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Less vacuum may reduce post–cryolipolysis adipose hyperplasia
KAUAI, HAWAII – Gentler vacuum pressure seems to reduce the risk of paradoxical adipose hyperplasia after cryolipolysis, according to Suzanne Kilmer, MD, director of the Laser and Skin Surgery Center of Northern California, Sacramento.
She and her colleagues have noticed a reduction with the newer CoolAdvantage applicators from Zeltiq Aesthetics, the manufacturer of CoolSculpting equipment. CoolAdvantage runs colder and with less suction than earlier applicators. “It seems to work equally as well,” but with shorter treatment times, less bruising, and less discomfort. Although paradoxical adipose hyperplasia (PAH) “is incredibly rare, it is something we want to reduce, and we do see decreased incidence with these new applicators,” Dr. Kilmer said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Typically, one CoolSculpting session will get rid of about 20%-25% of the fat sucked up into the cryolipolysis cup. There can be some discomfort, for instance, when ice crystals are massaged afterward. To ensure patient satisfaction, “you really need to be realistic about what they can expect. It’s likely to be more than one session,” she said.
Another newer option from the manufacturer is the CoolMini applicator for submental fat. Dr. Kilmer generally does two overlapping applications with the CoolMini in the same session, in order to cover as much chin fat as possible. There will be what looks like a stick of butter under the chin when the applicators are removed; it goes away after a few minutes of massage. Patient satisfaction is high, but there can be unveiling of the platysmal bands, which is “something you want to talk to patients about ahead of time,” she said.
She sometimes uses the CoolMini first, followed by the other recently available option for submental fat, deoxycholic acid (Kybella). “We shrink down everything we can with CoolSculpting, and then come back with Kybella to clean up whatever’s left.” Using this approach, patients are injected with less deoxycholic acid, with less inflammation, she said.
“I think you get more fat loss out of a given CoolSculpting treatment than you do with Kybella,” said Dr. Kilmer, who noted that deoxycholic acid is also an option for PAH.
As for going off label with CoolSculpting for jowls, “we’ve done it, and I tell everybody there’s a chance of a 2-3 month palsy. All you are really doing is demyelinating the nerve, not injuring it. If you do liposuction, you actually have a little bit of risk of actually injuring it. You can use a nerve stimulator to map out the nerves beforehand,” she said.
Dr. Kilmer is a consultant for Zeltiq Aesthetics, and an investigator on many of the company’s development trials. She’s also a consultant for Allergan, manufacturer of Kybella, which recently acquired Zeltiq. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – Gentler vacuum pressure seems to reduce the risk of paradoxical adipose hyperplasia after cryolipolysis, according to Suzanne Kilmer, MD, director of the Laser and Skin Surgery Center of Northern California, Sacramento.
She and her colleagues have noticed a reduction with the newer CoolAdvantage applicators from Zeltiq Aesthetics, the manufacturer of CoolSculpting equipment. CoolAdvantage runs colder and with less suction than earlier applicators. “It seems to work equally as well,” but with shorter treatment times, less bruising, and less discomfort. Although paradoxical adipose hyperplasia (PAH) “is incredibly rare, it is something we want to reduce, and we do see decreased incidence with these new applicators,” Dr. Kilmer said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Typically, one CoolSculpting session will get rid of about 20%-25% of the fat sucked up into the cryolipolysis cup. There can be some discomfort, for instance, when ice crystals are massaged afterward. To ensure patient satisfaction, “you really need to be realistic about what they can expect. It’s likely to be more than one session,” she said.
Another newer option from the manufacturer is the CoolMini applicator for submental fat. Dr. Kilmer generally does two overlapping applications with the CoolMini in the same session, in order to cover as much chin fat as possible. There will be what looks like a stick of butter under the chin when the applicators are removed; it goes away after a few minutes of massage. Patient satisfaction is high, but there can be unveiling of the platysmal bands, which is “something you want to talk to patients about ahead of time,” she said.
She sometimes uses the CoolMini first, followed by the other recently available option for submental fat, deoxycholic acid (Kybella). “We shrink down everything we can with CoolSculpting, and then come back with Kybella to clean up whatever’s left.” Using this approach, patients are injected with less deoxycholic acid, with less inflammation, she said.
“I think you get more fat loss out of a given CoolSculpting treatment than you do with Kybella,” said Dr. Kilmer, who noted that deoxycholic acid is also an option for PAH.
As for going off label with CoolSculpting for jowls, “we’ve done it, and I tell everybody there’s a chance of a 2-3 month palsy. All you are really doing is demyelinating the nerve, not injuring it. If you do liposuction, you actually have a little bit of risk of actually injuring it. You can use a nerve stimulator to map out the nerves beforehand,” she said.
Dr. Kilmer is a consultant for Zeltiq Aesthetics, and an investigator on many of the company’s development trials. She’s also a consultant for Allergan, manufacturer of Kybella, which recently acquired Zeltiq. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – Gentler vacuum pressure seems to reduce the risk of paradoxical adipose hyperplasia after cryolipolysis, according to Suzanne Kilmer, MD, director of the Laser and Skin Surgery Center of Northern California, Sacramento.
She and her colleagues have noticed a reduction with the newer CoolAdvantage applicators from Zeltiq Aesthetics, the manufacturer of CoolSculpting equipment. CoolAdvantage runs colder and with less suction than earlier applicators. “It seems to work equally as well,” but with shorter treatment times, less bruising, and less discomfort. Although paradoxical adipose hyperplasia (PAH) “is incredibly rare, it is something we want to reduce, and we do see decreased incidence with these new applicators,” Dr. Kilmer said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Typically, one CoolSculpting session will get rid of about 20%-25% of the fat sucked up into the cryolipolysis cup. There can be some discomfort, for instance, when ice crystals are massaged afterward. To ensure patient satisfaction, “you really need to be realistic about what they can expect. It’s likely to be more than one session,” she said.
Another newer option from the manufacturer is the CoolMini applicator for submental fat. Dr. Kilmer generally does two overlapping applications with the CoolMini in the same session, in order to cover as much chin fat as possible. There will be what looks like a stick of butter under the chin when the applicators are removed; it goes away after a few minutes of massage. Patient satisfaction is high, but there can be unveiling of the platysmal bands, which is “something you want to talk to patients about ahead of time,” she said.
She sometimes uses the CoolMini first, followed by the other recently available option for submental fat, deoxycholic acid (Kybella). “We shrink down everything we can with CoolSculpting, and then come back with Kybella to clean up whatever’s left.” Using this approach, patients are injected with less deoxycholic acid, with less inflammation, she said.
“I think you get more fat loss out of a given CoolSculpting treatment than you do with Kybella,” said Dr. Kilmer, who noted that deoxycholic acid is also an option for PAH.
As for going off label with CoolSculpting for jowls, “we’ve done it, and I tell everybody there’s a chance of a 2-3 month palsy. All you are really doing is demyelinating the nerve, not injuring it. If you do liposuction, you actually have a little bit of risk of actually injuring it. You can use a nerve stimulator to map out the nerves beforehand,” she said.
Dr. Kilmer is a consultant for Zeltiq Aesthetics, and an investigator on many of the company’s development trials. She’s also a consultant for Allergan, manufacturer of Kybella, which recently acquired Zeltiq. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
When to worry about congenital melanocytic nevi
KAUAI, HAWAII – according to Jennifer Huang, MD, a pediatric dermatologist at Boston Children’s Hospital.
Two or more nevi increase the risk of CNS involvement, which in turn increases the risk of malignant conversion by more than 16-fold.
Among the studies she cited was a 2017 literature review of 448 children with congenital nevi, 10 of whom developed melanoma: It arose in the skin in 2, the brain in 6, and an unknown location in 2. All 10 children were born with two or more nevi, and not all of them had large or giant nevi, which is a known risk factor for malignant conversion (Br J Dermatol. 2017 May;176[5]:1131-43).
“If the scanning brain MRI is normal, [children] might not have congenital melanocytic nevus syndrome, and would be at low risk for melanoma,” Dr. Huang said. “If it’s abnormal, they might be at high risk for melanoma.” In the 2017 study, the odds ratio for melanoma with an abnormal MRI was 16.7 (P = .001).
Both melanocytes and neuronal cells arise from the embryonic neural crest, which explains the link between congenital nevi and brain lesions. Almost all congenital nevi are associated with early postzygotic mutations in the NRAS gene, and it’s possible the mutations affect other neural crest cell lines, including in the CNS, she said.
It’s also important to remember that childhood melanoma often doesn’t follow the ABCDE (asymmetry, border irregularity, color not uniform, diameter greater than 6 mm, and evolving) signs of melanoma common in adults.
In a retrospective study of 70 children with melanoma or ambiguous melanocytic tumors, 40% of pubertal subjects and 60% of prepubertal participants did not meet conventional adult ABCDE criteria. The majority of cases were raised, even in color, less than 6 mm across, symmetric, and de novo (J Am Acad Dermatol. 2013 Jun;68[6]:913-25).
It turns out that rapid evolution in size, shape, and color is the number one, unifying factor in childhood melanomas. Other key clues include raised lesions with uniform color or no pigmentation at all. A modified ABCDE for pediatric melanoma has been proposed: amelanotic, bump/bleeding, color uniform, diameter variable, de novo, and evolution.
“The lesson to learn is not to ignore the traditional ABCDEs of melanoma, but to recognize that pediatric melanoma may present with different clinical characteristics, and to incorporate this awareness into our practice,” Dr. Huang said.
She did not have any disclosures. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – according to Jennifer Huang, MD, a pediatric dermatologist at Boston Children’s Hospital.
Two or more nevi increase the risk of CNS involvement, which in turn increases the risk of malignant conversion by more than 16-fold.
Among the studies she cited was a 2017 literature review of 448 children with congenital nevi, 10 of whom developed melanoma: It arose in the skin in 2, the brain in 6, and an unknown location in 2. All 10 children were born with two or more nevi, and not all of them had large or giant nevi, which is a known risk factor for malignant conversion (Br J Dermatol. 2017 May;176[5]:1131-43).
“If the scanning brain MRI is normal, [children] might not have congenital melanocytic nevus syndrome, and would be at low risk for melanoma,” Dr. Huang said. “If it’s abnormal, they might be at high risk for melanoma.” In the 2017 study, the odds ratio for melanoma with an abnormal MRI was 16.7 (P = .001).
Both melanocytes and neuronal cells arise from the embryonic neural crest, which explains the link between congenital nevi and brain lesions. Almost all congenital nevi are associated with early postzygotic mutations in the NRAS gene, and it’s possible the mutations affect other neural crest cell lines, including in the CNS, she said.
It’s also important to remember that childhood melanoma often doesn’t follow the ABCDE (asymmetry, border irregularity, color not uniform, diameter greater than 6 mm, and evolving) signs of melanoma common in adults.
In a retrospective study of 70 children with melanoma or ambiguous melanocytic tumors, 40% of pubertal subjects and 60% of prepubertal participants did not meet conventional adult ABCDE criteria. The majority of cases were raised, even in color, less than 6 mm across, symmetric, and de novo (J Am Acad Dermatol. 2013 Jun;68[6]:913-25).
It turns out that rapid evolution in size, shape, and color is the number one, unifying factor in childhood melanomas. Other key clues include raised lesions with uniform color or no pigmentation at all. A modified ABCDE for pediatric melanoma has been proposed: amelanotic, bump/bleeding, color uniform, diameter variable, de novo, and evolution.
“The lesson to learn is not to ignore the traditional ABCDEs of melanoma, but to recognize that pediatric melanoma may present with different clinical characteristics, and to incorporate this awareness into our practice,” Dr. Huang said.
She did not have any disclosures. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – according to Jennifer Huang, MD, a pediatric dermatologist at Boston Children’s Hospital.
Two or more nevi increase the risk of CNS involvement, which in turn increases the risk of malignant conversion by more than 16-fold.
Among the studies she cited was a 2017 literature review of 448 children with congenital nevi, 10 of whom developed melanoma: It arose in the skin in 2, the brain in 6, and an unknown location in 2. All 10 children were born with two or more nevi, and not all of them had large or giant nevi, which is a known risk factor for malignant conversion (Br J Dermatol. 2017 May;176[5]:1131-43).
“If the scanning brain MRI is normal, [children] might not have congenital melanocytic nevus syndrome, and would be at low risk for melanoma,” Dr. Huang said. “If it’s abnormal, they might be at high risk for melanoma.” In the 2017 study, the odds ratio for melanoma with an abnormal MRI was 16.7 (P = .001).
Both melanocytes and neuronal cells arise from the embryonic neural crest, which explains the link between congenital nevi and brain lesions. Almost all congenital nevi are associated with early postzygotic mutations in the NRAS gene, and it’s possible the mutations affect other neural crest cell lines, including in the CNS, she said.
It’s also important to remember that childhood melanoma often doesn’t follow the ABCDE (asymmetry, border irregularity, color not uniform, diameter greater than 6 mm, and evolving) signs of melanoma common in adults.
In a retrospective study of 70 children with melanoma or ambiguous melanocytic tumors, 40% of pubertal subjects and 60% of prepubertal participants did not meet conventional adult ABCDE criteria. The majority of cases were raised, even in color, less than 6 mm across, symmetric, and de novo (J Am Acad Dermatol. 2013 Jun;68[6]:913-25).
It turns out that rapid evolution in size, shape, and color is the number one, unifying factor in childhood melanomas. Other key clues include raised lesions with uniform color or no pigmentation at all. A modified ABCDE for pediatric melanoma has been proposed: amelanotic, bump/bleeding, color uniform, diameter variable, de novo, and evolution.
“The lesson to learn is not to ignore the traditional ABCDEs of melanoma, but to recognize that pediatric melanoma may present with different clinical characteristics, and to incorporate this awareness into our practice,” Dr. Huang said.
She did not have any disclosures. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Consider drug holidays for BCC patients on hedgehog inhibitors
KAUAI, HAWAII – according to Kishwer Nehal, MD, director of Mohs micrographic and dermatologic surgery at Memorial Sloan Kettering Cancer Center, New York.
That’s important because, although some patients have a good response to vismodegib, more – about 80% – have side effects that make it necessary to stop treatment, including muscle spasms and weight loss, among other problems. Side effects often come on quickly and can become intolerable after a few months of treatment, so physicians have looked for alternative dosing regimens to hold them off, with some success.
Compared with those on continuous dosing, fewer patients on intermittent dosing discontinued treatment for adverse events (23% versus 31%). Patients on intermittent dosing also experienced fewer grade 3 adverse events (31% versus 44%) and were on treatment for a longer period of time (a median of 71.4 weeks versus 37.6 weeks).
Meanwhile, among those on intermittent dosing, the number of BCCs was reduced in more than half of the patients in both interrupted treatment groups, but more so in the 12-weeks-on/8-weeks-off group (Lancet Oncol. 2017 Mar; 18[3]:404-12).
Other treatment options are being explored for vismodegib, as well as for sonidegib (Odomzo), another hedgehog signaling pathway inhibitor approved for advanced BCC. Ongoing trials are looking at the use of hedgehog inhibitors with radiation, and for shrinking tumors before surgery, Dr. Nehal said
For now, however, surgery remains the mainstay of treatment for BCC; both biologics are indicated for when other treatments fail or are not feasible. For high-risk BCC (meaning high risk for recurrence, based on infiltrative or poorly defined histology, perineural or bony involvement, or location on the face, for instance), “surgery with clear margins remains the goal and is the most effective treatment. For a high-risk [BCC], you pretty much need surgery,” she said.
Recurrence is less likely with Mohs surgery than with standard excision. When Mohs isn’t available, “you should wait for the pathology report before reconstruction,” she said.
“Radiation for high-risk [BCC] is really reserved for nonsurgical candidates,” Dr. Nehal commented. There are only two scenarios to consider radiation in high-risk BCC, “and they really have no proven benefit in any sort of prospective trial. One is if you cannot, after exhaustive surgery, clear your very high risk [BCC].” The other is if there is “really large nerve involvement, greater than 0.1 mm, or such extensive perineural involvement that surgery is unlikely to be successful,” she said.
Dr. Nehal had no relevant disclosures. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – according to Kishwer Nehal, MD, director of Mohs micrographic and dermatologic surgery at Memorial Sloan Kettering Cancer Center, New York.
That’s important because, although some patients have a good response to vismodegib, more – about 80% – have side effects that make it necessary to stop treatment, including muscle spasms and weight loss, among other problems. Side effects often come on quickly and can become intolerable after a few months of treatment, so physicians have looked for alternative dosing regimens to hold them off, with some success.
Compared with those on continuous dosing, fewer patients on intermittent dosing discontinued treatment for adverse events (23% versus 31%). Patients on intermittent dosing also experienced fewer grade 3 adverse events (31% versus 44%) and were on treatment for a longer period of time (a median of 71.4 weeks versus 37.6 weeks).
Meanwhile, among those on intermittent dosing, the number of BCCs was reduced in more than half of the patients in both interrupted treatment groups, but more so in the 12-weeks-on/8-weeks-off group (Lancet Oncol. 2017 Mar; 18[3]:404-12).
Other treatment options are being explored for vismodegib, as well as for sonidegib (Odomzo), another hedgehog signaling pathway inhibitor approved for advanced BCC. Ongoing trials are looking at the use of hedgehog inhibitors with radiation, and for shrinking tumors before surgery, Dr. Nehal said
For now, however, surgery remains the mainstay of treatment for BCC; both biologics are indicated for when other treatments fail or are not feasible. For high-risk BCC (meaning high risk for recurrence, based on infiltrative or poorly defined histology, perineural or bony involvement, or location on the face, for instance), “surgery with clear margins remains the goal and is the most effective treatment. For a high-risk [BCC], you pretty much need surgery,” she said.
Recurrence is less likely with Mohs surgery than with standard excision. When Mohs isn’t available, “you should wait for the pathology report before reconstruction,” she said.
“Radiation for high-risk [BCC] is really reserved for nonsurgical candidates,” Dr. Nehal commented. There are only two scenarios to consider radiation in high-risk BCC, “and they really have no proven benefit in any sort of prospective trial. One is if you cannot, after exhaustive surgery, clear your very high risk [BCC].” The other is if there is “really large nerve involvement, greater than 0.1 mm, or such extensive perineural involvement that surgery is unlikely to be successful,” she said.
Dr. Nehal had no relevant disclosures. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – according to Kishwer Nehal, MD, director of Mohs micrographic and dermatologic surgery at Memorial Sloan Kettering Cancer Center, New York.
That’s important because, although some patients have a good response to vismodegib, more – about 80% – have side effects that make it necessary to stop treatment, including muscle spasms and weight loss, among other problems. Side effects often come on quickly and can become intolerable after a few months of treatment, so physicians have looked for alternative dosing regimens to hold them off, with some success.
Compared with those on continuous dosing, fewer patients on intermittent dosing discontinued treatment for adverse events (23% versus 31%). Patients on intermittent dosing also experienced fewer grade 3 adverse events (31% versus 44%) and were on treatment for a longer period of time (a median of 71.4 weeks versus 37.6 weeks).
Meanwhile, among those on intermittent dosing, the number of BCCs was reduced in more than half of the patients in both interrupted treatment groups, but more so in the 12-weeks-on/8-weeks-off group (Lancet Oncol. 2017 Mar; 18[3]:404-12).
Other treatment options are being explored for vismodegib, as well as for sonidegib (Odomzo), another hedgehog signaling pathway inhibitor approved for advanced BCC. Ongoing trials are looking at the use of hedgehog inhibitors with radiation, and for shrinking tumors before surgery, Dr. Nehal said
For now, however, surgery remains the mainstay of treatment for BCC; both biologics are indicated for when other treatments fail or are not feasible. For high-risk BCC (meaning high risk for recurrence, based on infiltrative or poorly defined histology, perineural or bony involvement, or location on the face, for instance), “surgery with clear margins remains the goal and is the most effective treatment. For a high-risk [BCC], you pretty much need surgery,” she said.
Recurrence is less likely with Mohs surgery than with standard excision. When Mohs isn’t available, “you should wait for the pathology report before reconstruction,” she said.
“Radiation for high-risk [BCC] is really reserved for nonsurgical candidates,” Dr. Nehal commented. There are only two scenarios to consider radiation in high-risk BCC, “and they really have no proven benefit in any sort of prospective trial. One is if you cannot, after exhaustive surgery, clear your very high risk [BCC].” The other is if there is “really large nerve involvement, greater than 0.1 mm, or such extensive perineural involvement that surgery is unlikely to be successful,” she said.
Dr. Nehal had no relevant disclosures. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Phase 3 trials show halobetasol/tazarotene lotion works for psoriasis
KAUAI, HAWAII – in two phase 3 randomized, double-blind, multicenter clinical trials, Linda Stein Gold, MD, reported at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
The fixed combination of halobetasol 0.01%/tazarotene 0.045% lotion takes advantage of an observation made 20 years ago: When tazarotene is combined with a potent topical corticosteroid, therapeutic efficacy is amplified synergistically while the problematic local side effects of each agent are diminished, explained Dr. Stein Gold, director of dermatology research at the Henry Ford Health System, Detroit.
“Tazarotene: Great for acne, but think of it again for psoriasis,” Dr. Stein Gold said. “It makes sense. Tazarotene improves differentiation of the skin; it decreases inflammation; it decreases proliferation – it does all the good things that we want to do for psoriasis.
“It’s got a little bit of baggage, though,” she continued. “It’s pregnancy Category X, so you have to make sure a woman who is or may become pregnant is not using it. And there are some side effects. It can be tough to use. When you use it in psoriasis you can get local irritation up to 30% of the time.”
The two parallel phase 3 randomized trials plus a separate phase 2 study, all of which Dr. Stein Gold was involved in, showed that the efficacy of the investigational halobetasol/tazarotene fixed combination was greater than either component alone, side effects were minimized, and efficacy remained durable 4 weeks after the 8-week treatment course ended.
The not-yet-published phase 3 trials included 418 patients with moderate to severe psoriasis randomized 2:1 to once-daily application of halobetasol/tazarotene or its vehicle for 8 weeks. Treatment success, defined as at least a two-grade improvement from baseline in Investigator’s Global Assessment score plus a score of clear or almost clear, was documented at 8 weeks in 35.8% of the halobetasol/tazarotene group in one study and 45.3% in the other, compared with 7% and 12.5% of controls, respectively.
In addition, after 8 weeks, affected body surface area was reduced by a mean of 32.8% in one study and by 42.5% in the other. There was also at least a two-grade improvement in plaque erythema at the target lesion site in 42.2% and 49.6% of halobetasol/tazarotene–treated patients in the two trials. A two-grade improvement in plaque elevation was noted in 59.3% and 59.7% of patients, while for plaque scaling, the figures were 59.4% and 62.9%.
“What we found in the two sister studies was statistically significant success in getting those plaques from moderate/severe all the way down to clear/almost clear,” Dr. Stein Gold said.
The most frequently reported treatment-emergent adverse events included contact dermatitis in 7.4% of the active treatment group and application site pain in 2.6%. Most side effects were mild or moderate in nature.
The phase 2 study, which included 212 psoriasis patients, looked specifically at maintenance of efficacy after end of treatment. Here, halobetasol/tazarotene showed durability of therapeutic benefit: 4 weeks after completing the 8-week course of once-daily halobetasol/tazarotene, 38.2% of patients still met the criteria for treatment success. The minimal skin atrophy that arose during treatment largely resolved during the subsequent 4 weeks off treatment.
The clinical trials were supported by Valeant. Dr. Stein Gold reported receiving research grants from and serving as a consultant to, paid speaker for, and scientific advisory board member for Valeant and numerous other pharmaceutical companies active in dermatologic drug development.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – in two phase 3 randomized, double-blind, multicenter clinical trials, Linda Stein Gold, MD, reported at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
The fixed combination of halobetasol 0.01%/tazarotene 0.045% lotion takes advantage of an observation made 20 years ago: When tazarotene is combined with a potent topical corticosteroid, therapeutic efficacy is amplified synergistically while the problematic local side effects of each agent are diminished, explained Dr. Stein Gold, director of dermatology research at the Henry Ford Health System, Detroit.
“Tazarotene: Great for acne, but think of it again for psoriasis,” Dr. Stein Gold said. “It makes sense. Tazarotene improves differentiation of the skin; it decreases inflammation; it decreases proliferation – it does all the good things that we want to do for psoriasis.
“It’s got a little bit of baggage, though,” she continued. “It’s pregnancy Category X, so you have to make sure a woman who is or may become pregnant is not using it. And there are some side effects. It can be tough to use. When you use it in psoriasis you can get local irritation up to 30% of the time.”
The two parallel phase 3 randomized trials plus a separate phase 2 study, all of which Dr. Stein Gold was involved in, showed that the efficacy of the investigational halobetasol/tazarotene fixed combination was greater than either component alone, side effects were minimized, and efficacy remained durable 4 weeks after the 8-week treatment course ended.
The not-yet-published phase 3 trials included 418 patients with moderate to severe psoriasis randomized 2:1 to once-daily application of halobetasol/tazarotene or its vehicle for 8 weeks. Treatment success, defined as at least a two-grade improvement from baseline in Investigator’s Global Assessment score plus a score of clear or almost clear, was documented at 8 weeks in 35.8% of the halobetasol/tazarotene group in one study and 45.3% in the other, compared with 7% and 12.5% of controls, respectively.
In addition, after 8 weeks, affected body surface area was reduced by a mean of 32.8% in one study and by 42.5% in the other. There was also at least a two-grade improvement in plaque erythema at the target lesion site in 42.2% and 49.6% of halobetasol/tazarotene–treated patients in the two trials. A two-grade improvement in plaque elevation was noted in 59.3% and 59.7% of patients, while for plaque scaling, the figures were 59.4% and 62.9%.
“What we found in the two sister studies was statistically significant success in getting those plaques from moderate/severe all the way down to clear/almost clear,” Dr. Stein Gold said.
The most frequently reported treatment-emergent adverse events included contact dermatitis in 7.4% of the active treatment group and application site pain in 2.6%. Most side effects were mild or moderate in nature.
The phase 2 study, which included 212 psoriasis patients, looked specifically at maintenance of efficacy after end of treatment. Here, halobetasol/tazarotene showed durability of therapeutic benefit: 4 weeks after completing the 8-week course of once-daily halobetasol/tazarotene, 38.2% of patients still met the criteria for treatment success. The minimal skin atrophy that arose during treatment largely resolved during the subsequent 4 weeks off treatment.
The clinical trials were supported by Valeant. Dr. Stein Gold reported receiving research grants from and serving as a consultant to, paid speaker for, and scientific advisory board member for Valeant and numerous other pharmaceutical companies active in dermatologic drug development.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – in two phase 3 randomized, double-blind, multicenter clinical trials, Linda Stein Gold, MD, reported at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
The fixed combination of halobetasol 0.01%/tazarotene 0.045% lotion takes advantage of an observation made 20 years ago: When tazarotene is combined with a potent topical corticosteroid, therapeutic efficacy is amplified synergistically while the problematic local side effects of each agent are diminished, explained Dr. Stein Gold, director of dermatology research at the Henry Ford Health System, Detroit.
“Tazarotene: Great for acne, but think of it again for psoriasis,” Dr. Stein Gold said. “It makes sense. Tazarotene improves differentiation of the skin; it decreases inflammation; it decreases proliferation – it does all the good things that we want to do for psoriasis.
“It’s got a little bit of baggage, though,” she continued. “It’s pregnancy Category X, so you have to make sure a woman who is or may become pregnant is not using it. And there are some side effects. It can be tough to use. When you use it in psoriasis you can get local irritation up to 30% of the time.”
The two parallel phase 3 randomized trials plus a separate phase 2 study, all of which Dr. Stein Gold was involved in, showed that the efficacy of the investigational halobetasol/tazarotene fixed combination was greater than either component alone, side effects were minimized, and efficacy remained durable 4 weeks after the 8-week treatment course ended.
The not-yet-published phase 3 trials included 418 patients with moderate to severe psoriasis randomized 2:1 to once-daily application of halobetasol/tazarotene or its vehicle for 8 weeks. Treatment success, defined as at least a two-grade improvement from baseline in Investigator’s Global Assessment score plus a score of clear or almost clear, was documented at 8 weeks in 35.8% of the halobetasol/tazarotene group in one study and 45.3% in the other, compared with 7% and 12.5% of controls, respectively.
In addition, after 8 weeks, affected body surface area was reduced by a mean of 32.8% in one study and by 42.5% in the other. There was also at least a two-grade improvement in plaque erythema at the target lesion site in 42.2% and 49.6% of halobetasol/tazarotene–treated patients in the two trials. A two-grade improvement in plaque elevation was noted in 59.3% and 59.7% of patients, while for plaque scaling, the figures were 59.4% and 62.9%.
“What we found in the two sister studies was statistically significant success in getting those plaques from moderate/severe all the way down to clear/almost clear,” Dr. Stein Gold said.
The most frequently reported treatment-emergent adverse events included contact dermatitis in 7.4% of the active treatment group and application site pain in 2.6%. Most side effects were mild or moderate in nature.
The phase 2 study, which included 212 psoriasis patients, looked specifically at maintenance of efficacy after end of treatment. Here, halobetasol/tazarotene showed durability of therapeutic benefit: 4 weeks after completing the 8-week course of once-daily halobetasol/tazarotene, 38.2% of patients still met the criteria for treatment success. The minimal skin atrophy that arose during treatment largely resolved during the subsequent 4 weeks off treatment.
The clinical trials were supported by Valeant. Dr. Stein Gold reported receiving research grants from and serving as a consultant to, paid speaker for, and scientific advisory board member for Valeant and numerous other pharmaceutical companies active in dermatologic drug development.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Here comes bimekizumab, the newest IL-17 inhibitor
KAUAI, HAWAII –
And that’s not all: Much the same was true in patients with psoriatic arthritis in the parallel phase 2b BE ACTIVE study and for ankylosing spondylitis in the BE AGILE study. BE ABLE was a double-blind, 12-week, multicenter, five-arm, placebo-controlled, dose-ranging study of 250 psoriasis patients randomized to various doses of subcutaneous bimekizumab or placebo every 4 weeks. The primary outcome – the PASI 90 response rate at 12 weeks, rather than the lower-bar PASI 75 endpoint more typically used in clinical trials – was 79% at the optimal dose. The PASI 100 rate – complete clearance of disease – at 12 weeks was 60%, Craig L. Leonardi, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
lthough Dr. Leonardi is a distinguished psoriasis clinical trialist, he wasn’t involved in the BE ABLE study. Only top line results have been announced to date, although publication of the BE ABLE, BE AGILE, and BE ACTIVE results and presentations at major medical meetings are pending.
Bimekizumab is a humanized IgG1 monoclonal antibody which uniquely neutralizes both IL-17A and IL-17F. In contrast, secukinumab (Cosentyx) and ixekizumab (Taltz) specifically inhibit IL-17A, while brodalumab (Siliq) is a pan-IL-17 receptor antagonist, inhibiting the IL-17 A, A/F, E, F, and C receptors. The impressive clinical outcomes of the three BE phase 2b studies validate the notion that IL-17F is an important cytokine in tissue inflammation across a range of dermatologic and rheumatologic diseases.
A long-term extension of BE ABLE is ongoing. In addition, a phase 3 randomized trial of bimekizumab versus adalimumab (Humira) versus placebo in 450 psoriasis patients is now recruiting, as is a separate phase 3 placebo-controlled head to head comparison of bimekizumab versus ustekinumab (Stelara).
The BE ACTIVE study included 206 psoriatic arthritis patients. At the top dose of bimekizumab, the week 12 rate of at least a 50% improvement in joint symptoms, or ACR 50 response, was 46%, compared with 7% in placebo-treated controls. Patients with concomitant psoriasis over at least 3% of their body surface area demonstrated a 65% PASI 90 response rate at 12 weeks.
BE AGILE included 303 patients with ankylosing spondylitis. Forty-seven percent of those randomized to the top-performing dose of bimekizumab had at least a 40% improvement in their Ankylosing Spondylitis Activity Score, or ASAS 40, at week 12, as did 13% in the placebo arm.
Bimekizumab is being developed by UCB, which is planning additional studies advancing the biologic in all three diseases studied in the phase 2b trials.
Dr. Leonardi reported receiving research grants from well over a dozen pharmaceutical companies and serving as a consultant to UCB and others.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII –
And that’s not all: Much the same was true in patients with psoriatic arthritis in the parallel phase 2b BE ACTIVE study and for ankylosing spondylitis in the BE AGILE study. BE ABLE was a double-blind, 12-week, multicenter, five-arm, placebo-controlled, dose-ranging study of 250 psoriasis patients randomized to various doses of subcutaneous bimekizumab or placebo every 4 weeks. The primary outcome – the PASI 90 response rate at 12 weeks, rather than the lower-bar PASI 75 endpoint more typically used in clinical trials – was 79% at the optimal dose. The PASI 100 rate – complete clearance of disease – at 12 weeks was 60%, Craig L. Leonardi, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
lthough Dr. Leonardi is a distinguished psoriasis clinical trialist, he wasn’t involved in the BE ABLE study. Only top line results have been announced to date, although publication of the BE ABLE, BE AGILE, and BE ACTIVE results and presentations at major medical meetings are pending.
Bimekizumab is a humanized IgG1 monoclonal antibody which uniquely neutralizes both IL-17A and IL-17F. In contrast, secukinumab (Cosentyx) and ixekizumab (Taltz) specifically inhibit IL-17A, while brodalumab (Siliq) is a pan-IL-17 receptor antagonist, inhibiting the IL-17 A, A/F, E, F, and C receptors. The impressive clinical outcomes of the three BE phase 2b studies validate the notion that IL-17F is an important cytokine in tissue inflammation across a range of dermatologic and rheumatologic diseases.
A long-term extension of BE ABLE is ongoing. In addition, a phase 3 randomized trial of bimekizumab versus adalimumab (Humira) versus placebo in 450 psoriasis patients is now recruiting, as is a separate phase 3 placebo-controlled head to head comparison of bimekizumab versus ustekinumab (Stelara).
The BE ACTIVE study included 206 psoriatic arthritis patients. At the top dose of bimekizumab, the week 12 rate of at least a 50% improvement in joint symptoms, or ACR 50 response, was 46%, compared with 7% in placebo-treated controls. Patients with concomitant psoriasis over at least 3% of their body surface area demonstrated a 65% PASI 90 response rate at 12 weeks.
BE AGILE included 303 patients with ankylosing spondylitis. Forty-seven percent of those randomized to the top-performing dose of bimekizumab had at least a 40% improvement in their Ankylosing Spondylitis Activity Score, or ASAS 40, at week 12, as did 13% in the placebo arm.
Bimekizumab is being developed by UCB, which is planning additional studies advancing the biologic in all three diseases studied in the phase 2b trials.
Dr. Leonardi reported receiving research grants from well over a dozen pharmaceutical companies and serving as a consultant to UCB and others.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII –
And that’s not all: Much the same was true in patients with psoriatic arthritis in the parallel phase 2b BE ACTIVE study and for ankylosing spondylitis in the BE AGILE study. BE ABLE was a double-blind, 12-week, multicenter, five-arm, placebo-controlled, dose-ranging study of 250 psoriasis patients randomized to various doses of subcutaneous bimekizumab or placebo every 4 weeks. The primary outcome – the PASI 90 response rate at 12 weeks, rather than the lower-bar PASI 75 endpoint more typically used in clinical trials – was 79% at the optimal dose. The PASI 100 rate – complete clearance of disease – at 12 weeks was 60%, Craig L. Leonardi, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
lthough Dr. Leonardi is a distinguished psoriasis clinical trialist, he wasn’t involved in the BE ABLE study. Only top line results have been announced to date, although publication of the BE ABLE, BE AGILE, and BE ACTIVE results and presentations at major medical meetings are pending.
Bimekizumab is a humanized IgG1 monoclonal antibody which uniquely neutralizes both IL-17A and IL-17F. In contrast, secukinumab (Cosentyx) and ixekizumab (Taltz) specifically inhibit IL-17A, while brodalumab (Siliq) is a pan-IL-17 receptor antagonist, inhibiting the IL-17 A, A/F, E, F, and C receptors. The impressive clinical outcomes of the three BE phase 2b studies validate the notion that IL-17F is an important cytokine in tissue inflammation across a range of dermatologic and rheumatologic diseases.
A long-term extension of BE ABLE is ongoing. In addition, a phase 3 randomized trial of bimekizumab versus adalimumab (Humira) versus placebo in 450 psoriasis patients is now recruiting, as is a separate phase 3 placebo-controlled head to head comparison of bimekizumab versus ustekinumab (Stelara).
The BE ACTIVE study included 206 psoriatic arthritis patients. At the top dose of bimekizumab, the week 12 rate of at least a 50% improvement in joint symptoms, or ACR 50 response, was 46%, compared with 7% in placebo-treated controls. Patients with concomitant psoriasis over at least 3% of their body surface area demonstrated a 65% PASI 90 response rate at 12 weeks.
BE AGILE included 303 patients with ankylosing spondylitis. Forty-seven percent of those randomized to the top-performing dose of bimekizumab had at least a 40% improvement in their Ankylosing Spondylitis Activity Score, or ASAS 40, at week 12, as did 13% in the placebo arm.
Bimekizumab is being developed by UCB, which is planning additional studies advancing the biologic in all three diseases studied in the phase 2b trials.
Dr. Leonardi reported receiving research grants from well over a dozen pharmaceutical companies and serving as a consultant to UCB and others.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Dermatology practice gaps: Missed diagnoses
KAUAI, HAWAII – Up to 130,000 patients hospitalized for treatment of lower extremity cellulitis annually in the United States turn out to have been misdiagnosed – and therein lies an opportunity for dermatologists to make a difference, according to Erik J. Stratman, MD, chairman of the department of dermatology at the Marshfield (Wisc.) Clinic.
As a section editor for UptoDate, he monitors the medical literature to identify , which he defines as things he and, he suspects, many other dermatologists are “either doing or not doing in practice that we shouldn’t or should be doing,” he explained at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
At the Hawaii meeting, he zeroed in on two such practice gaps pertaining to missed diagnoses.
Lower extremity cellulitis
A 2017 American Academy of Dermatology report on the national burden of skin disease contained eye-popping figures on the heavy toll of cellulitis. Cellulitis is the most common form of skin and soft tissue infection (SSTI). To put that into perspective, the annual incidence of SSTIs is 10-fold greater than that of pneumonia. Indeed, SSTIs account for 10% of all infectious disease–related hospitalizations across the country. There are 2.3 million emergency department visits per year for cellulitis, 14%-17% of which result in hospitalization (J Am Acad Dermatol. 2017 May;76[5]:958-972.e2).
Dr. Stratman, who is on the board of directors of the American Board of Dermatology, was favorably impressed with the work of a multicenter group of investigators who scrutinized 259 consecutive patients admitted with a diagnosis of lower extremity cellulitis through the emergency department at Massachusetts General Hospital in Boston. Seventy-nine of them (30.5%), were found to be misdiagnosed. Fifty-two of the 79 misdiagnosed patients had been admitted primarily for treatment of their supposed cellulitis: 44 of these 52, or 85%, didn’t require hospitalization, and 48 of the 52, or 92%, received unnecessary antibiotics.
Extrapolating from this experience, with application of cost data provided by the U.S. Agency for Healthcare Research and Quality, the investigators estimated that misdiagnosis of cellulitis results in 50,000 to 130,000 unnecessary hospitalizations annually. These hospitalizations for what the investigators termed “pseudocellulitis,” the majority of which is stasis dermatitis, resulted in inpatient costs estimated at up to $515 million per year. The unnecessary hospitalizations also led to an estimated 9,000 nosocomial infections, up to 5,000 Clostridium difficile infections, and a projected two to six cases of anaphylaxis resulting from exposure to the unnecessary antibiotics (JAMA Dermatol. 2017;153[2]:141-6).
Dr. Stratman said that the large Massachusetts General Hospital study mirrors his own experience when called upon to do a hospital consultation, as well as that of other dermatologists he has spoken with: “The number-one reason we get consulted is for stuff that is wrongfully admitted, mainly cellulitis.”
The investigators then went on to develop a simple prediction model for lower extremity cellulitis based upon their data. It’s called the ALT-70 score, an acronym for Asymmetric, Leukocytosis, Tachycardia, and Age greater than 70. A patient gets 3 points if one leg is affected, zero if both are. Age 70 or more is worth 2 points. A heart rate of 90 beats per minute or higher gets 1 point, as does a WBC of at least 10,000 per uL. A score of 0-2 spells at least an 83% likelihood that the patient has pseudocellulitis, while a score of 5 or points indicates at least an 82% likelihood of true cellulitis (J Am Acad Dermatol. 2017 Apr;76[4]:618-625.e2).
“If you don’t reach a score of 3, you’d better think a little bit harder before you hang that bag of vancomycin,” Dr. Stratman observed.
He ascribed the huge problem of misdiagnosed lower extremity cellulitis to several causes: emergency medicine physicians, hospitalists, and primary care physicians receive minimal dermatology training. In addition, there are no reliable diagnostic studies for the infection, and dermatologists are seldom consulted on patients with red legs, either because there are no dermatologists in a particular community or they don’t want to be consulted.
“It’s not all the dermatologists’ fault. Have you tried to get credentialed at a hospital lately? It’s a 1½-inch stack of papers and 8½ hours of electronic medical record training, if you’re lucky. So there are definitely barriers to overcoming this gap,” Dr. Stratman pointed out.
The best solution, he continued, is for dermatologists to take the initiative in educating hospitalists, emergency medicine specialists, and primary care physicians on the common mimickers of cellulitis, especially stasis dermatitis and contact dermatitis. This can happen through grand rounds presentations and feedback to consulting physicians.
“I think dermatologists have to take the lead on this,” Dr. Stratman said.
Underscreening for autoimmune thyroid disease in vitiligo patients
The international Vitiligo Working Group, citing evidence that 19% of patients with vitiligo have concomitant autoimmune thyroid disease and that the risk of developing this endocrine disease doubles every 5 years that a patient has vitiligo, has issued a call to action for dermatologists to ensure that their patients with vitiligo undergo periodic screening (J Am Acad Dermatol. 2017 Jul;77[1]:1-13).
This recommendation was based upon insights provided by a French prospective, observational study of 626 patients with vitiligo. The French investigators found that the risk of autoimmune thyroid disease doubled every 5 years and was associated with female sex, younger age at vitiligo onset, vitiligo on the trunk, and a personal history of autoimmune disease. They recommended screening every 2 years for thyroid-stimulating hormone and free thyroxine levels, as well as checking for serum antithyroperoxidase antibodies (Br J Dermatol. 2013 Apr;168[4]:756-61).
Dr. Stratman noted that some dermatologists may feel that ordering thyroid screening tests is outside their scope of practice. In that case, it’s important to engage with their vitiligo patient’s primary care physician to make sure the screening gets done.
He reported having no financial conflicts of interest regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – Up to 130,000 patients hospitalized for treatment of lower extremity cellulitis annually in the United States turn out to have been misdiagnosed – and therein lies an opportunity for dermatologists to make a difference, according to Erik J. Stratman, MD, chairman of the department of dermatology at the Marshfield (Wisc.) Clinic.
As a section editor for UptoDate, he monitors the medical literature to identify , which he defines as things he and, he suspects, many other dermatologists are “either doing or not doing in practice that we shouldn’t or should be doing,” he explained at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
At the Hawaii meeting, he zeroed in on two such practice gaps pertaining to missed diagnoses.
Lower extremity cellulitis
A 2017 American Academy of Dermatology report on the national burden of skin disease contained eye-popping figures on the heavy toll of cellulitis. Cellulitis is the most common form of skin and soft tissue infection (SSTI). To put that into perspective, the annual incidence of SSTIs is 10-fold greater than that of pneumonia. Indeed, SSTIs account for 10% of all infectious disease–related hospitalizations across the country. There are 2.3 million emergency department visits per year for cellulitis, 14%-17% of which result in hospitalization (J Am Acad Dermatol. 2017 May;76[5]:958-972.e2).
Dr. Stratman, who is on the board of directors of the American Board of Dermatology, was favorably impressed with the work of a multicenter group of investigators who scrutinized 259 consecutive patients admitted with a diagnosis of lower extremity cellulitis through the emergency department at Massachusetts General Hospital in Boston. Seventy-nine of them (30.5%), were found to be misdiagnosed. Fifty-two of the 79 misdiagnosed patients had been admitted primarily for treatment of their supposed cellulitis: 44 of these 52, or 85%, didn’t require hospitalization, and 48 of the 52, or 92%, received unnecessary antibiotics.
Extrapolating from this experience, with application of cost data provided by the U.S. Agency for Healthcare Research and Quality, the investigators estimated that misdiagnosis of cellulitis results in 50,000 to 130,000 unnecessary hospitalizations annually. These hospitalizations for what the investigators termed “pseudocellulitis,” the majority of which is stasis dermatitis, resulted in inpatient costs estimated at up to $515 million per year. The unnecessary hospitalizations also led to an estimated 9,000 nosocomial infections, up to 5,000 Clostridium difficile infections, and a projected two to six cases of anaphylaxis resulting from exposure to the unnecessary antibiotics (JAMA Dermatol. 2017;153[2]:141-6).
Dr. Stratman said that the large Massachusetts General Hospital study mirrors his own experience when called upon to do a hospital consultation, as well as that of other dermatologists he has spoken with: “The number-one reason we get consulted is for stuff that is wrongfully admitted, mainly cellulitis.”
The investigators then went on to develop a simple prediction model for lower extremity cellulitis based upon their data. It’s called the ALT-70 score, an acronym for Asymmetric, Leukocytosis, Tachycardia, and Age greater than 70. A patient gets 3 points if one leg is affected, zero if both are. Age 70 or more is worth 2 points. A heart rate of 90 beats per minute or higher gets 1 point, as does a WBC of at least 10,000 per uL. A score of 0-2 spells at least an 83% likelihood that the patient has pseudocellulitis, while a score of 5 or points indicates at least an 82% likelihood of true cellulitis (J Am Acad Dermatol. 2017 Apr;76[4]:618-625.e2).
“If you don’t reach a score of 3, you’d better think a little bit harder before you hang that bag of vancomycin,” Dr. Stratman observed.
He ascribed the huge problem of misdiagnosed lower extremity cellulitis to several causes: emergency medicine physicians, hospitalists, and primary care physicians receive minimal dermatology training. In addition, there are no reliable diagnostic studies for the infection, and dermatologists are seldom consulted on patients with red legs, either because there are no dermatologists in a particular community or they don’t want to be consulted.
“It’s not all the dermatologists’ fault. Have you tried to get credentialed at a hospital lately? It’s a 1½-inch stack of papers and 8½ hours of electronic medical record training, if you’re lucky. So there are definitely barriers to overcoming this gap,” Dr. Stratman pointed out.
The best solution, he continued, is for dermatologists to take the initiative in educating hospitalists, emergency medicine specialists, and primary care physicians on the common mimickers of cellulitis, especially stasis dermatitis and contact dermatitis. This can happen through grand rounds presentations and feedback to consulting physicians.
“I think dermatologists have to take the lead on this,” Dr. Stratman said.
Underscreening for autoimmune thyroid disease in vitiligo patients
The international Vitiligo Working Group, citing evidence that 19% of patients with vitiligo have concomitant autoimmune thyroid disease and that the risk of developing this endocrine disease doubles every 5 years that a patient has vitiligo, has issued a call to action for dermatologists to ensure that their patients with vitiligo undergo periodic screening (J Am Acad Dermatol. 2017 Jul;77[1]:1-13).
This recommendation was based upon insights provided by a French prospective, observational study of 626 patients with vitiligo. The French investigators found that the risk of autoimmune thyroid disease doubled every 5 years and was associated with female sex, younger age at vitiligo onset, vitiligo on the trunk, and a personal history of autoimmune disease. They recommended screening every 2 years for thyroid-stimulating hormone and free thyroxine levels, as well as checking for serum antithyroperoxidase antibodies (Br J Dermatol. 2013 Apr;168[4]:756-61).
Dr. Stratman noted that some dermatologists may feel that ordering thyroid screening tests is outside their scope of practice. In that case, it’s important to engage with their vitiligo patient’s primary care physician to make sure the screening gets done.
He reported having no financial conflicts of interest regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – Up to 130,000 patients hospitalized for treatment of lower extremity cellulitis annually in the United States turn out to have been misdiagnosed – and therein lies an opportunity for dermatologists to make a difference, according to Erik J. Stratman, MD, chairman of the department of dermatology at the Marshfield (Wisc.) Clinic.
As a section editor for UptoDate, he monitors the medical literature to identify , which he defines as things he and, he suspects, many other dermatologists are “either doing or not doing in practice that we shouldn’t or should be doing,” he explained at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
At the Hawaii meeting, he zeroed in on two such practice gaps pertaining to missed diagnoses.
Lower extremity cellulitis
A 2017 American Academy of Dermatology report on the national burden of skin disease contained eye-popping figures on the heavy toll of cellulitis. Cellulitis is the most common form of skin and soft tissue infection (SSTI). To put that into perspective, the annual incidence of SSTIs is 10-fold greater than that of pneumonia. Indeed, SSTIs account for 10% of all infectious disease–related hospitalizations across the country. There are 2.3 million emergency department visits per year for cellulitis, 14%-17% of which result in hospitalization (J Am Acad Dermatol. 2017 May;76[5]:958-972.e2).
Dr. Stratman, who is on the board of directors of the American Board of Dermatology, was favorably impressed with the work of a multicenter group of investigators who scrutinized 259 consecutive patients admitted with a diagnosis of lower extremity cellulitis through the emergency department at Massachusetts General Hospital in Boston. Seventy-nine of them (30.5%), were found to be misdiagnosed. Fifty-two of the 79 misdiagnosed patients had been admitted primarily for treatment of their supposed cellulitis: 44 of these 52, or 85%, didn’t require hospitalization, and 48 of the 52, or 92%, received unnecessary antibiotics.
Extrapolating from this experience, with application of cost data provided by the U.S. Agency for Healthcare Research and Quality, the investigators estimated that misdiagnosis of cellulitis results in 50,000 to 130,000 unnecessary hospitalizations annually. These hospitalizations for what the investigators termed “pseudocellulitis,” the majority of which is stasis dermatitis, resulted in inpatient costs estimated at up to $515 million per year. The unnecessary hospitalizations also led to an estimated 9,000 nosocomial infections, up to 5,000 Clostridium difficile infections, and a projected two to six cases of anaphylaxis resulting from exposure to the unnecessary antibiotics (JAMA Dermatol. 2017;153[2]:141-6).
Dr. Stratman said that the large Massachusetts General Hospital study mirrors his own experience when called upon to do a hospital consultation, as well as that of other dermatologists he has spoken with: “The number-one reason we get consulted is for stuff that is wrongfully admitted, mainly cellulitis.”
The investigators then went on to develop a simple prediction model for lower extremity cellulitis based upon their data. It’s called the ALT-70 score, an acronym for Asymmetric, Leukocytosis, Tachycardia, and Age greater than 70. A patient gets 3 points if one leg is affected, zero if both are. Age 70 or more is worth 2 points. A heart rate of 90 beats per minute or higher gets 1 point, as does a WBC of at least 10,000 per uL. A score of 0-2 spells at least an 83% likelihood that the patient has pseudocellulitis, while a score of 5 or points indicates at least an 82% likelihood of true cellulitis (J Am Acad Dermatol. 2017 Apr;76[4]:618-625.e2).
“If you don’t reach a score of 3, you’d better think a little bit harder before you hang that bag of vancomycin,” Dr. Stratman observed.
He ascribed the huge problem of misdiagnosed lower extremity cellulitis to several causes: emergency medicine physicians, hospitalists, and primary care physicians receive minimal dermatology training. In addition, there are no reliable diagnostic studies for the infection, and dermatologists are seldom consulted on patients with red legs, either because there are no dermatologists in a particular community or they don’t want to be consulted.
“It’s not all the dermatologists’ fault. Have you tried to get credentialed at a hospital lately? It’s a 1½-inch stack of papers and 8½ hours of electronic medical record training, if you’re lucky. So there are definitely barriers to overcoming this gap,” Dr. Stratman pointed out.
The best solution, he continued, is for dermatologists to take the initiative in educating hospitalists, emergency medicine specialists, and primary care physicians on the common mimickers of cellulitis, especially stasis dermatitis and contact dermatitis. This can happen through grand rounds presentations and feedback to consulting physicians.
“I think dermatologists have to take the lead on this,” Dr. Stratman said.
Underscreening for autoimmune thyroid disease in vitiligo patients
The international Vitiligo Working Group, citing evidence that 19% of patients with vitiligo have concomitant autoimmune thyroid disease and that the risk of developing this endocrine disease doubles every 5 years that a patient has vitiligo, has issued a call to action for dermatologists to ensure that their patients with vitiligo undergo periodic screening (J Am Acad Dermatol. 2017 Jul;77[1]:1-13).
This recommendation was based upon insights provided by a French prospective, observational study of 626 patients with vitiligo. The French investigators found that the risk of autoimmune thyroid disease doubled every 5 years and was associated with female sex, younger age at vitiligo onset, vitiligo on the trunk, and a personal history of autoimmune disease. They recommended screening every 2 years for thyroid-stimulating hormone and free thyroxine levels, as well as checking for serum antithyroperoxidase antibodies (Br J Dermatol. 2013 Apr;168[4]:756-61).
Dr. Stratman noted that some dermatologists may feel that ordering thyroid screening tests is outside their scope of practice. In that case, it’s important to engage with their vitiligo patient’s primary care physician to make sure the screening gets done.
He reported having no financial conflicts of interest regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
VIDEO: With tinea capitis, don’t be fooled by a Wood’s lamp
KAUAI, HAWAII – When it comes to diagnosing tinea capitis, you really can’t rely on a Wood’s lamp, according to pediatric dermatologist Robert Silverman, MD.
The Wood’s lamp generally misses the most common cause of tinea capitis in urban and suburban environments today, Trichophyton tonsurans, said Dr. Silverman, a pediatric dermatologist and clinical associate professor in the department of pediatrics at Georgetown University, Washington.
The dermatoscope, which “will allow you to see what is called the black dots of tinea capitis very, very closely,” is far better, he said in an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation
He explained the limitations of the Wood’s lamp in this setting, and what to look for with a dermatoscope. He had other tips to share, too, from years of experience treating the condition, including how to differentiate tinea capitis on exam from its most common mimics, why it’s best to include a counter stain when using potassium hydroxide, and how to motivate parents to wash their child’s hair more frequently to reduce spores on the hair and scalp.
Dr. Silverman disclosed relationships with Pierre Fabre, Pfizer, and Regeneron.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – When it comes to diagnosing tinea capitis, you really can’t rely on a Wood’s lamp, according to pediatric dermatologist Robert Silverman, MD.
The Wood’s lamp generally misses the most common cause of tinea capitis in urban and suburban environments today, Trichophyton tonsurans, said Dr. Silverman, a pediatric dermatologist and clinical associate professor in the department of pediatrics at Georgetown University, Washington.
The dermatoscope, which “will allow you to see what is called the black dots of tinea capitis very, very closely,” is far better, he said in an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation
He explained the limitations of the Wood’s lamp in this setting, and what to look for with a dermatoscope. He had other tips to share, too, from years of experience treating the condition, including how to differentiate tinea capitis on exam from its most common mimics, why it’s best to include a counter stain when using potassium hydroxide, and how to motivate parents to wash their child’s hair more frequently to reduce spores on the hair and scalp.
Dr. Silverman disclosed relationships with Pierre Fabre, Pfizer, and Regeneron.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – When it comes to diagnosing tinea capitis, you really can’t rely on a Wood’s lamp, according to pediatric dermatologist Robert Silverman, MD.
The Wood’s lamp generally misses the most common cause of tinea capitis in urban and suburban environments today, Trichophyton tonsurans, said Dr. Silverman, a pediatric dermatologist and clinical associate professor in the department of pediatrics at Georgetown University, Washington.
The dermatoscope, which “will allow you to see what is called the black dots of tinea capitis very, very closely,” is far better, he said in an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation
He explained the limitations of the Wood’s lamp in this setting, and what to look for with a dermatoscope. He had other tips to share, too, from years of experience treating the condition, including how to differentiate tinea capitis on exam from its most common mimics, why it’s best to include a counter stain when using potassium hydroxide, and how to motivate parents to wash their child’s hair more frequently to reduce spores on the hair and scalp.
Dr. Silverman disclosed relationships with Pierre Fabre, Pfizer, and Regeneron.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM SDEF HAWAII DERMATOLOGY SEMINAR
VIDEO: Off-label dupilumab finding a home in pediatric AD
KAUAI, HAWAII – Pediatric dermatologists aren’t waiting for Food and Drug Administration approval to try dupilumab (Dupixent) for their patients with severe atopic dermatitis.
It’s not approved in children, but the possibility of good control without the side effects of cyclosporine and other alternatives is too much to resist. A phase 2, company-sponsored study reported Eczema Area and Severity Index score improvements of up to 76% in pediatric patients treated with dupilumab, an interleukin-4 and IL-13 signaling blocker approved in 2017 for moderate to severe AD in adults.
Large pediatric trials are pending, but with results like that, “many of us just feel if it was our own kid, and we could get dupilumab, we would like to do that first,” said Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego.
It’s not just dupilumab that’s causing excitement. With almost 20 biologics in the pipeline, eczema seems poised to undergo a revolution in treatment much like psoriasis has in recent years.
Dr. Eichenfield explained (Eucrisa), a topical nonsteroidal phosphodiesterase-4 inhibitor approved for mild to moderate AD for children and adults ages two and older in December 2016, which doesn’t seem to have the duration limits of steroids, he said in an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Treatment of pediatric AD is “going to be a very different picture over the next few years,” he said.
Dr. Eichenfield is a consultant or investigator for many companies, including Regeneron/Sanofi, Genentech, Novartis, Pfizer, Lilly, and Allergan.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – Pediatric dermatologists aren’t waiting for Food and Drug Administration approval to try dupilumab (Dupixent) for their patients with severe atopic dermatitis.
It’s not approved in children, but the possibility of good control without the side effects of cyclosporine and other alternatives is too much to resist. A phase 2, company-sponsored study reported Eczema Area and Severity Index score improvements of up to 76% in pediatric patients treated with dupilumab, an interleukin-4 and IL-13 signaling blocker approved in 2017 for moderate to severe AD in adults.
Large pediatric trials are pending, but with results like that, “many of us just feel if it was our own kid, and we could get dupilumab, we would like to do that first,” said Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego.
It’s not just dupilumab that’s causing excitement. With almost 20 biologics in the pipeline, eczema seems poised to undergo a revolution in treatment much like psoriasis has in recent years.
Dr. Eichenfield explained (Eucrisa), a topical nonsteroidal phosphodiesterase-4 inhibitor approved for mild to moderate AD for children and adults ages two and older in December 2016, which doesn’t seem to have the duration limits of steroids, he said in an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Treatment of pediatric AD is “going to be a very different picture over the next few years,” he said.
Dr. Eichenfield is a consultant or investigator for many companies, including Regeneron/Sanofi, Genentech, Novartis, Pfizer, Lilly, and Allergan.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – Pediatric dermatologists aren’t waiting for Food and Drug Administration approval to try dupilumab (Dupixent) for their patients with severe atopic dermatitis.
It’s not approved in children, but the possibility of good control without the side effects of cyclosporine and other alternatives is too much to resist. A phase 2, company-sponsored study reported Eczema Area and Severity Index score improvements of up to 76% in pediatric patients treated with dupilumab, an interleukin-4 and IL-13 signaling blocker approved in 2017 for moderate to severe AD in adults.
Large pediatric trials are pending, but with results like that, “many of us just feel if it was our own kid, and we could get dupilumab, we would like to do that first,” said Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego.
It’s not just dupilumab that’s causing excitement. With almost 20 biologics in the pipeline, eczema seems poised to undergo a revolution in treatment much like psoriasis has in recent years.
Dr. Eichenfield explained (Eucrisa), a topical nonsteroidal phosphodiesterase-4 inhibitor approved for mild to moderate AD for children and adults ages two and older in December 2016, which doesn’t seem to have the duration limits of steroids, he said in an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Treatment of pediatric AD is “going to be a very different picture over the next few years,” he said.
Dr. Eichenfield is a consultant or investigator for many companies, including Regeneron/Sanofi, Genentech, Novartis, Pfizer, Lilly, and Allergan.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM SDEF HAWAII DERMATOLOGY SEMINAR
Get ready for certolizumab for psoriasis
KAUAI, HAWAII – When certolizumab pegol receives marketing approval for moderate to severe psoriasis – which experts say is a virtual lock – it will offer a singular advantage over current anti–tumor necrosis factor (anti-TNF) biologics: strong evidence of safety in pregnancy.
“ ” Kenneth B. Gordon, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Lots of women and their families are understandably deeply concerned about using powerful, transformative medications during pregnancy, even though they know from experience how debilitating inadequately treated psoriasis can be.
“Many women of childbearing potential would find [certolizumab] to be a preferential agent if they’re planning to become pregnant,” said Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
He cited the CRIB (A Multicenter, Postmarketing Study Evaluating the Transfer of Cimzia From the Mother to the Infant via the Placenta) study results presented by Alexa B. Kimball, MD, at the 2017 annual meeting of the European Academy of Dermatology and Venereology in Geneva as a major step forward in establishing the safety of certolizumab during pregnancy.
CRIB was a prospective postmarketing pharmacokinetic study that evaluated placental transfer of certolizumab from 16 pregnant women on the biologic to their infants. All of the mothers received their last dose of certolizumab for rheumatoid arthritis or other approved indications within 35 days of delivery. Blood samples were collected from mothers, newborns, and umbilical cords within 1 hour of delivery, and again from the infants at weeks 4 and 8 after delivery.
Only one infant had a detectable plasma level of certolizumab at birth, and it was barely measurable at 0.042 mcg/mL, as compared with 49.4 mcg/mL in the mother’s plasma. This is consistent with the fact that certolizumab’s pegylated arm allows only minimal or no placental transfer from mother to infant, so there is essentially no third trimester in utero fetal exposure. In contrast, as Dr. Kimball noted, other anti-TNF biologics lack a pegylated arm and thus preferentially cross the placenta, creating a theoretical increased risk of maternal pregnancy complications and/or congenital malformations.
Dr. Kimball, professor of dermatology at Harvard Medical School and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, both in Boston, also has been deeply involved in an ongoing registry (sponsored by certolizumab manufacturer UCB) of several hundred women on certolizumab in pregnancy. The data have reassuringly shown no increased risk of maternal pregnancy complications such as preeclampsia, gestational diabetes, or preterm birth, nor any increase in or pattern of congenital malformations, compared with background rates in the general population.
Dr. Gordon said that while he understands the concerns, he personally doesn’t think the class-wide safety of TNF inhibitors in pregnancy and lactation is a big issue.
“My argument is that anti-TNF agents have been used very frequently in women of childbearing age, and also in women who are pregnant or lactating. And there have not been any side effect signals from that,” he explained.
The prospects of gaining an expanded indication for certolizumab in psoriasis hinge in part on the impressive results of the pivotal phase 3, randomized, double-blind, placebo-controlled CIMPASI-1 and CIMPASI-2 trials. In CIMPASI-1, the week-48 Psoriasis Area and Severity Index (PASI) 75 and PASI 90 response rates were 87.1% and 60.2%, respectively, in patients on the biologic at 400 mg every 2 weeks; among those on certolizumab at 200 mg every 2 weeks, the rates were 67.2% and 42.8%. In CIMPASI-2, the PASI 75 and PASI 90 rates were 81.3% and 62.0% at 400 mg and 78.7% and 59.6% with 200 mg every 2 weeks.
There were no cases of tuberculosis or any other significant safety concerns through 48 weeks, Dr. Gordon said.
“Certolizumab is coming soon for psoriasis,” predicted Craig L. Leonardi, MD, a psoriasis researcher at Saint Louis University. “The data are very impressive. It’s a high-performance drug. There’s no reason why this drug shouldn’t be approved.”
Since Dr. Kimball’s presentation of the CRIB data at the 2017 annual meeting of the European Academy of Dermatology and Venereology, the study has been published (Ann Rheum Dis. 2018 Feb;77[2]:228-33).
Dr. Gordon reported receiving research support from and serving as a paid consultant to numerous pharmaceutical companies developing new psoriasis therapies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – When certolizumab pegol receives marketing approval for moderate to severe psoriasis – which experts say is a virtual lock – it will offer a singular advantage over current anti–tumor necrosis factor (anti-TNF) biologics: strong evidence of safety in pregnancy.
“ ” Kenneth B. Gordon, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Lots of women and their families are understandably deeply concerned about using powerful, transformative medications during pregnancy, even though they know from experience how debilitating inadequately treated psoriasis can be.
“Many women of childbearing potential would find [certolizumab] to be a preferential agent if they’re planning to become pregnant,” said Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
He cited the CRIB (A Multicenter, Postmarketing Study Evaluating the Transfer of Cimzia From the Mother to the Infant via the Placenta) study results presented by Alexa B. Kimball, MD, at the 2017 annual meeting of the European Academy of Dermatology and Venereology in Geneva as a major step forward in establishing the safety of certolizumab during pregnancy.
CRIB was a prospective postmarketing pharmacokinetic study that evaluated placental transfer of certolizumab from 16 pregnant women on the biologic to their infants. All of the mothers received their last dose of certolizumab for rheumatoid arthritis or other approved indications within 35 days of delivery. Blood samples were collected from mothers, newborns, and umbilical cords within 1 hour of delivery, and again from the infants at weeks 4 and 8 after delivery.
Only one infant had a detectable plasma level of certolizumab at birth, and it was barely measurable at 0.042 mcg/mL, as compared with 49.4 mcg/mL in the mother’s plasma. This is consistent with the fact that certolizumab’s pegylated arm allows only minimal or no placental transfer from mother to infant, so there is essentially no third trimester in utero fetal exposure. In contrast, as Dr. Kimball noted, other anti-TNF biologics lack a pegylated arm and thus preferentially cross the placenta, creating a theoretical increased risk of maternal pregnancy complications and/or congenital malformations.
Dr. Kimball, professor of dermatology at Harvard Medical School and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, both in Boston, also has been deeply involved in an ongoing registry (sponsored by certolizumab manufacturer UCB) of several hundred women on certolizumab in pregnancy. The data have reassuringly shown no increased risk of maternal pregnancy complications such as preeclampsia, gestational diabetes, or preterm birth, nor any increase in or pattern of congenital malformations, compared with background rates in the general population.
Dr. Gordon said that while he understands the concerns, he personally doesn’t think the class-wide safety of TNF inhibitors in pregnancy and lactation is a big issue.
“My argument is that anti-TNF agents have been used very frequently in women of childbearing age, and also in women who are pregnant or lactating. And there have not been any side effect signals from that,” he explained.
The prospects of gaining an expanded indication for certolizumab in psoriasis hinge in part on the impressive results of the pivotal phase 3, randomized, double-blind, placebo-controlled CIMPASI-1 and CIMPASI-2 trials. In CIMPASI-1, the week-48 Psoriasis Area and Severity Index (PASI) 75 and PASI 90 response rates were 87.1% and 60.2%, respectively, in patients on the biologic at 400 mg every 2 weeks; among those on certolizumab at 200 mg every 2 weeks, the rates were 67.2% and 42.8%. In CIMPASI-2, the PASI 75 and PASI 90 rates were 81.3% and 62.0% at 400 mg and 78.7% and 59.6% with 200 mg every 2 weeks.
There were no cases of tuberculosis or any other significant safety concerns through 48 weeks, Dr. Gordon said.
“Certolizumab is coming soon for psoriasis,” predicted Craig L. Leonardi, MD, a psoriasis researcher at Saint Louis University. “The data are very impressive. It’s a high-performance drug. There’s no reason why this drug shouldn’t be approved.”
Since Dr. Kimball’s presentation of the CRIB data at the 2017 annual meeting of the European Academy of Dermatology and Venereology, the study has been published (Ann Rheum Dis. 2018 Feb;77[2]:228-33).
Dr. Gordon reported receiving research support from and serving as a paid consultant to numerous pharmaceutical companies developing new psoriasis therapies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – When certolizumab pegol receives marketing approval for moderate to severe psoriasis – which experts say is a virtual lock – it will offer a singular advantage over current anti–tumor necrosis factor (anti-TNF) biologics: strong evidence of safety in pregnancy.
“ ” Kenneth B. Gordon, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Lots of women and their families are understandably deeply concerned about using powerful, transformative medications during pregnancy, even though they know from experience how debilitating inadequately treated psoriasis can be.
“Many women of childbearing potential would find [certolizumab] to be a preferential agent if they’re planning to become pregnant,” said Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
He cited the CRIB (A Multicenter, Postmarketing Study Evaluating the Transfer of Cimzia From the Mother to the Infant via the Placenta) study results presented by Alexa B. Kimball, MD, at the 2017 annual meeting of the European Academy of Dermatology and Venereology in Geneva as a major step forward in establishing the safety of certolizumab during pregnancy.
CRIB was a prospective postmarketing pharmacokinetic study that evaluated placental transfer of certolizumab from 16 pregnant women on the biologic to their infants. All of the mothers received their last dose of certolizumab for rheumatoid arthritis or other approved indications within 35 days of delivery. Blood samples were collected from mothers, newborns, and umbilical cords within 1 hour of delivery, and again from the infants at weeks 4 and 8 after delivery.
Only one infant had a detectable plasma level of certolizumab at birth, and it was barely measurable at 0.042 mcg/mL, as compared with 49.4 mcg/mL in the mother’s plasma. This is consistent with the fact that certolizumab’s pegylated arm allows only minimal or no placental transfer from mother to infant, so there is essentially no third trimester in utero fetal exposure. In contrast, as Dr. Kimball noted, other anti-TNF biologics lack a pegylated arm and thus preferentially cross the placenta, creating a theoretical increased risk of maternal pregnancy complications and/or congenital malformations.
Dr. Kimball, professor of dermatology at Harvard Medical School and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, both in Boston, also has been deeply involved in an ongoing registry (sponsored by certolizumab manufacturer UCB) of several hundred women on certolizumab in pregnancy. The data have reassuringly shown no increased risk of maternal pregnancy complications such as preeclampsia, gestational diabetes, or preterm birth, nor any increase in or pattern of congenital malformations, compared with background rates in the general population.
Dr. Gordon said that while he understands the concerns, he personally doesn’t think the class-wide safety of TNF inhibitors in pregnancy and lactation is a big issue.
“My argument is that anti-TNF agents have been used very frequently in women of childbearing age, and also in women who are pregnant or lactating. And there have not been any side effect signals from that,” he explained.
The prospects of gaining an expanded indication for certolizumab in psoriasis hinge in part on the impressive results of the pivotal phase 3, randomized, double-blind, placebo-controlled CIMPASI-1 and CIMPASI-2 trials. In CIMPASI-1, the week-48 Psoriasis Area and Severity Index (PASI) 75 and PASI 90 response rates were 87.1% and 60.2%, respectively, in patients on the biologic at 400 mg every 2 weeks; among those on certolizumab at 200 mg every 2 weeks, the rates were 67.2% and 42.8%. In CIMPASI-2, the PASI 75 and PASI 90 rates were 81.3% and 62.0% at 400 mg and 78.7% and 59.6% with 200 mg every 2 weeks.
There were no cases of tuberculosis or any other significant safety concerns through 48 weeks, Dr. Gordon said.
“Certolizumab is coming soon for psoriasis,” predicted Craig L. Leonardi, MD, a psoriasis researcher at Saint Louis University. “The data are very impressive. It’s a high-performance drug. There’s no reason why this drug shouldn’t be approved.”
Since Dr. Kimball’s presentation of the CRIB data at the 2017 annual meeting of the European Academy of Dermatology and Venereology, the study has been published (Ann Rheum Dis. 2018 Feb;77[2]:228-33).
Dr. Gordon reported receiving research support from and serving as a paid consultant to numerous pharmaceutical companies developing new psoriasis therapies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
VIDEO: The skinny on patch testing
KAUAI, HAWAII – .
That’s sometimes the assumption, but it’s incorrect, according to Mark Davis, MD, chair of the department of dermatology at the Mayo Clinic, Rochester, Minn. Tixocortol is the marker for topical steroid allergy in many series of patch tests, but there is research showing that it is a marker for one class of topical steroids, and “there’s substantial literature saying that if you’re only reacting to tixocortol pivalate, it should be safe to use other classes of topical steroids,” he said.
It’s also important to remember that skin patch tests need to be checked on day 5, not just day 3; it’s the only way to differentiate a true skin allergy from mere skin irritation, and it does matter.
Dr. Davis explained those issues and more – including what to do with minor reactions and how to use the T.R.U.E. TEST kit – in an interview filled with pearls at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Meanwhile, during a presentation at the meeting, he noted two newer options to help allergic patients find skin care products they won’t react to: the Mayo Clinic’s SkinSAFE database and the Contact Allergen Management Program from the American Contact Dermatitis Society.
Dr. Davis had no disclosures.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – .
That’s sometimes the assumption, but it’s incorrect, according to Mark Davis, MD, chair of the department of dermatology at the Mayo Clinic, Rochester, Minn. Tixocortol is the marker for topical steroid allergy in many series of patch tests, but there is research showing that it is a marker for one class of topical steroids, and “there’s substantial literature saying that if you’re only reacting to tixocortol pivalate, it should be safe to use other classes of topical steroids,” he said.
It’s also important to remember that skin patch tests need to be checked on day 5, not just day 3; it’s the only way to differentiate a true skin allergy from mere skin irritation, and it does matter.
Dr. Davis explained those issues and more – including what to do with minor reactions and how to use the T.R.U.E. TEST kit – in an interview filled with pearls at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Meanwhile, during a presentation at the meeting, he noted two newer options to help allergic patients find skin care products they won’t react to: the Mayo Clinic’s SkinSAFE database and the Contact Allergen Management Program from the American Contact Dermatitis Society.
Dr. Davis had no disclosures.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – .
That’s sometimes the assumption, but it’s incorrect, according to Mark Davis, MD, chair of the department of dermatology at the Mayo Clinic, Rochester, Minn. Tixocortol is the marker for topical steroid allergy in many series of patch tests, but there is research showing that it is a marker for one class of topical steroids, and “there’s substantial literature saying that if you’re only reacting to tixocortol pivalate, it should be safe to use other classes of topical steroids,” he said.
It’s also important to remember that skin patch tests need to be checked on day 5, not just day 3; it’s the only way to differentiate a true skin allergy from mere skin irritation, and it does matter.
Dr. Davis explained those issues and more – including what to do with minor reactions and how to use the T.R.U.E. TEST kit – in an interview filled with pearls at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Meanwhile, during a presentation at the meeting, he noted two newer options to help allergic patients find skin care products they won’t react to: the Mayo Clinic’s SkinSAFE database and the Contact Allergen Management Program from the American Contact Dermatitis Society.
Dr. Davis had no disclosures.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM SDEF HAWAII DERMATOLOGY SEMINAR
