Conference Coverage

Students have similar confidence levels during a simulated laparoscopic vaginal cuff suturing task whether they train with the current standard laparoscopic simulator or a newer gynecology-specific simulator, a randomized trial found.

Participants who trained on the gynecology-specific simulator, known as Essentials in Minimally Invasive Gynecology (EMIG), reported higher confidence scores, but differences between the groups were not statistically significant, a researcher reported at the annual meeting sponsored by AAGL, held virtually this year.

The study compared EMIG with Fundamentals of Laparoscopic Surgery (FLS), a laparoscopic simulator that general surgeons launched in 2004.

In 2018, the American Board of Obstetrics and Gynecology announced an FLS requirement for residents graduating after May 31, 2020. The same year, the AAGL began validating EMIG. AAGL developed the simulator in response to a growing trend for minimally invasive approaches and to provide a training tool geared toward gynecologists, said Emily G. Lin, MD, an obstetrics and gynecology resident at McGaw Medical Center at Northwestern University in Chicago.
 

A comparison of the two simulators

The simulators use different port placement and operator positioning. The operating fields within the box trainers also differ. In EMIG, laparoscopic tasks take place within a bowl that simulates a confined workspace similar to a pelvis, whereas FLS tasks take place in an open box trainer environment, Dr. Lin said.

To compare students’ self-reported confidence levels after performing a laparoscopic vaginal cuff suturing task after training with EMIG or FLS, Dr. Lin and colleagues conducted a randomized controlled trial.

The researchers recruited 45 participants who were preclinical medical students or premedical college students without prior training experience. Participants were randomized to EMIG or FLS training. After watching instructional videos about their simulator tasks and the vaginal cuff suturing task, they attempted the vaginal cuff suturing task as a pretest.

They then trained for about 2 hours on their assigned simulator. Training for both groups included practicing peg transfer and intracorporeal knot tying. In addition, the EMIG group trained on a running suture task, and the FLS group trained on a ligating loop task.

After training, participants retried the vaginal cuff suturing task. Participants subsequently rated their confidence during each simulation task on a 5-point Likert scale.

Confidence levels on the peg transfer (4.13 with EMIG vs. 4.10 with FLS), intracorporeal knot tying (3.0 with EMIG vs. 2.86 with FLS) and vaginal cuff suturing (2.46 with EMIG vs. 2.05 with FLS) were similar for both groups.

The study was small, included only one training session, and included only three of the five tasks for each simulator because of time and cost constraints, Dr. Lin noted.
 

Using simulation in residency training

The study was well designed and sheds light on inevitable comparisons between FLS and EMIG, Ido Sirota, MD, MHA, of New York-Presbyterian Queens, said in a discussion following the research presentation.

“The field of medical simulation has developed tremendously in the past decade,” Dr. Sirota said. “The paradigm that used to be common in our field – of see one, do one, teach one – belongs to the past. ... Current trainees need extensive practice on their surgical skills in a simulation setting before” entering the operating room.

A 2017 review found that simulation may be a useful adjunct to residency training.

And in a pilot study, EMIG’s laparoscopic and hysteroscopic simulation systems were considered to have good face validity, Dr. Sirota noted.

Using a gynecology-specific simulation may have advantages.

“In this day and age when we are trying to differentiate ourselves as a subspecialty, there is a great value to developing our own simulation-based curricula to validate our surgical skills during training, as well as for maintenance throughout our career,” Dr. Sirota said. “We as a subspecialty need specific tests tailored to our surgical procedures.”

Dr. Sirota disclosed consulting for Medtronic, Activ Surgical, Heracure, and HT, and he is on the speakers bureau for Medtronic. Dr. Lin had no relevant financial disclosures.

jremaly@mdedge.com

SOURCE: Lin E et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.593.

Students have similar confidence levels during a simulated laparoscopic vaginal cuff suturing task whether they train with the current standard laparoscopic simulator or a newer gynecology-specific simulator, a randomized trial found.

Participants who trained on the gynecology-specific simulator, known as Essentials in Minimally Invasive Gynecology (EMIG), reported higher confidence scores, but differences between the groups were not statistically significant, a researcher reported at the annual meeting sponsored by AAGL, held virtually this year.

The study compared EMIG with Fundamentals of Laparoscopic Surgery (FLS), a laparoscopic simulator that general surgeons launched in 2004.

In 2018, the American Board of Obstetrics and Gynecology announced an FLS requirement for residents graduating after May 31, 2020. The same year, the AAGL began validating EMIG. AAGL developed the simulator in response to a growing trend for minimally invasive approaches and to provide a training tool geared toward gynecologists, said Emily G. Lin, MD, an obstetrics and gynecology resident at McGaw Medical Center at Northwestern University in Chicago.
 

A comparison of the two simulators

The simulators use different port placement and operator positioning. The operating fields within the box trainers also differ. In EMIG, laparoscopic tasks take place within a bowl that simulates a confined workspace similar to a pelvis, whereas FLS tasks take place in an open box trainer environment, Dr. Lin said.

To compare students’ self-reported confidence levels after performing a laparoscopic vaginal cuff suturing task after training with EMIG or FLS, Dr. Lin and colleagues conducted a randomized controlled trial.

The researchers recruited 45 participants who were preclinical medical students or premedical college students without prior training experience. Participants were randomized to EMIG or FLS training. After watching instructional videos about their simulator tasks and the vaginal cuff suturing task, they attempted the vaginal cuff suturing task as a pretest.

They then trained for about 2 hours on their assigned simulator. Training for both groups included practicing peg transfer and intracorporeal knot tying. In addition, the EMIG group trained on a running suture task, and the FLS group trained on a ligating loop task.

After training, participants retried the vaginal cuff suturing task. Participants subsequently rated their confidence during each simulation task on a 5-point Likert scale.

Confidence levels on the peg transfer (4.13 with EMIG vs. 4.10 with FLS), intracorporeal knot tying (3.0 with EMIG vs. 2.86 with FLS) and vaginal cuff suturing (2.46 with EMIG vs. 2.05 with FLS) were similar for both groups.

The study was small, included only one training session, and included only three of the five tasks for each simulator because of time and cost constraints, Dr. Lin noted.
 

Using simulation in residency training

The study was well designed and sheds light on inevitable comparisons between FLS and EMIG, Ido Sirota, MD, MHA, of New York-Presbyterian Queens, said in a discussion following the research presentation.

“The field of medical simulation has developed tremendously in the past decade,” Dr. Sirota said. “The paradigm that used to be common in our field – of see one, do one, teach one – belongs to the past. ... Current trainees need extensive practice on their surgical skills in a simulation setting before” entering the operating room.

A 2017 review found that simulation may be a useful adjunct to residency training.

And in a pilot study, EMIG’s laparoscopic and hysteroscopic simulation systems were considered to have good face validity, Dr. Sirota noted.

Using a gynecology-specific simulation may have advantages.

“In this day and age when we are trying to differentiate ourselves as a subspecialty, there is a great value to developing our own simulation-based curricula to validate our surgical skills during training, as well as for maintenance throughout our career,” Dr. Sirota said. “We as a subspecialty need specific tests tailored to our surgical procedures.”

Dr. Sirota disclosed consulting for Medtronic, Activ Surgical, Heracure, and HT, and he is on the speakers bureau for Medtronic. Dr. Lin had no relevant financial disclosures.

jremaly@mdedge.com

SOURCE: Lin E et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.593.

Students have similar confidence levels during a simulated laparoscopic vaginal cuff suturing task whether they train with the current standard laparoscopic simulator or a newer gynecology-specific simulator, a randomized trial found.

Participants who trained on the gynecology-specific simulator, known as Essentials in Minimally Invasive Gynecology (EMIG), reported higher confidence scores, but differences between the groups were not statistically significant, a researcher reported at the annual meeting sponsored by AAGL, held virtually this year.

The study compared EMIG with Fundamentals of Laparoscopic Surgery (FLS), a laparoscopic simulator that general surgeons launched in 2004.

In 2018, the American Board of Obstetrics and Gynecology announced an FLS requirement for residents graduating after May 31, 2020. The same year, the AAGL began validating EMIG. AAGL developed the simulator in response to a growing trend for minimally invasive approaches and to provide a training tool geared toward gynecologists, said Emily G. Lin, MD, an obstetrics and gynecology resident at McGaw Medical Center at Northwestern University in Chicago.
 

A comparison of the two simulators

The simulators use different port placement and operator positioning. The operating fields within the box trainers also differ. In EMIG, laparoscopic tasks take place within a bowl that simulates a confined workspace similar to a pelvis, whereas FLS tasks take place in an open box trainer environment, Dr. Lin said.

To compare students’ self-reported confidence levels after performing a laparoscopic vaginal cuff suturing task after training with EMIG or FLS, Dr. Lin and colleagues conducted a randomized controlled trial.

The researchers recruited 45 participants who were preclinical medical students or premedical college students without prior training experience. Participants were randomized to EMIG or FLS training. After watching instructional videos about their simulator tasks and the vaginal cuff suturing task, they attempted the vaginal cuff suturing task as a pretest.

They then trained for about 2 hours on their assigned simulator. Training for both groups included practicing peg transfer and intracorporeal knot tying. In addition, the EMIG group trained on a running suture task, and the FLS group trained on a ligating loop task.

After training, participants retried the vaginal cuff suturing task. Participants subsequently rated their confidence during each simulation task on a 5-point Likert scale.

Confidence levels on the peg transfer (4.13 with EMIG vs. 4.10 with FLS), intracorporeal knot tying (3.0 with EMIG vs. 2.86 with FLS) and vaginal cuff suturing (2.46 with EMIG vs. 2.05 with FLS) were similar for both groups.

The study was small, included only one training session, and included only three of the five tasks for each simulator because of time and cost constraints, Dr. Lin noted.
 

Using simulation in residency training

The study was well designed and sheds light on inevitable comparisons between FLS and EMIG, Ido Sirota, MD, MHA, of New York-Presbyterian Queens, said in a discussion following the research presentation.

“The field of medical simulation has developed tremendously in the past decade,” Dr. Sirota said. “The paradigm that used to be common in our field – of see one, do one, teach one – belongs to the past. ... Current trainees need extensive practice on their surgical skills in a simulation setting before” entering the operating room.

A 2017 review found that simulation may be a useful adjunct to residency training.

And in a pilot study, EMIG’s laparoscopic and hysteroscopic simulation systems were considered to have good face validity, Dr. Sirota noted.

Using a gynecology-specific simulation may have advantages.

“In this day and age when we are trying to differentiate ourselves as a subspecialty, there is a great value to developing our own simulation-based curricula to validate our surgical skills during training, as well as for maintenance throughout our career,” Dr. Sirota said. “We as a subspecialty need specific tests tailored to our surgical procedures.”

Dr. Sirota disclosed consulting for Medtronic, Activ Surgical, Heracure, and HT, and he is on the speakers bureau for Medtronic. Dr. Lin had no relevant financial disclosures.

jremaly@mdedge.com

SOURCE: Lin E et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.593.

A healthy dose of skepticism is reasonable when evaluating new technologies to potentially use in your practice, but being overly critical can backfire, according to E. Victor Ross, MD.

During a virtual course on laser and aesthetic skin therapy, he noted that dermatologists may be evaluating new technologies in roles as an investigator or provider, or as a provider who buys the equipment outright, without any direct compensation from industry. “If you’re doing investigative work, you’re already in a conflicted situation because you’re trying to serve two masters,” said Dr. Ross, who directs the Scripps Clinic Laser and Cosmetic Dermatology Center in San Diego. “You’re trying to advance science and to make sure your reputation is intact and maybe even enhanced, but you’re also kind of at the whim of industry, because they have a goal. Sometimes the goals are similar. Your goal is to advance the technology and advance patient care, but they have a goal of selling equipment. Those goals should be compatible, and they should be in the same pathway; they should be parallel.”

Being too critical as an investigator/researcher of new technologies can hinder further interactions with industry. “Sometimes your criticism can be premature, and small changes in the technology and/or waiting for results can validate the technology,” he said. “Maybe it’s a skin-tightening technology, or maybe there’s something you don’t like about it; you have a prototype and you say: ‘This is not so great,’ but these are studies that take a long time to evaluate, like hair removal. Generally, if you’re a big critic, after a while, nobody wants to hear it. So, you can’t be overly critical. I think you can be skeptical, but not overly critical.”

On the other hand, Dr. Ross continued, if you cheerlead for the device industry, your reputation may be sold to the highest bidder. “You may compromise your ability to be trusted in future work or presentations. I’ve regretted some things I said many years ago, not because I was being dishonest but because I really wasn’t as skeptical as I should have been about the types of results I was getting. You do tend to get on a bandwagon; you want everything to be positive,” he said, adding: “The other thing that can happen is, if things don’t work out with other buyers, they’re going to say, ‘I can’t get the same results.’ If somebody can’t replicate what you’re doing, it’s going to put your reputation on the line to some degree. So, you have to be very careful.”

Before agreeing to evaluate a new technology as an investigator or in your own practice, Dr. Ross recommended asking yourself if the intervention makes sense on a gross or microanatomic level. “There should be a physical basis for how it works, and ideally there should be some histology that backs it up,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “Where is the data to support the outcomes? If it is your own data, how skeptical have you been in its acquisition and assessment?”

When evaluating a new technology, Dr. Ross recommended starting with test spots and low settings. “It behooves you not to be too aggressive because there are some untoward things you may not see right away.” He advised evaluating short- and long-term outcomes and being wary of devices that heat very deeply and rely on long-term outcomes, such as hair removal, acne improvement, scar improvement, and skin tightening – all of which require long intervals for assessment. As one of his “Ross Rules” states: “The deeper the heating and the less focused the heating, the less we can expect results.” Another Ross Rule calls for being skeptical about technologies without an immediate finding that can be “seen” on routine histology. “To me, the deeper the procedure, particularly if it’s not fractional, the confidence of my outcome is diminished,” he said. “The exception is any intervention that relies on selective photothermolysis.”

Using new technologies in practice

Dr. Ross also offered tips on how to properly incorporate newly approved technologies into your practice safely, including the use of visual endpoints. “That’s tough for technologies like laser liposuction or fractional technologies, where we rely more on ‘guidelines’ than endpoints,” he said. In addition, he recommended gradually increasing settings and using test areas to stall and/or hone techniques. “It’s exciting, but you’re like a test pilot. You want to be careful that you are doing things that are not likely to risk the patient. Try some off-the-face applications first. When you’re using a new technology, push a little harder with each patient so you can find a safe zone for that technology. You don’t have to get it all in one treatment session. Be conservative. Anticipate that you may be underassessing the immediate response.”

Above all, be careful. “Use your judgment more than laser company-prescribed settings,” he said. “Most companies have the go-by settings on the low side for patient protection, but sometimes efficacy suffers. Use cautiously on friends and family. If you treat a spouse or a friend and things don’t go perfectly, that’s always a recipe for a problem.”

Dr. Ross reported having received financial grants and research grants from Candela, Cutera, Lumenis, and Lutronic; consulting fees from Palomar; and honoraria from Cynosure, Cutera, and Lumenis. He has also received research funding from Venous Concepts, Pulsed Biosciences, and Cynosure.

dbrunk@mdege.com

A healthy dose of skepticism is reasonable when evaluating new technologies to potentially use in your practice, but being overly critical can backfire, according to E. Victor Ross, MD.

During a virtual course on laser and aesthetic skin therapy, he noted that dermatologists may be evaluating new technologies in roles as an investigator or provider, or as a provider who buys the equipment outright, without any direct compensation from industry. “If you’re doing investigative work, you’re already in a conflicted situation because you’re trying to serve two masters,” said Dr. Ross, who directs the Scripps Clinic Laser and Cosmetic Dermatology Center in San Diego. “You’re trying to advance science and to make sure your reputation is intact and maybe even enhanced, but you’re also kind of at the whim of industry, because they have a goal. Sometimes the goals are similar. Your goal is to advance the technology and advance patient care, but they have a goal of selling equipment. Those goals should be compatible, and they should be in the same pathway; they should be parallel.”

Being too critical as an investigator/researcher of new technologies can hinder further interactions with industry. “Sometimes your criticism can be premature, and small changes in the technology and/or waiting for results can validate the technology,” he said. “Maybe it’s a skin-tightening technology, or maybe there’s something you don’t like about it; you have a prototype and you say: ‘This is not so great,’ but these are studies that take a long time to evaluate, like hair removal. Generally, if you’re a big critic, after a while, nobody wants to hear it. So, you can’t be overly critical. I think you can be skeptical, but not overly critical.”

On the other hand, Dr. Ross continued, if you cheerlead for the device industry, your reputation may be sold to the highest bidder. “You may compromise your ability to be trusted in future work or presentations. I’ve regretted some things I said many years ago, not because I was being dishonest but because I really wasn’t as skeptical as I should have been about the types of results I was getting. You do tend to get on a bandwagon; you want everything to be positive,” he said, adding: “The other thing that can happen is, if things don’t work out with other buyers, they’re going to say, ‘I can’t get the same results.’ If somebody can’t replicate what you’re doing, it’s going to put your reputation on the line to some degree. So, you have to be very careful.”

Before agreeing to evaluate a new technology as an investigator or in your own practice, Dr. Ross recommended asking yourself if the intervention makes sense on a gross or microanatomic level. “There should be a physical basis for how it works, and ideally there should be some histology that backs it up,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “Where is the data to support the outcomes? If it is your own data, how skeptical have you been in its acquisition and assessment?”

When evaluating a new technology, Dr. Ross recommended starting with test spots and low settings. “It behooves you not to be too aggressive because there are some untoward things you may not see right away.” He advised evaluating short- and long-term outcomes and being wary of devices that heat very deeply and rely on long-term outcomes, such as hair removal, acne improvement, scar improvement, and skin tightening – all of which require long intervals for assessment. As one of his “Ross Rules” states: “The deeper the heating and the less focused the heating, the less we can expect results.” Another Ross Rule calls for being skeptical about technologies without an immediate finding that can be “seen” on routine histology. “To me, the deeper the procedure, particularly if it’s not fractional, the confidence of my outcome is diminished,” he said. “The exception is any intervention that relies on selective photothermolysis.”

Using new technologies in practice

Dr. Ross also offered tips on how to properly incorporate newly approved technologies into your practice safely, including the use of visual endpoints. “That’s tough for technologies like laser liposuction or fractional technologies, where we rely more on ‘guidelines’ than endpoints,” he said. In addition, he recommended gradually increasing settings and using test areas to stall and/or hone techniques. “It’s exciting, but you’re like a test pilot. You want to be careful that you are doing things that are not likely to risk the patient. Try some off-the-face applications first. When you’re using a new technology, push a little harder with each patient so you can find a safe zone for that technology. You don’t have to get it all in one treatment session. Be conservative. Anticipate that you may be underassessing the immediate response.”

Above all, be careful. “Use your judgment more than laser company-prescribed settings,” he said. “Most companies have the go-by settings on the low side for patient protection, but sometimes efficacy suffers. Use cautiously on friends and family. If you treat a spouse or a friend and things don’t go perfectly, that’s always a recipe for a problem.”

Dr. Ross reported having received financial grants and research grants from Candela, Cutera, Lumenis, and Lutronic; consulting fees from Palomar; and honoraria from Cynosure, Cutera, and Lumenis. He has also received research funding from Venous Concepts, Pulsed Biosciences, and Cynosure.

dbrunk@mdege.com

A healthy dose of skepticism is reasonable when evaluating new technologies to potentially use in your practice, but being overly critical can backfire, according to E. Victor Ross, MD.

During a virtual course on laser and aesthetic skin therapy, he noted that dermatologists may be evaluating new technologies in roles as an investigator or provider, or as a provider who buys the equipment outright, without any direct compensation from industry. “If you’re doing investigative work, you’re already in a conflicted situation because you’re trying to serve two masters,” said Dr. Ross, who directs the Scripps Clinic Laser and Cosmetic Dermatology Center in San Diego. “You’re trying to advance science and to make sure your reputation is intact and maybe even enhanced, but you’re also kind of at the whim of industry, because they have a goal. Sometimes the goals are similar. Your goal is to advance the technology and advance patient care, but they have a goal of selling equipment. Those goals should be compatible, and they should be in the same pathway; they should be parallel.”

Being too critical as an investigator/researcher of new technologies can hinder further interactions with industry. “Sometimes your criticism can be premature, and small changes in the technology and/or waiting for results can validate the technology,” he said. “Maybe it’s a skin-tightening technology, or maybe there’s something you don’t like about it; you have a prototype and you say: ‘This is not so great,’ but these are studies that take a long time to evaluate, like hair removal. Generally, if you’re a big critic, after a while, nobody wants to hear it. So, you can’t be overly critical. I think you can be skeptical, but not overly critical.”

On the other hand, Dr. Ross continued, if you cheerlead for the device industry, your reputation may be sold to the highest bidder. “You may compromise your ability to be trusted in future work or presentations. I’ve regretted some things I said many years ago, not because I was being dishonest but because I really wasn’t as skeptical as I should have been about the types of results I was getting. You do tend to get on a bandwagon; you want everything to be positive,” he said, adding: “The other thing that can happen is, if things don’t work out with other buyers, they’re going to say, ‘I can’t get the same results.’ If somebody can’t replicate what you’re doing, it’s going to put your reputation on the line to some degree. So, you have to be very careful.”

Before agreeing to evaluate a new technology as an investigator or in your own practice, Dr. Ross recommended asking yourself if the intervention makes sense on a gross or microanatomic level. “There should be a physical basis for how it works, and ideally there should be some histology that backs it up,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “Where is the data to support the outcomes? If it is your own data, how skeptical have you been in its acquisition and assessment?”

When evaluating a new technology, Dr. Ross recommended starting with test spots and low settings. “It behooves you not to be too aggressive because there are some untoward things you may not see right away.” He advised evaluating short- and long-term outcomes and being wary of devices that heat very deeply and rely on long-term outcomes, such as hair removal, acne improvement, scar improvement, and skin tightening – all of which require long intervals for assessment. As one of his “Ross Rules” states: “The deeper the heating and the less focused the heating, the less we can expect results.” Another Ross Rule calls for being skeptical about technologies without an immediate finding that can be “seen” on routine histology. “To me, the deeper the procedure, particularly if it’s not fractional, the confidence of my outcome is diminished,” he said. “The exception is any intervention that relies on selective photothermolysis.”

Using new technologies in practice

Dr. Ross also offered tips on how to properly incorporate newly approved technologies into your practice safely, including the use of visual endpoints. “That’s tough for technologies like laser liposuction or fractional technologies, where we rely more on ‘guidelines’ than endpoints,” he said. In addition, he recommended gradually increasing settings and using test areas to stall and/or hone techniques. “It’s exciting, but you’re like a test pilot. You want to be careful that you are doing things that are not likely to risk the patient. Try some off-the-face applications first. When you’re using a new technology, push a little harder with each patient so you can find a safe zone for that technology. You don’t have to get it all in one treatment session. Be conservative. Anticipate that you may be underassessing the immediate response.”

Above all, be careful. “Use your judgment more than laser company-prescribed settings,” he said. “Most companies have the go-by settings on the low side for patient protection, but sometimes efficacy suffers. Use cautiously on friends and family. If you treat a spouse or a friend and things don’t go perfectly, that’s always a recipe for a problem.”

Dr. Ross reported having received financial grants and research grants from Candela, Cutera, Lumenis, and Lutronic; consulting fees from Palomar; and honoraria from Cynosure, Cutera, and Lumenis. He has also received research funding from Venous Concepts, Pulsed Biosciences, and Cynosure.

dbrunk@mdege.com

When a patient with cancer develops venous thromboembolism despite anticoagulation, how to help them comes down to clinical judgment, according to hematologist Neil Zakai, MD, associate professor at the University of Vermont, Burlington.

“Unfortunately,” when it comes to “anticoagulation failure, we are entering an evidence free-zone,” with no large trials to guide management and only a few guiding principles, he said during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

The first thing is to check if there was an inciting incident, such as medical noncompliance, an infection, or an interruption of anticoagulation. Dr. Zakai said he’s even had cancer patients develop heparin-induced thrombocytopenia when switched to enoxaparin from a direct oral anticoagulants (DOAC) for a procedure.

Once the underlying problem is addressed, patients may be able to continue with their original anticoagulant.

However, cancer progression is the main reason anticoagulation fails. “In general, it is very difficult to control cancer thrombosis if you can’t control cancer progression,” Dr. Zakai said.

In those cases, he steps up anticoagulation. Prophylactic dosing is increased to full treatment dosing, and patients on a DOAC are generally switched to a low molecular weight heparin (LMWH).

If patients are already on LMWH once daily, they will be bumped up to twice daily dosing; for instance, enoxaparin 1 mg/kg b.i.d. instead of 1.5 mg/kg q.d. Dr. Zakai said he’s gone as high at 2 or even 2.5 mg/kg to control thrombosis, without excessive bleeding.

In general, anticoagulation for thrombosis prophylaxis continues as long as the cancer is active, and certainly while patients are on hormonal treatments such as tamoxifen, which increases the risk.

Dr. Zakai stressed that both thrombosis and bleeding risk change for cancer patients over time, and treatment needs to keep up.

“I continuously assess the risk and benefit of anticoagulation. At certain times” such as during and for a few months after hospitalization, thrombosis risk increases; at other times, bleeding risk is higher. “You need to actively change your anticoagulation during those periods,” and tailor therapy based on transient risk factors. “People with cancer have peaks and troughs for their risk that we don’t take advantage of,” he said.

Dr. Zakai generally favors apixaban or enoxaparin for prophylaxis, carefully monitoring patients for bleeding and, for the DOAC, drug interactions with antiemetics, dexamethasone, and certain chemotherapy drugs.

He noted a recent trial that found a 59% reduction in venous thromboembolism risk in ambulatory cancer patients with apixaban 2.5 mg twice daily over 6 months, versus placebo, and a 6% absolute reduction, but at the cost of a twofold increase in bleeding risk, with an absolute 1.7% increase.

Dr. Zakai cautioned that patients in trials are selected for higher VTE and lower bleeding risks, so outcomes might “poorly reflect real world populations.” Dr. Zakai did not have any industry disclosures. The conference was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

aotto@mdedge.com

When a patient with cancer develops venous thromboembolism despite anticoagulation, how to help them comes down to clinical judgment, according to hematologist Neil Zakai, MD, associate professor at the University of Vermont, Burlington.

“Unfortunately,” when it comes to “anticoagulation failure, we are entering an evidence free-zone,” with no large trials to guide management and only a few guiding principles, he said during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

The first thing is to check if there was an inciting incident, such as medical noncompliance, an infection, or an interruption of anticoagulation. Dr. Zakai said he’s even had cancer patients develop heparin-induced thrombocytopenia when switched to enoxaparin from a direct oral anticoagulants (DOAC) for a procedure.

Once the underlying problem is addressed, patients may be able to continue with their original anticoagulant.

However, cancer progression is the main reason anticoagulation fails. “In general, it is very difficult to control cancer thrombosis if you can’t control cancer progression,” Dr. Zakai said.

In those cases, he steps up anticoagulation. Prophylactic dosing is increased to full treatment dosing, and patients on a DOAC are generally switched to a low molecular weight heparin (LMWH).

If patients are already on LMWH once daily, they will be bumped up to twice daily dosing; for instance, enoxaparin 1 mg/kg b.i.d. instead of 1.5 mg/kg q.d. Dr. Zakai said he’s gone as high at 2 or even 2.5 mg/kg to control thrombosis, without excessive bleeding.

In general, anticoagulation for thrombosis prophylaxis continues as long as the cancer is active, and certainly while patients are on hormonal treatments such as tamoxifen, which increases the risk.

Dr. Zakai stressed that both thrombosis and bleeding risk change for cancer patients over time, and treatment needs to keep up.

“I continuously assess the risk and benefit of anticoagulation. At certain times” such as during and for a few months after hospitalization, thrombosis risk increases; at other times, bleeding risk is higher. “You need to actively change your anticoagulation during those periods,” and tailor therapy based on transient risk factors. “People with cancer have peaks and troughs for their risk that we don’t take advantage of,” he said.

Dr. Zakai generally favors apixaban or enoxaparin for prophylaxis, carefully monitoring patients for bleeding and, for the DOAC, drug interactions with antiemetics, dexamethasone, and certain chemotherapy drugs.

He noted a recent trial that found a 59% reduction in venous thromboembolism risk in ambulatory cancer patients with apixaban 2.5 mg twice daily over 6 months, versus placebo, and a 6% absolute reduction, but at the cost of a twofold increase in bleeding risk, with an absolute 1.7% increase.

Dr. Zakai cautioned that patients in trials are selected for higher VTE and lower bleeding risks, so outcomes might “poorly reflect real world populations.” Dr. Zakai did not have any industry disclosures. The conference was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

aotto@mdedge.com

When a patient with cancer develops venous thromboembolism despite anticoagulation, how to help them comes down to clinical judgment, according to hematologist Neil Zakai, MD, associate professor at the University of Vermont, Burlington.

“Unfortunately,” when it comes to “anticoagulation failure, we are entering an evidence free-zone,” with no large trials to guide management and only a few guiding principles, he said during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

The first thing is to check if there was an inciting incident, such as medical noncompliance, an infection, or an interruption of anticoagulation. Dr. Zakai said he’s even had cancer patients develop heparin-induced thrombocytopenia when switched to enoxaparin from a direct oral anticoagulants (DOAC) for a procedure.

Once the underlying problem is addressed, patients may be able to continue with their original anticoagulant.

However, cancer progression is the main reason anticoagulation fails. “In general, it is very difficult to control cancer thrombosis if you can’t control cancer progression,” Dr. Zakai said.

In those cases, he steps up anticoagulation. Prophylactic dosing is increased to full treatment dosing, and patients on a DOAC are generally switched to a low molecular weight heparin (LMWH).

If patients are already on LMWH once daily, they will be bumped up to twice daily dosing; for instance, enoxaparin 1 mg/kg b.i.d. instead of 1.5 mg/kg q.d. Dr. Zakai said he’s gone as high at 2 or even 2.5 mg/kg to control thrombosis, without excessive bleeding.

In general, anticoagulation for thrombosis prophylaxis continues as long as the cancer is active, and certainly while patients are on hormonal treatments such as tamoxifen, which increases the risk.

Dr. Zakai stressed that both thrombosis and bleeding risk change for cancer patients over time, and treatment needs to keep up.

“I continuously assess the risk and benefit of anticoagulation. At certain times” such as during and for a few months after hospitalization, thrombosis risk increases; at other times, bleeding risk is higher. “You need to actively change your anticoagulation during those periods,” and tailor therapy based on transient risk factors. “People with cancer have peaks and troughs for their risk that we don’t take advantage of,” he said.

Dr. Zakai generally favors apixaban or enoxaparin for prophylaxis, carefully monitoring patients for bleeding and, for the DOAC, drug interactions with antiemetics, dexamethasone, and certain chemotherapy drugs.

He noted a recent trial that found a 59% reduction in venous thromboembolism risk in ambulatory cancer patients with apixaban 2.5 mg twice daily over 6 months, versus placebo, and a 6% absolute reduction, but at the cost of a twofold increase in bleeding risk, with an absolute 1.7% increase.

Dr. Zakai cautioned that patients in trials are selected for higher VTE and lower bleeding risks, so outcomes might “poorly reflect real world populations.” Dr. Zakai did not have any industry disclosures. The conference was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

aotto@mdedge.com

Instead of flying out to San Diego in California and soaking up a bit of sunshine in between listening to new research presentations, hematologists from around the world will be glued to their computer screens next weekend, tuning into the 62nd American Society of Hematology annual meeting.  

Like many other conferences this year, the ASH meeting will be virtual because of the continuing COVID-19 pandemic, although the dates remain the same: Dec. 5-8.  

This is the premier hematology event of the year, and the largest hematology conference in the world, with around 3,500 abstracts presented this year, commented Aaron T. Gerds, MD, chair of ASH’s Committee on Communications.
 

Ruxolitinib in chronic GvHD

“One of the things that people come to ASH for is to hear about practice-changing clinical trials, and this year is no exception,” said ASH secretary Robert Brodsky, MD.

In a preview webinar, he highlighted four abstracts that offer opportunities to change practice and revamp the current standards of care.

One clinical trial that is “almost certainly a practice changer,” he said, is the REACH 3 study (abstract 77) of the JAK inhibitor ruxolitinib (Jakafi, Incyte) in patients with chronic graft-versus-host disease (GvHD) after a stem cell transplant.

“This has been really hard to treat in patients undergoing allogeneic bone marrow transplants,” said Brodsky. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement, and even steroids don’t work that well.”

There is currently no approved second-line therapy for chronic forms of GvHD, he emphasized. The main endpoint of the trial was overall response rate, which was doubled with ruxolitinib compared to the best available therapy (50% vs 25%).

“This is the first successful phase 3 trial for chronic GvHD,” Brodsky commented.  
 

Transplants for older patients with MDS

Transplant offers the only curative option for myelodysplastic syndromes (MDS), but typically this option is offered to younger patients because benefits for older adults have not been well-defined, Brodsky noted.

New data from a clinical trial conducted in patients with advanced MDS aged 50-75 years (abstract 75) offers the most definitive evidence to date that allogeneic hematopoietic cell transplantation (AHCT) can significantly improve outcomes for older adults.  

It’s clear that transplant is the standard of care in younger patients, Brodsky commented, and although there is a trend of offering it to older patients, some are not getting referred and instead are being offered palliative care. “The thinking is that bone marrow transplant would be too toxic in this age group,” he said. “But what is very clear here is that, in an intent-to-treat analysis, there was a significant survival advantage – 48% versus 27% at 3 years for transplantation – and it was seen across all subgroups.”
 

Subcutaneous daratumumab

New data on a subcutaneous formulation of daratumumab (Darzalex, Janssen), which is usually given by intravenous infusion, will be presented from the APOLLO trial (abstract 412) in patients with relapsed/refractory multiple myeloma.

Patients who received subcutaneous daratumumab combined with pomalidomide and dexamethasone had a 37% reduction in disease progression or death compared to those who received pomalidomide and dexamethasone alone.

“From previous years we’ve learned that daratumumab has had a major impact on outcomes in multiple myeloma,” said Brodsky. “The nice thing about the subcutaneous formulation is that it can be administered quickly and in an outpatient setting, which is especially important in the COVID era.”  
 

Negative data with tranexamic acid

The fourth abstract highlighted by Brodsky is a negative study, but its findings can help guide clinical practice, he said. The a-TREAT study (abstract 2) showed that, despite being routinely used in the clinical setting, tranexamic acid does not prevent bleeding when administered prophylactically to severely thrombocytopenic patients undergoing treatment for hematologic malignancies.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”
 

‘Very exciting’ news about gene therapy

Brodsky also highlighted several late-breaking abstract that will be presented at the meeting.

In particular, the first data on a gene therapy for hemophilia B (abstract LBA-6) are “very, very exciting,” he said. The HOPE-B trial showed a 96% response rate among patients with hemophilia B who were treated with etranacogene dezaparvovec, an investigational gene therapy composed of an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX.

Brodsky pointed out that this was a large trial with 54 patients, but importantly, it included patients with pre-existing anti-AAV5 neutralizing antibodies. “About 40% of patients have naturally occurring antibodies to AAV5, and they have been excluded from previous trials because it was thought they wouldn’t take the vector,” said Brodsky. “But only one patient didn’t get a response.”

Following a single dose of etranacogene dezaparvovec, Factor IX activity increased into the mild to normal range without the need for prophylactic immunosuppression. Treated patients were able to discontinue prophylaxis and bleeding was controlled in most of the cohort.

“This is a big advance and we are getting very close to the point where gene therapy is going to be standard of care for some forms of hemophilia,” said Brodsky. However, he added that “we will still need to see more patients and have longer follow-up.”

He added that, with time, the technology behind gene therapy will probably become less expensive and more accessible to more patients, which will help become a standard of care.

This is also the hope for the technology behind chimeric antigen receptor T-cell (CAR-T) therapy, he added. At present, this cellular therapy is manufactured individually for each patient and is very expensive, but work on “off-the-shelf” products is underway. This topic will be explored during the presidential symposium, entitled, “Universal Donor Solutions in Hematology.”

New data on one of the currently available CAR-T cell products will be presented at the meeting. The phase 2 ZUMA-5 trial showed that axicabtagene ciloleucel (Axi-Cel) may be a viable option for some patients with high-risk non-Hodgkin lymphoma who have not responded to standard treatments (abstract 700).

At a median follow-up of almost 18 months, 92% of participants achieved an objective response, and 78% achieved a complete response to the treatment. By 12 months, 72% were still in response, and at 17.5 months, 64% were still in response.

“We were very impressed with the magnitude of the responses, and also the durability,” said senior study author Caron Jacobson, MD, of the Dana-Farber Cancer Institute, Boston, in a press release. “I was also struck early on by how favorable the safety profile was compared to what we’ve been seeing in the fast-growing lymphomas, such as large B cell lymphoma.”
 

Race and bloods cancers

ASH president Stephanie Lee, MD, MPH, highlighted several abstracts on disparities that will be presented at the meeting. One of these, which is to be presented during the plenary session, is an analysis of patient survival in acute myeloid leukemia (AML) (abstract 6).

It found that “self-reported race was the best indicator of survival,” noted Lee.

Overall survival at 3 years was 41% in White patients versus 32% in Black patients, a difference that was highly significant, she noted.

Part of the study also evaluated patients who were all on the same chemotherapy protocol, “so there was no effect of different treatment since they were on therapy determined by the trial,” said Lee.

Black patients were less likely to have normal cytogenetics compared with White patients (38% vs 51%; P = .01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%; P = .04), but higher frequencies of spliceosome gene mutations (24% vs 12%; P = .009). Therefore, the results showed race was an independent prognosticator of poor survival in AML, aside from established molecular markers.

A special scientific session on race will be held on Dec. 5, Lee noted. While other abstracts consider race from the patient side, this session will focus on the scientist’s side, she explained, and address questions such as: “What are the implications of diversity and racism? And how does that impact scientists who are from underrepresented minorities?” 
 

COVID-19 and blood disorders

Lee also highlighted a study (abstract 215) that analyzed emerging data from the ASH Research Collaborative COVID-19 Registry for Hematology, which was developed to look at outcomes of COVID-19 infection in patients with underlying blood disorders.

An analysis of data from 250 patients at 74 sites around the world found that overall mortality was 28%. “This supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality from COVID-19 infection,” say the authors.

“We do need real-world data to see how SARS-CoV-2 is affecting our patients with hematologic diseases or those who don’t have a hematologic disease but who are then infected with the coronavirus and develop a hematologic problem like blood clots,” said Lee.

“More data will be coming in, but this is a good example of trying to harness real-world information to learn things until we have more controlled trials.”
 

‘Fireside chat’ with Fauci

COVID-19 will be on the agenda for a special session billed as a “fireside chat” with Anthony Fauci, MD, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

“This will be kicking off our meeting on Saturday morning,” said Lee.

This article first appeared on Medscape.com.

Instead of flying out to San Diego in California and soaking up a bit of sunshine in between listening to new research presentations, hematologists from around the world will be glued to their computer screens next weekend, tuning into the 62nd American Society of Hematology annual meeting.  

Like many other conferences this year, the ASH meeting will be virtual because of the continuing COVID-19 pandemic, although the dates remain the same: Dec. 5-8.  

This is the premier hematology event of the year, and the largest hematology conference in the world, with around 3,500 abstracts presented this year, commented Aaron T. Gerds, MD, chair of ASH’s Committee on Communications.
 

Ruxolitinib in chronic GvHD

“One of the things that people come to ASH for is to hear about practice-changing clinical trials, and this year is no exception,” said ASH secretary Robert Brodsky, MD.

In a preview webinar, he highlighted four abstracts that offer opportunities to change practice and revamp the current standards of care.

One clinical trial that is “almost certainly a practice changer,” he said, is the REACH 3 study (abstract 77) of the JAK inhibitor ruxolitinib (Jakafi, Incyte) in patients with chronic graft-versus-host disease (GvHD) after a stem cell transplant.

“This has been really hard to treat in patients undergoing allogeneic bone marrow transplants,” said Brodsky. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement, and even steroids don’t work that well.”

There is currently no approved second-line therapy for chronic forms of GvHD, he emphasized. The main endpoint of the trial was overall response rate, which was doubled with ruxolitinib compared to the best available therapy (50% vs 25%).

“This is the first successful phase 3 trial for chronic GvHD,” Brodsky commented.  
 

Transplants for older patients with MDS

Transplant offers the only curative option for myelodysplastic syndromes (MDS), but typically this option is offered to younger patients because benefits for older adults have not been well-defined, Brodsky noted.

New data from a clinical trial conducted in patients with advanced MDS aged 50-75 years (abstract 75) offers the most definitive evidence to date that allogeneic hematopoietic cell transplantation (AHCT) can significantly improve outcomes for older adults.  

It’s clear that transplant is the standard of care in younger patients, Brodsky commented, and although there is a trend of offering it to older patients, some are not getting referred and instead are being offered palliative care. “The thinking is that bone marrow transplant would be too toxic in this age group,” he said. “But what is very clear here is that, in an intent-to-treat analysis, there was a significant survival advantage – 48% versus 27% at 3 years for transplantation – and it was seen across all subgroups.”
 

Subcutaneous daratumumab

New data on a subcutaneous formulation of daratumumab (Darzalex, Janssen), which is usually given by intravenous infusion, will be presented from the APOLLO trial (abstract 412) in patients with relapsed/refractory multiple myeloma.

Patients who received subcutaneous daratumumab combined with pomalidomide and dexamethasone had a 37% reduction in disease progression or death compared to those who received pomalidomide and dexamethasone alone.

“From previous years we’ve learned that daratumumab has had a major impact on outcomes in multiple myeloma,” said Brodsky. “The nice thing about the subcutaneous formulation is that it can be administered quickly and in an outpatient setting, which is especially important in the COVID era.”  
 

Negative data with tranexamic acid

The fourth abstract highlighted by Brodsky is a negative study, but its findings can help guide clinical practice, he said. The a-TREAT study (abstract 2) showed that, despite being routinely used in the clinical setting, tranexamic acid does not prevent bleeding when administered prophylactically to severely thrombocytopenic patients undergoing treatment for hematologic malignancies.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”
 

‘Very exciting’ news about gene therapy

Brodsky also highlighted several late-breaking abstract that will be presented at the meeting.

In particular, the first data on a gene therapy for hemophilia B (abstract LBA-6) are “very, very exciting,” he said. The HOPE-B trial showed a 96% response rate among patients with hemophilia B who were treated with etranacogene dezaparvovec, an investigational gene therapy composed of an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX.

Brodsky pointed out that this was a large trial with 54 patients, but importantly, it included patients with pre-existing anti-AAV5 neutralizing antibodies. “About 40% of patients have naturally occurring antibodies to AAV5, and they have been excluded from previous trials because it was thought they wouldn’t take the vector,” said Brodsky. “But only one patient didn’t get a response.”

Following a single dose of etranacogene dezaparvovec, Factor IX activity increased into the mild to normal range without the need for prophylactic immunosuppression. Treated patients were able to discontinue prophylaxis and bleeding was controlled in most of the cohort.

“This is a big advance and we are getting very close to the point where gene therapy is going to be standard of care for some forms of hemophilia,” said Brodsky. However, he added that “we will still need to see more patients and have longer follow-up.”

He added that, with time, the technology behind gene therapy will probably become less expensive and more accessible to more patients, which will help become a standard of care.

This is also the hope for the technology behind chimeric antigen receptor T-cell (CAR-T) therapy, he added. At present, this cellular therapy is manufactured individually for each patient and is very expensive, but work on “off-the-shelf” products is underway. This topic will be explored during the presidential symposium, entitled, “Universal Donor Solutions in Hematology.”

New data on one of the currently available CAR-T cell products will be presented at the meeting. The phase 2 ZUMA-5 trial showed that axicabtagene ciloleucel (Axi-Cel) may be a viable option for some patients with high-risk non-Hodgkin lymphoma who have not responded to standard treatments (abstract 700).

At a median follow-up of almost 18 months, 92% of participants achieved an objective response, and 78% achieved a complete response to the treatment. By 12 months, 72% were still in response, and at 17.5 months, 64% were still in response.

“We were very impressed with the magnitude of the responses, and also the durability,” said senior study author Caron Jacobson, MD, of the Dana-Farber Cancer Institute, Boston, in a press release. “I was also struck early on by how favorable the safety profile was compared to what we’ve been seeing in the fast-growing lymphomas, such as large B cell lymphoma.”
 

Race and bloods cancers

ASH president Stephanie Lee, MD, MPH, highlighted several abstracts on disparities that will be presented at the meeting. One of these, which is to be presented during the plenary session, is an analysis of patient survival in acute myeloid leukemia (AML) (abstract 6).

It found that “self-reported race was the best indicator of survival,” noted Lee.

Overall survival at 3 years was 41% in White patients versus 32% in Black patients, a difference that was highly significant, she noted.

Part of the study also evaluated patients who were all on the same chemotherapy protocol, “so there was no effect of different treatment since they were on therapy determined by the trial,” said Lee.

Black patients were less likely to have normal cytogenetics compared with White patients (38% vs 51%; P = .01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%; P = .04), but higher frequencies of spliceosome gene mutations (24% vs 12%; P = .009). Therefore, the results showed race was an independent prognosticator of poor survival in AML, aside from established molecular markers.

A special scientific session on race will be held on Dec. 5, Lee noted. While other abstracts consider race from the patient side, this session will focus on the scientist’s side, she explained, and address questions such as: “What are the implications of diversity and racism? And how does that impact scientists who are from underrepresented minorities?” 
 

COVID-19 and blood disorders

Lee also highlighted a study (abstract 215) that analyzed emerging data from the ASH Research Collaborative COVID-19 Registry for Hematology, which was developed to look at outcomes of COVID-19 infection in patients with underlying blood disorders.

An analysis of data from 250 patients at 74 sites around the world found that overall mortality was 28%. “This supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality from COVID-19 infection,” say the authors.

“We do need real-world data to see how SARS-CoV-2 is affecting our patients with hematologic diseases or those who don’t have a hematologic disease but who are then infected with the coronavirus and develop a hematologic problem like blood clots,” said Lee.

“More data will be coming in, but this is a good example of trying to harness real-world information to learn things until we have more controlled trials.”
 

‘Fireside chat’ with Fauci

COVID-19 will be on the agenda for a special session billed as a “fireside chat” with Anthony Fauci, MD, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

“This will be kicking off our meeting on Saturday morning,” said Lee.

This article first appeared on Medscape.com.

Instead of flying out to San Diego in California and soaking up a bit of sunshine in between listening to new research presentations, hematologists from around the world will be glued to their computer screens next weekend, tuning into the 62nd American Society of Hematology annual meeting.  

Like many other conferences this year, the ASH meeting will be virtual because of the continuing COVID-19 pandemic, although the dates remain the same: Dec. 5-8.  

This is the premier hematology event of the year, and the largest hematology conference in the world, with around 3,500 abstracts presented this year, commented Aaron T. Gerds, MD, chair of ASH’s Committee on Communications.
 

Ruxolitinib in chronic GvHD

“One of the things that people come to ASH for is to hear about practice-changing clinical trials, and this year is no exception,” said ASH secretary Robert Brodsky, MD.

In a preview webinar, he highlighted four abstracts that offer opportunities to change practice and revamp the current standards of care.

One clinical trial that is “almost certainly a practice changer,” he said, is the REACH 3 study (abstract 77) of the JAK inhibitor ruxolitinib (Jakafi, Incyte) in patients with chronic graft-versus-host disease (GvHD) after a stem cell transplant.

“This has been really hard to treat in patients undergoing allogeneic bone marrow transplants,” said Brodsky. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement, and even steroids don’t work that well.”

There is currently no approved second-line therapy for chronic forms of GvHD, he emphasized. The main endpoint of the trial was overall response rate, which was doubled with ruxolitinib compared to the best available therapy (50% vs 25%).

“This is the first successful phase 3 trial for chronic GvHD,” Brodsky commented.  
 

Transplants for older patients with MDS

Transplant offers the only curative option for myelodysplastic syndromes (MDS), but typically this option is offered to younger patients because benefits for older adults have not been well-defined, Brodsky noted.

New data from a clinical trial conducted in patients with advanced MDS aged 50-75 years (abstract 75) offers the most definitive evidence to date that allogeneic hematopoietic cell transplantation (AHCT) can significantly improve outcomes for older adults.  

It’s clear that transplant is the standard of care in younger patients, Brodsky commented, and although there is a trend of offering it to older patients, some are not getting referred and instead are being offered palliative care. “The thinking is that bone marrow transplant would be too toxic in this age group,” he said. “But what is very clear here is that, in an intent-to-treat analysis, there was a significant survival advantage – 48% versus 27% at 3 years for transplantation – and it was seen across all subgroups.”
 

Subcutaneous daratumumab

New data on a subcutaneous formulation of daratumumab (Darzalex, Janssen), which is usually given by intravenous infusion, will be presented from the APOLLO trial (abstract 412) in patients with relapsed/refractory multiple myeloma.

Patients who received subcutaneous daratumumab combined with pomalidomide and dexamethasone had a 37% reduction in disease progression or death compared to those who received pomalidomide and dexamethasone alone.

“From previous years we’ve learned that daratumumab has had a major impact on outcomes in multiple myeloma,” said Brodsky. “The nice thing about the subcutaneous formulation is that it can be administered quickly and in an outpatient setting, which is especially important in the COVID era.”  
 

Negative data with tranexamic acid

The fourth abstract highlighted by Brodsky is a negative study, but its findings can help guide clinical practice, he said. The a-TREAT study (abstract 2) showed that, despite being routinely used in the clinical setting, tranexamic acid does not prevent bleeding when administered prophylactically to severely thrombocytopenic patients undergoing treatment for hematologic malignancies.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”
 

‘Very exciting’ news about gene therapy

Brodsky also highlighted several late-breaking abstract that will be presented at the meeting.

In particular, the first data on a gene therapy for hemophilia B (abstract LBA-6) are “very, very exciting,” he said. The HOPE-B trial showed a 96% response rate among patients with hemophilia B who were treated with etranacogene dezaparvovec, an investigational gene therapy composed of an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX.

Brodsky pointed out that this was a large trial with 54 patients, but importantly, it included patients with pre-existing anti-AAV5 neutralizing antibodies. “About 40% of patients have naturally occurring antibodies to AAV5, and they have been excluded from previous trials because it was thought they wouldn’t take the vector,” said Brodsky. “But only one patient didn’t get a response.”

Following a single dose of etranacogene dezaparvovec, Factor IX activity increased into the mild to normal range without the need for prophylactic immunosuppression. Treated patients were able to discontinue prophylaxis and bleeding was controlled in most of the cohort.

“This is a big advance and we are getting very close to the point where gene therapy is going to be standard of care for some forms of hemophilia,” said Brodsky. However, he added that “we will still need to see more patients and have longer follow-up.”

He added that, with time, the technology behind gene therapy will probably become less expensive and more accessible to more patients, which will help become a standard of care.

This is also the hope for the technology behind chimeric antigen receptor T-cell (CAR-T) therapy, he added. At present, this cellular therapy is manufactured individually for each patient and is very expensive, but work on “off-the-shelf” products is underway. This topic will be explored during the presidential symposium, entitled, “Universal Donor Solutions in Hematology.”

New data on one of the currently available CAR-T cell products will be presented at the meeting. The phase 2 ZUMA-5 trial showed that axicabtagene ciloleucel (Axi-Cel) may be a viable option for some patients with high-risk non-Hodgkin lymphoma who have not responded to standard treatments (abstract 700).

At a median follow-up of almost 18 months, 92% of participants achieved an objective response, and 78% achieved a complete response to the treatment. By 12 months, 72% were still in response, and at 17.5 months, 64% were still in response.

“We were very impressed with the magnitude of the responses, and also the durability,” said senior study author Caron Jacobson, MD, of the Dana-Farber Cancer Institute, Boston, in a press release. “I was also struck early on by how favorable the safety profile was compared to what we’ve been seeing in the fast-growing lymphomas, such as large B cell lymphoma.”
 

Race and bloods cancers

ASH president Stephanie Lee, MD, MPH, highlighted several abstracts on disparities that will be presented at the meeting. One of these, which is to be presented during the plenary session, is an analysis of patient survival in acute myeloid leukemia (AML) (abstract 6).

It found that “self-reported race was the best indicator of survival,” noted Lee.

Overall survival at 3 years was 41% in White patients versus 32% in Black patients, a difference that was highly significant, she noted.

Part of the study also evaluated patients who were all on the same chemotherapy protocol, “so there was no effect of different treatment since they were on therapy determined by the trial,” said Lee.

Black patients were less likely to have normal cytogenetics compared with White patients (38% vs 51%; P = .01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%; P = .04), but higher frequencies of spliceosome gene mutations (24% vs 12%; P = .009). Therefore, the results showed race was an independent prognosticator of poor survival in AML, aside from established molecular markers.

A special scientific session on race will be held on Dec. 5, Lee noted. While other abstracts consider race from the patient side, this session will focus on the scientist’s side, she explained, and address questions such as: “What are the implications of diversity and racism? And how does that impact scientists who are from underrepresented minorities?” 
 

COVID-19 and blood disorders

Lee also highlighted a study (abstract 215) that analyzed emerging data from the ASH Research Collaborative COVID-19 Registry for Hematology, which was developed to look at outcomes of COVID-19 infection in patients with underlying blood disorders.

An analysis of data from 250 patients at 74 sites around the world found that overall mortality was 28%. “This supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality from COVID-19 infection,” say the authors.

“We do need real-world data to see how SARS-CoV-2 is affecting our patients with hematologic diseases or those who don’t have a hematologic disease but who are then infected with the coronavirus and develop a hematologic problem like blood clots,” said Lee.

“More data will be coming in, but this is a good example of trying to harness real-world information to learn things until we have more controlled trials.”
 

‘Fireside chat’ with Fauci

COVID-19 will be on the agenda for a special session billed as a “fireside chat” with Anthony Fauci, MD, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

“This will be kicking off our meeting on Saturday morning,” said Lee.

This article first appeared on Medscape.com.

It’s high time to say farewell to the traditional categorization of psoriasis severity into mild, moderate, or severe disease, according to the International Psoriasis Council.

The mild/moderate/severe categorization is vague and defined differently by different organizations and in different countries. It often underestimates disease severity because it ignores psoriasis involvement in particularly tough-to-treat special areas, including the scalp, palms, soles, face, nails, and genitalia, Bruce E. Strober, MD, PhD, asserted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year. He chaired an IPC project in which prominent psoriasis experts in 32 countries employed a Delphi consensus approach aimed at achieving agreement on a more practical recategorization of psoriasis severity for use in both daily clinical practice and enrolling appropriate participants in clinical trials. What emerged was a simplified dichotomous categorization system.

“What we came up with is a very sensible approach to defining whether patients should get either topical or systemic therapy. In fact, there are only two groups of patients in psoriasis: those who should get topicals alone, and those who should get systemic therapy. It’s topicals or systemics,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., who also works in private practice in Cromwell, Conn.

Under the IPC classification, psoriasis patients are candidates for systemic therapy if they meet at least one of three criteria: body surface area of involvement greater than 10%, disease involving the previously mentioned special areas, or failure of topical therapy.

“This approach is about practically treating patients who are in need,” Dr. Strober said. “If patients meet just one of these three criteria they can move on to our current toolbox of systemic therapies, be they older systemic treatments, apremilast, phototherapy, or 1 of the 11 biologics currently approved for the treatment of psoriasis. The key point is that for patients with moderate to severe psoriasis – or should I say, systemic therapy–appropriate psoriasis – treatment should be based on individual patient characteristics. We don’t work on a stepwise approach. If a patient walks in with more than 10% body surface area involved, don’t make them fail topicals; you can go right to systemics.”

European dermatologists often use the Psoriasis Area and Severity Index (PASI) score to characterize disease severity and monitor response to therapy. In contrast, American dermatologists generally find PASI too complex and time-consuming for use in clinical practice, relying instead on the amount of body surface area involved with psoriasis. Neither of these measures incorporates disease involvement in special areas, which when present ought to automatically place a patient in the systemic therapy–appropriate category, according to Dr. Strober.

“I find this [IPC recategorization] a very practical approach. I hope you write this down and use this in your own practice,” Dr. Strober said.

The full IPC report was published in the Journal of the American Academy of Dermatology.

The IPC psoriasis severity reclassification project was unfunded. Dr. Strober reported receiving institutional research funding from and serving as a paid consultant to more than two dozen pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

It’s high time to say farewell to the traditional categorization of psoriasis severity into mild, moderate, or severe disease, according to the International Psoriasis Council.

The mild/moderate/severe categorization is vague and defined differently by different organizations and in different countries. It often underestimates disease severity because it ignores psoriasis involvement in particularly tough-to-treat special areas, including the scalp, palms, soles, face, nails, and genitalia, Bruce E. Strober, MD, PhD, asserted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year. He chaired an IPC project in which prominent psoriasis experts in 32 countries employed a Delphi consensus approach aimed at achieving agreement on a more practical recategorization of psoriasis severity for use in both daily clinical practice and enrolling appropriate participants in clinical trials. What emerged was a simplified dichotomous categorization system.

“What we came up with is a very sensible approach to defining whether patients should get either topical or systemic therapy. In fact, there are only two groups of patients in psoriasis: those who should get topicals alone, and those who should get systemic therapy. It’s topicals or systemics,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., who also works in private practice in Cromwell, Conn.

Under the IPC classification, psoriasis patients are candidates for systemic therapy if they meet at least one of three criteria: body surface area of involvement greater than 10%, disease involving the previously mentioned special areas, or failure of topical therapy.

“This approach is about practically treating patients who are in need,” Dr. Strober said. “If patients meet just one of these three criteria they can move on to our current toolbox of systemic therapies, be they older systemic treatments, apremilast, phototherapy, or 1 of the 11 biologics currently approved for the treatment of psoriasis. The key point is that for patients with moderate to severe psoriasis – or should I say, systemic therapy–appropriate psoriasis – treatment should be based on individual patient characteristics. We don’t work on a stepwise approach. If a patient walks in with more than 10% body surface area involved, don’t make them fail topicals; you can go right to systemics.”

European dermatologists often use the Psoriasis Area and Severity Index (PASI) score to characterize disease severity and monitor response to therapy. In contrast, American dermatologists generally find PASI too complex and time-consuming for use in clinical practice, relying instead on the amount of body surface area involved with psoriasis. Neither of these measures incorporates disease involvement in special areas, which when present ought to automatically place a patient in the systemic therapy–appropriate category, according to Dr. Strober.

“I find this [IPC recategorization] a very practical approach. I hope you write this down and use this in your own practice,” Dr. Strober said.

The full IPC report was published in the Journal of the American Academy of Dermatology.

The IPC psoriasis severity reclassification project was unfunded. Dr. Strober reported receiving institutional research funding from and serving as a paid consultant to more than two dozen pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

It’s high time to say farewell to the traditional categorization of psoriasis severity into mild, moderate, or severe disease, according to the International Psoriasis Council.

The mild/moderate/severe categorization is vague and defined differently by different organizations and in different countries. It often underestimates disease severity because it ignores psoriasis involvement in particularly tough-to-treat special areas, including the scalp, palms, soles, face, nails, and genitalia, Bruce E. Strober, MD, PhD, asserted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year. He chaired an IPC project in which prominent psoriasis experts in 32 countries employed a Delphi consensus approach aimed at achieving agreement on a more practical recategorization of psoriasis severity for use in both daily clinical practice and enrolling appropriate participants in clinical trials. What emerged was a simplified dichotomous categorization system.

“What we came up with is a very sensible approach to defining whether patients should get either topical or systemic therapy. In fact, there are only two groups of patients in psoriasis: those who should get topicals alone, and those who should get systemic therapy. It’s topicals or systemics,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., who also works in private practice in Cromwell, Conn.

Under the IPC classification, psoriasis patients are candidates for systemic therapy if they meet at least one of three criteria: body surface area of involvement greater than 10%, disease involving the previously mentioned special areas, or failure of topical therapy.

“This approach is about practically treating patients who are in need,” Dr. Strober said. “If patients meet just one of these three criteria they can move on to our current toolbox of systemic therapies, be they older systemic treatments, apremilast, phototherapy, or 1 of the 11 biologics currently approved for the treatment of psoriasis. The key point is that for patients with moderate to severe psoriasis – or should I say, systemic therapy–appropriate psoriasis – treatment should be based on individual patient characteristics. We don’t work on a stepwise approach. If a patient walks in with more than 10% body surface area involved, don’t make them fail topicals; you can go right to systemics.”

European dermatologists often use the Psoriasis Area and Severity Index (PASI) score to characterize disease severity and monitor response to therapy. In contrast, American dermatologists generally find PASI too complex and time-consuming for use in clinical practice, relying instead on the amount of body surface area involved with psoriasis. Neither of these measures incorporates disease involvement in special areas, which when present ought to automatically place a patient in the systemic therapy–appropriate category, according to Dr. Strober.

“I find this [IPC recategorization] a very practical approach. I hope you write this down and use this in your own practice,” Dr. Strober said.

The full IPC report was published in the Journal of the American Academy of Dermatology.

The IPC psoriasis severity reclassification project was unfunded. Dr. Strober reported receiving institutional research funding from and serving as a paid consultant to more than two dozen pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

Many laser and light-based technologies fall short when it comes to treating people of color, according to Haley L. Marks, PhD.

For one thing, melanin’s extinction overlaps with common laser lines, which affects the safety and efficacy of laser treatments in dermatology, but also in imaging and wearable devices that use LEDs in the visible range. “Pheomelanin and eumelanin are chemically very similar and both have this property of having very high extinction coefficients in the visible range, meaning that melanins both absorb and scatter light which we commonly use for laser treatments and for wearable medical devices,” Dr. Marks, a research scientist in dermatology at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “Melanins also shadow a number of other biological signals that we look for in the skin, such as those from hemoglobin.”

A number of different scales can be used to estimate the amount of eumelanin, or darkly pigmented melanin, in the skin, but the most famous is Fitzpatrick skin typing, the classification system that ranges from I to VI originally intended to quantify the skin’s response to UV light. “It’s so famous that it’s used in the emoji modifier of the Unicode Consortium lookup table,” said Dr. Marks, who spoke on behalf of the Wellman Anti-Racism Effort (WARE), a grassroots working group within the Wellman Center for Photomedicine at Massachusetts General Hospital. (The mission of the group is to eradicate racism in STEM, medicine, and academia starting with its own research and Center.)

Dr. Marks referred to a Northwestern University study published in 2013, which found that both patients and dermatologists failed to accurately determine Fitzpatrick skin type (FST) when compared with reflectance spectrophotometry used to measure melanin index objectively. “There is a need to classify skin type with reliable questions with responses suitable for all skin types,” the authors concluded.

Plenty more can go wrong when clinicians ignore or misunderstand the role of melanin as a background contrast agent, Dr. Marks continued. She cited the common misconception that melanomas do not occur in darker pigmented skin, a topic discussed in an article published online in January 2020 in Cancer Cytopathology.

“While they do occur at a lower rate, this misconception leads to an alarmingly low survival rate for black melanoma patients,” Dr. Marks said. “Acral lentiginous melanoma is one example of this. It is not related to sun exposure, yet it occurs in 30% to 70% of melanomas in black patients. This also exposes a mortality rate of 1 in 3 for Black melanoma patients, compared with 1 in 11 for White patients. In fact, Black patients face a lower survival for most cancers, often attributed to social and economic disparities rather than biological differences.”

Another significant contributing factor may be the lack of data and awareness of clinical research related to patients with skin of color. The Skin of Color Society’s “Find a Doctor” database is attempting to address this by improving patients’ access to board-certified dermatologists who specialize in skin of color. “Some of the discrepancies in dermatology education, screening, and treatment for Black, indigenous, and people of color is likely attributed to the fact that only 4.5% of images in general medical textbooks show darker skin, as they are only 5% of clinical trial participants despite making up 17% of the U.S. population,” Dr. Marks said at the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. Mind The Gap, a handbook of clinical signs and symptoms in black and brown skin, was published in 2020 by students and staff at St. George’s University of London. It can be downloaded for free.

Some 40 years after Kodak was criticized for not acknowledging inherent biases in their film stocks based on its “Kodak Shirley” color correction card, Dr. Marks said that camera makers are still ignoring racial bias in their technologies. “This is likely a ‘garbage in, garbage out’ phenomenon,” she said. “Due to the lack of diverse images, these biases get ingrained into machine learning models themselves, either because patients were not served in the first place, resulting in missing data, or because of mislabeling due to a lack of knowledge in properly classifying these images. So, while machine learning has the potential to step in where dermatologists fall short, we must be very diligent about recognizing any bias we are ingraining into these algorithms,” she said.

“That said, no technology is ‘born racist,’ of course; it is up to us to prevent history from repeating itself and prevent these biases from being ingrained in our work,” she added. “We can start by holding ourselves and others accountable when designing studies that have exclusion criteria, by challenging our sponsors on the exclusion of Fitzpatrick V and VI if you feel it is not scientifically sound, and by ensuring inclusive algorithm development. If these things are not possible, please use a disclaimer to make these limitations clear.”

According to Dr. Marks and WARE, clinicians can increase diversity in clinical trials by widening eligibility criteria, tapping into community-based medical centers, connecting with patient advocacy groups, using point-of-care and telemedicine technologies, supporting diversity-focused public policy on a larger scale, and making diversity an internal mandate, “within your institution, and within yourselves.”

Some community efforts stemming from Wellman inventions so far include the Texas-based Removery INK-nitiative program, which removes racist and hateful tattoos for free via laser tattoo removal technology that was invented at Wellman. Dr. Marks and her WARE colleagues also work with the Dream Beam Foundation, which is a global initiative bringing laser-based technologies to children in Vietnam, Armenia, Israel, Brazil, and Lebanon.

Dr. Marks reported having no financial disclosures.

dbrunk@mdedge.com

Many laser and light-based technologies fall short when it comes to treating people of color, according to Haley L. Marks, PhD.

For one thing, melanin’s extinction overlaps with common laser lines, which affects the safety and efficacy of laser treatments in dermatology, but also in imaging and wearable devices that use LEDs in the visible range. “Pheomelanin and eumelanin are chemically very similar and both have this property of having very high extinction coefficients in the visible range, meaning that melanins both absorb and scatter light which we commonly use for laser treatments and for wearable medical devices,” Dr. Marks, a research scientist in dermatology at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “Melanins also shadow a number of other biological signals that we look for in the skin, such as those from hemoglobin.”

A number of different scales can be used to estimate the amount of eumelanin, or darkly pigmented melanin, in the skin, but the most famous is Fitzpatrick skin typing, the classification system that ranges from I to VI originally intended to quantify the skin’s response to UV light. “It’s so famous that it’s used in the emoji modifier of the Unicode Consortium lookup table,” said Dr. Marks, who spoke on behalf of the Wellman Anti-Racism Effort (WARE), a grassroots working group within the Wellman Center for Photomedicine at Massachusetts General Hospital. (The mission of the group is to eradicate racism in STEM, medicine, and academia starting with its own research and Center.)

Dr. Marks referred to a Northwestern University study published in 2013, which found that both patients and dermatologists failed to accurately determine Fitzpatrick skin type (FST) when compared with reflectance spectrophotometry used to measure melanin index objectively. “There is a need to classify skin type with reliable questions with responses suitable for all skin types,” the authors concluded.

Plenty more can go wrong when clinicians ignore or misunderstand the role of melanin as a background contrast agent, Dr. Marks continued. She cited the common misconception that melanomas do not occur in darker pigmented skin, a topic discussed in an article published online in January 2020 in Cancer Cytopathology.

“While they do occur at a lower rate, this misconception leads to an alarmingly low survival rate for black melanoma patients,” Dr. Marks said. “Acral lentiginous melanoma is one example of this. It is not related to sun exposure, yet it occurs in 30% to 70% of melanomas in black patients. This also exposes a mortality rate of 1 in 3 for Black melanoma patients, compared with 1 in 11 for White patients. In fact, Black patients face a lower survival for most cancers, often attributed to social and economic disparities rather than biological differences.”

Another significant contributing factor may be the lack of data and awareness of clinical research related to patients with skin of color. The Skin of Color Society’s “Find a Doctor” database is attempting to address this by improving patients’ access to board-certified dermatologists who specialize in skin of color. “Some of the discrepancies in dermatology education, screening, and treatment for Black, indigenous, and people of color is likely attributed to the fact that only 4.5% of images in general medical textbooks show darker skin, as they are only 5% of clinical trial participants despite making up 17% of the U.S. population,” Dr. Marks said at the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. Mind The Gap, a handbook of clinical signs and symptoms in black and brown skin, was published in 2020 by students and staff at St. George’s University of London. It can be downloaded for free.

Some 40 years after Kodak was criticized for not acknowledging inherent biases in their film stocks based on its “Kodak Shirley” color correction card, Dr. Marks said that camera makers are still ignoring racial bias in their technologies. “This is likely a ‘garbage in, garbage out’ phenomenon,” she said. “Due to the lack of diverse images, these biases get ingrained into machine learning models themselves, either because patients were not served in the first place, resulting in missing data, or because of mislabeling due to a lack of knowledge in properly classifying these images. So, while machine learning has the potential to step in where dermatologists fall short, we must be very diligent about recognizing any bias we are ingraining into these algorithms,” she said.

“That said, no technology is ‘born racist,’ of course; it is up to us to prevent history from repeating itself and prevent these biases from being ingrained in our work,” she added. “We can start by holding ourselves and others accountable when designing studies that have exclusion criteria, by challenging our sponsors on the exclusion of Fitzpatrick V and VI if you feel it is not scientifically sound, and by ensuring inclusive algorithm development. If these things are not possible, please use a disclaimer to make these limitations clear.”

According to Dr. Marks and WARE, clinicians can increase diversity in clinical trials by widening eligibility criteria, tapping into community-based medical centers, connecting with patient advocacy groups, using point-of-care and telemedicine technologies, supporting diversity-focused public policy on a larger scale, and making diversity an internal mandate, “within your institution, and within yourselves.”

Some community efforts stemming from Wellman inventions so far include the Texas-based Removery INK-nitiative program, which removes racist and hateful tattoos for free via laser tattoo removal technology that was invented at Wellman. Dr. Marks and her WARE colleagues also work with the Dream Beam Foundation, which is a global initiative bringing laser-based technologies to children in Vietnam, Armenia, Israel, Brazil, and Lebanon.

Dr. Marks reported having no financial disclosures.

dbrunk@mdedge.com

Many laser and light-based technologies fall short when it comes to treating people of color, according to Haley L. Marks, PhD.

For one thing, melanin’s extinction overlaps with common laser lines, which affects the safety and efficacy of laser treatments in dermatology, but also in imaging and wearable devices that use LEDs in the visible range. “Pheomelanin and eumelanin are chemically very similar and both have this property of having very high extinction coefficients in the visible range, meaning that melanins both absorb and scatter light which we commonly use for laser treatments and for wearable medical devices,” Dr. Marks, a research scientist in dermatology at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “Melanins also shadow a number of other biological signals that we look for in the skin, such as those from hemoglobin.”

A number of different scales can be used to estimate the amount of eumelanin, or darkly pigmented melanin, in the skin, but the most famous is Fitzpatrick skin typing, the classification system that ranges from I to VI originally intended to quantify the skin’s response to UV light. “It’s so famous that it’s used in the emoji modifier of the Unicode Consortium lookup table,” said Dr. Marks, who spoke on behalf of the Wellman Anti-Racism Effort (WARE), a grassroots working group within the Wellman Center for Photomedicine at Massachusetts General Hospital. (The mission of the group is to eradicate racism in STEM, medicine, and academia starting with its own research and Center.)

Dr. Marks referred to a Northwestern University study published in 2013, which found that both patients and dermatologists failed to accurately determine Fitzpatrick skin type (FST) when compared with reflectance spectrophotometry used to measure melanin index objectively. “There is a need to classify skin type with reliable questions with responses suitable for all skin types,” the authors concluded.

Plenty more can go wrong when clinicians ignore or misunderstand the role of melanin as a background contrast agent, Dr. Marks continued. She cited the common misconception that melanomas do not occur in darker pigmented skin, a topic discussed in an article published online in January 2020 in Cancer Cytopathology.

“While they do occur at a lower rate, this misconception leads to an alarmingly low survival rate for black melanoma patients,” Dr. Marks said. “Acral lentiginous melanoma is one example of this. It is not related to sun exposure, yet it occurs in 30% to 70% of melanomas in black patients. This also exposes a mortality rate of 1 in 3 for Black melanoma patients, compared with 1 in 11 for White patients. In fact, Black patients face a lower survival for most cancers, often attributed to social and economic disparities rather than biological differences.”

Another significant contributing factor may be the lack of data and awareness of clinical research related to patients with skin of color. The Skin of Color Society’s “Find a Doctor” database is attempting to address this by improving patients’ access to board-certified dermatologists who specialize in skin of color. “Some of the discrepancies in dermatology education, screening, and treatment for Black, indigenous, and people of color is likely attributed to the fact that only 4.5% of images in general medical textbooks show darker skin, as they are only 5% of clinical trial participants despite making up 17% of the U.S. population,” Dr. Marks said at the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. Mind The Gap, a handbook of clinical signs and symptoms in black and brown skin, was published in 2020 by students and staff at St. George’s University of London. It can be downloaded for free.

Some 40 years after Kodak was criticized for not acknowledging inherent biases in their film stocks based on its “Kodak Shirley” color correction card, Dr. Marks said that camera makers are still ignoring racial bias in their technologies. “This is likely a ‘garbage in, garbage out’ phenomenon,” she said. “Due to the lack of diverse images, these biases get ingrained into machine learning models themselves, either because patients were not served in the first place, resulting in missing data, or because of mislabeling due to a lack of knowledge in properly classifying these images. So, while machine learning has the potential to step in where dermatologists fall short, we must be very diligent about recognizing any bias we are ingraining into these algorithms,” she said.

“That said, no technology is ‘born racist,’ of course; it is up to us to prevent history from repeating itself and prevent these biases from being ingrained in our work,” she added. “We can start by holding ourselves and others accountable when designing studies that have exclusion criteria, by challenging our sponsors on the exclusion of Fitzpatrick V and VI if you feel it is not scientifically sound, and by ensuring inclusive algorithm development. If these things are not possible, please use a disclaimer to make these limitations clear.”

According to Dr. Marks and WARE, clinicians can increase diversity in clinical trials by widening eligibility criteria, tapping into community-based medical centers, connecting with patient advocacy groups, using point-of-care and telemedicine technologies, supporting diversity-focused public policy on a larger scale, and making diversity an internal mandate, “within your institution, and within yourselves.”

Some community efforts stemming from Wellman inventions so far include the Texas-based Removery INK-nitiative program, which removes racist and hateful tattoos for free via laser tattoo removal technology that was invented at Wellman. Dr. Marks and her WARE colleagues also work with the Dream Beam Foundation, which is a global initiative bringing laser-based technologies to children in Vietnam, Armenia, Israel, Brazil, and Lebanon.

Dr. Marks reported having no financial disclosures.

dbrunk@mdedge.com

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.

“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”

Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.

A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.

“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.

Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.

“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.

The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.

“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.

 

Durability of response and safety

“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.

Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.

Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.

“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.

There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.

Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.

Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.

For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
 

What about IL-12/23 and IL-23 inhibitors in PsA?

In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.

An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.

Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.

“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”

Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.

A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.

“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.

Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.

“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.

The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.

“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.

 

Durability of response and safety

“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.

Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.

Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.

“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.

There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.

Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.

Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.

For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
 

What about IL-12/23 and IL-23 inhibitors in PsA?

In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.

An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.

Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.

“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”

Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.

A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.

“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.

Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.

“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.

The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.

“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.

 

Durability of response and safety

“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.

Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.

Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.

“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.

There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.

Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.

Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.

For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
 

What about IL-12/23 and IL-23 inhibitors in PsA?

In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.

An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.

Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

Most potential complications associated with filler and neuromodulator injections can be managed or prevented, and the right protocols can help in the rare cases of serious complications, Katie Beleznay, MD, of the University of British Columbia, Vancouver, said in a virtual presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The number of reported cases of vascular complications in patients receiving fillers has increased in recent years, said Dr. Beleznay, who also treats patients in private practice in Vancouver. However, knowing the facial anatomy and recognizing that there is no “one-size-fits-all” approach goes a long way in preventing and managing complications.

In terms of neuromodulators such as Botox, the upper face is the most common area for treatment, and potential complications include eyelid ptosis, brow ptosis, and the “Spock brow,” Dr. Beleznay noted. For example, patients won’t be able to engage elevator muscles, such as the frontalis, if too much neuromodulator is injected. But, a couple of units in the upper forehead can help make the effect look natural, soften the lines, without being too frozen.

To help avoid eyelid ptosis with neuromodulators, inject at least one centimeter above the supraorbital rim at the midpupillary line, Dr. Beleznay advised. “I will feel the muscle,” because some brows are drawn or microbladed on, she noted. Patients who develop eyelid ptosis can be treated with apraclonidine drops.

To avoid brow ptosis with neuromodulators, it is important to assess the anatomy at baseline, Dr. Beleznay said. Some patients like to be able to lift their brows, and too much Botox will prevent their doing so. In order to mitigate this, it is important to treat brow depressors to balance and provide lift, and staying above the first horizontal forehead rhytid when injecting can help reduce brow ptosis risk.

Remember when injecting the upper face there are several glabellar contraction patterns, so “be sure you are targeting the treatment for the muscle pulling pattern that you see,” she said.
 

Complications associated with fillers

When injecting fillers, there are rare complications, including blindness, that are worth acknowledging, said Dr. Beleznay, lead author of a study on global cases of blindness caused by fillers published in 2015, including 98 cases up to 2015, and another 48 cases in a study published in 2019.

The highest-risk areas for causing blindness with fillers are the glabella and the nose, but “anywhere you are injecting is at risk for this complication,” she commented.

Explaining the mechanism of action for blindness resulting from filler injections, she said: “When the tip of the needle gets into the vessel, if you put enough pressure on the plunger, the filler can travel retrograde in the vessel back into the ophthalmic artery system, and then travels distally and blocks blood supply to the retina,” causing vision complications.

Understanding the potential mechanism for these complications informs preventive strategies, Dr. Beleznay emphasized.

If vision complications from fillers occur, they are likely to happen immediately, she said. There could be skin involvement or stroke-like features in addition to vision complications, so it is important to screen for these conditions as well if patients complain of vision loss.

Tips for prevention

Knowing the anatomy is the first step to maximize safe placement of fillers, Dr. Beleznay said. For example, the glabella is a high-risk location and includes the supraorbital and supratrochlear arteries, which start deep and become more superficial as they travel up the forehead.

When Dr. Beleznay injects in the glabella area, “I will do a true intradermal injection using tiny microdroplets, because that feels safest to me.” A video with additional details on surface anatomy and safer planes for injecting is available online to members of the American Society of Dermatologic Surgery.

Other tips to reduce the risk of vascular complications include injecting slowly and with a minimal amount of pressure, Dr. Beleznay emphasized. Injecting in small increments, moving the needle tip between injections, and using a cannula also may help reduce risk.

Always ask and use caution if patients have had other recent surgical procedures, she added.

Vascular complications such as blindness can be devastating, but the overall risks remain low. It’s important that clinicians know their anatomy, educate patients, and have prepared treatment protocols in place in the event of serious complications, Dr. Beleznay noted.

Dr. Beleznay disclosed relationships as an investigator, speaker, and/or consultant with AbbVie, Actelion, Allergan, Almirall, Amgen, Bausch Health, Celgene, Cipher, Evolus, Galderma, Johnson & Johnson, L’Oreal, Leo, Merz, Novartis, Procter & Gamble, Prollenium, Revance, Sandoz, Sanofi, Valeant, Vichy, and Zeltiq.

MedscapeLive and this news organization are owned by the same parent company.

Most potential complications associated with filler and neuromodulator injections can be managed or prevented, and the right protocols can help in the rare cases of serious complications, Katie Beleznay, MD, of the University of British Columbia, Vancouver, said in a virtual presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The number of reported cases of vascular complications in patients receiving fillers has increased in recent years, said Dr. Beleznay, who also treats patients in private practice in Vancouver. However, knowing the facial anatomy and recognizing that there is no “one-size-fits-all” approach goes a long way in preventing and managing complications.

In terms of neuromodulators such as Botox, the upper face is the most common area for treatment, and potential complications include eyelid ptosis, brow ptosis, and the “Spock brow,” Dr. Beleznay noted. For example, patients won’t be able to engage elevator muscles, such as the frontalis, if too much neuromodulator is injected. But, a couple of units in the upper forehead can help make the effect look natural, soften the lines, without being too frozen.

To help avoid eyelid ptosis with neuromodulators, inject at least one centimeter above the supraorbital rim at the midpupillary line, Dr. Beleznay advised. “I will feel the muscle,” because some brows are drawn or microbladed on, she noted. Patients who develop eyelid ptosis can be treated with apraclonidine drops.

To avoid brow ptosis with neuromodulators, it is important to assess the anatomy at baseline, Dr. Beleznay said. Some patients like to be able to lift their brows, and too much Botox will prevent their doing so. In order to mitigate this, it is important to treat brow depressors to balance and provide lift, and staying above the first horizontal forehead rhytid when injecting can help reduce brow ptosis risk.

Remember when injecting the upper face there are several glabellar contraction patterns, so “be sure you are targeting the treatment for the muscle pulling pattern that you see,” she said.
 

Complications associated with fillers

When injecting fillers, there are rare complications, including blindness, that are worth acknowledging, said Dr. Beleznay, lead author of a study on global cases of blindness caused by fillers published in 2015, including 98 cases up to 2015, and another 48 cases in a study published in 2019.

The highest-risk areas for causing blindness with fillers are the glabella and the nose, but “anywhere you are injecting is at risk for this complication,” she commented.

Explaining the mechanism of action for blindness resulting from filler injections, she said: “When the tip of the needle gets into the vessel, if you put enough pressure on the plunger, the filler can travel retrograde in the vessel back into the ophthalmic artery system, and then travels distally and blocks blood supply to the retina,” causing vision complications.

Understanding the potential mechanism for these complications informs preventive strategies, Dr. Beleznay emphasized.

If vision complications from fillers occur, they are likely to happen immediately, she said. There could be skin involvement or stroke-like features in addition to vision complications, so it is important to screen for these conditions as well if patients complain of vision loss.

Tips for prevention

Knowing the anatomy is the first step to maximize safe placement of fillers, Dr. Beleznay said. For example, the glabella is a high-risk location and includes the supraorbital and supratrochlear arteries, which start deep and become more superficial as they travel up the forehead.

When Dr. Beleznay injects in the glabella area, “I will do a true intradermal injection using tiny microdroplets, because that feels safest to me.” A video with additional details on surface anatomy and safer planes for injecting is available online to members of the American Society of Dermatologic Surgery.

Other tips to reduce the risk of vascular complications include injecting slowly and with a minimal amount of pressure, Dr. Beleznay emphasized. Injecting in small increments, moving the needle tip between injections, and using a cannula also may help reduce risk.

Always ask and use caution if patients have had other recent surgical procedures, she added.

Vascular complications such as blindness can be devastating, but the overall risks remain low. It’s important that clinicians know their anatomy, educate patients, and have prepared treatment protocols in place in the event of serious complications, Dr. Beleznay noted.

Dr. Beleznay disclosed relationships as an investigator, speaker, and/or consultant with AbbVie, Actelion, Allergan, Almirall, Amgen, Bausch Health, Celgene, Cipher, Evolus, Galderma, Johnson & Johnson, L’Oreal, Leo, Merz, Novartis, Procter & Gamble, Prollenium, Revance, Sandoz, Sanofi, Valeant, Vichy, and Zeltiq.

MedscapeLive and this news organization are owned by the same parent company.

Most potential complications associated with filler and neuromodulator injections can be managed or prevented, and the right protocols can help in the rare cases of serious complications, Katie Beleznay, MD, of the University of British Columbia, Vancouver, said in a virtual presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The number of reported cases of vascular complications in patients receiving fillers has increased in recent years, said Dr. Beleznay, who also treats patients in private practice in Vancouver. However, knowing the facial anatomy and recognizing that there is no “one-size-fits-all” approach goes a long way in preventing and managing complications.

In terms of neuromodulators such as Botox, the upper face is the most common area for treatment, and potential complications include eyelid ptosis, brow ptosis, and the “Spock brow,” Dr. Beleznay noted. For example, patients won’t be able to engage elevator muscles, such as the frontalis, if too much neuromodulator is injected. But, a couple of units in the upper forehead can help make the effect look natural, soften the lines, without being too frozen.

To help avoid eyelid ptosis with neuromodulators, inject at least one centimeter above the supraorbital rim at the midpupillary line, Dr. Beleznay advised. “I will feel the muscle,” because some brows are drawn or microbladed on, she noted. Patients who develop eyelid ptosis can be treated with apraclonidine drops.

To avoid brow ptosis with neuromodulators, it is important to assess the anatomy at baseline, Dr. Beleznay said. Some patients like to be able to lift their brows, and too much Botox will prevent their doing so. In order to mitigate this, it is important to treat brow depressors to balance and provide lift, and staying above the first horizontal forehead rhytid when injecting can help reduce brow ptosis risk.

Remember when injecting the upper face there are several glabellar contraction patterns, so “be sure you are targeting the treatment for the muscle pulling pattern that you see,” she said.
 

Complications associated with fillers

When injecting fillers, there are rare complications, including blindness, that are worth acknowledging, said Dr. Beleznay, lead author of a study on global cases of blindness caused by fillers published in 2015, including 98 cases up to 2015, and another 48 cases in a study published in 2019.

The highest-risk areas for causing blindness with fillers are the glabella and the nose, but “anywhere you are injecting is at risk for this complication,” she commented.

Explaining the mechanism of action for blindness resulting from filler injections, she said: “When the tip of the needle gets into the vessel, if you put enough pressure on the plunger, the filler can travel retrograde in the vessel back into the ophthalmic artery system, and then travels distally and blocks blood supply to the retina,” causing vision complications.

Understanding the potential mechanism for these complications informs preventive strategies, Dr. Beleznay emphasized.

If vision complications from fillers occur, they are likely to happen immediately, she said. There could be skin involvement or stroke-like features in addition to vision complications, so it is important to screen for these conditions as well if patients complain of vision loss.

Tips for prevention

Knowing the anatomy is the first step to maximize safe placement of fillers, Dr. Beleznay said. For example, the glabella is a high-risk location and includes the supraorbital and supratrochlear arteries, which start deep and become more superficial as they travel up the forehead.

When Dr. Beleznay injects in the glabella area, “I will do a true intradermal injection using tiny microdroplets, because that feels safest to me.” A video with additional details on surface anatomy and safer planes for injecting is available online to members of the American Society of Dermatologic Surgery.

Other tips to reduce the risk of vascular complications include injecting slowly and with a minimal amount of pressure, Dr. Beleznay emphasized. Injecting in small increments, moving the needle tip between injections, and using a cannula also may help reduce risk.

Always ask and use caution if patients have had other recent surgical procedures, she added.

Vascular complications such as blindness can be devastating, but the overall risks remain low. It’s important that clinicians know their anatomy, educate patients, and have prepared treatment protocols in place in the event of serious complications, Dr. Beleznay noted.

Dr. Beleznay disclosed relationships as an investigator, speaker, and/or consultant with AbbVie, Actelion, Allergan, Almirall, Amgen, Bausch Health, Celgene, Cipher, Evolus, Galderma, Johnson & Johnson, L’Oreal, Leo, Merz, Novartis, Procter & Gamble, Prollenium, Revance, Sandoz, Sanofi, Valeant, Vichy, and Zeltiq.

MedscapeLive and this news organization are owned by the same parent company.

Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“We’ll have a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
 

Mild or moderate psoriasis

Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.

Pediatric studies

A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.

“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.

Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.

Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.

“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.

Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.

One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
 

Topical PDE-4 inhibitor shows promise

Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.

“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.

A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.

The phase 3 program is now recruiting participants.

Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“We’ll have a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
 

Mild or moderate psoriasis

Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.

Pediatric studies

A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.

“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.

Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.

Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.

“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.

Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.

One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
 

Topical PDE-4 inhibitor shows promise

Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.

“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.

A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.

The phase 3 program is now recruiting participants.

Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“We’ll have a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
 

Mild or moderate psoriasis

Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.

Pediatric studies

A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.

“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.

Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.

Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.

“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.

Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.

One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
 

Topical PDE-4 inhibitor shows promise

Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.

“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.

A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.

The phase 3 program is now recruiting participants.

Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

Immune checkpoint inhibitor (ICI) therapy does not increase the risk of developing or dying from COVID-19, according to a pair of studies presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.

However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.

In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).

In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).

Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
 

COVID-19 incidence with ICIs

Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.

The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).

In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).

Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.

“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”

COVID-19 mortality with ICIs

For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.

Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.

In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.

Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).

At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.

The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.

“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.

“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
 

ICI therapy can continue, with precautions

“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.

“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.

SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.

Immune checkpoint inhibitor (ICI) therapy does not increase the risk of developing or dying from COVID-19, according to a pair of studies presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.

However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.

In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).

In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).

Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
 

COVID-19 incidence with ICIs

Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.

The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).

In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).

Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.

“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”

COVID-19 mortality with ICIs

For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.

Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.

In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.

Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).

At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.

The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.

“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.

“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
 

ICI therapy can continue, with precautions

“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.

“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.

SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.

Immune checkpoint inhibitor (ICI) therapy does not increase the risk of developing or dying from COVID-19, according to a pair of studies presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.

However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.

In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).

In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).

Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
 

COVID-19 incidence with ICIs

Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.

The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).

In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).

Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.

“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”

COVID-19 mortality with ICIs

For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.

Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.

In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.

Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).

At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.

The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.

“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.

“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
 

ICI therapy can continue, with precautions

“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.

“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.

SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.