3.9%).

Moreover, patients randomized to FFR-guided PCI had lower rates of many adverse events. This included risk of bleeding (1.6% vs. 3.8%; P = .009 as defined by type ≥3 Bleeding Academic Research Consortium , acute kidney injury (0.1% vs. 0.9%; P = .04), atrial fibrillation (2.4% vs. 14.1%; P < .001) and rehospitalization within 30 days (5.5% vs. 10.2%; P < .001).

In the context of a modest increase in risk of MACE and the lower rate of several important treatment-related adverse events, the QOL advantages identified in this subanalysis “might be a reasonable topic for patient-shared decision-making,” Dr. Jeremias suggested.
 

New data might inform patient decision-making

He granted the possibility that well-informed patients might accept the modestly increased risk of MACE for one or more of the outcomes, such as a higher likelihood of an early return to work, that favored FFR-guided PCI.

This is the point of this subanalysis, agreed Dr. Zimmermann.

“It is all about shared decision-making,” he said. Also emphasizing that the negative trial endpoint of FAME 3 “was driven largely by an increased risk of revascularization,” he believes that these new data might be a basis for discussions with patients weighing relative risks and benefits.

There are more data to come, according to Dr. Zimmermann, who said that follow-up of up to 5 years is planned. The 3-year data will be made available in 2023.

Dr. Zimmermann reported no potential conflicts of interest. Dr. Jeremias reported financial relationships with Abbott, ACIST, Boston Scientific, and Volcano. The investigator-initiated trial received research grants from Abbott Vascular and Medtronic.

A new subanalysis of the FAME 3 trial, which failed to show that percutaneous intervention (PCI) guided by fractional flow reserve (FFR) is noninferior to coronary artery bypass grafting (CABG) for treating three-vessel coronary artery disease, has associated PCI with early quality of life (QOL) advantages, according to findings presented at the annual scientific sessions of the American College of Cardiology.

Despite a modestly greater risk of major adverse cardiac events (MACE) at the end of 12 months’ follow-up among those treated with FFR-guided PCI, the greater QOL early after the procedure might be relevant to patients weighing these options, according to Frederik M. Zimmerman, MD, of Catharina Hospital in Eindhoven, the Netherlands.

“FFR-guided PCI results in a faster improvement in quality of life than CABG during the first year after revascularization, and it improved working status in patients younger than 65 years of age,” Dr. Zimmermann said.

The primary results of FAME 3 were presented at the 2021 Transcatheter Cardiovascular Therapeutics annual meeting by lead author William F. Fearon, MD, of Stanford (Calif.) University and published simultaneously in the New England Journal of Medicine.

Rather than confirming the hypothesis that FFR-guided PCI is comparable with CABG for the primary composite MACE outcome death from any cause, myocardial infarction, stroke, or revascularization, the incidence of MACE at 12 months was 10.6% in those randomized to PCI and 6.9% in the group assigned to CABG.

This translated into a hazard ratio for MACE of 1.5, signifying a 50% increase in risk for FFR-guided PCI relative to CABG for the primary outcome, a difference that negated the study definition of noninferiority (P = .35).

In this new health-related subanalysis, which was published simultaneously with his ACC presentation, the groups were compared over 12 months for QOL as measured with European Quality of Life–5 dimensions (EQ-5D) scale, angina as measured with the Canadian Cardiovascular Classification (CCC) system, and employment.

Outcomes data available in >85% of patients

Of the 1,500 patients enrolled and randomized in FAME 3 (757 to FFR-guided PCI and 743 to CABG), this health outcomes subanalysis was performed with complete data at 12 months from 89% of those in the PCI group and 88% of those in the CABG group.

Ultimately, the study did not show differences in any of these measures at the end of 12 months, but there were significant differences in QOL and employment at earlier time points. In particular, the significantly different (P < .001) trajectory for QOL improvement at 1 and 6 months favored FFR-guided PCI whether evaluated with the EQ-5D instrument or an EQ visual analog scale.

Rates of angina defined by as CCC class of at least 2 were low after revascularization in both arms of the study, negating any opportunity for differences, but patients aged younger than 65 years were almost twice as likely to have returned to full- or part-time work 1 month after revascularization (60.2% vs. 33.1%), and they remained at higher odds for working at 12 months (68.1% vs. 57.4%).

In patients aged older than 65 years, return-to-work rates did not differ significantly at any time point.

These results suggest potentially clinically meaningful early advantages for FFR-guided PCI, but some experts questioned the rationale for reporting positive secondary findings from a negative trial.

“This subanalysis is curious,” said Allen Jeremias, MD, director of interventional cardiology research, Saint Francis Hospital, Roslyn, N.Y. He pointed out that reporting these data is an anomaly.
 

Subanalyses uncommon in negative trials

“CABG was found to be better, so why look at QOL,” said Dr. Jeremias, who was an ACC-invited expert to discuss the results. However, he went on to say, “this could be an exception to the rule.”

The reason, according to Dr. Jeremias, is that the absolute difference at 12 months between FFR-guided PCI and CABG for the MACE events of greatest concern – death, MI, or stroke – was only about 2% greater in the FFR-guided PCI group (7.3% vs. 5.2%). The biggest contributor to the difference in MACE in FAME 3 at 12 months was the higher rate of repeat revascularization (5.9% vs. 3.9%).

Moreover, patients randomized to FFR-guided PCI had lower rates of many adverse events. This included risk of bleeding (1.6% vs. 3.8%; P = .009 as defined by type ≥3 Bleeding Academic Research Consortium , acute kidney injury (0.1% vs. 0.9%; P = .04), atrial fibrillation (2.4% vs. 14.1%; P < .001) and rehospitalization within 30 days (5.5% vs. 10.2%; P < .001).

In the context of a modest increase in risk of MACE and the lower rate of several important treatment-related adverse events, the QOL advantages identified in this subanalysis “might be a reasonable topic for patient-shared decision-making,” Dr. Jeremias suggested.
 

New data might inform patient decision-making

He granted the possibility that well-informed patients might accept the modestly increased risk of MACE for one or more of the outcomes, such as a higher likelihood of an early return to work, that favored FFR-guided PCI.

This is the point of this subanalysis, agreed Dr. Zimmermann.

“It is all about shared decision-making,” he said. Also emphasizing that the negative trial endpoint of FAME 3 “was driven largely by an increased risk of revascularization,” he believes that these new data might be a basis for discussions with patients weighing relative risks and benefits.

There are more data to come, according to Dr. Zimmermann, who said that follow-up of up to 5 years is planned. The 3-year data will be made available in 2023.

Dr. Zimmermann reported no potential conflicts of interest. Dr. Jeremias reported financial relationships with Abbott, ACIST, Boston Scientific, and Volcano. The investigator-initiated trial received research grants from Abbott Vascular and Medtronic.

A new subanalysis of the FAME 3 trial, which failed to show that percutaneous intervention (PCI) guided by fractional flow reserve (FFR) is noninferior to coronary artery bypass grafting (CABG) for treating three-vessel coronary artery disease, has associated PCI with early quality of life (QOL) advantages, according to findings presented at the annual scientific sessions of the American College of Cardiology.

Despite a modestly greater risk of major adverse cardiac events (MACE) at the end of 12 months’ follow-up among those treated with FFR-guided PCI, the greater QOL early after the procedure might be relevant to patients weighing these options, according to Frederik M. Zimmerman, MD, of Catharina Hospital in Eindhoven, the Netherlands.

“FFR-guided PCI results in a faster improvement in quality of life than CABG during the first year after revascularization, and it improved working status in patients younger than 65 years of age,” Dr. Zimmermann said.

The primary results of FAME 3 were presented at the 2021 Transcatheter Cardiovascular Therapeutics annual meeting by lead author William F. Fearon, MD, of Stanford (Calif.) University and published simultaneously in the New England Journal of Medicine.

Rather than confirming the hypothesis that FFR-guided PCI is comparable with CABG for the primary composite MACE outcome death from any cause, myocardial infarction, stroke, or revascularization, the incidence of MACE at 12 months was 10.6% in those randomized to PCI and 6.9% in the group assigned to CABG.

This translated into a hazard ratio for MACE of 1.5, signifying a 50% increase in risk for FFR-guided PCI relative to CABG for the primary outcome, a difference that negated the study definition of noninferiority (P = .35).

In this new health-related subanalysis, which was published simultaneously with his ACC presentation, the groups were compared over 12 months for QOL as measured with European Quality of Life–5 dimensions (EQ-5D) scale, angina as measured with the Canadian Cardiovascular Classification (CCC) system, and employment.

Outcomes data available in >85% of patients

Of the 1,500 patients enrolled and randomized in FAME 3 (757 to FFR-guided PCI and 743 to CABG), this health outcomes subanalysis was performed with complete data at 12 months from 89% of those in the PCI group and 88% of those in the CABG group.

Ultimately, the study did not show differences in any of these measures at the end of 12 months, but there were significant differences in QOL and employment at earlier time points. In particular, the significantly different (P < .001) trajectory for QOL improvement at 1 and 6 months favored FFR-guided PCI whether evaluated with the EQ-5D instrument or an EQ visual analog scale.

Rates of angina defined by as CCC class of at least 2 were low after revascularization in both arms of the study, negating any opportunity for differences, but patients aged younger than 65 years were almost twice as likely to have returned to full- or part-time work 1 month after revascularization (60.2% vs. 33.1%), and they remained at higher odds for working at 12 months (68.1% vs. 57.4%).

In patients aged older than 65 years, return-to-work rates did not differ significantly at any time point.

These results suggest potentially clinically meaningful early advantages for FFR-guided PCI, but some experts questioned the rationale for reporting positive secondary findings from a negative trial.

“This subanalysis is curious,” said Allen Jeremias, MD, director of interventional cardiology research, Saint Francis Hospital, Roslyn, N.Y. He pointed out that reporting these data is an anomaly.
 

Subanalyses uncommon in negative trials

“CABG was found to be better, so why look at QOL,” said Dr. Jeremias, who was an ACC-invited expert to discuss the results. However, he went on to say, “this could be an exception to the rule.”

The reason, according to Dr. Jeremias, is that the absolute difference at 12 months between FFR-guided PCI and CABG for the MACE events of greatest concern – death, MI, or stroke – was only about 2% greater in the FFR-guided PCI group (7.3% vs. 5.2%). The biggest contributor to the difference in MACE in FAME 3 at 12 months was the higher rate of repeat revascularization (5.9% vs. 3.9%).

Moreover, patients randomized to FFR-guided PCI had lower rates of many adverse events. This included risk of bleeding (1.6% vs. 3.8%; P = .009 as defined by type ≥3 Bleeding Academic Research Consortium , acute kidney injury (0.1% vs. 0.9%; P = .04), atrial fibrillation (2.4% vs. 14.1%; P < .001) and rehospitalization within 30 days (5.5% vs. 10.2%; P < .001).

In the context of a modest increase in risk of MACE and the lower rate of several important treatment-related adverse events, the QOL advantages identified in this subanalysis “might be a reasonable topic for patient-shared decision-making,” Dr. Jeremias suggested.
 

New data might inform patient decision-making

He granted the possibility that well-informed patients might accept the modestly increased risk of MACE for one or more of the outcomes, such as a higher likelihood of an early return to work, that favored FFR-guided PCI.

This is the point of this subanalysis, agreed Dr. Zimmermann.

“It is all about shared decision-making,” he said. Also emphasizing that the negative trial endpoint of FAME 3 “was driven largely by an increased risk of revascularization,” he believes that these new data might be a basis for discussions with patients weighing relative risks and benefits.

There are more data to come, according to Dr. Zimmermann, who said that follow-up of up to 5 years is planned. The 3-year data will be made available in 2023.

Dr. Zimmermann reported no potential conflicts of interest. Dr. Jeremias reported financial relationships with Abbott, ACIST, Boston Scientific, and Volcano. The investigator-initiated trial received research grants from Abbott Vascular and Medtronic.

Pregnant women with even mild hypertension should receive blood pressure–lowering medications to reduce the likelihood of adverse outcomes for the mother and the child, according to a large, open-label, randomized trial.

“Treating to the blood pressure goal in this study reduced the risk of adverse events associated with pregnancy but did not impair fetal growth,” Alan T. Tita, MD, PhD, associate dean for Global and Women’s Health, University of Alabama, Birmingham, reported at the annual scientific sessions of the American College of Cardiology.

The question of whether to treat chronic hypertension during pregnancy has been “an international controversy for decades,” said Dr. Tita, who led the investigator-initiated Chronic Hypertension and Pregnancy (CHAP) trial.

For the composite primary outcome of severe preeclampsia, medically indicated preterm birth at less than 35 weeks of gestation, placental abruption, or fetal/neonatal death, the treatment of hypertension versus no treatment showed a relative risk reduction of 18% (30.2% vs. 37%, (hazard ratio, 0.82; P < .001).
 

Small for gestational age is primary safety endpoint

An increase in preeclampsia risk in women whose fetus was small for gestational age (SGA), a theoretical consequence of reductions in arterial pressure, was not seen. The rate of SGA, defined as below the 10^th percentile, was slightly higher in the treatment group (11.2% vs. 10.4%), but the difference did not approach significance (P = 0.76).

By answering this long-pending question, the CHAP data are “practice changing,” declared an ACC-invited commentator, Athena Poppas, MD, chief of cardiology and director of the Lifespan Cardiovascular Institute, Providence, R.I. She agreed that the need for treatment of mild chronic hypertension has been a dilemma for clinicians that is now acceptably resolved.

In this trial, 2,408 pregnant women with chronic mild hypertension defined as a blood pressure of 160/90 mm Hg were randomized to treatment with a goal blood pressure of less than 140/90 mm Hg or no treatment unless the blood pressure rose to at least 160/105. All women had singleton pregnancies. Enrollment before 23 weeks of gestation was required. Severe hypertension (at least 160/105 mm Hg) was an exclusion criterion, as were several comorbidities, such as kidney disease.
 

Combination therapy accepted for <140/90 mm Hg goal

The beta-blocker labetalol or the calcium channel blocker nifedipine as single agents were the preferred antihypertensive medications in the protocol, but other medications were permitted. To reach the blood pressure goal, the single-agent therapy was titrated to the maximum dose before starting a second agent.

After randomization the systolic and diastolic blood pressures fell in both groups, but they fell more and remained consistently lower in the active treatment group, particularly during the first 20 weeks after randomization, according to graphs displayed by Dr. Tita. Over the course of the study, the mean diastolic blood pressures were 129.5 and 132.6 mm Hg in the active treatment and control groups, respectively, while the systolic pressures were 79.1 vs. 81.5 mm Hg.

When the components of the primary outcome were evaluated separately, the greatest advantage of treatment was the reduction in the rate of severe eclampsia (23.3% vs. 29.1%; HR, 0.80: 95% confidence interval, 0.70-0.92) and preterm birth (12.2% vs. 16.7%; HR, 0.73: 95% CI, 0.60-0.89).

Across a large array of subgroups, including those with or without diabetes and those treated before or after 14 weeks of gestation, there was a consistent advantage for treatment, even if not statistically different. It is notable that 48% of patients were Black and 35% had a body mass index of at least 40. The active treatment was favored across all groups stratified by these characteristics.

Although the incidences of placental abruption (1.7% on treatment vs. 1.9% without) and fetal or neonatal death (3.5% vs. 4.3%) were lower in the active treatment group, they were uncommon events in both arms of the study. The differences did not reach statistical significance.
 

Maternal morbidity rates lower on treatment

Severe SGA, which was defined as below the 5^th percentile, was also numerically but not significantly higher in the control arm than in the group receiving treatment (5.1% vs. 5.5%), but the incidence of composite adverse maternal events was numerically lower (2.1% vs. 2.8%). The incidences of all components of maternal morbidity, such as maternal death (0.1% vs. 0.2%) pulmonary edema (0.4% vs. 0.9%), heart failure (0.1% vs. 0.1%), and acute kidney injury (0.8% vs. 1.2%), were either lower or the same on active treatment versus no treatment.

According to Dr. Tita, who called CHAP one of the largest and most diverse studies to address the value of treating mild hypertension in pregnancy, the American College of Obstetricians and Gynecologists (ACOG) is evaluating these data for changing their current guidelines for managing hypertension during pregnancy.

“The rate of chronic hypertension during pregnancy has been rising in the United States due to the increase in the average age of pregnant women and the rising rates of obesity,” Dr. Tita commented.

“We definitely needed these data,” said Mary Norine Walsh, MD, medical director, Ascension Saint Vincent Cardiovascular Research Institute, Indianapolis. Not only has the value of treating mild hypertension been unresolved, but Dr. Walsh pointed out that the rates of maternal mortality in the United States are rising and now generally exceed those of many other developed countries.

There are several features in the design of this trial that make the results even more salient to clinical practice, according to Dr. Walsh. This includes the fact that about half of patients enrolled were on Medicaid. As a result, the study confirmed benefit in what Dr. Walsh characterized as a “vulnerable” population.

“We will be busy now to make sure that our [pregnant] patients are achieving these target blood pressures,” Dr. Walsh said. She indicated that CHAP validates the treatment target of 140/90 mm Hg as a standard of care.

The results were published in the New England Journal of Medicine simultaneously with its ACC presentation.

The trial was funded by the National Heart, Lung, and Blood Institute. Dr. Tita reports research grants from Pfizer. Dr. Walsh reports a financial relationship with EBR Systems. Dr. Poppas reports no potential conflicts of interest.

Pregnant women with even mild hypertension should receive blood pressure–lowering medications to reduce the likelihood of adverse outcomes for the mother and the child, according to a large, open-label, randomized trial.

“Treating to the blood pressure goal in this study reduced the risk of adverse events associated with pregnancy but did not impair fetal growth,” Alan T. Tita, MD, PhD, associate dean for Global and Women’s Health, University of Alabama, Birmingham, reported at the annual scientific sessions of the American College of Cardiology.

The question of whether to treat chronic hypertension during pregnancy has been “an international controversy for decades,” said Dr. Tita, who led the investigator-initiated Chronic Hypertension and Pregnancy (CHAP) trial.

For the composite primary outcome of severe preeclampsia, medically indicated preterm birth at less than 35 weeks of gestation, placental abruption, or fetal/neonatal death, the treatment of hypertension versus no treatment showed a relative risk reduction of 18% (30.2% vs. 37%, (hazard ratio, 0.82; P < .001).
 

Small for gestational age is primary safety endpoint

An increase in preeclampsia risk in women whose fetus was small for gestational age (SGA), a theoretical consequence of reductions in arterial pressure, was not seen. The rate of SGA, defined as below the 10^th percentile, was slightly higher in the treatment group (11.2% vs. 10.4%), but the difference did not approach significance (P = 0.76).

By answering this long-pending question, the CHAP data are “practice changing,” declared an ACC-invited commentator, Athena Poppas, MD, chief of cardiology and director of the Lifespan Cardiovascular Institute, Providence, R.I. She agreed that the need for treatment of mild chronic hypertension has been a dilemma for clinicians that is now acceptably resolved.

In this trial, 2,408 pregnant women with chronic mild hypertension defined as a blood pressure of 160/90 mm Hg were randomized to treatment with a goal blood pressure of less than 140/90 mm Hg or no treatment unless the blood pressure rose to at least 160/105. All women had singleton pregnancies. Enrollment before 23 weeks of gestation was required. Severe hypertension (at least 160/105 mm Hg) was an exclusion criterion, as were several comorbidities, such as kidney disease.
 

Combination therapy accepted for <140/90 mm Hg goal

The beta-blocker labetalol or the calcium channel blocker nifedipine as single agents were the preferred antihypertensive medications in the protocol, but other medications were permitted. To reach the blood pressure goal, the single-agent therapy was titrated to the maximum dose before starting a second agent.

After randomization the systolic and diastolic blood pressures fell in both groups, but they fell more and remained consistently lower in the active treatment group, particularly during the first 20 weeks after randomization, according to graphs displayed by Dr. Tita. Over the course of the study, the mean diastolic blood pressures were 129.5 and 132.6 mm Hg in the active treatment and control groups, respectively, while the systolic pressures were 79.1 vs. 81.5 mm Hg.

When the components of the primary outcome were evaluated separately, the greatest advantage of treatment was the reduction in the rate of severe eclampsia (23.3% vs. 29.1%; HR, 0.80: 95% confidence interval, 0.70-0.92) and preterm birth (12.2% vs. 16.7%; HR, 0.73: 95% CI, 0.60-0.89).

Across a large array of subgroups, including those with or without diabetes and those treated before or after 14 weeks of gestation, there was a consistent advantage for treatment, even if not statistically different. It is notable that 48% of patients were Black and 35% had a body mass index of at least 40. The active treatment was favored across all groups stratified by these characteristics.

Although the incidences of placental abruption (1.7% on treatment vs. 1.9% without) and fetal or neonatal death (3.5% vs. 4.3%) were lower in the active treatment group, they were uncommon events in both arms of the study. The differences did not reach statistical significance.
 

Maternal morbidity rates lower on treatment

Severe SGA, which was defined as below the 5^th percentile, was also numerically but not significantly higher in the control arm than in the group receiving treatment (5.1% vs. 5.5%), but the incidence of composite adverse maternal events was numerically lower (2.1% vs. 2.8%). The incidences of all components of maternal morbidity, such as maternal death (0.1% vs. 0.2%) pulmonary edema (0.4% vs. 0.9%), heart failure (0.1% vs. 0.1%), and acute kidney injury (0.8% vs. 1.2%), were either lower or the same on active treatment versus no treatment.

According to Dr. Tita, who called CHAP one of the largest and most diverse studies to address the value of treating mild hypertension in pregnancy, the American College of Obstetricians and Gynecologists (ACOG) is evaluating these data for changing their current guidelines for managing hypertension during pregnancy.

“The rate of chronic hypertension during pregnancy has been rising in the United States due to the increase in the average age of pregnant women and the rising rates of obesity,” Dr. Tita commented.

“We definitely needed these data,” said Mary Norine Walsh, MD, medical director, Ascension Saint Vincent Cardiovascular Research Institute, Indianapolis. Not only has the value of treating mild hypertension been unresolved, but Dr. Walsh pointed out that the rates of maternal mortality in the United States are rising and now generally exceed those of many other developed countries.

There are several features in the design of this trial that make the results even more salient to clinical practice, according to Dr. Walsh. This includes the fact that about half of patients enrolled were on Medicaid. As a result, the study confirmed benefit in what Dr. Walsh characterized as a “vulnerable” population.

“We will be busy now to make sure that our [pregnant] patients are achieving these target blood pressures,” Dr. Walsh said. She indicated that CHAP validates the treatment target of 140/90 mm Hg as a standard of care.

The results were published in the New England Journal of Medicine simultaneously with its ACC presentation.

The trial was funded by the National Heart, Lung, and Blood Institute. Dr. Tita reports research grants from Pfizer. Dr. Walsh reports a financial relationship with EBR Systems. Dr. Poppas reports no potential conflicts of interest.

Pregnant women with even mild hypertension should receive blood pressure–lowering medications to reduce the likelihood of adverse outcomes for the mother and the child, according to a large, open-label, randomized trial.

“Treating to the blood pressure goal in this study reduced the risk of adverse events associated with pregnancy but did not impair fetal growth,” Alan T. Tita, MD, PhD, associate dean for Global and Women’s Health, University of Alabama, Birmingham, reported at the annual scientific sessions of the American College of Cardiology.

The question of whether to treat chronic hypertension during pregnancy has been “an international controversy for decades,” said Dr. Tita, who led the investigator-initiated Chronic Hypertension and Pregnancy (CHAP) trial.

For the composite primary outcome of severe preeclampsia, medically indicated preterm birth at less than 35 weeks of gestation, placental abruption, or fetal/neonatal death, the treatment of hypertension versus no treatment showed a relative risk reduction of 18% (30.2% vs. 37%, (hazard ratio, 0.82; P < .001).
 

Small for gestational age is primary safety endpoint

An increase in preeclampsia risk in women whose fetus was small for gestational age (SGA), a theoretical consequence of reductions in arterial pressure, was not seen. The rate of SGA, defined as below the 10^th percentile, was slightly higher in the treatment group (11.2% vs. 10.4%), but the difference did not approach significance (P = 0.76).

By answering this long-pending question, the CHAP data are “practice changing,” declared an ACC-invited commentator, Athena Poppas, MD, chief of cardiology and director of the Lifespan Cardiovascular Institute, Providence, R.I. She agreed that the need for treatment of mild chronic hypertension has been a dilemma for clinicians that is now acceptably resolved.

In this trial, 2,408 pregnant women with chronic mild hypertension defined as a blood pressure of 160/90 mm Hg were randomized to treatment with a goal blood pressure of less than 140/90 mm Hg or no treatment unless the blood pressure rose to at least 160/105. All women had singleton pregnancies. Enrollment before 23 weeks of gestation was required. Severe hypertension (at least 160/105 mm Hg) was an exclusion criterion, as were several comorbidities, such as kidney disease.
 

Combination therapy accepted for <140/90 mm Hg goal

The beta-blocker labetalol or the calcium channel blocker nifedipine as single agents were the preferred antihypertensive medications in the protocol, but other medications were permitted. To reach the blood pressure goal, the single-agent therapy was titrated to the maximum dose before starting a second agent.

After randomization the systolic and diastolic blood pressures fell in both groups, but they fell more and remained consistently lower in the active treatment group, particularly during the first 20 weeks after randomization, according to graphs displayed by Dr. Tita. Over the course of the study, the mean diastolic blood pressures were 129.5 and 132.6 mm Hg in the active treatment and control groups, respectively, while the systolic pressures were 79.1 vs. 81.5 mm Hg.

When the components of the primary outcome were evaluated separately, the greatest advantage of treatment was the reduction in the rate of severe eclampsia (23.3% vs. 29.1%; HR, 0.80: 95% confidence interval, 0.70-0.92) and preterm birth (12.2% vs. 16.7%; HR, 0.73: 95% CI, 0.60-0.89).

Across a large array of subgroups, including those with or without diabetes and those treated before or after 14 weeks of gestation, there was a consistent advantage for treatment, even if not statistically different. It is notable that 48% of patients were Black and 35% had a body mass index of at least 40. The active treatment was favored across all groups stratified by these characteristics.

Although the incidences of placental abruption (1.7% on treatment vs. 1.9% without) and fetal or neonatal death (3.5% vs. 4.3%) were lower in the active treatment group, they were uncommon events in both arms of the study. The differences did not reach statistical significance.
 

Maternal morbidity rates lower on treatment

Severe SGA, which was defined as below the 5^th percentile, was also numerically but not significantly higher in the control arm than in the group receiving treatment (5.1% vs. 5.5%), but the incidence of composite adverse maternal events was numerically lower (2.1% vs. 2.8%). The incidences of all components of maternal morbidity, such as maternal death (0.1% vs. 0.2%) pulmonary edema (0.4% vs. 0.9%), heart failure (0.1% vs. 0.1%), and acute kidney injury (0.8% vs. 1.2%), were either lower or the same on active treatment versus no treatment.

According to Dr. Tita, who called CHAP one of the largest and most diverse studies to address the value of treating mild hypertension in pregnancy, the American College of Obstetricians and Gynecologists (ACOG) is evaluating these data for changing their current guidelines for managing hypertension during pregnancy.

“The rate of chronic hypertension during pregnancy has been rising in the United States due to the increase in the average age of pregnant women and the rising rates of obesity,” Dr. Tita commented.

“We definitely needed these data,” said Mary Norine Walsh, MD, medical director, Ascension Saint Vincent Cardiovascular Research Institute, Indianapolis. Not only has the value of treating mild hypertension been unresolved, but Dr. Walsh pointed out that the rates of maternal mortality in the United States are rising and now generally exceed those of many other developed countries.

There are several features in the design of this trial that make the results even more salient to clinical practice, according to Dr. Walsh. This includes the fact that about half of patients enrolled were on Medicaid. As a result, the study confirmed benefit in what Dr. Walsh characterized as a “vulnerable” population.

“We will be busy now to make sure that our [pregnant] patients are achieving these target blood pressures,” Dr. Walsh said. She indicated that CHAP validates the treatment target of 140/90 mm Hg as a standard of care.

The results were published in the New England Journal of Medicine simultaneously with its ACC presentation.

The trial was funded by the National Heart, Lung, and Blood Institute. Dr. Tita reports research grants from Pfizer. Dr. Walsh reports a financial relationship with EBR Systems. Dr. Poppas reports no potential conflicts of interest.

BOSTON – For patients presenting with moderate to severe pemphigus, the choice of initial therapy has been distilled to a single agent: rituximab. This drug is more rapidly effective, more likely to provide sustained remission, better tolerated, and lowers health care costs, according to an expert summary at the annual meeting of the American Academy of Dermatology.

With rituximab “we are not only able to offer better efficacy, earlier and longer remissions, less side effects, less risk of relapse after a response, but it is actually cheaper,” reported Erin X. Wei, MD, director of the Bullous Diseases Clinic at Brigham and Women’s Hospital, Boston.

There are many treatments that reduce the inflammatory component of pemphigus. Corticosteroids, doxycycline, mycophenolate mofetil, azathioprine, and methotrexate are among those options commonly considered in the early control of this rare and potentially fatal autoimmune blistering disease of the skin, mouth, and other tissues.

Not all of these options have been compared directly in controlled trials, but Dr. Wei indicated that the preponderance of evidence is now on the side of rituximab as a first-line choice. For example, in the multicenter Ritux 3 trial, which compared a tapered regimen of prednisone alone to rituximab combined with a shorter and lower-dose prednisone taper in patients with pemphigus, complete response rates off therapy at 2 years were 89% in the rituximab group versus 34% in the group that received prednisone alone.

“This was quite a remarkable difference,” said Dr. Wei, who noted that remissions overall occurred faster in the rituximab group and were more durable once achieved.

No other treatment option has demonstrated this degree of relative benefit over corticosteroids, according to Dr. Wei. She said there is evidence that mycophenolate mofetil acts more rapidly, but it has not been shown to be superior for sustained complete response. Nor has azathioprine provided a clear advantage over steroids. There are no well-conducted comparisons of methotrexate and prednisone, according to Dr. Wei, assistant professor at Harvard Medical School, Boston.

Corticosteroids, doxycycline, and immunomodulators have been characterized as mainstays of early treatment in pemphigus, but Dr. Wei argued that the evidence supports starting with the most effective therapy first. There are many advantages to suppressing disease activity “as soon as possible” after diagnosis.

Early control “is associated with a more sustained remission, lower overall steroid use, and better quality of life,” said Dr. Wei, listing the hazards of starting with less effective therapy, and explaining why she has moved to rituximab as a first-line choice. According to her, there are data to support these advantages.

“Several studies have observed that rituximab, within the first 6 months of disease onset, is associated with a higher rate of complete response and a longer duration of complete response,” Dr. Wei said.

Intravenous immunoglobulin (IVIG) therapy is effective in many patients but less reliable, and it has other disadvantages relative to rituximab as a first-line therapy.

“IVIG in pemphigus works quickly when it works, but it is more expensive and it is more of an ongoing therapy relative to rituximab,” said Dr. Wei, referring to the lower likelihood of IVIG to provide sustained remissions.

The price of rituximab is high relative to prednisone or other immunomodulators, but management costs are ultimately reduced because of better disease control, according to Dr. Wei. She cited a Canadian study published several years ago in which health care costs in the 6 months prior to rituximab were compared to costs over 6 months after it was initiated.

In this cohort of 89 patients with pemphigus or pemphigoid, the average cost per patient for 6 months of care prior to starting rituximab was $42,231 in Canadian dollars. After treatment was started, the cost fell to $29,423, a 30% reduction, over the next 6 months.

“It takes rituximab up to 3 months or sometimes even longer to achieve its greatest benefit, making these results even more impressive,” Dr. Wei said.

The activity of rituximab to suppress autoreactive B-cells can be monitored with antidesmoglein autoantibody levels and by measuring CD20-positive cell percentages. Unlike severity of disease at baseline, which Dr. Wei said is not a reliable predictor of relapse risk, these can guide steroid tapering.

“If the patient is not making new autoantibodies, then tapering steroids can be considered safe,” Dr. Wei said.

One small case series cited by Dr. Wei has suggested that rituximab might be effectively employed as a maintenance therapy for pemphigus. The maintenance treatment, which initially consisted of 1 g of rituximab every 6 months, was evaluated in 11 patients with a history of severe and frequent relapses.

In this group, rituximab was first employed to achieve a complete response. The maintenance was initiated when patients were in remission. In some patients, the maintenance dose interval was extended to once every 12 months over time. During a mean follow-up of 4 years, all 11 patients remained in complete remission.

“This was a remarkable result,” said Dr. Wei, who noted that there were no serious adverse events associated with rituximab maintenance over this period. This cannot be considered a routine strategy without a large patient experience, according to Dr. Wei, but it does provide another piece of evidence that rituximab is effective and well tolerated.

There are no guidelines from a major organization that establish an evidence-based treatment algorithm for pemphigus, but Dr. Wei is not alone in considering early initiation of the most effective therapy as the best approach to sustained control.

“I agree that rituximab is a good first-line option for pemphigus patients,” said Kara Heelan, MBBCh, MD, a consultant dermatologist at the Royal Marsden and Lister Hospital, London. She was the first author of the cost-effectiveness study that Dr. Wei cited. The study was published when she was an associate in the division of dermatology at the University of Toronto.

By calling rituximab “a good” option rather than a potential standard, Dr. Heelan appeared to be more circumspect than Dr. Wei about its central role in the care of pemphigus, but she did agree in an interview that this agent “has been shown to be cost-effective.” In her study, this was an advantage attributed to relative efficacy and safety that reduced use of health care resources.
 

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

BOSTON – For patients presenting with moderate to severe pemphigus, the choice of initial therapy has been distilled to a single agent: rituximab. This drug is more rapidly effective, more likely to provide sustained remission, better tolerated, and lowers health care costs, according to an expert summary at the annual meeting of the American Academy of Dermatology.

With rituximab “we are not only able to offer better efficacy, earlier and longer remissions, less side effects, less risk of relapse after a response, but it is actually cheaper,” reported Erin X. Wei, MD, director of the Bullous Diseases Clinic at Brigham and Women’s Hospital, Boston.

There are many treatments that reduce the inflammatory component of pemphigus. Corticosteroids, doxycycline, mycophenolate mofetil, azathioprine, and methotrexate are among those options commonly considered in the early control of this rare and potentially fatal autoimmune blistering disease of the skin, mouth, and other tissues.

Not all of these options have been compared directly in controlled trials, but Dr. Wei indicated that the preponderance of evidence is now on the side of rituximab as a first-line choice. For example, in the multicenter Ritux 3 trial, which compared a tapered regimen of prednisone alone to rituximab combined with a shorter and lower-dose prednisone taper in patients with pemphigus, complete response rates off therapy at 2 years were 89% in the rituximab group versus 34% in the group that received prednisone alone.

“This was quite a remarkable difference,” said Dr. Wei, who noted that remissions overall occurred faster in the rituximab group and were more durable once achieved.

No other treatment option has demonstrated this degree of relative benefit over corticosteroids, according to Dr. Wei. She said there is evidence that mycophenolate mofetil acts more rapidly, but it has not been shown to be superior for sustained complete response. Nor has azathioprine provided a clear advantage over steroids. There are no well-conducted comparisons of methotrexate and prednisone, according to Dr. Wei, assistant professor at Harvard Medical School, Boston.

Corticosteroids, doxycycline, and immunomodulators have been characterized as mainstays of early treatment in pemphigus, but Dr. Wei argued that the evidence supports starting with the most effective therapy first. There are many advantages to suppressing disease activity “as soon as possible” after diagnosis.

Early control “is associated with a more sustained remission, lower overall steroid use, and better quality of life,” said Dr. Wei, listing the hazards of starting with less effective therapy, and explaining why she has moved to rituximab as a first-line choice. According to her, there are data to support these advantages.

“Several studies have observed that rituximab, within the first 6 months of disease onset, is associated with a higher rate of complete response and a longer duration of complete response,” Dr. Wei said.

Intravenous immunoglobulin (IVIG) therapy is effective in many patients but less reliable, and it has other disadvantages relative to rituximab as a first-line therapy.

“IVIG in pemphigus works quickly when it works, but it is more expensive and it is more of an ongoing therapy relative to rituximab,” said Dr. Wei, referring to the lower likelihood of IVIG to provide sustained remissions.

The price of rituximab is high relative to prednisone or other immunomodulators, but management costs are ultimately reduced because of better disease control, according to Dr. Wei. She cited a Canadian study published several years ago in which health care costs in the 6 months prior to rituximab were compared to costs over 6 months after it was initiated.

In this cohort of 89 patients with pemphigus or pemphigoid, the average cost per patient for 6 months of care prior to starting rituximab was $42,231 in Canadian dollars. After treatment was started, the cost fell to $29,423, a 30% reduction, over the next 6 months.

“It takes rituximab up to 3 months or sometimes even longer to achieve its greatest benefit, making these results even more impressive,” Dr. Wei said.

The activity of rituximab to suppress autoreactive B-cells can be monitored with antidesmoglein autoantibody levels and by measuring CD20-positive cell percentages. Unlike severity of disease at baseline, which Dr. Wei said is not a reliable predictor of relapse risk, these can guide steroid tapering.

“If the patient is not making new autoantibodies, then tapering steroids can be considered safe,” Dr. Wei said.

One small case series cited by Dr. Wei has suggested that rituximab might be effectively employed as a maintenance therapy for pemphigus. The maintenance treatment, which initially consisted of 1 g of rituximab every 6 months, was evaluated in 11 patients with a history of severe and frequent relapses.

In this group, rituximab was first employed to achieve a complete response. The maintenance was initiated when patients were in remission. In some patients, the maintenance dose interval was extended to once every 12 months over time. During a mean follow-up of 4 years, all 11 patients remained in complete remission.

“This was a remarkable result,” said Dr. Wei, who noted that there were no serious adverse events associated with rituximab maintenance over this period. This cannot be considered a routine strategy without a large patient experience, according to Dr. Wei, but it does provide another piece of evidence that rituximab is effective and well tolerated.

There are no guidelines from a major organization that establish an evidence-based treatment algorithm for pemphigus, but Dr. Wei is not alone in considering early initiation of the most effective therapy as the best approach to sustained control.

“I agree that rituximab is a good first-line option for pemphigus patients,” said Kara Heelan, MBBCh, MD, a consultant dermatologist at the Royal Marsden and Lister Hospital, London. She was the first author of the cost-effectiveness study that Dr. Wei cited. The study was published when she was an associate in the division of dermatology at the University of Toronto.

By calling rituximab “a good” option rather than a potential standard, Dr. Heelan appeared to be more circumspect than Dr. Wei about its central role in the care of pemphigus, but she did agree in an interview that this agent “has been shown to be cost-effective.” In her study, this was an advantage attributed to relative efficacy and safety that reduced use of health care resources.
 

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

BOSTON – For patients presenting with moderate to severe pemphigus, the choice of initial therapy has been distilled to a single agent: rituximab. This drug is more rapidly effective, more likely to provide sustained remission, better tolerated, and lowers health care costs, according to an expert summary at the annual meeting of the American Academy of Dermatology.

With rituximab “we are not only able to offer better efficacy, earlier and longer remissions, less side effects, less risk of relapse after a response, but it is actually cheaper,” reported Erin X. Wei, MD, director of the Bullous Diseases Clinic at Brigham and Women’s Hospital, Boston.

There are many treatments that reduce the inflammatory component of pemphigus. Corticosteroids, doxycycline, mycophenolate mofetil, azathioprine, and methotrexate are among those options commonly considered in the early control of this rare and potentially fatal autoimmune blistering disease of the skin, mouth, and other tissues.

Not all of these options have been compared directly in controlled trials, but Dr. Wei indicated that the preponderance of evidence is now on the side of rituximab as a first-line choice. For example, in the multicenter Ritux 3 trial, which compared a tapered regimen of prednisone alone to rituximab combined with a shorter and lower-dose prednisone taper in patients with pemphigus, complete response rates off therapy at 2 years were 89% in the rituximab group versus 34% in the group that received prednisone alone.

“This was quite a remarkable difference,” said Dr. Wei, who noted that remissions overall occurred faster in the rituximab group and were more durable once achieved.

No other treatment option has demonstrated this degree of relative benefit over corticosteroids, according to Dr. Wei. She said there is evidence that mycophenolate mofetil acts more rapidly, but it has not been shown to be superior for sustained complete response. Nor has azathioprine provided a clear advantage over steroids. There are no well-conducted comparisons of methotrexate and prednisone, according to Dr. Wei, assistant professor at Harvard Medical School, Boston.

Corticosteroids, doxycycline, and immunomodulators have been characterized as mainstays of early treatment in pemphigus, but Dr. Wei argued that the evidence supports starting with the most effective therapy first. There are many advantages to suppressing disease activity “as soon as possible” after diagnosis.

Early control “is associated with a more sustained remission, lower overall steroid use, and better quality of life,” said Dr. Wei, listing the hazards of starting with less effective therapy, and explaining why she has moved to rituximab as a first-line choice. According to her, there are data to support these advantages.

“Several studies have observed that rituximab, within the first 6 months of disease onset, is associated with a higher rate of complete response and a longer duration of complete response,” Dr. Wei said.

Intravenous immunoglobulin (IVIG) therapy is effective in many patients but less reliable, and it has other disadvantages relative to rituximab as a first-line therapy.

“IVIG in pemphigus works quickly when it works, but it is more expensive and it is more of an ongoing therapy relative to rituximab,” said Dr. Wei, referring to the lower likelihood of IVIG to provide sustained remissions.

The price of rituximab is high relative to prednisone or other immunomodulators, but management costs are ultimately reduced because of better disease control, according to Dr. Wei. She cited a Canadian study published several years ago in which health care costs in the 6 months prior to rituximab were compared to costs over 6 months after it was initiated.

In this cohort of 89 patients with pemphigus or pemphigoid, the average cost per patient for 6 months of care prior to starting rituximab was $42,231 in Canadian dollars. After treatment was started, the cost fell to $29,423, a 30% reduction, over the next 6 months.

“It takes rituximab up to 3 months or sometimes even longer to achieve its greatest benefit, making these results even more impressive,” Dr. Wei said.

The activity of rituximab to suppress autoreactive B-cells can be monitored with antidesmoglein autoantibody levels and by measuring CD20-positive cell percentages. Unlike severity of disease at baseline, which Dr. Wei said is not a reliable predictor of relapse risk, these can guide steroid tapering.

“If the patient is not making new autoantibodies, then tapering steroids can be considered safe,” Dr. Wei said.

One small case series cited by Dr. Wei has suggested that rituximab might be effectively employed as a maintenance therapy for pemphigus. The maintenance treatment, which initially consisted of 1 g of rituximab every 6 months, was evaluated in 11 patients with a history of severe and frequent relapses.

In this group, rituximab was first employed to achieve a complete response. The maintenance was initiated when patients were in remission. In some patients, the maintenance dose interval was extended to once every 12 months over time. During a mean follow-up of 4 years, all 11 patients remained in complete remission.

“This was a remarkable result,” said Dr. Wei, who noted that there were no serious adverse events associated with rituximab maintenance over this period. This cannot be considered a routine strategy without a large patient experience, according to Dr. Wei, but it does provide another piece of evidence that rituximab is effective and well tolerated.

There are no guidelines from a major organization that establish an evidence-based treatment algorithm for pemphigus, but Dr. Wei is not alone in considering early initiation of the most effective therapy as the best approach to sustained control.

“I agree that rituximab is a good first-line option for pemphigus patients,” said Kara Heelan, MBBCh, MD, a consultant dermatologist at the Royal Marsden and Lister Hospital, London. She was the first author of the cost-effectiveness study that Dr. Wei cited. The study was published when she was an associate in the division of dermatology at the University of Toronto.

By calling rituximab “a good” option rather than a potential standard, Dr. Heelan appeared to be more circumspect than Dr. Wei about its central role in the care of pemphigus, but she did agree in an interview that this agent “has been shown to be cost-effective.” In her study, this was an advantage attributed to relative efficacy and safety that reduced use of health care resources.
 

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

BOSTON – Requests for a medical waiver to avoid a second COVID-19 vaccine dose or a booster after cutaneous reactions to the first dose are not justified on the basis of risk, according to an analysis of several large sets of data presented at the annual meeting of the American Academy of Dermatology.

According to the data, “there are no serious adverse consequences from these cutaneous reactions,” said Esther Freeman, MD, PhD, director of Global Health Dermatology, Massachusetts General Hospital, Boston.

This is important because the risk of vaccine hesitancy goes up dramatically in patients who experience reactions to the first vaccine dose, according to follow-up of more than 50,000 employees vaccinated in the Mass General Brigham Healthcare System (MGBHS). According to Dr. Freeman, there was almost a fourfold increase in the rate of second-dose refusals for those with cutaneous reactions and a more than fourfold increase in those who developed angioedema.

Before the data were available, skin reactions were a source of concern among dermatologists and others involved in monitoring vaccine-related adverse events. Injection site reactions (ISRs) are associated with essentially every injectable vaccine, so these were expected, but a small proportion of patients developed large red plaques in the injection arm 7-8 days after the inoculation.

“These delayed reactions caused a lot of initial panic,” said Dr. Freeman, who counted herself among those alarmed about what the reactions might signify. “Was this cellulitis? Would the next dose cause anaphylaxis? We were concerned.”

This concern dissipated with the availability of more data. In a global registry that has so far captured more than 1,000 cutaneous reactions from 52 participating countries, it appears that about 2% of patients have a cutaneous reaction other than an ISR after the first dose. All resolve with minimal skin care or no treatment.

After the second dose, the proportion is lower. If there is a reaction, it typically occurs earlier and resolves more quickly.

“What we have learned is that fewer than half of patients who had a reaction to the first dose have a reaction to the second, and those who did have a reaction had a milder course,” said Dr. Freeman.

These data are “incredibly reassuring” on many levels, she explained. In addition, it allows clinicians to confidently explain to patients that there are no serious sequelae from the rashes, whether immediate or delayed, from the available COVID-19 vaccines.

“Every skin reaction I have seen is something we can treat through,” she added, noting that most reactions resolve with little or no supportive care. Following skin reactions, particularly the delayed lesions, it is not uncommon for patients to refuse a second shot. Some request a medical waiver to avoid further vaccine exposure. According to Dr. Freeman, this is unwarranted.

“I have granted exactly zero waivers,” she said. She explains to patients that these reactions have not been predictive of serious events, such as anaphylaxis. Although the trigger of the hypersensitivity reaction remains unknown, there is no evidence of serious consequences.

Delayed skin reactions are more commonly associated with the Moderna than the Pfizer vaccine. One notable difference between these vaccines is the greater content of mRNA in the Moderna formulation, but Freeman said that this is only one potential hypothesis for higher frequency of reactions to this version of the vaccine.

Patients with a history of allergic disease are more likely to develop a reaction but not significantly more likely to have a reaction that is more difficult to manage, according to Kimberly G. Blumenthal, MD, quality and safety officer for allergy, and codirector of the clinical epidemiology program in the division of rheumatology, allergy, and immunology at Mass General.

Massachusetts General Hospital

Anaphylaxis has been associated with COVD-19 vaccines just as it has with essentially every injectable vaccine, Dr. Blumenthal said during the same session. But the risk is very low, and it stays low even among those with a history of severe hypersensitivity reactions in the past.

Among the data collected from more than 52,000 vaccinated MGBHS employees, 0.9% had a history of severe allergic reaction to a prior vaccine. Of these, 11.6% had an allergic reaction to the COVID-19 vaccine. This was more than twice the 4.6% rate of allergic reactions among employees without a history of allergic reactions, but serious consequences were rare in both groups.

Of those with a reaction to the first dose, all but 2.4% took a subsequent dose. Again, serious reactions were exceedingly rare. These serious reactions did include anaphylaxis and hospitalization in 3% of patients, but there were no fatalities and all resolved.

The absence of serious sequelae from a reaction to a COVID-19 vaccine must be considered within the context of the benefit, which includes protection from death and hospitalization from the virus, according to Dr. Blumenthal. Citing the evidence that first-shot reactions are a source of vaccine hesitancy, she agreed that it is important to educate patients about relative risks.

“Even in our own cohort of MGBHS employees, we have people, including those who had been provaccine in the past, become hesitant,” commented Dr. Blumenthal, who said there are data from the Kaiser Permanente System showing similar vaccine reluctance following a first-shot reaction.

After more than 500 million doses of the Moderna and Pfizer vaccines had been administered worldwide, there was not a single reported death from anaphylaxis. Although Dr. Blumenthal said that an unconfirmed death of this type had been recently reported, she emphasized that this single death, if valid, is dwarfed by the lives saved with vaccination.

Asked about her strategy for counseling patients with vaccine hesitancy, Dr. Freeman said the body of safety data is large and compelling. There is overwhelming evidence of a favorable benefit-to-risk ratio overall and among those with a first-shot reaction.

“I can reassure them on the basis of the data,” Dr. Freeman said in an interview. “Less than half will have a reaction to the second shot and even if they do have a reaction, it is likely to be less severe.”

Although the main message is that vaccination is potentially lifesaving and far outweighs any risks, Freeman specifically gives this message to those hesitant to take a second shot after a first-shot reaction: “I can get you through it.”

Dr. Freeman encouraged health care professionals to report cases of COVID-19 vaccine–related dermatologic side effects to the American Academy of Dermatology / International League of Dermatologic Societies COVID-19 dermatology registry. Dermatologic manifestations of COVID-19 can also be reported to the registry.

Dr. Freeman disclosed receiving grants/research funding from the International League of Dermatologic Societies and from the National Institutes of Health. Dr. Blumenthal disclosed no relevant financial relationships.

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

BOSTON – Requests for a medical waiver to avoid a second COVID-19 vaccine dose or a booster after cutaneous reactions to the first dose are not justified on the basis of risk, according to an analysis of several large sets of data presented at the annual meeting of the American Academy of Dermatology.

According to the data, “there are no serious adverse consequences from these cutaneous reactions,” said Esther Freeman, MD, PhD, director of Global Health Dermatology, Massachusetts General Hospital, Boston.

This is important because the risk of vaccine hesitancy goes up dramatically in patients who experience reactions to the first vaccine dose, according to follow-up of more than 50,000 employees vaccinated in the Mass General Brigham Healthcare System (MGBHS). According to Dr. Freeman, there was almost a fourfold increase in the rate of second-dose refusals for those with cutaneous reactions and a more than fourfold increase in those who developed angioedema.

Before the data were available, skin reactions were a source of concern among dermatologists and others involved in monitoring vaccine-related adverse events. Injection site reactions (ISRs) are associated with essentially every injectable vaccine, so these were expected, but a small proportion of patients developed large red plaques in the injection arm 7-8 days after the inoculation.

“These delayed reactions caused a lot of initial panic,” said Dr. Freeman, who counted herself among those alarmed about what the reactions might signify. “Was this cellulitis? Would the next dose cause anaphylaxis? We were concerned.”

This concern dissipated with the availability of more data. In a global registry that has so far captured more than 1,000 cutaneous reactions from 52 participating countries, it appears that about 2% of patients have a cutaneous reaction other than an ISR after the first dose. All resolve with minimal skin care or no treatment.

After the second dose, the proportion is lower. If there is a reaction, it typically occurs earlier and resolves more quickly.

“What we have learned is that fewer than half of patients who had a reaction to the first dose have a reaction to the second, and those who did have a reaction had a milder course,” said Dr. Freeman.

These data are “incredibly reassuring” on many levels, she explained. In addition, it allows clinicians to confidently explain to patients that there are no serious sequelae from the rashes, whether immediate or delayed, from the available COVID-19 vaccines.

“Every skin reaction I have seen is something we can treat through,” she added, noting that most reactions resolve with little or no supportive care. Following skin reactions, particularly the delayed lesions, it is not uncommon for patients to refuse a second shot. Some request a medical waiver to avoid further vaccine exposure. According to Dr. Freeman, this is unwarranted.

“I have granted exactly zero waivers,” she said. She explains to patients that these reactions have not been predictive of serious events, such as anaphylaxis. Although the trigger of the hypersensitivity reaction remains unknown, there is no evidence of serious consequences.

Delayed skin reactions are more commonly associated with the Moderna than the Pfizer vaccine. One notable difference between these vaccines is the greater content of mRNA in the Moderna formulation, but Freeman said that this is only one potential hypothesis for higher frequency of reactions to this version of the vaccine.

Patients with a history of allergic disease are more likely to develop a reaction but not significantly more likely to have a reaction that is more difficult to manage, according to Kimberly G. Blumenthal, MD, quality and safety officer for allergy, and codirector of the clinical epidemiology program in the division of rheumatology, allergy, and immunology at Mass General.

Massachusetts General Hospital

Anaphylaxis has been associated with COVD-19 vaccines just as it has with essentially every injectable vaccine, Dr. Blumenthal said during the same session. But the risk is very low, and it stays low even among those with a history of severe hypersensitivity reactions in the past.

Among the data collected from more than 52,000 vaccinated MGBHS employees, 0.9% had a history of severe allergic reaction to a prior vaccine. Of these, 11.6% had an allergic reaction to the COVID-19 vaccine. This was more than twice the 4.6% rate of allergic reactions among employees without a history of allergic reactions, but serious consequences were rare in both groups.

Of those with a reaction to the first dose, all but 2.4% took a subsequent dose. Again, serious reactions were exceedingly rare. These serious reactions did include anaphylaxis and hospitalization in 3% of patients, but there were no fatalities and all resolved.

The absence of serious sequelae from a reaction to a COVID-19 vaccine must be considered within the context of the benefit, which includes protection from death and hospitalization from the virus, according to Dr. Blumenthal. Citing the evidence that first-shot reactions are a source of vaccine hesitancy, she agreed that it is important to educate patients about relative risks.

“Even in our own cohort of MGBHS employees, we have people, including those who had been provaccine in the past, become hesitant,” commented Dr. Blumenthal, who said there are data from the Kaiser Permanente System showing similar vaccine reluctance following a first-shot reaction.

After more than 500 million doses of the Moderna and Pfizer vaccines had been administered worldwide, there was not a single reported death from anaphylaxis. Although Dr. Blumenthal said that an unconfirmed death of this type had been recently reported, she emphasized that this single death, if valid, is dwarfed by the lives saved with vaccination.

Asked about her strategy for counseling patients with vaccine hesitancy, Dr. Freeman said the body of safety data is large and compelling. There is overwhelming evidence of a favorable benefit-to-risk ratio overall and among those with a first-shot reaction.

“I can reassure them on the basis of the data,” Dr. Freeman said in an interview. “Less than half will have a reaction to the second shot and even if they do have a reaction, it is likely to be less severe.”

Although the main message is that vaccination is potentially lifesaving and far outweighs any risks, Freeman specifically gives this message to those hesitant to take a second shot after a first-shot reaction: “I can get you through it.”

Dr. Freeman encouraged health care professionals to report cases of COVID-19 vaccine–related dermatologic side effects to the American Academy of Dermatology / International League of Dermatologic Societies COVID-19 dermatology registry. Dermatologic manifestations of COVID-19 can also be reported to the registry.

Dr. Freeman disclosed receiving grants/research funding from the International League of Dermatologic Societies and from the National Institutes of Health. Dr. Blumenthal disclosed no relevant financial relationships.

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

BOSTON – Requests for a medical waiver to avoid a second COVID-19 vaccine dose or a booster after cutaneous reactions to the first dose are not justified on the basis of risk, according to an analysis of several large sets of data presented at the annual meeting of the American Academy of Dermatology.

According to the data, “there are no serious adverse consequences from these cutaneous reactions,” said Esther Freeman, MD, PhD, director of Global Health Dermatology, Massachusetts General Hospital, Boston.

This is important because the risk of vaccine hesitancy goes up dramatically in patients who experience reactions to the first vaccine dose, according to follow-up of more than 50,000 employees vaccinated in the Mass General Brigham Healthcare System (MGBHS). According to Dr. Freeman, there was almost a fourfold increase in the rate of second-dose refusals for those with cutaneous reactions and a more than fourfold increase in those who developed angioedema.

Before the data were available, skin reactions were a source of concern among dermatologists and others involved in monitoring vaccine-related adverse events. Injection site reactions (ISRs) are associated with essentially every injectable vaccine, so these were expected, but a small proportion of patients developed large red plaques in the injection arm 7-8 days after the inoculation.

“These delayed reactions caused a lot of initial panic,” said Dr. Freeman, who counted herself among those alarmed about what the reactions might signify. “Was this cellulitis? Would the next dose cause anaphylaxis? We were concerned.”

This concern dissipated with the availability of more data. In a global registry that has so far captured more than 1,000 cutaneous reactions from 52 participating countries, it appears that about 2% of patients have a cutaneous reaction other than an ISR after the first dose. All resolve with minimal skin care or no treatment.

After the second dose, the proportion is lower. If there is a reaction, it typically occurs earlier and resolves more quickly.

“What we have learned is that fewer than half of patients who had a reaction to the first dose have a reaction to the second, and those who did have a reaction had a milder course,” said Dr. Freeman.

These data are “incredibly reassuring” on many levels, she explained. In addition, it allows clinicians to confidently explain to patients that there are no serious sequelae from the rashes, whether immediate or delayed, from the available COVID-19 vaccines.

“Every skin reaction I have seen is something we can treat through,” she added, noting that most reactions resolve with little or no supportive care. Following skin reactions, particularly the delayed lesions, it is not uncommon for patients to refuse a second shot. Some request a medical waiver to avoid further vaccine exposure. According to Dr. Freeman, this is unwarranted.

“I have granted exactly zero waivers,” she said. She explains to patients that these reactions have not been predictive of serious events, such as anaphylaxis. Although the trigger of the hypersensitivity reaction remains unknown, there is no evidence of serious consequences.

Delayed skin reactions are more commonly associated with the Moderna than the Pfizer vaccine. One notable difference between these vaccines is the greater content of mRNA in the Moderna formulation, but Freeman said that this is only one potential hypothesis for higher frequency of reactions to this version of the vaccine.

Patients with a history of allergic disease are more likely to develop a reaction but not significantly more likely to have a reaction that is more difficult to manage, according to Kimberly G. Blumenthal, MD, quality and safety officer for allergy, and codirector of the clinical epidemiology program in the division of rheumatology, allergy, and immunology at Mass General.

Massachusetts General Hospital

Anaphylaxis has been associated with COVD-19 vaccines just as it has with essentially every injectable vaccine, Dr. Blumenthal said during the same session. But the risk is very low, and it stays low even among those with a history of severe hypersensitivity reactions in the past.

Among the data collected from more than 52,000 vaccinated MGBHS employees, 0.9% had a history of severe allergic reaction to a prior vaccine. Of these, 11.6% had an allergic reaction to the COVID-19 vaccine. This was more than twice the 4.6% rate of allergic reactions among employees without a history of allergic reactions, but serious consequences were rare in both groups.

Of those with a reaction to the first dose, all but 2.4% took a subsequent dose. Again, serious reactions were exceedingly rare. These serious reactions did include anaphylaxis and hospitalization in 3% of patients, but there were no fatalities and all resolved.

The absence of serious sequelae from a reaction to a COVID-19 vaccine must be considered within the context of the benefit, which includes protection from death and hospitalization from the virus, according to Dr. Blumenthal. Citing the evidence that first-shot reactions are a source of vaccine hesitancy, she agreed that it is important to educate patients about relative risks.

“Even in our own cohort of MGBHS employees, we have people, including those who had been provaccine in the past, become hesitant,” commented Dr. Blumenthal, who said there are data from the Kaiser Permanente System showing similar vaccine reluctance following a first-shot reaction.

After more than 500 million doses of the Moderna and Pfizer vaccines had been administered worldwide, there was not a single reported death from anaphylaxis. Although Dr. Blumenthal said that an unconfirmed death of this type had been recently reported, she emphasized that this single death, if valid, is dwarfed by the lives saved with vaccination.

Asked about her strategy for counseling patients with vaccine hesitancy, Dr. Freeman said the body of safety data is large and compelling. There is overwhelming evidence of a favorable benefit-to-risk ratio overall and among those with a first-shot reaction.

“I can reassure them on the basis of the data,” Dr. Freeman said in an interview. “Less than half will have a reaction to the second shot and even if they do have a reaction, it is likely to be less severe.”

Although the main message is that vaccination is potentially lifesaving and far outweighs any risks, Freeman specifically gives this message to those hesitant to take a second shot after a first-shot reaction: “I can get you through it.”

Dr. Freeman encouraged health care professionals to report cases of COVID-19 vaccine–related dermatologic side effects to the American Academy of Dermatology / International League of Dermatologic Societies COVID-19 dermatology registry. Dermatologic manifestations of COVID-19 can also be reported to the registry.

Dr. Freeman disclosed receiving grants/research funding from the International League of Dermatologic Societies and from the National Institutes of Health. Dr. Blumenthal disclosed no relevant financial relationships.

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

BOSTON – The cost of care for the more than 14 million cases of cellulitis that occur each year in the United States is in the billions of dollars, but there are multiple opportunities, many involving dermatologists, to dramatically reduce these costs, according to an outline of strategies presented at the American Academy of Dermatology 2022 annual meeting in Boston.

“Cellulitis is misdiagnosed about one-third of the time, and that cost is very high,” reported Jennifer L. Adams, MD, assistant professor of dermatology, University of Nebraska, Omaha. She sees opportunities for dermatological consults to help weed through the many cellulitis mimickers, such as venous insufficiency or psoriasiform drug reactions, to prevent unnecessary admissions and ineffective therapy.

“There is a huge need for diagnostic accuracy as a means to deliver more cost-effective care,” Dr. Adams said.

Solving misdiagnosis is only part of the story. Costs of care are also ramped up by unnecessary hospitalizations. According to Dr. Adams, published criteria to triage emergency room patients with cellulitis to outpatient care are not always followed. In one review, 14% of admitted patients had met the criteria for outpatient treatment.

Cellulitis is a common skin infection that causes redness, swelling, and pain in the infected area, most often on the legs and feet.

Unnecessary hospitalizations for misdiagnosed cellulitis, which is associated with an average 4-day hospital stay, “range from $200 million to $500 million in avoidable direct healthcare costs,” Dr. Adams said.

Even for justifiable hospitalizations, there are still opportunities for cost savings. In one study, blood cultures were ordered in 73% of patients even though only 2% produced a finding relevant to care. According to Dr. Adams, most cellulitis cases are caused by the “usual suspects” – group A beta-hemolytic streptococcus, Streptococcus pneumoniae, and Staphylococcus aureus. The exceptions stand out by clinical criteria, such as known neutropenia, history of an animal bite, signs of Systemic Inflammatory Response Syndrome (SIRS), or a purulent appearance.

“Blood cultures are not cost-effective in uncomplicated cellulitis,” Dr. Adams said. She said there are numerous published algorithms to guide clinicians on decision-making in the management of soft tissue infections, including cellulitis, including a much-cited algorithm first published more than 15 years ago and updated in 2014.

Similarly, labs and imaging are commonly ordered with no strong likelihood that they will change management, she said. These types of decisions are also covered in published algorithms.

Strategies to prevent rehospitalization are another area where there is a large opportunity to reduce health care resources consumed by cellulitis. The rehospitalization rate at 30 days is approximately 10%, but many patients have recurrent episodes over years, according to Dr. Adams. The risk factors and the preventative measures have been well described.

“Scrupulous clinical care can reduce recurrence, and it is cost-effective,” said Dr. Adams, referring to control of edema, control of underlying conditions associated with increased risk, such as diabetes, and managing dry skin and erosions with topical agents or even moisturizers. Compression socks are a simple but effective tool, she added.

For patients with repeat episodes of cellulitis over years, Dr. Adams referred to a double-blind trial that associated a twice-daily dose of 250 mg penicillin with a 45% reduction in the risk of cellulitis recurrence over 1 year. At approximately $10 a month for this treatment, she said it is very cost-effective, although she acknowledged that recurrence rates of cellulitis climb back up when the penicillin is stopped.

“I think of this as a bridge while you work on addressing the venous insufficiency or other risk factors for cellulitis,” Dr. Adams said.

For reducing the costs of cellulitis, there is evidence that dermatologists can play a role. Dr. Adams cited a study that evaluated the impact of a dermatologist consultation for suspected cellulitis in the emergency room or within 24 hours of admission. Of 34 patients already prescribed antibiotics for presumed cellulitis, discontinuation was recommended in 82%. Of 39 admissions, pseudocellulitis was identified in 51%.

Extrapolating these data to national rates of cellulitis, there was an estimated savings of up to $200 million annually without any apparent increased risk of adverse outcomes, according to Dr. Adams.

When contacted about his experience, the senior investigator of that study, Arash Mostaghimi, MD, director of the Inpatient Dermatology Consult Service, Brigham and Women’s Hospital, Boston, largely agreed with the premise of Adam’s analysis. In particular, he said, avoiding misdiagnosis of cellulitis offers a major opportunity to lower costs while possibly improving care.

True of national practice and at the local level, “misdiagnosis of noninfectious inflammatory reactions such as cellulitis has substantial cost impacts,” Dr. Mostaghimi said in an interview. Based on evidence, the savings are derived directly from “unnecessary antibiotic exposure as well as inappropriate hospitalization.”

Following publication of his study, he became involved in addressing this issue at his institution.

“At Brigham and Women’s, we collaborated with colleagues in infectious disease and in the emergency department to create cellulitis protocols that identify patients at risk for misdiagnosis and facilitate early dermatology consultation for diagnostic confirmation,” he said.

Although there are algorithms to achieve this goal, he indicated that the expertise of dermatologists can quickly and efficiently differentiate inflammatory skin reactions and expedite appropriate care.

Dr. Adams and Dr. Mostaghimi have reported no relevant financial relationships.

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

BOSTON – The cost of care for the more than 14 million cases of cellulitis that occur each year in the United States is in the billions of dollars, but there are multiple opportunities, many involving dermatologists, to dramatically reduce these costs, according to an outline of strategies presented at the American Academy of Dermatology 2022 annual meeting in Boston.

“Cellulitis is misdiagnosed about one-third of the time, and that cost is very high,” reported Jennifer L. Adams, MD, assistant professor of dermatology, University of Nebraska, Omaha. She sees opportunities for dermatological consults to help weed through the many cellulitis mimickers, such as venous insufficiency or psoriasiform drug reactions, to prevent unnecessary admissions and ineffective therapy.

“There is a huge need for diagnostic accuracy as a means to deliver more cost-effective care,” Dr. Adams said.

Solving misdiagnosis is only part of the story. Costs of care are also ramped up by unnecessary hospitalizations. According to Dr. Adams, published criteria to triage emergency room patients with cellulitis to outpatient care are not always followed. In one review, 14% of admitted patients had met the criteria for outpatient treatment.

Cellulitis is a common skin infection that causes redness, swelling, and pain in the infected area, most often on the legs and feet.

Unnecessary hospitalizations for misdiagnosed cellulitis, which is associated with an average 4-day hospital stay, “range from $200 million to $500 million in avoidable direct healthcare costs,” Dr. Adams said.

Even for justifiable hospitalizations, there are still opportunities for cost savings. In one study, blood cultures were ordered in 73% of patients even though only 2% produced a finding relevant to care. According to Dr. Adams, most cellulitis cases are caused by the “usual suspects” – group A beta-hemolytic streptococcus, Streptococcus pneumoniae, and Staphylococcus aureus. The exceptions stand out by clinical criteria, such as known neutropenia, history of an animal bite, signs of Systemic Inflammatory Response Syndrome (SIRS), or a purulent appearance.

“Blood cultures are not cost-effective in uncomplicated cellulitis,” Dr. Adams said. She said there are numerous published algorithms to guide clinicians on decision-making in the management of soft tissue infections, including cellulitis, including a much-cited algorithm first published more than 15 years ago and updated in 2014.

Similarly, labs and imaging are commonly ordered with no strong likelihood that they will change management, she said. These types of decisions are also covered in published algorithms.

Strategies to prevent rehospitalization are another area where there is a large opportunity to reduce health care resources consumed by cellulitis. The rehospitalization rate at 30 days is approximately 10%, but many patients have recurrent episodes over years, according to Dr. Adams. The risk factors and the preventative measures have been well described.

“Scrupulous clinical care can reduce recurrence, and it is cost-effective,” said Dr. Adams, referring to control of edema, control of underlying conditions associated with increased risk, such as diabetes, and managing dry skin and erosions with topical agents or even moisturizers. Compression socks are a simple but effective tool, she added.

For patients with repeat episodes of cellulitis over years, Dr. Adams referred to a double-blind trial that associated a twice-daily dose of 250 mg penicillin with a 45% reduction in the risk of cellulitis recurrence over 1 year. At approximately $10 a month for this treatment, she said it is very cost-effective, although she acknowledged that recurrence rates of cellulitis climb back up when the penicillin is stopped.

“I think of this as a bridge while you work on addressing the venous insufficiency or other risk factors for cellulitis,” Dr. Adams said.

For reducing the costs of cellulitis, there is evidence that dermatologists can play a role. Dr. Adams cited a study that evaluated the impact of a dermatologist consultation for suspected cellulitis in the emergency room or within 24 hours of admission. Of 34 patients already prescribed antibiotics for presumed cellulitis, discontinuation was recommended in 82%. Of 39 admissions, pseudocellulitis was identified in 51%.

Extrapolating these data to national rates of cellulitis, there was an estimated savings of up to $200 million annually without any apparent increased risk of adverse outcomes, according to Dr. Adams.

When contacted about his experience, the senior investigator of that study, Arash Mostaghimi, MD, director of the Inpatient Dermatology Consult Service, Brigham and Women’s Hospital, Boston, largely agreed with the premise of Adam’s analysis. In particular, he said, avoiding misdiagnosis of cellulitis offers a major opportunity to lower costs while possibly improving care.

True of national practice and at the local level, “misdiagnosis of noninfectious inflammatory reactions such as cellulitis has substantial cost impacts,” Dr. Mostaghimi said in an interview. Based on evidence, the savings are derived directly from “unnecessary antibiotic exposure as well as inappropriate hospitalization.”

Following publication of his study, he became involved in addressing this issue at his institution.

“At Brigham and Women’s, we collaborated with colleagues in infectious disease and in the emergency department to create cellulitis protocols that identify patients at risk for misdiagnosis and facilitate early dermatology consultation for diagnostic confirmation,” he said.

Although there are algorithms to achieve this goal, he indicated that the expertise of dermatologists can quickly and efficiently differentiate inflammatory skin reactions and expedite appropriate care.

Dr. Adams and Dr. Mostaghimi have reported no relevant financial relationships.

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

BOSTON – The cost of care for the more than 14 million cases of cellulitis that occur each year in the United States is in the billions of dollars, but there are multiple opportunities, many involving dermatologists, to dramatically reduce these costs, according to an outline of strategies presented at the American Academy of Dermatology 2022 annual meeting in Boston.

“Cellulitis is misdiagnosed about one-third of the time, and that cost is very high,” reported Jennifer L. Adams, MD, assistant professor of dermatology, University of Nebraska, Omaha. She sees opportunities for dermatological consults to help weed through the many cellulitis mimickers, such as venous insufficiency or psoriasiform drug reactions, to prevent unnecessary admissions and ineffective therapy.

“There is a huge need for diagnostic accuracy as a means to deliver more cost-effective care,” Dr. Adams said.

Solving misdiagnosis is only part of the story. Costs of care are also ramped up by unnecessary hospitalizations. According to Dr. Adams, published criteria to triage emergency room patients with cellulitis to outpatient care are not always followed. In one review, 14% of admitted patients had met the criteria for outpatient treatment.

Cellulitis is a common skin infection that causes redness, swelling, and pain in the infected area, most often on the legs and feet.

Unnecessary hospitalizations for misdiagnosed cellulitis, which is associated with an average 4-day hospital stay, “range from $200 million to $500 million in avoidable direct healthcare costs,” Dr. Adams said.

Even for justifiable hospitalizations, there are still opportunities for cost savings. In one study, blood cultures were ordered in 73% of patients even though only 2% produced a finding relevant to care. According to Dr. Adams, most cellulitis cases are caused by the “usual suspects” – group A beta-hemolytic streptococcus, Streptococcus pneumoniae, and Staphylococcus aureus. The exceptions stand out by clinical criteria, such as known neutropenia, history of an animal bite, signs of Systemic Inflammatory Response Syndrome (SIRS), or a purulent appearance.

“Blood cultures are not cost-effective in uncomplicated cellulitis,” Dr. Adams said. She said there are numerous published algorithms to guide clinicians on decision-making in the management of soft tissue infections, including cellulitis, including a much-cited algorithm first published more than 15 years ago and updated in 2014.

Similarly, labs and imaging are commonly ordered with no strong likelihood that they will change management, she said. These types of decisions are also covered in published algorithms.

Strategies to prevent rehospitalization are another area where there is a large opportunity to reduce health care resources consumed by cellulitis. The rehospitalization rate at 30 days is approximately 10%, but many patients have recurrent episodes over years, according to Dr. Adams. The risk factors and the preventative measures have been well described.

“Scrupulous clinical care can reduce recurrence, and it is cost-effective,” said Dr. Adams, referring to control of edema, control of underlying conditions associated with increased risk, such as diabetes, and managing dry skin and erosions with topical agents or even moisturizers. Compression socks are a simple but effective tool, she added.

For patients with repeat episodes of cellulitis over years, Dr. Adams referred to a double-blind trial that associated a twice-daily dose of 250 mg penicillin with a 45% reduction in the risk of cellulitis recurrence over 1 year. At approximately $10 a month for this treatment, she said it is very cost-effective, although she acknowledged that recurrence rates of cellulitis climb back up when the penicillin is stopped.

“I think of this as a bridge while you work on addressing the venous insufficiency or other risk factors for cellulitis,” Dr. Adams said.

For reducing the costs of cellulitis, there is evidence that dermatologists can play a role. Dr. Adams cited a study that evaluated the impact of a dermatologist consultation for suspected cellulitis in the emergency room or within 24 hours of admission. Of 34 patients already prescribed antibiotics for presumed cellulitis, discontinuation was recommended in 82%. Of 39 admissions, pseudocellulitis was identified in 51%.

Extrapolating these data to national rates of cellulitis, there was an estimated savings of up to $200 million annually without any apparent increased risk of adverse outcomes, according to Dr. Adams.

When contacted about his experience, the senior investigator of that study, Arash Mostaghimi, MD, director of the Inpatient Dermatology Consult Service, Brigham and Women’s Hospital, Boston, largely agreed with the premise of Adam’s analysis. In particular, he said, avoiding misdiagnosis of cellulitis offers a major opportunity to lower costs while possibly improving care.

True of national practice and at the local level, “misdiagnosis of noninfectious inflammatory reactions such as cellulitis has substantial cost impacts,” Dr. Mostaghimi said in an interview. Based on evidence, the savings are derived directly from “unnecessary antibiotic exposure as well as inappropriate hospitalization.”

Following publication of his study, he became involved in addressing this issue at his institution.

“At Brigham and Women’s, we collaborated with colleagues in infectious disease and in the emergency department to create cellulitis protocols that identify patients at risk for misdiagnosis and facilitate early dermatology consultation for diagnostic confirmation,” he said.

Although there are algorithms to achieve this goal, he indicated that the expertise of dermatologists can quickly and efficiently differentiate inflammatory skin reactions and expedite appropriate care.

Dr. Adams and Dr. Mostaghimi have reported no relevant financial relationships.

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

BOSTON – The main feature of retronychia, a nail disorder of the toes, is the growth of new nail under prior nail growth. But this layering of nails is not always readily apparent on clinical examination, commonly leading to the wrong therapy and no resolution to the problem, according to an expert update at the annual meeting of the American Academy of Dermatology.

Misinterpretation of the yellow discoloration, a common feature of retronychia, means “many patients are maintained on antifungal therapy for years and years with no change in their condition,” reported Phoebe Rich, MD, director of the Nail Disorders Clinic, Oregon Health & Science University, Portland.

Infection is not commonly involved in retronychia, but importantly, antifungals and antibiotics “have no role in treating the underlying disorder,” Dr. Rich said.

The term retronychia and its description is only about 20 years old, according to Dr. Rich, who cited work by David A. de Berker, MBBS, PhD, a consultant dermatologist at University Hospitals in Bristol, England. His publication on this disorder appeared in 1999, with a more detailed description published about 10 years later.

Recently, the body of literature on this disorder has been growing, contributing to an increasing consensus about etiology, diagnosis, and treatments to consider in the context of causes and severity, Dr. Rich said.

Some but not all patients have abnormal formation of the nail bed, increasing susceptibility to retronychia, but trauma or microtrauma typically serve as a trigger in most cases. Dancing, high heels, steel-toed shoes, and other sources of trauma to the toes are implicated.

Whether or not patients have an inherent susceptibility, injury separates the existing nail from the matrix and nail bed so that newly forming nail begins to grow under the nail rather continuing to push out the old nail.

Susceptibility is increased substantially in individuals with a shortened nail bed, according to Dr. Rich. In severe cases, when there is simply inadequate nail bed for the nail growth to attach, recurrence is common or even inevitable. Even when the nail is removed and regrowth appears normal at the end of a year, those patients with very short nail beds cannot count on a cure.

“Due to the slow growth of nails, it might take 2 or 3 years for the problem to recur,” Dr. Rich cautioned. For this reason, cure rates reported for the various interventions at 1 year might not predict longer-term benefit.

Retronychia is usually a clinical diagnosis based on the presence of the increased bulk of the toenail when overlapping nails cannot be seen. This is not necessarily a single overgrowth. In some cases, multiple layers of nails are stacked one on top of the other. Xanthonychia (yellow nail) is usually present.

“The layering might not be visible without removing the nail,” said Dr. Rich, explaining one reason that the diagnosis is sometimes missed. Ultrasound is a noninvasive means to confirm the problem, although Rich warned that imaging is not necessarily reimbursed.

“There is no diagnosis by histopathology, so it cannot be confirmed with biopsy,” Dr. Rich said.

Treatments range from conservative strategies, particularly topical or intralesional steroids in mild cases, to more invasive procedures such as clipping of the nail plate or surgical avulsion. All can be effective when used appropriately, according to Dr. Rich.

“The more invasive procedures are the more effective, but the caveat is they are also associated with more complications,” said Dr. Rich, citing, for example, the risk of nail dystrophies. Because of the increasing number of studies, the relative benefits and risks of retronychia treatment have now been summarized in a recent review. Dr. Rich suggested the review is one of the most recent and detailed evaluations of the topic that “I encourage everyone to read.”

Despite progress in describing retronychia, Dr. Rich said that there might be more to learn about risk. In particular, she cited the work of Dana W. Stern, MD, a specialist in nail disorders who is in private practice in New York. Dr. Stern is pursuing a hypothesis that at least some cases are caused by potentially targetable biomechanical issues.

“I have observed that many of the younger patients in my practice with retronychia seem to have atypical foot anatomy,” Dr. Stern said in an interview. “I am collecting cases and hoping to explore this issue in more depth.”

She said that foot anatomy in relationship to retronychia has not been adequately evaluated.

“In my review of the literature, I could not find a single study that showed imagery of the feet,” she said. She is considering a collaboration with others, including Rich, to explore this as a factor in retronychia.

Asked about risk of misdiagnosis, Dr. Stern reiterated some of the points made by Dr. Rich. In particular, she agreed that discolored nails alone should not be a reason to initiate antimycotic therapy without considering the possibility of retronychia.

“So many providers are not familiar with the diagnosis, and only 50% of yellow thickened nails are in fact onychomycosis,” she said. “We end up seeing a plethora of patients [with retronychia] who are unfortunately misdiagnosed for years.”

Dr. Rich reported financial relationships with numerous pharmaceutical companies. Dr. Stern reported a financial relationship with Rare Beauty Brands. Neither Dr. Rich nor Dr. Stern said they had any disclosures related to this topic.

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

BOSTON – The main feature of retronychia, a nail disorder of the toes, is the growth of new nail under prior nail growth. But this layering of nails is not always readily apparent on clinical examination, commonly leading to the wrong therapy and no resolution to the problem, according to an expert update at the annual meeting of the American Academy of Dermatology.

Misinterpretation of the yellow discoloration, a common feature of retronychia, means “many patients are maintained on antifungal therapy for years and years with no change in their condition,” reported Phoebe Rich, MD, director of the Nail Disorders Clinic, Oregon Health & Science University, Portland.

Infection is not commonly involved in retronychia, but importantly, antifungals and antibiotics “have no role in treating the underlying disorder,” Dr. Rich said.

The term retronychia and its description is only about 20 years old, according to Dr. Rich, who cited work by David A. de Berker, MBBS, PhD, a consultant dermatologist at University Hospitals in Bristol, England. His publication on this disorder appeared in 1999, with a more detailed description published about 10 years later.

Recently, the body of literature on this disorder has been growing, contributing to an increasing consensus about etiology, diagnosis, and treatments to consider in the context of causes and severity, Dr. Rich said.

Some but not all patients have abnormal formation of the nail bed, increasing susceptibility to retronychia, but trauma or microtrauma typically serve as a trigger in most cases. Dancing, high heels, steel-toed shoes, and other sources of trauma to the toes are implicated.

Whether or not patients have an inherent susceptibility, injury separates the existing nail from the matrix and nail bed so that newly forming nail begins to grow under the nail rather continuing to push out the old nail.

Susceptibility is increased substantially in individuals with a shortened nail bed, according to Dr. Rich. In severe cases, when there is simply inadequate nail bed for the nail growth to attach, recurrence is common or even inevitable. Even when the nail is removed and regrowth appears normal at the end of a year, those patients with very short nail beds cannot count on a cure.

“Due to the slow growth of nails, it might take 2 or 3 years for the problem to recur,” Dr. Rich cautioned. For this reason, cure rates reported for the various interventions at 1 year might not predict longer-term benefit.

Retronychia is usually a clinical diagnosis based on the presence of the increased bulk of the toenail when overlapping nails cannot be seen. This is not necessarily a single overgrowth. In some cases, multiple layers of nails are stacked one on top of the other. Xanthonychia (yellow nail) is usually present.

“The layering might not be visible without removing the nail,” said Dr. Rich, explaining one reason that the diagnosis is sometimes missed. Ultrasound is a noninvasive means to confirm the problem, although Rich warned that imaging is not necessarily reimbursed.

“There is no diagnosis by histopathology, so it cannot be confirmed with biopsy,” Dr. Rich said.

Treatments range from conservative strategies, particularly topical or intralesional steroids in mild cases, to more invasive procedures such as clipping of the nail plate or surgical avulsion. All can be effective when used appropriately, according to Dr. Rich.

“The more invasive procedures are the more effective, but the caveat is they are also associated with more complications,” said Dr. Rich, citing, for example, the risk of nail dystrophies. Because of the increasing number of studies, the relative benefits and risks of retronychia treatment have now been summarized in a recent review. Dr. Rich suggested the review is one of the most recent and detailed evaluations of the topic that “I encourage everyone to read.”

Despite progress in describing retronychia, Dr. Rich said that there might be more to learn about risk. In particular, she cited the work of Dana W. Stern, MD, a specialist in nail disorders who is in private practice in New York. Dr. Stern is pursuing a hypothesis that at least some cases are caused by potentially targetable biomechanical issues.

“I have observed that many of the younger patients in my practice with retronychia seem to have atypical foot anatomy,” Dr. Stern said in an interview. “I am collecting cases and hoping to explore this issue in more depth.”

She said that foot anatomy in relationship to retronychia has not been adequately evaluated.

“In my review of the literature, I could not find a single study that showed imagery of the feet,” she said. She is considering a collaboration with others, including Rich, to explore this as a factor in retronychia.

Asked about risk of misdiagnosis, Dr. Stern reiterated some of the points made by Dr. Rich. In particular, she agreed that discolored nails alone should not be a reason to initiate antimycotic therapy without considering the possibility of retronychia.

“So many providers are not familiar with the diagnosis, and only 50% of yellow thickened nails are in fact onychomycosis,” she said. “We end up seeing a plethora of patients [with retronychia] who are unfortunately misdiagnosed for years.”

Dr. Rich reported financial relationships with numerous pharmaceutical companies. Dr. Stern reported a financial relationship with Rare Beauty Brands. Neither Dr. Rich nor Dr. Stern said they had any disclosures related to this topic.

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

BOSTON – The main feature of retronychia, a nail disorder of the toes, is the growth of new nail under prior nail growth. But this layering of nails is not always readily apparent on clinical examination, commonly leading to the wrong therapy and no resolution to the problem, according to an expert update at the annual meeting of the American Academy of Dermatology.

Misinterpretation of the yellow discoloration, a common feature of retronychia, means “many patients are maintained on antifungal therapy for years and years with no change in their condition,” reported Phoebe Rich, MD, director of the Nail Disorders Clinic, Oregon Health & Science University, Portland.

Infection is not commonly involved in retronychia, but importantly, antifungals and antibiotics “have no role in treating the underlying disorder,” Dr. Rich said.

The term retronychia and its description is only about 20 years old, according to Dr. Rich, who cited work by David A. de Berker, MBBS, PhD, a consultant dermatologist at University Hospitals in Bristol, England. His publication on this disorder appeared in 1999, with a more detailed description published about 10 years later.

Recently, the body of literature on this disorder has been growing, contributing to an increasing consensus about etiology, diagnosis, and treatments to consider in the context of causes and severity, Dr. Rich said.

Some but not all patients have abnormal formation of the nail bed, increasing susceptibility to retronychia, but trauma or microtrauma typically serve as a trigger in most cases. Dancing, high heels, steel-toed shoes, and other sources of trauma to the toes are implicated.

Whether or not patients have an inherent susceptibility, injury separates the existing nail from the matrix and nail bed so that newly forming nail begins to grow under the nail rather continuing to push out the old nail.

Susceptibility is increased substantially in individuals with a shortened nail bed, according to Dr. Rich. In severe cases, when there is simply inadequate nail bed for the nail growth to attach, recurrence is common or even inevitable. Even when the nail is removed and regrowth appears normal at the end of a year, those patients with very short nail beds cannot count on a cure.

“Due to the slow growth of nails, it might take 2 or 3 years for the problem to recur,” Dr. Rich cautioned. For this reason, cure rates reported for the various interventions at 1 year might not predict longer-term benefit.

Retronychia is usually a clinical diagnosis based on the presence of the increased bulk of the toenail when overlapping nails cannot be seen. This is not necessarily a single overgrowth. In some cases, multiple layers of nails are stacked one on top of the other. Xanthonychia (yellow nail) is usually present.

“The layering might not be visible without removing the nail,” said Dr. Rich, explaining one reason that the diagnosis is sometimes missed. Ultrasound is a noninvasive means to confirm the problem, although Rich warned that imaging is not necessarily reimbursed.

“There is no diagnosis by histopathology, so it cannot be confirmed with biopsy,” Dr. Rich said.

Treatments range from conservative strategies, particularly topical or intralesional steroids in mild cases, to more invasive procedures such as clipping of the nail plate or surgical avulsion. All can be effective when used appropriately, according to Dr. Rich.

“The more invasive procedures are the more effective, but the caveat is they are also associated with more complications,” said Dr. Rich, citing, for example, the risk of nail dystrophies. Because of the increasing number of studies, the relative benefits and risks of retronychia treatment have now been summarized in a recent review. Dr. Rich suggested the review is one of the most recent and detailed evaluations of the topic that “I encourage everyone to read.”

Despite progress in describing retronychia, Dr. Rich said that there might be more to learn about risk. In particular, she cited the work of Dana W. Stern, MD, a specialist in nail disorders who is in private practice in New York. Dr. Stern is pursuing a hypothesis that at least some cases are caused by potentially targetable biomechanical issues.

“I have observed that many of the younger patients in my practice with retronychia seem to have atypical foot anatomy,” Dr. Stern said in an interview. “I am collecting cases and hoping to explore this issue in more depth.”

She said that foot anatomy in relationship to retronychia has not been adequately evaluated.

“In my review of the literature, I could not find a single study that showed imagery of the feet,” she said. She is considering a collaboration with others, including Rich, to explore this as a factor in retronychia.

Asked about risk of misdiagnosis, Dr. Stern reiterated some of the points made by Dr. Rich. In particular, she agreed that discolored nails alone should not be a reason to initiate antimycotic therapy without considering the possibility of retronychia.

“So many providers are not familiar with the diagnosis, and only 50% of yellow thickened nails are in fact onychomycosis,” she said. “We end up seeing a plethora of patients [with retronychia] who are unfortunately misdiagnosed for years.”

Dr. Rich reported financial relationships with numerous pharmaceutical companies. Dr. Stern reported a financial relationship with Rare Beauty Brands. Neither Dr. Rich nor Dr. Stern said they had any disclosures related to this topic.

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

BOSTON – After several promising early phase studies, an injectable hyaluronic gel has been associated with sustained improvements in the appearance of the jaw in patients with poor jawline definition, according to data from what study authors characterized as a “pivotal” randomized multicenter trial. The results were presented during a late-breaking research session at the annual meeting of the American Academy of Dermatology.

The primary outcome, assessed at 6 months, was at least a 1-point improvement in a photonumeric scale used to grade jawline sagging, reported Jeremy Green, MD, Skin Associates of South Florida, Coral Gables.

When those randomized to the hyaluronic filler gel VYC-25L (Vycross, Juvéderm) were compared with untreated controls, 68.5% versus 38.4% met the criterion for benefit at 6 months. Importantly, the effect in treated patients was sustained when reevaluated at 12 months. Green reported that the response is generally sustained at the maximum follow-up, now out to 17 months.
 

Most enrolled patients are severely affected

In this study, 208 patients with severe (74%) or moderate loss of jawline definition were randomized in a 3:1 ratio to receive the filler or serve as controls. The initially untreated controls received the gel after the primary outcome analysis at 6 months.

The hyaluronic gel was injected at five sites along the jawline. The mean age of participants was 58 years. The majority were women, and most were White.

Dermatologists blinded to treatment compared photos at 6 months with those taken at baseline using the photonumeric grading system of 1-5. Change in patient satisfaction at 6 months and again at 12 months relative to baseline was also evaluated.

From baseline, when 28.9% of participants reported satisfaction on the Global Aesthetic Improvement Scale (GAIS), rates rose to 89.0% at month 6. There was a decline at month 12, but 79.9% remained satisfied after this period of follow-up.

Most patients experienced injection site reactions that were mainly mild to moderate and all resolved within several days of treatment. Pain with mastication was initially reported by 1.9%, but again this complaint was also mild and transient. All complaints had largely resolved by day 3.

The results are consistent with several previous clinical studies of VYC-25L for the same indication. In a similarly designed trial conducted in Europe that also used a 3:1 randomization scheme, the primary outcome assessed at 3 months was change in facial angle. Relative to controls, the angle improved by 2.51 degrees (P < .0001).

Patient satisfaction supports filler benefit

In the similar European trial, the clinical significance of the objective primary outcome also was supported by patient satisfaction assessed with several instruments, including the GAIS. Some degree of swelling or tenderness was experienced by almost all patients after injection, but none were serious, and all resolved.

In another trial, 202 patients with chin retrusion were randomized in a 3:1 ratio to VYC-25L or a control group. In that study, the primary outcome was at least a 1-point improvement in the Allergan Chin Retrusion Scale at 6 months. This advantage for treatment (56.3% vs. 27.5%) was again supported by several instruments for evaluating patient satisfaction, including GAIS.

As in the other studies, most patients had injection site reactions. Although all resolved within days of treatment, one patient left the study after experiencing cellulitis and injection-site inflammation.

Dissatisfaction with jawline definition is a relatively common complaint in Dr. Green’s experience, who said that there is a need for more effective and well-tolerated treatments. Given the efficacy, tolerability, and safety of VYC-25L in this controlled study, he suggested this product has potential utility.

In the field of cosmetic dermatology, there appears to be incremental progress in fillers with favorable clinical characteristics, according to Sandy U. Tsao, MD, a dermatologic surgeon at Massachusetts General Hospital, Boston.

“We are seeing filler lasting longer and longer,” she said, commenting specifically about the results presented by Dr. Green. She called sustained aesthetic improvement at 12 months for the filler in this study “really exciting.”

Dr. Green has reported financial relationships with numerous pharmaceutical companies. Dr. Tsao has reported financial relationships with Epiphany Dermatology, Lazarus AI, and UpToDate.

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

BOSTON – After several promising early phase studies, an injectable hyaluronic gel has been associated with sustained improvements in the appearance of the jaw in patients with poor jawline definition, according to data from what study authors characterized as a “pivotal” randomized multicenter trial. The results were presented during a late-breaking research session at the annual meeting of the American Academy of Dermatology.

The primary outcome, assessed at 6 months, was at least a 1-point improvement in a photonumeric scale used to grade jawline sagging, reported Jeremy Green, MD, Skin Associates of South Florida, Coral Gables.

When those randomized to the hyaluronic filler gel VYC-25L (Vycross, Juvéderm) were compared with untreated controls, 68.5% versus 38.4% met the criterion for benefit at 6 months. Importantly, the effect in treated patients was sustained when reevaluated at 12 months. Green reported that the response is generally sustained at the maximum follow-up, now out to 17 months.
 

Most enrolled patients are severely affected

In this study, 208 patients with severe (74%) or moderate loss of jawline definition were randomized in a 3:1 ratio to receive the filler or serve as controls. The initially untreated controls received the gel after the primary outcome analysis at 6 months.

The hyaluronic gel was injected at five sites along the jawline. The mean age of participants was 58 years. The majority were women, and most were White.

Dermatologists blinded to treatment compared photos at 6 months with those taken at baseline using the photonumeric grading system of 1-5. Change in patient satisfaction at 6 months and again at 12 months relative to baseline was also evaluated.

From baseline, when 28.9% of participants reported satisfaction on the Global Aesthetic Improvement Scale (GAIS), rates rose to 89.0% at month 6. There was a decline at month 12, but 79.9% remained satisfied after this period of follow-up.

Most patients experienced injection site reactions that were mainly mild to moderate and all resolved within several days of treatment. Pain with mastication was initially reported by 1.9%, but again this complaint was also mild and transient. All complaints had largely resolved by day 3.

The results are consistent with several previous clinical studies of VYC-25L for the same indication. In a similarly designed trial conducted in Europe that also used a 3:1 randomization scheme, the primary outcome assessed at 3 months was change in facial angle. Relative to controls, the angle improved by 2.51 degrees (P < .0001).

Patient satisfaction supports filler benefit

In the similar European trial, the clinical significance of the objective primary outcome also was supported by patient satisfaction assessed with several instruments, including the GAIS. Some degree of swelling or tenderness was experienced by almost all patients after injection, but none were serious, and all resolved.

In another trial, 202 patients with chin retrusion were randomized in a 3:1 ratio to VYC-25L or a control group. In that study, the primary outcome was at least a 1-point improvement in the Allergan Chin Retrusion Scale at 6 months. This advantage for treatment (56.3% vs. 27.5%) was again supported by several instruments for evaluating patient satisfaction, including GAIS.

As in the other studies, most patients had injection site reactions. Although all resolved within days of treatment, one patient left the study after experiencing cellulitis and injection-site inflammation.

Dissatisfaction with jawline definition is a relatively common complaint in Dr. Green’s experience, who said that there is a need for more effective and well-tolerated treatments. Given the efficacy, tolerability, and safety of VYC-25L in this controlled study, he suggested this product has potential utility.

In the field of cosmetic dermatology, there appears to be incremental progress in fillers with favorable clinical characteristics, according to Sandy U. Tsao, MD, a dermatologic surgeon at Massachusetts General Hospital, Boston.

“We are seeing filler lasting longer and longer,” she said, commenting specifically about the results presented by Dr. Green. She called sustained aesthetic improvement at 12 months for the filler in this study “really exciting.”

Dr. Green has reported financial relationships with numerous pharmaceutical companies. Dr. Tsao has reported financial relationships with Epiphany Dermatology, Lazarus AI, and UpToDate.

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

BOSTON – After several promising early phase studies, an injectable hyaluronic gel has been associated with sustained improvements in the appearance of the jaw in patients with poor jawline definition, according to data from what study authors characterized as a “pivotal” randomized multicenter trial. The results were presented during a late-breaking research session at the annual meeting of the American Academy of Dermatology.

The primary outcome, assessed at 6 months, was at least a 1-point improvement in a photonumeric scale used to grade jawline sagging, reported Jeremy Green, MD, Skin Associates of South Florida, Coral Gables.

When those randomized to the hyaluronic filler gel VYC-25L (Vycross, Juvéderm) were compared with untreated controls, 68.5% versus 38.4% met the criterion for benefit at 6 months. Importantly, the effect in treated patients was sustained when reevaluated at 12 months. Green reported that the response is generally sustained at the maximum follow-up, now out to 17 months.
 

Most enrolled patients are severely affected

In this study, 208 patients with severe (74%) or moderate loss of jawline definition were randomized in a 3:1 ratio to receive the filler or serve as controls. The initially untreated controls received the gel after the primary outcome analysis at 6 months.

The hyaluronic gel was injected at five sites along the jawline. The mean age of participants was 58 years. The majority were women, and most were White.

Dermatologists blinded to treatment compared photos at 6 months with those taken at baseline using the photonumeric grading system of 1-5. Change in patient satisfaction at 6 months and again at 12 months relative to baseline was also evaluated.

From baseline, when 28.9% of participants reported satisfaction on the Global Aesthetic Improvement Scale (GAIS), rates rose to 89.0% at month 6. There was a decline at month 12, but 79.9% remained satisfied after this period of follow-up.

Most patients experienced injection site reactions that were mainly mild to moderate and all resolved within several days of treatment. Pain with mastication was initially reported by 1.9%, but again this complaint was also mild and transient. All complaints had largely resolved by day 3.

The results are consistent with several previous clinical studies of VYC-25L for the same indication. In a similarly designed trial conducted in Europe that also used a 3:1 randomization scheme, the primary outcome assessed at 3 months was change in facial angle. Relative to controls, the angle improved by 2.51 degrees (P < .0001).

Patient satisfaction supports filler benefit

In the similar European trial, the clinical significance of the objective primary outcome also was supported by patient satisfaction assessed with several instruments, including the GAIS. Some degree of swelling or tenderness was experienced by almost all patients after injection, but none were serious, and all resolved.

In another trial, 202 patients with chin retrusion were randomized in a 3:1 ratio to VYC-25L or a control group. In that study, the primary outcome was at least a 1-point improvement in the Allergan Chin Retrusion Scale at 6 months. This advantage for treatment (56.3% vs. 27.5%) was again supported by several instruments for evaluating patient satisfaction, including GAIS.

As in the other studies, most patients had injection site reactions. Although all resolved within days of treatment, one patient left the study after experiencing cellulitis and injection-site inflammation.

Dissatisfaction with jawline definition is a relatively common complaint in Dr. Green’s experience, who said that there is a need for more effective and well-tolerated treatments. Given the efficacy, tolerability, and safety of VYC-25L in this controlled study, he suggested this product has potential utility.

In the field of cosmetic dermatology, there appears to be incremental progress in fillers with favorable clinical characteristics, according to Sandy U. Tsao, MD, a dermatologic surgeon at Massachusetts General Hospital, Boston.

“We are seeing filler lasting longer and longer,” she said, commenting specifically about the results presented by Dr. Green. She called sustained aesthetic improvement at 12 months for the filler in this study “really exciting.”

Dr. Green has reported financial relationships with numerous pharmaceutical companies. Dr. Tsao has reported financial relationships with Epiphany Dermatology, Lazarus AI, and UpToDate.

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

Platelet-rich plasma (PRP) has become a hot commodity in the multibillion-dollar hair-loss treatment industry, but there is no gold standard for how to prepare or administer the highly technique-dependent treatment, which creates plenty of room for suboptimal results, according to several experts at the annual meeting of the American Academy of Dermatology.

“The process is the product,” emphasized Terrence Keaney, MD, clinical associate professor at George Washington University, Washington, as well as cofounder of SkinDC, a private practice in Arlington, Va. He characterized PRP as a “growth factor cytokine cocktail,” for which relative benefits are fully dependent on the ingredients.

In other words, the efficacy of PRP is mostly dependent on the multiple steps in which blood drawn from a patient is separated into its components, processed to create a platelet-rich product, and then administered to the patient by injection or in conjunction with microneedles. While the goal is a platelet concentration two- to fivefold greater than that found in whole blood, this is not as straightforward as it sounds.
 

Many PRP device kits available

“There are a ton of [centrifuge] devices on the market and a lot of differences in the methodology in optimizing the platelet concentration,” Dr. Keaney explained. In addition, there are numerous proprietary collection tubes using different types of anticoagulants and different separator gels that also play a role in the goal of optimizing a platelet-rich and readily activated product.

“Recognize that each step in the preparation of PRP introduces a source of variation that affects the composition and efficacy of the final product,” said Steven Krueger, MD, who is completing his residency in dermatology at the University of Massachusetts, Worcester, but who has become an expert in the field. He contributed a chapter on this topic in the recently published book, Aesthetic Clinician’s Guide to Platelet Rich Plasma.

The importance of technique is reflected in inconsistent results from published controlled trials. Unfortunately, the authors of many studies have failed to provide details of their protocol. Ultimately, Dr. Krueger said this lack of clarity among available protocols has created a serious obstacle for establishing which steps are important and how to move the field forward.

Dr. Keaney agreed. Because of the frequent lack of details about how PRP was processed in available studies, the effort to draw conclusions about the experiences at different centers is like “comparing apples to oranges.”

“What is the ideal dose and concentrate? We don’t know,” Dr. Keaney said.

The first centrifuge device to receive regulatory approval was developed for orthopedic indications more than 20 years ago. There are now at least 20 centrifuge devices with 510K Food and Drug Administration clearance for separating blood components to produce PRP. The 510K designation means that they are “substantially equivalent” to an already approved device, but Dr. Krueger cautioned that their use in preparing PRP for treatment of hair loss remains off label.

Substandard devices are marketed

In the rapidly expanding world of PRP, there is also a growing array of PRP kits. Some of these kits have been cleared by the FDA but others have not. Dr. Krueger warned that collection tubes are being marketed that are substandard imitations of better-established products. He specifically cautioned against do-it-yourself PRP kits, which are likely to be less effective for isolating platelets and can also be contaminated with pyogenes that cause infection.

“Please use an FDA-cleared kit,” he said, warning that the risk of failing to do so is not just associated with lack of efficacy but also a significant risk of serious adverse events.

Of the centrifuge devices, both Dr. Krueger and Dr. Keaney generally recommend single-spin over double-spin devices, particularly at centers with a limited volume of PRP-based hair loss interventions. These are generally simpler.

Once the PRP has been properly prepared, the efficacy of PRP upon application can also be influenced by strategies for activation. Although the exact mechanism of PRP in stimulating hair growth is incompletely defined, the role of platelets in releasing growth factors is believed to be critical. There are a number of methods to stimulate platelets upon administration, such as exposure to endogenous collagen or thrombin or exogenous chemicals, such as calcium chloride, but again, techniques differ and the optimal approach is unknown.

One concern is the recent and largely unregulated growth of regenerative cell and tissue products for treating a large array of clinical disorders or cosmetic issues, according to Dr. Keaney. He warned of a “wild, wild west mentality” that has attracted providers with inadequate training and experience. In turn, this is now attracting the attention of the FDA as well as those involved in enforcing FDA directives.

“There is definitely more scrutiny of regenerative products,” he said, noting that he is careful about how he markets PRP. While it is reasonable to offer this off-label treatment as an in-office procedure, he noted that it is illegal to advertise off-label products. He reported that he has become more prudent when including this option among hair regrowth services provided in his practice.

Omer E. Ibrahim, MD, a dermatologist affiliated with Chicago Cosmetic Surgery and Dermatology, agreed. While he also feels there is good evidence to support PRP as a hair loss treatment option, particularly for androgenic alopecia, he also expressed caution about promoting this approach in exclusion of other options.

“Patients ask me for a PRP consultation, but there is no such thing as a PRP consultation in my practice,” Dr. Ibrahim said. He incorporates PRP into other strategies. “I stress that it is one part of a multipronged approach,” he added.

Dr. Ibrahim has reported financial relationships with Alastin Skincare, Allergan, Eclipse Medical, Galderma USA, and Revision Skincare. Dr. Keaney has reported financial relationships with Allergan, DermTech, Evolus, Galderma USA, Merz Aesthetics, Revance Therapeutics, and Syneron Candela. Dr. Krueger has reported no relevant financial relationships.

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

Platelet-rich plasma (PRP) has become a hot commodity in the multibillion-dollar hair-loss treatment industry, but there is no gold standard for how to prepare or administer the highly technique-dependent treatment, which creates plenty of room for suboptimal results, according to several experts at the annual meeting of the American Academy of Dermatology.

“The process is the product,” emphasized Terrence Keaney, MD, clinical associate professor at George Washington University, Washington, as well as cofounder of SkinDC, a private practice in Arlington, Va. He characterized PRP as a “growth factor cytokine cocktail,” for which relative benefits are fully dependent on the ingredients.

In other words, the efficacy of PRP is mostly dependent on the multiple steps in which blood drawn from a patient is separated into its components, processed to create a platelet-rich product, and then administered to the patient by injection or in conjunction with microneedles. While the goal is a platelet concentration two- to fivefold greater than that found in whole blood, this is not as straightforward as it sounds.
 

Many PRP device kits available

“There are a ton of [centrifuge] devices on the market and a lot of differences in the methodology in optimizing the platelet concentration,” Dr. Keaney explained. In addition, there are numerous proprietary collection tubes using different types of anticoagulants and different separator gels that also play a role in the goal of optimizing a platelet-rich and readily activated product.

“Recognize that each step in the preparation of PRP introduces a source of variation that affects the composition and efficacy of the final product,” said Steven Krueger, MD, who is completing his residency in dermatology at the University of Massachusetts, Worcester, but who has become an expert in the field. He contributed a chapter on this topic in the recently published book, Aesthetic Clinician’s Guide to Platelet Rich Plasma.

The importance of technique is reflected in inconsistent results from published controlled trials. Unfortunately, the authors of many studies have failed to provide details of their protocol. Ultimately, Dr. Krueger said this lack of clarity among available protocols has created a serious obstacle for establishing which steps are important and how to move the field forward.

Dr. Keaney agreed. Because of the frequent lack of details about how PRP was processed in available studies, the effort to draw conclusions about the experiences at different centers is like “comparing apples to oranges.”

“What is the ideal dose and concentrate? We don’t know,” Dr. Keaney said.

The first centrifuge device to receive regulatory approval was developed for orthopedic indications more than 20 years ago. There are now at least 20 centrifuge devices with 510K Food and Drug Administration clearance for separating blood components to produce PRP. The 510K designation means that they are “substantially equivalent” to an already approved device, but Dr. Krueger cautioned that their use in preparing PRP for treatment of hair loss remains off label.

Substandard devices are marketed

In the rapidly expanding world of PRP, there is also a growing array of PRP kits. Some of these kits have been cleared by the FDA but others have not. Dr. Krueger warned that collection tubes are being marketed that are substandard imitations of better-established products. He specifically cautioned against do-it-yourself PRP kits, which are likely to be less effective for isolating platelets and can also be contaminated with pyogenes that cause infection.

“Please use an FDA-cleared kit,” he said, warning that the risk of failing to do so is not just associated with lack of efficacy but also a significant risk of serious adverse events.

Of the centrifuge devices, both Dr. Krueger and Dr. Keaney generally recommend single-spin over double-spin devices, particularly at centers with a limited volume of PRP-based hair loss interventions. These are generally simpler.

Once the PRP has been properly prepared, the efficacy of PRP upon application can also be influenced by strategies for activation. Although the exact mechanism of PRP in stimulating hair growth is incompletely defined, the role of platelets in releasing growth factors is believed to be critical. There are a number of methods to stimulate platelets upon administration, such as exposure to endogenous collagen or thrombin or exogenous chemicals, such as calcium chloride, but again, techniques differ and the optimal approach is unknown.

One concern is the recent and largely unregulated growth of regenerative cell and tissue products for treating a large array of clinical disorders or cosmetic issues, according to Dr. Keaney. He warned of a “wild, wild west mentality” that has attracted providers with inadequate training and experience. In turn, this is now attracting the attention of the FDA as well as those involved in enforcing FDA directives.

“There is definitely more scrutiny of regenerative products,” he said, noting that he is careful about how he markets PRP. While it is reasonable to offer this off-label treatment as an in-office procedure, he noted that it is illegal to advertise off-label products. He reported that he has become more prudent when including this option among hair regrowth services provided in his practice.

Omer E. Ibrahim, MD, a dermatologist affiliated with Chicago Cosmetic Surgery and Dermatology, agreed. While he also feels there is good evidence to support PRP as a hair loss treatment option, particularly for androgenic alopecia, he also expressed caution about promoting this approach in exclusion of other options.

“Patients ask me for a PRP consultation, but there is no such thing as a PRP consultation in my practice,” Dr. Ibrahim said. He incorporates PRP into other strategies. “I stress that it is one part of a multipronged approach,” he added.

Dr. Ibrahim has reported financial relationships with Alastin Skincare, Allergan, Eclipse Medical, Galderma USA, and Revision Skincare. Dr. Keaney has reported financial relationships with Allergan, DermTech, Evolus, Galderma USA, Merz Aesthetics, Revance Therapeutics, and Syneron Candela. Dr. Krueger has reported no relevant financial relationships.

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

Platelet-rich plasma (PRP) has become a hot commodity in the multibillion-dollar hair-loss treatment industry, but there is no gold standard for how to prepare or administer the highly technique-dependent treatment, which creates plenty of room for suboptimal results, according to several experts at the annual meeting of the American Academy of Dermatology.

“The process is the product,” emphasized Terrence Keaney, MD, clinical associate professor at George Washington University, Washington, as well as cofounder of SkinDC, a private practice in Arlington, Va. He characterized PRP as a “growth factor cytokine cocktail,” for which relative benefits are fully dependent on the ingredients.

In other words, the efficacy of PRP is mostly dependent on the multiple steps in which blood drawn from a patient is separated into its components, processed to create a platelet-rich product, and then administered to the patient by injection or in conjunction with microneedles. While the goal is a platelet concentration two- to fivefold greater than that found in whole blood, this is not as straightforward as it sounds.
 

Many PRP device kits available

“There are a ton of [centrifuge] devices on the market and a lot of differences in the methodology in optimizing the platelet concentration,” Dr. Keaney explained. In addition, there are numerous proprietary collection tubes using different types of anticoagulants and different separator gels that also play a role in the goal of optimizing a platelet-rich and readily activated product.

“Recognize that each step in the preparation of PRP introduces a source of variation that affects the composition and efficacy of the final product,” said Steven Krueger, MD, who is completing his residency in dermatology at the University of Massachusetts, Worcester, but who has become an expert in the field. He contributed a chapter on this topic in the recently published book, Aesthetic Clinician’s Guide to Platelet Rich Plasma.

The importance of technique is reflected in inconsistent results from published controlled trials. Unfortunately, the authors of many studies have failed to provide details of their protocol. Ultimately, Dr. Krueger said this lack of clarity among available protocols has created a serious obstacle for establishing which steps are important and how to move the field forward.

Dr. Keaney agreed. Because of the frequent lack of details about how PRP was processed in available studies, the effort to draw conclusions about the experiences at different centers is like “comparing apples to oranges.”

“What is the ideal dose and concentrate? We don’t know,” Dr. Keaney said.

The first centrifuge device to receive regulatory approval was developed for orthopedic indications more than 20 years ago. There are now at least 20 centrifuge devices with 510K Food and Drug Administration clearance for separating blood components to produce PRP. The 510K designation means that they are “substantially equivalent” to an already approved device, but Dr. Krueger cautioned that their use in preparing PRP for treatment of hair loss remains off label.

Substandard devices are marketed

In the rapidly expanding world of PRP, there is also a growing array of PRP kits. Some of these kits have been cleared by the FDA but others have not. Dr. Krueger warned that collection tubes are being marketed that are substandard imitations of better-established products. He specifically cautioned against do-it-yourself PRP kits, which are likely to be less effective for isolating platelets and can also be contaminated with pyogenes that cause infection.

“Please use an FDA-cleared kit,” he said, warning that the risk of failing to do so is not just associated with lack of efficacy but also a significant risk of serious adverse events.

Of the centrifuge devices, both Dr. Krueger and Dr. Keaney generally recommend single-spin over double-spin devices, particularly at centers with a limited volume of PRP-based hair loss interventions. These are generally simpler.

Once the PRP has been properly prepared, the efficacy of PRP upon application can also be influenced by strategies for activation. Although the exact mechanism of PRP in stimulating hair growth is incompletely defined, the role of platelets in releasing growth factors is believed to be critical. There are a number of methods to stimulate platelets upon administration, such as exposure to endogenous collagen or thrombin or exogenous chemicals, such as calcium chloride, but again, techniques differ and the optimal approach is unknown.

One concern is the recent and largely unregulated growth of regenerative cell and tissue products for treating a large array of clinical disorders or cosmetic issues, according to Dr. Keaney. He warned of a “wild, wild west mentality” that has attracted providers with inadequate training and experience. In turn, this is now attracting the attention of the FDA as well as those involved in enforcing FDA directives.

“There is definitely more scrutiny of regenerative products,” he said, noting that he is careful about how he markets PRP. While it is reasonable to offer this off-label treatment as an in-office procedure, he noted that it is illegal to advertise off-label products. He reported that he has become more prudent when including this option among hair regrowth services provided in his practice.

Omer E. Ibrahim, MD, a dermatologist affiliated with Chicago Cosmetic Surgery and Dermatology, agreed. While he also feels there is good evidence to support PRP as a hair loss treatment option, particularly for androgenic alopecia, he also expressed caution about promoting this approach in exclusion of other options.

“Patients ask me for a PRP consultation, but there is no such thing as a PRP consultation in my practice,” Dr. Ibrahim said. He incorporates PRP into other strategies. “I stress that it is one part of a multipronged approach,” he added.

Dr. Ibrahim has reported financial relationships with Alastin Skincare, Allergan, Eclipse Medical, Galderma USA, and Revision Skincare. Dr. Keaney has reported financial relationships with Allergan, DermTech, Evolus, Galderma USA, Merz Aesthetics, Revance Therapeutics, and Syneron Candela. Dr. Krueger has reported no relevant financial relationships.

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

More than 18 months after the Watchman FLX device was licensed by the Food and Drug Administration for closure of the left atrial appendage (LAA), a prospective analysis of registry data presented at CRT 2022, sponsored by MedStar Heart & Vascular Institute, supports its safely outside of the clinical trial setting.

The data, drawn from the LAA occlusion registry of the National Cardiovascular Data Registry, showed a mortality rate at 45 days of under 1.0%, which was consistent with the acceptably low rate of other adverse events, according to Samir R. Kapadia, MD, chair of cardiovascular medicine at the Cleveland Clinic.

Only 0.5% had a pericardial effusion within 45 days of LAA closure that required intervention. Of those without effusion, 95% had a leak of less than 3 mm and 82% had no leak at all, according to Dr. Kapadia.

Patients enrolled in this analysis, called SURPASS (Surveillance Post Approval Analysis Plan), had undergone left atrial closure with the device from August 2020 to September 2022. There were no exclusion criteria. Ultimately, 2 years of follow-up is planned.

With more than 16,000 patients enrolled, the data on 14,363 patients in this initial 45-day analysis represents “the largest number of Watchman FLX patients evaluated to date,” Dr. Kapadia reported.
 

Device implantation success 97.5%

The Watchman FLX, which is delivered to the left atrial appendage by a transcatheter approach, was deployed successfully in 97.5% of all 16,048 patients enrolled in the registry. In the 398 cases without successful deployment, the anatomy was not conducive in nearly 70%. Other reasons included failure to meet device-release criteria and change in patient condition.

The outcomes of interest at 45 days were ischemic strokes, systemic emboli, device-related thrombi, device embolization, and bleeding. The primary endpoints at 2 years will be strokes and thrombotic events.

For stroke, the incidence within 45 days was 0.39%. About 25% of the strokes were hemorrhagic and the remainder were ischemic. There was 1 systemic embolism (0.01%), 5 device embolizations (0.03%), and 30 device-related thrombotic events (0.24%). Major bleeding occurred in 508 patients (3.55%).

For context, Dr. Kapadia compared these results to those observed in the PINNACLE FLX trial, which was a nonrandomized but prospective study of the Watchman FLX published about 1 year ago. In PINNACLE FLX, the enrollment was open to patients indicated for oral anticoagulation but who had an appropriate rationale for seeking a nonpharmacological alternative.

Taken from different studies, the outcomes at 45 days should not be construed as a direct comparison, but the similarity of the results can be considered reassuring, according to Dr. Kapadia.

For the composite safety endpoint of all-cause death, ischemic stroke, systemic embolism, or implantation-related events requiring intervention, the rates in SURPASS (0.4%) and PINNACLE FLX (0.5%) were nearly identical. Device leak rates (82.0% vs. 82.8%), stroke rates (0.4% vs. 0.7%), and all-cause death rates (0.9% vs. 0.5%) were also similar.

The similarity of the SURPASS and PINNACLE FLX data provides another level of reassurance.

“The SURPASS registry confirms the safety of the Watchman Flex in the real-world experience when the device is being used by many different operators in a large patient population,” Dr. Kapadia said in an interview.

In “appropriately selected patients,” the SURPASS data confirm that the Watchman FLX device “provides a safe and effective treatment option,” he added.

Relative to the PINNACLE FLX study, which enrolled 400 patients, it is noteworthy that the median age in SURPASS was older (76 vs. 73.8 years), a potential disadvantage in demonstrating comparable safety. The proportion of non-White patients was similar (6.7% vs. 6.3%). SURPASS had a higher proportion of women (40% vs. 35.5%).

Mitchel L. Zoler/MDedge News

The SURPASS data are credible, according to Vivek Y. Reddy, MD, director of cardiac arrhythmia services, Mount Sinai Health System, New York.

“While there are certainly limitations to registry data, I do feel pretty confident that these procedural complication and success rates [in SURPASS] do indeed reflect reality,” said Dr. Reddy, who was a coauthor of the PINNACLE FLX trial. In general, the SURPASS data “mirror most of our clinical experiences in routine clinical practice.”

With these registry data backing up multiple clinical studies, Dr. Reddy concluded, “I do believe that it is fair to say that Watchman-FLX implantation is a quite safe procedure.”

Dr. Kapadia reported no potential conflicts of interest. Dr. Reddy reported a financial relationship with Boston Scientific.

More than 18 months after the Watchman FLX device was licensed by the Food and Drug Administration for closure of the left atrial appendage (LAA), a prospective analysis of registry data presented at CRT 2022, sponsored by MedStar Heart & Vascular Institute, supports its safely outside of the clinical trial setting.

The data, drawn from the LAA occlusion registry of the National Cardiovascular Data Registry, showed a mortality rate at 45 days of under 1.0%, which was consistent with the acceptably low rate of other adverse events, according to Samir R. Kapadia, MD, chair of cardiovascular medicine at the Cleveland Clinic.

Only 0.5% had a pericardial effusion within 45 days of LAA closure that required intervention. Of those without effusion, 95% had a leak of less than 3 mm and 82% had no leak at all, according to Dr. Kapadia.

Patients enrolled in this analysis, called SURPASS (Surveillance Post Approval Analysis Plan), had undergone left atrial closure with the device from August 2020 to September 2022. There were no exclusion criteria. Ultimately, 2 years of follow-up is planned.

With more than 16,000 patients enrolled, the data on 14,363 patients in this initial 45-day analysis represents “the largest number of Watchman FLX patients evaluated to date,” Dr. Kapadia reported.
 

Device implantation success 97.5%

The Watchman FLX, which is delivered to the left atrial appendage by a transcatheter approach, was deployed successfully in 97.5% of all 16,048 patients enrolled in the registry. In the 398 cases without successful deployment, the anatomy was not conducive in nearly 70%. Other reasons included failure to meet device-release criteria and change in patient condition.

The outcomes of interest at 45 days were ischemic strokes, systemic emboli, device-related thrombi, device embolization, and bleeding. The primary endpoints at 2 years will be strokes and thrombotic events.

For stroke, the incidence within 45 days was 0.39%. About 25% of the strokes were hemorrhagic and the remainder were ischemic. There was 1 systemic embolism (0.01%), 5 device embolizations (0.03%), and 30 device-related thrombotic events (0.24%). Major bleeding occurred in 508 patients (3.55%).

For context, Dr. Kapadia compared these results to those observed in the PINNACLE FLX trial, which was a nonrandomized but prospective study of the Watchman FLX published about 1 year ago. In PINNACLE FLX, the enrollment was open to patients indicated for oral anticoagulation but who had an appropriate rationale for seeking a nonpharmacological alternative.

Taken from different studies, the outcomes at 45 days should not be construed as a direct comparison, but the similarity of the results can be considered reassuring, according to Dr. Kapadia.

For the composite safety endpoint of all-cause death, ischemic stroke, systemic embolism, or implantation-related events requiring intervention, the rates in SURPASS (0.4%) and PINNACLE FLX (0.5%) were nearly identical. Device leak rates (82.0% vs. 82.8%), stroke rates (0.4% vs. 0.7%), and all-cause death rates (0.9% vs. 0.5%) were also similar.

The similarity of the SURPASS and PINNACLE FLX data provides another level of reassurance.

“The SURPASS registry confirms the safety of the Watchman Flex in the real-world experience when the device is being used by many different operators in a large patient population,” Dr. Kapadia said in an interview.

In “appropriately selected patients,” the SURPASS data confirm that the Watchman FLX device “provides a safe and effective treatment option,” he added.

Relative to the PINNACLE FLX study, which enrolled 400 patients, it is noteworthy that the median age in SURPASS was older (76 vs. 73.8 years), a potential disadvantage in demonstrating comparable safety. The proportion of non-White patients was similar (6.7% vs. 6.3%). SURPASS had a higher proportion of women (40% vs. 35.5%).

Mitchel L. Zoler/MDedge News

The SURPASS data are credible, according to Vivek Y. Reddy, MD, director of cardiac arrhythmia services, Mount Sinai Health System, New York.

“While there are certainly limitations to registry data, I do feel pretty confident that these procedural complication and success rates [in SURPASS] do indeed reflect reality,” said Dr. Reddy, who was a coauthor of the PINNACLE FLX trial. In general, the SURPASS data “mirror most of our clinical experiences in routine clinical practice.”

With these registry data backing up multiple clinical studies, Dr. Reddy concluded, “I do believe that it is fair to say that Watchman-FLX implantation is a quite safe procedure.”

Dr. Kapadia reported no potential conflicts of interest. Dr. Reddy reported a financial relationship with Boston Scientific.

More than 18 months after the Watchman FLX device was licensed by the Food and Drug Administration for closure of the left atrial appendage (LAA), a prospective analysis of registry data presented at CRT 2022, sponsored by MedStar Heart & Vascular Institute, supports its safely outside of the clinical trial setting.

The data, drawn from the LAA occlusion registry of the National Cardiovascular Data Registry, showed a mortality rate at 45 days of under 1.0%, which was consistent with the acceptably low rate of other adverse events, according to Samir R. Kapadia, MD, chair of cardiovascular medicine at the Cleveland Clinic.

Only 0.5% had a pericardial effusion within 45 days of LAA closure that required intervention. Of those without effusion, 95% had a leak of less than 3 mm and 82% had no leak at all, according to Dr. Kapadia.

Patients enrolled in this analysis, called SURPASS (Surveillance Post Approval Analysis Plan), had undergone left atrial closure with the device from August 2020 to September 2022. There were no exclusion criteria. Ultimately, 2 years of follow-up is planned.

With more than 16,000 patients enrolled, the data on 14,363 patients in this initial 45-day analysis represents “the largest number of Watchman FLX patients evaluated to date,” Dr. Kapadia reported.
 

Device implantation success 97.5%

The Watchman FLX, which is delivered to the left atrial appendage by a transcatheter approach, was deployed successfully in 97.5% of all 16,048 patients enrolled in the registry. In the 398 cases without successful deployment, the anatomy was not conducive in nearly 70%. Other reasons included failure to meet device-release criteria and change in patient condition.

The outcomes of interest at 45 days were ischemic strokes, systemic emboli, device-related thrombi, device embolization, and bleeding. The primary endpoints at 2 years will be strokes and thrombotic events.

For stroke, the incidence within 45 days was 0.39%. About 25% of the strokes were hemorrhagic and the remainder were ischemic. There was 1 systemic embolism (0.01%), 5 device embolizations (0.03%), and 30 device-related thrombotic events (0.24%). Major bleeding occurred in 508 patients (3.55%).

For context, Dr. Kapadia compared these results to those observed in the PINNACLE FLX trial, which was a nonrandomized but prospective study of the Watchman FLX published about 1 year ago. In PINNACLE FLX, the enrollment was open to patients indicated for oral anticoagulation but who had an appropriate rationale for seeking a nonpharmacological alternative.

Taken from different studies, the outcomes at 45 days should not be construed as a direct comparison, but the similarity of the results can be considered reassuring, according to Dr. Kapadia.

For the composite safety endpoint of all-cause death, ischemic stroke, systemic embolism, or implantation-related events requiring intervention, the rates in SURPASS (0.4%) and PINNACLE FLX (0.5%) were nearly identical. Device leak rates (82.0% vs. 82.8%), stroke rates (0.4% vs. 0.7%), and all-cause death rates (0.9% vs. 0.5%) were also similar.

The similarity of the SURPASS and PINNACLE FLX data provides another level of reassurance.

“The SURPASS registry confirms the safety of the Watchman Flex in the real-world experience when the device is being used by many different operators in a large patient population,” Dr. Kapadia said in an interview.

In “appropriately selected patients,” the SURPASS data confirm that the Watchman FLX device “provides a safe and effective treatment option,” he added.

Relative to the PINNACLE FLX study, which enrolled 400 patients, it is noteworthy that the median age in SURPASS was older (76 vs. 73.8 years), a potential disadvantage in demonstrating comparable safety. The proportion of non-White patients was similar (6.7% vs. 6.3%). SURPASS had a higher proportion of women (40% vs. 35.5%).

Mitchel L. Zoler/MDedge News

The SURPASS data are credible, according to Vivek Y. Reddy, MD, director of cardiac arrhythmia services, Mount Sinai Health System, New York.

“While there are certainly limitations to registry data, I do feel pretty confident that these procedural complication and success rates [in SURPASS] do indeed reflect reality,” said Dr. Reddy, who was a coauthor of the PINNACLE FLX trial. In general, the SURPASS data “mirror most of our clinical experiences in routine clinical practice.”

With these registry data backing up multiple clinical studies, Dr. Reddy concluded, “I do believe that it is fair to say that Watchman-FLX implantation is a quite safe procedure.”

Dr. Kapadia reported no potential conflicts of interest. Dr. Reddy reported a financial relationship with Boston Scientific.