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Anti-CD20s linked to higher COVID-19 severity in MS
Like other people, a biostatistician told neurologists. With the exception of anti-CD20s, registries also suggest that disease-modifying therapies (DMTs) don’t cause higher degrees of severity.
“It’s good news since it’s important for patients to stay on these treatments,” said Amber Salter, PhD, MPH, an assistant professor at Washington University, St. Louis, in a follow-up interview following her presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Salter reported on the findings of several MS/COVID-19 registries from around the world, including the COViMS Registry, which is supported by the Consortium of MS Centers, the MS Society of Canada, and the National MS Society. It tracks patients who developed COVID-19 while also having MS, neuromyelitis optica, or MOG antibody disease.
The registry began collecting data in April 2020 and is ongoing. As of Jan. 29, 2021, 2,059 patients had been tracked; 85% of cases were confirmed by laboratory tests. Nearly all patients (97%) were from the United States, with about 21% from New York state. Nearly 76% were female, the average age was 48. About 70% were non-Hispanic White, 18% were African American; 83% had relapsing remitting MS, and 17% had progressive MS.
“We found that 11.5% of MS patients were reported being hospitalized, while 4.2% were admitted to the ICU or ventilated and 3% had died,” Dr. Salter said. Not surprisingly, the death rate was highest (21%) in patients aged 75 years or older, compared with 11% of those aged 65-74 years. Those with more severe cases – those who were nonambulatory – had a death rate of 18%, compared with 0.6% of those who were fully ambulatory and 4% of those who walked with assistance.
“A lot of the risks [for COVID-19 severity] we see in the general population are risks in the MS population,” Dr. Salter said.
Dr. Salter also summarized the results of other international registries. After adjustment, a registry in Italy linked the anti-CD20 drugs ocrelizumab or rituximab (odds ratio, 2.37, P = .015) and recent use of methylprednisolone (OR, 5.2; P = .001) to more severe courses of COVID-19, compared with other DMTs. And a global data-sharing project linked anti-CD20s to more severe outcomes, compared with other DMTs (hospitalization, adjusted prevalence ratio, 1.49; ICU admission, aPR, 2.55; and ventilation, aPR, 3.05).
In an interview, neurologist Lauren Gluck, MD, of Albert Einstein College of Medicine and Montefiore Medical Center, both in New York, cautioned that prescribing anti-CD20s now “requires a more complex informed consent process with patients and outlining of risk as well as strategies to minimize contracting the infection.”
Moving forward, she advised colleagues to “keep treating MS with DMTs. Preventing MS attacks will help keep patients out of the hospital and limit need for high-dose steroids.” And she cautioned that “avoiding action due to inaccurate fear of DMTs and COVID-19 may put your patients at unnecessary risk of relapses and accumulated disability. Educate your patients on the reality of the COVID19 pandemic, their personal risk of exposure, and strategies to minimize their risk.”
Fortunately, vaccinations offer protection against COVID-19 in patients with MS, although patients are clearly concerned about potential risks. “A frequent concern is whether the vaccines are safe for MS patients in general and if they could incite MS relapses,” neurologist Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, said in an interview. “The American Academy of Neurology guidelines have not found a connection between vaccination and MS relapses. Having COVID-19 infection can trigger MS relapses, so clearly the benefit from the vaccine outweighs any potential risks. Obviously, it is not advisable to take any vaccine during an active relapse, but vaccines are safe otherwise when given during remission.”
Dr. Salter and Dr. Gluck reported no relevant disclosures. Dr. Abboud reports consulting fees from Biogen, Genentech, Bristol-Myers Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myers Squibb, Genentech, and Sanofi-Genzyme.
Like other people, a biostatistician told neurologists. With the exception of anti-CD20s, registries also suggest that disease-modifying therapies (DMTs) don’t cause higher degrees of severity.
“It’s good news since it’s important for patients to stay on these treatments,” said Amber Salter, PhD, MPH, an assistant professor at Washington University, St. Louis, in a follow-up interview following her presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Salter reported on the findings of several MS/COVID-19 registries from around the world, including the COViMS Registry, which is supported by the Consortium of MS Centers, the MS Society of Canada, and the National MS Society. It tracks patients who developed COVID-19 while also having MS, neuromyelitis optica, or MOG antibody disease.
The registry began collecting data in April 2020 and is ongoing. As of Jan. 29, 2021, 2,059 patients had been tracked; 85% of cases were confirmed by laboratory tests. Nearly all patients (97%) were from the United States, with about 21% from New York state. Nearly 76% were female, the average age was 48. About 70% were non-Hispanic White, 18% were African American; 83% had relapsing remitting MS, and 17% had progressive MS.
“We found that 11.5% of MS patients were reported being hospitalized, while 4.2% were admitted to the ICU or ventilated and 3% had died,” Dr. Salter said. Not surprisingly, the death rate was highest (21%) in patients aged 75 years or older, compared with 11% of those aged 65-74 years. Those with more severe cases – those who were nonambulatory – had a death rate of 18%, compared with 0.6% of those who were fully ambulatory and 4% of those who walked with assistance.
“A lot of the risks [for COVID-19 severity] we see in the general population are risks in the MS population,” Dr. Salter said.
Dr. Salter also summarized the results of other international registries. After adjustment, a registry in Italy linked the anti-CD20 drugs ocrelizumab or rituximab (odds ratio, 2.37, P = .015) and recent use of methylprednisolone (OR, 5.2; P = .001) to more severe courses of COVID-19, compared with other DMTs. And a global data-sharing project linked anti-CD20s to more severe outcomes, compared with other DMTs (hospitalization, adjusted prevalence ratio, 1.49; ICU admission, aPR, 2.55; and ventilation, aPR, 3.05).
In an interview, neurologist Lauren Gluck, MD, of Albert Einstein College of Medicine and Montefiore Medical Center, both in New York, cautioned that prescribing anti-CD20s now “requires a more complex informed consent process with patients and outlining of risk as well as strategies to minimize contracting the infection.”
Moving forward, she advised colleagues to “keep treating MS with DMTs. Preventing MS attacks will help keep patients out of the hospital and limit need for high-dose steroids.” And she cautioned that “avoiding action due to inaccurate fear of DMTs and COVID-19 may put your patients at unnecessary risk of relapses and accumulated disability. Educate your patients on the reality of the COVID19 pandemic, their personal risk of exposure, and strategies to minimize their risk.”
Fortunately, vaccinations offer protection against COVID-19 in patients with MS, although patients are clearly concerned about potential risks. “A frequent concern is whether the vaccines are safe for MS patients in general and if they could incite MS relapses,” neurologist Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, said in an interview. “The American Academy of Neurology guidelines have not found a connection between vaccination and MS relapses. Having COVID-19 infection can trigger MS relapses, so clearly the benefit from the vaccine outweighs any potential risks. Obviously, it is not advisable to take any vaccine during an active relapse, but vaccines are safe otherwise when given during remission.”
Dr. Salter and Dr. Gluck reported no relevant disclosures. Dr. Abboud reports consulting fees from Biogen, Genentech, Bristol-Myers Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myers Squibb, Genentech, and Sanofi-Genzyme.
Like other people, a biostatistician told neurologists. With the exception of anti-CD20s, registries also suggest that disease-modifying therapies (DMTs) don’t cause higher degrees of severity.
“It’s good news since it’s important for patients to stay on these treatments,” said Amber Salter, PhD, MPH, an assistant professor at Washington University, St. Louis, in a follow-up interview following her presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Salter reported on the findings of several MS/COVID-19 registries from around the world, including the COViMS Registry, which is supported by the Consortium of MS Centers, the MS Society of Canada, and the National MS Society. It tracks patients who developed COVID-19 while also having MS, neuromyelitis optica, or MOG antibody disease.
The registry began collecting data in April 2020 and is ongoing. As of Jan. 29, 2021, 2,059 patients had been tracked; 85% of cases were confirmed by laboratory tests. Nearly all patients (97%) were from the United States, with about 21% from New York state. Nearly 76% were female, the average age was 48. About 70% were non-Hispanic White, 18% were African American; 83% had relapsing remitting MS, and 17% had progressive MS.
“We found that 11.5% of MS patients were reported being hospitalized, while 4.2% were admitted to the ICU or ventilated and 3% had died,” Dr. Salter said. Not surprisingly, the death rate was highest (21%) in patients aged 75 years or older, compared with 11% of those aged 65-74 years. Those with more severe cases – those who were nonambulatory – had a death rate of 18%, compared with 0.6% of those who were fully ambulatory and 4% of those who walked with assistance.
“A lot of the risks [for COVID-19 severity] we see in the general population are risks in the MS population,” Dr. Salter said.
Dr. Salter also summarized the results of other international registries. After adjustment, a registry in Italy linked the anti-CD20 drugs ocrelizumab or rituximab (odds ratio, 2.37, P = .015) and recent use of methylprednisolone (OR, 5.2; P = .001) to more severe courses of COVID-19, compared with other DMTs. And a global data-sharing project linked anti-CD20s to more severe outcomes, compared with other DMTs (hospitalization, adjusted prevalence ratio, 1.49; ICU admission, aPR, 2.55; and ventilation, aPR, 3.05).
In an interview, neurologist Lauren Gluck, MD, of Albert Einstein College of Medicine and Montefiore Medical Center, both in New York, cautioned that prescribing anti-CD20s now “requires a more complex informed consent process with patients and outlining of risk as well as strategies to minimize contracting the infection.”
Moving forward, she advised colleagues to “keep treating MS with DMTs. Preventing MS attacks will help keep patients out of the hospital and limit need for high-dose steroids.” And she cautioned that “avoiding action due to inaccurate fear of DMTs and COVID-19 may put your patients at unnecessary risk of relapses and accumulated disability. Educate your patients on the reality of the COVID19 pandemic, their personal risk of exposure, and strategies to minimize their risk.”
Fortunately, vaccinations offer protection against COVID-19 in patients with MS, although patients are clearly concerned about potential risks. “A frequent concern is whether the vaccines are safe for MS patients in general and if they could incite MS relapses,” neurologist Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, said in an interview. “The American Academy of Neurology guidelines have not found a connection between vaccination and MS relapses. Having COVID-19 infection can trigger MS relapses, so clearly the benefit from the vaccine outweighs any potential risks. Obviously, it is not advisable to take any vaccine during an active relapse, but vaccines are safe otherwise when given during remission.”
Dr. Salter and Dr. Gluck reported no relevant disclosures. Dr. Abboud reports consulting fees from Biogen, Genentech, Bristol-Myers Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myers Squibb, Genentech, and Sanofi-Genzyme.
FROM ACTRIMS FORUM 2021
What drives treatment satisfaction among adults with atopic dermatitis?
.
Satisfaction scores were higher when specialists prescribed systemic therapy, but were lower when nonspecialists prescribed systemic therapy and when specialists prescribed only topical therapy.
Those are among key findings from an analysis of the Medical Expenditure Panel Surveys reported by Brian T. Cheng during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium.
“AD management is complex,” said Mr. Cheng, a medical student at Northwestern University, Chicago. “It includes patient education about trigger avoidance, over-the-counter and prescription topical therapies, as well as systemic therapies. Previous studies have shown major decrements to quality of life as well as atopic and non-atopic comorbidities in these patients. The burden of AD and their comorbidities, as well as their management, may impact patient satisfaction.”
Prior studies have demonstrated that patient satisfaction is associated with improvements in clinical outcomes, increased patient retention, and reduced malpractice claims (Br J Dermatol. 2001 Oct;145[4]:617-23, Arch Dermatol 2008 Feb;144[2]:263-5). However, since data on patient satisfaction in AD are limited, Mr. Cheng and the study’s senior author, Jonathan I. Silverberg, MD, PhD, MPH, set out to examine overall patient satisfaction among adults with AD, to determine associations of patient satisfaction with patterns of health care utilization, and to identify predictors of higher satisfaction among these adults.
The researchers conducted a cross-sectional retrospective analysis of 3,810 patients from the 2000-2015 Medical Expenditure Panel Surveys, representative surveys of the U.S. noninstitutionalized population conducted annually by the Agency for Healthcare Research and Quality. They used ICD-9 codes 691 and 692 to determine AD diagnosis and five Consumer Assessment of Health Plans Survey (CAHPS) questions to assess patients’ satisfaction with their clinicians. “These questions have been extensively validated to correlate with global satisfaction,” Mr. Cheng said. “These are not disease-specific and allow for comparison across multiple diseases.”
Next, the researchers created a composite satisfaction score based on the methods of Anthony Jerant, MD, of the University of California, Davis, and colleagues. They adjusted each question in the CAHPS survey to have an equal weight and then summed these into a composite satisfaction score. “We examined patient satisfaction comparing across diseases, and based on the guidelines from the AHRQ to isolate that impact of patient-physician interaction, we adjusted for sociodemographics, mental and physical health status, self-reported health rating, as well as multimorbidity and comorbid diseases.”
Compared with adults who are healthy, adults with AD had lower patient satisfaction overall. “Moreover, people with AD had lower satisfaction compared to those with psoriasis, which may reflect more substantial itch burden as well as the greater comorbid disease challenges in management,” Mr. Cheng said. “It may also reflect the renaissance in psoriasis treatment over the last 10-20 years, giving a wider spectrum of treatment and thus a higher patient satisfaction.”
Among adults with AD, lower satisfaction was consistent across all domains of CAHPS. For the question of “How often health providers listen carefully to you” the adjusted OR (aOR) was 0.87 (P = .008). For the question of “How often health providers explain things in a way that was easy to understand” the aOR was 0.89 (P = .003). For the question of “How often health providers spent enough time with you” the aOR was 0.86 (P = .0001). For “How often providers showed respect for what you had to say” the aOR was 0.91 (P = .02).
Recognizing that treatment regimens are complex and used differently by provider type, the researchers examined interactions between specialists (dermatologists and allergists) and treatment type. “Previous studies found dermatologists treat more severe, chronic AD,” Mr. Cheng said. “We found here that there was lower satisfaction among those treated with topical therapy and by specialists, which may reflect inadequate disease control. We also found lower satisfaction among those treated with systemic therapy by primary care physicians. This may reflect that these patients are not achieving optimal therapy. We found that satisfaction was highest among those treated with systemic therapy and by dermatologists and allergists.”
Socioeconomic, racial/ethnic, and health care disparities were observed in terms of satisfaction among this cohort. The following characteristics were significantly associated with lower patient satisfaction, compared with the general cohort of adults with AD: poor to low income (aOR, –1.82; P less than .0001), multiracial/other race (aOR, –2.34; P = .0001), Hispanic ethnicity (aOR, –1.40; P = .007), and having no insurance coverage (aOR, –4.53; P less than .0001).
“Moreover, those with multimorbidity had even lower satisfaction,” Mr. Cheng said. “In previous studies, AD has been linked with many other comorbidities. This may reflect that these patients are not being adequately managed overall. So, there’s a need here for multidisciplinary care to ensure that all of these comorbidities and the full spectrum of symptoms are being managed adequately.”
He concluded that future research is needed to determine strategies to optimize patient satisfaction in adults with AD.
“I’m not sure how much more provocative you can get in terms of data,” added Dr. Silverberg, director of clinical research and contact dermatitis at George Washington University, Washington. “It’s really eye-opening. I think many clinicians may feel like they’re doing a perfect job in managing this disease. These data suggest that at least at the national level that may not be the case.”
Mr. Cheng reported having no financial disclosures. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
.
Satisfaction scores were higher when specialists prescribed systemic therapy, but were lower when nonspecialists prescribed systemic therapy and when specialists prescribed only topical therapy.
Those are among key findings from an analysis of the Medical Expenditure Panel Surveys reported by Brian T. Cheng during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium.
“AD management is complex,” said Mr. Cheng, a medical student at Northwestern University, Chicago. “It includes patient education about trigger avoidance, over-the-counter and prescription topical therapies, as well as systemic therapies. Previous studies have shown major decrements to quality of life as well as atopic and non-atopic comorbidities in these patients. The burden of AD and their comorbidities, as well as their management, may impact patient satisfaction.”
Prior studies have demonstrated that patient satisfaction is associated with improvements in clinical outcomes, increased patient retention, and reduced malpractice claims (Br J Dermatol. 2001 Oct;145[4]:617-23, Arch Dermatol 2008 Feb;144[2]:263-5). However, since data on patient satisfaction in AD are limited, Mr. Cheng and the study’s senior author, Jonathan I. Silverberg, MD, PhD, MPH, set out to examine overall patient satisfaction among adults with AD, to determine associations of patient satisfaction with patterns of health care utilization, and to identify predictors of higher satisfaction among these adults.
The researchers conducted a cross-sectional retrospective analysis of 3,810 patients from the 2000-2015 Medical Expenditure Panel Surveys, representative surveys of the U.S. noninstitutionalized population conducted annually by the Agency for Healthcare Research and Quality. They used ICD-9 codes 691 and 692 to determine AD diagnosis and five Consumer Assessment of Health Plans Survey (CAHPS) questions to assess patients’ satisfaction with their clinicians. “These questions have been extensively validated to correlate with global satisfaction,” Mr. Cheng said. “These are not disease-specific and allow for comparison across multiple diseases.”
Next, the researchers created a composite satisfaction score based on the methods of Anthony Jerant, MD, of the University of California, Davis, and colleagues. They adjusted each question in the CAHPS survey to have an equal weight and then summed these into a composite satisfaction score. “We examined patient satisfaction comparing across diseases, and based on the guidelines from the AHRQ to isolate that impact of patient-physician interaction, we adjusted for sociodemographics, mental and physical health status, self-reported health rating, as well as multimorbidity and comorbid diseases.”
Compared with adults who are healthy, adults with AD had lower patient satisfaction overall. “Moreover, people with AD had lower satisfaction compared to those with psoriasis, which may reflect more substantial itch burden as well as the greater comorbid disease challenges in management,” Mr. Cheng said. “It may also reflect the renaissance in psoriasis treatment over the last 10-20 years, giving a wider spectrum of treatment and thus a higher patient satisfaction.”
Among adults with AD, lower satisfaction was consistent across all domains of CAHPS. For the question of “How often health providers listen carefully to you” the adjusted OR (aOR) was 0.87 (P = .008). For the question of “How often health providers explain things in a way that was easy to understand” the aOR was 0.89 (P = .003). For the question of “How often health providers spent enough time with you” the aOR was 0.86 (P = .0001). For “How often providers showed respect for what you had to say” the aOR was 0.91 (P = .02).
Recognizing that treatment regimens are complex and used differently by provider type, the researchers examined interactions between specialists (dermatologists and allergists) and treatment type. “Previous studies found dermatologists treat more severe, chronic AD,” Mr. Cheng said. “We found here that there was lower satisfaction among those treated with topical therapy and by specialists, which may reflect inadequate disease control. We also found lower satisfaction among those treated with systemic therapy by primary care physicians. This may reflect that these patients are not achieving optimal therapy. We found that satisfaction was highest among those treated with systemic therapy and by dermatologists and allergists.”
Socioeconomic, racial/ethnic, and health care disparities were observed in terms of satisfaction among this cohort. The following characteristics were significantly associated with lower patient satisfaction, compared with the general cohort of adults with AD: poor to low income (aOR, –1.82; P less than .0001), multiracial/other race (aOR, –2.34; P = .0001), Hispanic ethnicity (aOR, –1.40; P = .007), and having no insurance coverage (aOR, –4.53; P less than .0001).
“Moreover, those with multimorbidity had even lower satisfaction,” Mr. Cheng said. “In previous studies, AD has been linked with many other comorbidities. This may reflect that these patients are not being adequately managed overall. So, there’s a need here for multidisciplinary care to ensure that all of these comorbidities and the full spectrum of symptoms are being managed adequately.”
He concluded that future research is needed to determine strategies to optimize patient satisfaction in adults with AD.
“I’m not sure how much more provocative you can get in terms of data,” added Dr. Silverberg, director of clinical research and contact dermatitis at George Washington University, Washington. “It’s really eye-opening. I think many clinicians may feel like they’re doing a perfect job in managing this disease. These data suggest that at least at the national level that may not be the case.”
Mr. Cheng reported having no financial disclosures. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
.
Satisfaction scores were higher when specialists prescribed systemic therapy, but were lower when nonspecialists prescribed systemic therapy and when specialists prescribed only topical therapy.
Those are among key findings from an analysis of the Medical Expenditure Panel Surveys reported by Brian T. Cheng during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium.
“AD management is complex,” said Mr. Cheng, a medical student at Northwestern University, Chicago. “It includes patient education about trigger avoidance, over-the-counter and prescription topical therapies, as well as systemic therapies. Previous studies have shown major decrements to quality of life as well as atopic and non-atopic comorbidities in these patients. The burden of AD and their comorbidities, as well as their management, may impact patient satisfaction.”
Prior studies have demonstrated that patient satisfaction is associated with improvements in clinical outcomes, increased patient retention, and reduced malpractice claims (Br J Dermatol. 2001 Oct;145[4]:617-23, Arch Dermatol 2008 Feb;144[2]:263-5). However, since data on patient satisfaction in AD are limited, Mr. Cheng and the study’s senior author, Jonathan I. Silverberg, MD, PhD, MPH, set out to examine overall patient satisfaction among adults with AD, to determine associations of patient satisfaction with patterns of health care utilization, and to identify predictors of higher satisfaction among these adults.
The researchers conducted a cross-sectional retrospective analysis of 3,810 patients from the 2000-2015 Medical Expenditure Panel Surveys, representative surveys of the U.S. noninstitutionalized population conducted annually by the Agency for Healthcare Research and Quality. They used ICD-9 codes 691 and 692 to determine AD diagnosis and five Consumer Assessment of Health Plans Survey (CAHPS) questions to assess patients’ satisfaction with their clinicians. “These questions have been extensively validated to correlate with global satisfaction,” Mr. Cheng said. “These are not disease-specific and allow for comparison across multiple diseases.”
Next, the researchers created a composite satisfaction score based on the methods of Anthony Jerant, MD, of the University of California, Davis, and colleagues. They adjusted each question in the CAHPS survey to have an equal weight and then summed these into a composite satisfaction score. “We examined patient satisfaction comparing across diseases, and based on the guidelines from the AHRQ to isolate that impact of patient-physician interaction, we adjusted for sociodemographics, mental and physical health status, self-reported health rating, as well as multimorbidity and comorbid diseases.”
Compared with adults who are healthy, adults with AD had lower patient satisfaction overall. “Moreover, people with AD had lower satisfaction compared to those with psoriasis, which may reflect more substantial itch burden as well as the greater comorbid disease challenges in management,” Mr. Cheng said. “It may also reflect the renaissance in psoriasis treatment over the last 10-20 years, giving a wider spectrum of treatment and thus a higher patient satisfaction.”
Among adults with AD, lower satisfaction was consistent across all domains of CAHPS. For the question of “How often health providers listen carefully to you” the adjusted OR (aOR) was 0.87 (P = .008). For the question of “How often health providers explain things in a way that was easy to understand” the aOR was 0.89 (P = .003). For the question of “How often health providers spent enough time with you” the aOR was 0.86 (P = .0001). For “How often providers showed respect for what you had to say” the aOR was 0.91 (P = .02).
Recognizing that treatment regimens are complex and used differently by provider type, the researchers examined interactions between specialists (dermatologists and allergists) and treatment type. “Previous studies found dermatologists treat more severe, chronic AD,” Mr. Cheng said. “We found here that there was lower satisfaction among those treated with topical therapy and by specialists, which may reflect inadequate disease control. We also found lower satisfaction among those treated with systemic therapy by primary care physicians. This may reflect that these patients are not achieving optimal therapy. We found that satisfaction was highest among those treated with systemic therapy and by dermatologists and allergists.”
Socioeconomic, racial/ethnic, and health care disparities were observed in terms of satisfaction among this cohort. The following characteristics were significantly associated with lower patient satisfaction, compared with the general cohort of adults with AD: poor to low income (aOR, –1.82; P less than .0001), multiracial/other race (aOR, –2.34; P = .0001), Hispanic ethnicity (aOR, –1.40; P = .007), and having no insurance coverage (aOR, –4.53; P less than .0001).
“Moreover, those with multimorbidity had even lower satisfaction,” Mr. Cheng said. “In previous studies, AD has been linked with many other comorbidities. This may reflect that these patients are not being adequately managed overall. So, there’s a need here for multidisciplinary care to ensure that all of these comorbidities and the full spectrum of symptoms are being managed adequately.”
He concluded that future research is needed to determine strategies to optimize patient satisfaction in adults with AD.
“I’m not sure how much more provocative you can get in terms of data,” added Dr. Silverberg, director of clinical research and contact dermatitis at George Washington University, Washington. “It’s really eye-opening. I think many clinicians may feel like they’re doing a perfect job in managing this disease. These data suggest that at least at the national level that may not be the case.”
Mr. Cheng reported having no financial disclosures. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
FROM REVOLUTIONIZING AD 2020
Certain DMTs in MS may attenuate COVID-19 vaccines
“There’s no reason to think any of the three authorized vaccines are in any way more dangerous in people with MS, or in the context of MS DMTs. It’s only a question of whether certain DMTs will influence the degree of benefit you get from the vaccine,” said Amit Bar-Or, MD, director of the Center for Neuroinflammation and Neurotherapeutics, chief of the multiple sclerosis division, and Melissa and Paul Anderson President’s Distinguished Professor at the University of Pennsylvania, Philadelphia. He spoke at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, and he also answered questions in a follow-up interview.
“The merits of being protected by the COVID-19 vaccines far outweigh any risks that one would consider associated with vaccines and individuals with MS,” said Dr. Bar-Or. “And there’s reason to think that the RNA vaccines may even be safer than prior, more traditional vaccines. They are nonlive, noninactivated vaccines, and there is no risk in terms of interacting with MS.”
Where do DMTs fit in? In an interview, Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, also in Cleveland, said there’s reason for caution regarding DMTs that deplete immune cells or entrap them in the lymph nodes. “What is not clearly known is the effect of the fumarates, which do not act through cell depletion but can occasionally deplete immune cells as a side effect. These likely have no negative effect on vaccine efficacy in patients with normal immune cell count but may have a negative effect in those with significant immune cell reduction. Luckily, significant immune cell reduction is rare in patients taking fumarates.”
In addition, he said, “interferons and natalizumab are generally thought to have no impact on vaccine efficacy while glatiramer acetate and teriflunomide are thought to have no or only little impact on vaccines. Most of these concepts are derived from studies of non–COVID-19 vaccines.”
Dr. Bar-Or highlighted specific DMTs. Teriflunomide (Aubagio) “has a relatively mild effect on the immune system and is not thought to be particularly immune suppressive or deplete immune cells,” Dr. Bar-Or said, as shown in a 2015 study he led (Neurol Neuroimmunol Neuroinflamm. 2015 Feb 12;2[2]:e70). In contrast, a 2020 study, also led by Dr. Bar-Or, showed that nonlive vaccinations given after treatment with ocrelizumab (Ocrevus) – an anti-CD20 monoclonal antibody – are “attenuated, compared with untreated or interferon-beta–treated patients, but they can still be expected to be protective.”
Dr. Bar-Or pointed to National MS Society guidelines about the timing of the Pfizer and Moderna mRNA vaccines for patients with MS who are on DMT. In patients with stable MS, the society recommends no adjustments in timing for patients starting or remaining on several DMTs. The list includes teriflunomide, glatiramer acetate (Copaxone), and dimethyl fumarate, among others.
Patients shouldn’t start fingolimod (Gilenya), siponimod (Mayzent), or ozanimod (Zeposia) until 4 weeks or more after their second vaccine dose, the guidelines suggest. Vaccine doses are recommended 3-5 days after the final dose of high-dose steroids. And there are more complicated recommendations regarding a number of other DMTs – ocrelizumab, ofatumumab (Kesimpta), alemtuzumab (Lemtrada), cladribine (Mavenclad), and rituximab (Rituxan).
Dr. Bar-Or cautioned that the guidelines are an imperfect “first pass” and are being updated.
He added that the guidelines are not set in stone: “Scheduling is not always possible in terms of adjusting the vaccine timing. Patients in general are recommended to take the vaccine when it becomes available, as it may be more important for them to get the vaccine than to try to time the vaccine relative to the DMT.”
Guidance regarding the newly authorized Johnson & Johnson vaccine is expected soon, said neurologist Barbara Giesser, MD, of Pacific Neuroscience Institute in Santa Monica, Calif., in an interview. As for her advice to patients, she said that, “in general, I am recommending that patients get [vaccinated] as soon as it is available to them with adjustment of timing of some DMTs as may be appropriate.”
Dr. Bar-Or has received consulting fees and/or grant support from – or participated as a speaker in events sponsored by – Accure, Atara Biotherapeutics, Biogen, Bristol-Myer Squibb/Celgene/Receptos, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. He also receives research funding from various organizations and agencies. Dr. Abboud reported receiving consulting fees from Biogen, Genentech, Bristol-Myer Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myer Squibb, Genentech, and Sanofi-Genzyme. Dr. Giesser reports no disclosures.
“There’s no reason to think any of the three authorized vaccines are in any way more dangerous in people with MS, or in the context of MS DMTs. It’s only a question of whether certain DMTs will influence the degree of benefit you get from the vaccine,” said Amit Bar-Or, MD, director of the Center for Neuroinflammation and Neurotherapeutics, chief of the multiple sclerosis division, and Melissa and Paul Anderson President’s Distinguished Professor at the University of Pennsylvania, Philadelphia. He spoke at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, and he also answered questions in a follow-up interview.
“The merits of being protected by the COVID-19 vaccines far outweigh any risks that one would consider associated with vaccines and individuals with MS,” said Dr. Bar-Or. “And there’s reason to think that the RNA vaccines may even be safer than prior, more traditional vaccines. They are nonlive, noninactivated vaccines, and there is no risk in terms of interacting with MS.”
Where do DMTs fit in? In an interview, Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, also in Cleveland, said there’s reason for caution regarding DMTs that deplete immune cells or entrap them in the lymph nodes. “What is not clearly known is the effect of the fumarates, which do not act through cell depletion but can occasionally deplete immune cells as a side effect. These likely have no negative effect on vaccine efficacy in patients with normal immune cell count but may have a negative effect in those with significant immune cell reduction. Luckily, significant immune cell reduction is rare in patients taking fumarates.”
In addition, he said, “interferons and natalizumab are generally thought to have no impact on vaccine efficacy while glatiramer acetate and teriflunomide are thought to have no or only little impact on vaccines. Most of these concepts are derived from studies of non–COVID-19 vaccines.”
Dr. Bar-Or highlighted specific DMTs. Teriflunomide (Aubagio) “has a relatively mild effect on the immune system and is not thought to be particularly immune suppressive or deplete immune cells,” Dr. Bar-Or said, as shown in a 2015 study he led (Neurol Neuroimmunol Neuroinflamm. 2015 Feb 12;2[2]:e70). In contrast, a 2020 study, also led by Dr. Bar-Or, showed that nonlive vaccinations given after treatment with ocrelizumab (Ocrevus) – an anti-CD20 monoclonal antibody – are “attenuated, compared with untreated or interferon-beta–treated patients, but they can still be expected to be protective.”
Dr. Bar-Or pointed to National MS Society guidelines about the timing of the Pfizer and Moderna mRNA vaccines for patients with MS who are on DMT. In patients with stable MS, the society recommends no adjustments in timing for patients starting or remaining on several DMTs. The list includes teriflunomide, glatiramer acetate (Copaxone), and dimethyl fumarate, among others.
Patients shouldn’t start fingolimod (Gilenya), siponimod (Mayzent), or ozanimod (Zeposia) until 4 weeks or more after their second vaccine dose, the guidelines suggest. Vaccine doses are recommended 3-5 days after the final dose of high-dose steroids. And there are more complicated recommendations regarding a number of other DMTs – ocrelizumab, ofatumumab (Kesimpta), alemtuzumab (Lemtrada), cladribine (Mavenclad), and rituximab (Rituxan).
Dr. Bar-Or cautioned that the guidelines are an imperfect “first pass” and are being updated.
He added that the guidelines are not set in stone: “Scheduling is not always possible in terms of adjusting the vaccine timing. Patients in general are recommended to take the vaccine when it becomes available, as it may be more important for them to get the vaccine than to try to time the vaccine relative to the DMT.”
Guidance regarding the newly authorized Johnson & Johnson vaccine is expected soon, said neurologist Barbara Giesser, MD, of Pacific Neuroscience Institute in Santa Monica, Calif., in an interview. As for her advice to patients, she said that, “in general, I am recommending that patients get [vaccinated] as soon as it is available to them with adjustment of timing of some DMTs as may be appropriate.”
Dr. Bar-Or has received consulting fees and/or grant support from – or participated as a speaker in events sponsored by – Accure, Atara Biotherapeutics, Biogen, Bristol-Myer Squibb/Celgene/Receptos, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. He also receives research funding from various organizations and agencies. Dr. Abboud reported receiving consulting fees from Biogen, Genentech, Bristol-Myer Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myer Squibb, Genentech, and Sanofi-Genzyme. Dr. Giesser reports no disclosures.
“There’s no reason to think any of the three authorized vaccines are in any way more dangerous in people with MS, or in the context of MS DMTs. It’s only a question of whether certain DMTs will influence the degree of benefit you get from the vaccine,” said Amit Bar-Or, MD, director of the Center for Neuroinflammation and Neurotherapeutics, chief of the multiple sclerosis division, and Melissa and Paul Anderson President’s Distinguished Professor at the University of Pennsylvania, Philadelphia. He spoke at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, and he also answered questions in a follow-up interview.
“The merits of being protected by the COVID-19 vaccines far outweigh any risks that one would consider associated with vaccines and individuals with MS,” said Dr. Bar-Or. “And there’s reason to think that the RNA vaccines may even be safer than prior, more traditional vaccines. They are nonlive, noninactivated vaccines, and there is no risk in terms of interacting with MS.”
Where do DMTs fit in? In an interview, Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, also in Cleveland, said there’s reason for caution regarding DMTs that deplete immune cells or entrap them in the lymph nodes. “What is not clearly known is the effect of the fumarates, which do not act through cell depletion but can occasionally deplete immune cells as a side effect. These likely have no negative effect on vaccine efficacy in patients with normal immune cell count but may have a negative effect in those with significant immune cell reduction. Luckily, significant immune cell reduction is rare in patients taking fumarates.”
In addition, he said, “interferons and natalizumab are generally thought to have no impact on vaccine efficacy while glatiramer acetate and teriflunomide are thought to have no or only little impact on vaccines. Most of these concepts are derived from studies of non–COVID-19 vaccines.”
Dr. Bar-Or highlighted specific DMTs. Teriflunomide (Aubagio) “has a relatively mild effect on the immune system and is not thought to be particularly immune suppressive or deplete immune cells,” Dr. Bar-Or said, as shown in a 2015 study he led (Neurol Neuroimmunol Neuroinflamm. 2015 Feb 12;2[2]:e70). In contrast, a 2020 study, also led by Dr. Bar-Or, showed that nonlive vaccinations given after treatment with ocrelizumab (Ocrevus) – an anti-CD20 monoclonal antibody – are “attenuated, compared with untreated or interferon-beta–treated patients, but they can still be expected to be protective.”
Dr. Bar-Or pointed to National MS Society guidelines about the timing of the Pfizer and Moderna mRNA vaccines for patients with MS who are on DMT. In patients with stable MS, the society recommends no adjustments in timing for patients starting or remaining on several DMTs. The list includes teriflunomide, glatiramer acetate (Copaxone), and dimethyl fumarate, among others.
Patients shouldn’t start fingolimod (Gilenya), siponimod (Mayzent), or ozanimod (Zeposia) until 4 weeks or more after their second vaccine dose, the guidelines suggest. Vaccine doses are recommended 3-5 days after the final dose of high-dose steroids. And there are more complicated recommendations regarding a number of other DMTs – ocrelizumab, ofatumumab (Kesimpta), alemtuzumab (Lemtrada), cladribine (Mavenclad), and rituximab (Rituxan).
Dr. Bar-Or cautioned that the guidelines are an imperfect “first pass” and are being updated.
He added that the guidelines are not set in stone: “Scheduling is not always possible in terms of adjusting the vaccine timing. Patients in general are recommended to take the vaccine when it becomes available, as it may be more important for them to get the vaccine than to try to time the vaccine relative to the DMT.”
Guidance regarding the newly authorized Johnson & Johnson vaccine is expected soon, said neurologist Barbara Giesser, MD, of Pacific Neuroscience Institute in Santa Monica, Calif., in an interview. As for her advice to patients, she said that, “in general, I am recommending that patients get [vaccinated] as soon as it is available to them with adjustment of timing of some DMTs as may be appropriate.”
Dr. Bar-Or has received consulting fees and/or grant support from – or participated as a speaker in events sponsored by – Accure, Atara Biotherapeutics, Biogen, Bristol-Myer Squibb/Celgene/Receptos, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. He also receives research funding from various organizations and agencies. Dr. Abboud reported receiving consulting fees from Biogen, Genentech, Bristol-Myer Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myer Squibb, Genentech, and Sanofi-Genzyme. Dr. Giesser reports no disclosures.
FROM ACTRIMS FORUM 2021
Energy-based devices: Expert shares treatment tips for rosacea, scars
, according to a 2020 international consensus publication that Jeremy B. Green, MD, reviewed during a virtual course on laser and aesthetic skin therapy.
During his presentation, he also reviewed laser treatment of scars. “Erythema is an indicator of scar activity,” said Dr. Green, a dermatologist in Coral Gables, Fla. “So, with flat, red scars, vascular devices are the first choice. If you’re going to treat with multiple lasers in a single session, use the vascular laser first, followed by a resurfacing laser if needed. If you treat with a resurfacing laser first, you’ll cause erythema and edema and you’ll obscure that blood vessel target.”
The manuscript, which was created by a panel of 26 dermatologists and plastic and reconstructive surgeons from 13 different countries, also calls for using scar treatment settings that are lower than those used for port wine stains, with mild purpura as the clinical endpoint to strive for.
Vascular lasers are also the expert panel’s first choice when a scar is painful or pruritic, while the second choice is an ablative fractional laser with intralesional triamcinolone and/or 5-fluorouracil (5-FU). “If the scar is hypertrophic, I will combine a vascular laser, then a nonablative or an ablative fractional laser, then intralesional triamcinolone mixed with 5-FU,” said Dr. Green, who was not involved in drafting the recommendations.
As for the first treatment of choice, 80% of the experts chose a pulsed dye laser, while others chose the KTP laser, intense pulsed light (IPL) and the neodymium yttrium aluminum garnet (Nd:YAG) laser. With regard to settings, when using a PDL and a 10-mm spot size, 41% of experts recommend a fluence of 5-6 J/cm2, 27% recommend a fluence of 4-5 J/cm2, and 27% recommend a fluence of 6-7 J/cm2. Pertaining to pulse duration, 50% favor 1.5 milliseconds, 18% use 3 milliseconds, and 18% use .45 milliseconds.
As for timing post surgery, 70% report treating less than 1 week after surgery and 90% report treating within 1 month post surgery. “I prefer to treat about 1 week after sutures are removed so the skin is re-epithelialized,” Dr. Green said. “The bottom line is, with postsurgical, posttraumatic scars, once the skin is healed, the sooner you get at it, the better.”
Rosacea
He also discussed the microvascular effects of PDL in combination with oxymetazoline 1% cream, an alpha1A adrenoceptor agonist, which is approved by the Food and Drug Administration for treatment of persistent facial erythema associated with rosacea. “This has been a hot topic lately,” Dr. Green said. “When the studies were done for FDA approval, there was an observation that vasodilation occurs 5 minutes after application of oxymetazoline, so the venule diameter increases. Sixty minutes after application, vasoconstriction happens, which is the desired clinical effect for patients with facial erythema.”
In a mouse study, researchers led by Bernard Choi, PhD, and Kristin M. Kelly, MD, of the Beckman Laser Institute and Medical Clinic, University of California, Irvine, found that the combination protocol of oxymetazoline application, followed 5 minutes later by PDL, induced persistent vascular shutdown 7 days after irradiation. Vascular shutdown occurred in 67% of vessels treated with oxymetazoline plus PDL at day 7 vs. 17% in those treated with saline plus PDL.
“This is fascinating,” Dr. Green said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “There is no publication I’m aware of in humans that has explored this timing, but I have used oxymetazoline in my clinic in patients with stubborn erythema and treated them with the vascular laser 5 minutes later.”
In a separate open-label study of 46 patients with moderate to severe facial erythema associated with rosacea, researchers found that oxymetazoline 1% as adjunctive therapy with energy-based therapy was safe and well tolerated, and reduced facial erythema in patients with moderate to severe persistent facial erythema associated with rosacea. Energy sources used were the PDL, KTP, or IPL.
In a study presented during the 2020 American Society for Laser Medicine & Surgery meeting, researchers led by Pooja Sodha, MD, of George Washington University, Washington, conducted a pilot trial of PDL plus oxymetazoline 1% cream for erythematotelangiectatic rosacea. Between baseline and 6 months’ follow-up the Clinician’s Erythema Assessment score fell from 4 to 2.
“Of note, I would also throw the kitchen sink at these patients medically, meaning I love topical ivermectin 1% cream,” Dr. Green said. “In some cases I’ll even use oral ivermectin and an oral tetracycline class antibiotic.”
He reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.
, according to a 2020 international consensus publication that Jeremy B. Green, MD, reviewed during a virtual course on laser and aesthetic skin therapy.
During his presentation, he also reviewed laser treatment of scars. “Erythema is an indicator of scar activity,” said Dr. Green, a dermatologist in Coral Gables, Fla. “So, with flat, red scars, vascular devices are the first choice. If you’re going to treat with multiple lasers in a single session, use the vascular laser first, followed by a resurfacing laser if needed. If you treat with a resurfacing laser first, you’ll cause erythema and edema and you’ll obscure that blood vessel target.”
The manuscript, which was created by a panel of 26 dermatologists and plastic and reconstructive surgeons from 13 different countries, also calls for using scar treatment settings that are lower than those used for port wine stains, with mild purpura as the clinical endpoint to strive for.
Vascular lasers are also the expert panel’s first choice when a scar is painful or pruritic, while the second choice is an ablative fractional laser with intralesional triamcinolone and/or 5-fluorouracil (5-FU). “If the scar is hypertrophic, I will combine a vascular laser, then a nonablative or an ablative fractional laser, then intralesional triamcinolone mixed with 5-FU,” said Dr. Green, who was not involved in drafting the recommendations.
As for the first treatment of choice, 80% of the experts chose a pulsed dye laser, while others chose the KTP laser, intense pulsed light (IPL) and the neodymium yttrium aluminum garnet (Nd:YAG) laser. With regard to settings, when using a PDL and a 10-mm spot size, 41% of experts recommend a fluence of 5-6 J/cm2, 27% recommend a fluence of 4-5 J/cm2, and 27% recommend a fluence of 6-7 J/cm2. Pertaining to pulse duration, 50% favor 1.5 milliseconds, 18% use 3 milliseconds, and 18% use .45 milliseconds.
As for timing post surgery, 70% report treating less than 1 week after surgery and 90% report treating within 1 month post surgery. “I prefer to treat about 1 week after sutures are removed so the skin is re-epithelialized,” Dr. Green said. “The bottom line is, with postsurgical, posttraumatic scars, once the skin is healed, the sooner you get at it, the better.”
Rosacea
He also discussed the microvascular effects of PDL in combination with oxymetazoline 1% cream, an alpha1A adrenoceptor agonist, which is approved by the Food and Drug Administration for treatment of persistent facial erythema associated with rosacea. “This has been a hot topic lately,” Dr. Green said. “When the studies were done for FDA approval, there was an observation that vasodilation occurs 5 minutes after application of oxymetazoline, so the venule diameter increases. Sixty minutes after application, vasoconstriction happens, which is the desired clinical effect for patients with facial erythema.”
In a mouse study, researchers led by Bernard Choi, PhD, and Kristin M. Kelly, MD, of the Beckman Laser Institute and Medical Clinic, University of California, Irvine, found that the combination protocol of oxymetazoline application, followed 5 minutes later by PDL, induced persistent vascular shutdown 7 days after irradiation. Vascular shutdown occurred in 67% of vessels treated with oxymetazoline plus PDL at day 7 vs. 17% in those treated with saline plus PDL.
“This is fascinating,” Dr. Green said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “There is no publication I’m aware of in humans that has explored this timing, but I have used oxymetazoline in my clinic in patients with stubborn erythema and treated them with the vascular laser 5 minutes later.”
In a separate open-label study of 46 patients with moderate to severe facial erythema associated with rosacea, researchers found that oxymetazoline 1% as adjunctive therapy with energy-based therapy was safe and well tolerated, and reduced facial erythema in patients with moderate to severe persistent facial erythema associated with rosacea. Energy sources used were the PDL, KTP, or IPL.
In a study presented during the 2020 American Society for Laser Medicine & Surgery meeting, researchers led by Pooja Sodha, MD, of George Washington University, Washington, conducted a pilot trial of PDL plus oxymetazoline 1% cream for erythematotelangiectatic rosacea. Between baseline and 6 months’ follow-up the Clinician’s Erythema Assessment score fell from 4 to 2.
“Of note, I would also throw the kitchen sink at these patients medically, meaning I love topical ivermectin 1% cream,” Dr. Green said. “In some cases I’ll even use oral ivermectin and an oral tetracycline class antibiotic.”
He reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.
, according to a 2020 international consensus publication that Jeremy B. Green, MD, reviewed during a virtual course on laser and aesthetic skin therapy.
During his presentation, he also reviewed laser treatment of scars. “Erythema is an indicator of scar activity,” said Dr. Green, a dermatologist in Coral Gables, Fla. “So, with flat, red scars, vascular devices are the first choice. If you’re going to treat with multiple lasers in a single session, use the vascular laser first, followed by a resurfacing laser if needed. If you treat with a resurfacing laser first, you’ll cause erythema and edema and you’ll obscure that blood vessel target.”
The manuscript, which was created by a panel of 26 dermatologists and plastic and reconstructive surgeons from 13 different countries, also calls for using scar treatment settings that are lower than those used for port wine stains, with mild purpura as the clinical endpoint to strive for.
Vascular lasers are also the expert panel’s first choice when a scar is painful or pruritic, while the second choice is an ablative fractional laser with intralesional triamcinolone and/or 5-fluorouracil (5-FU). “If the scar is hypertrophic, I will combine a vascular laser, then a nonablative or an ablative fractional laser, then intralesional triamcinolone mixed with 5-FU,” said Dr. Green, who was not involved in drafting the recommendations.
As for the first treatment of choice, 80% of the experts chose a pulsed dye laser, while others chose the KTP laser, intense pulsed light (IPL) and the neodymium yttrium aluminum garnet (Nd:YAG) laser. With regard to settings, when using a PDL and a 10-mm spot size, 41% of experts recommend a fluence of 5-6 J/cm2, 27% recommend a fluence of 4-5 J/cm2, and 27% recommend a fluence of 6-7 J/cm2. Pertaining to pulse duration, 50% favor 1.5 milliseconds, 18% use 3 milliseconds, and 18% use .45 milliseconds.
As for timing post surgery, 70% report treating less than 1 week after surgery and 90% report treating within 1 month post surgery. “I prefer to treat about 1 week after sutures are removed so the skin is re-epithelialized,” Dr. Green said. “The bottom line is, with postsurgical, posttraumatic scars, once the skin is healed, the sooner you get at it, the better.”
Rosacea
He also discussed the microvascular effects of PDL in combination with oxymetazoline 1% cream, an alpha1A adrenoceptor agonist, which is approved by the Food and Drug Administration for treatment of persistent facial erythema associated with rosacea. “This has been a hot topic lately,” Dr. Green said. “When the studies were done for FDA approval, there was an observation that vasodilation occurs 5 minutes after application of oxymetazoline, so the venule diameter increases. Sixty minutes after application, vasoconstriction happens, which is the desired clinical effect for patients with facial erythema.”
In a mouse study, researchers led by Bernard Choi, PhD, and Kristin M. Kelly, MD, of the Beckman Laser Institute and Medical Clinic, University of California, Irvine, found that the combination protocol of oxymetazoline application, followed 5 minutes later by PDL, induced persistent vascular shutdown 7 days after irradiation. Vascular shutdown occurred in 67% of vessels treated with oxymetazoline plus PDL at day 7 vs. 17% in those treated with saline plus PDL.
“This is fascinating,” Dr. Green said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “There is no publication I’m aware of in humans that has explored this timing, but I have used oxymetazoline in my clinic in patients with stubborn erythema and treated them with the vascular laser 5 minutes later.”
In a separate open-label study of 46 patients with moderate to severe facial erythema associated with rosacea, researchers found that oxymetazoline 1% as adjunctive therapy with energy-based therapy was safe and well tolerated, and reduced facial erythema in patients with moderate to severe persistent facial erythema associated with rosacea. Energy sources used were the PDL, KTP, or IPL.
In a study presented during the 2020 American Society for Laser Medicine & Surgery meeting, researchers led by Pooja Sodha, MD, of George Washington University, Washington, conducted a pilot trial of PDL plus oxymetazoline 1% cream for erythematotelangiectatic rosacea. Between baseline and 6 months’ follow-up the Clinician’s Erythema Assessment score fell from 4 to 2.
“Of note, I would also throw the kitchen sink at these patients medically, meaning I love topical ivermectin 1% cream,” Dr. Green said. “In some cases I’ll even use oral ivermectin and an oral tetracycline class antibiotic.”
He reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.
EXPERT ANALYSIS FROM A LASER & AESTHETIC SKIN THERAPY COURSE
Sleep apnea and cognitive impairment are common bedfellows
“The study shows obstructive sleep apnea is common in patients with cognitive impairment. The results suggest that people with cognitive impairment should be assessed for sleep apnea if they have difficulty with sleep or if they demonstrate sleep-related symptoms,” said study investigator David Colelli, MSc, research coordinator at Sunnybrook Health Sciences Centre in Toronto.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology..
Linked to cognitive impairment
OSA is a common sleep disorder and is associated with an increased risk of developing cognitive impairment. It is also prevalent in the general population, but even more common among patients with dementia.
However, the investigators noted, the frequency and predictors of OSA have not been well established in Alzheimer’s disease and other related conditions such as vascular dementia.
The investigators had conducted a previous feasibility study investigating a home sleep monitor as an OSA screening tool. The current research examined potential correlations between OSA detected by this monitor and cognitive impairment.
The study included 67 patients with cognitive impairment due to neurodegenerative or vascular disease. The range of disorders included Alzheimer’s disease, mild cognitive impairment caused by Alzheimer’s disease, dementia caused by Parkinson’s or Lewy body disease, and vascular conditions.
Participants had a mean age of 72.8 years and 44.8% were male. The mean body mass index (BMI) was 25.6 kg/m2.
These participants completed a home sleep apnea test, which is an alternative to polysomnography for the detection of OSA.
Researchers identified OSA in 52.2% of the study population. This, Mr. Colelli said, “is in the range” of other research investigating sleep and cognitive impairment.
“In the general population, however, this number is a lot lower – in the 10%-20% range depending on the population or country you’re looking at,” Mr. Colelli said.
He emphasized that, without an objective sleep test, some patients may be unaware of their sleep issues. Those with cognitive impairment may “misjudge how they’re sleeping,” especially if they sleep without a partner, so it’s possible that sleep disorder symptoms often go undetected.
Bidirectional relationship?
Participants answered questionnaires on sleep, cognition, and mood. They also completed the 30-point Montreal Cognitive Assessment (MoCA) to assess language, visuospatial abilities, memory and recall, and abstract thinking.
Scores on this test range from 0 to 30, with a score of 26 or higher signifying normal, 18-25 indicating mild cognitive impairment, and 17 or lower indicating moderate to severe cognitive impairment. The average score for study participants with OSA was 20.5, compared with 23.6 for those without the sleep disorder.
Results showed OSA was significantly associated with a lower score on the MoCA scale (odds ratio, 0.40; P = .048). “This demonstrated an association of OSA with lower cognitive scores,” Mr. Colelli said.
The analysis also showed that OSA severity was correlated with actigraphy-derived sleep variables, including lower total sleep time, greater sleep onset latency, lower sleep efficiency, and more awakenings.
The study was too small to determine whether a specific diagnosis of cognitive impairment affected the link to OSA, Mr. Colelli said. “But definitely future research should be directed towards looking at this.”
Obesity is a risk factor for OSA, but the mean BMI in the study was not in the obese range of 30 and over. This, Mr. Colelli said, suggests that sleep apnea may present differently in those with cognitive impairment.
“Sleep apnea in this population might not present with the typical risk factors of obesity or snoring or feeling tired.”
While the new study “adds to the understanding that there’s a link between sleep and cognitive impairment, the direction of that link isn’t entirely clear,” Mr. Colelli said.
“It’s slowly becoming appreciated that the relationship might be bidirectionality, where sleep apnea might be contributing to the cognitive impairment and cognitive impairment could be contributing to the sleep issues.”
The study highlights how essential sleep is to mental health, Mr. Colelli said. “I feel, and I’m sure you do too, that if you don’t get good sleep, you feel tired during the day and you may not have the best concentration or memory.”
Identifying sleep issues in patients with cognitive impairment is important, as treatment and management of these issues could affect outcomes including cognition and quality of life, he added.
“Future research should be directed to see if treatment of sleep disorders with continuous positive airway pressure (CPAP), which is the gold standard, and various other treatments, can improve outcomes.” Future research should also examine OSA prevalence in larger cohorts.
Common, undertreated
Commenting on the resaerch, Lei Gao, MD, assistant professor of anesthesia at Harvard Medical School, Boston, whose areas of expertise include disorders of cognition, sleep, and circadian rhythm, believes the findings are important. “It highlights how common and potentially undertreated OSA is in this age group, and in particular, its link to cognitive impairment.”
OSA is often associated with significant comorbidities, as well as sleep disruption, Dr. Gao noted. One of the study’s strengths was including objective assessment of sleep using actigraphy. “It will be interesting to see to what extent the OSA link to cognitive impairment is via poor sleep or disrupted circadian rest/activity cycles.”
It would also be interesting “to tease out whether OSA is more linked to dementia of vascular etiologies due to common risk factors, or whether it is pervasive to all forms of dementia,” he added.
A version of this article first appeared on Medscape.com.
“The study shows obstructive sleep apnea is common in patients with cognitive impairment. The results suggest that people with cognitive impairment should be assessed for sleep apnea if they have difficulty with sleep or if they demonstrate sleep-related symptoms,” said study investigator David Colelli, MSc, research coordinator at Sunnybrook Health Sciences Centre in Toronto.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology..
Linked to cognitive impairment
OSA is a common sleep disorder and is associated with an increased risk of developing cognitive impairment. It is also prevalent in the general population, but even more common among patients with dementia.
However, the investigators noted, the frequency and predictors of OSA have not been well established in Alzheimer’s disease and other related conditions such as vascular dementia.
The investigators had conducted a previous feasibility study investigating a home sleep monitor as an OSA screening tool. The current research examined potential correlations between OSA detected by this monitor and cognitive impairment.
The study included 67 patients with cognitive impairment due to neurodegenerative or vascular disease. The range of disorders included Alzheimer’s disease, mild cognitive impairment caused by Alzheimer’s disease, dementia caused by Parkinson’s or Lewy body disease, and vascular conditions.
Participants had a mean age of 72.8 years and 44.8% were male. The mean body mass index (BMI) was 25.6 kg/m2.
These participants completed a home sleep apnea test, which is an alternative to polysomnography for the detection of OSA.
Researchers identified OSA in 52.2% of the study population. This, Mr. Colelli said, “is in the range” of other research investigating sleep and cognitive impairment.
“In the general population, however, this number is a lot lower – in the 10%-20% range depending on the population or country you’re looking at,” Mr. Colelli said.
He emphasized that, without an objective sleep test, some patients may be unaware of their sleep issues. Those with cognitive impairment may “misjudge how they’re sleeping,” especially if they sleep without a partner, so it’s possible that sleep disorder symptoms often go undetected.
Bidirectional relationship?
Participants answered questionnaires on sleep, cognition, and mood. They also completed the 30-point Montreal Cognitive Assessment (MoCA) to assess language, visuospatial abilities, memory and recall, and abstract thinking.
Scores on this test range from 0 to 30, with a score of 26 or higher signifying normal, 18-25 indicating mild cognitive impairment, and 17 or lower indicating moderate to severe cognitive impairment. The average score for study participants with OSA was 20.5, compared with 23.6 for those without the sleep disorder.
Results showed OSA was significantly associated with a lower score on the MoCA scale (odds ratio, 0.40; P = .048). “This demonstrated an association of OSA with lower cognitive scores,” Mr. Colelli said.
The analysis also showed that OSA severity was correlated with actigraphy-derived sleep variables, including lower total sleep time, greater sleep onset latency, lower sleep efficiency, and more awakenings.
The study was too small to determine whether a specific diagnosis of cognitive impairment affected the link to OSA, Mr. Colelli said. “But definitely future research should be directed towards looking at this.”
Obesity is a risk factor for OSA, but the mean BMI in the study was not in the obese range of 30 and over. This, Mr. Colelli said, suggests that sleep apnea may present differently in those with cognitive impairment.
“Sleep apnea in this population might not present with the typical risk factors of obesity or snoring or feeling tired.”
While the new study “adds to the understanding that there’s a link between sleep and cognitive impairment, the direction of that link isn’t entirely clear,” Mr. Colelli said.
“It’s slowly becoming appreciated that the relationship might be bidirectionality, where sleep apnea might be contributing to the cognitive impairment and cognitive impairment could be contributing to the sleep issues.”
The study highlights how essential sleep is to mental health, Mr. Colelli said. “I feel, and I’m sure you do too, that if you don’t get good sleep, you feel tired during the day and you may not have the best concentration or memory.”
Identifying sleep issues in patients with cognitive impairment is important, as treatment and management of these issues could affect outcomes including cognition and quality of life, he added.
“Future research should be directed to see if treatment of sleep disorders with continuous positive airway pressure (CPAP), which is the gold standard, and various other treatments, can improve outcomes.” Future research should also examine OSA prevalence in larger cohorts.
Common, undertreated
Commenting on the resaerch, Lei Gao, MD, assistant professor of anesthesia at Harvard Medical School, Boston, whose areas of expertise include disorders of cognition, sleep, and circadian rhythm, believes the findings are important. “It highlights how common and potentially undertreated OSA is in this age group, and in particular, its link to cognitive impairment.”
OSA is often associated with significant comorbidities, as well as sleep disruption, Dr. Gao noted. One of the study’s strengths was including objective assessment of sleep using actigraphy. “It will be interesting to see to what extent the OSA link to cognitive impairment is via poor sleep or disrupted circadian rest/activity cycles.”
It would also be interesting “to tease out whether OSA is more linked to dementia of vascular etiologies due to common risk factors, or whether it is pervasive to all forms of dementia,” he added.
A version of this article first appeared on Medscape.com.
“The study shows obstructive sleep apnea is common in patients with cognitive impairment. The results suggest that people with cognitive impairment should be assessed for sleep apnea if they have difficulty with sleep or if they demonstrate sleep-related symptoms,” said study investigator David Colelli, MSc, research coordinator at Sunnybrook Health Sciences Centre in Toronto.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology..
Linked to cognitive impairment
OSA is a common sleep disorder and is associated with an increased risk of developing cognitive impairment. It is also prevalent in the general population, but even more common among patients with dementia.
However, the investigators noted, the frequency and predictors of OSA have not been well established in Alzheimer’s disease and other related conditions such as vascular dementia.
The investigators had conducted a previous feasibility study investigating a home sleep monitor as an OSA screening tool. The current research examined potential correlations between OSA detected by this monitor and cognitive impairment.
The study included 67 patients with cognitive impairment due to neurodegenerative or vascular disease. The range of disorders included Alzheimer’s disease, mild cognitive impairment caused by Alzheimer’s disease, dementia caused by Parkinson’s or Lewy body disease, and vascular conditions.
Participants had a mean age of 72.8 years and 44.8% were male. The mean body mass index (BMI) was 25.6 kg/m2.
These participants completed a home sleep apnea test, which is an alternative to polysomnography for the detection of OSA.
Researchers identified OSA in 52.2% of the study population. This, Mr. Colelli said, “is in the range” of other research investigating sleep and cognitive impairment.
“In the general population, however, this number is a lot lower – in the 10%-20% range depending on the population or country you’re looking at,” Mr. Colelli said.
He emphasized that, without an objective sleep test, some patients may be unaware of their sleep issues. Those with cognitive impairment may “misjudge how they’re sleeping,” especially if they sleep without a partner, so it’s possible that sleep disorder symptoms often go undetected.
Bidirectional relationship?
Participants answered questionnaires on sleep, cognition, and mood. They also completed the 30-point Montreal Cognitive Assessment (MoCA) to assess language, visuospatial abilities, memory and recall, and abstract thinking.
Scores on this test range from 0 to 30, with a score of 26 or higher signifying normal, 18-25 indicating mild cognitive impairment, and 17 or lower indicating moderate to severe cognitive impairment. The average score for study participants with OSA was 20.5, compared with 23.6 for those without the sleep disorder.
Results showed OSA was significantly associated with a lower score on the MoCA scale (odds ratio, 0.40; P = .048). “This demonstrated an association of OSA with lower cognitive scores,” Mr. Colelli said.
The analysis also showed that OSA severity was correlated with actigraphy-derived sleep variables, including lower total sleep time, greater sleep onset latency, lower sleep efficiency, and more awakenings.
The study was too small to determine whether a specific diagnosis of cognitive impairment affected the link to OSA, Mr. Colelli said. “But definitely future research should be directed towards looking at this.”
Obesity is a risk factor for OSA, but the mean BMI in the study was not in the obese range of 30 and over. This, Mr. Colelli said, suggests that sleep apnea may present differently in those with cognitive impairment.
“Sleep apnea in this population might not present with the typical risk factors of obesity or snoring or feeling tired.”
While the new study “adds to the understanding that there’s a link between sleep and cognitive impairment, the direction of that link isn’t entirely clear,” Mr. Colelli said.
“It’s slowly becoming appreciated that the relationship might be bidirectionality, where sleep apnea might be contributing to the cognitive impairment and cognitive impairment could be contributing to the sleep issues.”
The study highlights how essential sleep is to mental health, Mr. Colelli said. “I feel, and I’m sure you do too, that if you don’t get good sleep, you feel tired during the day and you may not have the best concentration or memory.”
Identifying sleep issues in patients with cognitive impairment is important, as treatment and management of these issues could affect outcomes including cognition and quality of life, he added.
“Future research should be directed to see if treatment of sleep disorders with continuous positive airway pressure (CPAP), which is the gold standard, and various other treatments, can improve outcomes.” Future research should also examine OSA prevalence in larger cohorts.
Common, undertreated
Commenting on the resaerch, Lei Gao, MD, assistant professor of anesthesia at Harvard Medical School, Boston, whose areas of expertise include disorders of cognition, sleep, and circadian rhythm, believes the findings are important. “It highlights how common and potentially undertreated OSA is in this age group, and in particular, its link to cognitive impairment.”
OSA is often associated with significant comorbidities, as well as sleep disruption, Dr. Gao noted. One of the study’s strengths was including objective assessment of sleep using actigraphy. “It will be interesting to see to what extent the OSA link to cognitive impairment is via poor sleep or disrupted circadian rest/activity cycles.”
It would also be interesting “to tease out whether OSA is more linked to dementia of vascular etiologies due to common risk factors, or whether it is pervasive to all forms of dementia,” he added.
A version of this article first appeared on Medscape.com.
FROM AAN 2021
Do antidepressants increase the risk of brain bleeds?
Contrary to previous findings, results of a large observational study show. However, at least one expert urged caution in interpreting the finding.
“These findings are important, especially since depression is common after stroke and SSRIs are some of the first drugs considered for people,” Mithilesh Siddu, MD, of the University of Miami/Jackson Memorial Hospital, also in Miami, said in a statement.
However, Dr. Siddu said “more research is needed to confirm our findings and to also examine if SSRIs prescribed after a stroke may be linked to risk of a second stroke.”
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Widely prescribed
SSRIs, the most widely prescribed antidepressant in the United States, have previously been linked to an increased risk of ICH, possibly as a result of impaired platelet function.
To investigate further, the researchers analyzed data from the Florida Stroke Registry (FSR). They identified 127,915 patients who suffered ICH from January 2010 to December 2019 and for whom information on antidepressant use was available.
They analyzed the proportion of cases presenting with ICH among antidepressant users and the rate of SSRI prescription among stroke patients discharged on antidepressant therapy.
The researchers found that 11% of those who had been prescribed antidepressants had an ICH, compared with 14% of those who had not.
Antidepressant users were more likely to be female; non-Hispanic White; have hypertension; have diabetes; and use oral anticoagulants, antiplatelets, and statins prior to hospital presentation for ICH.
In multivariable analyses adjusting for age, race, prior history of hypertension, diabetes and prior oral anticoagulant, antiplatelet and statin use, antidepressant users were just as likely to present with spontaneous ICH as nonantidepressant users (odds ratio, 0.92; 95% confidence interval, 0.85-1.01).
A total of 3.4% of all ICH patients and 9% of those in whom specific antidepressant information was available were discharged home on an antidepressant, most commonly an SSRI (74%).
The authors noted a key limitation of the study: Some details regarding the length, dosage, and type of antidepressants were not available.
Interpret with caution
In a comment, Shaheen Lakhan, MD, PhD, a neurologist in Newton, Mass., and executive director of the Global Neuroscience Initiative Foundation, urged caution in making any firm conclusions based on this study.
“We have two questions here: One, is SSRI use a risk factor for first-time intracerebral hemorrhage, and two, is SSRI use after an ICH a risk factor for additional hemorrhages,” said Dr. Lakhan, who was not involved with the study.
“This study incompletely addresses the first because it is known that SSRIs have a variety of potencies. For instance, paroxetine is a strong inhibitor of serotonin reuptake, whereas bupropion is weak. Hypothetically, the former has a greater risk of ICH. Because this study did not stratify by type of antidepressant, it is not possible to tease these out,” Dr. Lakhan said.
“The second question is completely unaddressed by this study and is the real concern in clinical practice, because the chance of rebleed is much higher than the risk of first-time ICH in the general population,” he added.
The study had no specific funding. Dr. Siddu and Dr. Lakhan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Contrary to previous findings, results of a large observational study show. However, at least one expert urged caution in interpreting the finding.
“These findings are important, especially since depression is common after stroke and SSRIs are some of the first drugs considered for people,” Mithilesh Siddu, MD, of the University of Miami/Jackson Memorial Hospital, also in Miami, said in a statement.
However, Dr. Siddu said “more research is needed to confirm our findings and to also examine if SSRIs prescribed after a stroke may be linked to risk of a second stroke.”
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Widely prescribed
SSRIs, the most widely prescribed antidepressant in the United States, have previously been linked to an increased risk of ICH, possibly as a result of impaired platelet function.
To investigate further, the researchers analyzed data from the Florida Stroke Registry (FSR). They identified 127,915 patients who suffered ICH from January 2010 to December 2019 and for whom information on antidepressant use was available.
They analyzed the proportion of cases presenting with ICH among antidepressant users and the rate of SSRI prescription among stroke patients discharged on antidepressant therapy.
The researchers found that 11% of those who had been prescribed antidepressants had an ICH, compared with 14% of those who had not.
Antidepressant users were more likely to be female; non-Hispanic White; have hypertension; have diabetes; and use oral anticoagulants, antiplatelets, and statins prior to hospital presentation for ICH.
In multivariable analyses adjusting for age, race, prior history of hypertension, diabetes and prior oral anticoagulant, antiplatelet and statin use, antidepressant users were just as likely to present with spontaneous ICH as nonantidepressant users (odds ratio, 0.92; 95% confidence interval, 0.85-1.01).
A total of 3.4% of all ICH patients and 9% of those in whom specific antidepressant information was available were discharged home on an antidepressant, most commonly an SSRI (74%).
The authors noted a key limitation of the study: Some details regarding the length, dosage, and type of antidepressants were not available.
Interpret with caution
In a comment, Shaheen Lakhan, MD, PhD, a neurologist in Newton, Mass., and executive director of the Global Neuroscience Initiative Foundation, urged caution in making any firm conclusions based on this study.
“We have two questions here: One, is SSRI use a risk factor for first-time intracerebral hemorrhage, and two, is SSRI use after an ICH a risk factor for additional hemorrhages,” said Dr. Lakhan, who was not involved with the study.
“This study incompletely addresses the first because it is known that SSRIs have a variety of potencies. For instance, paroxetine is a strong inhibitor of serotonin reuptake, whereas bupropion is weak. Hypothetically, the former has a greater risk of ICH. Because this study did not stratify by type of antidepressant, it is not possible to tease these out,” Dr. Lakhan said.
“The second question is completely unaddressed by this study and is the real concern in clinical practice, because the chance of rebleed is much higher than the risk of first-time ICH in the general population,” he added.
The study had no specific funding. Dr. Siddu and Dr. Lakhan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Contrary to previous findings, results of a large observational study show. However, at least one expert urged caution in interpreting the finding.
“These findings are important, especially since depression is common after stroke and SSRIs are some of the first drugs considered for people,” Mithilesh Siddu, MD, of the University of Miami/Jackson Memorial Hospital, also in Miami, said in a statement.
However, Dr. Siddu said “more research is needed to confirm our findings and to also examine if SSRIs prescribed after a stroke may be linked to risk of a second stroke.”
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Widely prescribed
SSRIs, the most widely prescribed antidepressant in the United States, have previously been linked to an increased risk of ICH, possibly as a result of impaired platelet function.
To investigate further, the researchers analyzed data from the Florida Stroke Registry (FSR). They identified 127,915 patients who suffered ICH from January 2010 to December 2019 and for whom information on antidepressant use was available.
They analyzed the proportion of cases presenting with ICH among antidepressant users and the rate of SSRI prescription among stroke patients discharged on antidepressant therapy.
The researchers found that 11% of those who had been prescribed antidepressants had an ICH, compared with 14% of those who had not.
Antidepressant users were more likely to be female; non-Hispanic White; have hypertension; have diabetes; and use oral anticoagulants, antiplatelets, and statins prior to hospital presentation for ICH.
In multivariable analyses adjusting for age, race, prior history of hypertension, diabetes and prior oral anticoagulant, antiplatelet and statin use, antidepressant users were just as likely to present with spontaneous ICH as nonantidepressant users (odds ratio, 0.92; 95% confidence interval, 0.85-1.01).
A total of 3.4% of all ICH patients and 9% of those in whom specific antidepressant information was available were discharged home on an antidepressant, most commonly an SSRI (74%).
The authors noted a key limitation of the study: Some details regarding the length, dosage, and type of antidepressants were not available.
Interpret with caution
In a comment, Shaheen Lakhan, MD, PhD, a neurologist in Newton, Mass., and executive director of the Global Neuroscience Initiative Foundation, urged caution in making any firm conclusions based on this study.
“We have two questions here: One, is SSRI use a risk factor for first-time intracerebral hemorrhage, and two, is SSRI use after an ICH a risk factor for additional hemorrhages,” said Dr. Lakhan, who was not involved with the study.
“This study incompletely addresses the first because it is known that SSRIs have a variety of potencies. For instance, paroxetine is a strong inhibitor of serotonin reuptake, whereas bupropion is weak. Hypothetically, the former has a greater risk of ICH. Because this study did not stratify by type of antidepressant, it is not possible to tease these out,” Dr. Lakhan said.
“The second question is completely unaddressed by this study and is the real concern in clinical practice, because the chance of rebleed is much higher than the risk of first-time ICH in the general population,” he added.
The study had no specific funding. Dr. Siddu and Dr. Lakhan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAN 2021
Natalizumab postinfusion reactions rare; is monitoring necessary?
new studies show.
Collectively, the results suggest the need to rethink the drug’s mandatory 1-hour postinfusion observation period – particularly when unnecessarily spending time in medical settings is discouraged because of concerns regarding COVID-19, the researchers concluded.
Their findings “highlight a potential opportunity to improve and streamline the infusion and postinfusion monitoring process,” reported the authors of one of the studies. The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Infusion reactions were rare
“In this systematic review of almost 10,000 natalizumab infusions, all infusion-related adverse events were mild, and no clinically relevant safety concerns were associated with natalizumab infusions,” they said.
The 1-hour postinfusion observation period for natalizumab, approved for the treatment of relapsing remitting MS (RRMS), is mandated by the Food and Drug Administration, as well as the European Medicines Agency, and applies to each dose, regardless of treatment duration, owing to concerns of infusion reactions. However, previous evidence has indicated that reactions are rare and are usually mild.
In addition to adding burden to the treatment regimen for patients and providers alike, any extended time in an environment where there is concern of heightened risk for SARS-CoV-2 exposure is a concern.
To evaluate the frequency, severity, and timing of infusion reactions, Yujie Wang, MD, of the department of neurology at the University of Washington, Seattle, and colleagues reviewed medical records of all patients who received natalizumab at the University of Washington MS Center’s infusion suite between July 2012 and September 2020.
Among 333 patients with RRMS, 9,682 infusions of natalizumab were provided over the study period, with a mean of 27 infusions per patient (range, 1-174). The mean age of the patients was 41 years, and 87 (26%) were male.
Overall, 33 infusion-related adverse events were reported in 26 patients, representing 0.34% of total infusions and 7.8% of patients.
In 77% of cases, the adverse event occurred during the infusion. In 92% of cases, the adverse event occurred within the first 6 months of treatment.
All of the events were described as mild. The most common were itching, gastrointestinal problems, headache, and flushing.
None of the reactions required emergency care or hospitalization. Symptoms were either self-managed or were managed easily with standard care. The treatment was continued in all cases.
“For physicians and providers who care for patients with MS and are comfortable with infusible therapies, it is no surprise that rates of clinically significant infusion reactions were low,” Dr. Wang said. “It is indeed consistent with prior studies that reactions generally occur during rather than post infusion.”
The authors underscored the array of potential benefits in making changes to the requirement. “Anticipated benefits may include reducing SARS-CoV2 exposure risks for patients and staff, reducing patients’ treatment burden, increasing efficiency, as well as improving access to care without neglecting patient safety.”
Additional studies show consistent findings
Several other recent studies have shown similar results. In a study published in Multiple Sclerosis in October 2020, researchers with the Amsterdam University Medical Center found that, among 14,174 natalizumab infusions provided to 225 patients with RRMS between 2006 and 2018, 276 infusion-related adverse events occurred (1.95%) among 60 patients.
There were 11 severe infusion-related adverse events in nine patients (4.0%). All documented severe reactions occurred during the infusion. Among 19 moderate adverse events, 17 occurred during the infusion.
The researchers noted that the majority of patients who experienced severe infusion reactions had detectable antibodies against natalizumab. Such antibodies are associated with a higher risk for infusion-related adverse events.
Patients who did not have any symptoms of a reaction during the infusion had no clinically relevant moderate or severe reactions.
“Thus, the need for postinfusion observation will depend on the patients’ clinical status during the infusion,” they wrote. “Consequently, our data suggest that patients who do not have an infusion-related adverse event while receiving natalizumab treatment do not need to stay in the hospital for an additional observation hour.”
Rapid infusion protocol
In another recent study published in Multiple Sclerosis and Related Disorders in January 2021, researchers in Australia reported on the use of a rapid infusion protocol of natalizumab and ocrelizumab. The protocol was implemented to reduce the amount of time patients are required to spend in clinical settings during the COVID-19 pandemic.
In their analysis of 269 rapid infusions of natalizumab and 100 rapid infusions of ocrelizumab, there were two infusion-related reactions in the natalizumab group and eight in the ocrelizumab group.
All the reactions were mild to moderate, and no discontinuations were required. None of the reactions occurred during the postinfusion observation period.
“In the setting of COVID-19 pandemic, rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis,” the authors wrote.
Under the rapid infusion protocol, patients receive three standard doses for 1 hour followed by 30 minutes of observation. In addition, infusions are reduced to 30 minutes, explained lead author Louise Rath, of clinical neurosciences, Alfred Health, in Melbourne.
“For our cohort of patients, the side effects were minimal,” she said.
“Rapid infusions allowed patients to have option of hospital in-home or office, ensuring work was not at risk by infusion,” she added. “Our governance has been very supportive, and we will be keeping rapid infusion post COVID.”
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new studies show.
Collectively, the results suggest the need to rethink the drug’s mandatory 1-hour postinfusion observation period – particularly when unnecessarily spending time in medical settings is discouraged because of concerns regarding COVID-19, the researchers concluded.
Their findings “highlight a potential opportunity to improve and streamline the infusion and postinfusion monitoring process,” reported the authors of one of the studies. The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Infusion reactions were rare
“In this systematic review of almost 10,000 natalizumab infusions, all infusion-related adverse events were mild, and no clinically relevant safety concerns were associated with natalizumab infusions,” they said.
The 1-hour postinfusion observation period for natalizumab, approved for the treatment of relapsing remitting MS (RRMS), is mandated by the Food and Drug Administration, as well as the European Medicines Agency, and applies to each dose, regardless of treatment duration, owing to concerns of infusion reactions. However, previous evidence has indicated that reactions are rare and are usually mild.
In addition to adding burden to the treatment regimen for patients and providers alike, any extended time in an environment where there is concern of heightened risk for SARS-CoV-2 exposure is a concern.
To evaluate the frequency, severity, and timing of infusion reactions, Yujie Wang, MD, of the department of neurology at the University of Washington, Seattle, and colleagues reviewed medical records of all patients who received natalizumab at the University of Washington MS Center’s infusion suite between July 2012 and September 2020.
Among 333 patients with RRMS, 9,682 infusions of natalizumab were provided over the study period, with a mean of 27 infusions per patient (range, 1-174). The mean age of the patients was 41 years, and 87 (26%) were male.
Overall, 33 infusion-related adverse events were reported in 26 patients, representing 0.34% of total infusions and 7.8% of patients.
In 77% of cases, the adverse event occurred during the infusion. In 92% of cases, the adverse event occurred within the first 6 months of treatment.
All of the events were described as mild. The most common were itching, gastrointestinal problems, headache, and flushing.
None of the reactions required emergency care or hospitalization. Symptoms were either self-managed or were managed easily with standard care. The treatment was continued in all cases.
“For physicians and providers who care for patients with MS and are comfortable with infusible therapies, it is no surprise that rates of clinically significant infusion reactions were low,” Dr. Wang said. “It is indeed consistent with prior studies that reactions generally occur during rather than post infusion.”
The authors underscored the array of potential benefits in making changes to the requirement. “Anticipated benefits may include reducing SARS-CoV2 exposure risks for patients and staff, reducing patients’ treatment burden, increasing efficiency, as well as improving access to care without neglecting patient safety.”
Additional studies show consistent findings
Several other recent studies have shown similar results. In a study published in Multiple Sclerosis in October 2020, researchers with the Amsterdam University Medical Center found that, among 14,174 natalizumab infusions provided to 225 patients with RRMS between 2006 and 2018, 276 infusion-related adverse events occurred (1.95%) among 60 patients.
There were 11 severe infusion-related adverse events in nine patients (4.0%). All documented severe reactions occurred during the infusion. Among 19 moderate adverse events, 17 occurred during the infusion.
The researchers noted that the majority of patients who experienced severe infusion reactions had detectable antibodies against natalizumab. Such antibodies are associated with a higher risk for infusion-related adverse events.
Patients who did not have any symptoms of a reaction during the infusion had no clinically relevant moderate or severe reactions.
“Thus, the need for postinfusion observation will depend on the patients’ clinical status during the infusion,” they wrote. “Consequently, our data suggest that patients who do not have an infusion-related adverse event while receiving natalizumab treatment do not need to stay in the hospital for an additional observation hour.”
Rapid infusion protocol
In another recent study published in Multiple Sclerosis and Related Disorders in January 2021, researchers in Australia reported on the use of a rapid infusion protocol of natalizumab and ocrelizumab. The protocol was implemented to reduce the amount of time patients are required to spend in clinical settings during the COVID-19 pandemic.
In their analysis of 269 rapid infusions of natalizumab and 100 rapid infusions of ocrelizumab, there were two infusion-related reactions in the natalizumab group and eight in the ocrelizumab group.
All the reactions were mild to moderate, and no discontinuations were required. None of the reactions occurred during the postinfusion observation period.
“In the setting of COVID-19 pandemic, rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis,” the authors wrote.
Under the rapid infusion protocol, patients receive three standard doses for 1 hour followed by 30 minutes of observation. In addition, infusions are reduced to 30 minutes, explained lead author Louise Rath, of clinical neurosciences, Alfred Health, in Melbourne.
“For our cohort of patients, the side effects were minimal,” she said.
“Rapid infusions allowed patients to have option of hospital in-home or office, ensuring work was not at risk by infusion,” she added. “Our governance has been very supportive, and we will be keeping rapid infusion post COVID.”
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new studies show.
Collectively, the results suggest the need to rethink the drug’s mandatory 1-hour postinfusion observation period – particularly when unnecessarily spending time in medical settings is discouraged because of concerns regarding COVID-19, the researchers concluded.
Their findings “highlight a potential opportunity to improve and streamline the infusion and postinfusion monitoring process,” reported the authors of one of the studies. The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Infusion reactions were rare
“In this systematic review of almost 10,000 natalizumab infusions, all infusion-related adverse events were mild, and no clinically relevant safety concerns were associated with natalizumab infusions,” they said.
The 1-hour postinfusion observation period for natalizumab, approved for the treatment of relapsing remitting MS (RRMS), is mandated by the Food and Drug Administration, as well as the European Medicines Agency, and applies to each dose, regardless of treatment duration, owing to concerns of infusion reactions. However, previous evidence has indicated that reactions are rare and are usually mild.
In addition to adding burden to the treatment regimen for patients and providers alike, any extended time in an environment where there is concern of heightened risk for SARS-CoV-2 exposure is a concern.
To evaluate the frequency, severity, and timing of infusion reactions, Yujie Wang, MD, of the department of neurology at the University of Washington, Seattle, and colleagues reviewed medical records of all patients who received natalizumab at the University of Washington MS Center’s infusion suite between July 2012 and September 2020.
Among 333 patients with RRMS, 9,682 infusions of natalizumab were provided over the study period, with a mean of 27 infusions per patient (range, 1-174). The mean age of the patients was 41 years, and 87 (26%) were male.
Overall, 33 infusion-related adverse events were reported in 26 patients, representing 0.34% of total infusions and 7.8% of patients.
In 77% of cases, the adverse event occurred during the infusion. In 92% of cases, the adverse event occurred within the first 6 months of treatment.
All of the events were described as mild. The most common were itching, gastrointestinal problems, headache, and flushing.
None of the reactions required emergency care or hospitalization. Symptoms were either self-managed or were managed easily with standard care. The treatment was continued in all cases.
“For physicians and providers who care for patients with MS and are comfortable with infusible therapies, it is no surprise that rates of clinically significant infusion reactions were low,” Dr. Wang said. “It is indeed consistent with prior studies that reactions generally occur during rather than post infusion.”
The authors underscored the array of potential benefits in making changes to the requirement. “Anticipated benefits may include reducing SARS-CoV2 exposure risks for patients and staff, reducing patients’ treatment burden, increasing efficiency, as well as improving access to care without neglecting patient safety.”
Additional studies show consistent findings
Several other recent studies have shown similar results. In a study published in Multiple Sclerosis in October 2020, researchers with the Amsterdam University Medical Center found that, among 14,174 natalizumab infusions provided to 225 patients with RRMS between 2006 and 2018, 276 infusion-related adverse events occurred (1.95%) among 60 patients.
There were 11 severe infusion-related adverse events in nine patients (4.0%). All documented severe reactions occurred during the infusion. Among 19 moderate adverse events, 17 occurred during the infusion.
The researchers noted that the majority of patients who experienced severe infusion reactions had detectable antibodies against natalizumab. Such antibodies are associated with a higher risk for infusion-related adverse events.
Patients who did not have any symptoms of a reaction during the infusion had no clinically relevant moderate or severe reactions.
“Thus, the need for postinfusion observation will depend on the patients’ clinical status during the infusion,” they wrote. “Consequently, our data suggest that patients who do not have an infusion-related adverse event while receiving natalizumab treatment do not need to stay in the hospital for an additional observation hour.”
Rapid infusion protocol
In another recent study published in Multiple Sclerosis and Related Disorders in January 2021, researchers in Australia reported on the use of a rapid infusion protocol of natalizumab and ocrelizumab. The protocol was implemented to reduce the amount of time patients are required to spend in clinical settings during the COVID-19 pandemic.
In their analysis of 269 rapid infusions of natalizumab and 100 rapid infusions of ocrelizumab, there were two infusion-related reactions in the natalizumab group and eight in the ocrelizumab group.
All the reactions were mild to moderate, and no discontinuations were required. None of the reactions occurred during the postinfusion observation period.
“In the setting of COVID-19 pandemic, rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis,” the authors wrote.
Under the rapid infusion protocol, patients receive three standard doses for 1 hour followed by 30 minutes of observation. In addition, infusions are reduced to 30 minutes, explained lead author Louise Rath, of clinical neurosciences, Alfred Health, in Melbourne.
“For our cohort of patients, the side effects were minimal,” she said.
“Rapid infusions allowed patients to have option of hospital in-home or office, ensuring work was not at risk by infusion,” she added. “Our governance has been very supportive, and we will be keeping rapid infusion post COVID.”
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACTRIMS 2021
Novel oral agent effective in teens with atopic dermatitis
Abrocitinib, an investigational drug proven to be a safe and effective treatment for moderate to severe atopic dermatitis (AD) in adults 18 years and older, is also safe and effective in patients aged 12-17 years, according to a randomized trial of the oral, once-daily Janus kinase (JAK) 1 selective inhibitor, used in combination with medicated topical therapy.
The results, from the phase 3 JADE TEEN study, were presented during an oral abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.
“We’re very excited about the introduction of oral JAKs into our armamentarium for atopic dermatitis,” lead author Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and chief of pediatric and adolescent dermatology, Rady Children’s Hospital, also in San Diego, said in an interview.
AD ranges in severity, and there is a great deal of moderate to severe AD that has a tremendous negative impact on the individual, Dr. Eichenfield said. “Traditionally we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control.”
JAK inhibitors are effective mediators of the inflammation response that occurs in moderate to severe AD. They inhibit the stimulation of the JAK pathway and allow anti-inflammatory effects and therefore have potential, especially in more severe disease, Dr. Eichenfield said.
In the current study, which is a spin-off of the original study that looked at abrocitinib in adults, he and his team randomly assigned 285 teens (mean age, 14.9 years; 50.9% male; 56.1% White) with moderate to severe AD to receive one of the following treatments for 12 weeks: abrocitinib 200 mg plus topical therapy (95); abrocitinib 100 mg plus topical therapy (95); or placebo, which consisted of topical therapy alone (95).
The primary endpoints were an Investigator’s Global Assessment response of clear or almost clear (scores of 0 and 1, respectively), with an improvement of at least 2 points, and an improvement in Eczema Area and Severity Index score of at least 75% at week 12.
Secondary endpoints included an improvement in Peak Pruritus Numerical Rating Scale (PP-NRS) response of at least 4 points at week 12.
The teens who received abrocitinib along with medicated topical therapy showed significant improvement in the severity of their AD at the end of the 12-week period, compared with those in the placebo group.
“The percentage of patients achieving essentially no itch, as captured in the fact that more than half of those on the higher dose of abrocitinib made it to no itch, is a new data point and is important to note,” Dr. Eichenfield said. “A lot of the other medicines don’t really get a significant percentage of the population to an itch score of 0 to 1. This drug brought about a rapid and profound itch relief.”
He added: “The results from JADE TEEN extend the drug’s utility in this younger population and show that abrocitinib performs the same with regard to efficacy and safety in the teenagers. Having atopic dermatitis that does not respond to treatment is especially hard for adolescents, but now we know that abrocitinib will be safe and effective and so we now have something to offer these kids.”
“Abrocitinib achieved a good response in this study that was statistically significant, compared to standard treatment,” Jonathan A. Bernstein, MD, professor of medicine at the University of Cincinnati, commented in an interview.
“JAK inhibitors are very promising, and this study adds to that promise. They play an important role in atopic dermatitis, so obviously, teenagers with AD represent an important population,” said Dr. Bernstein, who was not part of the study. “These results are very encouraging, and I think that we will probably see some of these JAK inhibitors approved by the FDA, if not this year, probably next.”
The study was sponsored by Pfizer. Dr. Eichenfield serves as an investigator, speaker, and consultant for Pfizer; and as an investigator, speaker, consultant, and/or is on a data safety monitoring board for AbbVie, Almirall, Amgen, Arcutis, Asana, Dermavant, Dermira, Forte, Galderma, Ichnos/Glenmark, Incyte, LEO, Lilly, L’Oreal, Novartis, Regeneron, Sanofi-Genzyme, and Verrica. Dr. Bernstein disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Abrocitinib, an investigational drug proven to be a safe and effective treatment for moderate to severe atopic dermatitis (AD) in adults 18 years and older, is also safe and effective in patients aged 12-17 years, according to a randomized trial of the oral, once-daily Janus kinase (JAK) 1 selective inhibitor, used in combination with medicated topical therapy.
The results, from the phase 3 JADE TEEN study, were presented during an oral abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.
“We’re very excited about the introduction of oral JAKs into our armamentarium for atopic dermatitis,” lead author Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and chief of pediatric and adolescent dermatology, Rady Children’s Hospital, also in San Diego, said in an interview.
AD ranges in severity, and there is a great deal of moderate to severe AD that has a tremendous negative impact on the individual, Dr. Eichenfield said. “Traditionally we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control.”
JAK inhibitors are effective mediators of the inflammation response that occurs in moderate to severe AD. They inhibit the stimulation of the JAK pathway and allow anti-inflammatory effects and therefore have potential, especially in more severe disease, Dr. Eichenfield said.
In the current study, which is a spin-off of the original study that looked at abrocitinib in adults, he and his team randomly assigned 285 teens (mean age, 14.9 years; 50.9% male; 56.1% White) with moderate to severe AD to receive one of the following treatments for 12 weeks: abrocitinib 200 mg plus topical therapy (95); abrocitinib 100 mg plus topical therapy (95); or placebo, which consisted of topical therapy alone (95).
The primary endpoints were an Investigator’s Global Assessment response of clear or almost clear (scores of 0 and 1, respectively), with an improvement of at least 2 points, and an improvement in Eczema Area and Severity Index score of at least 75% at week 12.
Secondary endpoints included an improvement in Peak Pruritus Numerical Rating Scale (PP-NRS) response of at least 4 points at week 12.
The teens who received abrocitinib along with medicated topical therapy showed significant improvement in the severity of their AD at the end of the 12-week period, compared with those in the placebo group.
“The percentage of patients achieving essentially no itch, as captured in the fact that more than half of those on the higher dose of abrocitinib made it to no itch, is a new data point and is important to note,” Dr. Eichenfield said. “A lot of the other medicines don’t really get a significant percentage of the population to an itch score of 0 to 1. This drug brought about a rapid and profound itch relief.”
He added: “The results from JADE TEEN extend the drug’s utility in this younger population and show that abrocitinib performs the same with regard to efficacy and safety in the teenagers. Having atopic dermatitis that does not respond to treatment is especially hard for adolescents, but now we know that abrocitinib will be safe and effective and so we now have something to offer these kids.”
“Abrocitinib achieved a good response in this study that was statistically significant, compared to standard treatment,” Jonathan A. Bernstein, MD, professor of medicine at the University of Cincinnati, commented in an interview.
“JAK inhibitors are very promising, and this study adds to that promise. They play an important role in atopic dermatitis, so obviously, teenagers with AD represent an important population,” said Dr. Bernstein, who was not part of the study. “These results are very encouraging, and I think that we will probably see some of these JAK inhibitors approved by the FDA, if not this year, probably next.”
The study was sponsored by Pfizer. Dr. Eichenfield serves as an investigator, speaker, and consultant for Pfizer; and as an investigator, speaker, consultant, and/or is on a data safety monitoring board for AbbVie, Almirall, Amgen, Arcutis, Asana, Dermavant, Dermira, Forte, Galderma, Ichnos/Glenmark, Incyte, LEO, Lilly, L’Oreal, Novartis, Regeneron, Sanofi-Genzyme, and Verrica. Dr. Bernstein disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Abrocitinib, an investigational drug proven to be a safe and effective treatment for moderate to severe atopic dermatitis (AD) in adults 18 years and older, is also safe and effective in patients aged 12-17 years, according to a randomized trial of the oral, once-daily Janus kinase (JAK) 1 selective inhibitor, used in combination with medicated topical therapy.
The results, from the phase 3 JADE TEEN study, were presented during an oral abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.
“We’re very excited about the introduction of oral JAKs into our armamentarium for atopic dermatitis,” lead author Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and chief of pediatric and adolescent dermatology, Rady Children’s Hospital, also in San Diego, said in an interview.
AD ranges in severity, and there is a great deal of moderate to severe AD that has a tremendous negative impact on the individual, Dr. Eichenfield said. “Traditionally we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control.”
JAK inhibitors are effective mediators of the inflammation response that occurs in moderate to severe AD. They inhibit the stimulation of the JAK pathway and allow anti-inflammatory effects and therefore have potential, especially in more severe disease, Dr. Eichenfield said.
In the current study, which is a spin-off of the original study that looked at abrocitinib in adults, he and his team randomly assigned 285 teens (mean age, 14.9 years; 50.9% male; 56.1% White) with moderate to severe AD to receive one of the following treatments for 12 weeks: abrocitinib 200 mg plus topical therapy (95); abrocitinib 100 mg plus topical therapy (95); or placebo, which consisted of topical therapy alone (95).
The primary endpoints were an Investigator’s Global Assessment response of clear or almost clear (scores of 0 and 1, respectively), with an improvement of at least 2 points, and an improvement in Eczema Area and Severity Index score of at least 75% at week 12.
Secondary endpoints included an improvement in Peak Pruritus Numerical Rating Scale (PP-NRS) response of at least 4 points at week 12.
The teens who received abrocitinib along with medicated topical therapy showed significant improvement in the severity of their AD at the end of the 12-week period, compared with those in the placebo group.
“The percentage of patients achieving essentially no itch, as captured in the fact that more than half of those on the higher dose of abrocitinib made it to no itch, is a new data point and is important to note,” Dr. Eichenfield said. “A lot of the other medicines don’t really get a significant percentage of the population to an itch score of 0 to 1. This drug brought about a rapid and profound itch relief.”
He added: “The results from JADE TEEN extend the drug’s utility in this younger population and show that abrocitinib performs the same with regard to efficacy and safety in the teenagers. Having atopic dermatitis that does not respond to treatment is especially hard for adolescents, but now we know that abrocitinib will be safe and effective and so we now have something to offer these kids.”
“Abrocitinib achieved a good response in this study that was statistically significant, compared to standard treatment,” Jonathan A. Bernstein, MD, professor of medicine at the University of Cincinnati, commented in an interview.
“JAK inhibitors are very promising, and this study adds to that promise. They play an important role in atopic dermatitis, so obviously, teenagers with AD represent an important population,” said Dr. Bernstein, who was not part of the study. “These results are very encouraging, and I think that we will probably see some of these JAK inhibitors approved by the FDA, if not this year, probably next.”
The study was sponsored by Pfizer. Dr. Eichenfield serves as an investigator, speaker, and consultant for Pfizer; and as an investigator, speaker, consultant, and/or is on a data safety monitoring board for AbbVie, Almirall, Amgen, Arcutis, Asana, Dermavant, Dermira, Forte, Galderma, Ichnos/Glenmark, Incyte, LEO, Lilly, L’Oreal, Novartis, Regeneron, Sanofi-Genzyme, and Verrica. Dr. Bernstein disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Maribavir seen as superior to other antivirals for CMV clearance post transplant
Maribavir, an investigational antiviral agent with a novel mechanism of action, was superior to other antiviral strategies at clearing cytomegalovirus (CMV) viremia and controlling symptoms in hematopoietic cell or solid-organ transplant recipients, results of a phase 3 clinical trial showed.
CMV viremia clearance at study week 8 was seen in 55.7% of all patients randomized to receive maribavir, compared with 23.9% for patients assigned to receive investigator-assigned therapy (IAT), Francisco Marty, MD, from the Dana-Farber Cancer Institute in Boston reported at the Transplant & Cellular Therapies Meetings.
“Maribavir’s benefit was driven by lower incidence of treatment-limiting toxicities, compared with IAT,” he said a late-breaking abstract session during the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
“Available anti-CMV antivirals are limited by development of resistance and toxicities, particularly myelosuppression with the use of valganciclovir and nephrotoxicity with the use of foscarnet and cidofovir. Alternative treatment options are required to address this unmet medical need,” he said.
Maribavir inhibits the CMV UL97 protein kinase and is thought to affect several critical processes in CMV replication, including viral DNA synthesis, viral gene expression, encapsidation, and egress of mature capsids from the nucleus.
Details of trial
In the phase 3 SHP620-30e trial (NCT02931539), Dr. Marty and colleagues enrolled patients with relapsed or refractory CMV infections after hematopoietic cell transplant (HCT) or solid-organ transplant (SOT) and after stratification by transplant type and screening CMV DNA level randomly assigned them on a 2:1 basis to receive either maribavir 400 mg twice daily (235 patients) or IAT (117 patients), consisting of either ganciclovir/valganciclovir, foscarnet, cidofovir, or combined foscarnet and val/ganciclovir.
The primary endpoint of viremia clearance at 8 weeks was defined as plasma CMV DNA less than 137 IU/mL in two consecutive tests at a central laboratory at least 5 days apart beginning at the end of week 8.
The trial met its primary endpoint, with a viremia clearance rate of 55.7% with maribavir versus 23.9% with IAT.
The viremia clearance rates were similar in each of the transplant groups: 55.9% versus 20.8%, respectively, in patients who underwent HCT, and 55.6% versus 26.1% in patients who underwent SOT (P < .001).
Clearance rates among patients with CMV DNA below 9,100 IU/mL at baseline were 62.1% with maribavir versus 24.7% with IAT. Among patients with baseline CMV DNA of 9100 IU/mL or above, the respective rates were 43.9% versus 21.9%.
CMV viremia clearance continued from week 8 to week 16 in 18.7% of patients assigned to maribavir and to 10.3% of patients randomized to IAT (P < .013).
The median time to first CMV viremia clearance as 22 days with maribavir versus 27 days with IAT (P = .039).
All-cause mortality was similar between the groups, at 11.5% versus 11.1%, respectively.
The incidences of serious and severe treatment-emergent adverse events (TEAE) were 38.5% and 32.1%, respectively, in the maribavir group, and 37.1% and 37.9% in the IAT group.
Any TEAE leading to study drug discontinuation was less common with maribavir, occurring in 13.2% of patients, compared with 31.9% of patients on IAT. Serious TEAEs leading to drug discontinuation occurred in 8.5% versus 14.7%, respectively.
Serious TEAEs leading to death occurred in 6.8% of patients on maribavir versus 5.2% of those on IAT.
Role of letermovir
In the question-and-answer session following the presentation, comoderator Monalisa Ghosh, MD, from the University of Michigan, Ann Arbor, asked whether any patients in the study were currently on letermovir (Prevymis) prophylaxis, and whether any patients had previously been treated with letermovir but had CMV reactivation and were then treated on study.
Dr. Marty noted that the trial was designed before letermovir was approved for CMV prophylaxis in adults who have undergone an allogeneic HCT.
“Nobody was on letermovir at the beginning of the trial,” he replied, but noted that some patients who were enrolled and had infections that were refractory or resistant to valganciclovir, foscarnet, or a combination of the two received letermovir as secondary prophylaxis.
“I haven’t got the data to tell you how often [letermovir] was used; I think part of the lack of mortality benefit [with maribavir] may be due to the fact that people jumped into secondary prophylaxis with letermovir to minimize the toxicities that we saw,” he said.
Although maribavir has not as of this writing received Food and Drug Administration approval, the drug may be available to some patients through a compassionate-use program from Takeda, Dr. Marty noted.
The study was funded by Shire ViroPharma. Dr. Marty disclosed research funding from Shire and from others. Dr. Ghosh had no relevant disclosures.
Maribavir, an investigational antiviral agent with a novel mechanism of action, was superior to other antiviral strategies at clearing cytomegalovirus (CMV) viremia and controlling symptoms in hematopoietic cell or solid-organ transplant recipients, results of a phase 3 clinical trial showed.
CMV viremia clearance at study week 8 was seen in 55.7% of all patients randomized to receive maribavir, compared with 23.9% for patients assigned to receive investigator-assigned therapy (IAT), Francisco Marty, MD, from the Dana-Farber Cancer Institute in Boston reported at the Transplant & Cellular Therapies Meetings.
“Maribavir’s benefit was driven by lower incidence of treatment-limiting toxicities, compared with IAT,” he said a late-breaking abstract session during the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
“Available anti-CMV antivirals are limited by development of resistance and toxicities, particularly myelosuppression with the use of valganciclovir and nephrotoxicity with the use of foscarnet and cidofovir. Alternative treatment options are required to address this unmet medical need,” he said.
Maribavir inhibits the CMV UL97 protein kinase and is thought to affect several critical processes in CMV replication, including viral DNA synthesis, viral gene expression, encapsidation, and egress of mature capsids from the nucleus.
Details of trial
In the phase 3 SHP620-30e trial (NCT02931539), Dr. Marty and colleagues enrolled patients with relapsed or refractory CMV infections after hematopoietic cell transplant (HCT) or solid-organ transplant (SOT) and after stratification by transplant type and screening CMV DNA level randomly assigned them on a 2:1 basis to receive either maribavir 400 mg twice daily (235 patients) or IAT (117 patients), consisting of either ganciclovir/valganciclovir, foscarnet, cidofovir, or combined foscarnet and val/ganciclovir.
The primary endpoint of viremia clearance at 8 weeks was defined as plasma CMV DNA less than 137 IU/mL in two consecutive tests at a central laboratory at least 5 days apart beginning at the end of week 8.
The trial met its primary endpoint, with a viremia clearance rate of 55.7% with maribavir versus 23.9% with IAT.
The viremia clearance rates were similar in each of the transplant groups: 55.9% versus 20.8%, respectively, in patients who underwent HCT, and 55.6% versus 26.1% in patients who underwent SOT (P < .001).
Clearance rates among patients with CMV DNA below 9,100 IU/mL at baseline were 62.1% with maribavir versus 24.7% with IAT. Among patients with baseline CMV DNA of 9100 IU/mL or above, the respective rates were 43.9% versus 21.9%.
CMV viremia clearance continued from week 8 to week 16 in 18.7% of patients assigned to maribavir and to 10.3% of patients randomized to IAT (P < .013).
The median time to first CMV viremia clearance as 22 days with maribavir versus 27 days with IAT (P = .039).
All-cause mortality was similar between the groups, at 11.5% versus 11.1%, respectively.
The incidences of serious and severe treatment-emergent adverse events (TEAE) were 38.5% and 32.1%, respectively, in the maribavir group, and 37.1% and 37.9% in the IAT group.
Any TEAE leading to study drug discontinuation was less common with maribavir, occurring in 13.2% of patients, compared with 31.9% of patients on IAT. Serious TEAEs leading to drug discontinuation occurred in 8.5% versus 14.7%, respectively.
Serious TEAEs leading to death occurred in 6.8% of patients on maribavir versus 5.2% of those on IAT.
Role of letermovir
In the question-and-answer session following the presentation, comoderator Monalisa Ghosh, MD, from the University of Michigan, Ann Arbor, asked whether any patients in the study were currently on letermovir (Prevymis) prophylaxis, and whether any patients had previously been treated with letermovir but had CMV reactivation and were then treated on study.
Dr. Marty noted that the trial was designed before letermovir was approved for CMV prophylaxis in adults who have undergone an allogeneic HCT.
“Nobody was on letermovir at the beginning of the trial,” he replied, but noted that some patients who were enrolled and had infections that were refractory or resistant to valganciclovir, foscarnet, or a combination of the two received letermovir as secondary prophylaxis.
“I haven’t got the data to tell you how often [letermovir] was used; I think part of the lack of mortality benefit [with maribavir] may be due to the fact that people jumped into secondary prophylaxis with letermovir to minimize the toxicities that we saw,” he said.
Although maribavir has not as of this writing received Food and Drug Administration approval, the drug may be available to some patients through a compassionate-use program from Takeda, Dr. Marty noted.
The study was funded by Shire ViroPharma. Dr. Marty disclosed research funding from Shire and from others. Dr. Ghosh had no relevant disclosures.
Maribavir, an investigational antiviral agent with a novel mechanism of action, was superior to other antiviral strategies at clearing cytomegalovirus (CMV) viremia and controlling symptoms in hematopoietic cell or solid-organ transplant recipients, results of a phase 3 clinical trial showed.
CMV viremia clearance at study week 8 was seen in 55.7% of all patients randomized to receive maribavir, compared with 23.9% for patients assigned to receive investigator-assigned therapy (IAT), Francisco Marty, MD, from the Dana-Farber Cancer Institute in Boston reported at the Transplant & Cellular Therapies Meetings.
“Maribavir’s benefit was driven by lower incidence of treatment-limiting toxicities, compared with IAT,” he said a late-breaking abstract session during the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
“Available anti-CMV antivirals are limited by development of resistance and toxicities, particularly myelosuppression with the use of valganciclovir and nephrotoxicity with the use of foscarnet and cidofovir. Alternative treatment options are required to address this unmet medical need,” he said.
Maribavir inhibits the CMV UL97 protein kinase and is thought to affect several critical processes in CMV replication, including viral DNA synthesis, viral gene expression, encapsidation, and egress of mature capsids from the nucleus.
Details of trial
In the phase 3 SHP620-30e trial (NCT02931539), Dr. Marty and colleagues enrolled patients with relapsed or refractory CMV infections after hematopoietic cell transplant (HCT) or solid-organ transplant (SOT) and after stratification by transplant type and screening CMV DNA level randomly assigned them on a 2:1 basis to receive either maribavir 400 mg twice daily (235 patients) or IAT (117 patients), consisting of either ganciclovir/valganciclovir, foscarnet, cidofovir, or combined foscarnet and val/ganciclovir.
The primary endpoint of viremia clearance at 8 weeks was defined as plasma CMV DNA less than 137 IU/mL in two consecutive tests at a central laboratory at least 5 days apart beginning at the end of week 8.
The trial met its primary endpoint, with a viremia clearance rate of 55.7% with maribavir versus 23.9% with IAT.
The viremia clearance rates were similar in each of the transplant groups: 55.9% versus 20.8%, respectively, in patients who underwent HCT, and 55.6% versus 26.1% in patients who underwent SOT (P < .001).
Clearance rates among patients with CMV DNA below 9,100 IU/mL at baseline were 62.1% with maribavir versus 24.7% with IAT. Among patients with baseline CMV DNA of 9100 IU/mL or above, the respective rates were 43.9% versus 21.9%.
CMV viremia clearance continued from week 8 to week 16 in 18.7% of patients assigned to maribavir and to 10.3% of patients randomized to IAT (P < .013).
The median time to first CMV viremia clearance as 22 days with maribavir versus 27 days with IAT (P = .039).
All-cause mortality was similar between the groups, at 11.5% versus 11.1%, respectively.
The incidences of serious and severe treatment-emergent adverse events (TEAE) were 38.5% and 32.1%, respectively, in the maribavir group, and 37.1% and 37.9% in the IAT group.
Any TEAE leading to study drug discontinuation was less common with maribavir, occurring in 13.2% of patients, compared with 31.9% of patients on IAT. Serious TEAEs leading to drug discontinuation occurred in 8.5% versus 14.7%, respectively.
Serious TEAEs leading to death occurred in 6.8% of patients on maribavir versus 5.2% of those on IAT.
Role of letermovir
In the question-and-answer session following the presentation, comoderator Monalisa Ghosh, MD, from the University of Michigan, Ann Arbor, asked whether any patients in the study were currently on letermovir (Prevymis) prophylaxis, and whether any patients had previously been treated with letermovir but had CMV reactivation and were then treated on study.
Dr. Marty noted that the trial was designed before letermovir was approved for CMV prophylaxis in adults who have undergone an allogeneic HCT.
“Nobody was on letermovir at the beginning of the trial,” he replied, but noted that some patients who were enrolled and had infections that were refractory or resistant to valganciclovir, foscarnet, or a combination of the two received letermovir as secondary prophylaxis.
“I haven’t got the data to tell you how often [letermovir] was used; I think part of the lack of mortality benefit [with maribavir] may be due to the fact that people jumped into secondary prophylaxis with letermovir to minimize the toxicities that we saw,” he said.
Although maribavir has not as of this writing received Food and Drug Administration approval, the drug may be available to some patients through a compassionate-use program from Takeda, Dr. Marty noted.
The study was funded by Shire ViroPharma. Dr. Marty disclosed research funding from Shire and from others. Dr. Ghosh had no relevant disclosures.
FROM TCT 2021
Recent psoriasis pathophysiology insights carry treatment implications
at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually.
Among these unexpected developments was the startling finding that skin inflammation in mild psoriasis is at least as great as in severe disease; evidence that psoriasis may actually be an autoimmune disease rather than a nonspecific immune-mediated disease; and the newly appreciated importance of interleukin-19 (IL-19) in keratinocyte proliferation, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“Our understanding of the pathophysiology of psoriasis is still a work in progress,” the dermatologist observed.
Immunoregulatory deficits in mild vs. severe psoriasis
Conventional wisdom has held that mild psoriasis as defined by limited affected body surface area involves less skin inflammation than more extensive severe psoriasis, so less-potent topical therapies are appropriate. Not so, according to Dr. Gordon, who highlighted work by James G. Krueger, MD, PhD, head of the laboratory of investigative dermatology at Rockefeller University, New York, and coinvestigators. They demonstrated that overall skin inflammation expressed as the sum of T-cell activation and IL-19-mediated epidermal responses didn’t differ in lesions of mild as compared with severe psoriasis. Indeed, mild skin lesions featured a greater number of T-cells, stronger expression of proinflammatory cytokine IL-17A, and greater expression of the central psoriasis transcriptome. The big difference between skin lesions of mild versus severe psoriasis was that severe psoriasis was characterized by strikingly weaker expression of immunoregulatory genes, including programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), than that of mild lesions.
The implication is that IL-17-targeted therapies may be of benefit in a much larger segment of the psoriatic population: namely, those with mild disease, who comprise the majority of psoriasis patients by a wide margin, according to the investigators.
Dr. Gordon concurs.
“The primary problem in psoriasis is not so much the inflammatory activity, but the ability to turn off the activity,” he explained. “That implies that if a patient wants to get clear or have significant improvement in disease, you can’t use a less effective medication just because they have less amount of disease. You’re going to need to treat it just as aggressively because the great majority of our medications block the proinflammatory pathways.”
The deficit in immunoregulatory action identified by Dr. Krueger and colleagues in patients with severe disease could provide a novel therapeutic target. If the deficient immunoregulation could be boosted, it might achieve disease control without need for continuous anti-inflammatory therapy.
Autoimmunity in psoriasis
“When I started work in psoriasis, we always thought there would be a common antigen for the immune process in the disease. We never found it. So for that reason, we sort of put it aside and called psoriasis a nonspecific immune-mediated disease,” Dr. Gordon recalled.
That view is being reexamined. “While we’re not completely certain, there is now some evidence that there might be autoimmunity in psoriasis,” he said.
He cited work by an international team of investigators who identified the cathelicidin antimicrobial peptide LL37 as being overexpressed in psoriatic skin, where it appears to serve as a T-cell autoantigen. LL37-specific CD4+ and CD8+ T-cells are skin homing: They can infiltrate lesional skin, where they produce interferon-gamma and proinflammatory Th17 cytokines. The investigators reported that levels of circulating LL37-specific T cells correlated with disease activity such that they were found in three-quarters of patients with moderate to severe plaque psoriasis.
“As LL37 is able to activate innate immune cells and break innate tolerance to self-nucleic acids, it represents an even more appealing target to treat psoriasis. Therapeutic targeting of LL37-specific T cells may provide new avenues to prevent or treat psoriasis without inducing indiscriminate immunosuppression,” the investigators concluded.
Similarly, German investigators have identified ADAMTS-like protein 5 (ADAMTSL5) as an autoantigen specific for melanocytes in psoriasis patients who possess the central psoriasis risk gene, known as HLA-C*06:02, which is present in two-thirds of patients with psoriasis. They proposed that their newly recognized autoimmune pathway may explain how HLA-C*06.02 predisposes to psoriasis.
Growing clinical relevance of IL-19
It’s now well-established that IL-17 is the pivotal force driving the changes in keratinocytes that define the visible expressions of psoriasis, including plaque scale and thickness, which are due to abnormal keratinocyte maturation and proliferation, respectively. Less well appreciated is the fact that IL-17-activated keratinocytes produce IL-19, which feeds back and further stimulates keratinocyte proliferation.
In light of mounting evidence that IL-19 plays an important role in the pathogenesis of psoriasis and that naked eye assessment of visible psoriasis may not reflect the true extent of inflammation, Brian J. Nickoloff, MD, PhD, and coworkers at Lilly Research Laboratories have developed a novel serum IL-19 immunoassay that appears to provide a much-needed objective biomarker of disease activity in psoriasis patients. They demonstrated that serum IL-19 levels correlated with Psoriasis Area and Severity Index scores, and that treatment with the anti-IL-17A biologic ixekizumab (Taltz) led to rapid reduction of IL-19 down to a normal level.
Moreover, following withdrawal of ixekizumab, IL-19 levels rose prior to clinical relapse, then dropped again in response to retreatment. The hope is that this assay will serve as an accurate tool for assessment of response to therapy.
Dr. Gordon reported receiving research funding and/or honoraria from more than a dozen pharmaceutical companies involved in psoriasis therapy.
MedscapeLive and this news organization are owned by the same parent company.
at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually.
Among these unexpected developments was the startling finding that skin inflammation in mild psoriasis is at least as great as in severe disease; evidence that psoriasis may actually be an autoimmune disease rather than a nonspecific immune-mediated disease; and the newly appreciated importance of interleukin-19 (IL-19) in keratinocyte proliferation, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“Our understanding of the pathophysiology of psoriasis is still a work in progress,” the dermatologist observed.
Immunoregulatory deficits in mild vs. severe psoriasis
Conventional wisdom has held that mild psoriasis as defined by limited affected body surface area involves less skin inflammation than more extensive severe psoriasis, so less-potent topical therapies are appropriate. Not so, according to Dr. Gordon, who highlighted work by James G. Krueger, MD, PhD, head of the laboratory of investigative dermatology at Rockefeller University, New York, and coinvestigators. They demonstrated that overall skin inflammation expressed as the sum of T-cell activation and IL-19-mediated epidermal responses didn’t differ in lesions of mild as compared with severe psoriasis. Indeed, mild skin lesions featured a greater number of T-cells, stronger expression of proinflammatory cytokine IL-17A, and greater expression of the central psoriasis transcriptome. The big difference between skin lesions of mild versus severe psoriasis was that severe psoriasis was characterized by strikingly weaker expression of immunoregulatory genes, including programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), than that of mild lesions.
The implication is that IL-17-targeted therapies may be of benefit in a much larger segment of the psoriatic population: namely, those with mild disease, who comprise the majority of psoriasis patients by a wide margin, according to the investigators.
Dr. Gordon concurs.
“The primary problem in psoriasis is not so much the inflammatory activity, but the ability to turn off the activity,” he explained. “That implies that if a patient wants to get clear or have significant improvement in disease, you can’t use a less effective medication just because they have less amount of disease. You’re going to need to treat it just as aggressively because the great majority of our medications block the proinflammatory pathways.”
The deficit in immunoregulatory action identified by Dr. Krueger and colleagues in patients with severe disease could provide a novel therapeutic target. If the deficient immunoregulation could be boosted, it might achieve disease control without need for continuous anti-inflammatory therapy.
Autoimmunity in psoriasis
“When I started work in psoriasis, we always thought there would be a common antigen for the immune process in the disease. We never found it. So for that reason, we sort of put it aside and called psoriasis a nonspecific immune-mediated disease,” Dr. Gordon recalled.
That view is being reexamined. “While we’re not completely certain, there is now some evidence that there might be autoimmunity in psoriasis,” he said.
He cited work by an international team of investigators who identified the cathelicidin antimicrobial peptide LL37 as being overexpressed in psoriatic skin, where it appears to serve as a T-cell autoantigen. LL37-specific CD4+ and CD8+ T-cells are skin homing: They can infiltrate lesional skin, where they produce interferon-gamma and proinflammatory Th17 cytokines. The investigators reported that levels of circulating LL37-specific T cells correlated with disease activity such that they were found in three-quarters of patients with moderate to severe plaque psoriasis.
“As LL37 is able to activate innate immune cells and break innate tolerance to self-nucleic acids, it represents an even more appealing target to treat psoriasis. Therapeutic targeting of LL37-specific T cells may provide new avenues to prevent or treat psoriasis without inducing indiscriminate immunosuppression,” the investigators concluded.
Similarly, German investigators have identified ADAMTS-like protein 5 (ADAMTSL5) as an autoantigen specific for melanocytes in psoriasis patients who possess the central psoriasis risk gene, known as HLA-C*06:02, which is present in two-thirds of patients with psoriasis. They proposed that their newly recognized autoimmune pathway may explain how HLA-C*06.02 predisposes to psoriasis.
Growing clinical relevance of IL-19
It’s now well-established that IL-17 is the pivotal force driving the changes in keratinocytes that define the visible expressions of psoriasis, including plaque scale and thickness, which are due to abnormal keratinocyte maturation and proliferation, respectively. Less well appreciated is the fact that IL-17-activated keratinocytes produce IL-19, which feeds back and further stimulates keratinocyte proliferation.
In light of mounting evidence that IL-19 plays an important role in the pathogenesis of psoriasis and that naked eye assessment of visible psoriasis may not reflect the true extent of inflammation, Brian J. Nickoloff, MD, PhD, and coworkers at Lilly Research Laboratories have developed a novel serum IL-19 immunoassay that appears to provide a much-needed objective biomarker of disease activity in psoriasis patients. They demonstrated that serum IL-19 levels correlated with Psoriasis Area and Severity Index scores, and that treatment with the anti-IL-17A biologic ixekizumab (Taltz) led to rapid reduction of IL-19 down to a normal level.
Moreover, following withdrawal of ixekizumab, IL-19 levels rose prior to clinical relapse, then dropped again in response to retreatment. The hope is that this assay will serve as an accurate tool for assessment of response to therapy.
Dr. Gordon reported receiving research funding and/or honoraria from more than a dozen pharmaceutical companies involved in psoriasis therapy.
MedscapeLive and this news organization are owned by the same parent company.
at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually.
Among these unexpected developments was the startling finding that skin inflammation in mild psoriasis is at least as great as in severe disease; evidence that psoriasis may actually be an autoimmune disease rather than a nonspecific immune-mediated disease; and the newly appreciated importance of interleukin-19 (IL-19) in keratinocyte proliferation, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“Our understanding of the pathophysiology of psoriasis is still a work in progress,” the dermatologist observed.
Immunoregulatory deficits in mild vs. severe psoriasis
Conventional wisdom has held that mild psoriasis as defined by limited affected body surface area involves less skin inflammation than more extensive severe psoriasis, so less-potent topical therapies are appropriate. Not so, according to Dr. Gordon, who highlighted work by James G. Krueger, MD, PhD, head of the laboratory of investigative dermatology at Rockefeller University, New York, and coinvestigators. They demonstrated that overall skin inflammation expressed as the sum of T-cell activation and IL-19-mediated epidermal responses didn’t differ in lesions of mild as compared with severe psoriasis. Indeed, mild skin lesions featured a greater number of T-cells, stronger expression of proinflammatory cytokine IL-17A, and greater expression of the central psoriasis transcriptome. The big difference between skin lesions of mild versus severe psoriasis was that severe psoriasis was characterized by strikingly weaker expression of immunoregulatory genes, including programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), than that of mild lesions.
The implication is that IL-17-targeted therapies may be of benefit in a much larger segment of the psoriatic population: namely, those with mild disease, who comprise the majority of psoriasis patients by a wide margin, according to the investigators.
Dr. Gordon concurs.
“The primary problem in psoriasis is not so much the inflammatory activity, but the ability to turn off the activity,” he explained. “That implies that if a patient wants to get clear or have significant improvement in disease, you can’t use a less effective medication just because they have less amount of disease. You’re going to need to treat it just as aggressively because the great majority of our medications block the proinflammatory pathways.”
The deficit in immunoregulatory action identified by Dr. Krueger and colleagues in patients with severe disease could provide a novel therapeutic target. If the deficient immunoregulation could be boosted, it might achieve disease control without need for continuous anti-inflammatory therapy.
Autoimmunity in psoriasis
“When I started work in psoriasis, we always thought there would be a common antigen for the immune process in the disease. We never found it. So for that reason, we sort of put it aside and called psoriasis a nonspecific immune-mediated disease,” Dr. Gordon recalled.
That view is being reexamined. “While we’re not completely certain, there is now some evidence that there might be autoimmunity in psoriasis,” he said.
He cited work by an international team of investigators who identified the cathelicidin antimicrobial peptide LL37 as being overexpressed in psoriatic skin, where it appears to serve as a T-cell autoantigen. LL37-specific CD4+ and CD8+ T-cells are skin homing: They can infiltrate lesional skin, where they produce interferon-gamma and proinflammatory Th17 cytokines. The investigators reported that levels of circulating LL37-specific T cells correlated with disease activity such that they were found in three-quarters of patients with moderate to severe plaque psoriasis.
“As LL37 is able to activate innate immune cells and break innate tolerance to self-nucleic acids, it represents an even more appealing target to treat psoriasis. Therapeutic targeting of LL37-specific T cells may provide new avenues to prevent or treat psoriasis without inducing indiscriminate immunosuppression,” the investigators concluded.
Similarly, German investigators have identified ADAMTS-like protein 5 (ADAMTSL5) as an autoantigen specific for melanocytes in psoriasis patients who possess the central psoriasis risk gene, known as HLA-C*06:02, which is present in two-thirds of patients with psoriasis. They proposed that their newly recognized autoimmune pathway may explain how HLA-C*06.02 predisposes to psoriasis.
Growing clinical relevance of IL-19
It’s now well-established that IL-17 is the pivotal force driving the changes in keratinocytes that define the visible expressions of psoriasis, including plaque scale and thickness, which are due to abnormal keratinocyte maturation and proliferation, respectively. Less well appreciated is the fact that IL-17-activated keratinocytes produce IL-19, which feeds back and further stimulates keratinocyte proliferation.
In light of mounting evidence that IL-19 plays an important role in the pathogenesis of psoriasis and that naked eye assessment of visible psoriasis may not reflect the true extent of inflammation, Brian J. Nickoloff, MD, PhD, and coworkers at Lilly Research Laboratories have developed a novel serum IL-19 immunoassay that appears to provide a much-needed objective biomarker of disease activity in psoriasis patients. They demonstrated that serum IL-19 levels correlated with Psoriasis Area and Severity Index scores, and that treatment with the anti-IL-17A biologic ixekizumab (Taltz) led to rapid reduction of IL-19 down to a normal level.
Moreover, following withdrawal of ixekizumab, IL-19 levels rose prior to clinical relapse, then dropped again in response to retreatment. The hope is that this assay will serve as an accurate tool for assessment of response to therapy.
Dr. Gordon reported receiving research funding and/or honoraria from more than a dozen pharmaceutical companies involved in psoriasis therapy.
MedscapeLive and this news organization are owned by the same parent company.
FROM MEDSCAPELIVE LAS VEGAS DERMATOLOGY SEMINAR