Conference Coverage

Empagliflozin showed favorable effects on diuretic use and congestion symptoms in patients with heart failure with reduced ejection fraction (HFrEF), but the oral sodium glucose cotransporter 2 (SGLT2) inhibitor did not improve the primary endpoint of improved exercise capacity in the EMPERIAL-Reduced trial, investigators reported at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

In the matching EMPERIAL-Preserved trial, conducted in patients with heart failure with preserved ejection fraction (HFpEF), empagliflozin (Jardiance) produced modest improvements in diuretic use, as well as a reduction in unscheduled outpatient visits, compared with placebo-treated controls, although these trends failed to achieve statistical significance. And as in the EMPERIAL-Reduced trial, the SGLT2 inhibitor didn’t move the needle at all on the primary endpoint of improved exercise capacity as measured by 6-minute hall walk distance.

EMPERIAL-Reduced and -Preserved were identically designed, concurrent, phase 3, double-blind, 12-week randomized trials of empagliflozin versus placebo in 312 patients with HFrEF and 315 with HFpEF, defined in EMPERIAL-preserved as a left ventricular ejection fraction above 40%. The majority of participants had type 2 diabetes.

From a baseline median 6-minute walk distance of about 300 meters, the 6-minute walk distance at week 12 was actually 4.0 meters worse in the empagliflozin-treated HFrEF patients than it was in controls and a mere 4.0 meters better than with placebo in empagliflozin-treated patients with HFpEF, reported William T. Abraham, MD, professor of medicine, director of the division of cardiovascular medicine, and associate dean at Ohio State University, Columbus.

He indicated that the audience shouldn’t make too much of the failure to achieve the primary endpoint in the two trials in light of the studies’ major limitations: namely, their relatively small size for purposes of evaluating clinical outcomes and the relatively short 12-week duration.

“In many ways, I would say it’s remarkable that we can observe a positive signal, a favorable signal, in outcomes around congestion. In the case of HFrEF it’s statistically significant, and in HFpEF it’s a trend towards improvement. Of course, there are larger trials ongoing that may confirm these observations. Hopefully the EMPERIAL trials predict a good outcome for those ongoing trials,” Dr. Abraham said.

Piotr Ponikowski, MD, presented the study results for the secondary outcomes of congestion symptoms, diuretic use, and utilization of health care resources. In EMPERIAL-Reduced, intensification of diuretic therapy – often a prelude to acute decompensation and a trip to the hospital – occurred at a rate of 4.5% with empagliflozin and 16.1% with placebo, for a highly significant 73% relative risk reduction. Intensification of loop diuretics occurred in 2.6% of the empagliflozin group and 14.2% of controls, for a 82% risk reduction.

“That’s a pretty significant effect,” observed Dr. Ponikowski, professor of cardiology and head of the department of heart diseases at the Medical University of Wroclaw (Poland).

Moreover, a congestion symptoms score comprising a summary of orthopnea, jugular veinous distention, and edema improved by 47% after 12 weeks on empagliflozin, a statistically significant and clinically meaningful improvement that grew in magnitude over time and at 12 weeks was twice as large, compared with the reduction in placebo group, he added.

There was a trend for fewer unscheduled outpatient visits in the empagliflozin arm of EMPERIAL-Reduced with a rate of 10.4%, compared with 25.8% in controls; however, this 26% reduction in relative risk did not achieve statistical significance.

Intensification of loop diuretics occurred in 9% of EMPERIAL-Preserved participants on empagliflozin and 13.5% on placebo, but this 34% reduction in risk didn’t reach significance.

Adverse events in the EMPERIAL trials were similar across the active treatment and placebo arms. The benign safety profile was similar to what was seen in the earlier major clinical trials of empagliflozin for treatment of type 2 diabetes.

Session chair Stephane Heymans, MD, PhD, of the University of Maastricht (the Netherlands) noted that a substantial minority of patients in EMPERIAL-Reduced were on the combined neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan (Entresto), whereas far fewer were in EMPERIAL-Preserved. He wondered if this greater use of background sacubitril/valsartan could explain empagliflozin’s greater efficacy in EMPERIAL-Reduced.

Highly unlikely, according to the investigators.

“It looks like, as is the case with most of our heart failure therapies, that we do see incremental value here. If you met the criteria for these trials, it appears you derived benefit from empagliflozin regardless of whether you were on an angiotensin receptor neprilysin inhibitor or not. I think that speaks to the incremental benefit of SGLT2 inhibitors on top of current guideline-directed medical therapy,” Dr. Abraham said.

Dr. Ponikowski observed that the same point was underscored in the DAPA-HF trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in patients with heart failure (DAPA-HF: N Engl J Med. 2019 Nov 21;381[21]:1995-2008).

“You’ll see that the mortality and morbidity and quality-of-life benefit is in those treated with dapagliflozin with or without angiotensin receptor neprilysin inhibition; so, regardless of background therapy. And the effect is especially clear in patients on both therapies,” the cardiologist said.

The EMPERIAL trials were sponsored by Boehringer Ingelheim. Dr. Abraham and Dr. Ponikowksi reported receiving consultant fees from the company for serving on the trials’ executive committee.

bjancin@mdedge.com

Empagliflozin showed favorable effects on diuretic use and congestion symptoms in patients with heart failure with reduced ejection fraction (HFrEF), but the oral sodium glucose cotransporter 2 (SGLT2) inhibitor did not improve the primary endpoint of improved exercise capacity in the EMPERIAL-Reduced trial, investigators reported at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

In the matching EMPERIAL-Preserved trial, conducted in patients with heart failure with preserved ejection fraction (HFpEF), empagliflozin (Jardiance) produced modest improvements in diuretic use, as well as a reduction in unscheduled outpatient visits, compared with placebo-treated controls, although these trends failed to achieve statistical significance. And as in the EMPERIAL-Reduced trial, the SGLT2 inhibitor didn’t move the needle at all on the primary endpoint of improved exercise capacity as measured by 6-minute hall walk distance.

EMPERIAL-Reduced and -Preserved were identically designed, concurrent, phase 3, double-blind, 12-week randomized trials of empagliflozin versus placebo in 312 patients with HFrEF and 315 with HFpEF, defined in EMPERIAL-preserved as a left ventricular ejection fraction above 40%. The majority of participants had type 2 diabetes.

From a baseline median 6-minute walk distance of about 300 meters, the 6-minute walk distance at week 12 was actually 4.0 meters worse in the empagliflozin-treated HFrEF patients than it was in controls and a mere 4.0 meters better than with placebo in empagliflozin-treated patients with HFpEF, reported William T. Abraham, MD, professor of medicine, director of the division of cardiovascular medicine, and associate dean at Ohio State University, Columbus.

He indicated that the audience shouldn’t make too much of the failure to achieve the primary endpoint in the two trials in light of the studies’ major limitations: namely, their relatively small size for purposes of evaluating clinical outcomes and the relatively short 12-week duration.

“In many ways, I would say it’s remarkable that we can observe a positive signal, a favorable signal, in outcomes around congestion. In the case of HFrEF it’s statistically significant, and in HFpEF it’s a trend towards improvement. Of course, there are larger trials ongoing that may confirm these observations. Hopefully the EMPERIAL trials predict a good outcome for those ongoing trials,” Dr. Abraham said.

Piotr Ponikowski, MD, presented the study results for the secondary outcomes of congestion symptoms, diuretic use, and utilization of health care resources. In EMPERIAL-Reduced, intensification of diuretic therapy – often a prelude to acute decompensation and a trip to the hospital – occurred at a rate of 4.5% with empagliflozin and 16.1% with placebo, for a highly significant 73% relative risk reduction. Intensification of loop diuretics occurred in 2.6% of the empagliflozin group and 14.2% of controls, for a 82% risk reduction.

“That’s a pretty significant effect,” observed Dr. Ponikowski, professor of cardiology and head of the department of heart diseases at the Medical University of Wroclaw (Poland).

Moreover, a congestion symptoms score comprising a summary of orthopnea, jugular veinous distention, and edema improved by 47% after 12 weeks on empagliflozin, a statistically significant and clinically meaningful improvement that grew in magnitude over time and at 12 weeks was twice as large, compared with the reduction in placebo group, he added.

There was a trend for fewer unscheduled outpatient visits in the empagliflozin arm of EMPERIAL-Reduced with a rate of 10.4%, compared with 25.8% in controls; however, this 26% reduction in relative risk did not achieve statistical significance.

Intensification of loop diuretics occurred in 9% of EMPERIAL-Preserved participants on empagliflozin and 13.5% on placebo, but this 34% reduction in risk didn’t reach significance.

Adverse events in the EMPERIAL trials were similar across the active treatment and placebo arms. The benign safety profile was similar to what was seen in the earlier major clinical trials of empagliflozin for treatment of type 2 diabetes.

Session chair Stephane Heymans, MD, PhD, of the University of Maastricht (the Netherlands) noted that a substantial minority of patients in EMPERIAL-Reduced were on the combined neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan (Entresto), whereas far fewer were in EMPERIAL-Preserved. He wondered if this greater use of background sacubitril/valsartan could explain empagliflozin’s greater efficacy in EMPERIAL-Reduced.

Highly unlikely, according to the investigators.

“It looks like, as is the case with most of our heart failure therapies, that we do see incremental value here. If you met the criteria for these trials, it appears you derived benefit from empagliflozin regardless of whether you were on an angiotensin receptor neprilysin inhibitor or not. I think that speaks to the incremental benefit of SGLT2 inhibitors on top of current guideline-directed medical therapy,” Dr. Abraham said.

Dr. Ponikowski observed that the same point was underscored in the DAPA-HF trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in patients with heart failure (DAPA-HF: N Engl J Med. 2019 Nov 21;381[21]:1995-2008).

“You’ll see that the mortality and morbidity and quality-of-life benefit is in those treated with dapagliflozin with or without angiotensin receptor neprilysin inhibition; so, regardless of background therapy. And the effect is especially clear in patients on both therapies,” the cardiologist said.

The EMPERIAL trials were sponsored by Boehringer Ingelheim. Dr. Abraham and Dr. Ponikowksi reported receiving consultant fees from the company for serving on the trials’ executive committee.

bjancin@mdedge.com

Empagliflozin showed favorable effects on diuretic use and congestion symptoms in patients with heart failure with reduced ejection fraction (HFrEF), but the oral sodium glucose cotransporter 2 (SGLT2) inhibitor did not improve the primary endpoint of improved exercise capacity in the EMPERIAL-Reduced trial, investigators reported at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

In the matching EMPERIAL-Preserved trial, conducted in patients with heart failure with preserved ejection fraction (HFpEF), empagliflozin (Jardiance) produced modest improvements in diuretic use, as well as a reduction in unscheduled outpatient visits, compared with placebo-treated controls, although these trends failed to achieve statistical significance. And as in the EMPERIAL-Reduced trial, the SGLT2 inhibitor didn’t move the needle at all on the primary endpoint of improved exercise capacity as measured by 6-minute hall walk distance.

EMPERIAL-Reduced and -Preserved were identically designed, concurrent, phase 3, double-blind, 12-week randomized trials of empagliflozin versus placebo in 312 patients with HFrEF and 315 with HFpEF, defined in EMPERIAL-preserved as a left ventricular ejection fraction above 40%. The majority of participants had type 2 diabetes.

From a baseline median 6-minute walk distance of about 300 meters, the 6-minute walk distance at week 12 was actually 4.0 meters worse in the empagliflozin-treated HFrEF patients than it was in controls and a mere 4.0 meters better than with placebo in empagliflozin-treated patients with HFpEF, reported William T. Abraham, MD, professor of medicine, director of the division of cardiovascular medicine, and associate dean at Ohio State University, Columbus.

He indicated that the audience shouldn’t make too much of the failure to achieve the primary endpoint in the two trials in light of the studies’ major limitations: namely, their relatively small size for purposes of evaluating clinical outcomes and the relatively short 12-week duration.

“In many ways, I would say it’s remarkable that we can observe a positive signal, a favorable signal, in outcomes around congestion. In the case of HFrEF it’s statistically significant, and in HFpEF it’s a trend towards improvement. Of course, there are larger trials ongoing that may confirm these observations. Hopefully the EMPERIAL trials predict a good outcome for those ongoing trials,” Dr. Abraham said.

Piotr Ponikowski, MD, presented the study results for the secondary outcomes of congestion symptoms, diuretic use, and utilization of health care resources. In EMPERIAL-Reduced, intensification of diuretic therapy – often a prelude to acute decompensation and a trip to the hospital – occurred at a rate of 4.5% with empagliflozin and 16.1% with placebo, for a highly significant 73% relative risk reduction. Intensification of loop diuretics occurred in 2.6% of the empagliflozin group and 14.2% of controls, for a 82% risk reduction.

“That’s a pretty significant effect,” observed Dr. Ponikowski, professor of cardiology and head of the department of heart diseases at the Medical University of Wroclaw (Poland).

Moreover, a congestion symptoms score comprising a summary of orthopnea, jugular veinous distention, and edema improved by 47% after 12 weeks on empagliflozin, a statistically significant and clinically meaningful improvement that grew in magnitude over time and at 12 weeks was twice as large, compared with the reduction in placebo group, he added.

There was a trend for fewer unscheduled outpatient visits in the empagliflozin arm of EMPERIAL-Reduced with a rate of 10.4%, compared with 25.8% in controls; however, this 26% reduction in relative risk did not achieve statistical significance.

Intensification of loop diuretics occurred in 9% of EMPERIAL-Preserved participants on empagliflozin and 13.5% on placebo, but this 34% reduction in risk didn’t reach significance.

Adverse events in the EMPERIAL trials were similar across the active treatment and placebo arms. The benign safety profile was similar to what was seen in the earlier major clinical trials of empagliflozin for treatment of type 2 diabetes.

Session chair Stephane Heymans, MD, PhD, of the University of Maastricht (the Netherlands) noted that a substantial minority of patients in EMPERIAL-Reduced were on the combined neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan (Entresto), whereas far fewer were in EMPERIAL-Preserved. He wondered if this greater use of background sacubitril/valsartan could explain empagliflozin’s greater efficacy in EMPERIAL-Reduced.

Highly unlikely, according to the investigators.

“It looks like, as is the case with most of our heart failure therapies, that we do see incremental value here. If you met the criteria for these trials, it appears you derived benefit from empagliflozin regardless of whether you were on an angiotensin receptor neprilysin inhibitor or not. I think that speaks to the incremental benefit of SGLT2 inhibitors on top of current guideline-directed medical therapy,” Dr. Abraham said.

Dr. Ponikowski observed that the same point was underscored in the DAPA-HF trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in patients with heart failure (DAPA-HF: N Engl J Med. 2019 Nov 21;381[21]:1995-2008).

“You’ll see that the mortality and morbidity and quality-of-life benefit is in those treated with dapagliflozin with or without angiotensin receptor neprilysin inhibition; so, regardless of background therapy. And the effect is especially clear in patients on both therapies,” the cardiologist said.

The EMPERIAL trials were sponsored by Boehringer Ingelheim. Dr. Abraham and Dr. Ponikowksi reported receiving consultant fees from the company for serving on the trials’ executive committee.

bjancin@mdedge.com

The DynamX Bioadaptor – arguably the most original concept in coronary stent design to come along in 3 decades – demonstrated excellent safety and efficacy in a 12-month international, proof-of-concept study, Stefan Verheye, MD, said at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

“There has been no fundamental change in stent design in over 30 years,” declared Dr. Verheye, codirector of the Antwerp (Belgium) Cardiovascular Center. “The DynamX Bioadaptor is a fundamental innovation in device design.”

The investigational device is a 71-mcm-thick, cobalt-chromium metal platform that elutes novolimus from a biodegradable polymer. Circumferential rings in low-stress sections of the device are held together by polymer connectors, and when the polymer erodes at about 6 months the stent segments are able to disengage from each other while maintaining longitudinal continuity. Dr. Verheye called this process “uncaging” the stented artery. The result is restoration of normal vessel angulation and compliance; the artery is no longer artificially straightened and constrained by a relatively stiff stent. Positive adaptive remodeling is preserved with enhanced vessel pulsatility and maintenance of lumenal area for good blood flow.

Dr. Verheye said the impetus for developing this outside-the-box novel stent platform lies in the recognition of a major unmet need for better drug-eluting stent (DES) performance. “Despite excellent acute outcomes, data with current-generation DES show long-term event rates are high and accrue at a rate of 2%-3% per year without a plateau.”

He was coprincipal investigator for the international study, which included 50 patients who received a DynamX Bioadaptor for a single de novo coronary artery lesion no more than 24 mm in length. The acute performance of the device was similar to that of second-generation DES, with a mean acute gain post procedure of 1.63 mm by quantitative coronary angiography and a mean late lumen loss of 0.12 mm when measured again at 9 or 12 months.

Intravascular ultrasound imaging showed a 3% increase in mean target vessel area and a 5% increase in the stented area from post procedure to 9 or 12 months’ follow-up, with no change in mean lumen area, all of which translates into maintenance of good blood flow over time. In contrast, what typically occurs following implantation of current DES is maintenance of target vessel and device areas, but with a loss in mean lumen area, the cardiologist noted.

There were two cardiac deaths but no cases of target lesion revascularization, device thrombosis, or strut fracture within 12 months of the procedure.

“The Bioadaptor performs similarly to second-generation DES in terms of implantation technique, deliverability, conformability, and radial strength during the healing phase, while showing the promise of mitigating the 2%-3% annualized event rate beyond 1 year,” Dr. Verheye concluded, adding, “Obviously, longer-term follow-up in comparative studies will be needed to show a reduction in the device-oriented events that have been observed with current DES.”

Session cochair Davide Capodanno, MD, PhD, of the University of Catania (Italy), declared: “This is an intriguing device because it’s metal, but it’s a kind of pulsatile metal after the biodegradation of the connectors. It’s something I’ve never seen.”

Discussant William Wijns, MD, PhD, said he was “thrilled” by the innovative aspect of the DynamX Bioadaptor, but he’s a long way from being persuaded that the device’s potential physiological advantages will translate into improved clinical outcomes relative to current DES.

“Don’t we all have a strange feeling of deja vu because all these anticipated benefits are the same as those we were told we would see with fully bioresorbable scaffolds? And we know so much after 10 years of experience with bioresorbable scaffolds that probably we will not accept this great story unless we get more and more evidence,” cautioned Dr. Wijns, professor of interventional cardiology at the National University of Ireland, Galway, and chairman of EuroPCR.

The claim regarding bioresorbable scaffolds was that, even though the acute results weren’t as good as with DES, that disadvantage would be outweighed by superior long-term clinical outcomes. But in fact the long-term outcomes turned out to be worse as well.

“We had to give up immediate results with the bioresorbable scaffolds. I don’t think we want to go that route again this time,” the cardiologist said.

Thus, the first thing that’s needed in order to make a convincing case for the Bioadaptor is evidence from a large, randomized, comparative trial demonstrating that the acute performance of the novel device is noninferior to that of current DES, including data on complex lesions. Such a study was supposed to be underway now but has been delayed by the COVID-19 pandemic, he noted.

Once there is evidence that the acute results with the Bioadaptor are truly comparable with those achieved with current DES, there will be a need for long-term data showing that the device reduces the 2%-3% annualized event rate seen with DES beyond 1 year, Dr. Wijns added.

Dr. Verheye reported receiving consultation fees from study sponsor Elixir Medical as well as from Biotronik. Dr. Wijns reported receiving research grants from MicroPort.

bjancin@mdedge.com

The DynamX Bioadaptor – arguably the most original concept in coronary stent design to come along in 3 decades – demonstrated excellent safety and efficacy in a 12-month international, proof-of-concept study, Stefan Verheye, MD, said at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

“There has been no fundamental change in stent design in over 30 years,” declared Dr. Verheye, codirector of the Antwerp (Belgium) Cardiovascular Center. “The DynamX Bioadaptor is a fundamental innovation in device design.”

The investigational device is a 71-mcm-thick, cobalt-chromium metal platform that elutes novolimus from a biodegradable polymer. Circumferential rings in low-stress sections of the device are held together by polymer connectors, and when the polymer erodes at about 6 months the stent segments are able to disengage from each other while maintaining longitudinal continuity. Dr. Verheye called this process “uncaging” the stented artery. The result is restoration of normal vessel angulation and compliance; the artery is no longer artificially straightened and constrained by a relatively stiff stent. Positive adaptive remodeling is preserved with enhanced vessel pulsatility and maintenance of lumenal area for good blood flow.

Dr. Verheye said the impetus for developing this outside-the-box novel stent platform lies in the recognition of a major unmet need for better drug-eluting stent (DES) performance. “Despite excellent acute outcomes, data with current-generation DES show long-term event rates are high and accrue at a rate of 2%-3% per year without a plateau.”

He was coprincipal investigator for the international study, which included 50 patients who received a DynamX Bioadaptor for a single de novo coronary artery lesion no more than 24 mm in length. The acute performance of the device was similar to that of second-generation DES, with a mean acute gain post procedure of 1.63 mm by quantitative coronary angiography and a mean late lumen loss of 0.12 mm when measured again at 9 or 12 months.

Intravascular ultrasound imaging showed a 3% increase in mean target vessel area and a 5% increase in the stented area from post procedure to 9 or 12 months’ follow-up, with no change in mean lumen area, all of which translates into maintenance of good blood flow over time. In contrast, what typically occurs following implantation of current DES is maintenance of target vessel and device areas, but with a loss in mean lumen area, the cardiologist noted.

There were two cardiac deaths but no cases of target lesion revascularization, device thrombosis, or strut fracture within 12 months of the procedure.

“The Bioadaptor performs similarly to second-generation DES in terms of implantation technique, deliverability, conformability, and radial strength during the healing phase, while showing the promise of mitigating the 2%-3% annualized event rate beyond 1 year,” Dr. Verheye concluded, adding, “Obviously, longer-term follow-up in comparative studies will be needed to show a reduction in the device-oriented events that have been observed with current DES.”

Session cochair Davide Capodanno, MD, PhD, of the University of Catania (Italy), declared: “This is an intriguing device because it’s metal, but it’s a kind of pulsatile metal after the biodegradation of the connectors. It’s something I’ve never seen.”

Discussant William Wijns, MD, PhD, said he was “thrilled” by the innovative aspect of the DynamX Bioadaptor, but he’s a long way from being persuaded that the device’s potential physiological advantages will translate into improved clinical outcomes relative to current DES.

“Don’t we all have a strange feeling of deja vu because all these anticipated benefits are the same as those we were told we would see with fully bioresorbable scaffolds? And we know so much after 10 years of experience with bioresorbable scaffolds that probably we will not accept this great story unless we get more and more evidence,” cautioned Dr. Wijns, professor of interventional cardiology at the National University of Ireland, Galway, and chairman of EuroPCR.

The claim regarding bioresorbable scaffolds was that, even though the acute results weren’t as good as with DES, that disadvantage would be outweighed by superior long-term clinical outcomes. But in fact the long-term outcomes turned out to be worse as well.

“We had to give up immediate results with the bioresorbable scaffolds. I don’t think we want to go that route again this time,” the cardiologist said.

Thus, the first thing that’s needed in order to make a convincing case for the Bioadaptor is evidence from a large, randomized, comparative trial demonstrating that the acute performance of the novel device is noninferior to that of current DES, including data on complex lesions. Such a study was supposed to be underway now but has been delayed by the COVID-19 pandemic, he noted.

Once there is evidence that the acute results with the Bioadaptor are truly comparable with those achieved with current DES, there will be a need for long-term data showing that the device reduces the 2%-3% annualized event rate seen with DES beyond 1 year, Dr. Wijns added.

Dr. Verheye reported receiving consultation fees from study sponsor Elixir Medical as well as from Biotronik. Dr. Wijns reported receiving research grants from MicroPort.

bjancin@mdedge.com

The DynamX Bioadaptor – arguably the most original concept in coronary stent design to come along in 3 decades – demonstrated excellent safety and efficacy in a 12-month international, proof-of-concept study, Stefan Verheye, MD, said at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

“There has been no fundamental change in stent design in over 30 years,” declared Dr. Verheye, codirector of the Antwerp (Belgium) Cardiovascular Center. “The DynamX Bioadaptor is a fundamental innovation in device design.”

The investigational device is a 71-mcm-thick, cobalt-chromium metal platform that elutes novolimus from a biodegradable polymer. Circumferential rings in low-stress sections of the device are held together by polymer connectors, and when the polymer erodes at about 6 months the stent segments are able to disengage from each other while maintaining longitudinal continuity. Dr. Verheye called this process “uncaging” the stented artery. The result is restoration of normal vessel angulation and compliance; the artery is no longer artificially straightened and constrained by a relatively stiff stent. Positive adaptive remodeling is preserved with enhanced vessel pulsatility and maintenance of lumenal area for good blood flow.

Dr. Verheye said the impetus for developing this outside-the-box novel stent platform lies in the recognition of a major unmet need for better drug-eluting stent (DES) performance. “Despite excellent acute outcomes, data with current-generation DES show long-term event rates are high and accrue at a rate of 2%-3% per year without a plateau.”

He was coprincipal investigator for the international study, which included 50 patients who received a DynamX Bioadaptor for a single de novo coronary artery lesion no more than 24 mm in length. The acute performance of the device was similar to that of second-generation DES, with a mean acute gain post procedure of 1.63 mm by quantitative coronary angiography and a mean late lumen loss of 0.12 mm when measured again at 9 or 12 months.

Intravascular ultrasound imaging showed a 3% increase in mean target vessel area and a 5% increase in the stented area from post procedure to 9 or 12 months’ follow-up, with no change in mean lumen area, all of which translates into maintenance of good blood flow over time. In contrast, what typically occurs following implantation of current DES is maintenance of target vessel and device areas, but with a loss in mean lumen area, the cardiologist noted.

There were two cardiac deaths but no cases of target lesion revascularization, device thrombosis, or strut fracture within 12 months of the procedure.

“The Bioadaptor performs similarly to second-generation DES in terms of implantation technique, deliverability, conformability, and radial strength during the healing phase, while showing the promise of mitigating the 2%-3% annualized event rate beyond 1 year,” Dr. Verheye concluded, adding, “Obviously, longer-term follow-up in comparative studies will be needed to show a reduction in the device-oriented events that have been observed with current DES.”

Session cochair Davide Capodanno, MD, PhD, of the University of Catania (Italy), declared: “This is an intriguing device because it’s metal, but it’s a kind of pulsatile metal after the biodegradation of the connectors. It’s something I’ve never seen.”

Discussant William Wijns, MD, PhD, said he was “thrilled” by the innovative aspect of the DynamX Bioadaptor, but he’s a long way from being persuaded that the device’s potential physiological advantages will translate into improved clinical outcomes relative to current DES.

“Don’t we all have a strange feeling of deja vu because all these anticipated benefits are the same as those we were told we would see with fully bioresorbable scaffolds? And we know so much after 10 years of experience with bioresorbable scaffolds that probably we will not accept this great story unless we get more and more evidence,” cautioned Dr. Wijns, professor of interventional cardiology at the National University of Ireland, Galway, and chairman of EuroPCR.

The claim regarding bioresorbable scaffolds was that, even though the acute results weren’t as good as with DES, that disadvantage would be outweighed by superior long-term clinical outcomes. But in fact the long-term outcomes turned out to be worse as well.

“We had to give up immediate results with the bioresorbable scaffolds. I don’t think we want to go that route again this time,” the cardiologist said.

Thus, the first thing that’s needed in order to make a convincing case for the Bioadaptor is evidence from a large, randomized, comparative trial demonstrating that the acute performance of the novel device is noninferior to that of current DES, including data on complex lesions. Such a study was supposed to be underway now but has been delayed by the COVID-19 pandemic, he noted.

Once there is evidence that the acute results with the Bioadaptor are truly comparable with those achieved with current DES, there will be a need for long-term data showing that the device reduces the 2%-3% annualized event rate seen with DES beyond 1 year, Dr. Wijns added.

Dr. Verheye reported receiving consultation fees from study sponsor Elixir Medical as well as from Biotronik. Dr. Wijns reported receiving research grants from MicroPort.

bjancin@mdedge.com

The absence of in-person school has harmed children in ways beyond loss of academic learning, according to Josh Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore. In addition to learning, school is a place where many children receive breakfast and lunch every day, as well as support services and the benefits of being in a safe and secure environment, Dr. Sharfstein said in a press briefing sponsored by Johns Hopkins University.

However, although it is an important priority for children to return to school, “we are in the midst of a pandemic that poses real risk,” he said.

In the press briefing, several experts shared ideas and considerations for safely reopening K-12 schools in the fall of 2020.

Data from other countries where schools have reopened, notably Austria and Denmark, have been reassuring about the lack of transmission of SARS-CoV-2 among children in a school setting, said Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins Center for Health Security. However, other countries where schools have reopened successfully have reported low levels of viral transmission locally, and a responsible strategy for school reopening in the United States should follow a similar plan, she said. In areas where transmission and infection rates are increasing “it may not be safe to reopen,” but in areas where rates are declining or stable, schools could potentially reopen if they follow safety measures.

Dr. Nuzzo suggested that schools should prioritize students who will benefit most from in-person learning, such as younger children and those with special needs. Considerations include protocols for handwashing and sanitation, and maintaining physical distance by creative use of outdoor classrooms (weather permitting) or other spaces within school buildings. Transportation to and from school also will be an issue to address, she noted.

None of the strategies being considered will completely eliminate risk of SARS-CoV-2 infection in school settings, so allowing parents and students to opt out and choose distance learning will be important as well, said Dr. Nuzzo. In addition, schools may need to consider alternative roles for teachers and staff who don’t feel comfortable being in contact with students and fellow staff members. “All of these things are going to be hard,” Dr. Nuzzo acknowledged. “Hard should not be a deterrent,” to reopening schools, but “we acknowledge the resources that schools will need in order to do this.”

At present, all 50 states and the District of Columbia have released some type of plan for reopening schools, said Megan Collins, MD, MPH, codirector the Johns Hopkins Consortium for School-Based Health Solutions.

Dr. Collins and colleagues have developed a school reopening tracker, which is “a national snapshot of current reopening plans that have been released,” she said. The tracker is being updated continuously as plans evolve. The eSchool+ K-12 School Reopening Tracker identifies 12 reopening categories that states could potentially address in the plans. These categories are divided into Operational and Ethics/Equity. The operational categories include:

• Core academics
• SARS-CoV-2 protection
• Before and after school programs
• School access and transportation
• Student health services
• Food and nutrition.

Ethics/equity categories include the following:

• Parent choice
• Teacher and staff choice
• Children of poverty and systemic disadvantage
• Children with special needs/English as second language/gifted and twice exceptional
• Privacy
• Engagement and transparency.

As of July 15, 2020, 16 states (Arizona, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, North Carolina, North Dakota, Ohio, Rhode Island, Tennessee, Texas, Virginia, Washington, and Wisconsin) had addressed all 12 categories in their reopening plans, Dr. Collins said.

School reopening plans must take equity issues into account, said Annette Anderson, PhD, of the Johns Hopkins University School of Education.

Specifically, developing learning plans for special education students and others at the most risk for learning loss will be essential. “The digital divide has become a digital canyon” in some areas, Dr. Anderson noted, and schools need to rethink eligibility and work to provide access to devices for online learning for all students.

In addition, schools need to convince parents that schools are safe. She recommended that schools consider inviting parents and families to visit buildings in advance of reopening so they can see the safety measures, such as space between desks, cleaning stations, and other protective strategies.

The message to pediatricians and health care professionals when counseling families about returning individual children to school is to consider the risk to the child and the family directly in the context of the local plans, Dr. Sharfstein said during a question and answer session. “One school system’s plan is one school system’s plan,” he said, and added that families who are concerned about the risk should have an online option. However, “if you see a thoughtful approach” to reopening, with safety steps taken and parents informed, with protocols such as keeping small groups of children together to reduce transmission, “it is a pretty good trade-off,” and that is why the American Academy of Pediatrics currently favors children returning to school, he said.

The briefing participants had no relevant financial conflicts to disclose.

The absence of in-person school has harmed children in ways beyond loss of academic learning, according to Josh Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore. In addition to learning, school is a place where many children receive breakfast and lunch every day, as well as support services and the benefits of being in a safe and secure environment, Dr. Sharfstein said in a press briefing sponsored by Johns Hopkins University.

However, although it is an important priority for children to return to school, “we are in the midst of a pandemic that poses real risk,” he said.

In the press briefing, several experts shared ideas and considerations for safely reopening K-12 schools in the fall of 2020.

Data from other countries where schools have reopened, notably Austria and Denmark, have been reassuring about the lack of transmission of SARS-CoV-2 among children in a school setting, said Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins Center for Health Security. However, other countries where schools have reopened successfully have reported low levels of viral transmission locally, and a responsible strategy for school reopening in the United States should follow a similar plan, she said. In areas where transmission and infection rates are increasing “it may not be safe to reopen,” but in areas where rates are declining or stable, schools could potentially reopen if they follow safety measures.

Dr. Nuzzo suggested that schools should prioritize students who will benefit most from in-person learning, such as younger children and those with special needs. Considerations include protocols for handwashing and sanitation, and maintaining physical distance by creative use of outdoor classrooms (weather permitting) or other spaces within school buildings. Transportation to and from school also will be an issue to address, she noted.

None of the strategies being considered will completely eliminate risk of SARS-CoV-2 infection in school settings, so allowing parents and students to opt out and choose distance learning will be important as well, said Dr. Nuzzo. In addition, schools may need to consider alternative roles for teachers and staff who don’t feel comfortable being in contact with students and fellow staff members. “All of these things are going to be hard,” Dr. Nuzzo acknowledged. “Hard should not be a deterrent,” to reopening schools, but “we acknowledge the resources that schools will need in order to do this.”

At present, all 50 states and the District of Columbia have released some type of plan for reopening schools, said Megan Collins, MD, MPH, codirector the Johns Hopkins Consortium for School-Based Health Solutions.

Dr. Collins and colleagues have developed a school reopening tracker, which is “a national snapshot of current reopening plans that have been released,” she said. The tracker is being updated continuously as plans evolve. The eSchool+ K-12 School Reopening Tracker identifies 12 reopening categories that states could potentially address in the plans. These categories are divided into Operational and Ethics/Equity. The operational categories include:

• Core academics
• SARS-CoV-2 protection
• Before and after school programs
• School access and transportation
• Student health services
• Food and nutrition.

Ethics/equity categories include the following:

• Parent choice
• Teacher and staff choice
• Children of poverty and systemic disadvantage
• Children with special needs/English as second language/gifted and twice exceptional
• Privacy
• Engagement and transparency.

As of July 15, 2020, 16 states (Arizona, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, North Carolina, North Dakota, Ohio, Rhode Island, Tennessee, Texas, Virginia, Washington, and Wisconsin) had addressed all 12 categories in their reopening plans, Dr. Collins said.

School reopening plans must take equity issues into account, said Annette Anderson, PhD, of the Johns Hopkins University School of Education.

Specifically, developing learning plans for special education students and others at the most risk for learning loss will be essential. “The digital divide has become a digital canyon” in some areas, Dr. Anderson noted, and schools need to rethink eligibility and work to provide access to devices for online learning for all students.

In addition, schools need to convince parents that schools are safe. She recommended that schools consider inviting parents and families to visit buildings in advance of reopening so they can see the safety measures, such as space between desks, cleaning stations, and other protective strategies.

The message to pediatricians and health care professionals when counseling families about returning individual children to school is to consider the risk to the child and the family directly in the context of the local plans, Dr. Sharfstein said during a question and answer session. “One school system’s plan is one school system’s plan,” he said, and added that families who are concerned about the risk should have an online option. However, “if you see a thoughtful approach” to reopening, with safety steps taken and parents informed, with protocols such as keeping small groups of children together to reduce transmission, “it is a pretty good trade-off,” and that is why the American Academy of Pediatrics currently favors children returning to school, he said.

The briefing participants had no relevant financial conflicts to disclose.

The absence of in-person school has harmed children in ways beyond loss of academic learning, according to Josh Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore. In addition to learning, school is a place where many children receive breakfast and lunch every day, as well as support services and the benefits of being in a safe and secure environment, Dr. Sharfstein said in a press briefing sponsored by Johns Hopkins University.

However, although it is an important priority for children to return to school, “we are in the midst of a pandemic that poses real risk,” he said.

In the press briefing, several experts shared ideas and considerations for safely reopening K-12 schools in the fall of 2020.

Data from other countries where schools have reopened, notably Austria and Denmark, have been reassuring about the lack of transmission of SARS-CoV-2 among children in a school setting, said Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins Center for Health Security. However, other countries where schools have reopened successfully have reported low levels of viral transmission locally, and a responsible strategy for school reopening in the United States should follow a similar plan, she said. In areas where transmission and infection rates are increasing “it may not be safe to reopen,” but in areas where rates are declining or stable, schools could potentially reopen if they follow safety measures.

Dr. Nuzzo suggested that schools should prioritize students who will benefit most from in-person learning, such as younger children and those with special needs. Considerations include protocols for handwashing and sanitation, and maintaining physical distance by creative use of outdoor classrooms (weather permitting) or other spaces within school buildings. Transportation to and from school also will be an issue to address, she noted.

None of the strategies being considered will completely eliminate risk of SARS-CoV-2 infection in school settings, so allowing parents and students to opt out and choose distance learning will be important as well, said Dr. Nuzzo. In addition, schools may need to consider alternative roles for teachers and staff who don’t feel comfortable being in contact with students and fellow staff members. “All of these things are going to be hard,” Dr. Nuzzo acknowledged. “Hard should not be a deterrent,” to reopening schools, but “we acknowledge the resources that schools will need in order to do this.”

At present, all 50 states and the District of Columbia have released some type of plan for reopening schools, said Megan Collins, MD, MPH, codirector the Johns Hopkins Consortium for School-Based Health Solutions.

Dr. Collins and colleagues have developed a school reopening tracker, which is “a national snapshot of current reopening plans that have been released,” she said. The tracker is being updated continuously as plans evolve. The eSchool+ K-12 School Reopening Tracker identifies 12 reopening categories that states could potentially address in the plans. These categories are divided into Operational and Ethics/Equity. The operational categories include:

• Core academics
• SARS-CoV-2 protection
• Before and after school programs
• School access and transportation
• Student health services
• Food and nutrition.

Ethics/equity categories include the following:

• Parent choice
• Teacher and staff choice
• Children of poverty and systemic disadvantage
• Children with special needs/English as second language/gifted and twice exceptional
• Privacy
• Engagement and transparency.

As of July 15, 2020, 16 states (Arizona, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, North Carolina, North Dakota, Ohio, Rhode Island, Tennessee, Texas, Virginia, Washington, and Wisconsin) had addressed all 12 categories in their reopening plans, Dr. Collins said.

School reopening plans must take equity issues into account, said Annette Anderson, PhD, of the Johns Hopkins University School of Education.

Specifically, developing learning plans for special education students and others at the most risk for learning loss will be essential. “The digital divide has become a digital canyon” in some areas, Dr. Anderson noted, and schools need to rethink eligibility and work to provide access to devices for online learning for all students.

In addition, schools need to convince parents that schools are safe. She recommended that schools consider inviting parents and families to visit buildings in advance of reopening so they can see the safety measures, such as space between desks, cleaning stations, and other protective strategies.

The message to pediatricians and health care professionals when counseling families about returning individual children to school is to consider the risk to the child and the family directly in the context of the local plans, Dr. Sharfstein said during a question and answer session. “One school system’s plan is one school system’s plan,” he said, and added that families who are concerned about the risk should have an online option. However, “if you see a thoughtful approach” to reopening, with safety steps taken and parents informed, with protocols such as keeping small groups of children together to reduce transmission, “it is a pretty good trade-off,” and that is why the American Academy of Pediatrics currently favors children returning to school, he said.

The briefing participants had no relevant financial conflicts to disclose.

COVID-19 has posed serious questions for patients with psoriatic disease and the clinicians who treat them. Both have serious concerns over whether psoriasis or the medications used to treat it pose additional risk for contracting COVID-19 or experiencing worse outcomes with illness.

At the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, experts gathered to discuss these concerns and what is known about the special risk factors for psoriatic disease patients.

Studies from a few registries have been done already among patients with autoimmune disease, and the results so far suggest that patients may be able to breathe a little easier. “I don’t see any data that suggests that use of immunosuppressives or having autoimmune disease increases your risk of acquiring it. I think most of the risk is driven by risk of exposure,” said Kevin Winthrop, MD, MPH, a professor of public health, infectious diseases, ophthalmology at Oregon Health & Science University, Portland, during a presentation.

That assertion was reinforced by data presented by Rebecca Haberman, MD, a rheumatologist at New York University Langone Health. Her group created the Web-Based Assessment of Autoimmune, Immune-Mediated, and Rheumatic Patients during the COVID-19 Pandemic (WARCOV) cohort study to address the question of whether patients with immune-mediated inflammatory disease (IMID), including inflammatory arthritis, psoriasis, or inflammatory bowel disease, should discontinue or modify their immunotherapy regimens in the face of potential exposure to COVID-19.

To date, the study has data on 1,122 patients; 604 with inflammatory arthritis, 128 of whom have tested positive for COVID-19. The team established a cohort using the first 86 IMID patients confirmed to have contracted COVID-19. The hospitalization rate was 16% overall, and use of corticosteroids was associated with increased hospitalization risk. A follow-up analysis looking at the first 103 inflammatory arthritis patients who contracted COVID-19 showed a hospitalization rate of 26% and a mortality of 4%. That hospitalization rate is similar to the general hospitalization rate estimated by the New York Department of Health, Dr. Haberman said in her presentation.

Risk factors associated with hospitalization included being older and having asthma or COPD, which is similar to the general population. Use of oral glucocorticoids was linked to a big increase in risk for hospitalization, even with doses less than 10 mg prednisone daily (odds ratio, 14.31; 95% confidence interval, 3.55-57.70). There were no links between use of any cytokine therapy and risk, but use of TNF inhibitors was associated with a reduced risk (OR, 0.35; 95% CI, 0.13-0.97), while use of JAK inhibitors was associated with greater risk (OR, 6.30; 95% CI, 1.68-23.69). The latter result is tentative because of a small sample size, and it was driven largely by the experiences of patients with psoriatic arthritis.

Another study, run by the COVID-19 Global Rheumatology Alliance, looked at 600 patients with rheumatic disease from 40 countries, and “found no smoking gun,” said Leonard Calabrese, DO, who leads the Cleveland Clinic’s section of clinical immunology, during his presentation. “People can develop this when they’re on hydroxychloroquine. They seem to do not remarkably bad or remarkably good. There is no adverse signal for biologics, but being on prednisone [at a dose of] more than 10 mg is not great,” said Dr. Calabrese, who also noted that other publications have supported these conclusions.

So given these findings, how should clinicians address patient concerns? In the absence of probable exposure, “we say it’s better to have a well-controlled IMID on therapy than a poorly-controlled IMID on submaximal therapy. We say stick to therapy and try to wean the prednisone down as low as possible,” Dr. Calabrese said.

More controversially, what should patients do if they have had a significant exposure, such as a close proximity, prolonged exposure encounter with an individual with documented COVID-19, or at high-risk of disease? Dr. Calabrese noted that the American College of Rheumatology (ACR) guidelines recommend that low-level immunomodulation can be continued, “with an asterisk if it’s hydroxychloroquine, and it is in most of our minds now that we know that it is not effective, and the toxicity in the COVID setting is still being worked out,” he said.

With respect to other immunosuppressants, the ACR recommends stopping them temporarily, although IL-6 inhibitors may be continued in select circumstances. Resumption of the therapeutics can resume after a negative COVID test or completion of a 2-week observation period.

When patients contract COVID-19, antimalarial medications can be continued because they have been studied. “But medium-level immunomodulators, in particular methotrexate, I have grave concerns about because it can inhibit the adaptive immune response and antibody formation,” he said. COVID-19 is a serious infection, and all serious biologics have a package insert saying to stop them in a serious infection. Again, IL-6 inhibitors may be considered an exception in the right circumstances. When to resume these medications remains unknown. “I think that’s a work in progress. Test-based versus clinic-based strategies are a matter of controversy,” Dr. Calabrese said.

Ultimately, the question of what to do with immunosuppressive therapies in this population will continue to be a challenge. “The only good answer is to follow the rules of social distancing and to wear a mask,” said Kristina Callis Duffin, MD, a cochair of the department of dermatology and associate professor of dermatology at the University of Utah, Salt Lake City.

COVID-19 has posed serious questions for patients with psoriatic disease and the clinicians who treat them. Both have serious concerns over whether psoriasis or the medications used to treat it pose additional risk for contracting COVID-19 or experiencing worse outcomes with illness.

At the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, experts gathered to discuss these concerns and what is known about the special risk factors for psoriatic disease patients.

Studies from a few registries have been done already among patients with autoimmune disease, and the results so far suggest that patients may be able to breathe a little easier. “I don’t see any data that suggests that use of immunosuppressives or having autoimmune disease increases your risk of acquiring it. I think most of the risk is driven by risk of exposure,” said Kevin Winthrop, MD, MPH, a professor of public health, infectious diseases, ophthalmology at Oregon Health & Science University, Portland, during a presentation.

That assertion was reinforced by data presented by Rebecca Haberman, MD, a rheumatologist at New York University Langone Health. Her group created the Web-Based Assessment of Autoimmune, Immune-Mediated, and Rheumatic Patients during the COVID-19 Pandemic (WARCOV) cohort study to address the question of whether patients with immune-mediated inflammatory disease (IMID), including inflammatory arthritis, psoriasis, or inflammatory bowel disease, should discontinue or modify their immunotherapy regimens in the face of potential exposure to COVID-19.

To date, the study has data on 1,122 patients; 604 with inflammatory arthritis, 128 of whom have tested positive for COVID-19. The team established a cohort using the first 86 IMID patients confirmed to have contracted COVID-19. The hospitalization rate was 16% overall, and use of corticosteroids was associated with increased hospitalization risk. A follow-up analysis looking at the first 103 inflammatory arthritis patients who contracted COVID-19 showed a hospitalization rate of 26% and a mortality of 4%. That hospitalization rate is similar to the general hospitalization rate estimated by the New York Department of Health, Dr. Haberman said in her presentation.

Risk factors associated with hospitalization included being older and having asthma or COPD, which is similar to the general population. Use of oral glucocorticoids was linked to a big increase in risk for hospitalization, even with doses less than 10 mg prednisone daily (odds ratio, 14.31; 95% confidence interval, 3.55-57.70). There were no links between use of any cytokine therapy and risk, but use of TNF inhibitors was associated with a reduced risk (OR, 0.35; 95% CI, 0.13-0.97), while use of JAK inhibitors was associated with greater risk (OR, 6.30; 95% CI, 1.68-23.69). The latter result is tentative because of a small sample size, and it was driven largely by the experiences of patients with psoriatic arthritis.

Another study, run by the COVID-19 Global Rheumatology Alliance, looked at 600 patients with rheumatic disease from 40 countries, and “found no smoking gun,” said Leonard Calabrese, DO, who leads the Cleveland Clinic’s section of clinical immunology, during his presentation. “People can develop this when they’re on hydroxychloroquine. They seem to do not remarkably bad or remarkably good. There is no adverse signal for biologics, but being on prednisone [at a dose of] more than 10 mg is not great,” said Dr. Calabrese, who also noted that other publications have supported these conclusions.

So given these findings, how should clinicians address patient concerns? In the absence of probable exposure, “we say it’s better to have a well-controlled IMID on therapy than a poorly-controlled IMID on submaximal therapy. We say stick to therapy and try to wean the prednisone down as low as possible,” Dr. Calabrese said.

More controversially, what should patients do if they have had a significant exposure, such as a close proximity, prolonged exposure encounter with an individual with documented COVID-19, or at high-risk of disease? Dr. Calabrese noted that the American College of Rheumatology (ACR) guidelines recommend that low-level immunomodulation can be continued, “with an asterisk if it’s hydroxychloroquine, and it is in most of our minds now that we know that it is not effective, and the toxicity in the COVID setting is still being worked out,” he said.

With respect to other immunosuppressants, the ACR recommends stopping them temporarily, although IL-6 inhibitors may be continued in select circumstances. Resumption of the therapeutics can resume after a negative COVID test or completion of a 2-week observation period.

When patients contract COVID-19, antimalarial medications can be continued because they have been studied. “But medium-level immunomodulators, in particular methotrexate, I have grave concerns about because it can inhibit the adaptive immune response and antibody formation,” he said. COVID-19 is a serious infection, and all serious biologics have a package insert saying to stop them in a serious infection. Again, IL-6 inhibitors may be considered an exception in the right circumstances. When to resume these medications remains unknown. “I think that’s a work in progress. Test-based versus clinic-based strategies are a matter of controversy,” Dr. Calabrese said.

Ultimately, the question of what to do with immunosuppressive therapies in this population will continue to be a challenge. “The only good answer is to follow the rules of social distancing and to wear a mask,” said Kristina Callis Duffin, MD, a cochair of the department of dermatology and associate professor of dermatology at the University of Utah, Salt Lake City.

COVID-19 has posed serious questions for patients with psoriatic disease and the clinicians who treat them. Both have serious concerns over whether psoriasis or the medications used to treat it pose additional risk for contracting COVID-19 or experiencing worse outcomes with illness.

At the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, experts gathered to discuss these concerns and what is known about the special risk factors for psoriatic disease patients.

Studies from a few registries have been done already among patients with autoimmune disease, and the results so far suggest that patients may be able to breathe a little easier. “I don’t see any data that suggests that use of immunosuppressives or having autoimmune disease increases your risk of acquiring it. I think most of the risk is driven by risk of exposure,” said Kevin Winthrop, MD, MPH, a professor of public health, infectious diseases, ophthalmology at Oregon Health & Science University, Portland, during a presentation.

That assertion was reinforced by data presented by Rebecca Haberman, MD, a rheumatologist at New York University Langone Health. Her group created the Web-Based Assessment of Autoimmune, Immune-Mediated, and Rheumatic Patients during the COVID-19 Pandemic (WARCOV) cohort study to address the question of whether patients with immune-mediated inflammatory disease (IMID), including inflammatory arthritis, psoriasis, or inflammatory bowel disease, should discontinue or modify their immunotherapy regimens in the face of potential exposure to COVID-19.

To date, the study has data on 1,122 patients; 604 with inflammatory arthritis, 128 of whom have tested positive for COVID-19. The team established a cohort using the first 86 IMID patients confirmed to have contracted COVID-19. The hospitalization rate was 16% overall, and use of corticosteroids was associated with increased hospitalization risk. A follow-up analysis looking at the first 103 inflammatory arthritis patients who contracted COVID-19 showed a hospitalization rate of 26% and a mortality of 4%. That hospitalization rate is similar to the general hospitalization rate estimated by the New York Department of Health, Dr. Haberman said in her presentation.

Risk factors associated with hospitalization included being older and having asthma or COPD, which is similar to the general population. Use of oral glucocorticoids was linked to a big increase in risk for hospitalization, even with doses less than 10 mg prednisone daily (odds ratio, 14.31; 95% confidence interval, 3.55-57.70). There were no links between use of any cytokine therapy and risk, but use of TNF inhibitors was associated with a reduced risk (OR, 0.35; 95% CI, 0.13-0.97), while use of JAK inhibitors was associated with greater risk (OR, 6.30; 95% CI, 1.68-23.69). The latter result is tentative because of a small sample size, and it was driven largely by the experiences of patients with psoriatic arthritis.

Another study, run by the COVID-19 Global Rheumatology Alliance, looked at 600 patients with rheumatic disease from 40 countries, and “found no smoking gun,” said Leonard Calabrese, DO, who leads the Cleveland Clinic’s section of clinical immunology, during his presentation. “People can develop this when they’re on hydroxychloroquine. They seem to do not remarkably bad or remarkably good. There is no adverse signal for biologics, but being on prednisone [at a dose of] more than 10 mg is not great,” said Dr. Calabrese, who also noted that other publications have supported these conclusions.

So given these findings, how should clinicians address patient concerns? In the absence of probable exposure, “we say it’s better to have a well-controlled IMID on therapy than a poorly-controlled IMID on submaximal therapy. We say stick to therapy and try to wean the prednisone down as low as possible,” Dr. Calabrese said.

More controversially, what should patients do if they have had a significant exposure, such as a close proximity, prolonged exposure encounter with an individual with documented COVID-19, or at high-risk of disease? Dr. Calabrese noted that the American College of Rheumatology (ACR) guidelines recommend that low-level immunomodulation can be continued, “with an asterisk if it’s hydroxychloroquine, and it is in most of our minds now that we know that it is not effective, and the toxicity in the COVID setting is still being worked out,” he said.

With respect to other immunosuppressants, the ACR recommends stopping them temporarily, although IL-6 inhibitors may be continued in select circumstances. Resumption of the therapeutics can resume after a negative COVID test or completion of a 2-week observation period.

When patients contract COVID-19, antimalarial medications can be continued because they have been studied. “But medium-level immunomodulators, in particular methotrexate, I have grave concerns about because it can inhibit the adaptive immune response and antibody formation,” he said. COVID-19 is a serious infection, and all serious biologics have a package insert saying to stop them in a serious infection. Again, IL-6 inhibitors may be considered an exception in the right circumstances. When to resume these medications remains unknown. “I think that’s a work in progress. Test-based versus clinic-based strategies are a matter of controversy,” Dr. Calabrese said.

Ultimately, the question of what to do with immunosuppressive therapies in this population will continue to be a challenge. “The only good answer is to follow the rules of social distancing and to wear a mask,” said Kristina Callis Duffin, MD, a cochair of the department of dermatology and associate professor of dermatology at the University of Utah, Salt Lake City.

Using a simple point-of-care (POC) finger prick device to measure blood glucose and lipid levels significantly increases rates of physical health checkups for patients with severe mental illness, new research shows.

In a UK pilot study, use of the Afinion 2 device (Abbott) was associated with a doubling of completed physical health checkups.

However, the effect only occurred in early-intervention services, in which clinicians may feel physical health checkups are most beneficial. This underlines the importance of staff training and payment incentives, the researchers note.

“Clearly, convenience is a great thing about these devices” for both the patient and the mental health clinician, Joseph Butler, MD, a psychiatry trainee at the University of Oxford, United Kingdom, told Medscape Medical News.

He noted that blood test results are rapid, which facilitates immediate discussion of a health management plan.

These tests are “independent from the lab, they’re independent from the general practitioner, and so in terms of convenience, we think it wins on both fronts,” Butler said.

The findings were scheduled to be presented at the Congress of the Schizophrenia International Research Society (SIRS) 2020, but the meeting was canceled because of the coronavirus pandemic.

Poor heart health

Previous research has shown that life expectancy of patients with severe mental illness is 15 to 20 years less than that of the general population, mostly because of complications from poor cardiovascular health.

In the United Kingdom, physical healthcare for patients with serious mental illness is provided by primary care clinicians and community mental health teams (CMHTs). The National Institute for Health and Care Excellence recommends an annual physical examination.

However, a recent audit in the south of England indicated that only 38% of patients with severe mental illness underwent complete physical examinations, primarily because blood glucose and lipid test panels had been omitted.

The researchers note that patients are typically advised to visit their general practitioner for blood tests, “which can be a challenge” for those with severe mental illness.

The Cardiovascular Monitoring in Mental Health (CARMEN) project involved distributing the Afinion 2 device for use in two CMHTs in Oxfordshire, United Kingdom, for 6 months. One CMHT was an early-intervention service, and the other was an adult mental health service.

Care coordinators received training on how to use the device as well as ongoing support to facilitate engagement with the device.

Rates of completion of blood testing and full physical examinations were compared between the intervention CMHTs and two matched control services – an early-intervention group, and an adult metal health services group in Buckinghamshire, a neighboring county.

Better completion rates

The investigators found that after the introduction of the POC, physical examination completion rates for the early-intervention service increased from 22.6% to 40.3% over 6 months.

In contrast, the percentage of physical examinations that were completed remained low in the control CMHT early-intervention service, at just 7.8%.

Direct comparison between the two services showed that use of the POC device was associated with a significant increase in the number of complete physical examinations, at a relative rate of 5.18 (P < .001).

Results were similar when the investigators examined rates at which A1c and lipid panels were completed.

However, there was no difference in completion of physical examinations in the adult mental health service group, for which rates were comparable to those in the control service.

Butler speculated that the way health checkups are funded in the United Kingdom might have contributed to the poor results with the device in the adult mental health service.

In early-intervention services, there is increased awareness of the importance of physical examinations, and funding is contingent on whether clinicians persuade patients to have the examinations.

Overall, the findings show that use of a POC device for physical examinations is acceptable to patients who have severe mental illness as well as to mental health care clinicians, the investigators note.

“In teams where it is well adopted, POC testing can improve physical health check completion...although our qualitative findings highlight important considerations for maximizing clinician engagement,” they add.

The researchers plan to repeat the study across the whole of the south of England, with early-intervention services in the west equipped with POC devices and those in the east serving as controls.

Similar findings

Commenting on the findings for Medscape Medical News, Joe Parks, MD, vice president and practice improvement and medical director at the National Council for Behavioral Health, Washington, DC, noted that he and his colleagues conducted a similar study in the mid-2000s.

Starting in 2004, they distributed a POC finger prick test device for use by community mental health teams to measure blood glucose and lipid levels.

“We required as a condition of payment that the providers get these lab results for everybody they served and report them centrally. Then, we databased them and benchmarked them, and we were able to show significant reductions in HbA1c’s over time,” said Parks, who was not involved with the current research.

Moreover, that program achieved corresponding savings of $23 to $24 million, he noted.

Although his study and the current study show that POC devices work, he emphasized that it’s not enough to make the devices available to clinicians.

“You also have to ensure the providers put it in their clinic workflows and use it with everybody. To do that, it really helps if you have the providers report the results, then give them report cards so they can see who’s doing it and who isn’t,” Parks said.

It wasn’t surprising that in the current study, the introduction of the POC device made less of an impact in the adult community services, he noted.

Although weight reduction is much slower in that setting, “you can still get better control of their lipids and HbA1c›s, and you get at their weight over time. You just have to program for that, too,» said Parks.

He added that it’s hard to achieve weight reduction of more than 5% or 10%, but many of these patients need a 25% to 30% reduction. “The only thing that’s going to get that is bariatric surgery,” he noted.

POC devices are not widely used in the United States.

“The payer paying for the care basically has to insist that [it] be used and then provide the machine and train the staff to use it,” Parks said.

It requires payers “to get actually involved in how providers organize and manage care, which they tend to not like to do. It’s silly because the only way any payer has to make anybody better is through the provider,” he noted.

Parks added that to increase uptake beyond the “motivated few” requires that it be made part of the workflow and not left up to clinician discretion.

The study was funded by the National Institute for Health Research. Butler and Parks have reported no relevant financial relationships.

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

Using a simple point-of-care (POC) finger prick device to measure blood glucose and lipid levels significantly increases rates of physical health checkups for patients with severe mental illness, new research shows.

In a UK pilot study, use of the Afinion 2 device (Abbott) was associated with a doubling of completed physical health checkups.

However, the effect only occurred in early-intervention services, in which clinicians may feel physical health checkups are most beneficial. This underlines the importance of staff training and payment incentives, the researchers note.

“Clearly, convenience is a great thing about these devices” for both the patient and the mental health clinician, Joseph Butler, MD, a psychiatry trainee at the University of Oxford, United Kingdom, told Medscape Medical News.

He noted that blood test results are rapid, which facilitates immediate discussion of a health management plan.

These tests are “independent from the lab, they’re independent from the general practitioner, and so in terms of convenience, we think it wins on both fronts,” Butler said.

The findings were scheduled to be presented at the Congress of the Schizophrenia International Research Society (SIRS) 2020, but the meeting was canceled because of the coronavirus pandemic.

Poor heart health

Previous research has shown that life expectancy of patients with severe mental illness is 15 to 20 years less than that of the general population, mostly because of complications from poor cardiovascular health.

In the United Kingdom, physical healthcare for patients with serious mental illness is provided by primary care clinicians and community mental health teams (CMHTs). The National Institute for Health and Care Excellence recommends an annual physical examination.

However, a recent audit in the south of England indicated that only 38% of patients with severe mental illness underwent complete physical examinations, primarily because blood glucose and lipid test panels had been omitted.

The researchers note that patients are typically advised to visit their general practitioner for blood tests, “which can be a challenge” for those with severe mental illness.

The Cardiovascular Monitoring in Mental Health (CARMEN) project involved distributing the Afinion 2 device for use in two CMHTs in Oxfordshire, United Kingdom, for 6 months. One CMHT was an early-intervention service, and the other was an adult mental health service.

Care coordinators received training on how to use the device as well as ongoing support to facilitate engagement with the device.

Rates of completion of blood testing and full physical examinations were compared between the intervention CMHTs and two matched control services – an early-intervention group, and an adult metal health services group in Buckinghamshire, a neighboring county.

Better completion rates

The investigators found that after the introduction of the POC, physical examination completion rates for the early-intervention service increased from 22.6% to 40.3% over 6 months.

In contrast, the percentage of physical examinations that were completed remained low in the control CMHT early-intervention service, at just 7.8%.

Direct comparison between the two services showed that use of the POC device was associated with a significant increase in the number of complete physical examinations, at a relative rate of 5.18 (P < .001).

Results were similar when the investigators examined rates at which A1c and lipid panels were completed.

However, there was no difference in completion of physical examinations in the adult mental health service group, for which rates were comparable to those in the control service.

Butler speculated that the way health checkups are funded in the United Kingdom might have contributed to the poor results with the device in the adult mental health service.

In early-intervention services, there is increased awareness of the importance of physical examinations, and funding is contingent on whether clinicians persuade patients to have the examinations.

Overall, the findings show that use of a POC device for physical examinations is acceptable to patients who have severe mental illness as well as to mental health care clinicians, the investigators note.

“In teams where it is well adopted, POC testing can improve physical health check completion...although our qualitative findings highlight important considerations for maximizing clinician engagement,” they add.

The researchers plan to repeat the study across the whole of the south of England, with early-intervention services in the west equipped with POC devices and those in the east serving as controls.

Similar findings

Commenting on the findings for Medscape Medical News, Joe Parks, MD, vice president and practice improvement and medical director at the National Council for Behavioral Health, Washington, DC, noted that he and his colleagues conducted a similar study in the mid-2000s.

Starting in 2004, they distributed a POC finger prick test device for use by community mental health teams to measure blood glucose and lipid levels.

“We required as a condition of payment that the providers get these lab results for everybody they served and report them centrally. Then, we databased them and benchmarked them, and we were able to show significant reductions in HbA1c’s over time,” said Parks, who was not involved with the current research.

Moreover, that program achieved corresponding savings of $23 to $24 million, he noted.

Although his study and the current study show that POC devices work, he emphasized that it’s not enough to make the devices available to clinicians.

“You also have to ensure the providers put it in their clinic workflows and use it with everybody. To do that, it really helps if you have the providers report the results, then give them report cards so they can see who’s doing it and who isn’t,” Parks said.

It wasn’t surprising that in the current study, the introduction of the POC device made less of an impact in the adult community services, he noted.

Although weight reduction is much slower in that setting, “you can still get better control of their lipids and HbA1c›s, and you get at their weight over time. You just have to program for that, too,» said Parks.

He added that it’s hard to achieve weight reduction of more than 5% or 10%, but many of these patients need a 25% to 30% reduction. “The only thing that’s going to get that is bariatric surgery,” he noted.

POC devices are not widely used in the United States.

“The payer paying for the care basically has to insist that [it] be used and then provide the machine and train the staff to use it,” Parks said.

It requires payers “to get actually involved in how providers organize and manage care, which they tend to not like to do. It’s silly because the only way any payer has to make anybody better is through the provider,” he noted.

Parks added that to increase uptake beyond the “motivated few” requires that it be made part of the workflow and not left up to clinician discretion.

The study was funded by the National Institute for Health Research. Butler and Parks have reported no relevant financial relationships.

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

Using a simple point-of-care (POC) finger prick device to measure blood glucose and lipid levels significantly increases rates of physical health checkups for patients with severe mental illness, new research shows.

In a UK pilot study, use of the Afinion 2 device (Abbott) was associated with a doubling of completed physical health checkups.

However, the effect only occurred in early-intervention services, in which clinicians may feel physical health checkups are most beneficial. This underlines the importance of staff training and payment incentives, the researchers note.

“Clearly, convenience is a great thing about these devices” for both the patient and the mental health clinician, Joseph Butler, MD, a psychiatry trainee at the University of Oxford, United Kingdom, told Medscape Medical News.

He noted that blood test results are rapid, which facilitates immediate discussion of a health management plan.

These tests are “independent from the lab, they’re independent from the general practitioner, and so in terms of convenience, we think it wins on both fronts,” Butler said.

The findings were scheduled to be presented at the Congress of the Schizophrenia International Research Society (SIRS) 2020, but the meeting was canceled because of the coronavirus pandemic.

Poor heart health

Previous research has shown that life expectancy of patients with severe mental illness is 15 to 20 years less than that of the general population, mostly because of complications from poor cardiovascular health.

In the United Kingdom, physical healthcare for patients with serious mental illness is provided by primary care clinicians and community mental health teams (CMHTs). The National Institute for Health and Care Excellence recommends an annual physical examination.

However, a recent audit in the south of England indicated that only 38% of patients with severe mental illness underwent complete physical examinations, primarily because blood glucose and lipid test panels had been omitted.

The researchers note that patients are typically advised to visit their general practitioner for blood tests, “which can be a challenge” for those with severe mental illness.

The Cardiovascular Monitoring in Mental Health (CARMEN) project involved distributing the Afinion 2 device for use in two CMHTs in Oxfordshire, United Kingdom, for 6 months. One CMHT was an early-intervention service, and the other was an adult mental health service.

Care coordinators received training on how to use the device as well as ongoing support to facilitate engagement with the device.

Rates of completion of blood testing and full physical examinations were compared between the intervention CMHTs and two matched control services – an early-intervention group, and an adult metal health services group in Buckinghamshire, a neighboring county.

Better completion rates

The investigators found that after the introduction of the POC, physical examination completion rates for the early-intervention service increased from 22.6% to 40.3% over 6 months.

In contrast, the percentage of physical examinations that were completed remained low in the control CMHT early-intervention service, at just 7.8%.

Direct comparison between the two services showed that use of the POC device was associated with a significant increase in the number of complete physical examinations, at a relative rate of 5.18 (P < .001).

Results were similar when the investigators examined rates at which A1c and lipid panels were completed.

However, there was no difference in completion of physical examinations in the adult mental health service group, for which rates were comparable to those in the control service.

Butler speculated that the way health checkups are funded in the United Kingdom might have contributed to the poor results with the device in the adult mental health service.

In early-intervention services, there is increased awareness of the importance of physical examinations, and funding is contingent on whether clinicians persuade patients to have the examinations.

Overall, the findings show that use of a POC device for physical examinations is acceptable to patients who have severe mental illness as well as to mental health care clinicians, the investigators note.

“In teams where it is well adopted, POC testing can improve physical health check completion...although our qualitative findings highlight important considerations for maximizing clinician engagement,” they add.

The researchers plan to repeat the study across the whole of the south of England, with early-intervention services in the west equipped with POC devices and those in the east serving as controls.

Similar findings

Commenting on the findings for Medscape Medical News, Joe Parks, MD, vice president and practice improvement and medical director at the National Council for Behavioral Health, Washington, DC, noted that he and his colleagues conducted a similar study in the mid-2000s.

Starting in 2004, they distributed a POC finger prick test device for use by community mental health teams to measure blood glucose and lipid levels.

“We required as a condition of payment that the providers get these lab results for everybody they served and report them centrally. Then, we databased them and benchmarked them, and we were able to show significant reductions in HbA1c’s over time,” said Parks, who was not involved with the current research.

Moreover, that program achieved corresponding savings of $23 to $24 million, he noted.

Although his study and the current study show that POC devices work, he emphasized that it’s not enough to make the devices available to clinicians.

“You also have to ensure the providers put it in their clinic workflows and use it with everybody. To do that, it really helps if you have the providers report the results, then give them report cards so they can see who’s doing it and who isn’t,” Parks said.

It wasn’t surprising that in the current study, the introduction of the POC device made less of an impact in the adult community services, he noted.

Although weight reduction is much slower in that setting, “you can still get better control of their lipids and HbA1c›s, and you get at their weight over time. You just have to program for that, too,» said Parks.

He added that it’s hard to achieve weight reduction of more than 5% or 10%, but many of these patients need a 25% to 30% reduction. “The only thing that’s going to get that is bariatric surgery,” he noted.

POC devices are not widely used in the United States.

“The payer paying for the care basically has to insist that [it] be used and then provide the machine and train the staff to use it,” Parks said.

It requires payers “to get actually involved in how providers organize and manage care, which they tend to not like to do. It’s silly because the only way any payer has to make anybody better is through the provider,” he noted.

Parks added that to increase uptake beyond the “motivated few” requires that it be made part of the workflow and not left up to clinician discretion.

The study was funded by the National Institute for Health Research. Butler and Parks have reported no relevant financial relationships.

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

Racial differences in the rates of atopic dermatitis appear to arise early in life, results from a single-center retrospective study found.

©Radist/Thinkstock

“Atopic dermatitis is a very common pediatric skin condition with significant morbidity for patients and their families,” lead study author Reesa L. Monir, MD, said during the virtual annual meeting of the Society for Pediatric Dermatology. “Existing studies show increased disease prevalence in Black and Asian children relative to White children, with conflicting data for Hispanic children. The methodology behind many of these existing studies, however, is somewhat questionable. Many were survey-based studies asking parents to remember a diagnosis of eczema or even asking parents to just report an itchy rash and using that as a diagnosis.”

For the current study, Dr. Monir and colleagues reviewed the records of 4,016 infants born between June 1, 2011, and April 30, 2017, who were followed in the University of Florida’s health care system. The researchers defined this as having two or more well-child visits after birth and at least one visit at 300 days of life or later, and the used documentation of specific ICD-9 or ICD-10 codes to capture an objective diagnosis of atopic dermatitis (AD). Of the 4,016 patients, 39.2% were Black, 38.5% were White, 7.1% were Hispanic, 5.3% were Asian, 6.5% were from other racial backgrounds, and 3.4% were multiracial.

Dr. Monir, who is a resident in the department of dermatology at the University of Florida, Gainesville, reported that Black infants had the highest prevalence of AD at 37%, followed by Asian infants (25.8%), Hispanic infants (24.1%), multiracial infants (23%), infants from other racial backgrounds (19.1%), and non-Hispanic White infants (17.9%). Compared with White infants, the odds ratio estimates for AD was highest for Black infants (OR, 2.62), followed by Asian infants (OR, 1.55), multiracial infants (OR, 1.42), Hispanic infants (OR, 1.41), and infants from other racial backgrounds (OR, .97).

On unadjusted analysis, the following factors were significantly associated with race: delivery mode (P = .006), insurance type (P less than .001), NICU stay (P less than .001), and gestational age (P less than .0001). However, on multivariate logistic regression, only two factors were significantly associated with the diagnosis of AD: race (P less than .0001) and NICU stay (P = .0385).

“When we looked at the early childhood period specifically, we found striking racial differences in the rates of AD arising early in life,” Dr. Monir concluded. “The diagnosis was independently associated with race and NICU stay. We suggest that further investigation into these disparities and ways we can mitigate them should focus on this early childhood period.”

The researchers reported having no relevant financial disclosures.

dbrunk@mdedge.com

Racial differences in the rates of atopic dermatitis appear to arise early in life, results from a single-center retrospective study found.

©Radist/Thinkstock

“Atopic dermatitis is a very common pediatric skin condition with significant morbidity for patients and their families,” lead study author Reesa L. Monir, MD, said during the virtual annual meeting of the Society for Pediatric Dermatology. “Existing studies show increased disease prevalence in Black and Asian children relative to White children, with conflicting data for Hispanic children. The methodology behind many of these existing studies, however, is somewhat questionable. Many were survey-based studies asking parents to remember a diagnosis of eczema or even asking parents to just report an itchy rash and using that as a diagnosis.”

For the current study, Dr. Monir and colleagues reviewed the records of 4,016 infants born between June 1, 2011, and April 30, 2017, who were followed in the University of Florida’s health care system. The researchers defined this as having two or more well-child visits after birth and at least one visit at 300 days of life or later, and the used documentation of specific ICD-9 or ICD-10 codes to capture an objective diagnosis of atopic dermatitis (AD). Of the 4,016 patients, 39.2% were Black, 38.5% were White, 7.1% were Hispanic, 5.3% were Asian, 6.5% were from other racial backgrounds, and 3.4% were multiracial.

Dr. Monir, who is a resident in the department of dermatology at the University of Florida, Gainesville, reported that Black infants had the highest prevalence of AD at 37%, followed by Asian infants (25.8%), Hispanic infants (24.1%), multiracial infants (23%), infants from other racial backgrounds (19.1%), and non-Hispanic White infants (17.9%). Compared with White infants, the odds ratio estimates for AD was highest for Black infants (OR, 2.62), followed by Asian infants (OR, 1.55), multiracial infants (OR, 1.42), Hispanic infants (OR, 1.41), and infants from other racial backgrounds (OR, .97).

On unadjusted analysis, the following factors were significantly associated with race: delivery mode (P = .006), insurance type (P less than .001), NICU stay (P less than .001), and gestational age (P less than .0001). However, on multivariate logistic regression, only two factors were significantly associated with the diagnosis of AD: race (P less than .0001) and NICU stay (P = .0385).

“When we looked at the early childhood period specifically, we found striking racial differences in the rates of AD arising early in life,” Dr. Monir concluded. “The diagnosis was independently associated with race and NICU stay. We suggest that further investigation into these disparities and ways we can mitigate them should focus on this early childhood period.”

The researchers reported having no relevant financial disclosures.

dbrunk@mdedge.com

Racial differences in the rates of atopic dermatitis appear to arise early in life, results from a single-center retrospective study found.

©Radist/Thinkstock

“Atopic dermatitis is a very common pediatric skin condition with significant morbidity for patients and their families,” lead study author Reesa L. Monir, MD, said during the virtual annual meeting of the Society for Pediatric Dermatology. “Existing studies show increased disease prevalence in Black and Asian children relative to White children, with conflicting data for Hispanic children. The methodology behind many of these existing studies, however, is somewhat questionable. Many were survey-based studies asking parents to remember a diagnosis of eczema or even asking parents to just report an itchy rash and using that as a diagnosis.”

For the current study, Dr. Monir and colleagues reviewed the records of 4,016 infants born between June 1, 2011, and April 30, 2017, who were followed in the University of Florida’s health care system. The researchers defined this as having two or more well-child visits after birth and at least one visit at 300 days of life or later, and the used documentation of specific ICD-9 or ICD-10 codes to capture an objective diagnosis of atopic dermatitis (AD). Of the 4,016 patients, 39.2% were Black, 38.5% were White, 7.1% were Hispanic, 5.3% were Asian, 6.5% were from other racial backgrounds, and 3.4% were multiracial.

Dr. Monir, who is a resident in the department of dermatology at the University of Florida, Gainesville, reported that Black infants had the highest prevalence of AD at 37%, followed by Asian infants (25.8%), Hispanic infants (24.1%), multiracial infants (23%), infants from other racial backgrounds (19.1%), and non-Hispanic White infants (17.9%). Compared with White infants, the odds ratio estimates for AD was highest for Black infants (OR, 2.62), followed by Asian infants (OR, 1.55), multiracial infants (OR, 1.42), Hispanic infants (OR, 1.41), and infants from other racial backgrounds (OR, .97).

On unadjusted analysis, the following factors were significantly associated with race: delivery mode (P = .006), insurance type (P less than .001), NICU stay (P less than .001), and gestational age (P less than .0001). However, on multivariate logistic regression, only two factors were significantly associated with the diagnosis of AD: race (P less than .0001) and NICU stay (P = .0385).

“When we looked at the early childhood period specifically, we found striking racial differences in the rates of AD arising early in life,” Dr. Monir concluded. “The diagnosis was independently associated with race and NICU stay. We suggest that further investigation into these disparities and ways we can mitigate them should focus on this early childhood period.”

The researchers reported having no relevant financial disclosures.

dbrunk@mdedge.com

Rilzabrutinib, a novel oral reversible Bruton’s tyrosine kinase inhibitor, delivered rapid control of pemphigus disease activity accompanied by markedly reduced need for systemic corticosteroids in the phase 2b BELIEVE-PV trial, Dedee F. Murrell, MD, said at the virtual annual meeting of the American Academy of Dermatology.

Moreover, in sharp contrast to the standard first-line treatments for pemphigus – rituximab (Rituxan) and high-dose corticosteroids – the treatment-emergent adverse events that arose with 6 months of rilzabrutinib in BELIEVE-PV were uniformly mild to moderate and transient, added Dr. Murrell, professor of dermatology at the University of New South Wales and head of the department of dermatology at St. George University Hospital, Sydney.

The phase 2b BELIEVE-PV trial was a small, 24-week, open-label study that included six patients with newly diagnosed pemphigus and nine others with relapsing pemphigus. The primary endpoint was control of disease activity, defined as no new lesions appearing and established lesions beginning to heal. This was achieved in 9 of 15 patients (60%) at 4 weeks and in 13 patients by week 12. Meanwhile, the mean daily dose of prednisone fell from 21 mg at baseline to 6 mg at 24 weeks.

The mean score on the Pemphigus Disease Area Index (PDAI) dropped by 79% from a baseline of 15.5. Ten of 15 subjects improved to a PDAI of 0 or 1 – clear or almost clear skin – by week 24. The complete remission rate, defined as an absence of both new and established lesions while on no or a very low dose of prednisone, was 40% at week 24.

Treatment-emergent adverse events consisted of nausea in four patients, dizziness in two, and abdominal distension in two, all of which were grade 1 or 2.

Based upon these favorable results, the pivotal phase 3, double-blind, international PEGASUS trial is underway, led by Dr. Murrell. The trial will enroll 120 pemphigus patients, randomized to rilzabrutinib at 400 mg twice daily or placebo on top of background steroid tapering.

Rilzabrutinib is also in earlier-stage clinical trials for the treatment of immune thrombocytopenia.

Dr. Murrell reported serving as a consultant to Principia Biopharma, sponsor of the BELIEVE-PV and PEGASUS trials, and has received institutional research grants from numerous pharmaceutical companies.

bjancin@mdedge.com

SOURCE: Murrell DF. AAD 2020 LBCT.

Rilzabrutinib, a novel oral reversible Bruton’s tyrosine kinase inhibitor, delivered rapid control of pemphigus disease activity accompanied by markedly reduced need for systemic corticosteroids in the phase 2b BELIEVE-PV trial, Dedee F. Murrell, MD, said at the virtual annual meeting of the American Academy of Dermatology.

Moreover, in sharp contrast to the standard first-line treatments for pemphigus – rituximab (Rituxan) and high-dose corticosteroids – the treatment-emergent adverse events that arose with 6 months of rilzabrutinib in BELIEVE-PV were uniformly mild to moderate and transient, added Dr. Murrell, professor of dermatology at the University of New South Wales and head of the department of dermatology at St. George University Hospital, Sydney.

The phase 2b BELIEVE-PV trial was a small, 24-week, open-label study that included six patients with newly diagnosed pemphigus and nine others with relapsing pemphigus. The primary endpoint was control of disease activity, defined as no new lesions appearing and established lesions beginning to heal. This was achieved in 9 of 15 patients (60%) at 4 weeks and in 13 patients by week 12. Meanwhile, the mean daily dose of prednisone fell from 21 mg at baseline to 6 mg at 24 weeks.

The mean score on the Pemphigus Disease Area Index (PDAI) dropped by 79% from a baseline of 15.5. Ten of 15 subjects improved to a PDAI of 0 or 1 – clear or almost clear skin – by week 24. The complete remission rate, defined as an absence of both new and established lesions while on no or a very low dose of prednisone, was 40% at week 24.

Treatment-emergent adverse events consisted of nausea in four patients, dizziness in two, and abdominal distension in two, all of which were grade 1 or 2.

Based upon these favorable results, the pivotal phase 3, double-blind, international PEGASUS trial is underway, led by Dr. Murrell. The trial will enroll 120 pemphigus patients, randomized to rilzabrutinib at 400 mg twice daily or placebo on top of background steroid tapering.

Rilzabrutinib is also in earlier-stage clinical trials for the treatment of immune thrombocytopenia.

Dr. Murrell reported serving as a consultant to Principia Biopharma, sponsor of the BELIEVE-PV and PEGASUS trials, and has received institutional research grants from numerous pharmaceutical companies.

bjancin@mdedge.com

SOURCE: Murrell DF. AAD 2020 LBCT.

Rilzabrutinib, a novel oral reversible Bruton’s tyrosine kinase inhibitor, delivered rapid control of pemphigus disease activity accompanied by markedly reduced need for systemic corticosteroids in the phase 2b BELIEVE-PV trial, Dedee F. Murrell, MD, said at the virtual annual meeting of the American Academy of Dermatology.

Moreover, in sharp contrast to the standard first-line treatments for pemphigus – rituximab (Rituxan) and high-dose corticosteroids – the treatment-emergent adverse events that arose with 6 months of rilzabrutinib in BELIEVE-PV were uniformly mild to moderate and transient, added Dr. Murrell, professor of dermatology at the University of New South Wales and head of the department of dermatology at St. George University Hospital, Sydney.

The phase 2b BELIEVE-PV trial was a small, 24-week, open-label study that included six patients with newly diagnosed pemphigus and nine others with relapsing pemphigus. The primary endpoint was control of disease activity, defined as no new lesions appearing and established lesions beginning to heal. This was achieved in 9 of 15 patients (60%) at 4 weeks and in 13 patients by week 12. Meanwhile, the mean daily dose of prednisone fell from 21 mg at baseline to 6 mg at 24 weeks.

The mean score on the Pemphigus Disease Area Index (PDAI) dropped by 79% from a baseline of 15.5. Ten of 15 subjects improved to a PDAI of 0 or 1 – clear or almost clear skin – by week 24. The complete remission rate, defined as an absence of both new and established lesions while on no or a very low dose of prednisone, was 40% at week 24.

Treatment-emergent adverse events consisted of nausea in four patients, dizziness in two, and abdominal distension in two, all of which were grade 1 or 2.

Based upon these favorable results, the pivotal phase 3, double-blind, international PEGASUS trial is underway, led by Dr. Murrell. The trial will enroll 120 pemphigus patients, randomized to rilzabrutinib at 400 mg twice daily or placebo on top of background steroid tapering.

Rilzabrutinib is also in earlier-stage clinical trials for the treatment of immune thrombocytopenia.

Dr. Murrell reported serving as a consultant to Principia Biopharma, sponsor of the BELIEVE-PV and PEGASUS trials, and has received institutional research grants from numerous pharmaceutical companies.

bjancin@mdedge.com

SOURCE: Murrell DF. AAD 2020 LBCT.

Factor VIII expression was detected on liver biopsies at more than 2 years after a single infusion of adeno-associated virus (AAV) gene therapy for hemophilia A in two patients who were part of a recent phase 1/2 study and who participated in an optional liver biopsy substudy.

The persistent factor VIII (FVIII) expression seen in the two patients was consistent with the presence of circularized, full-length human FVIII-SQ DNA in the biopsy samples and was observed in one patients at week 201 after infusion with 6 x 10¹² vg/kg of the AAV serotype 5 human FVIII-SQ gene therapy(valoctocogene roxaparvovec) and in another at week 140 after infusion with 4×10¹³ vg/kg, Sylvia Fong, PhD, reported during the International Society of Thrombosis and Haemostasis virtual congress.

The first patient had no FVIII detected in the plasma at the time of biopsy. The second had 28.4% of normal FVIII activity detected at the time of biopsy, said Dr. Fong of BioMarin Pharmaceutical, noting that alanine aminotransferase levels were normal at the time of biopsy for both subjects.

“Valoctocogene roxaparvovec is currently being evaluated in a phase 3 clinical study,” Dr. Fong said. “Data from the phase 1/2 trial have demonstrated preliminary proof of concept that valoctocogene roxaparvovec treatment, in many cases, eliminated spontaneous bleeds and the need for prophylactic factor VIII replacement.

“In addition, an acceptable safety profile was observed.”

Data from that trial were presented at the World Federation of Hemophilia virtual summit in June.
 

Liver biopsy for factor VIII expression

The current exploratory liver biopsy substudy – the first-in-human liver biopsy study after gene therapy for hemophilia A – was open to all phase 1/2 study participants and was initiated in September 2019 with multiple aims, including improved understanding of the durability and variability of AAV gene therapy, she explained.

Histopathological examination revealed normal liver architecture with mild steatosis and no evidence of steatohepatitis or significant inflammation in either participant. In the 6×10¹² vg/kg– and 4×10¹³ vg/kg–treated participants, a dose-dependent increase was seen in the percentage of hepatocytes that stained positive for vector genomes (1.3% and 32%, respectively), she said.

“This was very exciting to see,” she said, referring to the 32% stain-positive rate in the patient who received the 4x10¹³ vg/kg dose. “Not only were we able to detect vector genomes more than 2 years post-dose, there seems to be quite a bit of signals in this patient sample.”

The findings were similar to those seen in preclinical nonhuman primate models, she noted.

Dose-dependent increases were also seen in quantities of circular full-length/ITR-fused vector genomes and in FVIII-SQ RNA vector genomes; liver hFVIII-SQ RNA levels were 7.67×10² copies/mcg and 6.77×10⁴ copies/µg in the 6×10¹² vg/kg–treated participant the 4×10¹³ vg/kg–treated participant, respectively.

The circularized genomes were present as monomers and concatemers in both participants, and “were presumably associated with long-term expression,” Dr. Fong said.

Both participants are clinically stable with no long-term hepatic issues, she said, noting that analyses of results from additional participants in the substudy will be shared as they become available.

To date, because of “precious small amounts” of tissue available from the biopsy samples, Dr. Fong said she and her colleagues had not looked for degradation of the vectors.

Session moderator Sebastien Lacroix-Desmazes, MD, of Centre de recherche des Cordeliers, Paris, asked: “Is there a plan [to do so] or not, because I guess it’s a very important point,” to which Dr. Fong said that it is a possibility if adequate samples become available.

Dr. Fong is an employee of BioMarin Pharmaceuticals.

sworcester@mdedge.com

SOURCE: Fong S. 2020 ISTH Congress, Abstract OC 03.4.

Factor VIII expression was detected on liver biopsies at more than 2 years after a single infusion of adeno-associated virus (AAV) gene therapy for hemophilia A in two patients who were part of a recent phase 1/2 study and who participated in an optional liver biopsy substudy.

The persistent factor VIII (FVIII) expression seen in the two patients was consistent with the presence of circularized, full-length human FVIII-SQ DNA in the biopsy samples and was observed in one patients at week 201 after infusion with 6 x 10¹² vg/kg of the AAV serotype 5 human FVIII-SQ gene therapy(valoctocogene roxaparvovec) and in another at week 140 after infusion with 4×10¹³ vg/kg, Sylvia Fong, PhD, reported during the International Society of Thrombosis and Haemostasis virtual congress.

The first patient had no FVIII detected in the plasma at the time of biopsy. The second had 28.4% of normal FVIII activity detected at the time of biopsy, said Dr. Fong of BioMarin Pharmaceutical, noting that alanine aminotransferase levels were normal at the time of biopsy for both subjects.

“Valoctocogene roxaparvovec is currently being evaluated in a phase 3 clinical study,” Dr. Fong said. “Data from the phase 1/2 trial have demonstrated preliminary proof of concept that valoctocogene roxaparvovec treatment, in many cases, eliminated spontaneous bleeds and the need for prophylactic factor VIII replacement.

“In addition, an acceptable safety profile was observed.”

Data from that trial were presented at the World Federation of Hemophilia virtual summit in June.
 

Liver biopsy for factor VIII expression

The current exploratory liver biopsy substudy – the first-in-human liver biopsy study after gene therapy for hemophilia A – was open to all phase 1/2 study participants and was initiated in September 2019 with multiple aims, including improved understanding of the durability and variability of AAV gene therapy, she explained.

Histopathological examination revealed normal liver architecture with mild steatosis and no evidence of steatohepatitis or significant inflammation in either participant. In the 6×10¹² vg/kg– and 4×10¹³ vg/kg–treated participants, a dose-dependent increase was seen in the percentage of hepatocytes that stained positive for vector genomes (1.3% and 32%, respectively), she said.

“This was very exciting to see,” she said, referring to the 32% stain-positive rate in the patient who received the 4x10¹³ vg/kg dose. “Not only were we able to detect vector genomes more than 2 years post-dose, there seems to be quite a bit of signals in this patient sample.”

The findings were similar to those seen in preclinical nonhuman primate models, she noted.

Dose-dependent increases were also seen in quantities of circular full-length/ITR-fused vector genomes and in FVIII-SQ RNA vector genomes; liver hFVIII-SQ RNA levels were 7.67×10² copies/mcg and 6.77×10⁴ copies/µg in the 6×10¹² vg/kg–treated participant the 4×10¹³ vg/kg–treated participant, respectively.

The circularized genomes were present as monomers and concatemers in both participants, and “were presumably associated with long-term expression,” Dr. Fong said.

Both participants are clinically stable with no long-term hepatic issues, she said, noting that analyses of results from additional participants in the substudy will be shared as they become available.

To date, because of “precious small amounts” of tissue available from the biopsy samples, Dr. Fong said she and her colleagues had not looked for degradation of the vectors.

Session moderator Sebastien Lacroix-Desmazes, MD, of Centre de recherche des Cordeliers, Paris, asked: “Is there a plan [to do so] or not, because I guess it’s a very important point,” to which Dr. Fong said that it is a possibility if adequate samples become available.

Dr. Fong is an employee of BioMarin Pharmaceuticals.

sworcester@mdedge.com

SOURCE: Fong S. 2020 ISTH Congress, Abstract OC 03.4.

Factor VIII expression was detected on liver biopsies at more than 2 years after a single infusion of adeno-associated virus (AAV) gene therapy for hemophilia A in two patients who were part of a recent phase 1/2 study and who participated in an optional liver biopsy substudy.

The persistent factor VIII (FVIII) expression seen in the two patients was consistent with the presence of circularized, full-length human FVIII-SQ DNA in the biopsy samples and was observed in one patients at week 201 after infusion with 6 x 10¹² vg/kg of the AAV serotype 5 human FVIII-SQ gene therapy(valoctocogene roxaparvovec) and in another at week 140 after infusion with 4×10¹³ vg/kg, Sylvia Fong, PhD, reported during the International Society of Thrombosis and Haemostasis virtual congress.

The first patient had no FVIII detected in the plasma at the time of biopsy. The second had 28.4% of normal FVIII activity detected at the time of biopsy, said Dr. Fong of BioMarin Pharmaceutical, noting that alanine aminotransferase levels were normal at the time of biopsy for both subjects.

“Valoctocogene roxaparvovec is currently being evaluated in a phase 3 clinical study,” Dr. Fong said. “Data from the phase 1/2 trial have demonstrated preliminary proof of concept that valoctocogene roxaparvovec treatment, in many cases, eliminated spontaneous bleeds and the need for prophylactic factor VIII replacement.

“In addition, an acceptable safety profile was observed.”

Data from that trial were presented at the World Federation of Hemophilia virtual summit in June.
 

Liver biopsy for factor VIII expression

The current exploratory liver biopsy substudy – the first-in-human liver biopsy study after gene therapy for hemophilia A – was open to all phase 1/2 study participants and was initiated in September 2019 with multiple aims, including improved understanding of the durability and variability of AAV gene therapy, she explained.

Histopathological examination revealed normal liver architecture with mild steatosis and no evidence of steatohepatitis or significant inflammation in either participant. In the 6×10¹² vg/kg– and 4×10¹³ vg/kg–treated participants, a dose-dependent increase was seen in the percentage of hepatocytes that stained positive for vector genomes (1.3% and 32%, respectively), she said.

“This was very exciting to see,” she said, referring to the 32% stain-positive rate in the patient who received the 4x10¹³ vg/kg dose. “Not only were we able to detect vector genomes more than 2 years post-dose, there seems to be quite a bit of signals in this patient sample.”

The findings were similar to those seen in preclinical nonhuman primate models, she noted.

Dose-dependent increases were also seen in quantities of circular full-length/ITR-fused vector genomes and in FVIII-SQ RNA vector genomes; liver hFVIII-SQ RNA levels were 7.67×10² copies/mcg and 6.77×10⁴ copies/µg in the 6×10¹² vg/kg–treated participant the 4×10¹³ vg/kg–treated participant, respectively.

The circularized genomes were present as monomers and concatemers in both participants, and “were presumably associated with long-term expression,” Dr. Fong said.

Both participants are clinically stable with no long-term hepatic issues, she said, noting that analyses of results from additional participants in the substudy will be shared as they become available.

To date, because of “precious small amounts” of tissue available from the biopsy samples, Dr. Fong said she and her colleagues had not looked for degradation of the vectors.

Session moderator Sebastien Lacroix-Desmazes, MD, of Centre de recherche des Cordeliers, Paris, asked: “Is there a plan [to do so] or not, because I guess it’s a very important point,” to which Dr. Fong said that it is a possibility if adequate samples become available.

Dr. Fong is an employee of BioMarin Pharmaceuticals.

sworcester@mdedge.com

SOURCE: Fong S. 2020 ISTH Congress, Abstract OC 03.4.

The conventional treatment mainstays for pemphigus are problematic during the COVID-19 pandemic, and a shift in disease management strategy is in order, Dedee F. Murrell, MD, said at the virtual annual meeting of the American Academy of Dermatology.

Together with physicians from the Mayo Clinic, Alexandria (Egypt) University, and Tehran (Iran) University, she recently published updated expert guidance for treatment of this severe, potentially fatal mucocutaneous autoimmune blistering disease, in a letter to the editor in the Journal of the American Academy of Dermatology. She presented some of the key recommendations at AAD 2020.

First off, rituximab (Rituxan), the only Food and Drug Administration–approved medication for moderate to severe pemphigus vulgaris and a biologic considered first-line therapy prepandemic, is ill-advised during the COVID-19 era. Its mechanism of benefit is through B-cell depletion. This is an irreversible effect, and reconstitution of B-cell immunity takes 6-12 months. The absence of this immunologic protection for such a long time poses potentially serious problems for pemphigus patients who become infected with SARS-CoV-2.

Also, the opportunity to administer intravenous infusions of the biologic becomes unpredictable during pandemic surges, when limitations on nonemergent medical care may be necessary, noted Dr. Murrell, professor of dermatology at the University of New South Wales and head of dermatology at St. George University Hospital, both in Sydney.

“We have taken the approach of postponing rituximab infusions temporarily, with the aim of delaying peak patient immunosuppression during peak COVID-19 incidence to reduce the risk of adverse outcomes,” Dr. Murrell and coauthors wrote in the letter (J Am Acad Dermatol. 2020 Jun;82[6]:e235-6).

The other traditional go-to therapy for pemphigus is corticosteroids. They’re effective, fast acting, and relatively inexpensive. But their nonselective immunosuppressive action boosts infection risk in general, and more specifically it increases the risk of developing severe forms of COVID-19 should a patient become infected with SARS-CoV-2.

“A basic therapeutic principle with particular importance during the pandemic is that glucocorticoids and steroid-sparing immunosuppressive agents, such as azathioprine and mycophenolate mofetil, should be tapered to the lowest effective dose. In active COVID-19 infection, immunosuppressive steroid-sparing medications should be discontinued when possible, although glucocorticoid cessation often cannot be considered due to risk for adrenal insufficiency,” the authors continued.

“Effective as adjuvant treatment in both pemphigus and COVID-19,intravenous immunoglobulin supports immunity and therefore may be useful in this setting,” they wrote. It’s not immunosuppressive, and, they noted, there’s good-quality evidence from a Japanese randomized, double-blind, controlled trial that a 5-day course of intravenous immunoglobulin is effective therapy for pemphigus (J Am Acad Dermatol. 2009 Apr;60[4]:595-603).

Moreover, intravenous immunoglobulin is also reportedly effective in severe COVID-19 (Open Forum Infect Dis. 2020 Mar 21. doi: 10.1093/ofid/ofaa102.).

Another option is to consider enrolling a patient with moderate or severe pemphigus vulgaris or foliaceus in the ongoing pivotal phase 3, international, double-blind, placebo-controlled PEGASUS trial of rilzabrutinib, a promising oral reversible Bruton tyrosine kinase inhibitor. The medication has a short half-life and a self-limited immunomodulatory effect. Moreover, the trial is set up for remote patient visits on an outpatient basis via teledermatology, so the 65-week study can continue despite the pandemic. Both newly diagnosed and relapsing patients are eligible for the trial, headed by Dr. Murrell. At AAD 2020 she reported encouraging results from a phase 2b trial of rilzabrutinib.

She is a consultant to Principia Biopharma, sponsor of the PEGASUS trial, and has received institutional research grants from numerous pharmaceutical companies.

bjancin@mdedge.com

The conventional treatment mainstays for pemphigus are problematic during the COVID-19 pandemic, and a shift in disease management strategy is in order, Dedee F. Murrell, MD, said at the virtual annual meeting of the American Academy of Dermatology.

Together with physicians from the Mayo Clinic, Alexandria (Egypt) University, and Tehran (Iran) University, she recently published updated expert guidance for treatment of this severe, potentially fatal mucocutaneous autoimmune blistering disease, in a letter to the editor in the Journal of the American Academy of Dermatology. She presented some of the key recommendations at AAD 2020.

First off, rituximab (Rituxan), the only Food and Drug Administration–approved medication for moderate to severe pemphigus vulgaris and a biologic considered first-line therapy prepandemic, is ill-advised during the COVID-19 era. Its mechanism of benefit is through B-cell depletion. This is an irreversible effect, and reconstitution of B-cell immunity takes 6-12 months. The absence of this immunologic protection for such a long time poses potentially serious problems for pemphigus patients who become infected with SARS-CoV-2.

Also, the opportunity to administer intravenous infusions of the biologic becomes unpredictable during pandemic surges, when limitations on nonemergent medical care may be necessary, noted Dr. Murrell, professor of dermatology at the University of New South Wales and head of dermatology at St. George University Hospital, both in Sydney.

“We have taken the approach of postponing rituximab infusions temporarily, with the aim of delaying peak patient immunosuppression during peak COVID-19 incidence to reduce the risk of adverse outcomes,” Dr. Murrell and coauthors wrote in the letter (J Am Acad Dermatol. 2020 Jun;82[6]:e235-6).

The other traditional go-to therapy for pemphigus is corticosteroids. They’re effective, fast acting, and relatively inexpensive. But their nonselective immunosuppressive action boosts infection risk in general, and more specifically it increases the risk of developing severe forms of COVID-19 should a patient become infected with SARS-CoV-2.

“A basic therapeutic principle with particular importance during the pandemic is that glucocorticoids and steroid-sparing immunosuppressive agents, such as azathioprine and mycophenolate mofetil, should be tapered to the lowest effective dose. In active COVID-19 infection, immunosuppressive steroid-sparing medications should be discontinued when possible, although glucocorticoid cessation often cannot be considered due to risk for adrenal insufficiency,” the authors continued.

“Effective as adjuvant treatment in both pemphigus and COVID-19,intravenous immunoglobulin supports immunity and therefore may be useful in this setting,” they wrote. It’s not immunosuppressive, and, they noted, there’s good-quality evidence from a Japanese randomized, double-blind, controlled trial that a 5-day course of intravenous immunoglobulin is effective therapy for pemphigus (J Am Acad Dermatol. 2009 Apr;60[4]:595-603).

Moreover, intravenous immunoglobulin is also reportedly effective in severe COVID-19 (Open Forum Infect Dis. 2020 Mar 21. doi: 10.1093/ofid/ofaa102.).

Another option is to consider enrolling a patient with moderate or severe pemphigus vulgaris or foliaceus in the ongoing pivotal phase 3, international, double-blind, placebo-controlled PEGASUS trial of rilzabrutinib, a promising oral reversible Bruton tyrosine kinase inhibitor. The medication has a short half-life and a self-limited immunomodulatory effect. Moreover, the trial is set up for remote patient visits on an outpatient basis via teledermatology, so the 65-week study can continue despite the pandemic. Both newly diagnosed and relapsing patients are eligible for the trial, headed by Dr. Murrell. At AAD 2020 she reported encouraging results from a phase 2b trial of rilzabrutinib.

She is a consultant to Principia Biopharma, sponsor of the PEGASUS trial, and has received institutional research grants from numerous pharmaceutical companies.

bjancin@mdedge.com

The conventional treatment mainstays for pemphigus are problematic during the COVID-19 pandemic, and a shift in disease management strategy is in order, Dedee F. Murrell, MD, said at the virtual annual meeting of the American Academy of Dermatology.

Together with physicians from the Mayo Clinic, Alexandria (Egypt) University, and Tehran (Iran) University, she recently published updated expert guidance for treatment of this severe, potentially fatal mucocutaneous autoimmune blistering disease, in a letter to the editor in the Journal of the American Academy of Dermatology. She presented some of the key recommendations at AAD 2020.

First off, rituximab (Rituxan), the only Food and Drug Administration–approved medication for moderate to severe pemphigus vulgaris and a biologic considered first-line therapy prepandemic, is ill-advised during the COVID-19 era. Its mechanism of benefit is through B-cell depletion. This is an irreversible effect, and reconstitution of B-cell immunity takes 6-12 months. The absence of this immunologic protection for such a long time poses potentially serious problems for pemphigus patients who become infected with SARS-CoV-2.

Also, the opportunity to administer intravenous infusions of the biologic becomes unpredictable during pandemic surges, when limitations on nonemergent medical care may be necessary, noted Dr. Murrell, professor of dermatology at the University of New South Wales and head of dermatology at St. George University Hospital, both in Sydney.

“We have taken the approach of postponing rituximab infusions temporarily, with the aim of delaying peak patient immunosuppression during peak COVID-19 incidence to reduce the risk of adverse outcomes,” Dr. Murrell and coauthors wrote in the letter (J Am Acad Dermatol. 2020 Jun;82[6]:e235-6).

The other traditional go-to therapy for pemphigus is corticosteroids. They’re effective, fast acting, and relatively inexpensive. But their nonselective immunosuppressive action boosts infection risk in general, and more specifically it increases the risk of developing severe forms of COVID-19 should a patient become infected with SARS-CoV-2.

“A basic therapeutic principle with particular importance during the pandemic is that glucocorticoids and steroid-sparing immunosuppressive agents, such as azathioprine and mycophenolate mofetil, should be tapered to the lowest effective dose. In active COVID-19 infection, immunosuppressive steroid-sparing medications should be discontinued when possible, although glucocorticoid cessation often cannot be considered due to risk for adrenal insufficiency,” the authors continued.

“Effective as adjuvant treatment in both pemphigus and COVID-19,intravenous immunoglobulin supports immunity and therefore may be useful in this setting,” they wrote. It’s not immunosuppressive, and, they noted, there’s good-quality evidence from a Japanese randomized, double-blind, controlled trial that a 5-day course of intravenous immunoglobulin is effective therapy for pemphigus (J Am Acad Dermatol. 2009 Apr;60[4]:595-603).

Moreover, intravenous immunoglobulin is also reportedly effective in severe COVID-19 (Open Forum Infect Dis. 2020 Mar 21. doi: 10.1093/ofid/ofaa102.).

Another option is to consider enrolling a patient with moderate or severe pemphigus vulgaris or foliaceus in the ongoing pivotal phase 3, international, double-blind, placebo-controlled PEGASUS trial of rilzabrutinib, a promising oral reversible Bruton tyrosine kinase inhibitor. The medication has a short half-life and a self-limited immunomodulatory effect. Moreover, the trial is set up for remote patient visits on an outpatient basis via teledermatology, so the 65-week study can continue despite the pandemic. Both newly diagnosed and relapsing patients are eligible for the trial, headed by Dr. Murrell. At AAD 2020 she reported encouraging results from a phase 2b trial of rilzabrutinib.

She is a consultant to Principia Biopharma, sponsor of the PEGASUS trial, and has received institutional research grants from numerous pharmaceutical companies.

bjancin@mdedge.com

When people were offered preexposure prophylaxis (PrEP) outside of traditional clinics, regardless of specific risk factors, as part of the Sustainable East Africa Research in Community Health (SEARCH) study, new HIV acquisitions dropped by 74%.

It’s a valuable lesson to providers around the world, said Catherine Koss, MD, assistant professor of medicine in HIV, infectious disease, and global medicine at the University of California, San Francisco.

“We haven’t really seen PrEP being scaled up and offered at such a broad level in communities,” Koss said during the International AIDS Conference 2020. “Offering PrEP in a way that’s more universal and with a low barrier to both men and women can result in reductions in incidence.”

The first part of SEARCH, which looked at the impact of universal testing and access to HIV treatment immediately after diagnosis, showed that the strategy resulted in a population-wide 30% reduction in new HIV acquisitions. In other words, treatment alone wasn’t enough to end the HIV epidemic.

But the researchers always knew “there were likely going to be new HIV infections,” even with universal HIV testing and treatment, Koss said.

So the second part of the study was designed to see whether PrEP — with the combination of tenofovir disoproxil fumarate plus emtricitabine (Truvada, Gilead Sciences) — could further reduce rates of HIV acquisition.
 

PrEP out in the community

During the PrEP part of the SEARCH study, researchers discussed HIV risk with adults in 16 communities in rural Kenya and Uganda during population-level testing that took place at health fairs, beaches, trading centers, other community sites, and even in participants’ homes. PrEP was offered to anyone in a relationship with someone living with HIV, to anyone determined to be at elevated risk for infection by a previously validated algorithm, and to anyone who did not fit those criteria but who wanted a prescription.

Of the 15,632 adults eligible for PrEP, 5,447 (35%) chose to start the HIV prevention pill.

A rapid-enrollment protocol meant that people received their prescription at the time of screening or soon after that. Participants underwent testing for HIV antibodies — also out in the community — at weeks 4 and 12, and every 12 weeks thereafter; this will continue out to week 144.

HIV-negative adults who were part of the larger SEARCH cohort in the year before PrEP was made available — and from the same communities — served as the control group.

Interim 60-week data show that the rate of acquisition was 74% lower in the PrEP group than in the control group (incidence rate ratio, 0.26; P = .01). In women, the acquisition rate was 76% lower (incidence rate ratio, 0.24; P = .04), and in men, it was 40% lower (incidence rate ratio, 0.60; P = .54).

The reduction was not significant for men, probably because so few men acquired HIV, Koss reported. The powerful drop in new HIV cases overall was related to PrEP use by women; cases in women fell from 1.52 to 0.40 per 100 person-years.

Blood tests showed that 72% of the people who acquired HIV during the study period had not taken a PrEP pill for at least 30 days before their diagnosis.

“Making PrEP more easily accessible and more community-based could be very powerful in the United States,” said Koss.

“Allowing people to test for HIV and start PrEP outside of health clinics or standard health facilities could help reach more people,” she told Medscape Medical News. “Many of the people who benefit from PrEP may not otherwise need to seek medical care regularly if they’re otherwise healthy and often young.”

When PrEP is made available — easily available —  people will pick it up, they will take it away, they will put it in their mouths, and they will not get HIV.

The findings were hailed by others in the field of HIV prevention.

“They’re fantastic,” said Jared Baeten, MD, vice dean of the School of Public Health and professor of global health, medicine, and epidemiology at the University of Washington in Seattle. He was involved in Partners PrEP, a study of PrEP use in mixed-HIV-status couples, the Partners Demonstration Project, and HOPE, a study of the dapivirine ring for HIV prevention.

“These data provide real evidence that when PrEP is made available — easily available — people will pick it up, they will take it away, they will put it in their mouths, and they will not get HIV,” he said in an interview.

Even more, they clarify something that has stymied American regulators and clinicians.

Early studies of PrEP use by single women were stopped because participants weren’t taking the pills; adherence was so low that researchers couldn’t show efficacy. Since then, various trials — including Partners PrEP — have shown that PrEP works in women, but doubts have lingered, leading women to “get the short end of the stick in discussions about PrEP,” Baeten explained.

“There really shouldn’t be questions anymore,” he said. “These findings should put to rest any question about women in Africa being able to benefit from PrEP.”

This article first appeared on Medscape.com.

When people were offered preexposure prophylaxis (PrEP) outside of traditional clinics, regardless of specific risk factors, as part of the Sustainable East Africa Research in Community Health (SEARCH) study, new HIV acquisitions dropped by 74%.

It’s a valuable lesson to providers around the world, said Catherine Koss, MD, assistant professor of medicine in HIV, infectious disease, and global medicine at the University of California, San Francisco.

“We haven’t really seen PrEP being scaled up and offered at such a broad level in communities,” Koss said during the International AIDS Conference 2020. “Offering PrEP in a way that’s more universal and with a low barrier to both men and women can result in reductions in incidence.”

The first part of SEARCH, which looked at the impact of universal testing and access to HIV treatment immediately after diagnosis, showed that the strategy resulted in a population-wide 30% reduction in new HIV acquisitions. In other words, treatment alone wasn’t enough to end the HIV epidemic.

But the researchers always knew “there were likely going to be new HIV infections,” even with universal HIV testing and treatment, Koss said.

So the second part of the study was designed to see whether PrEP — with the combination of tenofovir disoproxil fumarate plus emtricitabine (Truvada, Gilead Sciences) — could further reduce rates of HIV acquisition.
 

PrEP out in the community

During the PrEP part of the SEARCH study, researchers discussed HIV risk with adults in 16 communities in rural Kenya and Uganda during population-level testing that took place at health fairs, beaches, trading centers, other community sites, and even in participants’ homes. PrEP was offered to anyone in a relationship with someone living with HIV, to anyone determined to be at elevated risk for infection by a previously validated algorithm, and to anyone who did not fit those criteria but who wanted a prescription.

Of the 15,632 adults eligible for PrEP, 5,447 (35%) chose to start the HIV prevention pill.

A rapid-enrollment protocol meant that people received their prescription at the time of screening or soon after that. Participants underwent testing for HIV antibodies — also out in the community — at weeks 4 and 12, and every 12 weeks thereafter; this will continue out to week 144.

HIV-negative adults who were part of the larger SEARCH cohort in the year before PrEP was made available — and from the same communities — served as the control group.

Interim 60-week data show that the rate of acquisition was 74% lower in the PrEP group than in the control group (incidence rate ratio, 0.26; P = .01). In women, the acquisition rate was 76% lower (incidence rate ratio, 0.24; P = .04), and in men, it was 40% lower (incidence rate ratio, 0.60; P = .54).

The reduction was not significant for men, probably because so few men acquired HIV, Koss reported. The powerful drop in new HIV cases overall was related to PrEP use by women; cases in women fell from 1.52 to 0.40 per 100 person-years.

Blood tests showed that 72% of the people who acquired HIV during the study period had not taken a PrEP pill for at least 30 days before their diagnosis.

“Making PrEP more easily accessible and more community-based could be very powerful in the United States,” said Koss.

“Allowing people to test for HIV and start PrEP outside of health clinics or standard health facilities could help reach more people,” she told Medscape Medical News. “Many of the people who benefit from PrEP may not otherwise need to seek medical care regularly if they’re otherwise healthy and often young.”

When PrEP is made available — easily available —  people will pick it up, they will take it away, they will put it in their mouths, and they will not get HIV.

The findings were hailed by others in the field of HIV prevention.

“They’re fantastic,” said Jared Baeten, MD, vice dean of the School of Public Health and professor of global health, medicine, and epidemiology at the University of Washington in Seattle. He was involved in Partners PrEP, a study of PrEP use in mixed-HIV-status couples, the Partners Demonstration Project, and HOPE, a study of the dapivirine ring for HIV prevention.

“These data provide real evidence that when PrEP is made available — easily available — people will pick it up, they will take it away, they will put it in their mouths, and they will not get HIV,” he said in an interview.

Even more, they clarify something that has stymied American regulators and clinicians.

Early studies of PrEP use by single women were stopped because participants weren’t taking the pills; adherence was so low that researchers couldn’t show efficacy. Since then, various trials — including Partners PrEP — have shown that PrEP works in women, but doubts have lingered, leading women to “get the short end of the stick in discussions about PrEP,” Baeten explained.

“There really shouldn’t be questions anymore,” he said. “These findings should put to rest any question about women in Africa being able to benefit from PrEP.”

This article first appeared on Medscape.com.

When people were offered preexposure prophylaxis (PrEP) outside of traditional clinics, regardless of specific risk factors, as part of the Sustainable East Africa Research in Community Health (SEARCH) study, new HIV acquisitions dropped by 74%.

It’s a valuable lesson to providers around the world, said Catherine Koss, MD, assistant professor of medicine in HIV, infectious disease, and global medicine at the University of California, San Francisco.

“We haven’t really seen PrEP being scaled up and offered at such a broad level in communities,” Koss said during the International AIDS Conference 2020. “Offering PrEP in a way that’s more universal and with a low barrier to both men and women can result in reductions in incidence.”

The first part of SEARCH, which looked at the impact of universal testing and access to HIV treatment immediately after diagnosis, showed that the strategy resulted in a population-wide 30% reduction in new HIV acquisitions. In other words, treatment alone wasn’t enough to end the HIV epidemic.

But the researchers always knew “there were likely going to be new HIV infections,” even with universal HIV testing and treatment, Koss said.

So the second part of the study was designed to see whether PrEP — with the combination of tenofovir disoproxil fumarate plus emtricitabine (Truvada, Gilead Sciences) — could further reduce rates of HIV acquisition.
 

PrEP out in the community

During the PrEP part of the SEARCH study, researchers discussed HIV risk with adults in 16 communities in rural Kenya and Uganda during population-level testing that took place at health fairs, beaches, trading centers, other community sites, and even in participants’ homes. PrEP was offered to anyone in a relationship with someone living with HIV, to anyone determined to be at elevated risk for infection by a previously validated algorithm, and to anyone who did not fit those criteria but who wanted a prescription.

Of the 15,632 adults eligible for PrEP, 5,447 (35%) chose to start the HIV prevention pill.

A rapid-enrollment protocol meant that people received their prescription at the time of screening or soon after that. Participants underwent testing for HIV antibodies — also out in the community — at weeks 4 and 12, and every 12 weeks thereafter; this will continue out to week 144.

HIV-negative adults who were part of the larger SEARCH cohort in the year before PrEP was made available — and from the same communities — served as the control group.

Interim 60-week data show that the rate of acquisition was 74% lower in the PrEP group than in the control group (incidence rate ratio, 0.26; P = .01). In women, the acquisition rate was 76% lower (incidence rate ratio, 0.24; P = .04), and in men, it was 40% lower (incidence rate ratio, 0.60; P = .54).

The reduction was not significant for men, probably because so few men acquired HIV, Koss reported. The powerful drop in new HIV cases overall was related to PrEP use by women; cases in women fell from 1.52 to 0.40 per 100 person-years.

Blood tests showed that 72% of the people who acquired HIV during the study period had not taken a PrEP pill for at least 30 days before their diagnosis.

“Making PrEP more easily accessible and more community-based could be very powerful in the United States,” said Koss.

“Allowing people to test for HIV and start PrEP outside of health clinics or standard health facilities could help reach more people,” she told Medscape Medical News. “Many of the people who benefit from PrEP may not otherwise need to seek medical care regularly if they’re otherwise healthy and often young.”

When PrEP is made available — easily available —  people will pick it up, they will take it away, they will put it in their mouths, and they will not get HIV.

The findings were hailed by others in the field of HIV prevention.

“They’re fantastic,” said Jared Baeten, MD, vice dean of the School of Public Health and professor of global health, medicine, and epidemiology at the University of Washington in Seattle. He was involved in Partners PrEP, a study of PrEP use in mixed-HIV-status couples, the Partners Demonstration Project, and HOPE, a study of the dapivirine ring for HIV prevention.

“These data provide real evidence that when PrEP is made available — easily available — people will pick it up, they will take it away, they will put it in their mouths, and they will not get HIV,” he said in an interview.

Even more, they clarify something that has stymied American regulators and clinicians.

Early studies of PrEP use by single women were stopped because participants weren’t taking the pills; adherence was so low that researchers couldn’t show efficacy. Since then, various trials — including Partners PrEP — have shown that PrEP works in women, but doubts have lingered, leading women to “get the short end of the stick in discussions about PrEP,” Baeten explained.

“There really shouldn’t be questions anymore,” he said. “These findings should put to rest any question about women in Africa being able to benefit from PrEP.”

This article first appeared on Medscape.com.