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VIDEO: Cannabinoids in dermatology
SAN DIEGO – To date, most of the research on cannabinoids has been outside of dermatology, but these agents may eventually play an important role in the treatment of dermatologic diseases, according to Adam Friedman, MD, director of translational research, department of dermatology, at George Washington University, Washington.
for diseases like dermatomyositis, scleroderma, and lupus, Dr. Friedman said in a video interview at the annual meeting of the American Academy of Dermatology.
In this area, most progress has been made with a synthetic cannabinoid, ajulemic acid (also known as anabasum), which is designed to go after CB2 cannabinoid receptors, which have the anti-inflammatory effects, and not the CB1 receptors, which have the psychoactive effects, he explained. Results of phase 2 studies of ajulemic acid in dermatomyositis and systemic sclerosis have been “very promising,” he noted.
In collaboration with Albert Einstein College of Medicine, New York, he and his associates have studied the topical application of an endocannabinoid, anandamide (AEA), in nanoparticles in an animal model of cutaneous lupus. “We found that we can actually reverse the very classic, almost chronic cutaneous-like symptoms that we see in these animals if they go untreated,” he said.
In the interview, Dr. Friedman, who spoke about the potential of cannabinoids for the treatment of inflammatory and neoplastic diseases of the skin at the meeting, said that it is actually surprising that most research with cannabinoids to date has been outside of dermatology, “because our skin is chock full of cannabinoids; chock full of expression of cannabinoid receptors.”
Dr. Friedman disclosed that he has invented the nanotechnology licensed to Zylo Therapeutics. He is a member of the Dermatology News advisory board.
SAN DIEGO – To date, most of the research on cannabinoids has been outside of dermatology, but these agents may eventually play an important role in the treatment of dermatologic diseases, according to Adam Friedman, MD, director of translational research, department of dermatology, at George Washington University, Washington.
for diseases like dermatomyositis, scleroderma, and lupus, Dr. Friedman said in a video interview at the annual meeting of the American Academy of Dermatology.
In this area, most progress has been made with a synthetic cannabinoid, ajulemic acid (also known as anabasum), which is designed to go after CB2 cannabinoid receptors, which have the anti-inflammatory effects, and not the CB1 receptors, which have the psychoactive effects, he explained. Results of phase 2 studies of ajulemic acid in dermatomyositis and systemic sclerosis have been “very promising,” he noted.
In collaboration with Albert Einstein College of Medicine, New York, he and his associates have studied the topical application of an endocannabinoid, anandamide (AEA), in nanoparticles in an animal model of cutaneous lupus. “We found that we can actually reverse the very classic, almost chronic cutaneous-like symptoms that we see in these animals if they go untreated,” he said.
In the interview, Dr. Friedman, who spoke about the potential of cannabinoids for the treatment of inflammatory and neoplastic diseases of the skin at the meeting, said that it is actually surprising that most research with cannabinoids to date has been outside of dermatology, “because our skin is chock full of cannabinoids; chock full of expression of cannabinoid receptors.”
Dr. Friedman disclosed that he has invented the nanotechnology licensed to Zylo Therapeutics. He is a member of the Dermatology News advisory board.
SAN DIEGO – To date, most of the research on cannabinoids has been outside of dermatology, but these agents may eventually play an important role in the treatment of dermatologic diseases, according to Adam Friedman, MD, director of translational research, department of dermatology, at George Washington University, Washington.
for diseases like dermatomyositis, scleroderma, and lupus, Dr. Friedman said in a video interview at the annual meeting of the American Academy of Dermatology.
In this area, most progress has been made with a synthetic cannabinoid, ajulemic acid (also known as anabasum), which is designed to go after CB2 cannabinoid receptors, which have the anti-inflammatory effects, and not the CB1 receptors, which have the psychoactive effects, he explained. Results of phase 2 studies of ajulemic acid in dermatomyositis and systemic sclerosis have been “very promising,” he noted.
In collaboration with Albert Einstein College of Medicine, New York, he and his associates have studied the topical application of an endocannabinoid, anandamide (AEA), in nanoparticles in an animal model of cutaneous lupus. “We found that we can actually reverse the very classic, almost chronic cutaneous-like symptoms that we see in these animals if they go untreated,” he said.
In the interview, Dr. Friedman, who spoke about the potential of cannabinoids for the treatment of inflammatory and neoplastic diseases of the skin at the meeting, said that it is actually surprising that most research with cannabinoids to date has been outside of dermatology, “because our skin is chock full of cannabinoids; chock full of expression of cannabinoid receptors.”
Dr. Friedman disclosed that he has invented the nanotechnology licensed to Zylo Therapeutics. He is a member of the Dermatology News advisory board.
REPORTING FROM AAD 18
VIDEO: The return of Kaposi’s sarcoma
SAN DIEGO – Dermatologists, who served as crucial sentinels during the early years of the AIDS epidemic, should be alert for dermatologic signs and symptoms of HIV infection, according to Toby Maurer, MD, professor of clinical dermatology at the University of California, San Francisco.
“We’re now seeing a lot of HIV-infected patients presenting once again with skin symptoms,” including new-onset psoriasis, poorly controlled seborrheic dermatitis, and even Kaposi’s sarcoma, she said in a video interview at the annual meeting of the American Academy of Dermatology.
The upswing in cases of Kaposi’s sarcoma “comes as a shock to many dermatologists; they thought Kaposi’s sarcoma was a thing of the past,” added Dr. Maurer, who presented on HIV-associated skin conditions at the meeting.
“My whole plea is to remember that HIV has not gone away, that it keeps showing up, and that the skin symptoms absolutely show up,” she said. “It’s not on the radar as much as it should be.”
In her presentation, Dr. Maurer, who is also chief of dermatology at San Francisco General Hospital, said HIV and HIV medications have a variety of impacts on skin. For example, psoriasis gets worse when patients are off medication and better when they’re on it, she said, while molluscum contagiosum and herpes simplex can actually worsen when patients start HIV drugs. And, she said, a late start of AIDS drugs can worsen eczema.
In the interview, she discussed the impact of starting antiretrovirals late into the infection, when CD4 counts are low, on skin conditions, as well as possible reasons behind the increase in Kaposi’s sarcoma, and interactions between systemic dermatologic medications and some antiretrovirals.
Dr. Maurer reports no relevant disclosures.
SAN DIEGO – Dermatologists, who served as crucial sentinels during the early years of the AIDS epidemic, should be alert for dermatologic signs and symptoms of HIV infection, according to Toby Maurer, MD, professor of clinical dermatology at the University of California, San Francisco.
“We’re now seeing a lot of HIV-infected patients presenting once again with skin symptoms,” including new-onset psoriasis, poorly controlled seborrheic dermatitis, and even Kaposi’s sarcoma, she said in a video interview at the annual meeting of the American Academy of Dermatology.
The upswing in cases of Kaposi’s sarcoma “comes as a shock to many dermatologists; they thought Kaposi’s sarcoma was a thing of the past,” added Dr. Maurer, who presented on HIV-associated skin conditions at the meeting.
“My whole plea is to remember that HIV has not gone away, that it keeps showing up, and that the skin symptoms absolutely show up,” she said. “It’s not on the radar as much as it should be.”
In her presentation, Dr. Maurer, who is also chief of dermatology at San Francisco General Hospital, said HIV and HIV medications have a variety of impacts on skin. For example, psoriasis gets worse when patients are off medication and better when they’re on it, she said, while molluscum contagiosum and herpes simplex can actually worsen when patients start HIV drugs. And, she said, a late start of AIDS drugs can worsen eczema.
In the interview, she discussed the impact of starting antiretrovirals late into the infection, when CD4 counts are low, on skin conditions, as well as possible reasons behind the increase in Kaposi’s sarcoma, and interactions between systemic dermatologic medications and some antiretrovirals.
Dr. Maurer reports no relevant disclosures.
SAN DIEGO – Dermatologists, who served as crucial sentinels during the early years of the AIDS epidemic, should be alert for dermatologic signs and symptoms of HIV infection, according to Toby Maurer, MD, professor of clinical dermatology at the University of California, San Francisco.
“We’re now seeing a lot of HIV-infected patients presenting once again with skin symptoms,” including new-onset psoriasis, poorly controlled seborrheic dermatitis, and even Kaposi’s sarcoma, she said in a video interview at the annual meeting of the American Academy of Dermatology.
The upswing in cases of Kaposi’s sarcoma “comes as a shock to many dermatologists; they thought Kaposi’s sarcoma was a thing of the past,” added Dr. Maurer, who presented on HIV-associated skin conditions at the meeting.
“My whole plea is to remember that HIV has not gone away, that it keeps showing up, and that the skin symptoms absolutely show up,” she said. “It’s not on the radar as much as it should be.”
In her presentation, Dr. Maurer, who is also chief of dermatology at San Francisco General Hospital, said HIV and HIV medications have a variety of impacts on skin. For example, psoriasis gets worse when patients are off medication and better when they’re on it, she said, while molluscum contagiosum and herpes simplex can actually worsen when patients start HIV drugs. And, she said, a late start of AIDS drugs can worsen eczema.
In the interview, she discussed the impact of starting antiretrovirals late into the infection, when CD4 counts are low, on skin conditions, as well as possible reasons behind the increase in Kaposi’s sarcoma, and interactions between systemic dermatologic medications and some antiretrovirals.
Dr. Maurer reports no relevant disclosures.
REPORTING FROM AAD 18
Online psoriasis consultations shown equivalent to office visits
SAN DIEGO – Online consultations between dermatologists, patients with psoriasis, and the patients’ primary care physicians were as effective as in-person consultations in successfully treating the disease in a multicenter, randomized study of 296 patients.
“Innovative telehealth delivery models that emphasize collaboration, quality, and efficiency can be transformative to improving patient-centered outcomes in chronic disease,” April W. Armstrong, MD, said at the annual meeting of the American Academy of Dermatology. The online model she tested fostered “increased patient engagement” and provided “comprehensive specialist support,” said Dr. Armstrong, director of the psoriasis program at the University of Southern California, Los Angeles.
To objectively assess whether online consultations are as effective as in-person examinations, Dr. Armstrong and her associates at three U.S. centers randomized adult psoriasis patients from across the disease spectrum to receive 1 year of dermatology care either in person or online. Patients enrolled in the online arm received training in taking digital images of their skin lesions and uploading the data for remote access by their dermatologist and primary care physician. The frequency of in-person and online consultations was left to the discretion of each patient and his or her physician.
Among the 148 patients randomized to each arm, 17 in the online group and 13 in the in-person group withdrew from the study or were lost to follow-up. The researchers analyzed the results on an intention-to-treat basis.
They assessed three parameters of treatment efficacy that they measured at baseline and then every 3 months out to 1 year: Psoriasis Area and Severity Index, body surface area score, and patient global self-assessment. A comparison of changes between the two treatment arms after 1 year for the first two measures met the study’s prespecified definition of equivalence, Dr. Armstrong reported. The third measure, a patient’s global self-assessment, showed lower patient-assessed disease severity after 1 year among the patients managed online, compared with those managed in person.
The incidence of adverse events and serious adverse events was similar in the two treatment arms.
Dr. Armstrong had no relevant financial disclosures.
Source: Armstrong A et al. AAD 2018, abstract 6730..
SAN DIEGO – Online consultations between dermatologists, patients with psoriasis, and the patients’ primary care physicians were as effective as in-person consultations in successfully treating the disease in a multicenter, randomized study of 296 patients.
“Innovative telehealth delivery models that emphasize collaboration, quality, and efficiency can be transformative to improving patient-centered outcomes in chronic disease,” April W. Armstrong, MD, said at the annual meeting of the American Academy of Dermatology. The online model she tested fostered “increased patient engagement” and provided “comprehensive specialist support,” said Dr. Armstrong, director of the psoriasis program at the University of Southern California, Los Angeles.
To objectively assess whether online consultations are as effective as in-person examinations, Dr. Armstrong and her associates at three U.S. centers randomized adult psoriasis patients from across the disease spectrum to receive 1 year of dermatology care either in person or online. Patients enrolled in the online arm received training in taking digital images of their skin lesions and uploading the data for remote access by their dermatologist and primary care physician. The frequency of in-person and online consultations was left to the discretion of each patient and his or her physician.
Among the 148 patients randomized to each arm, 17 in the online group and 13 in the in-person group withdrew from the study or were lost to follow-up. The researchers analyzed the results on an intention-to-treat basis.
They assessed three parameters of treatment efficacy that they measured at baseline and then every 3 months out to 1 year: Psoriasis Area and Severity Index, body surface area score, and patient global self-assessment. A comparison of changes between the two treatment arms after 1 year for the first two measures met the study’s prespecified definition of equivalence, Dr. Armstrong reported. The third measure, a patient’s global self-assessment, showed lower patient-assessed disease severity after 1 year among the patients managed online, compared with those managed in person.
The incidence of adverse events and serious adverse events was similar in the two treatment arms.
Dr. Armstrong had no relevant financial disclosures.
Source: Armstrong A et al. AAD 2018, abstract 6730..
SAN DIEGO – Online consultations between dermatologists, patients with psoriasis, and the patients’ primary care physicians were as effective as in-person consultations in successfully treating the disease in a multicenter, randomized study of 296 patients.
“Innovative telehealth delivery models that emphasize collaboration, quality, and efficiency can be transformative to improving patient-centered outcomes in chronic disease,” April W. Armstrong, MD, said at the annual meeting of the American Academy of Dermatology. The online model she tested fostered “increased patient engagement” and provided “comprehensive specialist support,” said Dr. Armstrong, director of the psoriasis program at the University of Southern California, Los Angeles.
To objectively assess whether online consultations are as effective as in-person examinations, Dr. Armstrong and her associates at three U.S. centers randomized adult psoriasis patients from across the disease spectrum to receive 1 year of dermatology care either in person or online. Patients enrolled in the online arm received training in taking digital images of their skin lesions and uploading the data for remote access by their dermatologist and primary care physician. The frequency of in-person and online consultations was left to the discretion of each patient and his or her physician.
Among the 148 patients randomized to each arm, 17 in the online group and 13 in the in-person group withdrew from the study or were lost to follow-up. The researchers analyzed the results on an intention-to-treat basis.
They assessed three parameters of treatment efficacy that they measured at baseline and then every 3 months out to 1 year: Psoriasis Area and Severity Index, body surface area score, and patient global self-assessment. A comparison of changes between the two treatment arms after 1 year for the first two measures met the study’s prespecified definition of equivalence, Dr. Armstrong reported. The third measure, a patient’s global self-assessment, showed lower patient-assessed disease severity after 1 year among the patients managed online, compared with those managed in person.
The incidence of adverse events and serious adverse events was similar in the two treatment arms.
Dr. Armstrong had no relevant financial disclosures.
Source: Armstrong A et al. AAD 2018, abstract 6730..
REPORTING FROM AAD 18
Key clinical point: Online physician telemonitoring of psoriasis patients was equivalent to in-person management.
Major finding: After 1 year, changes in the Psoriasis Area and Severity Index in the two arms met the prespecified definition of equivalence.
Study details: A multicenter, randomized trial with 296 psoriasis patients in which outcomes were compared for online monitoring and in-person examinations.
Disclosures: Dr. Armstrong had no relevant financial disclosures.
Source: Armstrong A et al. AAD 18, abstract 6730.
VIDEO: Considering systemic disease in dermatology patients
SAN DIEGO – Be mindful of what lies below the skin.
That was the message of Joseph Merola, MD, during a session on “rheumatology for the dermatologist” at the annual meeting of the American Academy of Dermatology.
“The idea is really to start to try to get our dermatology colleagues thinking more systemically and outside of just the skin,” said Dr. Merola, a rheumatologist and dermatologist who is codirector of the center for skin and related musculoskeletal diseases at Brigham and Women’s Hospital, Boston.
“ in up to 30% of patients,” he noted.
He urged his colleagues to ask patients functional questions; for example, those pertaining to sicca symptoms; and how to parse out whether a patient’s joint pain is inflammatory or non-inflammatory.
In a video interview, Dr. Merola also discussed lab tests used to evaluate patients with lupus, the value of a simple urine test, and recent work on the development of the first international classification criteria set for discoid type skin lupus.
SAN DIEGO – Be mindful of what lies below the skin.
That was the message of Joseph Merola, MD, during a session on “rheumatology for the dermatologist” at the annual meeting of the American Academy of Dermatology.
“The idea is really to start to try to get our dermatology colleagues thinking more systemically and outside of just the skin,” said Dr. Merola, a rheumatologist and dermatologist who is codirector of the center for skin and related musculoskeletal diseases at Brigham and Women’s Hospital, Boston.
“ in up to 30% of patients,” he noted.
He urged his colleagues to ask patients functional questions; for example, those pertaining to sicca symptoms; and how to parse out whether a patient’s joint pain is inflammatory or non-inflammatory.
In a video interview, Dr. Merola also discussed lab tests used to evaluate patients with lupus, the value of a simple urine test, and recent work on the development of the first international classification criteria set for discoid type skin lupus.
SAN DIEGO – Be mindful of what lies below the skin.
That was the message of Joseph Merola, MD, during a session on “rheumatology for the dermatologist” at the annual meeting of the American Academy of Dermatology.
“The idea is really to start to try to get our dermatology colleagues thinking more systemically and outside of just the skin,” said Dr. Merola, a rheumatologist and dermatologist who is codirector of the center for skin and related musculoskeletal diseases at Brigham and Women’s Hospital, Boston.
“ in up to 30% of patients,” he noted.
He urged his colleagues to ask patients functional questions; for example, those pertaining to sicca symptoms; and how to parse out whether a patient’s joint pain is inflammatory or non-inflammatory.
In a video interview, Dr. Merola also discussed lab tests used to evaluate patients with lupus, the value of a simple urine test, and recent work on the development of the first international classification criteria set for discoid type skin lupus.
REPORTING FROM AAD 18
VIDEO: PPACMAN aims to advance the combined rheum-derm clinic approach in the community
SAN DIEGO – A new endeavor that aims to promote the concept of the combined clinic approach to caring for psoriatic patients is now underway.
PPACMAN (Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network) is made up of dermatologists and rheumatologists who play a key role in the management of psoriatic disease and are interested in combined clinics, with the mission “to nucleate psoriatic disease combined clinics and centers to advance a multilevel approach to psoriatic patients, increase disease awareness, and accelerate management,” according to Joseph Merola, MD, codirector of the center for skin and related musculoskeletal diseases at Brigham and Women’s Hospital, Boston.
There are now about 12 centers in North America with formal rheumatology-dermatology clinics for patients with psoriasis and psoriatic arthritis, including the one at Brigham and Women’s, where Dr. Merola and his colleagues have seen the “myriad benefits that come with having a combined clinic,” he said in a video interview at the annual meeting of the American Academy of Dermatology. The idea behind starting PPACMAN was to help form new clinics at academic centers but, also, “to start to catalyze local-regional partnerships in the community so we could get dermatologists and rheumatologists in the community to start interacting, communicating, [and] sharing patients,” he explained.
“The group is really very much focused on this mission of getting combined ... treatment models out there,” added Dr. Merola, president and chair of the board of PPACMAN, which is a 501c3 nonprofit organization.
In the interview, he discusses other benefits of the combined clinic model and other elements of the PPACMAN mission, including education and the potential for shared EMR templates.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN DIEGO – A new endeavor that aims to promote the concept of the combined clinic approach to caring for psoriatic patients is now underway.
PPACMAN (Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network) is made up of dermatologists and rheumatologists who play a key role in the management of psoriatic disease and are interested in combined clinics, with the mission “to nucleate psoriatic disease combined clinics and centers to advance a multilevel approach to psoriatic patients, increase disease awareness, and accelerate management,” according to Joseph Merola, MD, codirector of the center for skin and related musculoskeletal diseases at Brigham and Women’s Hospital, Boston.
There are now about 12 centers in North America with formal rheumatology-dermatology clinics for patients with psoriasis and psoriatic arthritis, including the one at Brigham and Women’s, where Dr. Merola and his colleagues have seen the “myriad benefits that come with having a combined clinic,” he said in a video interview at the annual meeting of the American Academy of Dermatology. The idea behind starting PPACMAN was to help form new clinics at academic centers but, also, “to start to catalyze local-regional partnerships in the community so we could get dermatologists and rheumatologists in the community to start interacting, communicating, [and] sharing patients,” he explained.
“The group is really very much focused on this mission of getting combined ... treatment models out there,” added Dr. Merola, president and chair of the board of PPACMAN, which is a 501c3 nonprofit organization.
In the interview, he discusses other benefits of the combined clinic model and other elements of the PPACMAN mission, including education and the potential for shared EMR templates.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN DIEGO – A new endeavor that aims to promote the concept of the combined clinic approach to caring for psoriatic patients is now underway.
PPACMAN (Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network) is made up of dermatologists and rheumatologists who play a key role in the management of psoriatic disease and are interested in combined clinics, with the mission “to nucleate psoriatic disease combined clinics and centers to advance a multilevel approach to psoriatic patients, increase disease awareness, and accelerate management,” according to Joseph Merola, MD, codirector of the center for skin and related musculoskeletal diseases at Brigham and Women’s Hospital, Boston.
There are now about 12 centers in North America with formal rheumatology-dermatology clinics for patients with psoriasis and psoriatic arthritis, including the one at Brigham and Women’s, where Dr. Merola and his colleagues have seen the “myriad benefits that come with having a combined clinic,” he said in a video interview at the annual meeting of the American Academy of Dermatology. The idea behind starting PPACMAN was to help form new clinics at academic centers but, also, “to start to catalyze local-regional partnerships in the community so we could get dermatologists and rheumatologists in the community to start interacting, communicating, [and] sharing patients,” he explained.
“The group is really very much focused on this mission of getting combined ... treatment models out there,” added Dr. Merola, president and chair of the board of PPACMAN, which is a 501c3 nonprofit organization.
In the interview, he discusses other benefits of the combined clinic model and other elements of the PPACMAN mission, including education and the potential for shared EMR templates.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
REPORTING FROM AAD 18
Could guselkumab be a disease-modifying agent in plaque psoriasis?
SAN DIEGO – Could some of the monoclonal antibodies posting striking results in psoriasis trials be doing more than quelling symptoms?
At least some researchers think so, as evidenced by a brief discussion during AAD 2018 of the durable responses some guselkumab-treated patients achieved in the VOYAGE 2 trial.
“Isn’t this amazing?” asked Kristian Reich, MD, after listening to several late-breaking, solidly positive trials of monoclonal antibodies for plaque psoriasis. “I think it’s fantastic that we now have drugs that clear 50% or more of a patient’s psoriasis. We should not be taking this for granted.”
VOYAGE 2 was an active-comparator, placebo-controlled study that pitted guselkumab against adalimumab (Humira) and placebo in a crossover design. It enrolled about 900 patients with moderate to severe plaque psoriasis.
Patients were randomized to 28 weeks of treatment in three arms: guselkumab 100 mg (weeks 0 and 4, then every 8 weeks); placebo for 16 weeks, then guselkumab 100 mg at weeks 16 and 20; or adalimumab (80 mg at week 0, then 40 mg at week 1, and every 2 weeks through week 23).
At 28 weeks, a total of 375 Psoriasis Area and Severity Index (PASI) 90 treatment responders in the guselkumab arm were rerandomized to either stay on guselkumab (n = 193) or withdraw to placebo (n = 182) until they lost whatever response they had gained at that point.
Although PASI 90 responses were much better maintained in the guselkumab group that stayed on therapy, they did not fade quickly. And although 89% of the maintenance group maintained their PASI 90 response at 48 weeks, 37% of those in the withdrawal group had still maintained that 90% improvement over baseline by 48 weeks.
“Is this drug opening the door to disease modification? Is it doing something that allows disease control even if we stop the therapy? This is what we see happening when we stop the drug in PASI 90 responders. Yes, the disease is coming back, but the median time to recurrence is more than 3 months.”
The cytokine profiles of these patients appear to support this idea, Dr. Reich contended.
“In the first 28 weeks, when they were all receiving the drug, their IL-23, IL-17A, and IL-17F levels were all going down rapidly. But this is the interesting part. In some patients who maintained their PASI response after withdrawal, those cytokines continued to be suppressed. They rose in patients who lost response. We need to do more tests to understand what’s going on here, but I do think the door is opening to what I would call disease modification.”
“I admit, I did at one time believe this story about disease modification,” said Dr. Papp, founder and president of Probity Medical Research in Waterloo, Ont. “But now I think we are simply seeing a pharmacokinetic effect. How can you reconcile what is clearly a pharmacologic and mechanistic perspective with this suggestion that you’re modifying disease?”
Session moderator Hensin Tsao, MD, suggested that the answer might lie in some unknown in-between territory.
“We do see about 10%-20% of patients in whom drug-free remission is not explained by pharmacokinetics. In some patients, the drug is long gone, and they are still clear of disease – and we don’t know how to talk about those patients yet. But we do need to study them because, for those people, clearly it is not a [pharmacokinetic] issue.”
Dr. Reich disclosed financial relationships with numerous pharmaceutical companies, including Janssen, which manufactures guselkumab. Dr. Papp also disclosed multiple relationships with drug manufacturers.
SOURCE: Gordon K et al. AAD 2018 Abstract 6748.
SAN DIEGO – Could some of the monoclonal antibodies posting striking results in psoriasis trials be doing more than quelling symptoms?
At least some researchers think so, as evidenced by a brief discussion during AAD 2018 of the durable responses some guselkumab-treated patients achieved in the VOYAGE 2 trial.
“Isn’t this amazing?” asked Kristian Reich, MD, after listening to several late-breaking, solidly positive trials of monoclonal antibodies for plaque psoriasis. “I think it’s fantastic that we now have drugs that clear 50% or more of a patient’s psoriasis. We should not be taking this for granted.”
VOYAGE 2 was an active-comparator, placebo-controlled study that pitted guselkumab against adalimumab (Humira) and placebo in a crossover design. It enrolled about 900 patients with moderate to severe plaque psoriasis.
Patients were randomized to 28 weeks of treatment in three arms: guselkumab 100 mg (weeks 0 and 4, then every 8 weeks); placebo for 16 weeks, then guselkumab 100 mg at weeks 16 and 20; or adalimumab (80 mg at week 0, then 40 mg at week 1, and every 2 weeks through week 23).
At 28 weeks, a total of 375 Psoriasis Area and Severity Index (PASI) 90 treatment responders in the guselkumab arm were rerandomized to either stay on guselkumab (n = 193) or withdraw to placebo (n = 182) until they lost whatever response they had gained at that point.
Although PASI 90 responses were much better maintained in the guselkumab group that stayed on therapy, they did not fade quickly. And although 89% of the maintenance group maintained their PASI 90 response at 48 weeks, 37% of those in the withdrawal group had still maintained that 90% improvement over baseline by 48 weeks.
“Is this drug opening the door to disease modification? Is it doing something that allows disease control even if we stop the therapy? This is what we see happening when we stop the drug in PASI 90 responders. Yes, the disease is coming back, but the median time to recurrence is more than 3 months.”
The cytokine profiles of these patients appear to support this idea, Dr. Reich contended.
“In the first 28 weeks, when they were all receiving the drug, their IL-23, IL-17A, and IL-17F levels were all going down rapidly. But this is the interesting part. In some patients who maintained their PASI response after withdrawal, those cytokines continued to be suppressed. They rose in patients who lost response. We need to do more tests to understand what’s going on here, but I do think the door is opening to what I would call disease modification.”
“I admit, I did at one time believe this story about disease modification,” said Dr. Papp, founder and president of Probity Medical Research in Waterloo, Ont. “But now I think we are simply seeing a pharmacokinetic effect. How can you reconcile what is clearly a pharmacologic and mechanistic perspective with this suggestion that you’re modifying disease?”
Session moderator Hensin Tsao, MD, suggested that the answer might lie in some unknown in-between territory.
“We do see about 10%-20% of patients in whom drug-free remission is not explained by pharmacokinetics. In some patients, the drug is long gone, and they are still clear of disease – and we don’t know how to talk about those patients yet. But we do need to study them because, for those people, clearly it is not a [pharmacokinetic] issue.”
Dr. Reich disclosed financial relationships with numerous pharmaceutical companies, including Janssen, which manufactures guselkumab. Dr. Papp also disclosed multiple relationships with drug manufacturers.
SOURCE: Gordon K et al. AAD 2018 Abstract 6748.
SAN DIEGO – Could some of the monoclonal antibodies posting striking results in psoriasis trials be doing more than quelling symptoms?
At least some researchers think so, as evidenced by a brief discussion during AAD 2018 of the durable responses some guselkumab-treated patients achieved in the VOYAGE 2 trial.
“Isn’t this amazing?” asked Kristian Reich, MD, after listening to several late-breaking, solidly positive trials of monoclonal antibodies for plaque psoriasis. “I think it’s fantastic that we now have drugs that clear 50% or more of a patient’s psoriasis. We should not be taking this for granted.”
VOYAGE 2 was an active-comparator, placebo-controlled study that pitted guselkumab against adalimumab (Humira) and placebo in a crossover design. It enrolled about 900 patients with moderate to severe plaque psoriasis.
Patients were randomized to 28 weeks of treatment in three arms: guselkumab 100 mg (weeks 0 and 4, then every 8 weeks); placebo for 16 weeks, then guselkumab 100 mg at weeks 16 and 20; or adalimumab (80 mg at week 0, then 40 mg at week 1, and every 2 weeks through week 23).
At 28 weeks, a total of 375 Psoriasis Area and Severity Index (PASI) 90 treatment responders in the guselkumab arm were rerandomized to either stay on guselkumab (n = 193) or withdraw to placebo (n = 182) until they lost whatever response they had gained at that point.
Although PASI 90 responses were much better maintained in the guselkumab group that stayed on therapy, they did not fade quickly. And although 89% of the maintenance group maintained their PASI 90 response at 48 weeks, 37% of those in the withdrawal group had still maintained that 90% improvement over baseline by 48 weeks.
“Is this drug opening the door to disease modification? Is it doing something that allows disease control even if we stop the therapy? This is what we see happening when we stop the drug in PASI 90 responders. Yes, the disease is coming back, but the median time to recurrence is more than 3 months.”
The cytokine profiles of these patients appear to support this idea, Dr. Reich contended.
“In the first 28 weeks, when they were all receiving the drug, their IL-23, IL-17A, and IL-17F levels were all going down rapidly. But this is the interesting part. In some patients who maintained their PASI response after withdrawal, those cytokines continued to be suppressed. They rose in patients who lost response. We need to do more tests to understand what’s going on here, but I do think the door is opening to what I would call disease modification.”
“I admit, I did at one time believe this story about disease modification,” said Dr. Papp, founder and president of Probity Medical Research in Waterloo, Ont. “But now I think we are simply seeing a pharmacokinetic effect. How can you reconcile what is clearly a pharmacologic and mechanistic perspective with this suggestion that you’re modifying disease?”
Session moderator Hensin Tsao, MD, suggested that the answer might lie in some unknown in-between territory.
“We do see about 10%-20% of patients in whom drug-free remission is not explained by pharmacokinetics. In some patients, the drug is long gone, and they are still clear of disease – and we don’t know how to talk about those patients yet. But we do need to study them because, for those people, clearly it is not a [pharmacokinetic] issue.”
Dr. Reich disclosed financial relationships with numerous pharmaceutical companies, including Janssen, which manufactures guselkumab. Dr. Papp also disclosed multiple relationships with drug manufacturers.
SOURCE: Gordon K et al. AAD 2018 Abstract 6748.
REPORTING FROM AAD 2018
Key clinical point: Guselkumab shows some signs of having a disease-modifying effect in moderate to severe psoriasis after 28 weeks of treatment.
Major finding: A total of 37% of patients who withdrew from guselkumab at 28 weeks had still maintained PASI 90 improvement over baseline at 48 weeks.
Study details: An analysis of randomization to drug continuation vs. withdrawal in 375 patients with PASI 90 response to guselkumab in the VOYAGE 2 trial.
Disclosures: Dr. Reich disclosed financial relationships with numerous pharmaceutical companies, including Janssen, which manufactures guselkumab. Dr. Papp also disclosed multiple relationships with drug manufacturers.
Source: Gordon K et al. AAD 2018 Abstract 6748.
Ustekinumab quells aortic inflammation in patients with severe psoriasis
SAN DIEGO – A 12-week course of ustekinumab significantly reduced inflammation in the aorta – an effect on par with the benefit of statins – in patients with moderate to severe plaque psoriasis.
Whether or not the reduction in aortic inflammation will translate into a reduction in cardiovascular risk remains to be determined, but investigators are very encouraged by the results of the Vascular Inflammation in Psoriasis-Ustekinumab (VIP-U) study, Joel M. Gelfand, MD, said at the annual meeting of the American Academy of Dermatology.
For the past decade, researchers have worked on the assumption that the chronic systemic inflammation of severe psoriasis overlaps with similar inflammatory pathways that drive atherosclerosis, plaques that rupture, and cardiovascular events.
Recently, they have employed fluorodeoxyglucose positron emission tomography (FDG-PET) to confirm some of this. Studies in 2011, 2015, and 2017 confirm that patients with severe plaque psoriasis can develop diffuse vascular inflammation with increased noncalcified coronary artery plaques. These more fragile plaques are the type that are prone to rupture and cause cardiovascular events, Dr. Gelfand said.
“In these studies, the more imaging signal we saw in the aorta, the higher the risk of a future cardiovascular event. In fact, we determined that patients with severe psoriasis can have increased aortic inflammation equivalent to a decade of aging. As your PASI [Psoriasis Area and Severity Index] score goes up, so does the amount of aortic inflammation. The anatomic consequence is that people develop a high risk of atherosclerotic plaques, and a higher rate of noncalcified coronary plaques that are more likely to lead to these events.”
The VIP-U study was conceived to examine whether calming psoriatic inflammation with ustekinumab (Stelara), an anti interleukin-12 and -23 antibody, could also improve vascular inflammation as measured by FDG-PET. The small study comprised 43 patients, half of whom received placebo and half of whom received two injections of ustekinumab: 45 or 90 mg depending on weight, at baseline and at week 4. There was an imaging assessment at week 12, after which the placebo patients crossed over to open-label ustekinumab every 2 weeks. Everyone was followed out to 64 weeks.
Dr. Gelfand reported the 12-week data; the 64-week data will be forthcoming later this year, he said.
The patients were typical for such a study, with a mean age of about 43 and a mean disease duration of 18 years. The mean body surface area was about 25%, and the mean PASI was 20. Most had been on prior therapy, including phototherapy, oral agents, and biologics.
Unsurprisingly, ustekinumab was significantly more effective than placebo in treating the psoriasis. At week 12, 10% of the placebo patients had achieved a PASI 75, compared with 77% of the ustekinumab patients. A Physicians Global Assessment (PGA) score of clear or almost clear occurred in 10% of those taking placebo and 64% of those taking the biologic.
However, the drug was also highly effective in reducing total aortic inflammation, Dr. Gelfand said. “In just 12 weeks, we saw a 6.6% reduction in total aortic inflammation among those taking ustekinumab, but a 12.1% increase in inflammation among those taking placebo. When you compare the delta, you see a highly statistically significant improvement in aortic inflammation in ustekinumab-treated patients, with the effect size similar to statin therapy.”
The benefit may be a class-associated one. Two recent similar studies of adalimumab, a tumor necrosis factor–alpha inhibitor, failed to find any improvement in vascular inflammation, compared with placebo.
“We need more information about the longer-term effects of ustekinumab treatment, as well as cardiometabolic biomarkers, and these are currently underway,” Dr. Gelfand said. “We also need additional trials to determine if this effect is due to the inhibition of IL-12, IL-23, or a combination. Cardiovascular studies will be necessary to fully determine the clinical implications of our findings.”
To refer a patient into the VIP studies, call 215-662-SKIN or email [email protected].
The National Institutes of Health and University of Pennsylvania sponsored the study. Dr. Gelfand reported no financial disclosures.
SOURCE: Gelfand J et al. AAD 2018 Abstract 6645
SAN DIEGO – A 12-week course of ustekinumab significantly reduced inflammation in the aorta – an effect on par with the benefit of statins – in patients with moderate to severe plaque psoriasis.
Whether or not the reduction in aortic inflammation will translate into a reduction in cardiovascular risk remains to be determined, but investigators are very encouraged by the results of the Vascular Inflammation in Psoriasis-Ustekinumab (VIP-U) study, Joel M. Gelfand, MD, said at the annual meeting of the American Academy of Dermatology.
For the past decade, researchers have worked on the assumption that the chronic systemic inflammation of severe psoriasis overlaps with similar inflammatory pathways that drive atherosclerosis, plaques that rupture, and cardiovascular events.
Recently, they have employed fluorodeoxyglucose positron emission tomography (FDG-PET) to confirm some of this. Studies in 2011, 2015, and 2017 confirm that patients with severe plaque psoriasis can develop diffuse vascular inflammation with increased noncalcified coronary artery plaques. These more fragile plaques are the type that are prone to rupture and cause cardiovascular events, Dr. Gelfand said.
“In these studies, the more imaging signal we saw in the aorta, the higher the risk of a future cardiovascular event. In fact, we determined that patients with severe psoriasis can have increased aortic inflammation equivalent to a decade of aging. As your PASI [Psoriasis Area and Severity Index] score goes up, so does the amount of aortic inflammation. The anatomic consequence is that people develop a high risk of atherosclerotic plaques, and a higher rate of noncalcified coronary plaques that are more likely to lead to these events.”
The VIP-U study was conceived to examine whether calming psoriatic inflammation with ustekinumab (Stelara), an anti interleukin-12 and -23 antibody, could also improve vascular inflammation as measured by FDG-PET. The small study comprised 43 patients, half of whom received placebo and half of whom received two injections of ustekinumab: 45 or 90 mg depending on weight, at baseline and at week 4. There was an imaging assessment at week 12, after which the placebo patients crossed over to open-label ustekinumab every 2 weeks. Everyone was followed out to 64 weeks.
Dr. Gelfand reported the 12-week data; the 64-week data will be forthcoming later this year, he said.
The patients were typical for such a study, with a mean age of about 43 and a mean disease duration of 18 years. The mean body surface area was about 25%, and the mean PASI was 20. Most had been on prior therapy, including phototherapy, oral agents, and biologics.
Unsurprisingly, ustekinumab was significantly more effective than placebo in treating the psoriasis. At week 12, 10% of the placebo patients had achieved a PASI 75, compared with 77% of the ustekinumab patients. A Physicians Global Assessment (PGA) score of clear or almost clear occurred in 10% of those taking placebo and 64% of those taking the biologic.
However, the drug was also highly effective in reducing total aortic inflammation, Dr. Gelfand said. “In just 12 weeks, we saw a 6.6% reduction in total aortic inflammation among those taking ustekinumab, but a 12.1% increase in inflammation among those taking placebo. When you compare the delta, you see a highly statistically significant improvement in aortic inflammation in ustekinumab-treated patients, with the effect size similar to statin therapy.”
The benefit may be a class-associated one. Two recent similar studies of adalimumab, a tumor necrosis factor–alpha inhibitor, failed to find any improvement in vascular inflammation, compared with placebo.
“We need more information about the longer-term effects of ustekinumab treatment, as well as cardiometabolic biomarkers, and these are currently underway,” Dr. Gelfand said. “We also need additional trials to determine if this effect is due to the inhibition of IL-12, IL-23, or a combination. Cardiovascular studies will be necessary to fully determine the clinical implications of our findings.”
To refer a patient into the VIP studies, call 215-662-SKIN or email [email protected].
The National Institutes of Health and University of Pennsylvania sponsored the study. Dr. Gelfand reported no financial disclosures.
SOURCE: Gelfand J et al. AAD 2018 Abstract 6645
SAN DIEGO – A 12-week course of ustekinumab significantly reduced inflammation in the aorta – an effect on par with the benefit of statins – in patients with moderate to severe plaque psoriasis.
Whether or not the reduction in aortic inflammation will translate into a reduction in cardiovascular risk remains to be determined, but investigators are very encouraged by the results of the Vascular Inflammation in Psoriasis-Ustekinumab (VIP-U) study, Joel M. Gelfand, MD, said at the annual meeting of the American Academy of Dermatology.
For the past decade, researchers have worked on the assumption that the chronic systemic inflammation of severe psoriasis overlaps with similar inflammatory pathways that drive atherosclerosis, plaques that rupture, and cardiovascular events.
Recently, they have employed fluorodeoxyglucose positron emission tomography (FDG-PET) to confirm some of this. Studies in 2011, 2015, and 2017 confirm that patients with severe plaque psoriasis can develop diffuse vascular inflammation with increased noncalcified coronary artery plaques. These more fragile plaques are the type that are prone to rupture and cause cardiovascular events, Dr. Gelfand said.
“In these studies, the more imaging signal we saw in the aorta, the higher the risk of a future cardiovascular event. In fact, we determined that patients with severe psoriasis can have increased aortic inflammation equivalent to a decade of aging. As your PASI [Psoriasis Area and Severity Index] score goes up, so does the amount of aortic inflammation. The anatomic consequence is that people develop a high risk of atherosclerotic plaques, and a higher rate of noncalcified coronary plaques that are more likely to lead to these events.”
The VIP-U study was conceived to examine whether calming psoriatic inflammation with ustekinumab (Stelara), an anti interleukin-12 and -23 antibody, could also improve vascular inflammation as measured by FDG-PET. The small study comprised 43 patients, half of whom received placebo and half of whom received two injections of ustekinumab: 45 or 90 mg depending on weight, at baseline and at week 4. There was an imaging assessment at week 12, after which the placebo patients crossed over to open-label ustekinumab every 2 weeks. Everyone was followed out to 64 weeks.
Dr. Gelfand reported the 12-week data; the 64-week data will be forthcoming later this year, he said.
The patients were typical for such a study, with a mean age of about 43 and a mean disease duration of 18 years. The mean body surface area was about 25%, and the mean PASI was 20. Most had been on prior therapy, including phototherapy, oral agents, and biologics.
Unsurprisingly, ustekinumab was significantly more effective than placebo in treating the psoriasis. At week 12, 10% of the placebo patients had achieved a PASI 75, compared with 77% of the ustekinumab patients. A Physicians Global Assessment (PGA) score of clear or almost clear occurred in 10% of those taking placebo and 64% of those taking the biologic.
However, the drug was also highly effective in reducing total aortic inflammation, Dr. Gelfand said. “In just 12 weeks, we saw a 6.6% reduction in total aortic inflammation among those taking ustekinumab, but a 12.1% increase in inflammation among those taking placebo. When you compare the delta, you see a highly statistically significant improvement in aortic inflammation in ustekinumab-treated patients, with the effect size similar to statin therapy.”
The benefit may be a class-associated one. Two recent similar studies of adalimumab, a tumor necrosis factor–alpha inhibitor, failed to find any improvement in vascular inflammation, compared with placebo.
“We need more information about the longer-term effects of ustekinumab treatment, as well as cardiometabolic biomarkers, and these are currently underway,” Dr. Gelfand said. “We also need additional trials to determine if this effect is due to the inhibition of IL-12, IL-23, or a combination. Cardiovascular studies will be necessary to fully determine the clinical implications of our findings.”
To refer a patient into the VIP studies, call 215-662-SKIN or email [email protected].
The National Institutes of Health and University of Pennsylvania sponsored the study. Dr. Gelfand reported no financial disclosures.
SOURCE: Gelfand J et al. AAD 2018 Abstract 6645
REPORTING FROM AAD 2018
Key clinical point:
Major finding: Aortic inflammation decreased by 6.6% in those taking ustekinumab, but increased by 12.1% in those taking placebo.
Study details: The randomized trial comprised 43 patients.
Disclosures: The National Institutes of Health and University of Pennsylvania sponsored the study. Dr. Gelfand made no financial disclosures.
Source: Gelfand J et al. AAD 2018 Abstract 6645.
Dual kinase inhibitor performs well in its first safety, efficacy study for atopic dermatitis
SAN DIEGO – A novel molecule that inhibits two major inflammatory pathways acquitted itself well in its first safety and efficacy clinical trial in patients with moderate to severe atopic dermatitis.
After 29 days, 100% of those taking the highest dose of the molecule, ASN002, achieved a 50% improvement in skin involvement.
“This is an interesting molecule,” Robert Bissonnette, MD, said at the annual meeting of the American Academy of Dermatology. “By targeting the entire JAK family, it inhibits cytokine signaling through IL-4 [interleukin-4], IL-13, IL-23, and thymic stromal lymphopoietin,” which plays a role in maturing T cells. The SYK inhibition targets IL-17, increases the terminal differentiation of keratinocytes, and inhibits B-cell signaling.
Dr. Bissonnette, president of Innovaderm Research presented the results in a late-breaking session at the meeting. Innovaderm designs, conducts, and analyzes dermatology clinical trials, and ran the study for Asana BioSciences.
In an Asana press release about the study results, CEO Sandeep Gupta, PhD, said that ASN002 “is the only oral compound in clinical development targeting JAK [including Tyk2] and SYK signaling, two clinically validated mechanisms.” He added that inhibition of JAK and SYK pathways “diminishes cytokine production and signaling including those mediated by Th2 and Th22 cytokines. Dysregulation of Th2 and Th22 cytokine pathways is implicated in the pathogenesis of atopic dermatitis.”
Safety was the primary endpoint in the phase 1b dose-ranging trial, but there were also several efficacy endpoints, Dr. Bissonnette said at the meeting. The study comprised 36 patients separated into three 12-patient groups. In each group, nine received the active drug every day, and three received a placebo. The first group received 20 mg ASN002 or placebo for 28 days, followed by the 14-day safety period. The next group received 40 mg ASN002 or placebo for 28 days, followed by the safety analysis. The third group followed the same treatment pattern, but received 80 mg of the drug.
All patients were aged 29-42 years. The Eczema Area and Severity Index (EASI) was imbalanced among the groups, ranging from 21 in the placebo group and 40-mg group, to 29 in the 20-mg and 80-mg groups. The Body Surface Area (BSA) index also differed between groups: 25% among the placebo patients, 45% in the 20-mg group, 32% in the 40-mg group, and 29% in the 80-mg group. The average Investigator Global Assessment (IGA) score was 3.
A pharmacokinetic analysis showed rapid uptake of the drug with a half-life of 10-14 hours depending on dose.
There were no concerning safety signals, Dr. Bissonnette said and no thromboembolic events, serious infections, or opportunistic infections. The most common adverse event was headache, which occurred at equal rates among the groups. The single serious adverse event was anxiety, which occurred in one patient taking 80 mg ASN002, 4 days after the medication was stopped, and was judged unrelated to ASN002.
There were no significant changes in any lab parameters, no changes in lipid profiles, and no hematologic abnormalities. One patient experienced an increase in creatinine phosphokinase, something that has been seen in other studies of JAK inhibitors, Dr. Bissonnette said.
The molecule performed well on secondary efficacy endpoints. By day 15, 63% of the 40-mg group and 75% of the 80-mg group had achieved EASI-50, and by day 29, these rates were 88% and 100%, respectively. These doses also performed well on the EASI-75 endpoint. By day 29, 63% of the 40-mg group and 50% of the 80-mg group had achieved a 75% improvement in EASI score.
The 40- and 80-mg groups also did well with regards to BSA improvement. By day 29, the 80-mg group had achieved a mean BSA reduction of 58%, and the 40-mg group a mean reduction of 64%. IGA tracked that improvement, with 25% of the 80-mg group and 38% of the 40-mg group achieving an IGA score of 1 or 0.
Itching responded well to ASN002, but here, the 20-mg dose threw investigators a bit of a curve ball. Pruritus decreased most in the 80-mg group (about 70% by the end of the study). But at 3 weeks, patients taking 20 mg and 40 mg were experiencing the same 30% decrease in itch. By 4 weeks, however, the scores had separated, with the 40-mg group landing at about a 40% reduction, and the 20-mg group rebounding to about a 20% reduction.
“I would say that this first trial of ASN002 showed clear efficacy in patients with moderate to severe atopic dermatitis, with rapid improvement itch and a large proportion of patients reaching EASI-50 as early as 2 weeks,” Dr. Bissonnette said.
Asana will soon initiate a phase 2b study of ASN002 in moderate to severe atopic dermatitis patients. Clinical studies in other dermatologic and autoimmune indications are under consideration, according to the company website.
Dr. Bissonnette is the president of Innovaderm Research, which was paid to run the ASN002 study.
SOURCE: Bissonnette R et al. AAD 2018, Abstract 6777
SAN DIEGO – A novel molecule that inhibits two major inflammatory pathways acquitted itself well in its first safety and efficacy clinical trial in patients with moderate to severe atopic dermatitis.
After 29 days, 100% of those taking the highest dose of the molecule, ASN002, achieved a 50% improvement in skin involvement.
“This is an interesting molecule,” Robert Bissonnette, MD, said at the annual meeting of the American Academy of Dermatology. “By targeting the entire JAK family, it inhibits cytokine signaling through IL-4 [interleukin-4], IL-13, IL-23, and thymic stromal lymphopoietin,” which plays a role in maturing T cells. The SYK inhibition targets IL-17, increases the terminal differentiation of keratinocytes, and inhibits B-cell signaling.
Dr. Bissonnette, president of Innovaderm Research presented the results in a late-breaking session at the meeting. Innovaderm designs, conducts, and analyzes dermatology clinical trials, and ran the study for Asana BioSciences.
In an Asana press release about the study results, CEO Sandeep Gupta, PhD, said that ASN002 “is the only oral compound in clinical development targeting JAK [including Tyk2] and SYK signaling, two clinically validated mechanisms.” He added that inhibition of JAK and SYK pathways “diminishes cytokine production and signaling including those mediated by Th2 and Th22 cytokines. Dysregulation of Th2 and Th22 cytokine pathways is implicated in the pathogenesis of atopic dermatitis.”
Safety was the primary endpoint in the phase 1b dose-ranging trial, but there were also several efficacy endpoints, Dr. Bissonnette said at the meeting. The study comprised 36 patients separated into three 12-patient groups. In each group, nine received the active drug every day, and three received a placebo. The first group received 20 mg ASN002 or placebo for 28 days, followed by the 14-day safety period. The next group received 40 mg ASN002 or placebo for 28 days, followed by the safety analysis. The third group followed the same treatment pattern, but received 80 mg of the drug.
All patients were aged 29-42 years. The Eczema Area and Severity Index (EASI) was imbalanced among the groups, ranging from 21 in the placebo group and 40-mg group, to 29 in the 20-mg and 80-mg groups. The Body Surface Area (BSA) index also differed between groups: 25% among the placebo patients, 45% in the 20-mg group, 32% in the 40-mg group, and 29% in the 80-mg group. The average Investigator Global Assessment (IGA) score was 3.
A pharmacokinetic analysis showed rapid uptake of the drug with a half-life of 10-14 hours depending on dose.
There were no concerning safety signals, Dr. Bissonnette said and no thromboembolic events, serious infections, or opportunistic infections. The most common adverse event was headache, which occurred at equal rates among the groups. The single serious adverse event was anxiety, which occurred in one patient taking 80 mg ASN002, 4 days after the medication was stopped, and was judged unrelated to ASN002.
There were no significant changes in any lab parameters, no changes in lipid profiles, and no hematologic abnormalities. One patient experienced an increase in creatinine phosphokinase, something that has been seen in other studies of JAK inhibitors, Dr. Bissonnette said.
The molecule performed well on secondary efficacy endpoints. By day 15, 63% of the 40-mg group and 75% of the 80-mg group had achieved EASI-50, and by day 29, these rates were 88% and 100%, respectively. These doses also performed well on the EASI-75 endpoint. By day 29, 63% of the 40-mg group and 50% of the 80-mg group had achieved a 75% improvement in EASI score.
The 40- and 80-mg groups also did well with regards to BSA improvement. By day 29, the 80-mg group had achieved a mean BSA reduction of 58%, and the 40-mg group a mean reduction of 64%. IGA tracked that improvement, with 25% of the 80-mg group and 38% of the 40-mg group achieving an IGA score of 1 or 0.
Itching responded well to ASN002, but here, the 20-mg dose threw investigators a bit of a curve ball. Pruritus decreased most in the 80-mg group (about 70% by the end of the study). But at 3 weeks, patients taking 20 mg and 40 mg were experiencing the same 30% decrease in itch. By 4 weeks, however, the scores had separated, with the 40-mg group landing at about a 40% reduction, and the 20-mg group rebounding to about a 20% reduction.
“I would say that this first trial of ASN002 showed clear efficacy in patients with moderate to severe atopic dermatitis, with rapid improvement itch and a large proportion of patients reaching EASI-50 as early as 2 weeks,” Dr. Bissonnette said.
Asana will soon initiate a phase 2b study of ASN002 in moderate to severe atopic dermatitis patients. Clinical studies in other dermatologic and autoimmune indications are under consideration, according to the company website.
Dr. Bissonnette is the president of Innovaderm Research, which was paid to run the ASN002 study.
SOURCE: Bissonnette R et al. AAD 2018, Abstract 6777
SAN DIEGO – A novel molecule that inhibits two major inflammatory pathways acquitted itself well in its first safety and efficacy clinical trial in patients with moderate to severe atopic dermatitis.
After 29 days, 100% of those taking the highest dose of the molecule, ASN002, achieved a 50% improvement in skin involvement.
“This is an interesting molecule,” Robert Bissonnette, MD, said at the annual meeting of the American Academy of Dermatology. “By targeting the entire JAK family, it inhibits cytokine signaling through IL-4 [interleukin-4], IL-13, IL-23, and thymic stromal lymphopoietin,” which plays a role in maturing T cells. The SYK inhibition targets IL-17, increases the terminal differentiation of keratinocytes, and inhibits B-cell signaling.
Dr. Bissonnette, president of Innovaderm Research presented the results in a late-breaking session at the meeting. Innovaderm designs, conducts, and analyzes dermatology clinical trials, and ran the study for Asana BioSciences.
In an Asana press release about the study results, CEO Sandeep Gupta, PhD, said that ASN002 “is the only oral compound in clinical development targeting JAK [including Tyk2] and SYK signaling, two clinically validated mechanisms.” He added that inhibition of JAK and SYK pathways “diminishes cytokine production and signaling including those mediated by Th2 and Th22 cytokines. Dysregulation of Th2 and Th22 cytokine pathways is implicated in the pathogenesis of atopic dermatitis.”
Safety was the primary endpoint in the phase 1b dose-ranging trial, but there were also several efficacy endpoints, Dr. Bissonnette said at the meeting. The study comprised 36 patients separated into three 12-patient groups. In each group, nine received the active drug every day, and three received a placebo. The first group received 20 mg ASN002 or placebo for 28 days, followed by the 14-day safety period. The next group received 40 mg ASN002 or placebo for 28 days, followed by the safety analysis. The third group followed the same treatment pattern, but received 80 mg of the drug.
All patients were aged 29-42 years. The Eczema Area and Severity Index (EASI) was imbalanced among the groups, ranging from 21 in the placebo group and 40-mg group, to 29 in the 20-mg and 80-mg groups. The Body Surface Area (BSA) index also differed between groups: 25% among the placebo patients, 45% in the 20-mg group, 32% in the 40-mg group, and 29% in the 80-mg group. The average Investigator Global Assessment (IGA) score was 3.
A pharmacokinetic analysis showed rapid uptake of the drug with a half-life of 10-14 hours depending on dose.
There were no concerning safety signals, Dr. Bissonnette said and no thromboembolic events, serious infections, or opportunistic infections. The most common adverse event was headache, which occurred at equal rates among the groups. The single serious adverse event was anxiety, which occurred in one patient taking 80 mg ASN002, 4 days after the medication was stopped, and was judged unrelated to ASN002.
There were no significant changes in any lab parameters, no changes in lipid profiles, and no hematologic abnormalities. One patient experienced an increase in creatinine phosphokinase, something that has been seen in other studies of JAK inhibitors, Dr. Bissonnette said.
The molecule performed well on secondary efficacy endpoints. By day 15, 63% of the 40-mg group and 75% of the 80-mg group had achieved EASI-50, and by day 29, these rates were 88% and 100%, respectively. These doses also performed well on the EASI-75 endpoint. By day 29, 63% of the 40-mg group and 50% of the 80-mg group had achieved a 75% improvement in EASI score.
The 40- and 80-mg groups also did well with regards to BSA improvement. By day 29, the 80-mg group had achieved a mean BSA reduction of 58%, and the 40-mg group a mean reduction of 64%. IGA tracked that improvement, with 25% of the 80-mg group and 38% of the 40-mg group achieving an IGA score of 1 or 0.
Itching responded well to ASN002, but here, the 20-mg dose threw investigators a bit of a curve ball. Pruritus decreased most in the 80-mg group (about 70% by the end of the study). But at 3 weeks, patients taking 20 mg and 40 mg were experiencing the same 30% decrease in itch. By 4 weeks, however, the scores had separated, with the 40-mg group landing at about a 40% reduction, and the 20-mg group rebounding to about a 20% reduction.
“I would say that this first trial of ASN002 showed clear efficacy in patients with moderate to severe atopic dermatitis, with rapid improvement itch and a large proportion of patients reaching EASI-50 as early as 2 weeks,” Dr. Bissonnette said.
Asana will soon initiate a phase 2b study of ASN002 in moderate to severe atopic dermatitis patients. Clinical studies in other dermatologic and autoimmune indications are under consideration, according to the company website.
Dr. Bissonnette is the president of Innovaderm Research, which was paid to run the ASN002 study.
SOURCE: Bissonnette R et al. AAD 2018, Abstract 6777
REPORTING FROM AAD 2018
Key clinical point: ASN002 calmed itch, improved skin involvement in moderate to severe atopic dermatitis.
Major finding: After 29 days, 100% of those taking 80-mg doses of ASN002 daily achieved a 50% improvement in EASI.
Study details: The randomized dose-escalation phase 1b study comprised 36 patients with moderate to severe atopic dermatitis.
Disclosures: Asana BioSciences sponsored the study. Dr. Bissonnette is CEO of Innovaderm Research, Montreal, which conducted the trial.
Source: Bissonnette R et al. AAD 2018, Abstract 6777.
VIDEO: With new therapies available, it’s the ‘decade of eczema,’ researcher says
SAN DIEGO – A long dry spell in the development of new atopic dermatitis (AD) medications came to an end in 2016 with the approval of a topical treatment, and last year brought the first biologic for AD to the market. With more targets and potential treatments being studied, “it’s the decade of eczema,” according to a leading researcher.
And I think we’ll have many more approvals in the next few years,” said Emma Guttman, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she was presenting a talk on the translational revolution in atopic dermatitis.
In the interview, she also discussed research showing that children with AD don’t have the same distribution of lesions as adults, and a study of young children, which found that during an early stage of the disease, when compared with adults, they showed much higher increases in Th17 similar to that seen in psoriasis. It will be interesting to see if “some drugs that work for psoriasis may work in children,” said Dr. Guttman, professor of dermatology and director of the laboratory of inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Guttman disclosed research support, consulting, or lecture fees from Regeneron, Sanofi, Pfizer, and other companies developing AD treatments.
SAN DIEGO – A long dry spell in the development of new atopic dermatitis (AD) medications came to an end in 2016 with the approval of a topical treatment, and last year brought the first biologic for AD to the market. With more targets and potential treatments being studied, “it’s the decade of eczema,” according to a leading researcher.
And I think we’ll have many more approvals in the next few years,” said Emma Guttman, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she was presenting a talk on the translational revolution in atopic dermatitis.
In the interview, she also discussed research showing that children with AD don’t have the same distribution of lesions as adults, and a study of young children, which found that during an early stage of the disease, when compared with adults, they showed much higher increases in Th17 similar to that seen in psoriasis. It will be interesting to see if “some drugs that work for psoriasis may work in children,” said Dr. Guttman, professor of dermatology and director of the laboratory of inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Guttman disclosed research support, consulting, or lecture fees from Regeneron, Sanofi, Pfizer, and other companies developing AD treatments.
SAN DIEGO – A long dry spell in the development of new atopic dermatitis (AD) medications came to an end in 2016 with the approval of a topical treatment, and last year brought the first biologic for AD to the market. With more targets and potential treatments being studied, “it’s the decade of eczema,” according to a leading researcher.
And I think we’ll have many more approvals in the next few years,” said Emma Guttman, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she was presenting a talk on the translational revolution in atopic dermatitis.
In the interview, she also discussed research showing that children with AD don’t have the same distribution of lesions as adults, and a study of young children, which found that during an early stage of the disease, when compared with adults, they showed much higher increases in Th17 similar to that seen in psoriasis. It will be interesting to see if “some drugs that work for psoriasis may work in children,” said Dr. Guttman, professor of dermatology and director of the laboratory of inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Guttman disclosed research support, consulting, or lecture fees from Regeneron, Sanofi, Pfizer, and other companies developing AD treatments.
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VIDEO: U.S. melanoma incidence hits all-time high
SAN DIEGO –
“Nobody’s quite sure why the [melanoma] rates are still rising so dramatically,” Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology. The increase remains even after adjustment of incidence rates for the increasing mean age of U.S. adults.
The American Cancer Society reported that the estimated annual incidence rate for invasive melanoma will be 91,270 cases for 2018, following what the society called a rapid rise in the rate for the past 30 years. Add to that the estimate of more than 87,000 U.S. cases of in situ melanoma for an overall annual U.S. rate of 178,560, Dr. Rigel said.
Melanoma has a latency of 5-20 years, “so what we’re seeing right now are the effects of what happened 5, 10, or 20 years ago,” said Dr. Rigel, a dermatologist at New York University.
During a talk at the meeting, Dr. Rigel said that based on current incident levels he projected a lifetime U.S. incidence rate of invasive melanoma of one case for every 40 adults by the end of this decade, and a lifetime incidence rate for either invasive or in situ melanoma of one case for every 20 adults by 2020.
A positive trend is that for the first time, the number of melanoma deaths has started to fall, with an estimated 9,320 deaths from melanoma in 2018 according to American Cancer Society statistics, down from a peak of 10,130 melanoma deaths in 2016, Dr. Rigel said.
SAN DIEGO –
“Nobody’s quite sure why the [melanoma] rates are still rising so dramatically,” Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology. The increase remains even after adjustment of incidence rates for the increasing mean age of U.S. adults.
The American Cancer Society reported that the estimated annual incidence rate for invasive melanoma will be 91,270 cases for 2018, following what the society called a rapid rise in the rate for the past 30 years. Add to that the estimate of more than 87,000 U.S. cases of in situ melanoma for an overall annual U.S. rate of 178,560, Dr. Rigel said.
Melanoma has a latency of 5-20 years, “so what we’re seeing right now are the effects of what happened 5, 10, or 20 years ago,” said Dr. Rigel, a dermatologist at New York University.
During a talk at the meeting, Dr. Rigel said that based on current incident levels he projected a lifetime U.S. incidence rate of invasive melanoma of one case for every 40 adults by the end of this decade, and a lifetime incidence rate for either invasive or in situ melanoma of one case for every 20 adults by 2020.
A positive trend is that for the first time, the number of melanoma deaths has started to fall, with an estimated 9,320 deaths from melanoma in 2018 according to American Cancer Society statistics, down from a peak of 10,130 melanoma deaths in 2016, Dr. Rigel said.
SAN DIEGO –
“Nobody’s quite sure why the [melanoma] rates are still rising so dramatically,” Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology. The increase remains even after adjustment of incidence rates for the increasing mean age of U.S. adults.
The American Cancer Society reported that the estimated annual incidence rate for invasive melanoma will be 91,270 cases for 2018, following what the society called a rapid rise in the rate for the past 30 years. Add to that the estimate of more than 87,000 U.S. cases of in situ melanoma for an overall annual U.S. rate of 178,560, Dr. Rigel said.
Melanoma has a latency of 5-20 years, “so what we’re seeing right now are the effects of what happened 5, 10, or 20 years ago,” said Dr. Rigel, a dermatologist at New York University.
During a talk at the meeting, Dr. Rigel said that based on current incident levels he projected a lifetime U.S. incidence rate of invasive melanoma of one case for every 40 adults by the end of this decade, and a lifetime incidence rate for either invasive or in situ melanoma of one case for every 20 adults by 2020.
A positive trend is that for the first time, the number of melanoma deaths has started to fall, with an estimated 9,320 deaths from melanoma in 2018 according to American Cancer Society statistics, down from a peak of 10,130 melanoma deaths in 2016, Dr. Rigel said.
REPORTING FROM AAD 18
