Conference Coverage

For patients undergoing transcatheter aortic valve replacement (TAVR), the intentional laceration technique of diseased valve leaflets called BASILICA is effective and reasonably safe for preventing coronary artery obstruction, according to a late-breaking study presented at CRT 2021 sponsored by MedStar Heart & Vascular Institute.

In a series of 214 patients entered into a registry over a recent 30-month period, leaflets posing risk were effectively traversed with the technique in 95% of cases, and complication rates were reasonably low with 30-day stroke and death rate of 3.4%, reported Jaffar M. Khan, BMBCH, PhD, cardiovascular branch of the National Heart, Lung, and Blood Institute.

The rate of complications is acceptable given the large potential risk, according to Dr. Khan. If coronary obstruction occurs, reported mortality rates have been as high as 50%. The 1-year survival rate in the registry following BASILICA was 84%.
 

Results should ‘push people toward BASILICA’

The acronym BASILICA stands for bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction. In the procedure, performed immediately before TAVR, guidewires are introduced to first traverse and then lacerate aortic leaflets threatening obstruction of a coronary artery.

In cases where diseased valve leaflets pose a risk of coronary obstruction, most interventionalists “are comfortable with surgery when patients are at low or intermediate risk, but the choices for high-risk patients are a snorkel stent or BASILICA. Given the limits of snorkel stenting, these data should be reassuring and push people toward BASILICA,” Dr. Khan said.

The 214 patients were entered into the registry from June 2015 to December 2020. The mean age was 74.9 years. Of valves treated, 73% were failed bioprosthetic devices. The remaining were native aortic valves. Solo BASILICA was performed in most patients, but 21.5% underwent a doppio procedure, meaning the laceration of two leaflets.

Despite BASILICA, 10 patients (4.7%) had some degree of coronary obstruction, including 5 with partial obstruction of the main coronary artery and 1 with partial obstruction of the right coronary artery. All of these partial obstructions were successfully treated with orthotopic stents.

An obstruction of the right coronary artery was successfully treated with balloon angioplasty. Another patient with significant left main coronary artery obstruction required cardiopulmonary bypass but was successfully treated with snorkel stenting. Of two patients with complete obstruction of the left main coronary artery caused by the skirt of the TAVR device, one died in hospital despite several maneuvers to restore perfusion.

Procedural complications included a mitral chord laceration, which subsequently led to valve replacement, and three guidewire transversals into surrounding tissue that did not result in serious sequelae. Hypotension requiring pressors occurred in 8.5%.

There was a “slight trend” for worse outcomes in those undergoing doppio rather than solo BASILICA, but the difference did not reach statistical significance. Cerebral embolic protection was offered to a minority of patients in this series. The trend for a lower risk of stroke in this group did not reach significance, Dr. Khan reported.
 

Best for high-volume centers, for now

Although these data support the conclusion that BASILICA “is feasible in a real-world setting,” Dr. Khan acknowledged that BASILICA might not be appropriate at low-volume centers. Dr. Khan cited data that indicates obstruction of a coronary artery by a diseased leaflet occurs in less than 1% of TAVR cases.

“Not every site doing a handful of TAVRs is going to want to tackle these cases, but those working in a high-volume center will from time to time encounter patients with coronary obstruction or who are at increased risk,” Dr. Khan said.

In North America, there has been a proctoring program to disseminate the skills required to perform BASILICA, according to Dr. Khan, who explained that proctors typically participate in two or three cases before these are performed without supervision.

So far, the uptake of BASILICA has been limited.

“BASILICA has not been catching on in EUROPE,” said Didier F. Loulmet, MD, chief of cardiac surgery at Tisch Hospital, New York University Langone Health. There might be several reasons, but Dr. Loulmet said that lack of a comparable proctoring program is one factor.”

“This is a relatively complex procedure performed in a small number of patients, so building up expertise is quite a challenge, particularly in small centers,” he added. He encouraged proctoring as “the way that it has to be propagated.”

The results presented by Dr. Khan on March 6 at CRT 2021 were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Khan has patents on several devices, including catheters to lacerate valve leaflet. Dr. Loulmet reported no potential conflicts of interest.

For patients undergoing transcatheter aortic valve replacement (TAVR), the intentional laceration technique of diseased valve leaflets called BASILICA is effective and reasonably safe for preventing coronary artery obstruction, according to a late-breaking study presented at CRT 2021 sponsored by MedStar Heart & Vascular Institute.

In a series of 214 patients entered into a registry over a recent 30-month period, leaflets posing risk were effectively traversed with the technique in 95% of cases, and complication rates were reasonably low with 30-day stroke and death rate of 3.4%, reported Jaffar M. Khan, BMBCH, PhD, cardiovascular branch of the National Heart, Lung, and Blood Institute.

The rate of complications is acceptable given the large potential risk, according to Dr. Khan. If coronary obstruction occurs, reported mortality rates have been as high as 50%. The 1-year survival rate in the registry following BASILICA was 84%.
 

Results should ‘push people toward BASILICA’

The acronym BASILICA stands for bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction. In the procedure, performed immediately before TAVR, guidewires are introduced to first traverse and then lacerate aortic leaflets threatening obstruction of a coronary artery.

In cases where diseased valve leaflets pose a risk of coronary obstruction, most interventionalists “are comfortable with surgery when patients are at low or intermediate risk, but the choices for high-risk patients are a snorkel stent or BASILICA. Given the limits of snorkel stenting, these data should be reassuring and push people toward BASILICA,” Dr. Khan said.

The 214 patients were entered into the registry from June 2015 to December 2020. The mean age was 74.9 years. Of valves treated, 73% were failed bioprosthetic devices. The remaining were native aortic valves. Solo BASILICA was performed in most patients, but 21.5% underwent a doppio procedure, meaning the laceration of two leaflets.

Despite BASILICA, 10 patients (4.7%) had some degree of coronary obstruction, including 5 with partial obstruction of the main coronary artery and 1 with partial obstruction of the right coronary artery. All of these partial obstructions were successfully treated with orthotopic stents.

An obstruction of the right coronary artery was successfully treated with balloon angioplasty. Another patient with significant left main coronary artery obstruction required cardiopulmonary bypass but was successfully treated with snorkel stenting. Of two patients with complete obstruction of the left main coronary artery caused by the skirt of the TAVR device, one died in hospital despite several maneuvers to restore perfusion.

Procedural complications included a mitral chord laceration, which subsequently led to valve replacement, and three guidewire transversals into surrounding tissue that did not result in serious sequelae. Hypotension requiring pressors occurred in 8.5%.

There was a “slight trend” for worse outcomes in those undergoing doppio rather than solo BASILICA, but the difference did not reach statistical significance. Cerebral embolic protection was offered to a minority of patients in this series. The trend for a lower risk of stroke in this group did not reach significance, Dr. Khan reported.
 

Best for high-volume centers, for now

Although these data support the conclusion that BASILICA “is feasible in a real-world setting,” Dr. Khan acknowledged that BASILICA might not be appropriate at low-volume centers. Dr. Khan cited data that indicates obstruction of a coronary artery by a diseased leaflet occurs in less than 1% of TAVR cases.

“Not every site doing a handful of TAVRs is going to want to tackle these cases, but those working in a high-volume center will from time to time encounter patients with coronary obstruction or who are at increased risk,” Dr. Khan said.

In North America, there has been a proctoring program to disseminate the skills required to perform BASILICA, according to Dr. Khan, who explained that proctors typically participate in two or three cases before these are performed without supervision.

So far, the uptake of BASILICA has been limited.

“BASILICA has not been catching on in EUROPE,” said Didier F. Loulmet, MD, chief of cardiac surgery at Tisch Hospital, New York University Langone Health. There might be several reasons, but Dr. Loulmet said that lack of a comparable proctoring program is one factor.”

“This is a relatively complex procedure performed in a small number of patients, so building up expertise is quite a challenge, particularly in small centers,” he added. He encouraged proctoring as “the way that it has to be propagated.”

The results presented by Dr. Khan on March 6 at CRT 2021 were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Khan has patents on several devices, including catheters to lacerate valve leaflet. Dr. Loulmet reported no potential conflicts of interest.

For patients undergoing transcatheter aortic valve replacement (TAVR), the intentional laceration technique of diseased valve leaflets called BASILICA is effective and reasonably safe for preventing coronary artery obstruction, according to a late-breaking study presented at CRT 2021 sponsored by MedStar Heart & Vascular Institute.

In a series of 214 patients entered into a registry over a recent 30-month period, leaflets posing risk were effectively traversed with the technique in 95% of cases, and complication rates were reasonably low with 30-day stroke and death rate of 3.4%, reported Jaffar M. Khan, BMBCH, PhD, cardiovascular branch of the National Heart, Lung, and Blood Institute.

The rate of complications is acceptable given the large potential risk, according to Dr. Khan. If coronary obstruction occurs, reported mortality rates have been as high as 50%. The 1-year survival rate in the registry following BASILICA was 84%.
 

Results should ‘push people toward BASILICA’

The acronym BASILICA stands for bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction. In the procedure, performed immediately before TAVR, guidewires are introduced to first traverse and then lacerate aortic leaflets threatening obstruction of a coronary artery.

In cases where diseased valve leaflets pose a risk of coronary obstruction, most interventionalists “are comfortable with surgery when patients are at low or intermediate risk, but the choices for high-risk patients are a snorkel stent or BASILICA. Given the limits of snorkel stenting, these data should be reassuring and push people toward BASILICA,” Dr. Khan said.

The 214 patients were entered into the registry from June 2015 to December 2020. The mean age was 74.9 years. Of valves treated, 73% were failed bioprosthetic devices. The remaining were native aortic valves. Solo BASILICA was performed in most patients, but 21.5% underwent a doppio procedure, meaning the laceration of two leaflets.

Despite BASILICA, 10 patients (4.7%) had some degree of coronary obstruction, including 5 with partial obstruction of the main coronary artery and 1 with partial obstruction of the right coronary artery. All of these partial obstructions were successfully treated with orthotopic stents.

An obstruction of the right coronary artery was successfully treated with balloon angioplasty. Another patient with significant left main coronary artery obstruction required cardiopulmonary bypass but was successfully treated with snorkel stenting. Of two patients with complete obstruction of the left main coronary artery caused by the skirt of the TAVR device, one died in hospital despite several maneuvers to restore perfusion.

Procedural complications included a mitral chord laceration, which subsequently led to valve replacement, and three guidewire transversals into surrounding tissue that did not result in serious sequelae. Hypotension requiring pressors occurred in 8.5%.

There was a “slight trend” for worse outcomes in those undergoing doppio rather than solo BASILICA, but the difference did not reach statistical significance. Cerebral embolic protection was offered to a minority of patients in this series. The trend for a lower risk of stroke in this group did not reach significance, Dr. Khan reported.
 

Best for high-volume centers, for now

Although these data support the conclusion that BASILICA “is feasible in a real-world setting,” Dr. Khan acknowledged that BASILICA might not be appropriate at low-volume centers. Dr. Khan cited data that indicates obstruction of a coronary artery by a diseased leaflet occurs in less than 1% of TAVR cases.

“Not every site doing a handful of TAVRs is going to want to tackle these cases, but those working in a high-volume center will from time to time encounter patients with coronary obstruction or who are at increased risk,” Dr. Khan said.

In North America, there has been a proctoring program to disseminate the skills required to perform BASILICA, according to Dr. Khan, who explained that proctors typically participate in two or three cases before these are performed without supervision.

So far, the uptake of BASILICA has been limited.

“BASILICA has not been catching on in EUROPE,” said Didier F. Loulmet, MD, chief of cardiac surgery at Tisch Hospital, New York University Langone Health. There might be several reasons, but Dr. Loulmet said that lack of a comparable proctoring program is one factor.”

“This is a relatively complex procedure performed in a small number of patients, so building up expertise is quite a challenge, particularly in small centers,” he added. He encouraged proctoring as “the way that it has to be propagated.”

The results presented by Dr. Khan on March 6 at CRT 2021 were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Khan has patents on several devices, including catheters to lacerate valve leaflet. Dr. Loulmet reported no potential conflicts of interest.

Both high and low serum sodium levels are associated with adverse outcomes for hospitalized patients with COVID-19, new research suggests.

In the retrospective study of 488 patients hospitalized with COVID-19 at one of two London hospitals between February and May 2020, hypernatremia (defined as serum sodium level >145 mmol/L) at any time point during hospital stay was associated with a threefold increase in inpatient mortality.

Hyponatremia (serum sodium level <135 mmol/L) was associated with twice the likelihood of requiring advanced ventilatory support. In-hospital mortality was also increased among patients with hypovolemic hyponatremia.

“Serum sodium values could be used in clinical practice to identify patients with COVID-19 at high risk of poor outcomes who would benefit from more intensive monitoring and judicious rehydration,” Ploutarchos Tzoulis, MD, PhD, and colleagues wrote in their article, which was published online on Feb. 24, 2021, in the Journal of Clinical Endocrinology and Metabolism.

The findings will be presented at the upcoming news conference held by the Endocrine Society
 

Should sodium be included in a risk calculator for COVID-19?

Dr. Tzoulis, professor of endocrinology at the University College London Medical School, said in an interview that “sodium could be incorporated in risk calculators across other routine biomarkers, such as white cell count, lymphocytes, and CRP [C-reactive protein], in order to provide a tool for dynamic risk stratification throughout the clinical course of COVID-19 and assist clinical decision-making.”

Moreover, he said, “we should follow less conservative strategies in the rate and amount of fluid resuscitation in order to prevent hypernatremia, which is induced by negative fluid balance and can often be iatrogenic.”

Asked to comment, Steven Q. Simpson, MD, professor of medicine in the division of pulmonary, critical care, and sleep medicine at the University of Kansas, Kansas City, said that the article is missing key results that would assist in interpreting of the findings.

“Data regarding diuretic use and sparing of fluid administration are not in the paper. ... It is simply not possible to tell whether serum sodium is a ‘predictor’ ... or if it is a side effect of other issues or actions taken by physicians in patients who are progressing poorly.

“To say that sodium needs to be included in a risk calculator is to subtly suggest that there is some causal association with mortality, and that has quite clearly not been established,” stressed Dr. Simpson, who is president of the American College of Chest Physicians but was not speaking for the organization.

He added: “The data are interesting, but not actionable. It is common practice in critical care medicine to adjust water and salt intake to maintain serum sodium within the normal range, so the paper really doesn’t change any behavior.”

Dr. Tzoulis said in an interview that, despite not having electronic medical record data on diuretic use or fluid input and output, “our acute physicians and intensivists at both study sites have been adamant that they’ve not routinely used diuretics in COVID-19 patients. Diuretics have been sparingly used in our cohort, and also the frequency of pulmonary edema was reported as below 5%.”

Regarding volume of fluid intake, Dr. Tzoulis noted, “At our hospital sites, the strategy has been that of cautious fluid resuscitation. In fact, the amount of fluid given has been reported by our physicians and intensivists as ‘on purpose much more conservative than the usual one adopted in patients with community-acquired pneumonia at risk of respiratory failure.’ ”
 

Hyper- and hyponatremia linked to adverse COVID-19 outcomes

In the study, 5.3% of the 488 patients had hypernatremia at hospital presentation, and 24.6% had hyponatremia. Of note, only 19% of those with hyponatremia underwent laboratory workup to determine the etiology. Of those, three quarters had hypovolemic hyponatremia, determined on the basis of a urinary sodium cutoff of 30 mmol/L.

The total in-hospital mortality rate was 31.1%. There was a strong, although nonsignificant, trend toward higher mortality in association with sodium status at admission. Death rates were 28.4%, 30.8%, and 46.1% for those who were normonatremic, hyponatremic, and hypernatremic, respectively (P = .07). Baseline serum sodium levels didn’t differ between survivors (137 mmol/L) and nonsurvivors (138 mmol/L).

In multivariable analysis, the occurrence of hypernatremia at any point during the first 5 days in the hospital was among three independent risk factors for higher in-hospital mortality (adjusted hazard ratio, 2.74; P = .02). The other risk factors were older age and higher CRP level.

Overall, hyponatremia was not associated with death (P = .41).

During hospitalization, 37.9% of patients remained normonatremic; 36.9% experienced hyponatremia; 10.9% had hypernatremia; and 14.3% had both conditions at some point during their stay.

In-hospital mortality was 21% among those with normonatremia, compared with 56.6% for those with hypernatremia (odds ratio, 3.05; P = .0038) and 45.7% for those with both (OR, 2.25; P < .0001).

The 28.3% mortality rate in the overall group that experienced hyponatremia didn’t differ significantly from the 21.1% in the normonatremic group (OR, 1.34; P = .16). However, the death rate was 40.9% among the subgroup that developed hypovolemic hyponatremia, significantly higher than the normonatremic group (OR, 2.59, P = .0017).

The incidence of hyponatremia decreased from 24.6% at admission to 14.1% 5 days later, whereas the frequency of hypernatremia rose from 5.3% to 13.8%.
 

Key finding: Link between hospital-acquired hypernatremia and death

“The key novel finding of our study was that hospital-acquired hypernatremia, rather than hypernatremia at admission, was a predictor for in-hospital mortality, with the worst prognosis being reported in patients with the largest increase in serum sodium in the first 5 days of hospitalization,” noted Dr. Tzoulis and colleagues.

Hypernatremia was present in 29.6% of nonsurvivors, compared with 5.2% in survivors.

Among 120 patients with hyponatremia at admission, 31.7% received advanced respiratory support, compared with 17.5% and 7.7% of those with normonatremia or hypernatremia, respectively (OR, 2.18; P = .0011).

In contrast, there was no difference in the proportions needing ventilatory support between those with hypernatremia and those with normonatremia (16.7% vs. 12.4%; OR, 1.44; P = .39).

Acute kidney injury occurred in 181 patients (37.1%). It was not related to serum sodium concentration at any time point.

Dr. Tzoulis and Dr. Simpson disclosed no relevant financial relationships.

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

Both high and low serum sodium levels are associated with adverse outcomes for hospitalized patients with COVID-19, new research suggests.

In the retrospective study of 488 patients hospitalized with COVID-19 at one of two London hospitals between February and May 2020, hypernatremia (defined as serum sodium level >145 mmol/L) at any time point during hospital stay was associated with a threefold increase in inpatient mortality.

Hyponatremia (serum sodium level <135 mmol/L) was associated with twice the likelihood of requiring advanced ventilatory support. In-hospital mortality was also increased among patients with hypovolemic hyponatremia.

“Serum sodium values could be used in clinical practice to identify patients with COVID-19 at high risk of poor outcomes who would benefit from more intensive monitoring and judicious rehydration,” Ploutarchos Tzoulis, MD, PhD, and colleagues wrote in their article, which was published online on Feb. 24, 2021, in the Journal of Clinical Endocrinology and Metabolism.

The findings will be presented at the upcoming news conference held by the Endocrine Society
 

Should sodium be included in a risk calculator for COVID-19?

Dr. Tzoulis, professor of endocrinology at the University College London Medical School, said in an interview that “sodium could be incorporated in risk calculators across other routine biomarkers, such as white cell count, lymphocytes, and CRP [C-reactive protein], in order to provide a tool for dynamic risk stratification throughout the clinical course of COVID-19 and assist clinical decision-making.”

Moreover, he said, “we should follow less conservative strategies in the rate and amount of fluid resuscitation in order to prevent hypernatremia, which is induced by negative fluid balance and can often be iatrogenic.”

Asked to comment, Steven Q. Simpson, MD, professor of medicine in the division of pulmonary, critical care, and sleep medicine at the University of Kansas, Kansas City, said that the article is missing key results that would assist in interpreting of the findings.

“Data regarding diuretic use and sparing of fluid administration are not in the paper. ... It is simply not possible to tell whether serum sodium is a ‘predictor’ ... or if it is a side effect of other issues or actions taken by physicians in patients who are progressing poorly.

“To say that sodium needs to be included in a risk calculator is to subtly suggest that there is some causal association with mortality, and that has quite clearly not been established,” stressed Dr. Simpson, who is president of the American College of Chest Physicians but was not speaking for the organization.

He added: “The data are interesting, but not actionable. It is common practice in critical care medicine to adjust water and salt intake to maintain serum sodium within the normal range, so the paper really doesn’t change any behavior.”

Dr. Tzoulis said in an interview that, despite not having electronic medical record data on diuretic use or fluid input and output, “our acute physicians and intensivists at both study sites have been adamant that they’ve not routinely used diuretics in COVID-19 patients. Diuretics have been sparingly used in our cohort, and also the frequency of pulmonary edema was reported as below 5%.”

Regarding volume of fluid intake, Dr. Tzoulis noted, “At our hospital sites, the strategy has been that of cautious fluid resuscitation. In fact, the amount of fluid given has been reported by our physicians and intensivists as ‘on purpose much more conservative than the usual one adopted in patients with community-acquired pneumonia at risk of respiratory failure.’ ”
 

Hyper- and hyponatremia linked to adverse COVID-19 outcomes

In the study, 5.3% of the 488 patients had hypernatremia at hospital presentation, and 24.6% had hyponatremia. Of note, only 19% of those with hyponatremia underwent laboratory workup to determine the etiology. Of those, three quarters had hypovolemic hyponatremia, determined on the basis of a urinary sodium cutoff of 30 mmol/L.

The total in-hospital mortality rate was 31.1%. There was a strong, although nonsignificant, trend toward higher mortality in association with sodium status at admission. Death rates were 28.4%, 30.8%, and 46.1% for those who were normonatremic, hyponatremic, and hypernatremic, respectively (P = .07). Baseline serum sodium levels didn’t differ between survivors (137 mmol/L) and nonsurvivors (138 mmol/L).

In multivariable analysis, the occurrence of hypernatremia at any point during the first 5 days in the hospital was among three independent risk factors for higher in-hospital mortality (adjusted hazard ratio, 2.74; P = .02). The other risk factors were older age and higher CRP level.

Overall, hyponatremia was not associated with death (P = .41).

During hospitalization, 37.9% of patients remained normonatremic; 36.9% experienced hyponatremia; 10.9% had hypernatremia; and 14.3% had both conditions at some point during their stay.

In-hospital mortality was 21% among those with normonatremia, compared with 56.6% for those with hypernatremia (odds ratio, 3.05; P = .0038) and 45.7% for those with both (OR, 2.25; P < .0001).

The 28.3% mortality rate in the overall group that experienced hyponatremia didn’t differ significantly from the 21.1% in the normonatremic group (OR, 1.34; P = .16). However, the death rate was 40.9% among the subgroup that developed hypovolemic hyponatremia, significantly higher than the normonatremic group (OR, 2.59, P = .0017).

The incidence of hyponatremia decreased from 24.6% at admission to 14.1% 5 days later, whereas the frequency of hypernatremia rose from 5.3% to 13.8%.
 

Key finding: Link between hospital-acquired hypernatremia and death

“The key novel finding of our study was that hospital-acquired hypernatremia, rather than hypernatremia at admission, was a predictor for in-hospital mortality, with the worst prognosis being reported in patients with the largest increase in serum sodium in the first 5 days of hospitalization,” noted Dr. Tzoulis and colleagues.

Hypernatremia was present in 29.6% of nonsurvivors, compared with 5.2% in survivors.

Among 120 patients with hyponatremia at admission, 31.7% received advanced respiratory support, compared with 17.5% and 7.7% of those with normonatremia or hypernatremia, respectively (OR, 2.18; P = .0011).

In contrast, there was no difference in the proportions needing ventilatory support between those with hypernatremia and those with normonatremia (16.7% vs. 12.4%; OR, 1.44; P = .39).

Acute kidney injury occurred in 181 patients (37.1%). It was not related to serum sodium concentration at any time point.

Dr. Tzoulis and Dr. Simpson disclosed no relevant financial relationships.

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

Both high and low serum sodium levels are associated with adverse outcomes for hospitalized patients with COVID-19, new research suggests.

In the retrospective study of 488 patients hospitalized with COVID-19 at one of two London hospitals between February and May 2020, hypernatremia (defined as serum sodium level >145 mmol/L) at any time point during hospital stay was associated with a threefold increase in inpatient mortality.

Hyponatremia (serum sodium level <135 mmol/L) was associated with twice the likelihood of requiring advanced ventilatory support. In-hospital mortality was also increased among patients with hypovolemic hyponatremia.

“Serum sodium values could be used in clinical practice to identify patients with COVID-19 at high risk of poor outcomes who would benefit from more intensive monitoring and judicious rehydration,” Ploutarchos Tzoulis, MD, PhD, and colleagues wrote in their article, which was published online on Feb. 24, 2021, in the Journal of Clinical Endocrinology and Metabolism.

The findings will be presented at the upcoming news conference held by the Endocrine Society
 

Should sodium be included in a risk calculator for COVID-19?

Dr. Tzoulis, professor of endocrinology at the University College London Medical School, said in an interview that “sodium could be incorporated in risk calculators across other routine biomarkers, such as white cell count, lymphocytes, and CRP [C-reactive protein], in order to provide a tool for dynamic risk stratification throughout the clinical course of COVID-19 and assist clinical decision-making.”

Moreover, he said, “we should follow less conservative strategies in the rate and amount of fluid resuscitation in order to prevent hypernatremia, which is induced by negative fluid balance and can often be iatrogenic.”

Asked to comment, Steven Q. Simpson, MD, professor of medicine in the division of pulmonary, critical care, and sleep medicine at the University of Kansas, Kansas City, said that the article is missing key results that would assist in interpreting of the findings.

“Data regarding diuretic use and sparing of fluid administration are not in the paper. ... It is simply not possible to tell whether serum sodium is a ‘predictor’ ... or if it is a side effect of other issues or actions taken by physicians in patients who are progressing poorly.

“To say that sodium needs to be included in a risk calculator is to subtly suggest that there is some causal association with mortality, and that has quite clearly not been established,” stressed Dr. Simpson, who is president of the American College of Chest Physicians but was not speaking for the organization.

He added: “The data are interesting, but not actionable. It is common practice in critical care medicine to adjust water and salt intake to maintain serum sodium within the normal range, so the paper really doesn’t change any behavior.”

Dr. Tzoulis said in an interview that, despite not having electronic medical record data on diuretic use or fluid input and output, “our acute physicians and intensivists at both study sites have been adamant that they’ve not routinely used diuretics in COVID-19 patients. Diuretics have been sparingly used in our cohort, and also the frequency of pulmonary edema was reported as below 5%.”

Regarding volume of fluid intake, Dr. Tzoulis noted, “At our hospital sites, the strategy has been that of cautious fluid resuscitation. In fact, the amount of fluid given has been reported by our physicians and intensivists as ‘on purpose much more conservative than the usual one adopted in patients with community-acquired pneumonia at risk of respiratory failure.’ ”
 

Hyper- and hyponatremia linked to adverse COVID-19 outcomes

In the study, 5.3% of the 488 patients had hypernatremia at hospital presentation, and 24.6% had hyponatremia. Of note, only 19% of those with hyponatremia underwent laboratory workup to determine the etiology. Of those, three quarters had hypovolemic hyponatremia, determined on the basis of a urinary sodium cutoff of 30 mmol/L.

The total in-hospital mortality rate was 31.1%. There was a strong, although nonsignificant, trend toward higher mortality in association with sodium status at admission. Death rates were 28.4%, 30.8%, and 46.1% for those who were normonatremic, hyponatremic, and hypernatremic, respectively (P = .07). Baseline serum sodium levels didn’t differ between survivors (137 mmol/L) and nonsurvivors (138 mmol/L).

In multivariable analysis, the occurrence of hypernatremia at any point during the first 5 days in the hospital was among three independent risk factors for higher in-hospital mortality (adjusted hazard ratio, 2.74; P = .02). The other risk factors were older age and higher CRP level.

Overall, hyponatremia was not associated with death (P = .41).

During hospitalization, 37.9% of patients remained normonatremic; 36.9% experienced hyponatremia; 10.9% had hypernatremia; and 14.3% had both conditions at some point during their stay.

In-hospital mortality was 21% among those with normonatremia, compared with 56.6% for those with hypernatremia (odds ratio, 3.05; P = .0038) and 45.7% for those with both (OR, 2.25; P < .0001).

The 28.3% mortality rate in the overall group that experienced hyponatremia didn’t differ significantly from the 21.1% in the normonatremic group (OR, 1.34; P = .16). However, the death rate was 40.9% among the subgroup that developed hypovolemic hyponatremia, significantly higher than the normonatremic group (OR, 2.59, P = .0017).

The incidence of hyponatremia decreased from 24.6% at admission to 14.1% 5 days later, whereas the frequency of hypernatremia rose from 5.3% to 13.8%.
 

Key finding: Link between hospital-acquired hypernatremia and death

“The key novel finding of our study was that hospital-acquired hypernatremia, rather than hypernatremia at admission, was a predictor for in-hospital mortality, with the worst prognosis being reported in patients with the largest increase in serum sodium in the first 5 days of hospitalization,” noted Dr. Tzoulis and colleagues.

Hypernatremia was present in 29.6% of nonsurvivors, compared with 5.2% in survivors.

Among 120 patients with hyponatremia at admission, 31.7% received advanced respiratory support, compared with 17.5% and 7.7% of those with normonatremia or hypernatremia, respectively (OR, 2.18; P = .0011).

In contrast, there was no difference in the proportions needing ventilatory support between those with hypernatremia and those with normonatremia (16.7% vs. 12.4%; OR, 1.44; P = .39).

Acute kidney injury occurred in 181 patients (37.1%). It was not related to serum sodium concentration at any time point.

Dr. Tzoulis and Dr. Simpson disclosed no relevant financial relationships.

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

A wide variety of medications exists for treating hyperhidrosis, a dermatologist told colleagues, but before prescribing anything to a pediatric patient, he recommended, ask the patient a simple question: “What bothers you the most?”

The answer will provide guidance for developing a step-by-step treatment strategy and help provide the patient “a set of realistic expectations in terms of what the response will look like,” George Hightower, MD, PhD, a pediatric dermatologist at Rady Children’s Hospital and the University of California, San Diego, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

A similar question-based approach will help guide therapy for patients with hidradenitis suppurativa (HS), he said.

With regards to hyperhidrosis, Dr. Hightower said that patients most commonly complain that their underarms are too smelly, too sweaty, and red, itchy, or painful. Causes, he said, can include irritation/contact dermatitis, folliculitis, and seborrheic dermatitis, as well as hyperhidrosis or HS.

Primary focal axillary hyperhidrosis is defined as focal, visible, excessive sweating for at least 6 months without an apparent cause plus at least two of the following characteristics: Sweating is bilateral and relatively symmetric, it impairs daily activities, it starts before the age of 25 with at least one episode per week (many patients have it daily), a family history of idiopathic hyperhidrosis is present, and focal sweating does not occur during sleep.

Secondary hyperhidrosis can be linked to other conditions, such as a spinal column injury, Dr. Hightower noted.

The first step on the treatment ladder is topical 20% aluminum chloride, which is available over the counter. This should be applied nightly for 1 week then every 1-2 weeks, Dr. Hightower recommended. All of his patients with hyperhidrosis have had at least one trial of this treatment.

The next option is daily topical treatment with 2.4% glycopyrronium tosylate (Qbrexza) cloths, approved by the Food and Drug Administration in 2018 for primary axillary hyperhidrosis in patients aged 9 and older. According to the prescribing information, dry mouth was by far the most common treatment-associated adverse effect in clinical trials (24% versus almost 6% among those on vehicle). As for skin reactions, erythema occurred in about 17% of both the intervention and vehicle groups, and burning/stinging occurred in 14% of those on treatment and almost 17% of those on vehicle.

“If they’re not able to get access to the cloths due to [insurance] coverage issues, or they don’t allow them to reach the clinical endpoint desired, then I use an oral daily glycopyrrolate pill,” Dr. Hightower said.

He recommends 1 mg to 6 mg daily of the anticholinergic drug, which has been used off-label for hyperhidrosis for several years. A 2012 study of 31 children with hyperhidrosis, he noted, supported the use of the drug. The retrospective study found that 90% of the patients, at a mean daily dose of 2 mg, experienced improvements, reported as major in 71%. In addition, patients experienced improvement within hours of taking the medication, and benefits disappeared within a day of stopping the medication. In the study, patients were on the treatment for an average of 2.1 years, and 29% experienced side effects, which were dose related; the most common were dry mouth in 26% and dry eyes in 10%.

According to goodrx.com, a month’s supply of 2 mg of the drug costs as little as $13 with a discount or coupon.

The next steps in treatment are procedural interventions such as microwave-based therapies.

Dr. Hightower said that patients should be advised that treatment may take years, and to encourage them to return for follow-up. He suggested this helpful message: “We’re still trying to find the best treatment for you, and we’ll need to see you back in the office.”
 

Hidradenitis suppurativa

Dr. Hightower said that too often, HS goes undiagnosed for a significant period of time, preventing patients from seeing a dermatologist for treatment. Hallmarks of HS include inflammatory nodules, abscesses, and scarring, he said. “It can be disfiguring, painful, embarrassing, and associated with significantly decreased quality of life. Early recognition in terms of making and solidifying the diagnosis is important so we can prevent further worsening of the disease.”

The goal of treatment include preventing scars and unnecessary emergency department visits, and stopping flares from worsening, Dr. Hightower said. For specifics, he pointed to clinical management guidelines released by the United States and Canadian hidradenitis suppurativa foundations in 2019.

Make sure to set individualized treatment goals and understand the impact of treatment on the patient’s interactions with family, school, and peers, he said. And keep in mind that “parent-defined goals may be different from patient-defined goals.”

Dr. Hightower reported no relevant disclosures. MedscapeLive and this news organization are owned by the same parent company

A wide variety of medications exists for treating hyperhidrosis, a dermatologist told colleagues, but before prescribing anything to a pediatric patient, he recommended, ask the patient a simple question: “What bothers you the most?”

The answer will provide guidance for developing a step-by-step treatment strategy and help provide the patient “a set of realistic expectations in terms of what the response will look like,” George Hightower, MD, PhD, a pediatric dermatologist at Rady Children’s Hospital and the University of California, San Diego, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

A similar question-based approach will help guide therapy for patients with hidradenitis suppurativa (HS), he said.

With regards to hyperhidrosis, Dr. Hightower said that patients most commonly complain that their underarms are too smelly, too sweaty, and red, itchy, or painful. Causes, he said, can include irritation/contact dermatitis, folliculitis, and seborrheic dermatitis, as well as hyperhidrosis or HS.

Primary focal axillary hyperhidrosis is defined as focal, visible, excessive sweating for at least 6 months without an apparent cause plus at least two of the following characteristics: Sweating is bilateral and relatively symmetric, it impairs daily activities, it starts before the age of 25 with at least one episode per week (many patients have it daily), a family history of idiopathic hyperhidrosis is present, and focal sweating does not occur during sleep.

Secondary hyperhidrosis can be linked to other conditions, such as a spinal column injury, Dr. Hightower noted.

The first step on the treatment ladder is topical 20% aluminum chloride, which is available over the counter. This should be applied nightly for 1 week then every 1-2 weeks, Dr. Hightower recommended. All of his patients with hyperhidrosis have had at least one trial of this treatment.

The next option is daily topical treatment with 2.4% glycopyrronium tosylate (Qbrexza) cloths, approved by the Food and Drug Administration in 2018 for primary axillary hyperhidrosis in patients aged 9 and older. According to the prescribing information, dry mouth was by far the most common treatment-associated adverse effect in clinical trials (24% versus almost 6% among those on vehicle). As for skin reactions, erythema occurred in about 17% of both the intervention and vehicle groups, and burning/stinging occurred in 14% of those on treatment and almost 17% of those on vehicle.

“If they’re not able to get access to the cloths due to [insurance] coverage issues, or they don’t allow them to reach the clinical endpoint desired, then I use an oral daily glycopyrrolate pill,” Dr. Hightower said.

He recommends 1 mg to 6 mg daily of the anticholinergic drug, which has been used off-label for hyperhidrosis for several years. A 2012 study of 31 children with hyperhidrosis, he noted, supported the use of the drug. The retrospective study found that 90% of the patients, at a mean daily dose of 2 mg, experienced improvements, reported as major in 71%. In addition, patients experienced improvement within hours of taking the medication, and benefits disappeared within a day of stopping the medication. In the study, patients were on the treatment for an average of 2.1 years, and 29% experienced side effects, which were dose related; the most common were dry mouth in 26% and dry eyes in 10%.

According to goodrx.com, a month’s supply of 2 mg of the drug costs as little as $13 with a discount or coupon.

The next steps in treatment are procedural interventions such as microwave-based therapies.

Dr. Hightower said that patients should be advised that treatment may take years, and to encourage them to return for follow-up. He suggested this helpful message: “We’re still trying to find the best treatment for you, and we’ll need to see you back in the office.”
 

Hidradenitis suppurativa

Dr. Hightower said that too often, HS goes undiagnosed for a significant period of time, preventing patients from seeing a dermatologist for treatment. Hallmarks of HS include inflammatory nodules, abscesses, and scarring, he said. “It can be disfiguring, painful, embarrassing, and associated with significantly decreased quality of life. Early recognition in terms of making and solidifying the diagnosis is important so we can prevent further worsening of the disease.”

The goal of treatment include preventing scars and unnecessary emergency department visits, and stopping flares from worsening, Dr. Hightower said. For specifics, he pointed to clinical management guidelines released by the United States and Canadian hidradenitis suppurativa foundations in 2019.

Make sure to set individualized treatment goals and understand the impact of treatment on the patient’s interactions with family, school, and peers, he said. And keep in mind that “parent-defined goals may be different from patient-defined goals.”

Dr. Hightower reported no relevant disclosures. MedscapeLive and this news organization are owned by the same parent company

A wide variety of medications exists for treating hyperhidrosis, a dermatologist told colleagues, but before prescribing anything to a pediatric patient, he recommended, ask the patient a simple question: “What bothers you the most?”

The answer will provide guidance for developing a step-by-step treatment strategy and help provide the patient “a set of realistic expectations in terms of what the response will look like,” George Hightower, MD, PhD, a pediatric dermatologist at Rady Children’s Hospital and the University of California, San Diego, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

A similar question-based approach will help guide therapy for patients with hidradenitis suppurativa (HS), he said.

With regards to hyperhidrosis, Dr. Hightower said that patients most commonly complain that their underarms are too smelly, too sweaty, and red, itchy, or painful. Causes, he said, can include irritation/contact dermatitis, folliculitis, and seborrheic dermatitis, as well as hyperhidrosis or HS.

Primary focal axillary hyperhidrosis is defined as focal, visible, excessive sweating for at least 6 months without an apparent cause plus at least two of the following characteristics: Sweating is bilateral and relatively symmetric, it impairs daily activities, it starts before the age of 25 with at least one episode per week (many patients have it daily), a family history of idiopathic hyperhidrosis is present, and focal sweating does not occur during sleep.

Secondary hyperhidrosis can be linked to other conditions, such as a spinal column injury, Dr. Hightower noted.

The first step on the treatment ladder is topical 20% aluminum chloride, which is available over the counter. This should be applied nightly for 1 week then every 1-2 weeks, Dr. Hightower recommended. All of his patients with hyperhidrosis have had at least one trial of this treatment.

The next option is daily topical treatment with 2.4% glycopyrronium tosylate (Qbrexza) cloths, approved by the Food and Drug Administration in 2018 for primary axillary hyperhidrosis in patients aged 9 and older. According to the prescribing information, dry mouth was by far the most common treatment-associated adverse effect in clinical trials (24% versus almost 6% among those on vehicle). As for skin reactions, erythema occurred in about 17% of both the intervention and vehicle groups, and burning/stinging occurred in 14% of those on treatment and almost 17% of those on vehicle.

“If they’re not able to get access to the cloths due to [insurance] coverage issues, or they don’t allow them to reach the clinical endpoint desired, then I use an oral daily glycopyrrolate pill,” Dr. Hightower said.

He recommends 1 mg to 6 mg daily of the anticholinergic drug, which has been used off-label for hyperhidrosis for several years. A 2012 study of 31 children with hyperhidrosis, he noted, supported the use of the drug. The retrospective study found that 90% of the patients, at a mean daily dose of 2 mg, experienced improvements, reported as major in 71%. In addition, patients experienced improvement within hours of taking the medication, and benefits disappeared within a day of stopping the medication. In the study, patients were on the treatment for an average of 2.1 years, and 29% experienced side effects, which were dose related; the most common were dry mouth in 26% and dry eyes in 10%.

According to goodrx.com, a month’s supply of 2 mg of the drug costs as little as $13 with a discount or coupon.

The next steps in treatment are procedural interventions such as microwave-based therapies.

Dr. Hightower said that patients should be advised that treatment may take years, and to encourage them to return for follow-up. He suggested this helpful message: “We’re still trying to find the best treatment for you, and we’ll need to see you back in the office.”
 

Hidradenitis suppurativa

Dr. Hightower said that too often, HS goes undiagnosed for a significant period of time, preventing patients from seeing a dermatologist for treatment. Hallmarks of HS include inflammatory nodules, abscesses, and scarring, he said. “It can be disfiguring, painful, embarrassing, and associated with significantly decreased quality of life. Early recognition in terms of making and solidifying the diagnosis is important so we can prevent further worsening of the disease.”

The goal of treatment include preventing scars and unnecessary emergency department visits, and stopping flares from worsening, Dr. Hightower said. For specifics, he pointed to clinical management guidelines released by the United States and Canadian hidradenitis suppurativa foundations in 2019.

Make sure to set individualized treatment goals and understand the impact of treatment on the patient’s interactions with family, school, and peers, he said. And keep in mind that “parent-defined goals may be different from patient-defined goals.”

Dr. Hightower reported no relevant disclosures. MedscapeLive and this news organization are owned by the same parent company

A novel minimal monitoring (MINMON) approach to hepatitis C virus (HCV) treatment was safe and achieved sustained virology response (SVR) compared to current clinical standards in treatment-naive patients without evidence of decompensated cirrhosis, according to a recent study.

©Jezperklauzen/ThinkStock

“This model may allow for HCV elimination, while minimizing resource use and face-to-face contact,” said investigator Sunil S. Solomon, MBBS, PhD, of Johns Hopkins University in Baltimore. “The COVID-19 pandemic has highlighted the urgent need for simple and safe models of HCV [care] delivery.”

Dr. Solomon described the new approach to HCV treatment during a presentation at this year’s Conference on Retroviruses and Opportunistic Infections virtual meeting.
 

Study design

ACTG A5360 was an international, single-arm, open-label, phase 4 trial that enrolled 400 patients across 38 treatment sites.

The researchers evaluated the efficacy and safety of the MINMON approach in treatment-naive individuals who had no evidence of decompensated cirrhosis. Study participants received a fixed-dose, single-tablet regimen of sofosbuvir 400 mg/velpatasvir 100 mg once daily for 12 weeks.

The MINMON approach comprised four key elements: no pretreatment genotyping, all tablets dispensed at study entry, no scheduled on-treatment clinic visits/labs, and two remote contacts at weeks 4 (adherence evaluation) and 22 (scheduled SVR visit). Unplanned visits for patients concerns were permitted.

Key eligibility criteria included active HCV infection (HCV RNA > 1,000 IU/mL) and no prior HCV treatment history. Persons with HIV coinfection (50% or less of sample) and compensated cirrhosis (20% or less of sample) were also eligible. Persons with chronic hepatitis B virus (HBV) infection and decompensated cirrhosis were excluded.

The primary efficacy endpoint was SVR, defined as HCV RNA less than the lower limit of quantification in the first sample at least 22 weeks post treatment initiation. The primary safety endpoint was any serious adverse events (AEs) occurring between treatment initiation and week 28.
 

Results

Among 400 patients enrolled, 399 (99.8%) were included in the primary efficacy analysis and 397 (99.3%) were included in the safety analysis. The median age of participants was 47 years, and 35% were female sex at birth. At baseline, 166 (42%) patients had HIV coinfection and 34 (9%) had compensated cirrhosis.

After analysis, the researchers found that remote contact was successful at weeks 4 and 22 for 394 (98.7%) and 335 (84.0%) participants, respectively.

In total, 15 (3.8%) participants recorded 21 unplanned visits, 3 (14.3%) of which were due to AEs, none of which were treatment related. Three participants reported losing study medications and one participant prematurely discontinued therapy due to an AE.

HCV RNA data at SVR were available for 396 participants. Overall, 379 patients (95.0%) achieved SVR (95% confidence interval [CI], 92.4%-96.7%).

“The study was not powered for SVR by subgroups, which explains why we observed wide confidence intervals in our forest plot,” Dr. Solomon said.

With respect to safety, serious AEs were reported in 14 (3.5%) participants through week 24 visit, none of which were treatment related or resulted in death.

Dr. Solomon acknowledged that a key limitation of the study was the single-arm design. As a result, there was no direct comparison to standard monitoring practices. In addition, these results may not be generalizable to all nonresearch treatment sites.

“The COVID-19 pandemic has required us to pivot clinical programs to minimize in-person contact, and promote more remote approaches, which is really the essence of the MINMON approach,” Dr. Solomon explained.

“There are really wonderful results in the population that was studied, but may reflect a more adherent patient population,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

During a discussion, Dr. Solomon noted that the MINMON approach may be further explored in patients who are actively injecting drugs, as these patients were not well represented in the present study.

Dr. Solomon disclosed financial relationships with Gilead Sciences and Abbott Diagnostics. The study was funded by the National Institutes of Health and Gilead Sciences.

A novel minimal monitoring (MINMON) approach to hepatitis C virus (HCV) treatment was safe and achieved sustained virology response (SVR) compared to current clinical standards in treatment-naive patients without evidence of decompensated cirrhosis, according to a recent study.

©Jezperklauzen/ThinkStock

“This model may allow for HCV elimination, while minimizing resource use and face-to-face contact,” said investigator Sunil S. Solomon, MBBS, PhD, of Johns Hopkins University in Baltimore. “The COVID-19 pandemic has highlighted the urgent need for simple and safe models of HCV [care] delivery.”

Dr. Solomon described the new approach to HCV treatment during a presentation at this year’s Conference on Retroviruses and Opportunistic Infections virtual meeting.
 

Study design

ACTG A5360 was an international, single-arm, open-label, phase 4 trial that enrolled 400 patients across 38 treatment sites.

The researchers evaluated the efficacy and safety of the MINMON approach in treatment-naive individuals who had no evidence of decompensated cirrhosis. Study participants received a fixed-dose, single-tablet regimen of sofosbuvir 400 mg/velpatasvir 100 mg once daily for 12 weeks.

The MINMON approach comprised four key elements: no pretreatment genotyping, all tablets dispensed at study entry, no scheduled on-treatment clinic visits/labs, and two remote contacts at weeks 4 (adherence evaluation) and 22 (scheduled SVR visit). Unplanned visits for patients concerns were permitted.

Key eligibility criteria included active HCV infection (HCV RNA > 1,000 IU/mL) and no prior HCV treatment history. Persons with HIV coinfection (50% or less of sample) and compensated cirrhosis (20% or less of sample) were also eligible. Persons with chronic hepatitis B virus (HBV) infection and decompensated cirrhosis were excluded.

The primary efficacy endpoint was SVR, defined as HCV RNA less than the lower limit of quantification in the first sample at least 22 weeks post treatment initiation. The primary safety endpoint was any serious adverse events (AEs) occurring between treatment initiation and week 28.
 

Results

Among 400 patients enrolled, 399 (99.8%) were included in the primary efficacy analysis and 397 (99.3%) were included in the safety analysis. The median age of participants was 47 years, and 35% were female sex at birth. At baseline, 166 (42%) patients had HIV coinfection and 34 (9%) had compensated cirrhosis.

After analysis, the researchers found that remote contact was successful at weeks 4 and 22 for 394 (98.7%) and 335 (84.0%) participants, respectively.

In total, 15 (3.8%) participants recorded 21 unplanned visits, 3 (14.3%) of which were due to AEs, none of which were treatment related. Three participants reported losing study medications and one participant prematurely discontinued therapy due to an AE.

HCV RNA data at SVR were available for 396 participants. Overall, 379 patients (95.0%) achieved SVR (95% confidence interval [CI], 92.4%-96.7%).

“The study was not powered for SVR by subgroups, which explains why we observed wide confidence intervals in our forest plot,” Dr. Solomon said.

With respect to safety, serious AEs were reported in 14 (3.5%) participants through week 24 visit, none of which were treatment related or resulted in death.

Dr. Solomon acknowledged that a key limitation of the study was the single-arm design. As a result, there was no direct comparison to standard monitoring practices. In addition, these results may not be generalizable to all nonresearch treatment sites.

“The COVID-19 pandemic has required us to pivot clinical programs to minimize in-person contact, and promote more remote approaches, which is really the essence of the MINMON approach,” Dr. Solomon explained.

“There are really wonderful results in the population that was studied, but may reflect a more adherent patient population,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

During a discussion, Dr. Solomon noted that the MINMON approach may be further explored in patients who are actively injecting drugs, as these patients were not well represented in the present study.

Dr. Solomon disclosed financial relationships with Gilead Sciences and Abbott Diagnostics. The study was funded by the National Institutes of Health and Gilead Sciences.

A novel minimal monitoring (MINMON) approach to hepatitis C virus (HCV) treatment was safe and achieved sustained virology response (SVR) compared to current clinical standards in treatment-naive patients without evidence of decompensated cirrhosis, according to a recent study.

©Jezperklauzen/ThinkStock

“This model may allow for HCV elimination, while minimizing resource use and face-to-face contact,” said investigator Sunil S. Solomon, MBBS, PhD, of Johns Hopkins University in Baltimore. “The COVID-19 pandemic has highlighted the urgent need for simple and safe models of HCV [care] delivery.”

Dr. Solomon described the new approach to HCV treatment during a presentation at this year’s Conference on Retroviruses and Opportunistic Infections virtual meeting.
 

Study design

ACTG A5360 was an international, single-arm, open-label, phase 4 trial that enrolled 400 patients across 38 treatment sites.

The researchers evaluated the efficacy and safety of the MINMON approach in treatment-naive individuals who had no evidence of decompensated cirrhosis. Study participants received a fixed-dose, single-tablet regimen of sofosbuvir 400 mg/velpatasvir 100 mg once daily for 12 weeks.

The MINMON approach comprised four key elements: no pretreatment genotyping, all tablets dispensed at study entry, no scheduled on-treatment clinic visits/labs, and two remote contacts at weeks 4 (adherence evaluation) and 22 (scheduled SVR visit). Unplanned visits for patients concerns were permitted.

Key eligibility criteria included active HCV infection (HCV RNA > 1,000 IU/mL) and no prior HCV treatment history. Persons with HIV coinfection (50% or less of sample) and compensated cirrhosis (20% or less of sample) were also eligible. Persons with chronic hepatitis B virus (HBV) infection and decompensated cirrhosis were excluded.

The primary efficacy endpoint was SVR, defined as HCV RNA less than the lower limit of quantification in the first sample at least 22 weeks post treatment initiation. The primary safety endpoint was any serious adverse events (AEs) occurring between treatment initiation and week 28.
 

Results

Among 400 patients enrolled, 399 (99.8%) were included in the primary efficacy analysis and 397 (99.3%) were included in the safety analysis. The median age of participants was 47 years, and 35% were female sex at birth. At baseline, 166 (42%) patients had HIV coinfection and 34 (9%) had compensated cirrhosis.

After analysis, the researchers found that remote contact was successful at weeks 4 and 22 for 394 (98.7%) and 335 (84.0%) participants, respectively.

In total, 15 (3.8%) participants recorded 21 unplanned visits, 3 (14.3%) of which were due to AEs, none of which were treatment related. Three participants reported losing study medications and one participant prematurely discontinued therapy due to an AE.

HCV RNA data at SVR were available for 396 participants. Overall, 379 patients (95.0%) achieved SVR (95% confidence interval [CI], 92.4%-96.7%).

“The study was not powered for SVR by subgroups, which explains why we observed wide confidence intervals in our forest plot,” Dr. Solomon said.

With respect to safety, serious AEs were reported in 14 (3.5%) participants through week 24 visit, none of which were treatment related or resulted in death.

Dr. Solomon acknowledged that a key limitation of the study was the single-arm design. As a result, there was no direct comparison to standard monitoring practices. In addition, these results may not be generalizable to all nonresearch treatment sites.

“The COVID-19 pandemic has required us to pivot clinical programs to minimize in-person contact, and promote more remote approaches, which is really the essence of the MINMON approach,” Dr. Solomon explained.

“There are really wonderful results in the population that was studied, but may reflect a more adherent patient population,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

During a discussion, Dr. Solomon noted that the MINMON approach may be further explored in patients who are actively injecting drugs, as these patients were not well represented in the present study.

Dr. Solomon disclosed financial relationships with Gilead Sciences and Abbott Diagnostics. The study was funded by the National Institutes of Health and Gilead Sciences.

Any level of hepatitis B virus (HBV) viremia was associated with increased hepatocellular carcinoma (HCC) risk in adults with HIV/HBV coinfection, according to new research presented at the Conference on Retroviruses and Opportunistic Infections (Abstract 136).

sarathsasidharan/Thinkstock

“Chronic HBV coinfection is common among people with HIV, but the determinants of HBV-associated HCC are not well characterized,” said presenter H. Nina Kim MD, MSc, of the University of Washington, Seattle. “We sought to identify factors that contribute to HCC development in persons with HIV/HBV coinfection to guide early detection and prevention measures.”

The researchers conducted a longitudinal cohort study within the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), a collaboration of single-site and multisite cohorts throughout the United States and Canada; 22 cohorts from NA-ACCORD were included in the analysis.

Potential HIV and HBV risk factors were examined, including viremia and CD4 percentage, as well as HBV DNA levels. Traditional risk factors for liver disease progression, including age, sex, and heavy alcohol use, were also assessed.

Eligible patients were 18 years of age or older who were followed for at least 6 months, had evidence of chronic HBV, and had HIV RNA or CD4+ cell measurement during this period. Persons with prevalent HCC at baseline were excluded.

The primary outcome was first occurrence of HCC, which was adjudicated by medical chart review and/or cancer registry. Multivariable Cox regression was used to determine adjusted hazard ratios of risk factors.
 

Results

Among 9,383 HIV/HBV-coinfected individuals identified, 8,354 (89%) were included in the analysis. The median age of participants was 43 years and 93.1% were male. Heavy alcohol use (35.3%) and chronic hepatitis C virus (HCV) coinfection (21.6%) were common among participants.

Among 8,354 eligible participants, 115 developed HCC over a median 6.9 years of follow-up (incidence rate, 1.8 events per 1,000 person-years; 95% confidence interval [CI], 1.5-2.1).

Independent risk factors for HCC were chronic HCV coinfection (adjusted hazard ratio [aHR], 1.60 [95% confidence interval, 1.07-2.39]), age 40 years and older (aHR, 2.14 [1.36-3.37]), and heavy alcohol use (aHR, 1.51 [1.03-2.21]); however, time-updated CD4+ percentage less than 14% (aHR, 1.03 [0.56-1.90]) and time-updated HIV RNA level over 500 copies/mL (aHR, 0.88 [0.55-1.41]) were not associated with HCC risk.

In a second model, among 3,054 patients who had HBV DNA measured, the risk of HCC was higher with HBV DNA levels greater than 200 IU/mL (aHR, 2.70 [1.23-5.93]), and the risk was particularly elevated at levels greater than 200,000 IU/mL (aHR, 4.34 [1.72-10.94]).

The researchers also found that the risk of HCC was significantly lower in patients with HBV DNA suppression less than 200 IU/mL receiving HBV-active ART for 1 year or more (aHR, 0.42 [0.24-0.73]). In addition, a dose-response relationship was observed between the duration of suppression and this protective effect.

Dr. Nina Kim acknowledged that a key limitation of the study was inconsistent monitoring of HBV DNA level while patients were on treatment. Furthermore, given the demographics of the cohort, these results may not be generalizable outside of North America.

“Our study was the first to show that any level of HBV viremia using 200 as a threshold of detection was associated with HCC risk in a large regionally diverse cohort of adults outside of Asia,” Dr. Kim said. “To gain maximal protective benefit from antiviral therapy for HCC prevention, sustained and ideally uninterrupted suppression of HBV may be necessary over years.”

“HIV/HBV coinfected patients can take much longer than a year to achieve less than 200 copies on HBV DNA due to their baseline levels, but we still don’t know if HBV therapy intensification could hasten this process,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

Dr. Kim disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institutes of Health, the Centers for Disease Control and Prevention, and the National Cancer Institute.

Any level of hepatitis B virus (HBV) viremia was associated with increased hepatocellular carcinoma (HCC) risk in adults with HIV/HBV coinfection, according to new research presented at the Conference on Retroviruses and Opportunistic Infections (Abstract 136).

sarathsasidharan/Thinkstock

“Chronic HBV coinfection is common among people with HIV, but the determinants of HBV-associated HCC are not well characterized,” said presenter H. Nina Kim MD, MSc, of the University of Washington, Seattle. “We sought to identify factors that contribute to HCC development in persons with HIV/HBV coinfection to guide early detection and prevention measures.”

The researchers conducted a longitudinal cohort study within the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), a collaboration of single-site and multisite cohorts throughout the United States and Canada; 22 cohorts from NA-ACCORD were included in the analysis.

Potential HIV and HBV risk factors were examined, including viremia and CD4 percentage, as well as HBV DNA levels. Traditional risk factors for liver disease progression, including age, sex, and heavy alcohol use, were also assessed.

Eligible patients were 18 years of age or older who were followed for at least 6 months, had evidence of chronic HBV, and had HIV RNA or CD4+ cell measurement during this period. Persons with prevalent HCC at baseline were excluded.

The primary outcome was first occurrence of HCC, which was adjudicated by medical chart review and/or cancer registry. Multivariable Cox regression was used to determine adjusted hazard ratios of risk factors.
 

Results

Among 9,383 HIV/HBV-coinfected individuals identified, 8,354 (89%) were included in the analysis. The median age of participants was 43 years and 93.1% were male. Heavy alcohol use (35.3%) and chronic hepatitis C virus (HCV) coinfection (21.6%) were common among participants.

Among 8,354 eligible participants, 115 developed HCC over a median 6.9 years of follow-up (incidence rate, 1.8 events per 1,000 person-years; 95% confidence interval [CI], 1.5-2.1).

Independent risk factors for HCC were chronic HCV coinfection (adjusted hazard ratio [aHR], 1.60 [95% confidence interval, 1.07-2.39]), age 40 years and older (aHR, 2.14 [1.36-3.37]), and heavy alcohol use (aHR, 1.51 [1.03-2.21]); however, time-updated CD4+ percentage less than 14% (aHR, 1.03 [0.56-1.90]) and time-updated HIV RNA level over 500 copies/mL (aHR, 0.88 [0.55-1.41]) were not associated with HCC risk.

In a second model, among 3,054 patients who had HBV DNA measured, the risk of HCC was higher with HBV DNA levels greater than 200 IU/mL (aHR, 2.70 [1.23-5.93]), and the risk was particularly elevated at levels greater than 200,000 IU/mL (aHR, 4.34 [1.72-10.94]).

The researchers also found that the risk of HCC was significantly lower in patients with HBV DNA suppression less than 200 IU/mL receiving HBV-active ART for 1 year or more (aHR, 0.42 [0.24-0.73]). In addition, a dose-response relationship was observed between the duration of suppression and this protective effect.

Dr. Nina Kim acknowledged that a key limitation of the study was inconsistent monitoring of HBV DNA level while patients were on treatment. Furthermore, given the demographics of the cohort, these results may not be generalizable outside of North America.

“Our study was the first to show that any level of HBV viremia using 200 as a threshold of detection was associated with HCC risk in a large regionally diverse cohort of adults outside of Asia,” Dr. Kim said. “To gain maximal protective benefit from antiviral therapy for HCC prevention, sustained and ideally uninterrupted suppression of HBV may be necessary over years.”

“HIV/HBV coinfected patients can take much longer than a year to achieve less than 200 copies on HBV DNA due to their baseline levels, but we still don’t know if HBV therapy intensification could hasten this process,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

Dr. Kim disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institutes of Health, the Centers for Disease Control and Prevention, and the National Cancer Institute.

Any level of hepatitis B virus (HBV) viremia was associated with increased hepatocellular carcinoma (HCC) risk in adults with HIV/HBV coinfection, according to new research presented at the Conference on Retroviruses and Opportunistic Infections (Abstract 136).

sarathsasidharan/Thinkstock

“Chronic HBV coinfection is common among people with HIV, but the determinants of HBV-associated HCC are not well characterized,” said presenter H. Nina Kim MD, MSc, of the University of Washington, Seattle. “We sought to identify factors that contribute to HCC development in persons with HIV/HBV coinfection to guide early detection and prevention measures.”

The researchers conducted a longitudinal cohort study within the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), a collaboration of single-site and multisite cohorts throughout the United States and Canada; 22 cohorts from NA-ACCORD were included in the analysis.

Potential HIV and HBV risk factors were examined, including viremia and CD4 percentage, as well as HBV DNA levels. Traditional risk factors for liver disease progression, including age, sex, and heavy alcohol use, were also assessed.

Eligible patients were 18 years of age or older who were followed for at least 6 months, had evidence of chronic HBV, and had HIV RNA or CD4+ cell measurement during this period. Persons with prevalent HCC at baseline were excluded.

The primary outcome was first occurrence of HCC, which was adjudicated by medical chart review and/or cancer registry. Multivariable Cox regression was used to determine adjusted hazard ratios of risk factors.
 

Results

Among 9,383 HIV/HBV-coinfected individuals identified, 8,354 (89%) were included in the analysis. The median age of participants was 43 years and 93.1% were male. Heavy alcohol use (35.3%) and chronic hepatitis C virus (HCV) coinfection (21.6%) were common among participants.

Among 8,354 eligible participants, 115 developed HCC over a median 6.9 years of follow-up (incidence rate, 1.8 events per 1,000 person-years; 95% confidence interval [CI], 1.5-2.1).

Independent risk factors for HCC were chronic HCV coinfection (adjusted hazard ratio [aHR], 1.60 [95% confidence interval, 1.07-2.39]), age 40 years and older (aHR, 2.14 [1.36-3.37]), and heavy alcohol use (aHR, 1.51 [1.03-2.21]); however, time-updated CD4+ percentage less than 14% (aHR, 1.03 [0.56-1.90]) and time-updated HIV RNA level over 500 copies/mL (aHR, 0.88 [0.55-1.41]) were not associated with HCC risk.

In a second model, among 3,054 patients who had HBV DNA measured, the risk of HCC was higher with HBV DNA levels greater than 200 IU/mL (aHR, 2.70 [1.23-5.93]), and the risk was particularly elevated at levels greater than 200,000 IU/mL (aHR, 4.34 [1.72-10.94]).

The researchers also found that the risk of HCC was significantly lower in patients with HBV DNA suppression less than 200 IU/mL receiving HBV-active ART for 1 year or more (aHR, 0.42 [0.24-0.73]). In addition, a dose-response relationship was observed between the duration of suppression and this protective effect.

Dr. Nina Kim acknowledged that a key limitation of the study was inconsistent monitoring of HBV DNA level while patients were on treatment. Furthermore, given the demographics of the cohort, these results may not be generalizable outside of North America.

“Our study was the first to show that any level of HBV viremia using 200 as a threshold of detection was associated with HCC risk in a large regionally diverse cohort of adults outside of Asia,” Dr. Kim said. “To gain maximal protective benefit from antiviral therapy for HCC prevention, sustained and ideally uninterrupted suppression of HBV may be necessary over years.”

“HIV/HBV coinfected patients can take much longer than a year to achieve less than 200 copies on HBV DNA due to their baseline levels, but we still don’t know if HBV therapy intensification could hasten this process,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

Dr. Kim disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institutes of Health, the Centers for Disease Control and Prevention, and the National Cancer Institute.

Multiple sclerosis (MS) affects Whites, African Americans, and Hispanics differently, a new study finds, and there are big gaps in how they respond to disease-modifying therapies (DMTs).

“Hispanics and African Americans develop a more severe disease course and accumulate more MS-related disability over time despite similar sociodemographic backgrounds and similar patterns of DMT use throughout their disease, suggesting that socioeconomic status and access to health care may not be the main determinants of health,” said neurologist Carlos Pérez, MD, of the University of Texas Health Science Center, Houston. He spoke at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis and in a follow-up interview.

“In addition,” Dr. Pérez said, “therapeutic responses to individual DMTs, as well as tolerance and side-effect profiles, are also variable among racial/ethnic groups.”

The researchers tracked 150 patients with MS at the University of Texas Health Science Center – 50 Whites, 50 African American, and 50 Hispanic – who were age and gender matched. The average age of the subjects was 45, and 74% of those in each group were women.

While educational levels between the groups were similar, African Americans had a much higher rate of lost employment because of disability (38%) than Hispanics (19%) and Whites (15%, P = .02). Fifty-seven patients (38%) needed escalation of therapy, and 63% were African American.

About 30% of subjects switched DMTs because of intolerance/adverse events, and 47% of those were African American. Interferons most commonly caused adverse effects in African Americans (61%), and Whites were the most likely to not tolerate glatiramer acetate (39%) than Hispanics (8%) and African Americans (13%).

What might be behind the disparities? “It is possible that genetic factors may play a greater role than previously thought. A recent study reported that Hispanic and African American patients with MS have higher levels of peripheral blood plasmablasts, which may provide indirect evidence for potential biological mechanisms underlying racial and clinical disparities in MS,” Dr. Pérez said. “These mechanisms appear to involve higher degrees of inflammation in the central nervous system. This may explain why African Americans may respond better to higher-efficacy therapies initially, when inflammatory processes predominate MS-related pathology, rather than at later stages of the disease when inflammation plays a less prominent role. Neurologists should consider higher-efficacy DMT as first line. We have begun to do this in our practice.”

Dr. Pérez said the findings offer other lessons. “Neurologists should consider that Caucasian patients tolerate glatiramer acetate less frequently, compared with other racial groups, and potentially consider using alternative DMTs unless the benefits outweigh the risks, such as during pregnancy.”

He also noted that African Americans treated with oral DMTs at baseline were more likely to develop worsening disability over time. “This argues in favor of infusion therapies as first-line treatment,” he said, adding that more Hispanics with MS were not on treatment – or discontinued treatment – compared with Whites and African Americans.
 

Close patient monitoring is key

Atlanta-area neurologist Mitzi Joi Williams, MD, who was asked to comment on the study findings, said in an interview that it “adds to the body of real-world evidence to assist understanding of MS in minority populations.”

She noted that African American patients who started on infusions appeared to be more stable. “There are a great deal of questions surrounding starting patients on injectables versus higher-efficacy therapy initially to prevent disability and this may lend credence to the need for closer examination of initial therapy for these patients. It is important to closely monitor patients and consider a switch in DMT if there is any clinical or radiologic progression, especially for African American and Hispanic patients since there is a great deal of data to suggest they may have more aggressive disease.”

Moving forward, more research like this is needed, she said. “Patients did all have insurance and were largely educated, but there could be other social determinants of health – i.e., transportation, lapses in insurance, or technology barriers – that may have led to worse outcomes.”

No study funding was reported, and Dr. Pérez reported no disclosures. Dr. Williams disclosed research support from EMD Serono, Genentech, and Novartis and advisory committee/consultant relationships with AbbVie, Biogen Idec, Bristol-Myers Squibb, EMD Serono, Genentech, Novartis, and Sanofi Genzyme.

Multiple sclerosis (MS) affects Whites, African Americans, and Hispanics differently, a new study finds, and there are big gaps in how they respond to disease-modifying therapies (DMTs).

“Hispanics and African Americans develop a more severe disease course and accumulate more MS-related disability over time despite similar sociodemographic backgrounds and similar patterns of DMT use throughout their disease, suggesting that socioeconomic status and access to health care may not be the main determinants of health,” said neurologist Carlos Pérez, MD, of the University of Texas Health Science Center, Houston. He spoke at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis and in a follow-up interview.

“In addition,” Dr. Pérez said, “therapeutic responses to individual DMTs, as well as tolerance and side-effect profiles, are also variable among racial/ethnic groups.”

The researchers tracked 150 patients with MS at the University of Texas Health Science Center – 50 Whites, 50 African American, and 50 Hispanic – who were age and gender matched. The average age of the subjects was 45, and 74% of those in each group were women.

While educational levels between the groups were similar, African Americans had a much higher rate of lost employment because of disability (38%) than Hispanics (19%) and Whites (15%, P = .02). Fifty-seven patients (38%) needed escalation of therapy, and 63% were African American.

About 30% of subjects switched DMTs because of intolerance/adverse events, and 47% of those were African American. Interferons most commonly caused adverse effects in African Americans (61%), and Whites were the most likely to not tolerate glatiramer acetate (39%) than Hispanics (8%) and African Americans (13%).

What might be behind the disparities? “It is possible that genetic factors may play a greater role than previously thought. A recent study reported that Hispanic and African American patients with MS have higher levels of peripheral blood plasmablasts, which may provide indirect evidence for potential biological mechanisms underlying racial and clinical disparities in MS,” Dr. Pérez said. “These mechanisms appear to involve higher degrees of inflammation in the central nervous system. This may explain why African Americans may respond better to higher-efficacy therapies initially, when inflammatory processes predominate MS-related pathology, rather than at later stages of the disease when inflammation plays a less prominent role. Neurologists should consider higher-efficacy DMT as first line. We have begun to do this in our practice.”

Dr. Pérez said the findings offer other lessons. “Neurologists should consider that Caucasian patients tolerate glatiramer acetate less frequently, compared with other racial groups, and potentially consider using alternative DMTs unless the benefits outweigh the risks, such as during pregnancy.”

He also noted that African Americans treated with oral DMTs at baseline were more likely to develop worsening disability over time. “This argues in favor of infusion therapies as first-line treatment,” he said, adding that more Hispanics with MS were not on treatment – or discontinued treatment – compared with Whites and African Americans.
 

Close patient monitoring is key

Atlanta-area neurologist Mitzi Joi Williams, MD, who was asked to comment on the study findings, said in an interview that it “adds to the body of real-world evidence to assist understanding of MS in minority populations.”

She noted that African American patients who started on infusions appeared to be more stable. “There are a great deal of questions surrounding starting patients on injectables versus higher-efficacy therapy initially to prevent disability and this may lend credence to the need for closer examination of initial therapy for these patients. It is important to closely monitor patients and consider a switch in DMT if there is any clinical or radiologic progression, especially for African American and Hispanic patients since there is a great deal of data to suggest they may have more aggressive disease.”

Moving forward, more research like this is needed, she said. “Patients did all have insurance and were largely educated, but there could be other social determinants of health – i.e., transportation, lapses in insurance, or technology barriers – that may have led to worse outcomes.”

No study funding was reported, and Dr. Pérez reported no disclosures. Dr. Williams disclosed research support from EMD Serono, Genentech, and Novartis and advisory committee/consultant relationships with AbbVie, Biogen Idec, Bristol-Myers Squibb, EMD Serono, Genentech, Novartis, and Sanofi Genzyme.

Multiple sclerosis (MS) affects Whites, African Americans, and Hispanics differently, a new study finds, and there are big gaps in how they respond to disease-modifying therapies (DMTs).

“Hispanics and African Americans develop a more severe disease course and accumulate more MS-related disability over time despite similar sociodemographic backgrounds and similar patterns of DMT use throughout their disease, suggesting that socioeconomic status and access to health care may not be the main determinants of health,” said neurologist Carlos Pérez, MD, of the University of Texas Health Science Center, Houston. He spoke at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis and in a follow-up interview.

“In addition,” Dr. Pérez said, “therapeutic responses to individual DMTs, as well as tolerance and side-effect profiles, are also variable among racial/ethnic groups.”

The researchers tracked 150 patients with MS at the University of Texas Health Science Center – 50 Whites, 50 African American, and 50 Hispanic – who were age and gender matched. The average age of the subjects was 45, and 74% of those in each group were women.

While educational levels between the groups were similar, African Americans had a much higher rate of lost employment because of disability (38%) than Hispanics (19%) and Whites (15%, P = .02). Fifty-seven patients (38%) needed escalation of therapy, and 63% were African American.

About 30% of subjects switched DMTs because of intolerance/adverse events, and 47% of those were African American. Interferons most commonly caused adverse effects in African Americans (61%), and Whites were the most likely to not tolerate glatiramer acetate (39%) than Hispanics (8%) and African Americans (13%).

What might be behind the disparities? “It is possible that genetic factors may play a greater role than previously thought. A recent study reported that Hispanic and African American patients with MS have higher levels of peripheral blood plasmablasts, which may provide indirect evidence for potential biological mechanisms underlying racial and clinical disparities in MS,” Dr. Pérez said. “These mechanisms appear to involve higher degrees of inflammation in the central nervous system. This may explain why African Americans may respond better to higher-efficacy therapies initially, when inflammatory processes predominate MS-related pathology, rather than at later stages of the disease when inflammation plays a less prominent role. Neurologists should consider higher-efficacy DMT as first line. We have begun to do this in our practice.”

Dr. Pérez said the findings offer other lessons. “Neurologists should consider that Caucasian patients tolerate glatiramer acetate less frequently, compared with other racial groups, and potentially consider using alternative DMTs unless the benefits outweigh the risks, such as during pregnancy.”

He also noted that African Americans treated with oral DMTs at baseline were more likely to develop worsening disability over time. “This argues in favor of infusion therapies as first-line treatment,” he said, adding that more Hispanics with MS were not on treatment – or discontinued treatment – compared with Whites and African Americans.
 

Close patient monitoring is key

Atlanta-area neurologist Mitzi Joi Williams, MD, who was asked to comment on the study findings, said in an interview that it “adds to the body of real-world evidence to assist understanding of MS in minority populations.”

She noted that African American patients who started on infusions appeared to be more stable. “There are a great deal of questions surrounding starting patients on injectables versus higher-efficacy therapy initially to prevent disability and this may lend credence to the need for closer examination of initial therapy for these patients. It is important to closely monitor patients and consider a switch in DMT if there is any clinical or radiologic progression, especially for African American and Hispanic patients since there is a great deal of data to suggest they may have more aggressive disease.”

Moving forward, more research like this is needed, she said. “Patients did all have insurance and were largely educated, but there could be other social determinants of health – i.e., transportation, lapses in insurance, or technology barriers – that may have led to worse outcomes.”

No study funding was reported, and Dr. Pérez reported no disclosures. Dr. Williams disclosed research support from EMD Serono, Genentech, and Novartis and advisory committee/consultant relationships with AbbVie, Biogen Idec, Bristol-Myers Squibb, EMD Serono, Genentech, Novartis, and Sanofi Genzyme.

While they’re extraordinarily expensive, a trio of newly approved medications is providing a variety of effective treatment options for patients with neuromyelitis optica spectrum disorder (NMOSD), a neurologist told colleagues.

“Patients have a choice of different options with different types of action. It’s good news,” said Sean J. Pittock, MD, of the Mayo Clinic in Rochester, Minn. “If you don’t stop the clinical attacks, patients can become very disabled very quickly. These medications have a significant impact in reducing the likelihood of having a clinical relapse. If you can stop the relapses, you certainly can eventually stop most – if not all – of the disability accrual.”

Dr. Pittock spoke at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis and answered follow-up questions in an interview.
 

Treatment advances for NMOSD

NMOSD, also known as NMO, is a relapsing autoimmune inflammatory disorder that causes recurrent optic neuritis and myelitis. It’s a rare disease, affecting 0.5-10 people per 100,000, mostly women.

Several recent trials have supported the use of the drugs eculizumab (Soliris), satralizumab (Enspryng) and inebilizumab (Uplizna) in NMOSD, Dr. Pittock said, and all have received Food and Drug Administration approval to treat the condition over the past 2 years. Dr. Pittock led the PREVENT trial of eculizumab, which showed a 94% reduction of relapse risk versus placebo.

The newly approved drugs are stunningly expensive. According to Dr. Pittock, eculizumab costs $710,000 a year, while inebilizumab runs $393,000 the first year, then $262,000 a year. Satralizumab is $219,000 the first year, then $190,000 a year. Assistance programs are available, Dr. Pittock said, “and we’ve not had any major problems in terms of initiation.”

The cost of rituximab (Rituxan), which has a history of use as an off-label treatment option, is $18,000 a year and dropping, according to Dr. Pittock. There’s also new research on rituximab: In 2020, a small Japanese trial (n = 38) reported prevention of relapses compared with placebo, but Dr. Pittock cautioned that “the placebo patients seem to have a more benign course or more benign phenotypes” than the intervention group.

“There’s no doubt that rituximab works, but does it work as well as the other medications that have been through more of a robust trial process?” he asked. Keep in mind, he added, that perhaps 20%-50% of patients will relapse on rituximab.

Dr. Pittock advised colleagues to consider factors like patient schedules and compliance when choosing a drug. Satralizumab is self-administered monthly, while inebilizumab and rituximab are infused every 6 months.
 

Progress in anti-MOG disease

The trials in NMOSD should spur studies of the drugs in anti–myelin oligodendrocyte glycoprotein (MOG) disease, he said. “I think we’ll see a more rapid move toward phase 3 trials because of the experience with NMO. We will just have to wait and see which medications enter trial.”

Anti-MOG disease, also known as MOG antibody disease (MOGAD) and anti-MOG–associated encephalomyelitis, is caused by anti-MOG antibodies. Optic neuritis is very common, and transverse myelitis can occur.

The condition “actually responds to different drugs than MS and has a different immune pathophysiology,” Dr. Pittock said.

He cautioned colleagues to be aware that “the ability of the antibody to tell you whether or not the patient has the disease is less clear for MOGAD than it is for other diseases. If your patient has a low titer of MOG antibody, and their phenotype really doesn’t look like [MOGAD], you really need to interpret that with significant caution.”

He also highlighted a 2018 report that offers guidance about diagnosis and when MOG-IgC antibody tests are appropriate in CNS demyelinating disease.

Dr. Pittock reported numerous disclosures plus patents issued or pending.

While they’re extraordinarily expensive, a trio of newly approved medications is providing a variety of effective treatment options for patients with neuromyelitis optica spectrum disorder (NMOSD), a neurologist told colleagues.

“Patients have a choice of different options with different types of action. It’s good news,” said Sean J. Pittock, MD, of the Mayo Clinic in Rochester, Minn. “If you don’t stop the clinical attacks, patients can become very disabled very quickly. These medications have a significant impact in reducing the likelihood of having a clinical relapse. If you can stop the relapses, you certainly can eventually stop most – if not all – of the disability accrual.”

Dr. Pittock spoke at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis and answered follow-up questions in an interview.
 

Treatment advances for NMOSD

NMOSD, also known as NMO, is a relapsing autoimmune inflammatory disorder that causes recurrent optic neuritis and myelitis. It’s a rare disease, affecting 0.5-10 people per 100,000, mostly women.

Several recent trials have supported the use of the drugs eculizumab (Soliris), satralizumab (Enspryng) and inebilizumab (Uplizna) in NMOSD, Dr. Pittock said, and all have received Food and Drug Administration approval to treat the condition over the past 2 years. Dr. Pittock led the PREVENT trial of eculizumab, which showed a 94% reduction of relapse risk versus placebo.

The newly approved drugs are stunningly expensive. According to Dr. Pittock, eculizumab costs $710,000 a year, while inebilizumab runs $393,000 the first year, then $262,000 a year. Satralizumab is $219,000 the first year, then $190,000 a year. Assistance programs are available, Dr. Pittock said, “and we’ve not had any major problems in terms of initiation.”

The cost of rituximab (Rituxan), which has a history of use as an off-label treatment option, is $18,000 a year and dropping, according to Dr. Pittock. There’s also new research on rituximab: In 2020, a small Japanese trial (n = 38) reported prevention of relapses compared with placebo, but Dr. Pittock cautioned that “the placebo patients seem to have a more benign course or more benign phenotypes” than the intervention group.

“There’s no doubt that rituximab works, but does it work as well as the other medications that have been through more of a robust trial process?” he asked. Keep in mind, he added, that perhaps 20%-50% of patients will relapse on rituximab.

Dr. Pittock advised colleagues to consider factors like patient schedules and compliance when choosing a drug. Satralizumab is self-administered monthly, while inebilizumab and rituximab are infused every 6 months.
 

Progress in anti-MOG disease

The trials in NMOSD should spur studies of the drugs in anti–myelin oligodendrocyte glycoprotein (MOG) disease, he said. “I think we’ll see a more rapid move toward phase 3 trials because of the experience with NMO. We will just have to wait and see which medications enter trial.”

Anti-MOG disease, also known as MOG antibody disease (MOGAD) and anti-MOG–associated encephalomyelitis, is caused by anti-MOG antibodies. Optic neuritis is very common, and transverse myelitis can occur.

The condition “actually responds to different drugs than MS and has a different immune pathophysiology,” Dr. Pittock said.

He cautioned colleagues to be aware that “the ability of the antibody to tell you whether or not the patient has the disease is less clear for MOGAD than it is for other diseases. If your patient has a low titer of MOG antibody, and their phenotype really doesn’t look like [MOGAD], you really need to interpret that with significant caution.”

He also highlighted a 2018 report that offers guidance about diagnosis and when MOG-IgC antibody tests are appropriate in CNS demyelinating disease.

Dr. Pittock reported numerous disclosures plus patents issued or pending.

While they’re extraordinarily expensive, a trio of newly approved medications is providing a variety of effective treatment options for patients with neuromyelitis optica spectrum disorder (NMOSD), a neurologist told colleagues.

“Patients have a choice of different options with different types of action. It’s good news,” said Sean J. Pittock, MD, of the Mayo Clinic in Rochester, Minn. “If you don’t stop the clinical attacks, patients can become very disabled very quickly. These medications have a significant impact in reducing the likelihood of having a clinical relapse. If you can stop the relapses, you certainly can eventually stop most – if not all – of the disability accrual.”

Dr. Pittock spoke at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis and answered follow-up questions in an interview.
 

Treatment advances for NMOSD

NMOSD, also known as NMO, is a relapsing autoimmune inflammatory disorder that causes recurrent optic neuritis and myelitis. It’s a rare disease, affecting 0.5-10 people per 100,000, mostly women.

Several recent trials have supported the use of the drugs eculizumab (Soliris), satralizumab (Enspryng) and inebilizumab (Uplizna) in NMOSD, Dr. Pittock said, and all have received Food and Drug Administration approval to treat the condition over the past 2 years. Dr. Pittock led the PREVENT trial of eculizumab, which showed a 94% reduction of relapse risk versus placebo.

The newly approved drugs are stunningly expensive. According to Dr. Pittock, eculizumab costs $710,000 a year, while inebilizumab runs $393,000 the first year, then $262,000 a year. Satralizumab is $219,000 the first year, then $190,000 a year. Assistance programs are available, Dr. Pittock said, “and we’ve not had any major problems in terms of initiation.”

The cost of rituximab (Rituxan), which has a history of use as an off-label treatment option, is $18,000 a year and dropping, according to Dr. Pittock. There’s also new research on rituximab: In 2020, a small Japanese trial (n = 38) reported prevention of relapses compared with placebo, but Dr. Pittock cautioned that “the placebo patients seem to have a more benign course or more benign phenotypes” than the intervention group.

“There’s no doubt that rituximab works, but does it work as well as the other medications that have been through more of a robust trial process?” he asked. Keep in mind, he added, that perhaps 20%-50% of patients will relapse on rituximab.

Dr. Pittock advised colleagues to consider factors like patient schedules and compliance when choosing a drug. Satralizumab is self-administered monthly, while inebilizumab and rituximab are infused every 6 months.
 

Progress in anti-MOG disease

The trials in NMOSD should spur studies of the drugs in anti–myelin oligodendrocyte glycoprotein (MOG) disease, he said. “I think we’ll see a more rapid move toward phase 3 trials because of the experience with NMO. We will just have to wait and see which medications enter trial.”

Anti-MOG disease, also known as MOG antibody disease (MOGAD) and anti-MOG–associated encephalomyelitis, is caused by anti-MOG antibodies. Optic neuritis is very common, and transverse myelitis can occur.

The condition “actually responds to different drugs than MS and has a different immune pathophysiology,” Dr. Pittock said.

He cautioned colleagues to be aware that “the ability of the antibody to tell you whether or not the patient has the disease is less clear for MOGAD than it is for other diseases. If your patient has a low titer of MOG antibody, and their phenotype really doesn’t look like [MOGAD], you really need to interpret that with significant caution.”

He also highlighted a 2018 report that offers guidance about diagnosis and when MOG-IgC antibody tests are appropriate in CNS demyelinating disease.

Dr. Pittock reported numerous disclosures plus patents issued or pending.

Nearly one-third of persons with hemophilia had neuropathic pain or altered central pain mechanisms, investigators in a small study found.

Among 30 patients with hemophilia, 9 (30%) had scores of 4 or greater on the 10-point Diabetic Neuropathy 4 (DN4) scale, indicating significant neuropathic pain, reported Nathalie Roussel, PhD, from the University of Antwerp (Belgium), at the annual congress of the European Association for Haemophilia and Allied Disorders.

“The results of this study show us that a large difference exists in pain assessments when we have consecutive sample of patients with hemophilia. These results also show that there are subgroups of patients with altered central pain mechanisms and other subgroups with neuropathic pain, and patients with neuropathic pain have a significantly worse quality of life that is not associated with joint structure and joint function,” she said.

“This is a very good abstract in my opinion, and it deserves more study,” commented hemophilia specialist Rajiv K. Pruthi, MBBS, from the Mayo Clinic in Rochester, Minn., who was not involved in the study.

Structural and functional tests

To get a better understanding of the complexities of ankle pain in persons with hemophilia, Dr. Roussel and colleagues recruited 30 adults followed at their center for moderate or severe hemophilia A or B who were on replacement therapy with factor VIII or factor IX concentrate.

They used MRI without contrast to look for structural alterations in both the talocrural and subtalar joints of both ankles in all patients using the International Prophylaxis Study Group Score, adapted for subtalar joint assessment.

The investigators also used the hemophilia joint health score to assess joint funding, and tests for limits on physical activity, including the Timed Up and Go Test, 2-minute walk test, and Hemophilia Activities Lists.

In addition, they assessed pain with Quantitative Sensory Testing, a noninvasive method for evaluating patient responses to heat, cold, and mechanical pressure. Other measures included questionnaires regarding neuropathic pain and quality of life.

The participants included 23 patients with severe and 3 with moderate hemophilia A, and 1 patient with severe and 3 with moderate hemophilia B. The mean patient age was 39.4 years.

In all, 24 of the 30 patients (80%) were on prophylaxis, and 9 (30%) reported using pain medications; 25 patients reported having some degree of pain.

On MRI, 48/60 (80%) of talocrural joints imaged had pathological findings, as did 41 of 60 (68%) subtalar joints.

“Despite the fact that these patients do not all suffer from ankle joint pain, a lot of them have signs of joint pathology,” Dr. Roussel said.

On the Brief Pain Inventory, only 5 patients had no reported pain, but 14 patients reported either three, five, or six painful locations, and 20 out of 30 patients reported that their ankles were the most affected joints.

Although the sample size was not large enough for statistical comparisons, there were also large variations in pain perception across hemophilia severity.

“This is an important finding, that also patients with moderate hemophilia can have intense pain,” Dr. Roussel said.

On the DN4 questionnaire, nine patients had scores of 4 or greater, indicating that their pain was neuropathic in origin.

When they compared the patients with neuropathic pain with those suffering from nonneuropathic pain, the investigators observed similar structural and joint function between the groups, but significantly worse reported quality of life for patients with neuropathic pain.

“This is a finding that merits further attention,” she commented.

In correlation analyses, the investigators also found that MRI scores did not correlate significantly with either hemophilia joint health score, physical function, participation in activities, or pressure pain thresholds.
 

Why the discrepancies?

Dr. Pruthi said in an interview that he has seen evidence from other studies showing that some patients with hemophilia who were on prophylaxis had MRI evidence of joint damage, while others who used on-demand therapy had none.

“That opens up a whole can of worms as to what are we dealing with here. Why do some patients end up with damage and others don’t?” he asked.

He said that the finding that the origin of pain in a large proportion of patients was neuropathic rather than arthritic in origin was new to him.

“It raises a lot of good questions: maybe we need to be managing pain in these patients with nonnarcotic approaches, and in this day and age with the opioid crisis it’s even more important to do that,” he said.

He hypothesized that degenerative arthritis may irritate nearby nerves, resulting in neuropathic pain.

The study was funded by EAHAD, with support from participating institutions. Dr. Roussel and Dr. Pruthi reported no conflicts of interest to declare.

Nearly one-third of persons with hemophilia had neuropathic pain or altered central pain mechanisms, investigators in a small study found.

Among 30 patients with hemophilia, 9 (30%) had scores of 4 or greater on the 10-point Diabetic Neuropathy 4 (DN4) scale, indicating significant neuropathic pain, reported Nathalie Roussel, PhD, from the University of Antwerp (Belgium), at the annual congress of the European Association for Haemophilia and Allied Disorders.

“The results of this study show us that a large difference exists in pain assessments when we have consecutive sample of patients with hemophilia. These results also show that there are subgroups of patients with altered central pain mechanisms and other subgroups with neuropathic pain, and patients with neuropathic pain have a significantly worse quality of life that is not associated with joint structure and joint function,” she said.

“This is a very good abstract in my opinion, and it deserves more study,” commented hemophilia specialist Rajiv K. Pruthi, MBBS, from the Mayo Clinic in Rochester, Minn., who was not involved in the study.

Structural and functional tests

To get a better understanding of the complexities of ankle pain in persons with hemophilia, Dr. Roussel and colleagues recruited 30 adults followed at their center for moderate or severe hemophilia A or B who were on replacement therapy with factor VIII or factor IX concentrate.

They used MRI without contrast to look for structural alterations in both the talocrural and subtalar joints of both ankles in all patients using the International Prophylaxis Study Group Score, adapted for subtalar joint assessment.

The investigators also used the hemophilia joint health score to assess joint funding, and tests for limits on physical activity, including the Timed Up and Go Test, 2-minute walk test, and Hemophilia Activities Lists.

In addition, they assessed pain with Quantitative Sensory Testing, a noninvasive method for evaluating patient responses to heat, cold, and mechanical pressure. Other measures included questionnaires regarding neuropathic pain and quality of life.

The participants included 23 patients with severe and 3 with moderate hemophilia A, and 1 patient with severe and 3 with moderate hemophilia B. The mean patient age was 39.4 years.

In all, 24 of the 30 patients (80%) were on prophylaxis, and 9 (30%) reported using pain medications; 25 patients reported having some degree of pain.

On MRI, 48/60 (80%) of talocrural joints imaged had pathological findings, as did 41 of 60 (68%) subtalar joints.

“Despite the fact that these patients do not all suffer from ankle joint pain, a lot of them have signs of joint pathology,” Dr. Roussel said.

On the Brief Pain Inventory, only 5 patients had no reported pain, but 14 patients reported either three, five, or six painful locations, and 20 out of 30 patients reported that their ankles were the most affected joints.

Although the sample size was not large enough for statistical comparisons, there were also large variations in pain perception across hemophilia severity.

“This is an important finding, that also patients with moderate hemophilia can have intense pain,” Dr. Roussel said.

On the DN4 questionnaire, nine patients had scores of 4 or greater, indicating that their pain was neuropathic in origin.

When they compared the patients with neuropathic pain with those suffering from nonneuropathic pain, the investigators observed similar structural and joint function between the groups, but significantly worse reported quality of life for patients with neuropathic pain.

“This is a finding that merits further attention,” she commented.

In correlation analyses, the investigators also found that MRI scores did not correlate significantly with either hemophilia joint health score, physical function, participation in activities, or pressure pain thresholds.
 

Why the discrepancies?

Dr. Pruthi said in an interview that he has seen evidence from other studies showing that some patients with hemophilia who were on prophylaxis had MRI evidence of joint damage, while others who used on-demand therapy had none.

“That opens up a whole can of worms as to what are we dealing with here. Why do some patients end up with damage and others don’t?” he asked.

He said that the finding that the origin of pain in a large proportion of patients was neuropathic rather than arthritic in origin was new to him.

“It raises a lot of good questions: maybe we need to be managing pain in these patients with nonnarcotic approaches, and in this day and age with the opioid crisis it’s even more important to do that,” he said.

He hypothesized that degenerative arthritis may irritate nearby nerves, resulting in neuropathic pain.

The study was funded by EAHAD, with support from participating institutions. Dr. Roussel and Dr. Pruthi reported no conflicts of interest to declare.

Nearly one-third of persons with hemophilia had neuropathic pain or altered central pain mechanisms, investigators in a small study found.

Among 30 patients with hemophilia, 9 (30%) had scores of 4 or greater on the 10-point Diabetic Neuropathy 4 (DN4) scale, indicating significant neuropathic pain, reported Nathalie Roussel, PhD, from the University of Antwerp (Belgium), at the annual congress of the European Association for Haemophilia and Allied Disorders.

“The results of this study show us that a large difference exists in pain assessments when we have consecutive sample of patients with hemophilia. These results also show that there are subgroups of patients with altered central pain mechanisms and other subgroups with neuropathic pain, and patients with neuropathic pain have a significantly worse quality of life that is not associated with joint structure and joint function,” she said.

“This is a very good abstract in my opinion, and it deserves more study,” commented hemophilia specialist Rajiv K. Pruthi, MBBS, from the Mayo Clinic in Rochester, Minn., who was not involved in the study.

Structural and functional tests

To get a better understanding of the complexities of ankle pain in persons with hemophilia, Dr. Roussel and colleagues recruited 30 adults followed at their center for moderate or severe hemophilia A or B who were on replacement therapy with factor VIII or factor IX concentrate.

They used MRI without contrast to look for structural alterations in both the talocrural and subtalar joints of both ankles in all patients using the International Prophylaxis Study Group Score, adapted for subtalar joint assessment.

The investigators also used the hemophilia joint health score to assess joint funding, and tests for limits on physical activity, including the Timed Up and Go Test, 2-minute walk test, and Hemophilia Activities Lists.

In addition, they assessed pain with Quantitative Sensory Testing, a noninvasive method for evaluating patient responses to heat, cold, and mechanical pressure. Other measures included questionnaires regarding neuropathic pain and quality of life.

The participants included 23 patients with severe and 3 with moderate hemophilia A, and 1 patient with severe and 3 with moderate hemophilia B. The mean patient age was 39.4 years.

In all, 24 of the 30 patients (80%) were on prophylaxis, and 9 (30%) reported using pain medications; 25 patients reported having some degree of pain.

On MRI, 48/60 (80%) of talocrural joints imaged had pathological findings, as did 41 of 60 (68%) subtalar joints.

“Despite the fact that these patients do not all suffer from ankle joint pain, a lot of them have signs of joint pathology,” Dr. Roussel said.

On the Brief Pain Inventory, only 5 patients had no reported pain, but 14 patients reported either three, five, or six painful locations, and 20 out of 30 patients reported that their ankles were the most affected joints.

Although the sample size was not large enough for statistical comparisons, there were also large variations in pain perception across hemophilia severity.

“This is an important finding, that also patients with moderate hemophilia can have intense pain,” Dr. Roussel said.

On the DN4 questionnaire, nine patients had scores of 4 or greater, indicating that their pain was neuropathic in origin.

When they compared the patients with neuropathic pain with those suffering from nonneuropathic pain, the investigators observed similar structural and joint function between the groups, but significantly worse reported quality of life for patients with neuropathic pain.

“This is a finding that merits further attention,” she commented.

In correlation analyses, the investigators also found that MRI scores did not correlate significantly with either hemophilia joint health score, physical function, participation in activities, or pressure pain thresholds.
 

Why the discrepancies?

Dr. Pruthi said in an interview that he has seen evidence from other studies showing that some patients with hemophilia who were on prophylaxis had MRI evidence of joint damage, while others who used on-demand therapy had none.

“That opens up a whole can of worms as to what are we dealing with here. Why do some patients end up with damage and others don’t?” he asked.

He said that the finding that the origin of pain in a large proportion of patients was neuropathic rather than arthritic in origin was new to him.

“It raises a lot of good questions: maybe we need to be managing pain in these patients with nonnarcotic approaches, and in this day and age with the opioid crisis it’s even more important to do that,” he said.

He hypothesized that degenerative arthritis may irritate nearby nerves, resulting in neuropathic pain.

The study was funded by EAHAD, with support from participating institutions. Dr. Roussel and Dr. Pruthi reported no conflicts of interest to declare.

Type 3 von Willebrand disease (VWD) is rare, but this form of the disease is associated with severe bleeding, particularly in muscles and joints, a bleeding disorders expert said.

“There’s a virtually complete deficiency in von Willebrand factor [in type 3 disease], so usually it’s defined as below 5 or in some studies below 3 IU/dL, but also due to the very low levels of von Willebrand factor, there’s also a very low level of factor VIII,” said Jeroen Eikenboom, MD, PhD, from Leiden (the Netherlands) University Medical Center.

“The inheritance pattern is autosomal recessive, and the prevalence is about 1 in a million,” he said during the annual congress of the European Association for Haemophilia and Allied Disorders.

Erik Adolf von Willenbrand, MD, PhD, first described this form of VWD in a family from the Åland Islands, an autonomous region of Finland. The disease, later discovered to be caused in this family by a cytosine deletion in exon 18 of the von Willebrand factor (VWF) gene, was associated with fatal bleeding events in several family members.

“As VWF is the carrier protein of factor VIII, the very low VWF level leads to a strongly reduced factor VIII level, comparable to the levels seen in mild to moderate hemophilia A. As a consequence, VWD type 3 has the combined characteristics of a primary as well as a secondary hemostasis defect,” Dr. Eikenboom explained in an abstract accompanying his talk.

Compared with VWD type 1 or 2, type 3 VWD is associated with bleeding episodes more commonly seen in patients with hemophilia A, notably mucocutaneous bleeding, bleeding after trauma or during surgery, and bleeding into joints and/or muscles.
 

Treatment

The goals of treatment for patients with type 3 VWD are to correct the dual hemostasis defects of impaired platelet adhesion because of low VWF levels, and the intrinsic coagulation defect because of levels of factor VIII.

Desmopressin is not effective in type 3 VWD, Dr. Eikenboom said, so treatment requires the use of either plasma-derived VWF, with or without factor VIII, or recombinant VWF.

In the United States, the only standalone VWF concentrate approved by the Food and Drug Administration is a recombinant product (Vonvendi), Three other human plasma–derived concentrates containing both VWF and factor VIII are also licensed (Alpanate, Humate-P, Wilate).

Clinicians prescribing the combined factor concentrates need to be aware of differences in pharmacokinetics between the products.

For example, following infusion of Wilate, which has equal amounts of von Willebrand factor and factor VIII, there is an increase in circulation of both von Willebrand factor and factor VIII and a similar decline in each factor over time.

In contrast, following an infusion of Humate-P, which contains lower levels of factor VIII, “interestingly, you see a secondary rise of factor VIII in Humate-P–infused patients, whereas the secondary rise is not visible in the Wilate patients,” he said.

Approximately 22% of patients with type 3 VWD also receive prophylaxis with VWF concentrate, which has been shown to decrease the median annualized bleeding rate from 25% to 6.1%.

Dr. Eikenboom cautioned that 5%-10% of patients with type 3 VWD may develop allo-antibodies against VWF concentrates, which can complicate treatment and carries risk of anaphylactic shock.

“It’s also been mentioned in literature that there may be an association with partial or complete von Willebrand factor gene deletions or nonsense mutations and the development of allo-antibodies,” he said.
 

Prophylaxis burdensome but helpful

Veronica H. Flood, MD, from the Medical College of Wisconsin, Milwaukee, who specializes in the treatment of patients with von Willebrand disease, follows a number of both girls and boys with type 3 VWD.

“Those are the people who will have bleeding into their joints, and for the girls, worse periods than some of those with other types of von Willebrand disease, and it is true that if you want to stop their bleeding, you cannot use desmopressin like we use in most other von Willebrand patients. They will need factor, although for the heavy menstrual bleeding you can use hormones or tranexamic acid – there are some other options for that,” she said in an interview.

She also noted that type 3 von Willebrand disease can be highly variable. For patients with especially frequent joint bleeding, her center recommends prophylaxis.

“Prophylaxis can be very burdensome for patients. You’re talking about IV therapy several times a week, but it’s very helpful for the joint bleeds. Episodic prophylaxis can be very helpful for heavy menstrual bleeding, and we actually have type 2, type 3, and some type 1 patients with bad enough nose bleeds that they end up on prophylaxis,” she said.

Patients with gastrointestinal bleeding are the most challenging to care for, she noted.

“You can put them on factor prophylaxis, but even that isn’t always enough to help some adults with bad GI bleeding, and we’re investigating other options for that,” she said.

Dr. Eikenboom disclosed research support from CSL Behring and honoraria (directed to his institution) for educational activities sponsored by Roche and Celgene. Dr. Flood reported having no conflicts of interest to disclose.

Type 3 von Willebrand disease (VWD) is rare, but this form of the disease is associated with severe bleeding, particularly in muscles and joints, a bleeding disorders expert said.

“There’s a virtually complete deficiency in von Willebrand factor [in type 3 disease], so usually it’s defined as below 5 or in some studies below 3 IU/dL, but also due to the very low levels of von Willebrand factor, there’s also a very low level of factor VIII,” said Jeroen Eikenboom, MD, PhD, from Leiden (the Netherlands) University Medical Center.

“The inheritance pattern is autosomal recessive, and the prevalence is about 1 in a million,” he said during the annual congress of the European Association for Haemophilia and Allied Disorders.

Erik Adolf von Willenbrand, MD, PhD, first described this form of VWD in a family from the Åland Islands, an autonomous region of Finland. The disease, later discovered to be caused in this family by a cytosine deletion in exon 18 of the von Willebrand factor (VWF) gene, was associated with fatal bleeding events in several family members.

“As VWF is the carrier protein of factor VIII, the very low VWF level leads to a strongly reduced factor VIII level, comparable to the levels seen in mild to moderate hemophilia A. As a consequence, VWD type 3 has the combined characteristics of a primary as well as a secondary hemostasis defect,” Dr. Eikenboom explained in an abstract accompanying his talk.

Compared with VWD type 1 or 2, type 3 VWD is associated with bleeding episodes more commonly seen in patients with hemophilia A, notably mucocutaneous bleeding, bleeding after trauma or during surgery, and bleeding into joints and/or muscles.
 

Treatment

The goals of treatment for patients with type 3 VWD are to correct the dual hemostasis defects of impaired platelet adhesion because of low VWF levels, and the intrinsic coagulation defect because of levels of factor VIII.

Desmopressin is not effective in type 3 VWD, Dr. Eikenboom said, so treatment requires the use of either plasma-derived VWF, with or without factor VIII, or recombinant VWF.

In the United States, the only standalone VWF concentrate approved by the Food and Drug Administration is a recombinant product (Vonvendi), Three other human plasma–derived concentrates containing both VWF and factor VIII are also licensed (Alpanate, Humate-P, Wilate).

Clinicians prescribing the combined factor concentrates need to be aware of differences in pharmacokinetics between the products.

For example, following infusion of Wilate, which has equal amounts of von Willebrand factor and factor VIII, there is an increase in circulation of both von Willebrand factor and factor VIII and a similar decline in each factor over time.

In contrast, following an infusion of Humate-P, which contains lower levels of factor VIII, “interestingly, you see a secondary rise of factor VIII in Humate-P–infused patients, whereas the secondary rise is not visible in the Wilate patients,” he said.

Approximately 22% of patients with type 3 VWD also receive prophylaxis with VWF concentrate, which has been shown to decrease the median annualized bleeding rate from 25% to 6.1%.

Dr. Eikenboom cautioned that 5%-10% of patients with type 3 VWD may develop allo-antibodies against VWF concentrates, which can complicate treatment and carries risk of anaphylactic shock.

“It’s also been mentioned in literature that there may be an association with partial or complete von Willebrand factor gene deletions or nonsense mutations and the development of allo-antibodies,” he said.
 

Prophylaxis burdensome but helpful

Veronica H. Flood, MD, from the Medical College of Wisconsin, Milwaukee, who specializes in the treatment of patients with von Willebrand disease, follows a number of both girls and boys with type 3 VWD.

“Those are the people who will have bleeding into their joints, and for the girls, worse periods than some of those with other types of von Willebrand disease, and it is true that if you want to stop their bleeding, you cannot use desmopressin like we use in most other von Willebrand patients. They will need factor, although for the heavy menstrual bleeding you can use hormones or tranexamic acid – there are some other options for that,” she said in an interview.

She also noted that type 3 von Willebrand disease can be highly variable. For patients with especially frequent joint bleeding, her center recommends prophylaxis.

“Prophylaxis can be very burdensome for patients. You’re talking about IV therapy several times a week, but it’s very helpful for the joint bleeds. Episodic prophylaxis can be very helpful for heavy menstrual bleeding, and we actually have type 2, type 3, and some type 1 patients with bad enough nose bleeds that they end up on prophylaxis,” she said.

Patients with gastrointestinal bleeding are the most challenging to care for, she noted.

“You can put them on factor prophylaxis, but even that isn’t always enough to help some adults with bad GI bleeding, and we’re investigating other options for that,” she said.

Dr. Eikenboom disclosed research support from CSL Behring and honoraria (directed to his institution) for educational activities sponsored by Roche and Celgene. Dr. Flood reported having no conflicts of interest to disclose.

Type 3 von Willebrand disease (VWD) is rare, but this form of the disease is associated with severe bleeding, particularly in muscles and joints, a bleeding disorders expert said.

“There’s a virtually complete deficiency in von Willebrand factor [in type 3 disease], so usually it’s defined as below 5 or in some studies below 3 IU/dL, but also due to the very low levels of von Willebrand factor, there’s also a very low level of factor VIII,” said Jeroen Eikenboom, MD, PhD, from Leiden (the Netherlands) University Medical Center.

“The inheritance pattern is autosomal recessive, and the prevalence is about 1 in a million,” he said during the annual congress of the European Association for Haemophilia and Allied Disorders.

Erik Adolf von Willenbrand, MD, PhD, first described this form of VWD in a family from the Åland Islands, an autonomous region of Finland. The disease, later discovered to be caused in this family by a cytosine deletion in exon 18 of the von Willebrand factor (VWF) gene, was associated with fatal bleeding events in several family members.

“As VWF is the carrier protein of factor VIII, the very low VWF level leads to a strongly reduced factor VIII level, comparable to the levels seen in mild to moderate hemophilia A. As a consequence, VWD type 3 has the combined characteristics of a primary as well as a secondary hemostasis defect,” Dr. Eikenboom explained in an abstract accompanying his talk.

Compared with VWD type 1 or 2, type 3 VWD is associated with bleeding episodes more commonly seen in patients with hemophilia A, notably mucocutaneous bleeding, bleeding after trauma or during surgery, and bleeding into joints and/or muscles.
 

Treatment

The goals of treatment for patients with type 3 VWD are to correct the dual hemostasis defects of impaired platelet adhesion because of low VWF levels, and the intrinsic coagulation defect because of levels of factor VIII.

Desmopressin is not effective in type 3 VWD, Dr. Eikenboom said, so treatment requires the use of either plasma-derived VWF, with or without factor VIII, or recombinant VWF.

In the United States, the only standalone VWF concentrate approved by the Food and Drug Administration is a recombinant product (Vonvendi), Three other human plasma–derived concentrates containing both VWF and factor VIII are also licensed (Alpanate, Humate-P, Wilate).

Clinicians prescribing the combined factor concentrates need to be aware of differences in pharmacokinetics between the products.

For example, following infusion of Wilate, which has equal amounts of von Willebrand factor and factor VIII, there is an increase in circulation of both von Willebrand factor and factor VIII and a similar decline in each factor over time.

In contrast, following an infusion of Humate-P, which contains lower levels of factor VIII, “interestingly, you see a secondary rise of factor VIII in Humate-P–infused patients, whereas the secondary rise is not visible in the Wilate patients,” he said.

Approximately 22% of patients with type 3 VWD also receive prophylaxis with VWF concentrate, which has been shown to decrease the median annualized bleeding rate from 25% to 6.1%.

Dr. Eikenboom cautioned that 5%-10% of patients with type 3 VWD may develop allo-antibodies against VWF concentrates, which can complicate treatment and carries risk of anaphylactic shock.

“It’s also been mentioned in literature that there may be an association with partial or complete von Willebrand factor gene deletions or nonsense mutations and the development of allo-antibodies,” he said.
 

Prophylaxis burdensome but helpful

Veronica H. Flood, MD, from the Medical College of Wisconsin, Milwaukee, who specializes in the treatment of patients with von Willebrand disease, follows a number of both girls and boys with type 3 VWD.

“Those are the people who will have bleeding into their joints, and for the girls, worse periods than some of those with other types of von Willebrand disease, and it is true that if you want to stop their bleeding, you cannot use desmopressin like we use in most other von Willebrand patients. They will need factor, although for the heavy menstrual bleeding you can use hormones or tranexamic acid – there are some other options for that,” she said in an interview.

She also noted that type 3 von Willebrand disease can be highly variable. For patients with especially frequent joint bleeding, her center recommends prophylaxis.

“Prophylaxis can be very burdensome for patients. You’re talking about IV therapy several times a week, but it’s very helpful for the joint bleeds. Episodic prophylaxis can be very helpful for heavy menstrual bleeding, and we actually have type 2, type 3, and some type 1 patients with bad enough nose bleeds that they end up on prophylaxis,” she said.

Patients with gastrointestinal bleeding are the most challenging to care for, she noted.

“You can put them on factor prophylaxis, but even that isn’t always enough to help some adults with bad GI bleeding, and we’re investigating other options for that,” she said.

Dr. Eikenboom disclosed research support from CSL Behring and honoraria (directed to his institution) for educational activities sponsored by Roche and Celgene. Dr. Flood reported having no conflicts of interest to disclose.

It’s been a banner year for treatment advances in systemic lupus erythematosus (SLE), with two drugs gaining approval for lupus nephritis while other promising molecules with novel mechanisms of action advanced smartly through the developmental pipeline, speakers agreed at the 2021 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“I think the most important thing in rheumatology in the last year is where we are now with lupus. With two drugs being approved for lupus nephritis, I think that’s really huge as we talk about treat-to-target,” said Alvin F. Wells, MD, PhD, a rheumatologist in Franklin, Wisc.

Martin Bergman, MD, concurred.

“Lupus has been blowing up in the past year. We have two new medications for lupus nephritis, we have two or three new mechanisms of action for therapy. I think that was one of the biggest things in rheumatology in the past year,” said Dr. Bergman, a rheumatologist at Drexel University in Philadelphia and in private practice in Ridley Park, Pa.

Together with Roy Fleischmann, MD, Dr. Wells spotlighted promising new molecules for the treatment of SLE, giant cell arteritis, vasculitis, rheumatoid arthritis, and osteoarthritis.
 

SLE

The two drugs approved in recent months specifically for lupus nephritis are voclosporin (Lupkynis) and belimumab (Benlysta), which has been approved for lupus for a decade. Voclosporin, an oral calcineurin inhibitor, is a modification of cyclosporine offering significant advantages over the older drug: It’s more potent, requires no dose titration, has a better safety profile, and is metabolized more quickly.

“A safer and easier-to-use calcineurin inhibitor is going to be huge,” Dr. Wells predicted.

Up for Food and Drug Administration review in the coming year on the basis of the positive phase 3 TULIP-1 and TULIP-2 trials is anifrolumab, a monoclonal antibody that binds to the type 1 interferon receptor subunit 1d. At 52 weeks in the pooled analysis, one or more SLE flares occurred in 33.6% of patients on anifrolumab and 42.9% of placebo-treated controls.

“This is not a blockbuster, but it’s a worthwhile addition, like belimumab,” according to Dr. Fleischmann, a rheumatologist at the University of Texas, Dallas.

Dr. Wells concurred, with a reservation: In a subgroup analysis of the TULIP trials, anifrolumab wasn’t significantly better than placebo in black patients, who tend to have more severe and tough-to-treat renal disease.

“Anifrolumab doesn’t look as effective as some other agents, and I’d be disinclined to give it to my black patients,” the rheumatologist said.

Dr. Fleischmann was far more enthusiastic about obinutuzumab (Gazyva), a humanized anti-CD20 monoclonal antibody already approved for the treatment of chronic lymphocytic leukemia and follicular lymphoma.

Bruce Jancin/MDedge News

A humanized monoclonal antibody known for now as BIIB059 demonstrated efficacy and was well tolerated in the phase 2 LILAC trial. BIIB059 binds to blood dendritic cell antigen 2 (BDCA2), a receptor specific to plasmacytoid dendritic cells, resulting in decreased production of type 1 interferon and other inflammatory cytokines. The LILAC trial included 132 SLE patients with active arthritis and skin disease who received subcutaneous injections of BIIB059 at 450 mg or placebo every 4 weeks, with an extra dose at week 2. The primary endpoint was met, with an absolute 15-joint reduction in the total number of tender or swollen joints from baseline to week 24 in the BIIB059 group, compared to an 11.6-joint reduction with placebo. In addition, the likelihood of an SRI-4 response at week 24 was 3.49-fold greater with BIIB059 than with placebo.

Dr. Wells noted that the BIIB059 group showed continued improvement from week 12 to week 24, unlike the response pattern seen with many biologics for rheumatoid arthritis, where a plateau is reached by 8-12 weeks.

Vasculitis

The positive results for the C5a receptor inhibitor avacopan for treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in the phase-3 ADVOCATE trial have been hailed by some rheumatologists as a major breakthrough, but Dr. Fleischmann isn’t so sure.

The trial randomized 331 patients to oral avacopan at 30 mg twice daily or oral prednisone, with all patients on either cyclophosphamide or rituximab. Avacopan was noninferior to prednisone in terms of remission at week 26, but superior to prednisone for sustained taper at week 52. The rate of serious adverse events was 45.1% with prednisone and 42.2% in the avacopan arm.

“This is a drug that’s going to be much, much more expensive than prednisone. There were people in our group who were ecstatic that this drug is going to come, but how much it’s going to be used, I don’t know,” Dr. Fleischmann said.

Dr. Wells said cost-benefit analyses will be needed in order to learn if avacopan’s anticipated high sticker price is offset by the cost of serious corticosteroid side effects such as avascular necrosis.
 

Giant cell arteritis

Mavrilimumab is a human monoclonal antibody that inhibits human granulocyte macrophage colony stimulating factor receptor alpha. It demonstrated impressive efficacy in a phase 2, double-blind, randomized, placebo-controlled trial conducted in 70 patients with biopsy-confirmed giant cell arteritis. Participants were on corticosteroids until they went into remission and were then randomized to mavrilimumab or placebo, with the steroids stopped. By week 26, 19% of patients in the mavrilimumab arm had flared, as compared to 46.4% of controls.

“This is a game changer,” Dr. Wells declared. “I struggle with these patients because I can’t get the IL-6 drugs approved for them. I need something else.”

Dr. Fleischmann has a good idea how he’ll use mavrilimumab, if it wins approval: “I think this is clearly a drug you would use in a patient you can’t get off steroids and you’re having all the steroid toxicity. I don’t know that you’d use it right away.”

Osteoarthritis

Dr. Fleischmann predicted that tanezumab, a monoclonal antibody directed against nerve growth factor, will win FDA approval in 2021 for the treatment of osteoarthritis pain in patients with an inadequate response or intolerance to standard-of-care NSAIDs and opioids. But he cautioned his colleagues not to expect too much from the biologic, which has a long and checkered developmental history.

“It works better than placebo. It does not work better than an NSAID or an opioid. So it should be reasonable in patients who cannot take an NSAID or cannot or will not take an opioid,” he said.

There are safety issues to be aware of with tanezumab, he added: clinically significant increased risks of peripheral neuropathy and joint space narrowing.
 

Rheumatoid arthritis

Dr. Wells thought one of the most interesting novel therapies for RA in the past year didn’t involve a pharmaceutical, but rather noninvasive auricular branch stimulation of the vagus nerve. He cited an open-label, 12-week, uncontrolled study in 27 patients with active RA who wore an ear clip for vagal nerve stimulation for 12 weeks. The mean Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) – the primary study endpoint – improved from 6.30 at baseline to 3.76 at week 12. The number of tender joints dropped from 12.17 to 4.7, while the swollen joint count went from 7.0 to 3.44. Pain scores improved from 75.23 to 43.3. Scores on the Health Assessment Questionnaire Disability Index improved from 1.59 to 1.05. There was no significant change in CRP. All in all, a modest clinical effect achieved noninvasively.

“The thing that did it for me was the effect on MRI from baseline: decreased synovitis, osteitis, and bone erosion scores,” Dr. Wells said. “This is noninvasive, so patients who want to do medical marijuana or CBD can put an earring on their auricular nerve.”

Dr. Fleischmann scoffed. “An open-label study, 27 patients? Let me see the real study,” he quipped.

Dr. Fleischmann reported receiving clinical trial research grants from and serving as a consultant to more than a dozen pharmaceutical companies. Dr. Wells serves as a consultant to MiCare Path.

bjancin@mdedge.com

It’s been a banner year for treatment advances in systemic lupus erythematosus (SLE), with two drugs gaining approval for lupus nephritis while other promising molecules with novel mechanisms of action advanced smartly through the developmental pipeline, speakers agreed at the 2021 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“I think the most important thing in rheumatology in the last year is where we are now with lupus. With two drugs being approved for lupus nephritis, I think that’s really huge as we talk about treat-to-target,” said Alvin F. Wells, MD, PhD, a rheumatologist in Franklin, Wisc.

Martin Bergman, MD, concurred.

“Lupus has been blowing up in the past year. We have two new medications for lupus nephritis, we have two or three new mechanisms of action for therapy. I think that was one of the biggest things in rheumatology in the past year,” said Dr. Bergman, a rheumatologist at Drexel University in Philadelphia and in private practice in Ridley Park, Pa.

Together with Roy Fleischmann, MD, Dr. Wells spotlighted promising new molecules for the treatment of SLE, giant cell arteritis, vasculitis, rheumatoid arthritis, and osteoarthritis.
 

SLE

The two drugs approved in recent months specifically for lupus nephritis are voclosporin (Lupkynis) and belimumab (Benlysta), which has been approved for lupus for a decade. Voclosporin, an oral calcineurin inhibitor, is a modification of cyclosporine offering significant advantages over the older drug: It’s more potent, requires no dose titration, has a better safety profile, and is metabolized more quickly.

“A safer and easier-to-use calcineurin inhibitor is going to be huge,” Dr. Wells predicted.

Up for Food and Drug Administration review in the coming year on the basis of the positive phase 3 TULIP-1 and TULIP-2 trials is anifrolumab, a monoclonal antibody that binds to the type 1 interferon receptor subunit 1d. At 52 weeks in the pooled analysis, one or more SLE flares occurred in 33.6% of patients on anifrolumab and 42.9% of placebo-treated controls.

“This is not a blockbuster, but it’s a worthwhile addition, like belimumab,” according to Dr. Fleischmann, a rheumatologist at the University of Texas, Dallas.

Dr. Wells concurred, with a reservation: In a subgroup analysis of the TULIP trials, anifrolumab wasn’t significantly better than placebo in black patients, who tend to have more severe and tough-to-treat renal disease.

“Anifrolumab doesn’t look as effective as some other agents, and I’d be disinclined to give it to my black patients,” the rheumatologist said.

Dr. Fleischmann was far more enthusiastic about obinutuzumab (Gazyva), a humanized anti-CD20 monoclonal antibody already approved for the treatment of chronic lymphocytic leukemia and follicular lymphoma.

Bruce Jancin/MDedge News

A humanized monoclonal antibody known for now as BIIB059 demonstrated efficacy and was well tolerated in the phase 2 LILAC trial. BIIB059 binds to blood dendritic cell antigen 2 (BDCA2), a receptor specific to plasmacytoid dendritic cells, resulting in decreased production of type 1 interferon and other inflammatory cytokines. The LILAC trial included 132 SLE patients with active arthritis and skin disease who received subcutaneous injections of BIIB059 at 450 mg or placebo every 4 weeks, with an extra dose at week 2. The primary endpoint was met, with an absolute 15-joint reduction in the total number of tender or swollen joints from baseline to week 24 in the BIIB059 group, compared to an 11.6-joint reduction with placebo. In addition, the likelihood of an SRI-4 response at week 24 was 3.49-fold greater with BIIB059 than with placebo.

Dr. Wells noted that the BIIB059 group showed continued improvement from week 12 to week 24, unlike the response pattern seen with many biologics for rheumatoid arthritis, where a plateau is reached by 8-12 weeks.

Vasculitis

The positive results for the C5a receptor inhibitor avacopan for treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in the phase-3 ADVOCATE trial have been hailed by some rheumatologists as a major breakthrough, but Dr. Fleischmann isn’t so sure.

The trial randomized 331 patients to oral avacopan at 30 mg twice daily or oral prednisone, with all patients on either cyclophosphamide or rituximab. Avacopan was noninferior to prednisone in terms of remission at week 26, but superior to prednisone for sustained taper at week 52. The rate of serious adverse events was 45.1% with prednisone and 42.2% in the avacopan arm.

“This is a drug that’s going to be much, much more expensive than prednisone. There were people in our group who were ecstatic that this drug is going to come, but how much it’s going to be used, I don’t know,” Dr. Fleischmann said.

Dr. Wells said cost-benefit analyses will be needed in order to learn if avacopan’s anticipated high sticker price is offset by the cost of serious corticosteroid side effects such as avascular necrosis.
 

Giant cell arteritis

Mavrilimumab is a human monoclonal antibody that inhibits human granulocyte macrophage colony stimulating factor receptor alpha. It demonstrated impressive efficacy in a phase 2, double-blind, randomized, placebo-controlled trial conducted in 70 patients with biopsy-confirmed giant cell arteritis. Participants were on corticosteroids until they went into remission and were then randomized to mavrilimumab or placebo, with the steroids stopped. By week 26, 19% of patients in the mavrilimumab arm had flared, as compared to 46.4% of controls.

“This is a game changer,” Dr. Wells declared. “I struggle with these patients because I can’t get the IL-6 drugs approved for them. I need something else.”

Dr. Fleischmann has a good idea how he’ll use mavrilimumab, if it wins approval: “I think this is clearly a drug you would use in a patient you can’t get off steroids and you’re having all the steroid toxicity. I don’t know that you’d use it right away.”

Osteoarthritis

Dr. Fleischmann predicted that tanezumab, a monoclonal antibody directed against nerve growth factor, will win FDA approval in 2021 for the treatment of osteoarthritis pain in patients with an inadequate response or intolerance to standard-of-care NSAIDs and opioids. But he cautioned his colleagues not to expect too much from the biologic, which has a long and checkered developmental history.

“It works better than placebo. It does not work better than an NSAID or an opioid. So it should be reasonable in patients who cannot take an NSAID or cannot or will not take an opioid,” he said.

There are safety issues to be aware of with tanezumab, he added: clinically significant increased risks of peripheral neuropathy and joint space narrowing.
 

Rheumatoid arthritis

Dr. Wells thought one of the most interesting novel therapies for RA in the past year didn’t involve a pharmaceutical, but rather noninvasive auricular branch stimulation of the vagus nerve. He cited an open-label, 12-week, uncontrolled study in 27 patients with active RA who wore an ear clip for vagal nerve stimulation for 12 weeks. The mean Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) – the primary study endpoint – improved from 6.30 at baseline to 3.76 at week 12. The number of tender joints dropped from 12.17 to 4.7, while the swollen joint count went from 7.0 to 3.44. Pain scores improved from 75.23 to 43.3. Scores on the Health Assessment Questionnaire Disability Index improved from 1.59 to 1.05. There was no significant change in CRP. All in all, a modest clinical effect achieved noninvasively.

“The thing that did it for me was the effect on MRI from baseline: decreased synovitis, osteitis, and bone erosion scores,” Dr. Wells said. “This is noninvasive, so patients who want to do medical marijuana or CBD can put an earring on their auricular nerve.”

Dr. Fleischmann scoffed. “An open-label study, 27 patients? Let me see the real study,” he quipped.

Dr. Fleischmann reported receiving clinical trial research grants from and serving as a consultant to more than a dozen pharmaceutical companies. Dr. Wells serves as a consultant to MiCare Path.

bjancin@mdedge.com

It’s been a banner year for treatment advances in systemic lupus erythematosus (SLE), with two drugs gaining approval for lupus nephritis while other promising molecules with novel mechanisms of action advanced smartly through the developmental pipeline, speakers agreed at the 2021 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“I think the most important thing in rheumatology in the last year is where we are now with lupus. With two drugs being approved for lupus nephritis, I think that’s really huge as we talk about treat-to-target,” said Alvin F. Wells, MD, PhD, a rheumatologist in Franklin, Wisc.

Martin Bergman, MD, concurred.

“Lupus has been blowing up in the past year. We have two new medications for lupus nephritis, we have two or three new mechanisms of action for therapy. I think that was one of the biggest things in rheumatology in the past year,” said Dr. Bergman, a rheumatologist at Drexel University in Philadelphia and in private practice in Ridley Park, Pa.

Together with Roy Fleischmann, MD, Dr. Wells spotlighted promising new molecules for the treatment of SLE, giant cell arteritis, vasculitis, rheumatoid arthritis, and osteoarthritis.
 

SLE

The two drugs approved in recent months specifically for lupus nephritis are voclosporin (Lupkynis) and belimumab (Benlysta), which has been approved for lupus for a decade. Voclosporin, an oral calcineurin inhibitor, is a modification of cyclosporine offering significant advantages over the older drug: It’s more potent, requires no dose titration, has a better safety profile, and is metabolized more quickly.

“A safer and easier-to-use calcineurin inhibitor is going to be huge,” Dr. Wells predicted.

Up for Food and Drug Administration review in the coming year on the basis of the positive phase 3 TULIP-1 and TULIP-2 trials is anifrolumab, a monoclonal antibody that binds to the type 1 interferon receptor subunit 1d. At 52 weeks in the pooled analysis, one or more SLE flares occurred in 33.6% of patients on anifrolumab and 42.9% of placebo-treated controls.

“This is not a blockbuster, but it’s a worthwhile addition, like belimumab,” according to Dr. Fleischmann, a rheumatologist at the University of Texas, Dallas.

Dr. Wells concurred, with a reservation: In a subgroup analysis of the TULIP trials, anifrolumab wasn’t significantly better than placebo in black patients, who tend to have more severe and tough-to-treat renal disease.

“Anifrolumab doesn’t look as effective as some other agents, and I’d be disinclined to give it to my black patients,” the rheumatologist said.

Dr. Fleischmann was far more enthusiastic about obinutuzumab (Gazyva), a humanized anti-CD20 monoclonal antibody already approved for the treatment of chronic lymphocytic leukemia and follicular lymphoma.

Bruce Jancin/MDedge News

A humanized monoclonal antibody known for now as BIIB059 demonstrated efficacy and was well tolerated in the phase 2 LILAC trial. BIIB059 binds to blood dendritic cell antigen 2 (BDCA2), a receptor specific to plasmacytoid dendritic cells, resulting in decreased production of type 1 interferon and other inflammatory cytokines. The LILAC trial included 132 SLE patients with active arthritis and skin disease who received subcutaneous injections of BIIB059 at 450 mg or placebo every 4 weeks, with an extra dose at week 2. The primary endpoint was met, with an absolute 15-joint reduction in the total number of tender or swollen joints from baseline to week 24 in the BIIB059 group, compared to an 11.6-joint reduction with placebo. In addition, the likelihood of an SRI-4 response at week 24 was 3.49-fold greater with BIIB059 than with placebo.

Dr. Wells noted that the BIIB059 group showed continued improvement from week 12 to week 24, unlike the response pattern seen with many biologics for rheumatoid arthritis, where a plateau is reached by 8-12 weeks.

Vasculitis

The positive results for the C5a receptor inhibitor avacopan for treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in the phase-3 ADVOCATE trial have been hailed by some rheumatologists as a major breakthrough, but Dr. Fleischmann isn’t so sure.

The trial randomized 331 patients to oral avacopan at 30 mg twice daily or oral prednisone, with all patients on either cyclophosphamide or rituximab. Avacopan was noninferior to prednisone in terms of remission at week 26, but superior to prednisone for sustained taper at week 52. The rate of serious adverse events was 45.1% with prednisone and 42.2% in the avacopan arm.

“This is a drug that’s going to be much, much more expensive than prednisone. There were people in our group who were ecstatic that this drug is going to come, but how much it’s going to be used, I don’t know,” Dr. Fleischmann said.

Dr. Wells said cost-benefit analyses will be needed in order to learn if avacopan’s anticipated high sticker price is offset by the cost of serious corticosteroid side effects such as avascular necrosis.
 

Giant cell arteritis

Mavrilimumab is a human monoclonal antibody that inhibits human granulocyte macrophage colony stimulating factor receptor alpha. It demonstrated impressive efficacy in a phase 2, double-blind, randomized, placebo-controlled trial conducted in 70 patients with biopsy-confirmed giant cell arteritis. Participants were on corticosteroids until they went into remission and were then randomized to mavrilimumab or placebo, with the steroids stopped. By week 26, 19% of patients in the mavrilimumab arm had flared, as compared to 46.4% of controls.

“This is a game changer,” Dr. Wells declared. “I struggle with these patients because I can’t get the IL-6 drugs approved for them. I need something else.”

Dr. Fleischmann has a good idea how he’ll use mavrilimumab, if it wins approval: “I think this is clearly a drug you would use in a patient you can’t get off steroids and you’re having all the steroid toxicity. I don’t know that you’d use it right away.”

Osteoarthritis

Dr. Fleischmann predicted that tanezumab, a monoclonal antibody directed against nerve growth factor, will win FDA approval in 2021 for the treatment of osteoarthritis pain in patients with an inadequate response or intolerance to standard-of-care NSAIDs and opioids. But he cautioned his colleagues not to expect too much from the biologic, which has a long and checkered developmental history.

“It works better than placebo. It does not work better than an NSAID or an opioid. So it should be reasonable in patients who cannot take an NSAID or cannot or will not take an opioid,” he said.

There are safety issues to be aware of with tanezumab, he added: clinically significant increased risks of peripheral neuropathy and joint space narrowing.
 

Rheumatoid arthritis

Dr. Wells thought one of the most interesting novel therapies for RA in the past year didn’t involve a pharmaceutical, but rather noninvasive auricular branch stimulation of the vagus nerve. He cited an open-label, 12-week, uncontrolled study in 27 patients with active RA who wore an ear clip for vagal nerve stimulation for 12 weeks. The mean Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) – the primary study endpoint – improved from 6.30 at baseline to 3.76 at week 12. The number of tender joints dropped from 12.17 to 4.7, while the swollen joint count went from 7.0 to 3.44. Pain scores improved from 75.23 to 43.3. Scores on the Health Assessment Questionnaire Disability Index improved from 1.59 to 1.05. There was no significant change in CRP. All in all, a modest clinical effect achieved noninvasively.

“The thing that did it for me was the effect on MRI from baseline: decreased synovitis, osteitis, and bone erosion scores,” Dr. Wells said. “This is noninvasive, so patients who want to do medical marijuana or CBD can put an earring on their auricular nerve.”

Dr. Fleischmann scoffed. “An open-label study, 27 patients? Let me see the real study,” he quipped.

Dr. Fleischmann reported receiving clinical trial research grants from and serving as a consultant to more than a dozen pharmaceutical companies. Dr. Wells serves as a consultant to MiCare Path.

bjancin@mdedge.com