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In vasculitis, the skin tells the story
MILAN – , Robert Micheletti, MD, said at the World Congress of Dermatology.
In granulomatous vasculitis, histiocytes and giant cells can play a significant role, explained Dr. Micheletti, director of the cutaneous vasculitis clinic at the University of Pennsylvania, Philadelphia. The condition may be secondary to an autoimmune disease such as lupus erythematosus or RA; a granulomatous disease such as Crohn’s disease or sarcoidosis; infections such as tuberculosis, a fungal disease, or herpes or zoster viruses, or lymphoma, Dr. Micheletti said.
However, a primary systemic vasculitis such as granulomatosis with polyangiitis (GPA; formerly known as Wegener’s polyangiitis) or eosinophilic granulomatosis with polyangiitis (EGPA; also known as Churg-Strauss vasculitis), giant cell arteritis, or Takayasu arteritis may also be responsible, he said. Occasionally, the culprit can also be a drug-induced vasculitis.
The physical examination gives clues to the size of involved vessels, which in turn helps to classify the vasculitis, Dr. Micheletti said.
When vasculitis affects small vessels, the skin findings will be palpable purpura, urticarial papules, vesicles, and petechiae, he said, adding that “The small vessel involvement accounts for the small size of the lesions, and complement cascade and inflammation account for the palpability of the lesions and the symptomatology.” As red blood cells extravasate from the affected vessels, nonblanching purpura develop, and gravity’s effect on the deposition of immune complex material dictates how lesions are distributed.
“Manifestations more typical of medium vessel vasculitis include subcutaneous nodules, livedo reticularis, retiform purpura, larger hemorrhagic bullae, and more significant ulceration and necrosis,” he said. “If such lesions are seen, suspect medium-vessel vasculitis or vasculitis overlapping small and medium vessels.” Cutaneous or systemic polyarteritis nodosa, antineutrophilic cytoplasmic autoantibody (ANCA)–associated vasculitis, and cryoglobulinemic vasculitis are examples, he added.
The particularities of renal manifestations of vasculitis also offer clues to the vessels involved. When a vasculitis patient has glomerulonephritis, suspect small-vessel involvement, Dr. Micheletti said. However, vasculitis affecting medium-sized vessels will cause renovascular hypertension and, potentially renal arterial aneurysms.
Nerves are typically spared in small-vessel vasculitis, while wrist or foot drop can be seen in mononeuritis multiplex.
Recently, the Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) looked at more than 6,800 patients at over 130 sites around the world, proposing new classification criteria for ANCA-associated vasculitis (AAV) and large-vessel vasculitis. The study found that skin findings are common in AAV, with 30%-50% of cases presenting initially with skin lesions. Petechiae and/or purpura are the most common of the skin manifestations, he said. By contrast, for EGPA, allergic and nonspecific findings were the most common findings.
Although skin biopsy can confirm the diagnosis in up to 94% of AAV cases, it’s underutilized and performed in less than half (24%-44%) of cases, Dr. Micheletti said. The study’s findings “demonstrate the importance of a good skin exam, as well as its utility for diagnosis” of vasculitis, he said.
An additional finding form the DCVAS study was that skin lesions can give clues to severity of vasculitis: “Among 1,184 patients with ANCA-associated vasculitis, those with cutaneous involvement were more likely to have systemic manifestations of disease, more likely to have such severe manifestations as glomerulonephritis, alveolar hemorrhage, and mononeuritis,” said Dr. Micheletti, with a hazard ratio of 2.0 among those individuals who had EGPA or GPA.
“Skin findings have diagnostic and, potentially, prognostic importance,” he said. “Use the physician exam and your clinical acumen to your advantage,” but always confirm vasculitis with a biopsy. “Clinicopathologic correlation is key.” A simple urinalysis will screen for renal involvement, and is of “paramount importance,” he added.
Dr. Micheletti reported that he had no relevant disclosures.
MILAN – , Robert Micheletti, MD, said at the World Congress of Dermatology.
In granulomatous vasculitis, histiocytes and giant cells can play a significant role, explained Dr. Micheletti, director of the cutaneous vasculitis clinic at the University of Pennsylvania, Philadelphia. The condition may be secondary to an autoimmune disease such as lupus erythematosus or RA; a granulomatous disease such as Crohn’s disease or sarcoidosis; infections such as tuberculosis, a fungal disease, or herpes or zoster viruses, or lymphoma, Dr. Micheletti said.
However, a primary systemic vasculitis such as granulomatosis with polyangiitis (GPA; formerly known as Wegener’s polyangiitis) or eosinophilic granulomatosis with polyangiitis (EGPA; also known as Churg-Strauss vasculitis), giant cell arteritis, or Takayasu arteritis may also be responsible, he said. Occasionally, the culprit can also be a drug-induced vasculitis.
The physical examination gives clues to the size of involved vessels, which in turn helps to classify the vasculitis, Dr. Micheletti said.
When vasculitis affects small vessels, the skin findings will be palpable purpura, urticarial papules, vesicles, and petechiae, he said, adding that “The small vessel involvement accounts for the small size of the lesions, and complement cascade and inflammation account for the palpability of the lesions and the symptomatology.” As red blood cells extravasate from the affected vessels, nonblanching purpura develop, and gravity’s effect on the deposition of immune complex material dictates how lesions are distributed.
“Manifestations more typical of medium vessel vasculitis include subcutaneous nodules, livedo reticularis, retiform purpura, larger hemorrhagic bullae, and more significant ulceration and necrosis,” he said. “If such lesions are seen, suspect medium-vessel vasculitis or vasculitis overlapping small and medium vessels.” Cutaneous or systemic polyarteritis nodosa, antineutrophilic cytoplasmic autoantibody (ANCA)–associated vasculitis, and cryoglobulinemic vasculitis are examples, he added.
The particularities of renal manifestations of vasculitis also offer clues to the vessels involved. When a vasculitis patient has glomerulonephritis, suspect small-vessel involvement, Dr. Micheletti said. However, vasculitis affecting medium-sized vessels will cause renovascular hypertension and, potentially renal arterial aneurysms.
Nerves are typically spared in small-vessel vasculitis, while wrist or foot drop can be seen in mononeuritis multiplex.
Recently, the Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) looked at more than 6,800 patients at over 130 sites around the world, proposing new classification criteria for ANCA-associated vasculitis (AAV) and large-vessel vasculitis. The study found that skin findings are common in AAV, with 30%-50% of cases presenting initially with skin lesions. Petechiae and/or purpura are the most common of the skin manifestations, he said. By contrast, for EGPA, allergic and nonspecific findings were the most common findings.
Although skin biopsy can confirm the diagnosis in up to 94% of AAV cases, it’s underutilized and performed in less than half (24%-44%) of cases, Dr. Micheletti said. The study’s findings “demonstrate the importance of a good skin exam, as well as its utility for diagnosis” of vasculitis, he said.
An additional finding form the DCVAS study was that skin lesions can give clues to severity of vasculitis: “Among 1,184 patients with ANCA-associated vasculitis, those with cutaneous involvement were more likely to have systemic manifestations of disease, more likely to have such severe manifestations as glomerulonephritis, alveolar hemorrhage, and mononeuritis,” said Dr. Micheletti, with a hazard ratio of 2.0 among those individuals who had EGPA or GPA.
“Skin findings have diagnostic and, potentially, prognostic importance,” he said. “Use the physician exam and your clinical acumen to your advantage,” but always confirm vasculitis with a biopsy. “Clinicopathologic correlation is key.” A simple urinalysis will screen for renal involvement, and is of “paramount importance,” he added.
Dr. Micheletti reported that he had no relevant disclosures.
MILAN – , Robert Micheletti, MD, said at the World Congress of Dermatology.
In granulomatous vasculitis, histiocytes and giant cells can play a significant role, explained Dr. Micheletti, director of the cutaneous vasculitis clinic at the University of Pennsylvania, Philadelphia. The condition may be secondary to an autoimmune disease such as lupus erythematosus or RA; a granulomatous disease such as Crohn’s disease or sarcoidosis; infections such as tuberculosis, a fungal disease, or herpes or zoster viruses, or lymphoma, Dr. Micheletti said.
However, a primary systemic vasculitis such as granulomatosis with polyangiitis (GPA; formerly known as Wegener’s polyangiitis) or eosinophilic granulomatosis with polyangiitis (EGPA; also known as Churg-Strauss vasculitis), giant cell arteritis, or Takayasu arteritis may also be responsible, he said. Occasionally, the culprit can also be a drug-induced vasculitis.
The physical examination gives clues to the size of involved vessels, which in turn helps to classify the vasculitis, Dr. Micheletti said.
When vasculitis affects small vessels, the skin findings will be palpable purpura, urticarial papules, vesicles, and petechiae, he said, adding that “The small vessel involvement accounts for the small size of the lesions, and complement cascade and inflammation account for the palpability of the lesions and the symptomatology.” As red blood cells extravasate from the affected vessels, nonblanching purpura develop, and gravity’s effect on the deposition of immune complex material dictates how lesions are distributed.
“Manifestations more typical of medium vessel vasculitis include subcutaneous nodules, livedo reticularis, retiform purpura, larger hemorrhagic bullae, and more significant ulceration and necrosis,” he said. “If such lesions are seen, suspect medium-vessel vasculitis or vasculitis overlapping small and medium vessels.” Cutaneous or systemic polyarteritis nodosa, antineutrophilic cytoplasmic autoantibody (ANCA)–associated vasculitis, and cryoglobulinemic vasculitis are examples, he added.
The particularities of renal manifestations of vasculitis also offer clues to the vessels involved. When a vasculitis patient has glomerulonephritis, suspect small-vessel involvement, Dr. Micheletti said. However, vasculitis affecting medium-sized vessels will cause renovascular hypertension and, potentially renal arterial aneurysms.
Nerves are typically spared in small-vessel vasculitis, while wrist or foot drop can be seen in mononeuritis multiplex.
Recently, the Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) looked at more than 6,800 patients at over 130 sites around the world, proposing new classification criteria for ANCA-associated vasculitis (AAV) and large-vessel vasculitis. The study found that skin findings are common in AAV, with 30%-50% of cases presenting initially with skin lesions. Petechiae and/or purpura are the most common of the skin manifestations, he said. By contrast, for EGPA, allergic and nonspecific findings were the most common findings.
Although skin biopsy can confirm the diagnosis in up to 94% of AAV cases, it’s underutilized and performed in less than half (24%-44%) of cases, Dr. Micheletti said. The study’s findings “demonstrate the importance of a good skin exam, as well as its utility for diagnosis” of vasculitis, he said.
An additional finding form the DCVAS study was that skin lesions can give clues to severity of vasculitis: “Among 1,184 patients with ANCA-associated vasculitis, those with cutaneous involvement were more likely to have systemic manifestations of disease, more likely to have such severe manifestations as glomerulonephritis, alveolar hemorrhage, and mononeuritis,” said Dr. Micheletti, with a hazard ratio of 2.0 among those individuals who had EGPA or GPA.
“Skin findings have diagnostic and, potentially, prognostic importance,” he said. “Use the physician exam and your clinical acumen to your advantage,” but always confirm vasculitis with a biopsy. “Clinicopathologic correlation is key.” A simple urinalysis will screen for renal involvement, and is of “paramount importance,” he added.
Dr. Micheletti reported that he had no relevant disclosures.
AT WCD2019
Consider adding chemical peels for your acne patients
MILAN – according to Dee Anna Glaser, MD.
Speaking at the World Congress of Dermatology, Dr. Glaser, director of clinical research and interim chair of the department of dermatology at Saint Louis University, said that in her practice, acne and actinic keratosis are the most common medical indications for chemical peels and that “acne is just a winner all the way around.”
For acne, she added: “Chemical peels can help both the comedonal and the inflammatory component. It should probably be combined with other therapies, and it does produce both an exfoliative and an anti-inflammatory benefit,.”
A variety of chemical peel formulations can be considered for acne, Dr. Glaser noted. “Typically, you’re going to use a light chemical peel,” such as glycolic or salicylic acid. Other options include Jessner’s solution or a light trichloroacetic acid formulation, she said, adding that tretinoin alone can also be considered.
In choosing between glycolic and salicylic acid, Dr. Glaser said, “salicylic acid should theoretically be the best agent because it is lipophilic and the glycolic acid is hydrophilic.” The reality of how these agents perform clinically, though, may sort out differently.
Dr. Glaser pointed to a double-blind, randomized controlled trial of the two agents in 20 women with facial acne. The severity of participants’ inflammatory acne was mild to moderate, with an average of 27 inflammatory lesions, and they had been on a stable prescription or over-the-counter acne regimen for at least 2 months (Dermatol Surg. 2008 Jan;34[1]:45-50).
Patients received six peels – one every 2 weeks – with 30% glycolic acid (an alpha-hydroxy acid) and 30% salicylic acid (a beta-hydroxy acid) in the split-face study.
All participants started at 4 minutes of exposure and increased up to 5 minutes as tolerated, although timing is only really important for glycolic acid, the same duration of exposure was maintained for each agent for the sake of consistency between arms, said Dr. Glaser, one of the investigators.
Sharing photographs of study participants, she observed that after six peels, “there really isn’t a significant difference.” Therefore, she added, “even though salicylic acid should be better, you can see that glycolic acid really held its own in this study.”
Dr. Glaser pointed out that a trend was seen for slightly better results with salicylic acid and results with this agent were more durable than those seen with glycolic acid. Patients reported fewer side effects on the beta-hydroxy–treated side as well.
She referred to another study, conducted in Japan, that used a double-blind, split-face design to compare 40% glycolic acid with a placebo that had a similarly low pH of 2.0. The 26 patients with moderate acne received five peels on a biweekly schedule, with glycolic acid significantly outperforming placebo. Among acne subtypes, noninflammatory acne improved more than inflammatory acne with glycolic acid (Dermatol Surg. 2014 Mar;40[3]:314-22).
Dr. Glaser said that in her own practice, she still tries to use salicylic acid for her acne patients,” though some patients prefer the experience of a glycolic acid peel, with which there’s likely to be less pain. “So if you have a preference, or your patient has a preference, you will probably be able to use the acid that works best for you,” she said.
Whatever peel is chosen, it should be considered an adjuvant to other topical and systemic acne therapies, Dr. Glaser stressed. “To maintain the results, you really do need to maintain the patient on some sort of standard acne therapy that you would normally do.”
Peels can also be an effective part of a multipronged approach that includes laser therapy and intralesional steroids, she said. However, peels can be considered for monotherapy in patients who don’t tolerate other acne therapies, and they can be used safely in pregnancy, she said.
As with all such treatments, dermatologists should remember to consider and counsel about herpes simplex virus prophylaxis and sun protection.
Dr. Glaser reported financial relationships with Galderma, Ulthera, Ortho, Allergan, Cellgene, and other pharmaceutical companies.
MILAN – according to Dee Anna Glaser, MD.
Speaking at the World Congress of Dermatology, Dr. Glaser, director of clinical research and interim chair of the department of dermatology at Saint Louis University, said that in her practice, acne and actinic keratosis are the most common medical indications for chemical peels and that “acne is just a winner all the way around.”
For acne, she added: “Chemical peels can help both the comedonal and the inflammatory component. It should probably be combined with other therapies, and it does produce both an exfoliative and an anti-inflammatory benefit,.”
A variety of chemical peel formulations can be considered for acne, Dr. Glaser noted. “Typically, you’re going to use a light chemical peel,” such as glycolic or salicylic acid. Other options include Jessner’s solution or a light trichloroacetic acid formulation, she said, adding that tretinoin alone can also be considered.
In choosing between glycolic and salicylic acid, Dr. Glaser said, “salicylic acid should theoretically be the best agent because it is lipophilic and the glycolic acid is hydrophilic.” The reality of how these agents perform clinically, though, may sort out differently.
Dr. Glaser pointed to a double-blind, randomized controlled trial of the two agents in 20 women with facial acne. The severity of participants’ inflammatory acne was mild to moderate, with an average of 27 inflammatory lesions, and they had been on a stable prescription or over-the-counter acne regimen for at least 2 months (Dermatol Surg. 2008 Jan;34[1]:45-50).
Patients received six peels – one every 2 weeks – with 30% glycolic acid (an alpha-hydroxy acid) and 30% salicylic acid (a beta-hydroxy acid) in the split-face study.
All participants started at 4 minutes of exposure and increased up to 5 minutes as tolerated, although timing is only really important for glycolic acid, the same duration of exposure was maintained for each agent for the sake of consistency between arms, said Dr. Glaser, one of the investigators.
Sharing photographs of study participants, she observed that after six peels, “there really isn’t a significant difference.” Therefore, she added, “even though salicylic acid should be better, you can see that glycolic acid really held its own in this study.”
Dr. Glaser pointed out that a trend was seen for slightly better results with salicylic acid and results with this agent were more durable than those seen with glycolic acid. Patients reported fewer side effects on the beta-hydroxy–treated side as well.
She referred to another study, conducted in Japan, that used a double-blind, split-face design to compare 40% glycolic acid with a placebo that had a similarly low pH of 2.0. The 26 patients with moderate acne received five peels on a biweekly schedule, with glycolic acid significantly outperforming placebo. Among acne subtypes, noninflammatory acne improved more than inflammatory acne with glycolic acid (Dermatol Surg. 2014 Mar;40[3]:314-22).
Dr. Glaser said that in her own practice, she still tries to use salicylic acid for her acne patients,” though some patients prefer the experience of a glycolic acid peel, with which there’s likely to be less pain. “So if you have a preference, or your patient has a preference, you will probably be able to use the acid that works best for you,” she said.
Whatever peel is chosen, it should be considered an adjuvant to other topical and systemic acne therapies, Dr. Glaser stressed. “To maintain the results, you really do need to maintain the patient on some sort of standard acne therapy that you would normally do.”
Peels can also be an effective part of a multipronged approach that includes laser therapy and intralesional steroids, she said. However, peels can be considered for monotherapy in patients who don’t tolerate other acne therapies, and they can be used safely in pregnancy, she said.
As with all such treatments, dermatologists should remember to consider and counsel about herpes simplex virus prophylaxis and sun protection.
Dr. Glaser reported financial relationships with Galderma, Ulthera, Ortho, Allergan, Cellgene, and other pharmaceutical companies.
MILAN – according to Dee Anna Glaser, MD.
Speaking at the World Congress of Dermatology, Dr. Glaser, director of clinical research and interim chair of the department of dermatology at Saint Louis University, said that in her practice, acne and actinic keratosis are the most common medical indications for chemical peels and that “acne is just a winner all the way around.”
For acne, she added: “Chemical peels can help both the comedonal and the inflammatory component. It should probably be combined with other therapies, and it does produce both an exfoliative and an anti-inflammatory benefit,.”
A variety of chemical peel formulations can be considered for acne, Dr. Glaser noted. “Typically, you’re going to use a light chemical peel,” such as glycolic or salicylic acid. Other options include Jessner’s solution or a light trichloroacetic acid formulation, she said, adding that tretinoin alone can also be considered.
In choosing between glycolic and salicylic acid, Dr. Glaser said, “salicylic acid should theoretically be the best agent because it is lipophilic and the glycolic acid is hydrophilic.” The reality of how these agents perform clinically, though, may sort out differently.
Dr. Glaser pointed to a double-blind, randomized controlled trial of the two agents in 20 women with facial acne. The severity of participants’ inflammatory acne was mild to moderate, with an average of 27 inflammatory lesions, and they had been on a stable prescription or over-the-counter acne regimen for at least 2 months (Dermatol Surg. 2008 Jan;34[1]:45-50).
Patients received six peels – one every 2 weeks – with 30% glycolic acid (an alpha-hydroxy acid) and 30% salicylic acid (a beta-hydroxy acid) in the split-face study.
All participants started at 4 minutes of exposure and increased up to 5 minutes as tolerated, although timing is only really important for glycolic acid, the same duration of exposure was maintained for each agent for the sake of consistency between arms, said Dr. Glaser, one of the investigators.
Sharing photographs of study participants, she observed that after six peels, “there really isn’t a significant difference.” Therefore, she added, “even though salicylic acid should be better, you can see that glycolic acid really held its own in this study.”
Dr. Glaser pointed out that a trend was seen for slightly better results with salicylic acid and results with this agent were more durable than those seen with glycolic acid. Patients reported fewer side effects on the beta-hydroxy–treated side as well.
She referred to another study, conducted in Japan, that used a double-blind, split-face design to compare 40% glycolic acid with a placebo that had a similarly low pH of 2.0. The 26 patients with moderate acne received five peels on a biweekly schedule, with glycolic acid significantly outperforming placebo. Among acne subtypes, noninflammatory acne improved more than inflammatory acne with glycolic acid (Dermatol Surg. 2014 Mar;40[3]:314-22).
Dr. Glaser said that in her own practice, she still tries to use salicylic acid for her acne patients,” though some patients prefer the experience of a glycolic acid peel, with which there’s likely to be less pain. “So if you have a preference, or your patient has a preference, you will probably be able to use the acid that works best for you,” she said.
Whatever peel is chosen, it should be considered an adjuvant to other topical and systemic acne therapies, Dr. Glaser stressed. “To maintain the results, you really do need to maintain the patient on some sort of standard acne therapy that you would normally do.”
Peels can also be an effective part of a multipronged approach that includes laser therapy and intralesional steroids, she said. However, peels can be considered for monotherapy in patients who don’t tolerate other acne therapies, and they can be used safely in pregnancy, she said.
As with all such treatments, dermatologists should remember to consider and counsel about herpes simplex virus prophylaxis and sun protection.
Dr. Glaser reported financial relationships with Galderma, Ulthera, Ortho, Allergan, Cellgene, and other pharmaceutical companies.
EXPERT ANALYSIS FROM WCD2019
Lenabasum, a novel cannabinoid, shows promise in dermatomyositis
MILAN – according to Victoria Werth, MD, who presented early-stage findings at the World Congress of Dermatology.
Lenabasum – previously known as anabasum – is a synthetic cannabinoid that binds to the CB2 receptor present on a variety of cells, including lymphocytes, explained Dr. Werth, professor of medicine at the University of Pennsylvania, Philadelphia, and chief of dermatology at the Philadelphia Veterans Administration Hospital. The nonpsychoactive compound’s mechanism of action helps prevent tissue thickening and fibrosis. In addition to its potential for dermatomyositis treatment, it is also being investigated as a treatment for cystic fibrosis, scleroderma, and lupus.
Dr. Werth added that earlier in vitro work with peripheral blood mononuclear cells of patients with dermatomyositis showed that lenabasum markedly suppressed the cells’ secretion of tumor necrosis factor–alpha, interferon-alpha, and interferon-beta (J Invest Dermatol. 2017 Nov;137[11]:2445-7). A randomized, placebo-controlled trial tested lenabasum, known in the trial as JBT-101, in 22 patients with skin-predominant myositis. The study was structured so patients took a half dose of lenabasum for 1 month, followed by 2 months of taking a full dose, and finally 1 month with no lenabasum dosing. Compared with placebo, scores on the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) were significantly improved with full dosing of lenabasum (P = .02), Dr. Werth said.
In this 16-week trial, the mean change in CDASI score dropped for participants in both the lenabasum and placebo groups for the first 4 weeks. After that, however, those taking lenabasum saw an improvement of about 8 points from baseline CDASI score at 8 weeks, while those taking placebo had a decline of 3 points (P = .05). The differences remained significant at trial’s end.
Patient-reported outcomes for pain were significantly better with lenabasum, with patients on lenabasum recording a decrease on the Patient-Reported Outcomes Measurement Information System–29 pain interference scale, while patients on placebo reported an increase in pain by the end of the study period (P = .026). Scores on two other patient-reported dermatomyositis scales were numerically improved for patients taking lenabasum, but the differences from the patients on placebo were not statistically significant, Dr. Werth said.
However, patients in the initial clinical trial were given the opportunity to continue in a long-term extension arm, and that group has seen the clinician-rated CDASI scores continue to fall, with a mean decrease of 22 points from baseline (about 12 further points from the mean for those on lenabasum in the initial trial) at the 68-week mark, she added.
Itch scores continued to drop as well, with a reduction of 3.7 points on the 5-D Itch scale by 68 weeks; at 16 weeks, the reduction for the lenabasum arm had been 1.3 points.
Skin samples taken from trial participants showed many fewer CD4 cells in those taking lenabasum, compared with placebo at week 12 of the initial study. Interferon-beta and -gamma levels also dropped in those taking lenabasum, but not in the placebo arm.
“Lenabasum has effects on cytokine signatures and inflammatory cells correlating with response to therapy,” Dr. Werth said, adding that the findings gave support for a planned global phase 3 clinical trial of lenabasum in dermatomyositis.
Dr. Werth reported receiving grants from Pfizer and Corbus, and consulting fees from Pfizer, Janssen, Neovacs, Idera Pharmaceuticals, Octapharma, CSL Behring, and Corbus Pharmaceuticals. The study was funded by Corbus, the National Institutes of Health, and the University of Pennsylvania.
Cannabinoids represent a broad class of chemical compounds originally comprised only phytocannabinoids – cannabinoids produced by the cannabis plant. The best-known and most-studied cannabinoids are tetrahydrocannabinol and cannabidiol, which are plant-derived, or “phyto”, cannabinoids. While tetrahydrocannabinol is best known for its mind-altering, munchy-causing properties, it was in fact the study of this illegal substance that led to the groundbreaking discovery of the human endocannabinoid system. (Meaning, we make our very own cannabinoids and receptors for them, which make up an extraordinary biological network that play a role in everything from sensations of pain and itch to mood, inflammation regulation, and wound healing.) Gold star for drugs?
It was this understanding that led to the development of synthetic cannabinoids, like ajulemic acid (aka lenabasum), all of which has created a flurry of investigative productivity and creativity to capitalize on these bioactive agents. That said, development, research and development, and even education in/on this area has been hindered for many years because of both regulatory limitations and negative public perceptions, given the Schedule 1 designation of every component of the cannabis plant (even nonpsychoactive actives) up until a few months ago with the passing of the Farm Bill (which made hemp legal).
However, the interest level among consumers, patients, and physicians is quickly growing regarding the effectiveness of cannabinoids in the treatment of a laundry list of skin conditions and symptoms, including psoriasis, atopic dermatitis, and wound healing. But there are just so many unanswered questions for anyone to be certain about the benefits. We recently published a study surveying 531 dermatologists to get a better idea about our community’s attitude and awareness on cannabinoids as therapeutics, and it turned out there’s a lot we all need to learn (J Drugs Dermatol. 2018 Dec 1;17[12]:1273-8). Some highlights of our findings:
- Dermatologists are being approached by their patients with questions on this subject matter, and this is more likely to occur in states where medical cannabis is legalized.
- While more than 90% of respondents agreed that this is an important area for research and development and 86% thought medical cannabinoids should be legal, more than 80% were not comfortable with their understanding or knowledge on this subject matter, which is not surprising given that 64% of respondents incorrectly responded that cannabidiol has psychoactive effects.
With the fast-tracking of lenabasum down the Food and Drug Administration approval pathway for not one but two diseases we as dermatologists manage, I am optimistic that this addition to our much needed armament will serve as further stimulus to expand the role of cannabinoids in the management of dermatologic diseases and spotlight the need for more education and research in this vastly underrecognized yet intriguing and promising space.
Adam Friedman, MD, is professor and interim chair of dermatology, director of translational research, and director of the supportive oncodermatology clinic at George Washington University, Washington, and is on the board of Dermatology News. Dr. Friedman is on the scientific advisory board for Corbus Pharmaceuticals.
Cannabinoids represent a broad class of chemical compounds originally comprised only phytocannabinoids – cannabinoids produced by the cannabis plant. The best-known and most-studied cannabinoids are tetrahydrocannabinol and cannabidiol, which are plant-derived, or “phyto”, cannabinoids. While tetrahydrocannabinol is best known for its mind-altering, munchy-causing properties, it was in fact the study of this illegal substance that led to the groundbreaking discovery of the human endocannabinoid system. (Meaning, we make our very own cannabinoids and receptors for them, which make up an extraordinary biological network that play a role in everything from sensations of pain and itch to mood, inflammation regulation, and wound healing.) Gold star for drugs?
It was this understanding that led to the development of synthetic cannabinoids, like ajulemic acid (aka lenabasum), all of which has created a flurry of investigative productivity and creativity to capitalize on these bioactive agents. That said, development, research and development, and even education in/on this area has been hindered for many years because of both regulatory limitations and negative public perceptions, given the Schedule 1 designation of every component of the cannabis plant (even nonpsychoactive actives) up until a few months ago with the passing of the Farm Bill (which made hemp legal).
However, the interest level among consumers, patients, and physicians is quickly growing regarding the effectiveness of cannabinoids in the treatment of a laundry list of skin conditions and symptoms, including psoriasis, atopic dermatitis, and wound healing. But there are just so many unanswered questions for anyone to be certain about the benefits. We recently published a study surveying 531 dermatologists to get a better idea about our community’s attitude and awareness on cannabinoids as therapeutics, and it turned out there’s a lot we all need to learn (J Drugs Dermatol. 2018 Dec 1;17[12]:1273-8). Some highlights of our findings:
- Dermatologists are being approached by their patients with questions on this subject matter, and this is more likely to occur in states where medical cannabis is legalized.
- While more than 90% of respondents agreed that this is an important area for research and development and 86% thought medical cannabinoids should be legal, more than 80% were not comfortable with their understanding or knowledge on this subject matter, which is not surprising given that 64% of respondents incorrectly responded that cannabidiol has psychoactive effects.
With the fast-tracking of lenabasum down the Food and Drug Administration approval pathway for not one but two diseases we as dermatologists manage, I am optimistic that this addition to our much needed armament will serve as further stimulus to expand the role of cannabinoids in the management of dermatologic diseases and spotlight the need for more education and research in this vastly underrecognized yet intriguing and promising space.
Adam Friedman, MD, is professor and interim chair of dermatology, director of translational research, and director of the supportive oncodermatology clinic at George Washington University, Washington, and is on the board of Dermatology News. Dr. Friedman is on the scientific advisory board for Corbus Pharmaceuticals.
Cannabinoids represent a broad class of chemical compounds originally comprised only phytocannabinoids – cannabinoids produced by the cannabis plant. The best-known and most-studied cannabinoids are tetrahydrocannabinol and cannabidiol, which are plant-derived, or “phyto”, cannabinoids. While tetrahydrocannabinol is best known for its mind-altering, munchy-causing properties, it was in fact the study of this illegal substance that led to the groundbreaking discovery of the human endocannabinoid system. (Meaning, we make our very own cannabinoids and receptors for them, which make up an extraordinary biological network that play a role in everything from sensations of pain and itch to mood, inflammation regulation, and wound healing.) Gold star for drugs?
It was this understanding that led to the development of synthetic cannabinoids, like ajulemic acid (aka lenabasum), all of which has created a flurry of investigative productivity and creativity to capitalize on these bioactive agents. That said, development, research and development, and even education in/on this area has been hindered for many years because of both regulatory limitations and negative public perceptions, given the Schedule 1 designation of every component of the cannabis plant (even nonpsychoactive actives) up until a few months ago with the passing of the Farm Bill (which made hemp legal).
However, the interest level among consumers, patients, and physicians is quickly growing regarding the effectiveness of cannabinoids in the treatment of a laundry list of skin conditions and symptoms, including psoriasis, atopic dermatitis, and wound healing. But there are just so many unanswered questions for anyone to be certain about the benefits. We recently published a study surveying 531 dermatologists to get a better idea about our community’s attitude and awareness on cannabinoids as therapeutics, and it turned out there’s a lot we all need to learn (J Drugs Dermatol. 2018 Dec 1;17[12]:1273-8). Some highlights of our findings:
- Dermatologists are being approached by their patients with questions on this subject matter, and this is more likely to occur in states where medical cannabis is legalized.
- While more than 90% of respondents agreed that this is an important area for research and development and 86% thought medical cannabinoids should be legal, more than 80% were not comfortable with their understanding or knowledge on this subject matter, which is not surprising given that 64% of respondents incorrectly responded that cannabidiol has psychoactive effects.
With the fast-tracking of lenabasum down the Food and Drug Administration approval pathway for not one but two diseases we as dermatologists manage, I am optimistic that this addition to our much needed armament will serve as further stimulus to expand the role of cannabinoids in the management of dermatologic diseases and spotlight the need for more education and research in this vastly underrecognized yet intriguing and promising space.
Adam Friedman, MD, is professor and interim chair of dermatology, director of translational research, and director of the supportive oncodermatology clinic at George Washington University, Washington, and is on the board of Dermatology News. Dr. Friedman is on the scientific advisory board for Corbus Pharmaceuticals.
MILAN – according to Victoria Werth, MD, who presented early-stage findings at the World Congress of Dermatology.
Lenabasum – previously known as anabasum – is a synthetic cannabinoid that binds to the CB2 receptor present on a variety of cells, including lymphocytes, explained Dr. Werth, professor of medicine at the University of Pennsylvania, Philadelphia, and chief of dermatology at the Philadelphia Veterans Administration Hospital. The nonpsychoactive compound’s mechanism of action helps prevent tissue thickening and fibrosis. In addition to its potential for dermatomyositis treatment, it is also being investigated as a treatment for cystic fibrosis, scleroderma, and lupus.
Dr. Werth added that earlier in vitro work with peripheral blood mononuclear cells of patients with dermatomyositis showed that lenabasum markedly suppressed the cells’ secretion of tumor necrosis factor–alpha, interferon-alpha, and interferon-beta (J Invest Dermatol. 2017 Nov;137[11]:2445-7). A randomized, placebo-controlled trial tested lenabasum, known in the trial as JBT-101, in 22 patients with skin-predominant myositis. The study was structured so patients took a half dose of lenabasum for 1 month, followed by 2 months of taking a full dose, and finally 1 month with no lenabasum dosing. Compared with placebo, scores on the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) were significantly improved with full dosing of lenabasum (P = .02), Dr. Werth said.
In this 16-week trial, the mean change in CDASI score dropped for participants in both the lenabasum and placebo groups for the first 4 weeks. After that, however, those taking lenabasum saw an improvement of about 8 points from baseline CDASI score at 8 weeks, while those taking placebo had a decline of 3 points (P = .05). The differences remained significant at trial’s end.
Patient-reported outcomes for pain were significantly better with lenabasum, with patients on lenabasum recording a decrease on the Patient-Reported Outcomes Measurement Information System–29 pain interference scale, while patients on placebo reported an increase in pain by the end of the study period (P = .026). Scores on two other patient-reported dermatomyositis scales were numerically improved for patients taking lenabasum, but the differences from the patients on placebo were not statistically significant, Dr. Werth said.
However, patients in the initial clinical trial were given the opportunity to continue in a long-term extension arm, and that group has seen the clinician-rated CDASI scores continue to fall, with a mean decrease of 22 points from baseline (about 12 further points from the mean for those on lenabasum in the initial trial) at the 68-week mark, she added.
Itch scores continued to drop as well, with a reduction of 3.7 points on the 5-D Itch scale by 68 weeks; at 16 weeks, the reduction for the lenabasum arm had been 1.3 points.
Skin samples taken from trial participants showed many fewer CD4 cells in those taking lenabasum, compared with placebo at week 12 of the initial study. Interferon-beta and -gamma levels also dropped in those taking lenabasum, but not in the placebo arm.
“Lenabasum has effects on cytokine signatures and inflammatory cells correlating with response to therapy,” Dr. Werth said, adding that the findings gave support for a planned global phase 3 clinical trial of lenabasum in dermatomyositis.
Dr. Werth reported receiving grants from Pfizer and Corbus, and consulting fees from Pfizer, Janssen, Neovacs, Idera Pharmaceuticals, Octapharma, CSL Behring, and Corbus Pharmaceuticals. The study was funded by Corbus, the National Institutes of Health, and the University of Pennsylvania.
MILAN – according to Victoria Werth, MD, who presented early-stage findings at the World Congress of Dermatology.
Lenabasum – previously known as anabasum – is a synthetic cannabinoid that binds to the CB2 receptor present on a variety of cells, including lymphocytes, explained Dr. Werth, professor of medicine at the University of Pennsylvania, Philadelphia, and chief of dermatology at the Philadelphia Veterans Administration Hospital. The nonpsychoactive compound’s mechanism of action helps prevent tissue thickening and fibrosis. In addition to its potential for dermatomyositis treatment, it is also being investigated as a treatment for cystic fibrosis, scleroderma, and lupus.
Dr. Werth added that earlier in vitro work with peripheral blood mononuclear cells of patients with dermatomyositis showed that lenabasum markedly suppressed the cells’ secretion of tumor necrosis factor–alpha, interferon-alpha, and interferon-beta (J Invest Dermatol. 2017 Nov;137[11]:2445-7). A randomized, placebo-controlled trial tested lenabasum, known in the trial as JBT-101, in 22 patients with skin-predominant myositis. The study was structured so patients took a half dose of lenabasum for 1 month, followed by 2 months of taking a full dose, and finally 1 month with no lenabasum dosing. Compared with placebo, scores on the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) were significantly improved with full dosing of lenabasum (P = .02), Dr. Werth said.
In this 16-week trial, the mean change in CDASI score dropped for participants in both the lenabasum and placebo groups for the first 4 weeks. After that, however, those taking lenabasum saw an improvement of about 8 points from baseline CDASI score at 8 weeks, while those taking placebo had a decline of 3 points (P = .05). The differences remained significant at trial’s end.
Patient-reported outcomes for pain were significantly better with lenabasum, with patients on lenabasum recording a decrease on the Patient-Reported Outcomes Measurement Information System–29 pain interference scale, while patients on placebo reported an increase in pain by the end of the study period (P = .026). Scores on two other patient-reported dermatomyositis scales were numerically improved for patients taking lenabasum, but the differences from the patients on placebo were not statistically significant, Dr. Werth said.
However, patients in the initial clinical trial were given the opportunity to continue in a long-term extension arm, and that group has seen the clinician-rated CDASI scores continue to fall, with a mean decrease of 22 points from baseline (about 12 further points from the mean for those on lenabasum in the initial trial) at the 68-week mark, she added.
Itch scores continued to drop as well, with a reduction of 3.7 points on the 5-D Itch scale by 68 weeks; at 16 weeks, the reduction for the lenabasum arm had been 1.3 points.
Skin samples taken from trial participants showed many fewer CD4 cells in those taking lenabasum, compared with placebo at week 12 of the initial study. Interferon-beta and -gamma levels also dropped in those taking lenabasum, but not in the placebo arm.
“Lenabasum has effects on cytokine signatures and inflammatory cells correlating with response to therapy,” Dr. Werth said, adding that the findings gave support for a planned global phase 3 clinical trial of lenabasum in dermatomyositis.
Dr. Werth reported receiving grants from Pfizer and Corbus, and consulting fees from Pfizer, Janssen, Neovacs, Idera Pharmaceuticals, Octapharma, CSL Behring, and Corbus Pharmaceuticals. The study was funded by Corbus, the National Institutes of Health, and the University of Pennsylvania.
EXPERT ANALYSIS FROM WCD2019
Novel topical psoriasis treatment targets nerve pathways
MILAN – A novel topical nonsteroidal treatment for psoriasis showed sufficient efficacy in phase 2b clinical trials to proceed to phase 3 studies, with improvements in severity, pain, and burning in adults with mild to moderate psoriasis.
At the end of 12 weeks of treatment, 29% of patients receiving the medication – which targets nerve pathways – experienced a decrease of at least 2 grades on the 5-point Investigator’s Global Assessment (IGA) scale, compared with 13% of those receiving the topical vehicle only (P = .036). A similar proportion of patients achieved 75% improvement on the Psoriasis Area and Severity Index (PASI-75)compared with those on vehicle alone (27% versus 13%; P = .045).
, said Paul F. Lizzul, MD, PhD, presenting the findings during a late-breaking abstract session at the World Congress of Dermatology.
Pruritus severity also dropped by about 60%, but the decrease did not differ significantly from the change seen with vehicle alone, said Dr. Lizzul, chief medical officer for Sienna Biopharmaceuticals, Westlake Village, Calif., which funded the study. He and his coinvestigators found this “interesting, surprising, and different from what we had seen previously,” he said. “We think a few things happened here,” including intensive querying on itch by means of daily diaries, a different approach than had been taken in the investigator’s earlier SNA-120 trials. “We think in this way we probably biased patients’ expectations, altering reporting on this subjective measure,” he added.
“There’s been really a lack of innovation in the topical world in developing nonsteroidal therapies for the majority of patients who are treated with topicals, said Dr. Lizzul. Keratinocytes within psoriatic plaques are known to have elevated levels of nerve growth factor (NGF), he explained. Together with tropomyosin receptor kinase A (TrkA), NGF is implicated in the pathogenesis of psoriasis; it stimulates keratinocyte hyperproliferation, is a factor in neurogenic inflammation, and contributes to pruritus. Upregulation of TrkA expression is seen in nerve fibers within pruritic psoriasis plaques as well, said Dr. Lizzul, senior author of the study. (The first author was Kristina Callis Duffin, MD, cochair of the dermatology department at the University of Utah, Salt Lake City.)
In fact, the pruritus that plagues many psoriasis patients, said Dr. Lizzul, may “serve as a clinical biomarker for elevated NGF/TrkA expression.” And certain clinical phenomena observed in psoriasis, such as the Koebner phenomenon and plaque resolution along the path of damaged nerves, provide other clues. “Clearly, astute clinicians going back many, many years have recognized the very important role that nerves and neuropeptides play in psoriasis,” he added.
SNA-120 targets NGF TrKA activity, and “achieves high local drug concentration in the skin, with low systemic availability,” he said.
The randomized, double-blind, vehicle-controlled study enrolled 208 adults with mild to moderate psoriasis (scores of 2 or 3 on the IGA), with pruritus of at least moderate intensity (5 or higher on a 10-point itch numeric rating scale, or I-NRS). The mean age of the patients was 50 years, and about half were male. Most (84%-90% across study arms) were white. At baseline, the mean I-NRS was 7.3-7.4, and the mean PASI score at baseline ranged from 5.9 to 6.5.
Patients were randomized to receive SNA-120 twice daily at either 0.05% (70 patients) or 0.5% (69 patients) in an ointment formulation, or vehicle alone twice daily (69 patients). Efficacy was tracked by measuring decrease in IGA by one or two grades, the number of patients achieving PASI-50 and PASI-75, reduction in itch, and a composite of a decrease of at least 2 grades on the IGA and having clear or almost clear skin.
The investigators also tracked reduction in burning and pain as measured on a 10-point numeric rating scale. Though itch scores didn’t differ significantly from reductions seen with the topical vehicle alone, pain and burning were both reduced significantly compared with vehicle by week 12 of the study (P = .033 for pain; P = .043 for burning).
All improvements were seen only with the lower dose, not the 0.5% dose of SNA-120, noted Dr. Lizzul, adding: “This is not necessarily surprising in the world of kinase inhibitors, where you can see these J-shaped or inverse dose-response curves.”
In addition to recording adverse events, the researchers assessed safety by obtaining laboratory values and electrocardiograms. Plasma SNA-120 levels at study weeks 2, 4, and 8 were obtained for pharmacokinetic analysis. Systemic uptake was virtually nil, and the safety profile overall was good, said Dr. Lizzul.
Next steps are phase 3 clinical trials that will evaluate global improvement as well as pain, burning, and itch in psoriasis, he noted.
Dr. Lizzul is an employee of Sienna Biopharmaceuticals, which is developing SNA-120.
MILAN – A novel topical nonsteroidal treatment for psoriasis showed sufficient efficacy in phase 2b clinical trials to proceed to phase 3 studies, with improvements in severity, pain, and burning in adults with mild to moderate psoriasis.
At the end of 12 weeks of treatment, 29% of patients receiving the medication – which targets nerve pathways – experienced a decrease of at least 2 grades on the 5-point Investigator’s Global Assessment (IGA) scale, compared with 13% of those receiving the topical vehicle only (P = .036). A similar proportion of patients achieved 75% improvement on the Psoriasis Area and Severity Index (PASI-75)compared with those on vehicle alone (27% versus 13%; P = .045).
, said Paul F. Lizzul, MD, PhD, presenting the findings during a late-breaking abstract session at the World Congress of Dermatology.
Pruritus severity also dropped by about 60%, but the decrease did not differ significantly from the change seen with vehicle alone, said Dr. Lizzul, chief medical officer for Sienna Biopharmaceuticals, Westlake Village, Calif., which funded the study. He and his coinvestigators found this “interesting, surprising, and different from what we had seen previously,” he said. “We think a few things happened here,” including intensive querying on itch by means of daily diaries, a different approach than had been taken in the investigator’s earlier SNA-120 trials. “We think in this way we probably biased patients’ expectations, altering reporting on this subjective measure,” he added.
“There’s been really a lack of innovation in the topical world in developing nonsteroidal therapies for the majority of patients who are treated with topicals, said Dr. Lizzul. Keratinocytes within psoriatic plaques are known to have elevated levels of nerve growth factor (NGF), he explained. Together with tropomyosin receptor kinase A (TrkA), NGF is implicated in the pathogenesis of psoriasis; it stimulates keratinocyte hyperproliferation, is a factor in neurogenic inflammation, and contributes to pruritus. Upregulation of TrkA expression is seen in nerve fibers within pruritic psoriasis plaques as well, said Dr. Lizzul, senior author of the study. (The first author was Kristina Callis Duffin, MD, cochair of the dermatology department at the University of Utah, Salt Lake City.)
In fact, the pruritus that plagues many psoriasis patients, said Dr. Lizzul, may “serve as a clinical biomarker for elevated NGF/TrkA expression.” And certain clinical phenomena observed in psoriasis, such as the Koebner phenomenon and plaque resolution along the path of damaged nerves, provide other clues. “Clearly, astute clinicians going back many, many years have recognized the very important role that nerves and neuropeptides play in psoriasis,” he added.
SNA-120 targets NGF TrKA activity, and “achieves high local drug concentration in the skin, with low systemic availability,” he said.
The randomized, double-blind, vehicle-controlled study enrolled 208 adults with mild to moderate psoriasis (scores of 2 or 3 on the IGA), with pruritus of at least moderate intensity (5 or higher on a 10-point itch numeric rating scale, or I-NRS). The mean age of the patients was 50 years, and about half were male. Most (84%-90% across study arms) were white. At baseline, the mean I-NRS was 7.3-7.4, and the mean PASI score at baseline ranged from 5.9 to 6.5.
Patients were randomized to receive SNA-120 twice daily at either 0.05% (70 patients) or 0.5% (69 patients) in an ointment formulation, or vehicle alone twice daily (69 patients). Efficacy was tracked by measuring decrease in IGA by one or two grades, the number of patients achieving PASI-50 and PASI-75, reduction in itch, and a composite of a decrease of at least 2 grades on the IGA and having clear or almost clear skin.
The investigators also tracked reduction in burning and pain as measured on a 10-point numeric rating scale. Though itch scores didn’t differ significantly from reductions seen with the topical vehicle alone, pain and burning were both reduced significantly compared with vehicle by week 12 of the study (P = .033 for pain; P = .043 for burning).
All improvements were seen only with the lower dose, not the 0.5% dose of SNA-120, noted Dr. Lizzul, adding: “This is not necessarily surprising in the world of kinase inhibitors, where you can see these J-shaped or inverse dose-response curves.”
In addition to recording adverse events, the researchers assessed safety by obtaining laboratory values and electrocardiograms. Plasma SNA-120 levels at study weeks 2, 4, and 8 were obtained for pharmacokinetic analysis. Systemic uptake was virtually nil, and the safety profile overall was good, said Dr. Lizzul.
Next steps are phase 3 clinical trials that will evaluate global improvement as well as pain, burning, and itch in psoriasis, he noted.
Dr. Lizzul is an employee of Sienna Biopharmaceuticals, which is developing SNA-120.
MILAN – A novel topical nonsteroidal treatment for psoriasis showed sufficient efficacy in phase 2b clinical trials to proceed to phase 3 studies, with improvements in severity, pain, and burning in adults with mild to moderate psoriasis.
At the end of 12 weeks of treatment, 29% of patients receiving the medication – which targets nerve pathways – experienced a decrease of at least 2 grades on the 5-point Investigator’s Global Assessment (IGA) scale, compared with 13% of those receiving the topical vehicle only (P = .036). A similar proportion of patients achieved 75% improvement on the Psoriasis Area and Severity Index (PASI-75)compared with those on vehicle alone (27% versus 13%; P = .045).
, said Paul F. Lizzul, MD, PhD, presenting the findings during a late-breaking abstract session at the World Congress of Dermatology.
Pruritus severity also dropped by about 60%, but the decrease did not differ significantly from the change seen with vehicle alone, said Dr. Lizzul, chief medical officer for Sienna Biopharmaceuticals, Westlake Village, Calif., which funded the study. He and his coinvestigators found this “interesting, surprising, and different from what we had seen previously,” he said. “We think a few things happened here,” including intensive querying on itch by means of daily diaries, a different approach than had been taken in the investigator’s earlier SNA-120 trials. “We think in this way we probably biased patients’ expectations, altering reporting on this subjective measure,” he added.
“There’s been really a lack of innovation in the topical world in developing nonsteroidal therapies for the majority of patients who are treated with topicals, said Dr. Lizzul. Keratinocytes within psoriatic plaques are known to have elevated levels of nerve growth factor (NGF), he explained. Together with tropomyosin receptor kinase A (TrkA), NGF is implicated in the pathogenesis of psoriasis; it stimulates keratinocyte hyperproliferation, is a factor in neurogenic inflammation, and contributes to pruritus. Upregulation of TrkA expression is seen in nerve fibers within pruritic psoriasis plaques as well, said Dr. Lizzul, senior author of the study. (The first author was Kristina Callis Duffin, MD, cochair of the dermatology department at the University of Utah, Salt Lake City.)
In fact, the pruritus that plagues many psoriasis patients, said Dr. Lizzul, may “serve as a clinical biomarker for elevated NGF/TrkA expression.” And certain clinical phenomena observed in psoriasis, such as the Koebner phenomenon and plaque resolution along the path of damaged nerves, provide other clues. “Clearly, astute clinicians going back many, many years have recognized the very important role that nerves and neuropeptides play in psoriasis,” he added.
SNA-120 targets NGF TrKA activity, and “achieves high local drug concentration in the skin, with low systemic availability,” he said.
The randomized, double-blind, vehicle-controlled study enrolled 208 adults with mild to moderate psoriasis (scores of 2 or 3 on the IGA), with pruritus of at least moderate intensity (5 or higher on a 10-point itch numeric rating scale, or I-NRS). The mean age of the patients was 50 years, and about half were male. Most (84%-90% across study arms) were white. At baseline, the mean I-NRS was 7.3-7.4, and the mean PASI score at baseline ranged from 5.9 to 6.5.
Patients were randomized to receive SNA-120 twice daily at either 0.05% (70 patients) or 0.5% (69 patients) in an ointment formulation, or vehicle alone twice daily (69 patients). Efficacy was tracked by measuring decrease in IGA by one or two grades, the number of patients achieving PASI-50 and PASI-75, reduction in itch, and a composite of a decrease of at least 2 grades on the IGA and having clear or almost clear skin.
The investigators also tracked reduction in burning and pain as measured on a 10-point numeric rating scale. Though itch scores didn’t differ significantly from reductions seen with the topical vehicle alone, pain and burning were both reduced significantly compared with vehicle by week 12 of the study (P = .033 for pain; P = .043 for burning).
All improvements were seen only with the lower dose, not the 0.5% dose of SNA-120, noted Dr. Lizzul, adding: “This is not necessarily surprising in the world of kinase inhibitors, where you can see these J-shaped or inverse dose-response curves.”
In addition to recording adverse events, the researchers assessed safety by obtaining laboratory values and electrocardiograms. Plasma SNA-120 levels at study weeks 2, 4, and 8 were obtained for pharmacokinetic analysis. Systemic uptake was virtually nil, and the safety profile overall was good, said Dr. Lizzul.
Next steps are phase 3 clinical trials that will evaluate global improvement as well as pain, burning, and itch in psoriasis, he noted.
Dr. Lizzul is an employee of Sienna Biopharmaceuticals, which is developing SNA-120.
REPORTING FROM WCD2019
Round 1: Biologics, JAK inhibitors training up for atopic dermatitis ‘boxing match’
MILAN – Get ready for a “boxing match” (AD), Thomas Bieber, MD, PhD, said in an oral presentation at the World Congress of Dermatology.
“In one corner of the ring you will have the biologics, and in the other corner of the ring, you will have the Janus kinase (JAK) inhibitors and some other small molecules,” said Dr. Bieber, medical director of dermatology and allergy, at University Hospital Bonn, Germany.
There will be no winner-take-all scenario, since AD is a heterogeneous disease for which a variety of treatments will be needed, Dr. Bieber noted. However, he said, there are clear differences in mode of action, safety, mode of application, price, and more that will be important as dermatologists weigh the choice of biologics versus JAK inhibitors for a specific patient.
“Currently, dupilumab is the only one that is on the market (in the European Union) and this molecule is really a revolution for us,” Dr. Bieber said at the meeting. “But we will see in the next years, many, many other molecules coming up.”
Beyond dupilumab (Dupixent), the interleukin-4 (IL-4) receptor alpha antagonist approved by the Food and Drug Administration in 2017, biologics under development include tralokinumab, lebrikizumab, and nemolizumab, among others. Development on the small molecule side includes agents such as ZPL-389, a histamine H4 receptor agonist, but is dominated by JAK inhibitors such as baricitinib(Olumiant), approved by the FDA in 2018 for rheumatoid arthritis; upadacitinib; and abrocitinib, according to Dr. Bieber.
There are advantages and disadvantages to each class of molecule, he said. For example, JAK inhibitors act very rapidly to control itch and improve exacerbations, while biologics are “much slower” and provide delayed control of inflammation, he said. In terms of safety, by contrast, biologics probably offer a “better” benefit-to-risk ratio, with no risk for drug-drug interactions and no monitoring needed, while JAK inhibitors appear to have a “narrow” therapeutic window, with a risk for drug-drug interactions and a need for some monitoring, he said.
JAK inhibitors come in a tablet formulation, which, from the patient perspective, may be more convenient and acceptable compared with repeated injections of biologics every 2 or 4 weeks, Dr. Bieber noted. Another point potentially in favor of JAK inhibitors is price: “I think the current situation tells us clearly that the biologics are the more expensive drugs, while the small molecules typically are much less expensive,” he said.
One theoretical advantage of biologics, he said, is the potential for disease modification, while the disease-modifying potential of JAK inhibitors is unclear, as of yet. “We have not had enough experience with all these molecules in order to understand how we can do that particular job, in terms of switching off the disease,” he said.
In terms of the need for patient stratification in the future, it’s a draw between biologics and JAK inhibitors, Dr. Bieber said. “You will not see any of these drugs doing 100 percent of the job in 100 percent of the patients, so to me, currently from my understanding of this disease, there is no one-size-fits-all molecule.”
Toward that end, machine learning and artificial intelligence may aid in evaluating large amounts of data to better understand AD phenotypes. “That’s really something that is a particular kind of challenge in the next years, in order to improve at-the-end drug development, and the management of our patients,” he concluded.
Dr. Bieber reported disclosures related to LEO Pharmaceuticals, Regeneron, and Sanofi.
MILAN – Get ready for a “boxing match” (AD), Thomas Bieber, MD, PhD, said in an oral presentation at the World Congress of Dermatology.
“In one corner of the ring you will have the biologics, and in the other corner of the ring, you will have the Janus kinase (JAK) inhibitors and some other small molecules,” said Dr. Bieber, medical director of dermatology and allergy, at University Hospital Bonn, Germany.
There will be no winner-take-all scenario, since AD is a heterogeneous disease for which a variety of treatments will be needed, Dr. Bieber noted. However, he said, there are clear differences in mode of action, safety, mode of application, price, and more that will be important as dermatologists weigh the choice of biologics versus JAK inhibitors for a specific patient.
“Currently, dupilumab is the only one that is on the market (in the European Union) and this molecule is really a revolution for us,” Dr. Bieber said at the meeting. “But we will see in the next years, many, many other molecules coming up.”
Beyond dupilumab (Dupixent), the interleukin-4 (IL-4) receptor alpha antagonist approved by the Food and Drug Administration in 2017, biologics under development include tralokinumab, lebrikizumab, and nemolizumab, among others. Development on the small molecule side includes agents such as ZPL-389, a histamine H4 receptor agonist, but is dominated by JAK inhibitors such as baricitinib(Olumiant), approved by the FDA in 2018 for rheumatoid arthritis; upadacitinib; and abrocitinib, according to Dr. Bieber.
There are advantages and disadvantages to each class of molecule, he said. For example, JAK inhibitors act very rapidly to control itch and improve exacerbations, while biologics are “much slower” and provide delayed control of inflammation, he said. In terms of safety, by contrast, biologics probably offer a “better” benefit-to-risk ratio, with no risk for drug-drug interactions and no monitoring needed, while JAK inhibitors appear to have a “narrow” therapeutic window, with a risk for drug-drug interactions and a need for some monitoring, he said.
JAK inhibitors come in a tablet formulation, which, from the patient perspective, may be more convenient and acceptable compared with repeated injections of biologics every 2 or 4 weeks, Dr. Bieber noted. Another point potentially in favor of JAK inhibitors is price: “I think the current situation tells us clearly that the biologics are the more expensive drugs, while the small molecules typically are much less expensive,” he said.
One theoretical advantage of biologics, he said, is the potential for disease modification, while the disease-modifying potential of JAK inhibitors is unclear, as of yet. “We have not had enough experience with all these molecules in order to understand how we can do that particular job, in terms of switching off the disease,” he said.
In terms of the need for patient stratification in the future, it’s a draw between biologics and JAK inhibitors, Dr. Bieber said. “You will not see any of these drugs doing 100 percent of the job in 100 percent of the patients, so to me, currently from my understanding of this disease, there is no one-size-fits-all molecule.”
Toward that end, machine learning and artificial intelligence may aid in evaluating large amounts of data to better understand AD phenotypes. “That’s really something that is a particular kind of challenge in the next years, in order to improve at-the-end drug development, and the management of our patients,” he concluded.
Dr. Bieber reported disclosures related to LEO Pharmaceuticals, Regeneron, and Sanofi.
MILAN – Get ready for a “boxing match” (AD), Thomas Bieber, MD, PhD, said in an oral presentation at the World Congress of Dermatology.
“In one corner of the ring you will have the biologics, and in the other corner of the ring, you will have the Janus kinase (JAK) inhibitors and some other small molecules,” said Dr. Bieber, medical director of dermatology and allergy, at University Hospital Bonn, Germany.
There will be no winner-take-all scenario, since AD is a heterogeneous disease for which a variety of treatments will be needed, Dr. Bieber noted. However, he said, there are clear differences in mode of action, safety, mode of application, price, and more that will be important as dermatologists weigh the choice of biologics versus JAK inhibitors for a specific patient.
“Currently, dupilumab is the only one that is on the market (in the European Union) and this molecule is really a revolution for us,” Dr. Bieber said at the meeting. “But we will see in the next years, many, many other molecules coming up.”
Beyond dupilumab (Dupixent), the interleukin-4 (IL-4) receptor alpha antagonist approved by the Food and Drug Administration in 2017, biologics under development include tralokinumab, lebrikizumab, and nemolizumab, among others. Development on the small molecule side includes agents such as ZPL-389, a histamine H4 receptor agonist, but is dominated by JAK inhibitors such as baricitinib(Olumiant), approved by the FDA in 2018 for rheumatoid arthritis; upadacitinib; and abrocitinib, according to Dr. Bieber.
There are advantages and disadvantages to each class of molecule, he said. For example, JAK inhibitors act very rapidly to control itch and improve exacerbations, while biologics are “much slower” and provide delayed control of inflammation, he said. In terms of safety, by contrast, biologics probably offer a “better” benefit-to-risk ratio, with no risk for drug-drug interactions and no monitoring needed, while JAK inhibitors appear to have a “narrow” therapeutic window, with a risk for drug-drug interactions and a need for some monitoring, he said.
JAK inhibitors come in a tablet formulation, which, from the patient perspective, may be more convenient and acceptable compared with repeated injections of biologics every 2 or 4 weeks, Dr. Bieber noted. Another point potentially in favor of JAK inhibitors is price: “I think the current situation tells us clearly that the biologics are the more expensive drugs, while the small molecules typically are much less expensive,” he said.
One theoretical advantage of biologics, he said, is the potential for disease modification, while the disease-modifying potential of JAK inhibitors is unclear, as of yet. “We have not had enough experience with all these molecules in order to understand how we can do that particular job, in terms of switching off the disease,” he said.
In terms of the need for patient stratification in the future, it’s a draw between biologics and JAK inhibitors, Dr. Bieber said. “You will not see any of these drugs doing 100 percent of the job in 100 percent of the patients, so to me, currently from my understanding of this disease, there is no one-size-fits-all molecule.”
Toward that end, machine learning and artificial intelligence may aid in evaluating large amounts of data to better understand AD phenotypes. “That’s really something that is a particular kind of challenge in the next years, in order to improve at-the-end drug development, and the management of our patients,” he concluded.
Dr. Bieber reported disclosures related to LEO Pharmaceuticals, Regeneron, and Sanofi.
EXPERT ANALYSIS FROM WCD2019
Ixekizumab boosts quality of life in genital psoriasis
MILAN – , according to data presented at the World Congress of Dermatology.
After 12 weeks of ixekizumab administration, nearly half of patients who received ixekizumab in the randomized, double-blind, placebo-controlled trial achieved a Dermatology Life Quality Index (DLQI) score of 0 or 1, compared with fewer than 5% of those receiving placebo. At the end of one year, 46.7% of the original ixekizumab group and 50.8% of those who transitioned to ixekizumab from placebo via an open-label extension arm achieved a DLQI of 0 or 1. A DLQI score of 0 or 1 on a 30-point scale indicated that psoriasis had no effect on health-related quality of life.
Among patients with plaque psoriasis, genital involvement is common – present in over 60% at some point during the disease course, Lyn Guenther, MD, of Guenther Dermatology Research Centre, London, Ont., and her colleagues wrote in the poster accompanying the presentation. Sexual health and overall quality of life can be negatively affected by genital psoriasis, they added.
In the study, adult patients were included if they had chronic plaque psoriasis present in genital and nongenital areas. For overall psoriasis and genital involvement, the Static Physician’s Global Assessment (sPGA) was 3 or greater, and total body surface area involvement was at least 1%. Also, patients had to have failed or been intolerant to at least one topical therapy for genital psoriasis.
Patients were excluded if they had genital pustules or vesicles, significant uncontrolled medical or psychiatric comorbidities, recent infection, or prior interleukin-17 antagonist treatment.
In all, patients received ixekizumab 160 mg (75 patients) or placebo (74) subcutaneously every 2 weeks during the initial 12-week study period. For the open-label extension arm, 74 patients in the active arm and 65 patients in the placebo arm went on to receive 80 mg of ixekizumab every 4 weeks, with a step-up option to every other week dosing depending on clinical response.
Patients were given the Short Form Health Survey (SF-36) at baseline and at week 12 and week 52; investigators recorded the mean change for baseline for both the physical and mental component.
Participants also completed the DLQI, which was administered nine times over the 52-week study period.
From baseline, SF-36 scores climbed in both the physical and mental domains for those on ixekizumab, wrote Dr. Guenther and her coinvestigators, with “improvements in all SF-36 domains” for those on ixekizumab at 12 weeks, which continued through week 52. For patients who transitioned to ixekizumab from placebo, “improvements in all SF-36 domains were achieved at week 52,” they wrote.
The mean change from baseline on the SF-36 for the ixekizumab population was 3.5 on the physical domain and 4.8 on the mental component. For the placebo-ixekizumab group, scores improved by a mean 4.5 on the physical domain and 4.9 on the mental domain. Those who stayed on ixekizumab saw some decline in SF-36 scores, with a physical component improvement of 2.5 and mental component improvement of 3.6 at 52 weeks.
Ixekizumab (Taltz), a monoclonal antibody targeting interleukin-17A, is approved for moderate to severe plaque psoriasis, and active psoriatic arthritis..
“Ixekizumab provided clinically meaningful and persistent improvements in HRQoL in patients with moderate to severe genital psoriasis,” wrote Dr. Guenther and her colleagues.
Dr. Guenther and two coauthors reported receiving remuneration from several pharmaceutical companies, including Eli Lilly, which funded the study. Four coauthors are employees and shareholders of Eli Lilly.
MILAN – , according to data presented at the World Congress of Dermatology.
After 12 weeks of ixekizumab administration, nearly half of patients who received ixekizumab in the randomized, double-blind, placebo-controlled trial achieved a Dermatology Life Quality Index (DLQI) score of 0 or 1, compared with fewer than 5% of those receiving placebo. At the end of one year, 46.7% of the original ixekizumab group and 50.8% of those who transitioned to ixekizumab from placebo via an open-label extension arm achieved a DLQI of 0 or 1. A DLQI score of 0 or 1 on a 30-point scale indicated that psoriasis had no effect on health-related quality of life.
Among patients with plaque psoriasis, genital involvement is common – present in over 60% at some point during the disease course, Lyn Guenther, MD, of Guenther Dermatology Research Centre, London, Ont., and her colleagues wrote in the poster accompanying the presentation. Sexual health and overall quality of life can be negatively affected by genital psoriasis, they added.
In the study, adult patients were included if they had chronic plaque psoriasis present in genital and nongenital areas. For overall psoriasis and genital involvement, the Static Physician’s Global Assessment (sPGA) was 3 or greater, and total body surface area involvement was at least 1%. Also, patients had to have failed or been intolerant to at least one topical therapy for genital psoriasis.
Patients were excluded if they had genital pustules or vesicles, significant uncontrolled medical or psychiatric comorbidities, recent infection, or prior interleukin-17 antagonist treatment.
In all, patients received ixekizumab 160 mg (75 patients) or placebo (74) subcutaneously every 2 weeks during the initial 12-week study period. For the open-label extension arm, 74 patients in the active arm and 65 patients in the placebo arm went on to receive 80 mg of ixekizumab every 4 weeks, with a step-up option to every other week dosing depending on clinical response.
Patients were given the Short Form Health Survey (SF-36) at baseline and at week 12 and week 52; investigators recorded the mean change for baseline for both the physical and mental component.
Participants also completed the DLQI, which was administered nine times over the 52-week study period.
From baseline, SF-36 scores climbed in both the physical and mental domains for those on ixekizumab, wrote Dr. Guenther and her coinvestigators, with “improvements in all SF-36 domains” for those on ixekizumab at 12 weeks, which continued through week 52. For patients who transitioned to ixekizumab from placebo, “improvements in all SF-36 domains were achieved at week 52,” they wrote.
The mean change from baseline on the SF-36 for the ixekizumab population was 3.5 on the physical domain and 4.8 on the mental component. For the placebo-ixekizumab group, scores improved by a mean 4.5 on the physical domain and 4.9 on the mental domain. Those who stayed on ixekizumab saw some decline in SF-36 scores, with a physical component improvement of 2.5 and mental component improvement of 3.6 at 52 weeks.
Ixekizumab (Taltz), a monoclonal antibody targeting interleukin-17A, is approved for moderate to severe plaque psoriasis, and active psoriatic arthritis..
“Ixekizumab provided clinically meaningful and persistent improvements in HRQoL in patients with moderate to severe genital psoriasis,” wrote Dr. Guenther and her colleagues.
Dr. Guenther and two coauthors reported receiving remuneration from several pharmaceutical companies, including Eli Lilly, which funded the study. Four coauthors are employees and shareholders of Eli Lilly.
MILAN – , according to data presented at the World Congress of Dermatology.
After 12 weeks of ixekizumab administration, nearly half of patients who received ixekizumab in the randomized, double-blind, placebo-controlled trial achieved a Dermatology Life Quality Index (DLQI) score of 0 or 1, compared with fewer than 5% of those receiving placebo. At the end of one year, 46.7% of the original ixekizumab group and 50.8% of those who transitioned to ixekizumab from placebo via an open-label extension arm achieved a DLQI of 0 or 1. A DLQI score of 0 or 1 on a 30-point scale indicated that psoriasis had no effect on health-related quality of life.
Among patients with plaque psoriasis, genital involvement is common – present in over 60% at some point during the disease course, Lyn Guenther, MD, of Guenther Dermatology Research Centre, London, Ont., and her colleagues wrote in the poster accompanying the presentation. Sexual health and overall quality of life can be negatively affected by genital psoriasis, they added.
In the study, adult patients were included if they had chronic plaque psoriasis present in genital and nongenital areas. For overall psoriasis and genital involvement, the Static Physician’s Global Assessment (sPGA) was 3 or greater, and total body surface area involvement was at least 1%. Also, patients had to have failed or been intolerant to at least one topical therapy for genital psoriasis.
Patients were excluded if they had genital pustules or vesicles, significant uncontrolled medical or psychiatric comorbidities, recent infection, or prior interleukin-17 antagonist treatment.
In all, patients received ixekizumab 160 mg (75 patients) or placebo (74) subcutaneously every 2 weeks during the initial 12-week study period. For the open-label extension arm, 74 patients in the active arm and 65 patients in the placebo arm went on to receive 80 mg of ixekizumab every 4 weeks, with a step-up option to every other week dosing depending on clinical response.
Patients were given the Short Form Health Survey (SF-36) at baseline and at week 12 and week 52; investigators recorded the mean change for baseline for both the physical and mental component.
Participants also completed the DLQI, which was administered nine times over the 52-week study period.
From baseline, SF-36 scores climbed in both the physical and mental domains for those on ixekizumab, wrote Dr. Guenther and her coinvestigators, with “improvements in all SF-36 domains” for those on ixekizumab at 12 weeks, which continued through week 52. For patients who transitioned to ixekizumab from placebo, “improvements in all SF-36 domains were achieved at week 52,” they wrote.
The mean change from baseline on the SF-36 for the ixekizumab population was 3.5 on the physical domain and 4.8 on the mental component. For the placebo-ixekizumab group, scores improved by a mean 4.5 on the physical domain and 4.9 on the mental domain. Those who stayed on ixekizumab saw some decline in SF-36 scores, with a physical component improvement of 2.5 and mental component improvement of 3.6 at 52 weeks.
Ixekizumab (Taltz), a monoclonal antibody targeting interleukin-17A, is approved for moderate to severe plaque psoriasis, and active psoriatic arthritis..
“Ixekizumab provided clinically meaningful and persistent improvements in HRQoL in patients with moderate to severe genital psoriasis,” wrote Dr. Guenther and her colleagues.
Dr. Guenther and two coauthors reported receiving remuneration from several pharmaceutical companies, including Eli Lilly, which funded the study. Four coauthors are employees and shareholders of Eli Lilly.
REPORTING FROM WCD2019
Real-world experience with dupilumab in AD mirrors clinical trial efficacy
MILAN – A retrospective, multicenter Maria Fargnoli, MD, reported at the World Congress of Dermatology.
By the end of 4 weeks of treatment, participants’ mean Eczema Area and Severity Index (EASI) score had dropped from 33.3 to 15.3, a 54.2% reduction. At 16 weeks, the mean EASI score was 9.2, a reduction of 72.5% from baseline (P less than .001 for both time points, compared with baseline). At 16 weeks, 87.2% of patients achieved EASI 50, 60.6% achieved EASI 75, and 32.4% achieved EASI 90.
“In a real-life context, dupilumab significantly improved disease severity, pruritus, sleep loss, and quality of life in adult moderate to severe atopic dermatitis patients,” said Dr. Fargnoli, presenting results of the study during a late-breaking abstract session at the meeting. “All measures improved at 4 weeks, and a further decline was seen at 16 weeks. … These results confirm data from clinical trials, and from other real-life experiences with dupilumab.”
The study, conducted in Italy, tracked outcomes for 109 patients treated for moderate to severe atopic dermatitis at 39 centers from June 2018 to February 2019. Adult patients with EASI scores of at least 24 with contraindications, failure, or intolerance of corticosteroid therapy were included and followed for at least 16 weeks. Those who had concomitant systemic anti-inflammatory or immunomodulator use were excluded, as were those with missing data, said Dr. Fargnoli, chair of the department of dermatology at the University of L’Aquila (Italy).
Patients were given a loading dose of two 300-mg subcutaneous injections of dupilumab, followed by 300-mg injections at 2-week intervals.
Patients were assessed at baseline and after 4 and 16 weeks of treatment. In addition to EASI score, itch and sleep were measured via numeric rating scales; mean itch scores dropped from 8.4 at baseline to 4.1 after 4 weeks, and to 2.5 at 16 weeks (P less than .001 for both time points, compared with baseline).
Sleep scores also improved, from a mean 6.9 at baseline to 3.3 at four weeks, and 1.9 at 16 weeks (P less than .001 for both time points, compared with baseline).
Patients also completed the Dermatology Life Quality Index. At the 4-week mark, patients saw a reduction to 8.3 points from the baseline score of 17.6 points (out of a possible 30, with higher scores indicating worse quality of life); scores dropped to 5.4 by week 16 (P less than .001 for both time points, compared with baseline).
Dupilumab was generally well tolerated, with conjunctivitis – seen in 11% of patients – being the most commonly reported adverse event. This falls in line with other recently published real-world studies of dupilumab, Dr. Fargnoli noted.
Efficacy, as measured by EASI reduction and improvement in itch and sleep, were also comparable between the Italian cohort and clinical trial results, as well as other real-life studies in Denmark, France, the Netherlands, and Spain, she said.
Patients, about one-third female, had a mean body mass index of about 24 kg/m2. Mean age was about 38 years (range, 19-80 years). The mean age of disease onset was about 14 years (range, 0-77 years).
Atopic dermatitis was characterized by phenotype for each patient; groupings included classic adult type (73%), nummular dermatitis (7%), prurigo (8%), and erythrodermic dermatitis (12%). About three in four patients (76.1%) had facial involvement; 61.5% had hand involvement, and 22.9% had genital involvement.
Allergic comorbidities were reported by many patients; 44.9% had rhinitis, 38.5% had asthma, 33% had conjunctivitis, and 15.6% reported food allergies. Other notable comorbidities included psychiatric or psychological conditions, present in 11% of patients, and hypertension or other cardiovascular disorders, seen in 9.1% of patients.
Most patients had tried treatment with both cyclosporine A and corticosteroids (88.9% and 88.1%, respectively). Almost half (45.8%) had tried UV-light therapy, and about a quarter had tried methotrexate.
“The results give real-life data on patterns of treatment response according to heterogeneous atopic dermatitis phenotypes, and on long-term efficacy and safety,” said Dr. Fargnoli.
The study was not funded by any company, according to Dr. Fargnoli. She has served on the advisory board for and has received honoraria for lectures and research grants from Sanofi-Genzyme.
MILAN – A retrospective, multicenter Maria Fargnoli, MD, reported at the World Congress of Dermatology.
By the end of 4 weeks of treatment, participants’ mean Eczema Area and Severity Index (EASI) score had dropped from 33.3 to 15.3, a 54.2% reduction. At 16 weeks, the mean EASI score was 9.2, a reduction of 72.5% from baseline (P less than .001 for both time points, compared with baseline). At 16 weeks, 87.2% of patients achieved EASI 50, 60.6% achieved EASI 75, and 32.4% achieved EASI 90.
“In a real-life context, dupilumab significantly improved disease severity, pruritus, sleep loss, and quality of life in adult moderate to severe atopic dermatitis patients,” said Dr. Fargnoli, presenting results of the study during a late-breaking abstract session at the meeting. “All measures improved at 4 weeks, and a further decline was seen at 16 weeks. … These results confirm data from clinical trials, and from other real-life experiences with dupilumab.”
The study, conducted in Italy, tracked outcomes for 109 patients treated for moderate to severe atopic dermatitis at 39 centers from June 2018 to February 2019. Adult patients with EASI scores of at least 24 with contraindications, failure, or intolerance of corticosteroid therapy were included and followed for at least 16 weeks. Those who had concomitant systemic anti-inflammatory or immunomodulator use were excluded, as were those with missing data, said Dr. Fargnoli, chair of the department of dermatology at the University of L’Aquila (Italy).
Patients were given a loading dose of two 300-mg subcutaneous injections of dupilumab, followed by 300-mg injections at 2-week intervals.
Patients were assessed at baseline and after 4 and 16 weeks of treatment. In addition to EASI score, itch and sleep were measured via numeric rating scales; mean itch scores dropped from 8.4 at baseline to 4.1 after 4 weeks, and to 2.5 at 16 weeks (P less than .001 for both time points, compared with baseline).
Sleep scores also improved, from a mean 6.9 at baseline to 3.3 at four weeks, and 1.9 at 16 weeks (P less than .001 for both time points, compared with baseline).
Patients also completed the Dermatology Life Quality Index. At the 4-week mark, patients saw a reduction to 8.3 points from the baseline score of 17.6 points (out of a possible 30, with higher scores indicating worse quality of life); scores dropped to 5.4 by week 16 (P less than .001 for both time points, compared with baseline).
Dupilumab was generally well tolerated, with conjunctivitis – seen in 11% of patients – being the most commonly reported adverse event. This falls in line with other recently published real-world studies of dupilumab, Dr. Fargnoli noted.
Efficacy, as measured by EASI reduction and improvement in itch and sleep, were also comparable between the Italian cohort and clinical trial results, as well as other real-life studies in Denmark, France, the Netherlands, and Spain, she said.
Patients, about one-third female, had a mean body mass index of about 24 kg/m2. Mean age was about 38 years (range, 19-80 years). The mean age of disease onset was about 14 years (range, 0-77 years).
Atopic dermatitis was characterized by phenotype for each patient; groupings included classic adult type (73%), nummular dermatitis (7%), prurigo (8%), and erythrodermic dermatitis (12%). About three in four patients (76.1%) had facial involvement; 61.5% had hand involvement, and 22.9% had genital involvement.
Allergic comorbidities were reported by many patients; 44.9% had rhinitis, 38.5% had asthma, 33% had conjunctivitis, and 15.6% reported food allergies. Other notable comorbidities included psychiatric or psychological conditions, present in 11% of patients, and hypertension or other cardiovascular disorders, seen in 9.1% of patients.
Most patients had tried treatment with both cyclosporine A and corticosteroids (88.9% and 88.1%, respectively). Almost half (45.8%) had tried UV-light therapy, and about a quarter had tried methotrexate.
“The results give real-life data on patterns of treatment response according to heterogeneous atopic dermatitis phenotypes, and on long-term efficacy and safety,” said Dr. Fargnoli.
The study was not funded by any company, according to Dr. Fargnoli. She has served on the advisory board for and has received honoraria for lectures and research grants from Sanofi-Genzyme.
MILAN – A retrospective, multicenter Maria Fargnoli, MD, reported at the World Congress of Dermatology.
By the end of 4 weeks of treatment, participants’ mean Eczema Area and Severity Index (EASI) score had dropped from 33.3 to 15.3, a 54.2% reduction. At 16 weeks, the mean EASI score was 9.2, a reduction of 72.5% from baseline (P less than .001 for both time points, compared with baseline). At 16 weeks, 87.2% of patients achieved EASI 50, 60.6% achieved EASI 75, and 32.4% achieved EASI 90.
“In a real-life context, dupilumab significantly improved disease severity, pruritus, sleep loss, and quality of life in adult moderate to severe atopic dermatitis patients,” said Dr. Fargnoli, presenting results of the study during a late-breaking abstract session at the meeting. “All measures improved at 4 weeks, and a further decline was seen at 16 weeks. … These results confirm data from clinical trials, and from other real-life experiences with dupilumab.”
The study, conducted in Italy, tracked outcomes for 109 patients treated for moderate to severe atopic dermatitis at 39 centers from June 2018 to February 2019. Adult patients with EASI scores of at least 24 with contraindications, failure, or intolerance of corticosteroid therapy were included and followed for at least 16 weeks. Those who had concomitant systemic anti-inflammatory or immunomodulator use were excluded, as were those with missing data, said Dr. Fargnoli, chair of the department of dermatology at the University of L’Aquila (Italy).
Patients were given a loading dose of two 300-mg subcutaneous injections of dupilumab, followed by 300-mg injections at 2-week intervals.
Patients were assessed at baseline and after 4 and 16 weeks of treatment. In addition to EASI score, itch and sleep were measured via numeric rating scales; mean itch scores dropped from 8.4 at baseline to 4.1 after 4 weeks, and to 2.5 at 16 weeks (P less than .001 for both time points, compared with baseline).
Sleep scores also improved, from a mean 6.9 at baseline to 3.3 at four weeks, and 1.9 at 16 weeks (P less than .001 for both time points, compared with baseline).
Patients also completed the Dermatology Life Quality Index. At the 4-week mark, patients saw a reduction to 8.3 points from the baseline score of 17.6 points (out of a possible 30, with higher scores indicating worse quality of life); scores dropped to 5.4 by week 16 (P less than .001 for both time points, compared with baseline).
Dupilumab was generally well tolerated, with conjunctivitis – seen in 11% of patients – being the most commonly reported adverse event. This falls in line with other recently published real-world studies of dupilumab, Dr. Fargnoli noted.
Efficacy, as measured by EASI reduction and improvement in itch and sleep, were also comparable between the Italian cohort and clinical trial results, as well as other real-life studies in Denmark, France, the Netherlands, and Spain, she said.
Patients, about one-third female, had a mean body mass index of about 24 kg/m2. Mean age was about 38 years (range, 19-80 years). The mean age of disease onset was about 14 years (range, 0-77 years).
Atopic dermatitis was characterized by phenotype for each patient; groupings included classic adult type (73%), nummular dermatitis (7%), prurigo (8%), and erythrodermic dermatitis (12%). About three in four patients (76.1%) had facial involvement; 61.5% had hand involvement, and 22.9% had genital involvement.
Allergic comorbidities were reported by many patients; 44.9% had rhinitis, 38.5% had asthma, 33% had conjunctivitis, and 15.6% reported food allergies. Other notable comorbidities included psychiatric or psychological conditions, present in 11% of patients, and hypertension or other cardiovascular disorders, seen in 9.1% of patients.
Most patients had tried treatment with both cyclosporine A and corticosteroids (88.9% and 88.1%, respectively). Almost half (45.8%) had tried UV-light therapy, and about a quarter had tried methotrexate.
“The results give real-life data on patterns of treatment response according to heterogeneous atopic dermatitis phenotypes, and on long-term efficacy and safety,” said Dr. Fargnoli.
The study was not funded by any company, according to Dr. Fargnoli. She has served on the advisory board for and has received honoraria for lectures and research grants from Sanofi-Genzyme.
REPORTING FROM WCD2019
Total margin control surgery warranted for high-risk keratinocyte carcinomas
MILAN – A recent meta-analysis found that total margin control surgery substantially cut the risk of recurrence in patients with high-risk keratinocyte carcinomas, Chrysalyne Schmults, MD, said at the World Congress of Dermatology.
While standard excision will cure the vast majority of low-risk basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), those classified as high risk are best treated with the advanced surgical procedure, also referred to as circumferential peripheral and deep margin assessment (CCPDMA), said Dr. Schmults, director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s Hospital in Boston.
For high-risk cases, CCPDMA has superior outcomes, compared with standard excision, according to results of the meta-analysis conducted by Dr. Schmults and colleagues. The meta-analysis has not yet been published.
The in the meta-analysis of medical literature from 1993 to 2017.
“This is a really big drop,” Dr. Schmults said. “If you do total margin control surgery on your perineural invasive cases, you’re going to drop your recurrence rate by two-thirds, and that’s a really big difference.”
For carcinomas without perineural invasion, the recurrence rate is about 4.5% for standard excision and about 2.0% for CCPDMA, the analysis showed. “That’s a difference, but it’s not a big enough difference that we’re going to start doing total margin control surgery on every single basal cell and squamous cell carcinoma that comes to us,” Dr. Schmults commented.
Using techniques such as Mohs surgery that allow for CCPDMA, nearly 100% of the surgical margin can be seen; by contrast, standard histology allows for visualization of only about 1% of the marginal surface, according to Dr. Schmults.
While CCPDMA may have superior outcomes for high-risk keratinocyte carcinomas, defining what constitutes high risk remains a challenge, particularly for patients with BCCs. “We don’t have good literature on which are the rare, bad basal cells,” she said.
But more clarity may be on the way. In a paper under review for publication on Brigham and Women’s Hospital (BWH) staging criteria for BCC, Dr. Schmults and colleagues describe a subset of patients with BCC at higher risk of metastasis and death based on specific high-risk tumor characteristics.
High risk is better defined for SCCs. According to the BWH classification system for cutaneous SCCs, developed by Dr. Schmults and colleagues, high-risk features include larger tumor diameter, poorly differentiated histology, perineural invasion, and tumor invasion beyond subcutaneous fat or to bone.
Patients with SCC classified as high stage by the BWH system have about a 25% risk of metastasis or death. “These patients really need that total margin control surgery,” Dr. Schmults said.
High-stage SCC patients who did not get Mohs surgery in a study (J Clin Oncol. 2014 Feb 1;32[4]:327-34) conducted by Dr. Schmults and her associates, had a quadrupling in risk of death from disease, compared with those who did get the procedure in a more recent study (J Am Acad Dermatol. 2019 Mar;80[3]:633-8).
“These are fairly small studies,” she pointed out. But the large meta-analysis she presented at the meeting showed the same result, “that the higher the stage, the worse your tumor is, and whether it’s basal cell or squamous cell, the greater the advantage for total margin control surgery.”
Dr. Schmults reported that she is the panel chair for the National Comprehensive Cancer Network guidelines on nonmelanoma skin cancer, and that she was a cutaneous SCC committee member for the 8th edition of the American Joint Committee on Cancer cancer staging system. She also participated in the development of the BWH staging system for SCC.
MILAN – A recent meta-analysis found that total margin control surgery substantially cut the risk of recurrence in patients with high-risk keratinocyte carcinomas, Chrysalyne Schmults, MD, said at the World Congress of Dermatology.
While standard excision will cure the vast majority of low-risk basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), those classified as high risk are best treated with the advanced surgical procedure, also referred to as circumferential peripheral and deep margin assessment (CCPDMA), said Dr. Schmults, director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s Hospital in Boston.
For high-risk cases, CCPDMA has superior outcomes, compared with standard excision, according to results of the meta-analysis conducted by Dr. Schmults and colleagues. The meta-analysis has not yet been published.
The in the meta-analysis of medical literature from 1993 to 2017.
“This is a really big drop,” Dr. Schmults said. “If you do total margin control surgery on your perineural invasive cases, you’re going to drop your recurrence rate by two-thirds, and that’s a really big difference.”
For carcinomas without perineural invasion, the recurrence rate is about 4.5% for standard excision and about 2.0% for CCPDMA, the analysis showed. “That’s a difference, but it’s not a big enough difference that we’re going to start doing total margin control surgery on every single basal cell and squamous cell carcinoma that comes to us,” Dr. Schmults commented.
Using techniques such as Mohs surgery that allow for CCPDMA, nearly 100% of the surgical margin can be seen; by contrast, standard histology allows for visualization of only about 1% of the marginal surface, according to Dr. Schmults.
While CCPDMA may have superior outcomes for high-risk keratinocyte carcinomas, defining what constitutes high risk remains a challenge, particularly for patients with BCCs. “We don’t have good literature on which are the rare, bad basal cells,” she said.
But more clarity may be on the way. In a paper under review for publication on Brigham and Women’s Hospital (BWH) staging criteria for BCC, Dr. Schmults and colleagues describe a subset of patients with BCC at higher risk of metastasis and death based on specific high-risk tumor characteristics.
High risk is better defined for SCCs. According to the BWH classification system for cutaneous SCCs, developed by Dr. Schmults and colleagues, high-risk features include larger tumor diameter, poorly differentiated histology, perineural invasion, and tumor invasion beyond subcutaneous fat or to bone.
Patients with SCC classified as high stage by the BWH system have about a 25% risk of metastasis or death. “These patients really need that total margin control surgery,” Dr. Schmults said.
High-stage SCC patients who did not get Mohs surgery in a study (J Clin Oncol. 2014 Feb 1;32[4]:327-34) conducted by Dr. Schmults and her associates, had a quadrupling in risk of death from disease, compared with those who did get the procedure in a more recent study (J Am Acad Dermatol. 2019 Mar;80[3]:633-8).
“These are fairly small studies,” she pointed out. But the large meta-analysis she presented at the meeting showed the same result, “that the higher the stage, the worse your tumor is, and whether it’s basal cell or squamous cell, the greater the advantage for total margin control surgery.”
Dr. Schmults reported that she is the panel chair for the National Comprehensive Cancer Network guidelines on nonmelanoma skin cancer, and that she was a cutaneous SCC committee member for the 8th edition of the American Joint Committee on Cancer cancer staging system. She also participated in the development of the BWH staging system for SCC.
MILAN – A recent meta-analysis found that total margin control surgery substantially cut the risk of recurrence in patients with high-risk keratinocyte carcinomas, Chrysalyne Schmults, MD, said at the World Congress of Dermatology.
While standard excision will cure the vast majority of low-risk basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), those classified as high risk are best treated with the advanced surgical procedure, also referred to as circumferential peripheral and deep margin assessment (CCPDMA), said Dr. Schmults, director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s Hospital in Boston.
For high-risk cases, CCPDMA has superior outcomes, compared with standard excision, according to results of the meta-analysis conducted by Dr. Schmults and colleagues. The meta-analysis has not yet been published.
The in the meta-analysis of medical literature from 1993 to 2017.
“This is a really big drop,” Dr. Schmults said. “If you do total margin control surgery on your perineural invasive cases, you’re going to drop your recurrence rate by two-thirds, and that’s a really big difference.”
For carcinomas without perineural invasion, the recurrence rate is about 4.5% for standard excision and about 2.0% for CCPDMA, the analysis showed. “That’s a difference, but it’s not a big enough difference that we’re going to start doing total margin control surgery on every single basal cell and squamous cell carcinoma that comes to us,” Dr. Schmults commented.
Using techniques such as Mohs surgery that allow for CCPDMA, nearly 100% of the surgical margin can be seen; by contrast, standard histology allows for visualization of only about 1% of the marginal surface, according to Dr. Schmults.
While CCPDMA may have superior outcomes for high-risk keratinocyte carcinomas, defining what constitutes high risk remains a challenge, particularly for patients with BCCs. “We don’t have good literature on which are the rare, bad basal cells,” she said.
But more clarity may be on the way. In a paper under review for publication on Brigham and Women’s Hospital (BWH) staging criteria for BCC, Dr. Schmults and colleagues describe a subset of patients with BCC at higher risk of metastasis and death based on specific high-risk tumor characteristics.
High risk is better defined for SCCs. According to the BWH classification system for cutaneous SCCs, developed by Dr. Schmults and colleagues, high-risk features include larger tumor diameter, poorly differentiated histology, perineural invasion, and tumor invasion beyond subcutaneous fat or to bone.
Patients with SCC classified as high stage by the BWH system have about a 25% risk of metastasis or death. “These patients really need that total margin control surgery,” Dr. Schmults said.
High-stage SCC patients who did not get Mohs surgery in a study (J Clin Oncol. 2014 Feb 1;32[4]:327-34) conducted by Dr. Schmults and her associates, had a quadrupling in risk of death from disease, compared with those who did get the procedure in a more recent study (J Am Acad Dermatol. 2019 Mar;80[3]:633-8).
“These are fairly small studies,” she pointed out. But the large meta-analysis she presented at the meeting showed the same result, “that the higher the stage, the worse your tumor is, and whether it’s basal cell or squamous cell, the greater the advantage for total margin control surgery.”
Dr. Schmults reported that she is the panel chair for the National Comprehensive Cancer Network guidelines on nonmelanoma skin cancer, and that she was a cutaneous SCC committee member for the 8th edition of the American Joint Committee on Cancer cancer staging system. She also participated in the development of the BWH staging system for SCC.
REPORTING FROM WCD2019
Severity, itch improvements remain steady with ruxolitinib for atopic dermatitis
MILAN – A in the 4-week open-label period of a 16-week randomized phase 2 study of adults with mild to moderate atopic dermatitis (AD), Leon H. Kircik, MD, said at the World Congress of Dermatology.
Improvements in disease severity and itch in patients receiving 1.5% ruxolitinib cream twice daily were sustained over the open-label period, said Dr. Kircik, a dermatologist in Louisville, Ky., affiliated with Mount Sinai Medical Center, New York.
Patients who switched from vehicle or 0.1% triamcinolone cream to the JAK1/2 selective inhibitor in the open-label period also experienced rapid improvements in disease severity and itch.
“This is a novel treatment that’s a topical JAK inhibitor, which so far we don’t have any in the market for atopic dermatitis, and it does have a very good efficacy and safety profile,” Dr. Kircik said during an oral presentation at the meeting.
Janus kinases modulate inflammatory cytokines implicated in AD, and may also directly modulate itch, Dr. Kircik noted.
The study comprised 307 adults with mild to moderate AD (Investigator’s Global Assessment [IGA] score of 2 or 3) and body surface area involvement of 3%-20%. They were randomized equally to six arms, including vehicle, triamcinolone cream, and ruxolitinib at dosages of 0.15%, 0.5%, 1.5% once daily, or the target dose level of 1.5% twice daily.
After an 8-week double-blind period, there was a 4-week open-label period during which patients randomized to vehicle or triamcinolone were switched to ruxolitinib, and then a 4-week follow-up period during which no treatment was given, Dr. Kircik said.
The mean age of the patients was 35 years, 54% were female, and the median duration of disease was 20.8 years.
In the double-blind period, 1.5% ruxolitinib cream twice daily significantly improved Eczema Area and Severity Index (EASI) score versus vehicle, Dr. Kircik said.
The mean change in EASI scores at weeks 2, 4, and 6 were 52.7%, 71.6%, and 78.5% for ruxolitinib, versus 4.8%, 15.5%, and 26.9% for vehicle (P less than .001 for all comparisons), according to Dr. Kircik.
The patients on the target ruxolitinib dose maintained the improvements in EASI score throughout the open label period, with mean improvement from baseline reaching 81.4% by week 10 and 84.9% by week 12.
Meanwhile, there was a sharp increase in mean EASI score improvement in patients switched to ruxolitinib, according to Dr. Kircik. In the vehicle arm, mean improvement leapt from 26.9% at week 8 to 78.4% by week 12.
Significant reductions in itch scores were seen within 36 hours of starting the 1.5% ruxolitinib cream, with itch Numeric Rating Scale (NRS) scores of –1.8 versus –0.2 for vehicle at that time point (P less than .0001), he added.
Reduction in itch score was similarly maintained in the ruxolitinib target dose group, and rapidly fell to similar levels for patients switched over to that treatment in the open-label period, Dr. Kircik said.
The target ruxolitinib dose was also noninferior to triamcinolone cream, for which mean change in EASI scores at weeks 2 and 4 were 40.0% and 59.8%, respectively.
Recruitment of patients in phase 3 studies of ruxolitinib cream for AD has just started, Dr. Kircik said.
The TRuE AD1 and TRuE AD2 studies are set to enroll 1,200 adolescents and adults with AD who will be randomized to ruxolitinib cream or vehicle, according to listings on ClinicalTrials.gov.
Dr. Kircik disclosed ties to several companies including Incyte, which was the sponsor of the phase 2 study and the phase 3 studies.
MILAN – A in the 4-week open-label period of a 16-week randomized phase 2 study of adults with mild to moderate atopic dermatitis (AD), Leon H. Kircik, MD, said at the World Congress of Dermatology.
Improvements in disease severity and itch in patients receiving 1.5% ruxolitinib cream twice daily were sustained over the open-label period, said Dr. Kircik, a dermatologist in Louisville, Ky., affiliated with Mount Sinai Medical Center, New York.
Patients who switched from vehicle or 0.1% triamcinolone cream to the JAK1/2 selective inhibitor in the open-label period also experienced rapid improvements in disease severity and itch.
“This is a novel treatment that’s a topical JAK inhibitor, which so far we don’t have any in the market for atopic dermatitis, and it does have a very good efficacy and safety profile,” Dr. Kircik said during an oral presentation at the meeting.
Janus kinases modulate inflammatory cytokines implicated in AD, and may also directly modulate itch, Dr. Kircik noted.
The study comprised 307 adults with mild to moderate AD (Investigator’s Global Assessment [IGA] score of 2 or 3) and body surface area involvement of 3%-20%. They were randomized equally to six arms, including vehicle, triamcinolone cream, and ruxolitinib at dosages of 0.15%, 0.5%, 1.5% once daily, or the target dose level of 1.5% twice daily.
After an 8-week double-blind period, there was a 4-week open-label period during which patients randomized to vehicle or triamcinolone were switched to ruxolitinib, and then a 4-week follow-up period during which no treatment was given, Dr. Kircik said.
The mean age of the patients was 35 years, 54% were female, and the median duration of disease was 20.8 years.
In the double-blind period, 1.5% ruxolitinib cream twice daily significantly improved Eczema Area and Severity Index (EASI) score versus vehicle, Dr. Kircik said.
The mean change in EASI scores at weeks 2, 4, and 6 were 52.7%, 71.6%, and 78.5% for ruxolitinib, versus 4.8%, 15.5%, and 26.9% for vehicle (P less than .001 for all comparisons), according to Dr. Kircik.
The patients on the target ruxolitinib dose maintained the improvements in EASI score throughout the open label period, with mean improvement from baseline reaching 81.4% by week 10 and 84.9% by week 12.
Meanwhile, there was a sharp increase in mean EASI score improvement in patients switched to ruxolitinib, according to Dr. Kircik. In the vehicle arm, mean improvement leapt from 26.9% at week 8 to 78.4% by week 12.
Significant reductions in itch scores were seen within 36 hours of starting the 1.5% ruxolitinib cream, with itch Numeric Rating Scale (NRS) scores of –1.8 versus –0.2 for vehicle at that time point (P less than .0001), he added.
Reduction in itch score was similarly maintained in the ruxolitinib target dose group, and rapidly fell to similar levels for patients switched over to that treatment in the open-label period, Dr. Kircik said.
The target ruxolitinib dose was also noninferior to triamcinolone cream, for which mean change in EASI scores at weeks 2 and 4 were 40.0% and 59.8%, respectively.
Recruitment of patients in phase 3 studies of ruxolitinib cream for AD has just started, Dr. Kircik said.
The TRuE AD1 and TRuE AD2 studies are set to enroll 1,200 adolescents and adults with AD who will be randomized to ruxolitinib cream or vehicle, according to listings on ClinicalTrials.gov.
Dr. Kircik disclosed ties to several companies including Incyte, which was the sponsor of the phase 2 study and the phase 3 studies.
MILAN – A in the 4-week open-label period of a 16-week randomized phase 2 study of adults with mild to moderate atopic dermatitis (AD), Leon H. Kircik, MD, said at the World Congress of Dermatology.
Improvements in disease severity and itch in patients receiving 1.5% ruxolitinib cream twice daily were sustained over the open-label period, said Dr. Kircik, a dermatologist in Louisville, Ky., affiliated with Mount Sinai Medical Center, New York.
Patients who switched from vehicle or 0.1% triamcinolone cream to the JAK1/2 selective inhibitor in the open-label period also experienced rapid improvements in disease severity and itch.
“This is a novel treatment that’s a topical JAK inhibitor, which so far we don’t have any in the market for atopic dermatitis, and it does have a very good efficacy and safety profile,” Dr. Kircik said during an oral presentation at the meeting.
Janus kinases modulate inflammatory cytokines implicated in AD, and may also directly modulate itch, Dr. Kircik noted.
The study comprised 307 adults with mild to moderate AD (Investigator’s Global Assessment [IGA] score of 2 or 3) and body surface area involvement of 3%-20%. They were randomized equally to six arms, including vehicle, triamcinolone cream, and ruxolitinib at dosages of 0.15%, 0.5%, 1.5% once daily, or the target dose level of 1.5% twice daily.
After an 8-week double-blind period, there was a 4-week open-label period during which patients randomized to vehicle or triamcinolone were switched to ruxolitinib, and then a 4-week follow-up period during which no treatment was given, Dr. Kircik said.
The mean age of the patients was 35 years, 54% were female, and the median duration of disease was 20.8 years.
In the double-blind period, 1.5% ruxolitinib cream twice daily significantly improved Eczema Area and Severity Index (EASI) score versus vehicle, Dr. Kircik said.
The mean change in EASI scores at weeks 2, 4, and 6 were 52.7%, 71.6%, and 78.5% for ruxolitinib, versus 4.8%, 15.5%, and 26.9% for vehicle (P less than .001 for all comparisons), according to Dr. Kircik.
The patients on the target ruxolitinib dose maintained the improvements in EASI score throughout the open label period, with mean improvement from baseline reaching 81.4% by week 10 and 84.9% by week 12.
Meanwhile, there was a sharp increase in mean EASI score improvement in patients switched to ruxolitinib, according to Dr. Kircik. In the vehicle arm, mean improvement leapt from 26.9% at week 8 to 78.4% by week 12.
Significant reductions in itch scores were seen within 36 hours of starting the 1.5% ruxolitinib cream, with itch Numeric Rating Scale (NRS) scores of –1.8 versus –0.2 for vehicle at that time point (P less than .0001), he added.
Reduction in itch score was similarly maintained in the ruxolitinib target dose group, and rapidly fell to similar levels for patients switched over to that treatment in the open-label period, Dr. Kircik said.
The target ruxolitinib dose was also noninferior to triamcinolone cream, for which mean change in EASI scores at weeks 2 and 4 were 40.0% and 59.8%, respectively.
Recruitment of patients in phase 3 studies of ruxolitinib cream for AD has just started, Dr. Kircik said.
The TRuE AD1 and TRuE AD2 studies are set to enroll 1,200 adolescents and adults with AD who will be randomized to ruxolitinib cream or vehicle, according to listings on ClinicalTrials.gov.
Dr. Kircik disclosed ties to several companies including Incyte, which was the sponsor of the phase 2 study and the phase 3 studies.
REPORTING FROM WCD2019
JAK inhibitors are the ‘near future’ of alopecia areata treatment
MILAN – Janus kinase (JAK) inhibitors have clear science supporting their use in alopecia areata, and an increasing number of positive studies demonstrate their efficacy in regrowing hair, Brett King, MD, PhD, said at the World Congress of Dermatology.
Although not yet specifically approved for , said Dr. King, associate professor of dermatology at Yale University, New Haven, Conn.
“JAK inhibitors are very much within our reach for the treatment of severe alopecia areata,” Dr. King said in an oral presentation on therapeutic advances for alopecia. “We need to follow the science,” he added. “We would not be here telling a story about JAK inhibitors and these other agents without very bright scientists, so we really have to applaud the people who made this the focus of their research.”
JAK science
The science supporting JAK inhibitors can be traced back to a 2014 report by Angela M. Christiano, PhD,, Raphael Clynes, of Columbia University, New York, and others showing that alopecia areata is driven by cytotoxic T lymphocytes, and is reversed by inhibition of the JAK/STAT pathway in mouse models of disease (Nat Med. 2014 Sep;20[9]:1043-9). Those investigators also reported near-complete regrowth of hair in three patients who received oral ruxolitinib, an inhibitor of JAK1 and JAK2, hinting at the potential clinical importance of this targeted approach.
As Dr. King explained, secretion of interleukin (IL)-15 from the hair follicle endothelial cell activates CD8+NKG2D+ T cells leading to secretion of interferon (IFN)-gamma, which has a receptor on the hair follicle epithelial cell, activating that cell to secrete more IL-15.
“IL-15 and IFN-gamma both signal through the JAK/STAT pathway,” he said. “There are over 50 cytokines that signal through the JAK/STAT pathway, including IFN-gamma and IL-15, and on binding their receptor at the cell surface, they pass the baton, if you will, to the JAK enzymes, of which there are 4 members – JAK1, 2, 3 and tyrosine kinase 2. These enzymes subsequently pass the baton to STAT, and STAT translocates to the nucleus, where transcription occurs and disease happens. So we have an opportunity then with a small molecule JAK inhibitor to mediate disease, such that if we give this person a JAK inhibitor, they should regrow hair.”
JAK data
A number of studies of JAK inhibitors support that science, including an open-label study of 66 patients treated with the JAK1/3 inhibitor tofacitinib twice daily (JCI Insight. 2016 Sep 22;1[15]:e89776). About one-third experienced a 50% or greater improvement from baseline, as measured by the severity of alopecia tool (SALT) score over 3 months of treatment, with adverse events limited to grade 1-2 infections, according to the authors, which included Dr. King.
Around the same time, results of an open-label study with ruxolitinib, a JAK1/2 inhibitor, were published showing that 9 of 12 patients had complete or near complete scalp hair regrowth over 6 months of treatment, he said.
In a subsequent retrospective study of 90 patients treated with tofacitinib, about 66%-70% of patients experienced regrowth of hair, depending on the dose received. However, that study also showed that hair regrowth was unlikely in patients with complete or near complete scalp hair loss for 10 years or more, Dr. King said. An additional study showed that tofacitinib may be effective in adolescents as in adults, or even more effective, he added, while another found that low-dose ruxolitinib was as effective as higher dose ruxolitinib for the treatment of severe alopecia areata.
News earlier in 2019 surrounded the results of two randomized, double-blind placebo controlled trials, reported at the annual American Academy of Dermatology meeting in Washington, DC, showing efficacy for investigational oral JAK-targeted agents, a JAK 1/2 inhibitor (CTP-543), and a TYK2/JAK1 inhibitor (PF-06700841) and a JAK3 inhibitor (PF-06651600).
“I think this really is the near future of alopecia areata treatment,” Dr. King said.
No success yet for topical JAKs
One area where JAK inhibitors have not shined yet is in topical formulations. In a pilot study of tofacitinib 2% ointment, only 1 of 10 patients had significant scalp hair growth, while a study of topical ruxolitinib was stopped early and results have not yet been reported, according to Dr. King. “As dermatologists, we’re always interested in topical therapy for skin disease, but I’m not sure that alopecia areata is a disease for which topical JAK inhibitors will be effective,” he said.
Dr. King reported disclosures related to Aclaris Therapeutics, Concert Pharmaceuticals, Dermavant Sciences, Eli Lilly, Pfizer, Regeneron, and Sanofi Genzyme.
MILAN – Janus kinase (JAK) inhibitors have clear science supporting their use in alopecia areata, and an increasing number of positive studies demonstrate their efficacy in regrowing hair, Brett King, MD, PhD, said at the World Congress of Dermatology.
Although not yet specifically approved for , said Dr. King, associate professor of dermatology at Yale University, New Haven, Conn.
“JAK inhibitors are very much within our reach for the treatment of severe alopecia areata,” Dr. King said in an oral presentation on therapeutic advances for alopecia. “We need to follow the science,” he added. “We would not be here telling a story about JAK inhibitors and these other agents without very bright scientists, so we really have to applaud the people who made this the focus of their research.”
JAK science
The science supporting JAK inhibitors can be traced back to a 2014 report by Angela M. Christiano, PhD,, Raphael Clynes, of Columbia University, New York, and others showing that alopecia areata is driven by cytotoxic T lymphocytes, and is reversed by inhibition of the JAK/STAT pathway in mouse models of disease (Nat Med. 2014 Sep;20[9]:1043-9). Those investigators also reported near-complete regrowth of hair in three patients who received oral ruxolitinib, an inhibitor of JAK1 and JAK2, hinting at the potential clinical importance of this targeted approach.
As Dr. King explained, secretion of interleukin (IL)-15 from the hair follicle endothelial cell activates CD8+NKG2D+ T cells leading to secretion of interferon (IFN)-gamma, which has a receptor on the hair follicle epithelial cell, activating that cell to secrete more IL-15.
“IL-15 and IFN-gamma both signal through the JAK/STAT pathway,” he said. “There are over 50 cytokines that signal through the JAK/STAT pathway, including IFN-gamma and IL-15, and on binding their receptor at the cell surface, they pass the baton, if you will, to the JAK enzymes, of which there are 4 members – JAK1, 2, 3 and tyrosine kinase 2. These enzymes subsequently pass the baton to STAT, and STAT translocates to the nucleus, where transcription occurs and disease happens. So we have an opportunity then with a small molecule JAK inhibitor to mediate disease, such that if we give this person a JAK inhibitor, they should regrow hair.”
JAK data
A number of studies of JAK inhibitors support that science, including an open-label study of 66 patients treated with the JAK1/3 inhibitor tofacitinib twice daily (JCI Insight. 2016 Sep 22;1[15]:e89776). About one-third experienced a 50% or greater improvement from baseline, as measured by the severity of alopecia tool (SALT) score over 3 months of treatment, with adverse events limited to grade 1-2 infections, according to the authors, which included Dr. King.
Around the same time, results of an open-label study with ruxolitinib, a JAK1/2 inhibitor, were published showing that 9 of 12 patients had complete or near complete scalp hair regrowth over 6 months of treatment, he said.
In a subsequent retrospective study of 90 patients treated with tofacitinib, about 66%-70% of patients experienced regrowth of hair, depending on the dose received. However, that study also showed that hair regrowth was unlikely in patients with complete or near complete scalp hair loss for 10 years or more, Dr. King said. An additional study showed that tofacitinib may be effective in adolescents as in adults, or even more effective, he added, while another found that low-dose ruxolitinib was as effective as higher dose ruxolitinib for the treatment of severe alopecia areata.
News earlier in 2019 surrounded the results of two randomized, double-blind placebo controlled trials, reported at the annual American Academy of Dermatology meeting in Washington, DC, showing efficacy for investigational oral JAK-targeted agents, a JAK 1/2 inhibitor (CTP-543), and a TYK2/JAK1 inhibitor (PF-06700841) and a JAK3 inhibitor (PF-06651600).
“I think this really is the near future of alopecia areata treatment,” Dr. King said.
No success yet for topical JAKs
One area where JAK inhibitors have not shined yet is in topical formulations. In a pilot study of tofacitinib 2% ointment, only 1 of 10 patients had significant scalp hair growth, while a study of topical ruxolitinib was stopped early and results have not yet been reported, according to Dr. King. “As dermatologists, we’re always interested in topical therapy for skin disease, but I’m not sure that alopecia areata is a disease for which topical JAK inhibitors will be effective,” he said.
Dr. King reported disclosures related to Aclaris Therapeutics, Concert Pharmaceuticals, Dermavant Sciences, Eli Lilly, Pfizer, Regeneron, and Sanofi Genzyme.
MILAN – Janus kinase (JAK) inhibitors have clear science supporting their use in alopecia areata, and an increasing number of positive studies demonstrate their efficacy in regrowing hair, Brett King, MD, PhD, said at the World Congress of Dermatology.
Although not yet specifically approved for , said Dr. King, associate professor of dermatology at Yale University, New Haven, Conn.
“JAK inhibitors are very much within our reach for the treatment of severe alopecia areata,” Dr. King said in an oral presentation on therapeutic advances for alopecia. “We need to follow the science,” he added. “We would not be here telling a story about JAK inhibitors and these other agents without very bright scientists, so we really have to applaud the people who made this the focus of their research.”
JAK science
The science supporting JAK inhibitors can be traced back to a 2014 report by Angela M. Christiano, PhD,, Raphael Clynes, of Columbia University, New York, and others showing that alopecia areata is driven by cytotoxic T lymphocytes, and is reversed by inhibition of the JAK/STAT pathway in mouse models of disease (Nat Med. 2014 Sep;20[9]:1043-9). Those investigators also reported near-complete regrowth of hair in three patients who received oral ruxolitinib, an inhibitor of JAK1 and JAK2, hinting at the potential clinical importance of this targeted approach.
As Dr. King explained, secretion of interleukin (IL)-15 from the hair follicle endothelial cell activates CD8+NKG2D+ T cells leading to secretion of interferon (IFN)-gamma, which has a receptor on the hair follicle epithelial cell, activating that cell to secrete more IL-15.
“IL-15 and IFN-gamma both signal through the JAK/STAT pathway,” he said. “There are over 50 cytokines that signal through the JAK/STAT pathway, including IFN-gamma and IL-15, and on binding their receptor at the cell surface, they pass the baton, if you will, to the JAK enzymes, of which there are 4 members – JAK1, 2, 3 and tyrosine kinase 2. These enzymes subsequently pass the baton to STAT, and STAT translocates to the nucleus, where transcription occurs and disease happens. So we have an opportunity then with a small molecule JAK inhibitor to mediate disease, such that if we give this person a JAK inhibitor, they should regrow hair.”
JAK data
A number of studies of JAK inhibitors support that science, including an open-label study of 66 patients treated with the JAK1/3 inhibitor tofacitinib twice daily (JCI Insight. 2016 Sep 22;1[15]:e89776). About one-third experienced a 50% or greater improvement from baseline, as measured by the severity of alopecia tool (SALT) score over 3 months of treatment, with adverse events limited to grade 1-2 infections, according to the authors, which included Dr. King.
Around the same time, results of an open-label study with ruxolitinib, a JAK1/2 inhibitor, were published showing that 9 of 12 patients had complete or near complete scalp hair regrowth over 6 months of treatment, he said.
In a subsequent retrospective study of 90 patients treated with tofacitinib, about 66%-70% of patients experienced regrowth of hair, depending on the dose received. However, that study also showed that hair regrowth was unlikely in patients with complete or near complete scalp hair loss for 10 years or more, Dr. King said. An additional study showed that tofacitinib may be effective in adolescents as in adults, or even more effective, he added, while another found that low-dose ruxolitinib was as effective as higher dose ruxolitinib for the treatment of severe alopecia areata.
News earlier in 2019 surrounded the results of two randomized, double-blind placebo controlled trials, reported at the annual American Academy of Dermatology meeting in Washington, DC, showing efficacy for investigational oral JAK-targeted agents, a JAK 1/2 inhibitor (CTP-543), and a TYK2/JAK1 inhibitor (PF-06700841) and a JAK3 inhibitor (PF-06651600).
“I think this really is the near future of alopecia areata treatment,” Dr. King said.
No success yet for topical JAKs
One area where JAK inhibitors have not shined yet is in topical formulations. In a pilot study of tofacitinib 2% ointment, only 1 of 10 patients had significant scalp hair growth, while a study of topical ruxolitinib was stopped early and results have not yet been reported, according to Dr. King. “As dermatologists, we’re always interested in topical therapy for skin disease, but I’m not sure that alopecia areata is a disease for which topical JAK inhibitors will be effective,” he said.
Dr. King reported disclosures related to Aclaris Therapeutics, Concert Pharmaceuticals, Dermavant Sciences, Eli Lilly, Pfizer, Regeneron, and Sanofi Genzyme.
EXPERT ANALYSIS FROM WCD2019