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Mitchel is a reporter for MDedge based in the Philadelphia area. He started with the company in 1992, when it was International Medical News Group (IMNG), and has since covered a range of medical specialties. Mitchel trained as a virologist at Roswell Park Memorial Institute in Buffalo, and then worked briefly as a researcher at Boston Children's Hospital before pivoting to journalism as a AAAS Mass Media Fellow in 1980. His first reporting job was with Science Digest magazine, and from the mid-1980s to early-1990s he was a reporter with Medical World News. @mitchelzoler
Hypertension guidelines unlikely to hold sway with PCPs
A new and long-anticipated guideline for diagnosing and managing hypertension by the American College of Cardiology, the American Heart Association, and nine other collaborating societies was finally released last fall. What happens now?
Will the top-line, seismic change that the new guidelines called for – treating many patients with hypertension to a blood pressure below 130/80 mm Hg – become the standard of care for U.S. medicine? And what about the several other novel steps the guideline calls for including more careful and methodical measurement of blood pressure with greater emphasis on out-of-office blood pressure monitoring, increased reliance on lifestyle interventions, running a formal calculation of a patient’s cardiovascular disease risk to identify patients who warrant drug treatment, development and attention to a care plan for each hypertensive patient, and a team approach to management?
In this two-part feature, a potential revolution in care will be explored.
ACC/AHA guidelines: More than just numbers
The ACC and AHA guideline (J Am Coll Cardiol. 2017 Nov 13. doi: 10.1016/j.jacc.2017.11.006) is “comprehensive. It addresses many issues around hypertension, not just what is a good [blood pressure] number and a bad number. This is important because this type of document has not existed for quite some time,” said Donald E. Casey Jr., MD, a member of the guideline-writing panel, an internal medicine physician, and chief clinical affairs officer at Medecision in Wayne, Pa.
“This is the first time that a [blood pressure] guideline has explicitly led with a strategy of calculating a person’s risk using the ACC/AHA risk calculator. It’s not ‘what is your blood pressure?’ but ‘what is your risk?’ This is not a one-size-fits-all guideline.”
The biggest wild card when handicapping the odds that the new guideline will take hold is how U.S. primary care physicians, the clinicians who stand on the front line of U.S. medicine for diagnosing and treating hypertension, respond. Their reaction remained an open issue during the weeks following release of the new guideline, in large part because its headline feature, the treatment target of less than 130/80 mm Hg, is at odds with what a competing guideline released just 8 months earlier from the American College of Physicians (ACP) and the American Academy of Family Practice (AAFP) called for, namely, a hypertension treatment target of less than 150/90 mm Hg in patients aged 60 years or older who need drug intervention (Ann Int Med. 2017 March 21; 166[6]:430-7).
Primary care pushes back
Although a significant part of the ACC/AHA guideline has either received endorsement from or is likely acceptable to the primary care organizations, including recommendations for improved blood pressure measurement and the key role for healthy lifestyle interventions, these two sides seem irreconcilable on the core issue of what is the target blood pressure for many patients when they are on antihypertensive drugs.
That inference turned into a reality in mid-December when the AAFP released a scathing critique of the ACC/AHA guidelines, and reaffirmed its endorsement of the controversial blood pressure target set by the panel appointed to the Eighth Joint National Committee (JNC 8), which in 2014 recommended a treatment target when using antihypertensive medications of less than 150/90 mm Hg for patients aged 60 years and older (JAMA 2014 Feb 5;311[5]:507-20).
A few weeks later, in late January, the ACP issued its own rejection of the core blood pressure target of the ACC/AHA guideline (Ann Int Med. 2018 Jan 23. doi: 10.7326/M17-3293). “Are the harms, costs, and complexity of care associated with this new target justified by the presumed benefits of labeling nearly half the U.S. [adult] population as unwell and subjecting them to treatment? We think not,” declared the statement from the ACP’s Clinical Guidelines Committee.
Although this ACP statement praised the ACC/AHA guideline in its “emphasis on the importance of blood pressure measurement technique and lifestyle changes,” it added that the guideline also “falls short in weighing the potential benefits against potential harms, costs, and anticipated variation in individual patient preferences.”
The statement went on to cite three specific flaws in the notion of using antihypertensive drugs to treat patients to less than 130/80 mm Hg: 1. Clinical trial results have not shown consistent evidence for benefit from a systolic blood pressure target of less than 130 mm Hg in older adults with diabetes or kidney disease. 2. Benefits are often overestimated and harms often underestimated when trial findings are applied to broad primary care populations. 3. No evidence from randomized controlled trials support a diastolic blood pressure target of less than 80 mm Hg.
Dr. Cohen said she agreed with a general target blood pressure of less than 130 mm Hg, while qualifying it with some caveats, and added that she did not agree that most patients should be treated to less than 80 mm Hg diastolic. “I will be less inclined to push for aggressive management in patients who are poorly functional, or those with many drug side effects or issues with polypharmacy. And given the evidence from ACCORD (N Engl J Med. 2010 April 29;362[17]:1575-85), I do not plan to apply stricter blood pressure control in patients with diabetes, and also not in patients with nonproteinuric chronic kidney disease.”
Dr. Ioannidis said in his JAMA commentary that the panel that wrote the ACC/AHA guidelines had “no conflicts of interest.” In the interview, he took issue with the AAFP’s objection to intellectual conflicts among some panel members.
“The concern raised by the AAFP is legitimate. Most cardiovascular medicine guidelines until now have been problematic because of overt financial conflicts of interest. Here is a guideline with no obvious financial conflicts of interest.” The ACC/AHA guideline document shows that across the entire list of guideline panel members no one had any financial disclosures.
“Intellectual conflict exists in every person who knows something about a certain field,” continued Dr. Ioannidis. “The only way to get rid of intellectual conflicts is to recruit people who know nothing about the subject. That’s not advisable. The problem is not an intellectual conflict in any one person – everyone has an intellectual conflict. The problem is stacking the membership of a guideline panel in a way that all or almost all have expressed a strong preference for some policy or strategy so that the guideline is bound to stick with this approach. While several members of the ACC/AHA had an intellectual conflict, I doubt there is a case for saying the entire committee was stacked.”
Goals for older adults: Irreconcilable differences?
How was it that the ACC/AHA guideline and the ACP/AAFP guideline reached such disparate conclusions about the appropriate blood pressure treatment target for patients aged 60 years or older?
“A critical difference between the two guidelines stems from how potential [treatment] harms and patient values and preferences were considered. Our review and the ACP/AAFP guidelines extensively considered harms and treatment burden associated with lower blood pressure treatment targets. Lower targets did not increase the risk for fractures, falls, or cognitive declines, but they were associated with more symptomatic hypotension, syncope, and greater medication burden. The ACP/AAFP believed that there is likely to be significant variation in how individual patients might weigh the small potential benefit of aggressive blood pressure control against the potential harms and treatment burden. The ACC/AHA guidelines and the systematic review on which they were based did not include an assessment of harms,” Dr. Kansagara said in an interview. Dr. Casey maintained that the ACC/AHA literature review did consider potential harms from treatment.
“The ACC/AHA guidelines also considered results from observational studies. The ACP/AAFP did not. A number of studies show that progressively higher levels of blood pressure are associated with higher rates of cardiovascular disease events and mortality. But some observational studies showed that blood pressures in the low to low-normal range are associated with higher mortality. The problem with observational studies is that there are many reasons why a population with higher blood pressure may have worse outcomes. That does not mean that using medication to reduce blood pressure will improve outcomes.”
Other experts noted that while the ACP/AAFP data review and guideline took the SPRINT results into account, their review occurred too soon to also include two other important analyses that came down in favor of the less than 130/80 mm Hg target and were included in the ACC/AHA review: A meta-analysis of 42 trials with more than 144,000 patients that showed patients treated to a systolic blood pressure of 120-124 mm Hg had significantly fewer deaths and cardiovascular disease events compared with patients with higher achieved blood pressures (JAMA Cardiology, 2017 July;2[7]:775-81); and a second meta-analysis of 17 trials with more than 55,000 patients that showed a target systolic pressure of less than 130 mm Hg produced the best balance of efficacy and safety (Am J Med. 2017 June;130[6]:707-19).
The bottom line, said Dr. Kansagara, is that regardless of which guideline a physician follows, the publication of both last year will mean that “patients and their providers will likely have more conversations about blood pressure treatment. Both guidelines underscore the need to at least consider lower blood pressure targets in patients at high cardiovascular disease risk or in those who have had a cardiovascular disease event.” As a result of the two 2017 guidelines “I think PCPs will pay more attention to blood pressure as a modifiable risk factor.”
Dr. Casey, Dr. Whelton, Dr. Cohen, Dr. Kansagara, and Dr. Ioannidis had no disclosures.
This is part one of a two-part series. Part two will explore how the approach to diagnosis and management of hypertension spelled out in the ACC/AHA guidelines fits into the protocol-driven, data-monitored, team-delivered primary care model that has come to dominate U.S. primary care in the decade following passage of the Affordable Care Act.
A new and long-anticipated guideline for diagnosing and managing hypertension by the American College of Cardiology, the American Heart Association, and nine other collaborating societies was finally released last fall. What happens now?
Will the top-line, seismic change that the new guidelines called for – treating many patients with hypertension to a blood pressure below 130/80 mm Hg – become the standard of care for U.S. medicine? And what about the several other novel steps the guideline calls for including more careful and methodical measurement of blood pressure with greater emphasis on out-of-office blood pressure monitoring, increased reliance on lifestyle interventions, running a formal calculation of a patient’s cardiovascular disease risk to identify patients who warrant drug treatment, development and attention to a care plan for each hypertensive patient, and a team approach to management?
In this two-part feature, a potential revolution in care will be explored.
ACC/AHA guidelines: More than just numbers
The ACC and AHA guideline (J Am Coll Cardiol. 2017 Nov 13. doi: 10.1016/j.jacc.2017.11.006) is “comprehensive. It addresses many issues around hypertension, not just what is a good [blood pressure] number and a bad number. This is important because this type of document has not existed for quite some time,” said Donald E. Casey Jr., MD, a member of the guideline-writing panel, an internal medicine physician, and chief clinical affairs officer at Medecision in Wayne, Pa.
“This is the first time that a [blood pressure] guideline has explicitly led with a strategy of calculating a person’s risk using the ACC/AHA risk calculator. It’s not ‘what is your blood pressure?’ but ‘what is your risk?’ This is not a one-size-fits-all guideline.”
The biggest wild card when handicapping the odds that the new guideline will take hold is how U.S. primary care physicians, the clinicians who stand on the front line of U.S. medicine for diagnosing and treating hypertension, respond. Their reaction remained an open issue during the weeks following release of the new guideline, in large part because its headline feature, the treatment target of less than 130/80 mm Hg, is at odds with what a competing guideline released just 8 months earlier from the American College of Physicians (ACP) and the American Academy of Family Practice (AAFP) called for, namely, a hypertension treatment target of less than 150/90 mm Hg in patients aged 60 years or older who need drug intervention (Ann Int Med. 2017 March 21; 166[6]:430-7).
Primary care pushes back
Although a significant part of the ACC/AHA guideline has either received endorsement from or is likely acceptable to the primary care organizations, including recommendations for improved blood pressure measurement and the key role for healthy lifestyle interventions, these two sides seem irreconcilable on the core issue of what is the target blood pressure for many patients when they are on antihypertensive drugs.
That inference turned into a reality in mid-December when the AAFP released a scathing critique of the ACC/AHA guidelines, and reaffirmed its endorsement of the controversial blood pressure target set by the panel appointed to the Eighth Joint National Committee (JNC 8), which in 2014 recommended a treatment target when using antihypertensive medications of less than 150/90 mm Hg for patients aged 60 years and older (JAMA 2014 Feb 5;311[5]:507-20).
A few weeks later, in late January, the ACP issued its own rejection of the core blood pressure target of the ACC/AHA guideline (Ann Int Med. 2018 Jan 23. doi: 10.7326/M17-3293). “Are the harms, costs, and complexity of care associated with this new target justified by the presumed benefits of labeling nearly half the U.S. [adult] population as unwell and subjecting them to treatment? We think not,” declared the statement from the ACP’s Clinical Guidelines Committee.
Although this ACP statement praised the ACC/AHA guideline in its “emphasis on the importance of blood pressure measurement technique and lifestyle changes,” it added that the guideline also “falls short in weighing the potential benefits against potential harms, costs, and anticipated variation in individual patient preferences.”
The statement went on to cite three specific flaws in the notion of using antihypertensive drugs to treat patients to less than 130/80 mm Hg: 1. Clinical trial results have not shown consistent evidence for benefit from a systolic blood pressure target of less than 130 mm Hg in older adults with diabetes or kidney disease. 2. Benefits are often overestimated and harms often underestimated when trial findings are applied to broad primary care populations. 3. No evidence from randomized controlled trials support a diastolic blood pressure target of less than 80 mm Hg.
Dr. Cohen said she agreed with a general target blood pressure of less than 130 mm Hg, while qualifying it with some caveats, and added that she did not agree that most patients should be treated to less than 80 mm Hg diastolic. “I will be less inclined to push for aggressive management in patients who are poorly functional, or those with many drug side effects or issues with polypharmacy. And given the evidence from ACCORD (N Engl J Med. 2010 April 29;362[17]:1575-85), I do not plan to apply stricter blood pressure control in patients with diabetes, and also not in patients with nonproteinuric chronic kidney disease.”
Dr. Ioannidis said in his JAMA commentary that the panel that wrote the ACC/AHA guidelines had “no conflicts of interest.” In the interview, he took issue with the AAFP’s objection to intellectual conflicts among some panel members.
“The concern raised by the AAFP is legitimate. Most cardiovascular medicine guidelines until now have been problematic because of overt financial conflicts of interest. Here is a guideline with no obvious financial conflicts of interest.” The ACC/AHA guideline document shows that across the entire list of guideline panel members no one had any financial disclosures.
“Intellectual conflict exists in every person who knows something about a certain field,” continued Dr. Ioannidis. “The only way to get rid of intellectual conflicts is to recruit people who know nothing about the subject. That’s not advisable. The problem is not an intellectual conflict in any one person – everyone has an intellectual conflict. The problem is stacking the membership of a guideline panel in a way that all or almost all have expressed a strong preference for some policy or strategy so that the guideline is bound to stick with this approach. While several members of the ACC/AHA had an intellectual conflict, I doubt there is a case for saying the entire committee was stacked.”
Goals for older adults: Irreconcilable differences?
How was it that the ACC/AHA guideline and the ACP/AAFP guideline reached such disparate conclusions about the appropriate blood pressure treatment target for patients aged 60 years or older?
“A critical difference between the two guidelines stems from how potential [treatment] harms and patient values and preferences were considered. Our review and the ACP/AAFP guidelines extensively considered harms and treatment burden associated with lower blood pressure treatment targets. Lower targets did not increase the risk for fractures, falls, or cognitive declines, but they were associated with more symptomatic hypotension, syncope, and greater medication burden. The ACP/AAFP believed that there is likely to be significant variation in how individual patients might weigh the small potential benefit of aggressive blood pressure control against the potential harms and treatment burden. The ACC/AHA guidelines and the systematic review on which they were based did not include an assessment of harms,” Dr. Kansagara said in an interview. Dr. Casey maintained that the ACC/AHA literature review did consider potential harms from treatment.
“The ACC/AHA guidelines also considered results from observational studies. The ACP/AAFP did not. A number of studies show that progressively higher levels of blood pressure are associated with higher rates of cardiovascular disease events and mortality. But some observational studies showed that blood pressures in the low to low-normal range are associated with higher mortality. The problem with observational studies is that there are many reasons why a population with higher blood pressure may have worse outcomes. That does not mean that using medication to reduce blood pressure will improve outcomes.”
Other experts noted that while the ACP/AAFP data review and guideline took the SPRINT results into account, their review occurred too soon to also include two other important analyses that came down in favor of the less than 130/80 mm Hg target and were included in the ACC/AHA review: A meta-analysis of 42 trials with more than 144,000 patients that showed patients treated to a systolic blood pressure of 120-124 mm Hg had significantly fewer deaths and cardiovascular disease events compared with patients with higher achieved blood pressures (JAMA Cardiology, 2017 July;2[7]:775-81); and a second meta-analysis of 17 trials with more than 55,000 patients that showed a target systolic pressure of less than 130 mm Hg produced the best balance of efficacy and safety (Am J Med. 2017 June;130[6]:707-19).
The bottom line, said Dr. Kansagara, is that regardless of which guideline a physician follows, the publication of both last year will mean that “patients and their providers will likely have more conversations about blood pressure treatment. Both guidelines underscore the need to at least consider lower blood pressure targets in patients at high cardiovascular disease risk or in those who have had a cardiovascular disease event.” As a result of the two 2017 guidelines “I think PCPs will pay more attention to blood pressure as a modifiable risk factor.”
Dr. Casey, Dr. Whelton, Dr. Cohen, Dr. Kansagara, and Dr. Ioannidis had no disclosures.
This is part one of a two-part series. Part two will explore how the approach to diagnosis and management of hypertension spelled out in the ACC/AHA guidelines fits into the protocol-driven, data-monitored, team-delivered primary care model that has come to dominate U.S. primary care in the decade following passage of the Affordable Care Act.
A new and long-anticipated guideline for diagnosing and managing hypertension by the American College of Cardiology, the American Heart Association, and nine other collaborating societies was finally released last fall. What happens now?
Will the top-line, seismic change that the new guidelines called for – treating many patients with hypertension to a blood pressure below 130/80 mm Hg – become the standard of care for U.S. medicine? And what about the several other novel steps the guideline calls for including more careful and methodical measurement of blood pressure with greater emphasis on out-of-office blood pressure monitoring, increased reliance on lifestyle interventions, running a formal calculation of a patient’s cardiovascular disease risk to identify patients who warrant drug treatment, development and attention to a care plan for each hypertensive patient, and a team approach to management?
In this two-part feature, a potential revolution in care will be explored.
ACC/AHA guidelines: More than just numbers
The ACC and AHA guideline (J Am Coll Cardiol. 2017 Nov 13. doi: 10.1016/j.jacc.2017.11.006) is “comprehensive. It addresses many issues around hypertension, not just what is a good [blood pressure] number and a bad number. This is important because this type of document has not existed for quite some time,” said Donald E. Casey Jr., MD, a member of the guideline-writing panel, an internal medicine physician, and chief clinical affairs officer at Medecision in Wayne, Pa.
“This is the first time that a [blood pressure] guideline has explicitly led with a strategy of calculating a person’s risk using the ACC/AHA risk calculator. It’s not ‘what is your blood pressure?’ but ‘what is your risk?’ This is not a one-size-fits-all guideline.”
The biggest wild card when handicapping the odds that the new guideline will take hold is how U.S. primary care physicians, the clinicians who stand on the front line of U.S. medicine for diagnosing and treating hypertension, respond. Their reaction remained an open issue during the weeks following release of the new guideline, in large part because its headline feature, the treatment target of less than 130/80 mm Hg, is at odds with what a competing guideline released just 8 months earlier from the American College of Physicians (ACP) and the American Academy of Family Practice (AAFP) called for, namely, a hypertension treatment target of less than 150/90 mm Hg in patients aged 60 years or older who need drug intervention (Ann Int Med. 2017 March 21; 166[6]:430-7).
Primary care pushes back
Although a significant part of the ACC/AHA guideline has either received endorsement from or is likely acceptable to the primary care organizations, including recommendations for improved blood pressure measurement and the key role for healthy lifestyle interventions, these two sides seem irreconcilable on the core issue of what is the target blood pressure for many patients when they are on antihypertensive drugs.
That inference turned into a reality in mid-December when the AAFP released a scathing critique of the ACC/AHA guidelines, and reaffirmed its endorsement of the controversial blood pressure target set by the panel appointed to the Eighth Joint National Committee (JNC 8), which in 2014 recommended a treatment target when using antihypertensive medications of less than 150/90 mm Hg for patients aged 60 years and older (JAMA 2014 Feb 5;311[5]:507-20).
A few weeks later, in late January, the ACP issued its own rejection of the core blood pressure target of the ACC/AHA guideline (Ann Int Med. 2018 Jan 23. doi: 10.7326/M17-3293). “Are the harms, costs, and complexity of care associated with this new target justified by the presumed benefits of labeling nearly half the U.S. [adult] population as unwell and subjecting them to treatment? We think not,” declared the statement from the ACP’s Clinical Guidelines Committee.
Although this ACP statement praised the ACC/AHA guideline in its “emphasis on the importance of blood pressure measurement technique and lifestyle changes,” it added that the guideline also “falls short in weighing the potential benefits against potential harms, costs, and anticipated variation in individual patient preferences.”
The statement went on to cite three specific flaws in the notion of using antihypertensive drugs to treat patients to less than 130/80 mm Hg: 1. Clinical trial results have not shown consistent evidence for benefit from a systolic blood pressure target of less than 130 mm Hg in older adults with diabetes or kidney disease. 2. Benefits are often overestimated and harms often underestimated when trial findings are applied to broad primary care populations. 3. No evidence from randomized controlled trials support a diastolic blood pressure target of less than 80 mm Hg.
Dr. Cohen said she agreed with a general target blood pressure of less than 130 mm Hg, while qualifying it with some caveats, and added that she did not agree that most patients should be treated to less than 80 mm Hg diastolic. “I will be less inclined to push for aggressive management in patients who are poorly functional, or those with many drug side effects or issues with polypharmacy. And given the evidence from ACCORD (N Engl J Med. 2010 April 29;362[17]:1575-85), I do not plan to apply stricter blood pressure control in patients with diabetes, and also not in patients with nonproteinuric chronic kidney disease.”
Dr. Ioannidis said in his JAMA commentary that the panel that wrote the ACC/AHA guidelines had “no conflicts of interest.” In the interview, he took issue with the AAFP’s objection to intellectual conflicts among some panel members.
“The concern raised by the AAFP is legitimate. Most cardiovascular medicine guidelines until now have been problematic because of overt financial conflicts of interest. Here is a guideline with no obvious financial conflicts of interest.” The ACC/AHA guideline document shows that across the entire list of guideline panel members no one had any financial disclosures.
“Intellectual conflict exists in every person who knows something about a certain field,” continued Dr. Ioannidis. “The only way to get rid of intellectual conflicts is to recruit people who know nothing about the subject. That’s not advisable. The problem is not an intellectual conflict in any one person – everyone has an intellectual conflict. The problem is stacking the membership of a guideline panel in a way that all or almost all have expressed a strong preference for some policy or strategy so that the guideline is bound to stick with this approach. While several members of the ACC/AHA had an intellectual conflict, I doubt there is a case for saying the entire committee was stacked.”
Goals for older adults: Irreconcilable differences?
How was it that the ACC/AHA guideline and the ACP/AAFP guideline reached such disparate conclusions about the appropriate blood pressure treatment target for patients aged 60 years or older?
“A critical difference between the two guidelines stems from how potential [treatment] harms and patient values and preferences were considered. Our review and the ACP/AAFP guidelines extensively considered harms and treatment burden associated with lower blood pressure treatment targets. Lower targets did not increase the risk for fractures, falls, or cognitive declines, but they were associated with more symptomatic hypotension, syncope, and greater medication burden. The ACP/AAFP believed that there is likely to be significant variation in how individual patients might weigh the small potential benefit of aggressive blood pressure control against the potential harms and treatment burden. The ACC/AHA guidelines and the systematic review on which they were based did not include an assessment of harms,” Dr. Kansagara said in an interview. Dr. Casey maintained that the ACC/AHA literature review did consider potential harms from treatment.
“The ACC/AHA guidelines also considered results from observational studies. The ACP/AAFP did not. A number of studies show that progressively higher levels of blood pressure are associated with higher rates of cardiovascular disease events and mortality. But some observational studies showed that blood pressures in the low to low-normal range are associated with higher mortality. The problem with observational studies is that there are many reasons why a population with higher blood pressure may have worse outcomes. That does not mean that using medication to reduce blood pressure will improve outcomes.”
Other experts noted that while the ACP/AAFP data review and guideline took the SPRINT results into account, their review occurred too soon to also include two other important analyses that came down in favor of the less than 130/80 mm Hg target and were included in the ACC/AHA review: A meta-analysis of 42 trials with more than 144,000 patients that showed patients treated to a systolic blood pressure of 120-124 mm Hg had significantly fewer deaths and cardiovascular disease events compared with patients with higher achieved blood pressures (JAMA Cardiology, 2017 July;2[7]:775-81); and a second meta-analysis of 17 trials with more than 55,000 patients that showed a target systolic pressure of less than 130 mm Hg produced the best balance of efficacy and safety (Am J Med. 2017 June;130[6]:707-19).
The bottom line, said Dr. Kansagara, is that regardless of which guideline a physician follows, the publication of both last year will mean that “patients and their providers will likely have more conversations about blood pressure treatment. Both guidelines underscore the need to at least consider lower blood pressure targets in patients at high cardiovascular disease risk or in those who have had a cardiovascular disease event.” As a result of the two 2017 guidelines “I think PCPs will pay more attention to blood pressure as a modifiable risk factor.”
Dr. Casey, Dr. Whelton, Dr. Cohen, Dr. Kansagara, and Dr. Ioannidis had no disclosures.
This is part one of a two-part series. Part two will explore how the approach to diagnosis and management of hypertension spelled out in the ACC/AHA guidelines fits into the protocol-driven, data-monitored, team-delivered primary care model that has come to dominate U.S. primary care in the decade following passage of the Affordable Care Act.
Dermatology residency match: Is the glut of applications for limited positions corrupting the process?
SAN DIEGO – Whether was the topic of discussion at a session on dermatoethics at the annual meeting of the American Academy of Dermatology.
“I think it is unethical and we need to address it,” Jane M. Grant-Kels, MD, said during the session. “What we are doing through the process of physicians getting into dermatology residency programs is telling them to lie to us and to do well on a single examination,” the United States Medical Licensing Examination.
Lionel G. Bercovitch, MD, is among the dermatologists who acknowledge the unarguable fact that application rates are high but don’t see it as a crisis of credibility.
“I don’t believe that dermatology match is broken, unethical, or unfair. The match is not perfect, but it’s fair,” contended Dr. Bercovitch, professor of dermatology at Brown University, Providence, R.I. “The problem [of an application glut] is real, but it’s not an ethical issue.”
Dr. Grant-Kels sees it in ethical terms because, in her view, “everyone is gaming the system. It makes applicants liars” when they profess interest in moving to a remote location or planning to practice a certain type of dermatology.
The “extremely competitive” process leads a majority of applicants to “shot gun” their filings to many programs such that dermatology residency programs are “deluged” with applications, Dr. Grant-Kels said. Data from the Association of American Medical Colleges for 2017 showed an average of just over 500 applications received by each U.S. dermatology residency program.
As a result, residency programs feel forced to apply blind filters that generally cull out more than a third of the applications received. Dr. Grant-Kels decried the need for programs to impose arbitrary barriers to entering dermatology based on a score from a single examination or other criteria like membership in Alpha Omega Alpha or current location.
“Blanket screening methods run the risk of excluding genuinely interested and qualified candidates who do not fall above a threshold. This violates the principal of nonmaleficence,” she said. “Screens are unfair.”
[polldaddy:{"method":"iframe","type":"survey","src":"//newspolls2017.polldaddy.com/s/dermatology-residency-match?iframe=1"}]
Dr. Grant-Kels proposed a pair of potential remedies: putting a cap on the number of applications someone can make and – a more realistic approach – mentors’ giving guidance to prospective applicants.
“It’s a problem that kids are applying to dermatology programs who have no business applying, who really don’t have a chance,” she said.
Dr. Bercovitch noted that most dermatology residency programs are too small and that, while the number of residency slots has been rising, it has not kept pace with increasing demand from physicians seeking residency slots. He saw no ethical reason for physicians to feel they should rein in the number of applications they file, and he said the only obligations for residency programs are to strictly adhere to the Match rules and both federal and state civil rights and labor laws and to be nondiscriminatory and avoid nepotism and conflicts of interest. Because programs cannot seriously consider nor interview several hundred applicants each year, some type of filtering is needed, and no filter is fair or perfect, he conceded.
“Filters are inherently unfair” to certain applicants, “but how else to effectively screen” hundreds of applications, Dr. Bercovitch asked.
“We need to talk about this. It’s not a good system. If we don’t talk about it, it will never change,” Dr. Grant-Kels said.
Dr. Grant-Kels and Dr. Bercovitch had no disclosures.
SAN DIEGO – Whether was the topic of discussion at a session on dermatoethics at the annual meeting of the American Academy of Dermatology.
“I think it is unethical and we need to address it,” Jane M. Grant-Kels, MD, said during the session. “What we are doing through the process of physicians getting into dermatology residency programs is telling them to lie to us and to do well on a single examination,” the United States Medical Licensing Examination.
Lionel G. Bercovitch, MD, is among the dermatologists who acknowledge the unarguable fact that application rates are high but don’t see it as a crisis of credibility.
“I don’t believe that dermatology match is broken, unethical, or unfair. The match is not perfect, but it’s fair,” contended Dr. Bercovitch, professor of dermatology at Brown University, Providence, R.I. “The problem [of an application glut] is real, but it’s not an ethical issue.”
Dr. Grant-Kels sees it in ethical terms because, in her view, “everyone is gaming the system. It makes applicants liars” when they profess interest in moving to a remote location or planning to practice a certain type of dermatology.
The “extremely competitive” process leads a majority of applicants to “shot gun” their filings to many programs such that dermatology residency programs are “deluged” with applications, Dr. Grant-Kels said. Data from the Association of American Medical Colleges for 2017 showed an average of just over 500 applications received by each U.S. dermatology residency program.
As a result, residency programs feel forced to apply blind filters that generally cull out more than a third of the applications received. Dr. Grant-Kels decried the need for programs to impose arbitrary barriers to entering dermatology based on a score from a single examination or other criteria like membership in Alpha Omega Alpha or current location.
“Blanket screening methods run the risk of excluding genuinely interested and qualified candidates who do not fall above a threshold. This violates the principal of nonmaleficence,” she said. “Screens are unfair.”
[polldaddy:{"method":"iframe","type":"survey","src":"//newspolls2017.polldaddy.com/s/dermatology-residency-match?iframe=1"}]
Dr. Grant-Kels proposed a pair of potential remedies: putting a cap on the number of applications someone can make and – a more realistic approach – mentors’ giving guidance to prospective applicants.
“It’s a problem that kids are applying to dermatology programs who have no business applying, who really don’t have a chance,” she said.
Dr. Bercovitch noted that most dermatology residency programs are too small and that, while the number of residency slots has been rising, it has not kept pace with increasing demand from physicians seeking residency slots. He saw no ethical reason for physicians to feel they should rein in the number of applications they file, and he said the only obligations for residency programs are to strictly adhere to the Match rules and both federal and state civil rights and labor laws and to be nondiscriminatory and avoid nepotism and conflicts of interest. Because programs cannot seriously consider nor interview several hundred applicants each year, some type of filtering is needed, and no filter is fair or perfect, he conceded.
“Filters are inherently unfair” to certain applicants, “but how else to effectively screen” hundreds of applications, Dr. Bercovitch asked.
“We need to talk about this. It’s not a good system. If we don’t talk about it, it will never change,” Dr. Grant-Kels said.
Dr. Grant-Kels and Dr. Bercovitch had no disclosures.
SAN DIEGO – Whether was the topic of discussion at a session on dermatoethics at the annual meeting of the American Academy of Dermatology.
“I think it is unethical and we need to address it,” Jane M. Grant-Kels, MD, said during the session. “What we are doing through the process of physicians getting into dermatology residency programs is telling them to lie to us and to do well on a single examination,” the United States Medical Licensing Examination.
Lionel G. Bercovitch, MD, is among the dermatologists who acknowledge the unarguable fact that application rates are high but don’t see it as a crisis of credibility.
“I don’t believe that dermatology match is broken, unethical, or unfair. The match is not perfect, but it’s fair,” contended Dr. Bercovitch, professor of dermatology at Brown University, Providence, R.I. “The problem [of an application glut] is real, but it’s not an ethical issue.”
Dr. Grant-Kels sees it in ethical terms because, in her view, “everyone is gaming the system. It makes applicants liars” when they profess interest in moving to a remote location or planning to practice a certain type of dermatology.
The “extremely competitive” process leads a majority of applicants to “shot gun” their filings to many programs such that dermatology residency programs are “deluged” with applications, Dr. Grant-Kels said. Data from the Association of American Medical Colleges for 2017 showed an average of just over 500 applications received by each U.S. dermatology residency program.
As a result, residency programs feel forced to apply blind filters that generally cull out more than a third of the applications received. Dr. Grant-Kels decried the need for programs to impose arbitrary barriers to entering dermatology based on a score from a single examination or other criteria like membership in Alpha Omega Alpha or current location.
“Blanket screening methods run the risk of excluding genuinely interested and qualified candidates who do not fall above a threshold. This violates the principal of nonmaleficence,” she said. “Screens are unfair.”
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Dr. Grant-Kels proposed a pair of potential remedies: putting a cap on the number of applications someone can make and – a more realistic approach – mentors’ giving guidance to prospective applicants.
“It’s a problem that kids are applying to dermatology programs who have no business applying, who really don’t have a chance,” she said.
Dr. Bercovitch noted that most dermatology residency programs are too small and that, while the number of residency slots has been rising, it has not kept pace with increasing demand from physicians seeking residency slots. He saw no ethical reason for physicians to feel they should rein in the number of applications they file, and he said the only obligations for residency programs are to strictly adhere to the Match rules and both federal and state civil rights and labor laws and to be nondiscriminatory and avoid nepotism and conflicts of interest. Because programs cannot seriously consider nor interview several hundred applicants each year, some type of filtering is needed, and no filter is fair or perfect, he conceded.
“Filters are inherently unfair” to certain applicants, “but how else to effectively screen” hundreds of applications, Dr. Bercovitch asked.
“We need to talk about this. It’s not a good system. If we don’t talk about it, it will never change,” Dr. Grant-Kels said.
Dr. Grant-Kels and Dr. Bercovitch had no disclosures.
EXPERT ANALYSIS FROM AAD 18
ALT-70 score outperformed thermal imaging for cellulitis diagnosis
SAN DIEGO – A simple scoring system surpassed thermal imaging for diagnosing lower extremity cellulitis in a head-to-head, single-center comparison in 67 patients.
The ALT-70 score – which tallies points for asymmetry, leukocytosis, tachycardia, and age of at least 70 years – produced a positive predictive value for lower-extremity cellulitis (LEC) of 80.4% and a negative predictive value of 90.9%, compared with values of 75.5% and 57.1%, respectively, for thermal imaging when researchers applied both methods to 67 patients, said David G. Li, a clinical research fellow in the department of dermatology at Brigham and Women’s Hospital, Boston, where the study was conducted.
The senior author of Mr. Li’s report, Arash Mostaghimi, MD, director of the inpatient consultation service, department of dermatology at Brigham and Women’s, was also lead investigator for the team of dermatology researchers – from his center and from Massachusetts General Hospital in Boston – who recently devised the ALT-70 scoring system for diagnosing LEC (J Amer Acad Dermatol. 2017 April;76[4]:618-25.e2).
The four-item survey can generate a score of 0-7, with a score of 0-2 suggesting need for additional monitoring, a score of 3-4 initiating a dermatology consult, and a score of 5-7 triggering immediate treatment for cellulitis, Mr. Li said. The 2017 review of ALT-70 showed that among 259 patients, those with a score of 0-2 had an 83% likelihood of having pseudocellulitis, while patients with a score of 5-7 had an 82% likelihood of having true cellulitis.
The current study enrolled 67 patients who had a presumptive diagnosis of LEC while in the emergency department or inpatient wards during a 7-month period. In addition to undergoing blinded assessment by both thermal imaging and by ALT-70 scoring, all patients also underwent blinded assessment by a board-certified dermatologist, who provided the definitive diagnosis. The attending dermatologists determined that 46 of the patients had true LEC and 21 patients did not.
The calculated sensitivity of ALT-70 was 97.8%, compared with 87.0% for thermal imaging. Specificity was 47.6% for ALT-70 and 38.1% for thermal imaging, Mr. Li reported at the annual meeting of the American Academy of Dermatology.
He also presented an analysis of the results when he combined both methods, with a positive on both assessments required to produce a positive LEC diagnosis. This resulted in a positive predictive value of 86.7%, slightly higher than the 80.4% from ALT-70 alone, but the combination produced a negative predictive value of 68.2%, substantially less than the 90.9% rate with ALT-70 alone. This demonstrated the “marginal benefit” from combining the two methods, he said.
In a receiver operating characteristic curve analysis, in which the area under the curve (c-statistic) reflects a diagnostic test’s validity, ALT-70 produced a c-statistic of 0.85, thermal imaging had a c-statistic of 0.63, and when combined, the c-statistic was 0.88.
Mr. Li called for validation of the findings using larger and different patient populations.
He had no reported disclosures.
SOURCE: Li DG et al. AAD 18, Abstract 6744.
SAN DIEGO – A simple scoring system surpassed thermal imaging for diagnosing lower extremity cellulitis in a head-to-head, single-center comparison in 67 patients.
The ALT-70 score – which tallies points for asymmetry, leukocytosis, tachycardia, and age of at least 70 years – produced a positive predictive value for lower-extremity cellulitis (LEC) of 80.4% and a negative predictive value of 90.9%, compared with values of 75.5% and 57.1%, respectively, for thermal imaging when researchers applied both methods to 67 patients, said David G. Li, a clinical research fellow in the department of dermatology at Brigham and Women’s Hospital, Boston, where the study was conducted.
The senior author of Mr. Li’s report, Arash Mostaghimi, MD, director of the inpatient consultation service, department of dermatology at Brigham and Women’s, was also lead investigator for the team of dermatology researchers – from his center and from Massachusetts General Hospital in Boston – who recently devised the ALT-70 scoring system for diagnosing LEC (J Amer Acad Dermatol. 2017 April;76[4]:618-25.e2).
The four-item survey can generate a score of 0-7, with a score of 0-2 suggesting need for additional monitoring, a score of 3-4 initiating a dermatology consult, and a score of 5-7 triggering immediate treatment for cellulitis, Mr. Li said. The 2017 review of ALT-70 showed that among 259 patients, those with a score of 0-2 had an 83% likelihood of having pseudocellulitis, while patients with a score of 5-7 had an 82% likelihood of having true cellulitis.
The current study enrolled 67 patients who had a presumptive diagnosis of LEC while in the emergency department or inpatient wards during a 7-month period. In addition to undergoing blinded assessment by both thermal imaging and by ALT-70 scoring, all patients also underwent blinded assessment by a board-certified dermatologist, who provided the definitive diagnosis. The attending dermatologists determined that 46 of the patients had true LEC and 21 patients did not.
The calculated sensitivity of ALT-70 was 97.8%, compared with 87.0% for thermal imaging. Specificity was 47.6% for ALT-70 and 38.1% for thermal imaging, Mr. Li reported at the annual meeting of the American Academy of Dermatology.
He also presented an analysis of the results when he combined both methods, with a positive on both assessments required to produce a positive LEC diagnosis. This resulted in a positive predictive value of 86.7%, slightly higher than the 80.4% from ALT-70 alone, but the combination produced a negative predictive value of 68.2%, substantially less than the 90.9% rate with ALT-70 alone. This demonstrated the “marginal benefit” from combining the two methods, he said.
In a receiver operating characteristic curve analysis, in which the area under the curve (c-statistic) reflects a diagnostic test’s validity, ALT-70 produced a c-statistic of 0.85, thermal imaging had a c-statistic of 0.63, and when combined, the c-statistic was 0.88.
Mr. Li called for validation of the findings using larger and different patient populations.
He had no reported disclosures.
SOURCE: Li DG et al. AAD 18, Abstract 6744.
SAN DIEGO – A simple scoring system surpassed thermal imaging for diagnosing lower extremity cellulitis in a head-to-head, single-center comparison in 67 patients.
The ALT-70 score – which tallies points for asymmetry, leukocytosis, tachycardia, and age of at least 70 years – produced a positive predictive value for lower-extremity cellulitis (LEC) of 80.4% and a negative predictive value of 90.9%, compared with values of 75.5% and 57.1%, respectively, for thermal imaging when researchers applied both methods to 67 patients, said David G. Li, a clinical research fellow in the department of dermatology at Brigham and Women’s Hospital, Boston, where the study was conducted.
The senior author of Mr. Li’s report, Arash Mostaghimi, MD, director of the inpatient consultation service, department of dermatology at Brigham and Women’s, was also lead investigator for the team of dermatology researchers – from his center and from Massachusetts General Hospital in Boston – who recently devised the ALT-70 scoring system for diagnosing LEC (J Amer Acad Dermatol. 2017 April;76[4]:618-25.e2).
The four-item survey can generate a score of 0-7, with a score of 0-2 suggesting need for additional monitoring, a score of 3-4 initiating a dermatology consult, and a score of 5-7 triggering immediate treatment for cellulitis, Mr. Li said. The 2017 review of ALT-70 showed that among 259 patients, those with a score of 0-2 had an 83% likelihood of having pseudocellulitis, while patients with a score of 5-7 had an 82% likelihood of having true cellulitis.
The current study enrolled 67 patients who had a presumptive diagnosis of LEC while in the emergency department or inpatient wards during a 7-month period. In addition to undergoing blinded assessment by both thermal imaging and by ALT-70 scoring, all patients also underwent blinded assessment by a board-certified dermatologist, who provided the definitive diagnosis. The attending dermatologists determined that 46 of the patients had true LEC and 21 patients did not.
The calculated sensitivity of ALT-70 was 97.8%, compared with 87.0% for thermal imaging. Specificity was 47.6% for ALT-70 and 38.1% for thermal imaging, Mr. Li reported at the annual meeting of the American Academy of Dermatology.
He also presented an analysis of the results when he combined both methods, with a positive on both assessments required to produce a positive LEC diagnosis. This resulted in a positive predictive value of 86.7%, slightly higher than the 80.4% from ALT-70 alone, but the combination produced a negative predictive value of 68.2%, substantially less than the 90.9% rate with ALT-70 alone. This demonstrated the “marginal benefit” from combining the two methods, he said.
In a receiver operating characteristic curve analysis, in which the area under the curve (c-statistic) reflects a diagnostic test’s validity, ALT-70 produced a c-statistic of 0.85, thermal imaging had a c-statistic of 0.63, and when combined, the c-statistic was 0.88.
Mr. Li called for validation of the findings using larger and different patient populations.
He had no reported disclosures.
SOURCE: Li DG et al. AAD 18, Abstract 6744.
REPORTING FROM AAD 18
Key clinical point: The ALT-70 score surpassed thermal imaging for diagnosing lower-extremity cellulitis.
Major finding: Positive and negative predictive values were 80.4% and 90.9% for ALT-70 and 75.5% and 57.1% for thermal imaging.
Study details: A single-center study with 67 patients.
Disclosures: Mr. Li had no disclosures.
Source: Li DG et al. AAD 18, Abstract 6744.
Thrombectomy’s success treating strokes prompts rethinking of selection criteria
LOS ANGELES – CT or magnetic resonance brain imaging of acute ischemic stroke patients was the key triage tool in two groundbreaking thrombectomy trials, DAWN and DEFUSE; results from both showed that patients found by imaging to have limited infarcted cores could safely benefit from endovascular thrombectomy, even when they are more than 6 hours out from their stroke onset, breaking the 6-hour barrier created 3 years ago by the first wave of thrombectomy trials.
But some stroke neurologists studying thrombectomy are now convinced that imaging is not needed and may actually harm acute ischemic stroke patients early on by introducing an unnecessary time delay when they present within the first 6 hours after stroke onset.
This new thinking on how to best use brain imaging in acute ischemic stroke patients is part of the rapid evolution of acute stroke management as experts process new data and refine their approach both within 6 hours of stroke onset and during the new treatment window of 6-24 hours post onset. The dramatic success achieved with thrombectomy in highly selected late-window patients prompted researchers to promote pushing the boundaries further to find less-selected late patients who could also potentially benefit from thrombectomy.
The downside of early imaging
“Early on, we have a mix of fast and slow progressors. Slow progressors are about a third to half the patients, so there is a lot of potential for [late] treatment, but the majority of patients during the first 6 hours after onset are fast progressors,” patients who won’t benefit from thrombectomy delivery beyond 6 hours, said Dr. Jovin, an interventional neurologist and director of the Stroke Institute of the University of Pittsburgh Medical Center.
“Time is very precious in the 0- to 6-hour window. When we’re dealing with a lot of fast progressors, we pay a price [in added time to treatment] for any imaging we do. We need to understand that this is a real price we pay, even when CT takes perhaps 24 minutes, and MRI adds about 12 minutes. It’s not the case in all patients that doing CT angiography just adds 5 minutes. It can take 15, 20 minutes,” especially at centers that don’t treat these types of stroke patients day in and day out. “There is no question that imaging slows us down,” Dr. Jovin said.
He highlighted that “the main role of imaging is to exclude patients from treatment, a treatment that has unbelievable effects.” Imaging can rule out patients who have a hemorrhage, lack an occlusion, have a large infarcted core, or have none of the brain at risk or just a small amount, he noted. “Excluding hemorrhage is reasonable, but we can do that in the angiography suite, when the patient is on the table. The main benefit from advanced imaging is to more precisely define the core,” but for most patients the size of their core is not important because the vast majority of acute ischemic stroke patients seen within 6 hours of onset have cores smaller than 70 mL.
“Is this much ado about nothing – especially because we punish all the other patients [with smaller cores] who need to be treated [quickly] when we do additional imaging?” asked Dr. Jovin, who was one of the two lead investigators for the Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo (DAWN) trial (N Engl J Med. 2018 Jan 4;378[1]:11-21). Another factor undercutting the value of imaging and determining core size is registry results that show patients who undergo thrombectomy with a large infarcted core are not harmed by treatment.
Current practice often uses imaging “to exclude the 20% of patients who may not have a large vessel occlusion or may not get benefit but whom we are unlikely to harm. But we harm the other 80% by delaying treatment by 30 minutes because of imaging. That’s why we need to rethink imaging and minimize its use.”
Dr. Jovin noted that at his center in Pittsburgh, the stroke institute staff began in 2013 to take patients transported from other stroke facilities and already diagnosed with a large vessel occlusion directly to the angiography suite, bypassing further brain imaging. By doing this, they cut their average door-to-groin puncture time down to 22 minutes from what had been an average of 81 minutes with imaging (Stroke. 2017 July;48[7]:1884-9). Right now the door-to-groin time is even lower, he added.
“Don’t waste time imaging,” said Dr. Nogueira, a stroke neurologist who is director of the neuroendovascular division of the Marcus Stroke and Neuroscience Center and professor of neurology, neurosurgery, and radiology at Emory University, both in Atlanta, as well as the second lead investigator for DAWN. “Time is crucial and trumps patient selection. Most selection criteria are informative rather than truly selective. It is important to understand that in every time window, we do not yet know who doesn’t benefit from treatment. Select faster, select less, and treat more” during the 0- to 6-hour window, he told his colleagues.
Expanding thrombectomy 6-24 hours after stroke onset
While Dr. Jovin and Dr. Nogueira called for more aggressive and less selective use of thrombectomy in patients who present within 6 hours of their stroke onset, they acknowledged that for patients who present during the 6- to 24-hour window, selection for thrombectomy should follow the rules applied in DAWN and in the more inclusive Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE 3) trial (N Engl J Med. 2018 Feb 22;378:708-18). That means using imaging to confirm that the patient’s infarcted core is within the enrollment ceiling, but both neurologists also downplayed the need for the more sophisticated imaging approaches that were often used in both trials as well as in current routine practice at comprehensive stroke centers. They agreed that noncontrast CT, a widely available method, seems adequate for patient selection, based on the admittedly limited data available right now.
Dr. Nogueira cited data from the Trevo stent retriever registry, collected from nearly 1,000 U.S. acute ischemic stroke patients who underwent thrombectomy with this device. (Researchers at the conference reported updated registry data with nearly 2,000 patients with findings similar to what Dr. Nogueira referenced.) Although these patients underwent treatment before results of DAWN and DEFUSE 3 came out and before release of the new U.S. acute stroke management guidelines (Stroke. 2018 Jan 24; doi: 10.1161/STR.0000000000000158) that endorsed targeted thrombectomy for patients 6-24 hours out from their stroke onset, 278 (28%) of the registry patients underwent thrombectomy treatment during the 6- to 24-hour time window. In this subgroup, 34 patients underwent noncontrast CT to assess their infarcted core prior to thrombectomy, while the other patients underwent perfusion CT, MRI, or both. The noncontrast CT patients had recanalization rates, adverse event rates, and 90-day modified Rankin Scale (mRS) scores comparable with those of patients assessed with more advanced imaging.
Based on this, “just looking at CT only seems reasonable. Noncontrast CT is a pretty valid way to select patients,” Dr. Nogueira said.
“This is the direction we should follow to simplify the paradigm for treating beyond 6 hours,” agreed Dr. Jovin, who also called for further advances in patient selection to expand the pool of patients who qualify for thrombectomy during the 6- to 24-hour postonset period.
“We want the DAWN results to be generalizable, to be simpler. We are exploring some more easily generalizable inclusion criteria that would allow us to treat more patients in more parts of the world,” Dr. Jovin added.
Both clinicians cited the remarkably low number needed to treat found in both DAWN and DEFUSE 3 of roughly three patients to produce one additional patient with a statistically significant and clinically meaningful improvement in their 90-day mRS score, compared with controls, as an unmistakable sign that the treatment in both trials was too targeted.
“When we planned the DAWN and DEFUSE 3 trials we didn’t expect how powerful the treatment effect would be. There are probably other patients who could also benefit, so how low can we go? How liberal can we be in our inclusion criteria and still get benefit?” Dr. Jovin asked.
“When intravenous TPA [tissue plasminogen activator] first came out, we went by the book [for patient selection], but as we got to know the treatment and became more comfortable with it, we began to bend the rules. Now we’re at the point of getting comfortable with endovascular treatment, and we need to figure out where to bend the rules by building the database. There is no doubt that the rules need bending because of the treatment effect that we’ve seen. We need to get our patients to endovascular treatment,” she said in her presentation at the conference.
But these physicians realize that for the time being, standard of care will follow the imaging and data processing primarily used in DAWN and DEFUSE 3, which not only involved perfusion CT or MRI but also a proprietary, automated image processing software, RAPID, that takes imaging data and calculates the amount and ratio of infarcted core and hypoperfused, ischemic brain tissue.
“I asked our imaging experts [at the University of Cincinnati] what should my threshold be [for mismatch between the infarcted core and ischemic tissue], and they said, ‘Use the automated software,’ ” Dr. Khatri said. If centers managing acute ischemic stroke patients don’t already have this software, “they need it. I think there is no way around that. It’s the only way we’ll be able to do this,” she commented. Most U.S. community hospitals that admit stroke patients currently lack this software, largely because of its high cost, she added.
“We’re struggling because it is very difficult to get some community hospitals – primary stroke centers – to invest in the software, but that’s really the only way we’ll be able to do this. There are issues of cost, and of getting technicians trained,” she noted.
That’s because DEFUSE 3 enrolled patients with a baseline National Institutes of Health Stroke Scale (NIHSS) score of at least 6, while patients in DAWN required a score of at least 10, a loosening that allowed inclusion of 31 patients with scores of 6-9 in DEFUSE 3. Another, less restrictive criterion was the patient’s prestroke mRS score, which could have been 0-2 in DEFUSE 3 but could be only 0-1 in DAWN. Thirteen of the DEFUSE 3 patients had prestroke mRS scores of 2. DEFUSE 3 also had somewhat more liberal criteria for the size of a patient’s infarcted core at enrollment, with 41 patients who would have been excluded from DAWN because of an overly large infarcted core, Dr. Albers said in his presentation at the conference.
Currently, for patients presenting more than 16 hours following their stroke onset but within 24 hours, the DAWN enrollment criteria exclusively determine which patients should get thrombectomy.
One area where these rules could be bent is by a more thoughtful approach to the prestroke mRS score rule out, such as patients with orthopedic or rheumatic complications that limit mobility and give them an mRS score of 3. “We don’t have data for patients with back pain who can’t walk. I currently take these patients to endovascular therapy, and I’m sure many others do, too,” Dr. Khatri said.
Another potential way to grow the inclusion criteria is to investigate thrombectomy in patients with larger infarcted cores than were enrolled in DAWN and DEFUSE 3, but assessing this will require a new prospective study, Dr. Albers said.
Running the 6- to 24-hour numbers
Adoption of the 6- to 24-hour time window for endovascular intervention in selected patients means that suddenly the U.S. acute stroke infrastructure needs to accommodate a significantly increased number of patients. Just how many added patients this means is uncertain for the time being, and will vary from region to region and center to center. Dr. Albers roughly guessed that the new late time window might double the number of stroke patients undergoing thrombectomy at his center in Stanford. Dr. Khatri put together a more data-driven but still very speculative estimate that at the University of Cincinnati, it will mean about 40% more stroke patients going to thrombectomy. She shared the numbers behind this estimate in a report she gave at the conference.
To calculate the incremental change produced by the late time window, she used data collected on 2,297 acute ischemic stroke patients from the Greater Cincinnati/Northern Kentucky region who were seen at the University of Cincinnati during 2010. Prior analysis by Dr. Khatri and her associates showed that 159 of these patients presented quickly enough and with an appropriate stroke to qualify for thrombolytic therapy, and that 29 patients would have qualified for thrombectomy performed during the 0- to 6-hour time window.
In the new analysis Dr. Khatri calculated that 791 patients presented at 5-23 hours, and of these 34 had other features that would have made them eligible for enrollment in DAWN. Because no imaging data existed for these 2010 patients, she applied an estimate that 22% of these patients would qualify by the size of their infarcted core and ischemic penumbra, resulting in seven additional thrombectomy-eligible patients. Accounting for patients who would qualify by the more liberal DEFUSE 3 criteria added another 5 patients for a total increment of 12 patients during 2010 who would have been eligible for thrombectomy, about 40% of the number from the 0- to 6-hour window.
She noted that “this is likely an underestimate,” and “too small a sample to project to national estimates,” but concluded that “resources must be adapted to account for this increased volume in endovascular treatment.”
Dr. Khatri acknowledged that the new 6- to 24-hour window for endovascular therapy, and concerns about imaging delays in 0- to 6-hour patients, raise challenging issues regarding the message to give U.S. clinicians about treating acute ischemic stroke patients.
“We have a mandate to figure it out in every region. There is no doubt that stroke patients need access to this care. We need to become a lot more aggressive with endovascular treatment. It’s so gratifying to see the outcomes that we’re seeing,” Dr. Khatri said. “A lot of work is needed to accommodate endovascular therapy–eligible patients in an extended time window. We need more refined prehospital triage tools, we need to adequately implement imaging software, and we need increased capacity to perform endovascular treatment with additional procedure suites, operators, and ICU beds.”
Dr. Jovin has been a consultant to Anaconda Biomed, Blockade Medical, Cerenovus, FreeOx Biotech, and Silk Road Medical. Dr. Nogueira has received travel expense reimbursement from Stryker. Dr. Khatri has been a consultant to Biogen, Medpace/Novartis, and St. Jude; has received travel support from Neuravi and EmstoPA; and has received research support from Genentech, Lumosa, and Neurospring. Dr. Albers has an ownership interest in iSchemaView, the company that markets the RAPID imaging software, and is a consultant to iSchemaView and Medtronic.
LOS ANGELES – CT or magnetic resonance brain imaging of acute ischemic stroke patients was the key triage tool in two groundbreaking thrombectomy trials, DAWN and DEFUSE; results from both showed that patients found by imaging to have limited infarcted cores could safely benefit from endovascular thrombectomy, even when they are more than 6 hours out from their stroke onset, breaking the 6-hour barrier created 3 years ago by the first wave of thrombectomy trials.
But some stroke neurologists studying thrombectomy are now convinced that imaging is not needed and may actually harm acute ischemic stroke patients early on by introducing an unnecessary time delay when they present within the first 6 hours after stroke onset.
This new thinking on how to best use brain imaging in acute ischemic stroke patients is part of the rapid evolution of acute stroke management as experts process new data and refine their approach both within 6 hours of stroke onset and during the new treatment window of 6-24 hours post onset. The dramatic success achieved with thrombectomy in highly selected late-window patients prompted researchers to promote pushing the boundaries further to find less-selected late patients who could also potentially benefit from thrombectomy.
The downside of early imaging
“Early on, we have a mix of fast and slow progressors. Slow progressors are about a third to half the patients, so there is a lot of potential for [late] treatment, but the majority of patients during the first 6 hours after onset are fast progressors,” patients who won’t benefit from thrombectomy delivery beyond 6 hours, said Dr. Jovin, an interventional neurologist and director of the Stroke Institute of the University of Pittsburgh Medical Center.
“Time is very precious in the 0- to 6-hour window. When we’re dealing with a lot of fast progressors, we pay a price [in added time to treatment] for any imaging we do. We need to understand that this is a real price we pay, even when CT takes perhaps 24 minutes, and MRI adds about 12 minutes. It’s not the case in all patients that doing CT angiography just adds 5 minutes. It can take 15, 20 minutes,” especially at centers that don’t treat these types of stroke patients day in and day out. “There is no question that imaging slows us down,” Dr. Jovin said.
He highlighted that “the main role of imaging is to exclude patients from treatment, a treatment that has unbelievable effects.” Imaging can rule out patients who have a hemorrhage, lack an occlusion, have a large infarcted core, or have none of the brain at risk or just a small amount, he noted. “Excluding hemorrhage is reasonable, but we can do that in the angiography suite, when the patient is on the table. The main benefit from advanced imaging is to more precisely define the core,” but for most patients the size of their core is not important because the vast majority of acute ischemic stroke patients seen within 6 hours of onset have cores smaller than 70 mL.
“Is this much ado about nothing – especially because we punish all the other patients [with smaller cores] who need to be treated [quickly] when we do additional imaging?” asked Dr. Jovin, who was one of the two lead investigators for the Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo (DAWN) trial (N Engl J Med. 2018 Jan 4;378[1]:11-21). Another factor undercutting the value of imaging and determining core size is registry results that show patients who undergo thrombectomy with a large infarcted core are not harmed by treatment.
Current practice often uses imaging “to exclude the 20% of patients who may not have a large vessel occlusion or may not get benefit but whom we are unlikely to harm. But we harm the other 80% by delaying treatment by 30 minutes because of imaging. That’s why we need to rethink imaging and minimize its use.”
Dr. Jovin noted that at his center in Pittsburgh, the stroke institute staff began in 2013 to take patients transported from other stroke facilities and already diagnosed with a large vessel occlusion directly to the angiography suite, bypassing further brain imaging. By doing this, they cut their average door-to-groin puncture time down to 22 minutes from what had been an average of 81 minutes with imaging (Stroke. 2017 July;48[7]:1884-9). Right now the door-to-groin time is even lower, he added.
“Don’t waste time imaging,” said Dr. Nogueira, a stroke neurologist who is director of the neuroendovascular division of the Marcus Stroke and Neuroscience Center and professor of neurology, neurosurgery, and radiology at Emory University, both in Atlanta, as well as the second lead investigator for DAWN. “Time is crucial and trumps patient selection. Most selection criteria are informative rather than truly selective. It is important to understand that in every time window, we do not yet know who doesn’t benefit from treatment. Select faster, select less, and treat more” during the 0- to 6-hour window, he told his colleagues.
Expanding thrombectomy 6-24 hours after stroke onset
While Dr. Jovin and Dr. Nogueira called for more aggressive and less selective use of thrombectomy in patients who present within 6 hours of their stroke onset, they acknowledged that for patients who present during the 6- to 24-hour window, selection for thrombectomy should follow the rules applied in DAWN and in the more inclusive Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE 3) trial (N Engl J Med. 2018 Feb 22;378:708-18). That means using imaging to confirm that the patient’s infarcted core is within the enrollment ceiling, but both neurologists also downplayed the need for the more sophisticated imaging approaches that were often used in both trials as well as in current routine practice at comprehensive stroke centers. They agreed that noncontrast CT, a widely available method, seems adequate for patient selection, based on the admittedly limited data available right now.
Dr. Nogueira cited data from the Trevo stent retriever registry, collected from nearly 1,000 U.S. acute ischemic stroke patients who underwent thrombectomy with this device. (Researchers at the conference reported updated registry data with nearly 2,000 patients with findings similar to what Dr. Nogueira referenced.) Although these patients underwent treatment before results of DAWN and DEFUSE 3 came out and before release of the new U.S. acute stroke management guidelines (Stroke. 2018 Jan 24; doi: 10.1161/STR.0000000000000158) that endorsed targeted thrombectomy for patients 6-24 hours out from their stroke onset, 278 (28%) of the registry patients underwent thrombectomy treatment during the 6- to 24-hour time window. In this subgroup, 34 patients underwent noncontrast CT to assess their infarcted core prior to thrombectomy, while the other patients underwent perfusion CT, MRI, or both. The noncontrast CT patients had recanalization rates, adverse event rates, and 90-day modified Rankin Scale (mRS) scores comparable with those of patients assessed with more advanced imaging.
Based on this, “just looking at CT only seems reasonable. Noncontrast CT is a pretty valid way to select patients,” Dr. Nogueira said.
“This is the direction we should follow to simplify the paradigm for treating beyond 6 hours,” agreed Dr. Jovin, who also called for further advances in patient selection to expand the pool of patients who qualify for thrombectomy during the 6- to 24-hour postonset period.
“We want the DAWN results to be generalizable, to be simpler. We are exploring some more easily generalizable inclusion criteria that would allow us to treat more patients in more parts of the world,” Dr. Jovin added.
Both clinicians cited the remarkably low number needed to treat found in both DAWN and DEFUSE 3 of roughly three patients to produce one additional patient with a statistically significant and clinically meaningful improvement in their 90-day mRS score, compared with controls, as an unmistakable sign that the treatment in both trials was too targeted.
“When we planned the DAWN and DEFUSE 3 trials we didn’t expect how powerful the treatment effect would be. There are probably other patients who could also benefit, so how low can we go? How liberal can we be in our inclusion criteria and still get benefit?” Dr. Jovin asked.
“When intravenous TPA [tissue plasminogen activator] first came out, we went by the book [for patient selection], but as we got to know the treatment and became more comfortable with it, we began to bend the rules. Now we’re at the point of getting comfortable with endovascular treatment, and we need to figure out where to bend the rules by building the database. There is no doubt that the rules need bending because of the treatment effect that we’ve seen. We need to get our patients to endovascular treatment,” she said in her presentation at the conference.
But these physicians realize that for the time being, standard of care will follow the imaging and data processing primarily used in DAWN and DEFUSE 3, which not only involved perfusion CT or MRI but also a proprietary, automated image processing software, RAPID, that takes imaging data and calculates the amount and ratio of infarcted core and hypoperfused, ischemic brain tissue.
“I asked our imaging experts [at the University of Cincinnati] what should my threshold be [for mismatch between the infarcted core and ischemic tissue], and they said, ‘Use the automated software,’ ” Dr. Khatri said. If centers managing acute ischemic stroke patients don’t already have this software, “they need it. I think there is no way around that. It’s the only way we’ll be able to do this,” she commented. Most U.S. community hospitals that admit stroke patients currently lack this software, largely because of its high cost, she added.
“We’re struggling because it is very difficult to get some community hospitals – primary stroke centers – to invest in the software, but that’s really the only way we’ll be able to do this. There are issues of cost, and of getting technicians trained,” she noted.
That’s because DEFUSE 3 enrolled patients with a baseline National Institutes of Health Stroke Scale (NIHSS) score of at least 6, while patients in DAWN required a score of at least 10, a loosening that allowed inclusion of 31 patients with scores of 6-9 in DEFUSE 3. Another, less restrictive criterion was the patient’s prestroke mRS score, which could have been 0-2 in DEFUSE 3 but could be only 0-1 in DAWN. Thirteen of the DEFUSE 3 patients had prestroke mRS scores of 2. DEFUSE 3 also had somewhat more liberal criteria for the size of a patient’s infarcted core at enrollment, with 41 patients who would have been excluded from DAWN because of an overly large infarcted core, Dr. Albers said in his presentation at the conference.
Currently, for patients presenting more than 16 hours following their stroke onset but within 24 hours, the DAWN enrollment criteria exclusively determine which patients should get thrombectomy.
One area where these rules could be bent is by a more thoughtful approach to the prestroke mRS score rule out, such as patients with orthopedic or rheumatic complications that limit mobility and give them an mRS score of 3. “We don’t have data for patients with back pain who can’t walk. I currently take these patients to endovascular therapy, and I’m sure many others do, too,” Dr. Khatri said.
Another potential way to grow the inclusion criteria is to investigate thrombectomy in patients with larger infarcted cores than were enrolled in DAWN and DEFUSE 3, but assessing this will require a new prospective study, Dr. Albers said.
Running the 6- to 24-hour numbers
Adoption of the 6- to 24-hour time window for endovascular intervention in selected patients means that suddenly the U.S. acute stroke infrastructure needs to accommodate a significantly increased number of patients. Just how many added patients this means is uncertain for the time being, and will vary from region to region and center to center. Dr. Albers roughly guessed that the new late time window might double the number of stroke patients undergoing thrombectomy at his center in Stanford. Dr. Khatri put together a more data-driven but still very speculative estimate that at the University of Cincinnati, it will mean about 40% more stroke patients going to thrombectomy. She shared the numbers behind this estimate in a report she gave at the conference.
To calculate the incremental change produced by the late time window, she used data collected on 2,297 acute ischemic stroke patients from the Greater Cincinnati/Northern Kentucky region who were seen at the University of Cincinnati during 2010. Prior analysis by Dr. Khatri and her associates showed that 159 of these patients presented quickly enough and with an appropriate stroke to qualify for thrombolytic therapy, and that 29 patients would have qualified for thrombectomy performed during the 0- to 6-hour time window.
In the new analysis Dr. Khatri calculated that 791 patients presented at 5-23 hours, and of these 34 had other features that would have made them eligible for enrollment in DAWN. Because no imaging data existed for these 2010 patients, she applied an estimate that 22% of these patients would qualify by the size of their infarcted core and ischemic penumbra, resulting in seven additional thrombectomy-eligible patients. Accounting for patients who would qualify by the more liberal DEFUSE 3 criteria added another 5 patients for a total increment of 12 patients during 2010 who would have been eligible for thrombectomy, about 40% of the number from the 0- to 6-hour window.
She noted that “this is likely an underestimate,” and “too small a sample to project to national estimates,” but concluded that “resources must be adapted to account for this increased volume in endovascular treatment.”
Dr. Khatri acknowledged that the new 6- to 24-hour window for endovascular therapy, and concerns about imaging delays in 0- to 6-hour patients, raise challenging issues regarding the message to give U.S. clinicians about treating acute ischemic stroke patients.
“We have a mandate to figure it out in every region. There is no doubt that stroke patients need access to this care. We need to become a lot more aggressive with endovascular treatment. It’s so gratifying to see the outcomes that we’re seeing,” Dr. Khatri said. “A lot of work is needed to accommodate endovascular therapy–eligible patients in an extended time window. We need more refined prehospital triage tools, we need to adequately implement imaging software, and we need increased capacity to perform endovascular treatment with additional procedure suites, operators, and ICU beds.”
Dr. Jovin has been a consultant to Anaconda Biomed, Blockade Medical, Cerenovus, FreeOx Biotech, and Silk Road Medical. Dr. Nogueira has received travel expense reimbursement from Stryker. Dr. Khatri has been a consultant to Biogen, Medpace/Novartis, and St. Jude; has received travel support from Neuravi and EmstoPA; and has received research support from Genentech, Lumosa, and Neurospring. Dr. Albers has an ownership interest in iSchemaView, the company that markets the RAPID imaging software, and is a consultant to iSchemaView and Medtronic.
LOS ANGELES – CT or magnetic resonance brain imaging of acute ischemic stroke patients was the key triage tool in two groundbreaking thrombectomy trials, DAWN and DEFUSE; results from both showed that patients found by imaging to have limited infarcted cores could safely benefit from endovascular thrombectomy, even when they are more than 6 hours out from their stroke onset, breaking the 6-hour barrier created 3 years ago by the first wave of thrombectomy trials.
But some stroke neurologists studying thrombectomy are now convinced that imaging is not needed and may actually harm acute ischemic stroke patients early on by introducing an unnecessary time delay when they present within the first 6 hours after stroke onset.
This new thinking on how to best use brain imaging in acute ischemic stroke patients is part of the rapid evolution of acute stroke management as experts process new data and refine their approach both within 6 hours of stroke onset and during the new treatment window of 6-24 hours post onset. The dramatic success achieved with thrombectomy in highly selected late-window patients prompted researchers to promote pushing the boundaries further to find less-selected late patients who could also potentially benefit from thrombectomy.
The downside of early imaging
“Early on, we have a mix of fast and slow progressors. Slow progressors are about a third to half the patients, so there is a lot of potential for [late] treatment, but the majority of patients during the first 6 hours after onset are fast progressors,” patients who won’t benefit from thrombectomy delivery beyond 6 hours, said Dr. Jovin, an interventional neurologist and director of the Stroke Institute of the University of Pittsburgh Medical Center.
“Time is very precious in the 0- to 6-hour window. When we’re dealing with a lot of fast progressors, we pay a price [in added time to treatment] for any imaging we do. We need to understand that this is a real price we pay, even when CT takes perhaps 24 minutes, and MRI adds about 12 minutes. It’s not the case in all patients that doing CT angiography just adds 5 minutes. It can take 15, 20 minutes,” especially at centers that don’t treat these types of stroke patients day in and day out. “There is no question that imaging slows us down,” Dr. Jovin said.
He highlighted that “the main role of imaging is to exclude patients from treatment, a treatment that has unbelievable effects.” Imaging can rule out patients who have a hemorrhage, lack an occlusion, have a large infarcted core, or have none of the brain at risk or just a small amount, he noted. “Excluding hemorrhage is reasonable, but we can do that in the angiography suite, when the patient is on the table. The main benefit from advanced imaging is to more precisely define the core,” but for most patients the size of their core is not important because the vast majority of acute ischemic stroke patients seen within 6 hours of onset have cores smaller than 70 mL.
“Is this much ado about nothing – especially because we punish all the other patients [with smaller cores] who need to be treated [quickly] when we do additional imaging?” asked Dr. Jovin, who was one of the two lead investigators for the Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo (DAWN) trial (N Engl J Med. 2018 Jan 4;378[1]:11-21). Another factor undercutting the value of imaging and determining core size is registry results that show patients who undergo thrombectomy with a large infarcted core are not harmed by treatment.
Current practice often uses imaging “to exclude the 20% of patients who may not have a large vessel occlusion or may not get benefit but whom we are unlikely to harm. But we harm the other 80% by delaying treatment by 30 minutes because of imaging. That’s why we need to rethink imaging and minimize its use.”
Dr. Jovin noted that at his center in Pittsburgh, the stroke institute staff began in 2013 to take patients transported from other stroke facilities and already diagnosed with a large vessel occlusion directly to the angiography suite, bypassing further brain imaging. By doing this, they cut their average door-to-groin puncture time down to 22 minutes from what had been an average of 81 minutes with imaging (Stroke. 2017 July;48[7]:1884-9). Right now the door-to-groin time is even lower, he added.
“Don’t waste time imaging,” said Dr. Nogueira, a stroke neurologist who is director of the neuroendovascular division of the Marcus Stroke and Neuroscience Center and professor of neurology, neurosurgery, and radiology at Emory University, both in Atlanta, as well as the second lead investigator for DAWN. “Time is crucial and trumps patient selection. Most selection criteria are informative rather than truly selective. It is important to understand that in every time window, we do not yet know who doesn’t benefit from treatment. Select faster, select less, and treat more” during the 0- to 6-hour window, he told his colleagues.
Expanding thrombectomy 6-24 hours after stroke onset
While Dr. Jovin and Dr. Nogueira called for more aggressive and less selective use of thrombectomy in patients who present within 6 hours of their stroke onset, they acknowledged that for patients who present during the 6- to 24-hour window, selection for thrombectomy should follow the rules applied in DAWN and in the more inclusive Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE 3) trial (N Engl J Med. 2018 Feb 22;378:708-18). That means using imaging to confirm that the patient’s infarcted core is within the enrollment ceiling, but both neurologists also downplayed the need for the more sophisticated imaging approaches that were often used in both trials as well as in current routine practice at comprehensive stroke centers. They agreed that noncontrast CT, a widely available method, seems adequate for patient selection, based on the admittedly limited data available right now.
Dr. Nogueira cited data from the Trevo stent retriever registry, collected from nearly 1,000 U.S. acute ischemic stroke patients who underwent thrombectomy with this device. (Researchers at the conference reported updated registry data with nearly 2,000 patients with findings similar to what Dr. Nogueira referenced.) Although these patients underwent treatment before results of DAWN and DEFUSE 3 came out and before release of the new U.S. acute stroke management guidelines (Stroke. 2018 Jan 24; doi: 10.1161/STR.0000000000000158) that endorsed targeted thrombectomy for patients 6-24 hours out from their stroke onset, 278 (28%) of the registry patients underwent thrombectomy treatment during the 6- to 24-hour time window. In this subgroup, 34 patients underwent noncontrast CT to assess their infarcted core prior to thrombectomy, while the other patients underwent perfusion CT, MRI, or both. The noncontrast CT patients had recanalization rates, adverse event rates, and 90-day modified Rankin Scale (mRS) scores comparable with those of patients assessed with more advanced imaging.
Based on this, “just looking at CT only seems reasonable. Noncontrast CT is a pretty valid way to select patients,” Dr. Nogueira said.
“This is the direction we should follow to simplify the paradigm for treating beyond 6 hours,” agreed Dr. Jovin, who also called for further advances in patient selection to expand the pool of patients who qualify for thrombectomy during the 6- to 24-hour postonset period.
“We want the DAWN results to be generalizable, to be simpler. We are exploring some more easily generalizable inclusion criteria that would allow us to treat more patients in more parts of the world,” Dr. Jovin added.
Both clinicians cited the remarkably low number needed to treat found in both DAWN and DEFUSE 3 of roughly three patients to produce one additional patient with a statistically significant and clinically meaningful improvement in their 90-day mRS score, compared with controls, as an unmistakable sign that the treatment in both trials was too targeted.
“When we planned the DAWN and DEFUSE 3 trials we didn’t expect how powerful the treatment effect would be. There are probably other patients who could also benefit, so how low can we go? How liberal can we be in our inclusion criteria and still get benefit?” Dr. Jovin asked.
“When intravenous TPA [tissue plasminogen activator] first came out, we went by the book [for patient selection], but as we got to know the treatment and became more comfortable with it, we began to bend the rules. Now we’re at the point of getting comfortable with endovascular treatment, and we need to figure out where to bend the rules by building the database. There is no doubt that the rules need bending because of the treatment effect that we’ve seen. We need to get our patients to endovascular treatment,” she said in her presentation at the conference.
But these physicians realize that for the time being, standard of care will follow the imaging and data processing primarily used in DAWN and DEFUSE 3, which not only involved perfusion CT or MRI but also a proprietary, automated image processing software, RAPID, that takes imaging data and calculates the amount and ratio of infarcted core and hypoperfused, ischemic brain tissue.
“I asked our imaging experts [at the University of Cincinnati] what should my threshold be [for mismatch between the infarcted core and ischemic tissue], and they said, ‘Use the automated software,’ ” Dr. Khatri said. If centers managing acute ischemic stroke patients don’t already have this software, “they need it. I think there is no way around that. It’s the only way we’ll be able to do this,” she commented. Most U.S. community hospitals that admit stroke patients currently lack this software, largely because of its high cost, she added.
“We’re struggling because it is very difficult to get some community hospitals – primary stroke centers – to invest in the software, but that’s really the only way we’ll be able to do this. There are issues of cost, and of getting technicians trained,” she noted.
That’s because DEFUSE 3 enrolled patients with a baseline National Institutes of Health Stroke Scale (NIHSS) score of at least 6, while patients in DAWN required a score of at least 10, a loosening that allowed inclusion of 31 patients with scores of 6-9 in DEFUSE 3. Another, less restrictive criterion was the patient’s prestroke mRS score, which could have been 0-2 in DEFUSE 3 but could be only 0-1 in DAWN. Thirteen of the DEFUSE 3 patients had prestroke mRS scores of 2. DEFUSE 3 also had somewhat more liberal criteria for the size of a patient’s infarcted core at enrollment, with 41 patients who would have been excluded from DAWN because of an overly large infarcted core, Dr. Albers said in his presentation at the conference.
Currently, for patients presenting more than 16 hours following their stroke onset but within 24 hours, the DAWN enrollment criteria exclusively determine which patients should get thrombectomy.
One area where these rules could be bent is by a more thoughtful approach to the prestroke mRS score rule out, such as patients with orthopedic or rheumatic complications that limit mobility and give them an mRS score of 3. “We don’t have data for patients with back pain who can’t walk. I currently take these patients to endovascular therapy, and I’m sure many others do, too,” Dr. Khatri said.
Another potential way to grow the inclusion criteria is to investigate thrombectomy in patients with larger infarcted cores than were enrolled in DAWN and DEFUSE 3, but assessing this will require a new prospective study, Dr. Albers said.
Running the 6- to 24-hour numbers
Adoption of the 6- to 24-hour time window for endovascular intervention in selected patients means that suddenly the U.S. acute stroke infrastructure needs to accommodate a significantly increased number of patients. Just how many added patients this means is uncertain for the time being, and will vary from region to region and center to center. Dr. Albers roughly guessed that the new late time window might double the number of stroke patients undergoing thrombectomy at his center in Stanford. Dr. Khatri put together a more data-driven but still very speculative estimate that at the University of Cincinnati, it will mean about 40% more stroke patients going to thrombectomy. She shared the numbers behind this estimate in a report she gave at the conference.
To calculate the incremental change produced by the late time window, she used data collected on 2,297 acute ischemic stroke patients from the Greater Cincinnati/Northern Kentucky region who were seen at the University of Cincinnati during 2010. Prior analysis by Dr. Khatri and her associates showed that 159 of these patients presented quickly enough and with an appropriate stroke to qualify for thrombolytic therapy, and that 29 patients would have qualified for thrombectomy performed during the 0- to 6-hour time window.
In the new analysis Dr. Khatri calculated that 791 patients presented at 5-23 hours, and of these 34 had other features that would have made them eligible for enrollment in DAWN. Because no imaging data existed for these 2010 patients, she applied an estimate that 22% of these patients would qualify by the size of their infarcted core and ischemic penumbra, resulting in seven additional thrombectomy-eligible patients. Accounting for patients who would qualify by the more liberal DEFUSE 3 criteria added another 5 patients for a total increment of 12 patients during 2010 who would have been eligible for thrombectomy, about 40% of the number from the 0- to 6-hour window.
She noted that “this is likely an underestimate,” and “too small a sample to project to national estimates,” but concluded that “resources must be adapted to account for this increased volume in endovascular treatment.”
Dr. Khatri acknowledged that the new 6- to 24-hour window for endovascular therapy, and concerns about imaging delays in 0- to 6-hour patients, raise challenging issues regarding the message to give U.S. clinicians about treating acute ischemic stroke patients.
“We have a mandate to figure it out in every region. There is no doubt that stroke patients need access to this care. We need to become a lot more aggressive with endovascular treatment. It’s so gratifying to see the outcomes that we’re seeing,” Dr. Khatri said. “A lot of work is needed to accommodate endovascular therapy–eligible patients in an extended time window. We need more refined prehospital triage tools, we need to adequately implement imaging software, and we need increased capacity to perform endovascular treatment with additional procedure suites, operators, and ICU beds.”
Dr. Jovin has been a consultant to Anaconda Biomed, Blockade Medical, Cerenovus, FreeOx Biotech, and Silk Road Medical. Dr. Nogueira has received travel expense reimbursement from Stryker. Dr. Khatri has been a consultant to Biogen, Medpace/Novartis, and St. Jude; has received travel support from Neuravi and EmstoPA; and has received research support from Genentech, Lumosa, and Neurospring. Dr. Albers has an ownership interest in iSchemaView, the company that markets the RAPID imaging software, and is a consultant to iSchemaView and Medtronic.
EXPERT ANALYSIS FROM ISC 2018
Online psoriasis consultations shown equivalent to office visits
SAN DIEGO – Online consultations between dermatologists, patients with psoriasis, and the patients’ primary care physicians were as effective as in-person consultations in successfully treating the disease in a multicenter, randomized study of 296 patients.
“Innovative telehealth delivery models that emphasize collaboration, quality, and efficiency can be transformative to improving patient-centered outcomes in chronic disease,” April W. Armstrong, MD, said at the annual meeting of the American Academy of Dermatology. The online model she tested fostered “increased patient engagement” and provided “comprehensive specialist support,” said Dr. Armstrong, director of the psoriasis program at the University of Southern California, Los Angeles.
To objectively assess whether online consultations are as effective as in-person examinations, Dr. Armstrong and her associates at three U.S. centers randomized adult psoriasis patients from across the disease spectrum to receive 1 year of dermatology care either in person or online. Patients enrolled in the online arm received training in taking digital images of their skin lesions and uploading the data for remote access by their dermatologist and primary care physician. The frequency of in-person and online consultations was left to the discretion of each patient and his or her physician.
Among the 148 patients randomized to each arm, 17 in the online group and 13 in the in-person group withdrew from the study or were lost to follow-up. The researchers analyzed the results on an intention-to-treat basis.
They assessed three parameters of treatment efficacy that they measured at baseline and then every 3 months out to 1 year: Psoriasis Area and Severity Index, body surface area score, and patient global self-assessment. A comparison of changes between the two treatment arms after 1 year for the first two measures met the study’s prespecified definition of equivalence, Dr. Armstrong reported. The third measure, a patient’s global self-assessment, showed lower patient-assessed disease severity after 1 year among the patients managed online, compared with those managed in person.
The incidence of adverse events and serious adverse events was similar in the two treatment arms.
Dr. Armstrong had no relevant financial disclosures.
Source: Armstrong A et al. AAD 2018, abstract 6730..
SAN DIEGO – Online consultations between dermatologists, patients with psoriasis, and the patients’ primary care physicians were as effective as in-person consultations in successfully treating the disease in a multicenter, randomized study of 296 patients.
“Innovative telehealth delivery models that emphasize collaboration, quality, and efficiency can be transformative to improving patient-centered outcomes in chronic disease,” April W. Armstrong, MD, said at the annual meeting of the American Academy of Dermatology. The online model she tested fostered “increased patient engagement” and provided “comprehensive specialist support,” said Dr. Armstrong, director of the psoriasis program at the University of Southern California, Los Angeles.
To objectively assess whether online consultations are as effective as in-person examinations, Dr. Armstrong and her associates at three U.S. centers randomized adult psoriasis patients from across the disease spectrum to receive 1 year of dermatology care either in person or online. Patients enrolled in the online arm received training in taking digital images of their skin lesions and uploading the data for remote access by their dermatologist and primary care physician. The frequency of in-person and online consultations was left to the discretion of each patient and his or her physician.
Among the 148 patients randomized to each arm, 17 in the online group and 13 in the in-person group withdrew from the study or were lost to follow-up. The researchers analyzed the results on an intention-to-treat basis.
They assessed three parameters of treatment efficacy that they measured at baseline and then every 3 months out to 1 year: Psoriasis Area and Severity Index, body surface area score, and patient global self-assessment. A comparison of changes between the two treatment arms after 1 year for the first two measures met the study’s prespecified definition of equivalence, Dr. Armstrong reported. The third measure, a patient’s global self-assessment, showed lower patient-assessed disease severity after 1 year among the patients managed online, compared with those managed in person.
The incidence of adverse events and serious adverse events was similar in the two treatment arms.
Dr. Armstrong had no relevant financial disclosures.
Source: Armstrong A et al. AAD 2018, abstract 6730..
SAN DIEGO – Online consultations between dermatologists, patients with psoriasis, and the patients’ primary care physicians were as effective as in-person consultations in successfully treating the disease in a multicenter, randomized study of 296 patients.
“Innovative telehealth delivery models that emphasize collaboration, quality, and efficiency can be transformative to improving patient-centered outcomes in chronic disease,” April W. Armstrong, MD, said at the annual meeting of the American Academy of Dermatology. The online model she tested fostered “increased patient engagement” and provided “comprehensive specialist support,” said Dr. Armstrong, director of the psoriasis program at the University of Southern California, Los Angeles.
To objectively assess whether online consultations are as effective as in-person examinations, Dr. Armstrong and her associates at three U.S. centers randomized adult psoriasis patients from across the disease spectrum to receive 1 year of dermatology care either in person or online. Patients enrolled in the online arm received training in taking digital images of their skin lesions and uploading the data for remote access by their dermatologist and primary care physician. The frequency of in-person and online consultations was left to the discretion of each patient and his or her physician.
Among the 148 patients randomized to each arm, 17 in the online group and 13 in the in-person group withdrew from the study or were lost to follow-up. The researchers analyzed the results on an intention-to-treat basis.
They assessed three parameters of treatment efficacy that they measured at baseline and then every 3 months out to 1 year: Psoriasis Area and Severity Index, body surface area score, and patient global self-assessment. A comparison of changes between the two treatment arms after 1 year for the first two measures met the study’s prespecified definition of equivalence, Dr. Armstrong reported. The third measure, a patient’s global self-assessment, showed lower patient-assessed disease severity after 1 year among the patients managed online, compared with those managed in person.
The incidence of adverse events and serious adverse events was similar in the two treatment arms.
Dr. Armstrong had no relevant financial disclosures.
Source: Armstrong A et al. AAD 2018, abstract 6730..
REPORTING FROM AAD 18
Key clinical point: Online physician telemonitoring of psoriasis patients was equivalent to in-person management.
Major finding: After 1 year, changes in the Psoriasis Area and Severity Index in the two arms met the prespecified definition of equivalence.
Study details: A multicenter, randomized trial with 296 psoriasis patients in which outcomes were compared for online monitoring and in-person examinations.
Disclosures: Dr. Armstrong had no relevant financial disclosures.
Source: Armstrong A et al. AAD 18, abstract 6730.
VIDEO: U.S. melanoma incidence hits all-time high
SAN DIEGO –
“Nobody’s quite sure why the [melanoma] rates are still rising so dramatically,” Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology. The increase remains even after adjustment of incidence rates for the increasing mean age of U.S. adults.
The American Cancer Society reported that the estimated annual incidence rate for invasive melanoma will be 91,270 cases for 2018, following what the society called a rapid rise in the rate for the past 30 years. Add to that the estimate of more than 87,000 U.S. cases of in situ melanoma for an overall annual U.S. rate of 178,560, Dr. Rigel said.
Melanoma has a latency of 5-20 years, “so what we’re seeing right now are the effects of what happened 5, 10, or 20 years ago,” said Dr. Rigel, a dermatologist at New York University.
During a talk at the meeting, Dr. Rigel said that based on current incident levels he projected a lifetime U.S. incidence rate of invasive melanoma of one case for every 40 adults by the end of this decade, and a lifetime incidence rate for either invasive or in situ melanoma of one case for every 20 adults by 2020.
A positive trend is that for the first time, the number of melanoma deaths has started to fall, with an estimated 9,320 deaths from melanoma in 2018 according to American Cancer Society statistics, down from a peak of 10,130 melanoma deaths in 2016, Dr. Rigel said.
SAN DIEGO –
“Nobody’s quite sure why the [melanoma] rates are still rising so dramatically,” Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology. The increase remains even after adjustment of incidence rates for the increasing mean age of U.S. adults.
The American Cancer Society reported that the estimated annual incidence rate for invasive melanoma will be 91,270 cases for 2018, following what the society called a rapid rise in the rate for the past 30 years. Add to that the estimate of more than 87,000 U.S. cases of in situ melanoma for an overall annual U.S. rate of 178,560, Dr. Rigel said.
Melanoma has a latency of 5-20 years, “so what we’re seeing right now are the effects of what happened 5, 10, or 20 years ago,” said Dr. Rigel, a dermatologist at New York University.
During a talk at the meeting, Dr. Rigel said that based on current incident levels he projected a lifetime U.S. incidence rate of invasive melanoma of one case for every 40 adults by the end of this decade, and a lifetime incidence rate for either invasive or in situ melanoma of one case for every 20 adults by 2020.
A positive trend is that for the first time, the number of melanoma deaths has started to fall, with an estimated 9,320 deaths from melanoma in 2018 according to American Cancer Society statistics, down from a peak of 10,130 melanoma deaths in 2016, Dr. Rigel said.
SAN DIEGO –
“Nobody’s quite sure why the [melanoma] rates are still rising so dramatically,” Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology. The increase remains even after adjustment of incidence rates for the increasing mean age of U.S. adults.
The American Cancer Society reported that the estimated annual incidence rate for invasive melanoma will be 91,270 cases for 2018, following what the society called a rapid rise in the rate for the past 30 years. Add to that the estimate of more than 87,000 U.S. cases of in situ melanoma for an overall annual U.S. rate of 178,560, Dr. Rigel said.
Melanoma has a latency of 5-20 years, “so what we’re seeing right now are the effects of what happened 5, 10, or 20 years ago,” said Dr. Rigel, a dermatologist at New York University.
During a talk at the meeting, Dr. Rigel said that based on current incident levels he projected a lifetime U.S. incidence rate of invasive melanoma of one case for every 40 adults by the end of this decade, and a lifetime incidence rate for either invasive or in situ melanoma of one case for every 20 adults by 2020.
A positive trend is that for the first time, the number of melanoma deaths has started to fall, with an estimated 9,320 deaths from melanoma in 2018 according to American Cancer Society statistics, down from a peak of 10,130 melanoma deaths in 2016, Dr. Rigel said.
REPORTING FROM AAD 18
VIDEO: Bioimpedance provides accurate assessment of Mohs surgical margins
SAN DIEGO – In assessing tumor-free margins during Mohs micrographic surgery for skin cancer, of histologic sections, in a single-center, pilot study of bioimpedance in 151 specimens from 50 consecutive patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
If the finding of high diagnostic accuracy using bioimpedance spectroscopy is confirmed in larger numbers of patients and specimens run at multiple sites, this approach could “potentially revolutionize what happens with the way Mohs sections are processed in the future” by potentially shaving many minutes off the duration of a standard procedure, Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology.
Usually, it takes 10-20 minutes to process and examine Mohs specimens at each stage of the surgical procedure to determine whether additional excision must remove residual cancer cells, said Dr. Rigel, a dermatologist at New York University. In contrast, assessment for residual cancer cells in the surgical field takes less than a minute using bioimpedance spectroscopy, which relies on differences in electrical conductivity between benign and cancerous cells to identify cancer cells remaining at the surgical margins.
The results of the study were presented in a poster at the meeting, by a research associate of Dr. Rigel’s, Ryan Svoboda, MD, of the National Society for Cutaneous Medicine, New York.
The researchers used a bioimpedance spectroscopy device made by NovaScan to assess 151 histology slides prepared during Mohs micrographic surgery on patients with nonmelanoma skin cancer, and compared the findings against the gold standard of histological slide examination. By this criterion, bioimpedance spectroscopy identified 105 true negatives and 2 false negatives, and 43 true positives and 1 false positive. Calculations showed that this equated to 95.6% sensitivity, 99.1% specificity, a 97.7% positive predictive value, and a 98.1% negative predictive value.
These may be underestimates of the accuracy of bioimpedance spectroscopy because the calculations presume that conventional histology is always correct, but Dr. Rigel noted that sometimes the histological diagnosis is wrong.
SOURCE: Svoboda R et al. Poster 7304.
SAN DIEGO – In assessing tumor-free margins during Mohs micrographic surgery for skin cancer, of histologic sections, in a single-center, pilot study of bioimpedance in 151 specimens from 50 consecutive patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
If the finding of high diagnostic accuracy using bioimpedance spectroscopy is confirmed in larger numbers of patients and specimens run at multiple sites, this approach could “potentially revolutionize what happens with the way Mohs sections are processed in the future” by potentially shaving many minutes off the duration of a standard procedure, Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology.
Usually, it takes 10-20 minutes to process and examine Mohs specimens at each stage of the surgical procedure to determine whether additional excision must remove residual cancer cells, said Dr. Rigel, a dermatologist at New York University. In contrast, assessment for residual cancer cells in the surgical field takes less than a minute using bioimpedance spectroscopy, which relies on differences in electrical conductivity between benign and cancerous cells to identify cancer cells remaining at the surgical margins.
The results of the study were presented in a poster at the meeting, by a research associate of Dr. Rigel’s, Ryan Svoboda, MD, of the National Society for Cutaneous Medicine, New York.
The researchers used a bioimpedance spectroscopy device made by NovaScan to assess 151 histology slides prepared during Mohs micrographic surgery on patients with nonmelanoma skin cancer, and compared the findings against the gold standard of histological slide examination. By this criterion, bioimpedance spectroscopy identified 105 true negatives and 2 false negatives, and 43 true positives and 1 false positive. Calculations showed that this equated to 95.6% sensitivity, 99.1% specificity, a 97.7% positive predictive value, and a 98.1% negative predictive value.
These may be underestimates of the accuracy of bioimpedance spectroscopy because the calculations presume that conventional histology is always correct, but Dr. Rigel noted that sometimes the histological diagnosis is wrong.
SOURCE: Svoboda R et al. Poster 7304.
SAN DIEGO – In assessing tumor-free margins during Mohs micrographic surgery for skin cancer, of histologic sections, in a single-center, pilot study of bioimpedance in 151 specimens from 50 consecutive patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
If the finding of high diagnostic accuracy using bioimpedance spectroscopy is confirmed in larger numbers of patients and specimens run at multiple sites, this approach could “potentially revolutionize what happens with the way Mohs sections are processed in the future” by potentially shaving many minutes off the duration of a standard procedure, Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology.
Usually, it takes 10-20 minutes to process and examine Mohs specimens at each stage of the surgical procedure to determine whether additional excision must remove residual cancer cells, said Dr. Rigel, a dermatologist at New York University. In contrast, assessment for residual cancer cells in the surgical field takes less than a minute using bioimpedance spectroscopy, which relies on differences in electrical conductivity between benign and cancerous cells to identify cancer cells remaining at the surgical margins.
The results of the study were presented in a poster at the meeting, by a research associate of Dr. Rigel’s, Ryan Svoboda, MD, of the National Society for Cutaneous Medicine, New York.
The researchers used a bioimpedance spectroscopy device made by NovaScan to assess 151 histology slides prepared during Mohs micrographic surgery on patients with nonmelanoma skin cancer, and compared the findings against the gold standard of histological slide examination. By this criterion, bioimpedance spectroscopy identified 105 true negatives and 2 false negatives, and 43 true positives and 1 false positive. Calculations showed that this equated to 95.6% sensitivity, 99.1% specificity, a 97.7% positive predictive value, and a 98.1% negative predictive value.
These may be underestimates of the accuracy of bioimpedance spectroscopy because the calculations presume that conventional histology is always correct, but Dr. Rigel noted that sometimes the histological diagnosis is wrong.
SOURCE: Svoboda R et al. Poster 7304.
REPORTING FROM AAD 18
Key clinical point: Bioimpedance spectroscopy showed excellent diagnostic accuracy for cancer cells on Mohs surgical margins.
Major finding: Bioimpedance spectroscopy had a sensitivity of 95.6% and specificity of 99.1% compared with Mohs histology.
Study details: A single-center pilot study with 151 Mohs surgical specimens taken from 50 patients.
Disclosures: The study was funded by NovaScan, the company developing the device tested in the study. Dr. Rigel has been a consultant to NovaScan and to Castle Biosciences, DermTech, Ferndale, Myriad, and Neutrogena, and has received research support from Castle and Neutrogena.
Source: Svoboda R et al. Poster 7304.
VIDEO: SPF 100 sunscreen outperformed SPF 50 in Vail study
SAN DIEGO – a finding that might interest consumers and prompt the Food and Drug Administration to continue to allow sunscreens to have labels listing sun protection factors greater than 50.*
“Our study results show pretty definitively that SPF 100 did significantly better than SPF 50 in a real world environment,” Darrell S. Rigel, MD, said at the annual meeting of the American Academy of Dermatology.
Dr. Rigel cited data that he and his associates recently published from 199 adults skiing on a sunny March day in Colorado. Participants applied a blinded sunscreen rated at SPF 50 to one side of their face all day and an SPF 100 sunscreen to the other side all day, and the researchers then ran a blinded assessment of images taken of each side at the end of the day. The sunburn on the SPF 50 side exceeded the other side in 55% of skiers, the two sides matched in 40%, and in 5% the sunburn was worse on the SPF 100 side (J Am Acad Dermatol. 2017 Dec 29. doi: 10.1016/j.jaad.2017.12.062).
“The SPF 50 side of the face was 11 times more likely to be sunburned than the SPF 100 side,” and for all the secondary endpoints and different ways of analyzing the data, the SPF 50 was not as effective as SPF 100, Dr. Rigel said in a video interview. Erythema appeared on 41% of the SPF 50–treated sides of participants faces, compared with 14% of the sides treated with SPF 100 sunscreen.
The results followed-up on a report from Dr. Rigel and his associates from 8 years ago that ran a similar comparison of two sunscreen potencies, SPF 85 and SPF 50, in 56 skiers, with similar results showing greater sunburn protection from the higher SPF sunscreen (J Am Acad Dermatol. 2010 Feb;62[2]:348-9). In 2011, the FDA proposed a new rule for SPF labeling that would cap the maximum SPF potency possible of 50, which created a label 50+ to designate unspecified SPF above 50. According to Dr. Rigel, the FDA rejected his 2010 study as documentation of incremental benefit above SPF 50 because of several flaws the agency found with that study, including not tracking sunscreen use by weight. He specifically designed the new, 199-subject study to address that and the FDA’s other concerns.
He and his associates decided to do the study because the FDA said in the monograph that, if the concerns were met, “they would accept the study as definitive,” said Dr. Rigel, a dermatologist at New York University.
The greater protection from SPF 100 sunscreen probably occurs because it’s “more forgiving” when used with inadequate application, he suggested. Allowing labeling that specifies SPF levels greater than 50 would help consumers pick sunscreen formulations that give greater protection, and it would encourage manufacturers to market sunscreens with higher SPF levels.
Dr. Rigel has been a consultant to Castle Biosciences, DermTech, Ferndale, Myriad, Neutrogena, and Novascan and has received research support from Castle and Neutrogena.
Correction, 2/22/18: Due to an editing error, an earlier version of this article implied incorrectly that sunscreen labels listing SPFs over 50 had been banned .
SAN DIEGO – a finding that might interest consumers and prompt the Food and Drug Administration to continue to allow sunscreens to have labels listing sun protection factors greater than 50.*
“Our study results show pretty definitively that SPF 100 did significantly better than SPF 50 in a real world environment,” Darrell S. Rigel, MD, said at the annual meeting of the American Academy of Dermatology.
Dr. Rigel cited data that he and his associates recently published from 199 adults skiing on a sunny March day in Colorado. Participants applied a blinded sunscreen rated at SPF 50 to one side of their face all day and an SPF 100 sunscreen to the other side all day, and the researchers then ran a blinded assessment of images taken of each side at the end of the day. The sunburn on the SPF 50 side exceeded the other side in 55% of skiers, the two sides matched in 40%, and in 5% the sunburn was worse on the SPF 100 side (J Am Acad Dermatol. 2017 Dec 29. doi: 10.1016/j.jaad.2017.12.062).
“The SPF 50 side of the face was 11 times more likely to be sunburned than the SPF 100 side,” and for all the secondary endpoints and different ways of analyzing the data, the SPF 50 was not as effective as SPF 100, Dr. Rigel said in a video interview. Erythema appeared on 41% of the SPF 50–treated sides of participants faces, compared with 14% of the sides treated with SPF 100 sunscreen.
The results followed-up on a report from Dr. Rigel and his associates from 8 years ago that ran a similar comparison of two sunscreen potencies, SPF 85 and SPF 50, in 56 skiers, with similar results showing greater sunburn protection from the higher SPF sunscreen (J Am Acad Dermatol. 2010 Feb;62[2]:348-9). In 2011, the FDA proposed a new rule for SPF labeling that would cap the maximum SPF potency possible of 50, which created a label 50+ to designate unspecified SPF above 50. According to Dr. Rigel, the FDA rejected his 2010 study as documentation of incremental benefit above SPF 50 because of several flaws the agency found with that study, including not tracking sunscreen use by weight. He specifically designed the new, 199-subject study to address that and the FDA’s other concerns.
He and his associates decided to do the study because the FDA said in the monograph that, if the concerns were met, “they would accept the study as definitive,” said Dr. Rigel, a dermatologist at New York University.
The greater protection from SPF 100 sunscreen probably occurs because it’s “more forgiving” when used with inadequate application, he suggested. Allowing labeling that specifies SPF levels greater than 50 would help consumers pick sunscreen formulations that give greater protection, and it would encourage manufacturers to market sunscreens with higher SPF levels.
Dr. Rigel has been a consultant to Castle Biosciences, DermTech, Ferndale, Myriad, Neutrogena, and Novascan and has received research support from Castle and Neutrogena.
Correction, 2/22/18: Due to an editing error, an earlier version of this article implied incorrectly that sunscreen labels listing SPFs over 50 had been banned .
SAN DIEGO – a finding that might interest consumers and prompt the Food and Drug Administration to continue to allow sunscreens to have labels listing sun protection factors greater than 50.*
“Our study results show pretty definitively that SPF 100 did significantly better than SPF 50 in a real world environment,” Darrell S. Rigel, MD, said at the annual meeting of the American Academy of Dermatology.
Dr. Rigel cited data that he and his associates recently published from 199 adults skiing on a sunny March day in Colorado. Participants applied a blinded sunscreen rated at SPF 50 to one side of their face all day and an SPF 100 sunscreen to the other side all day, and the researchers then ran a blinded assessment of images taken of each side at the end of the day. The sunburn on the SPF 50 side exceeded the other side in 55% of skiers, the two sides matched in 40%, and in 5% the sunburn was worse on the SPF 100 side (J Am Acad Dermatol. 2017 Dec 29. doi: 10.1016/j.jaad.2017.12.062).
“The SPF 50 side of the face was 11 times more likely to be sunburned than the SPF 100 side,” and for all the secondary endpoints and different ways of analyzing the data, the SPF 50 was not as effective as SPF 100, Dr. Rigel said in a video interview. Erythema appeared on 41% of the SPF 50–treated sides of participants faces, compared with 14% of the sides treated with SPF 100 sunscreen.
The results followed-up on a report from Dr. Rigel and his associates from 8 years ago that ran a similar comparison of two sunscreen potencies, SPF 85 and SPF 50, in 56 skiers, with similar results showing greater sunburn protection from the higher SPF sunscreen (J Am Acad Dermatol. 2010 Feb;62[2]:348-9). In 2011, the FDA proposed a new rule for SPF labeling that would cap the maximum SPF potency possible of 50, which created a label 50+ to designate unspecified SPF above 50. According to Dr. Rigel, the FDA rejected his 2010 study as documentation of incremental benefit above SPF 50 because of several flaws the agency found with that study, including not tracking sunscreen use by weight. He specifically designed the new, 199-subject study to address that and the FDA’s other concerns.
He and his associates decided to do the study because the FDA said in the monograph that, if the concerns were met, “they would accept the study as definitive,” said Dr. Rigel, a dermatologist at New York University.
The greater protection from SPF 100 sunscreen probably occurs because it’s “more forgiving” when used with inadequate application, he suggested. Allowing labeling that specifies SPF levels greater than 50 would help consumers pick sunscreen formulations that give greater protection, and it would encourage manufacturers to market sunscreens with higher SPF levels.
Dr. Rigel has been a consultant to Castle Biosciences, DermTech, Ferndale, Myriad, Neutrogena, and Novascan and has received research support from Castle and Neutrogena.
Correction, 2/22/18: Due to an editing error, an earlier version of this article implied incorrectly that sunscreen labels listing SPFs over 50 had been banned .
EXPERT ANALYSIS FROM AAD 18
Topical anticholinergic improved hyperhidrosis in children
SAN DIEGO – A topical anticholinergic drug, glycopyrronium tosylate, was as safe and effective for treating hyperhidrosis in children 9-16 years old as it was in adults in two phase 3 trials that included 25 treated children, raising the prospect it could become the first drug to gain Food and Drug Administration approval for treating pediatric hyperhidrosis.
“Topical glycopyrronium tosylate treatment may provide a much needed treatment option for those with primary axillary hyperhidrosis, including pediatric patients,” Adelaide A. Hebert, MD, said at the annual meeting of the American Academy of Dermatology.
The data she reported from a post hoc analysis included 25 children. 9-16 years old, who received a daily, topical application of glycopyrronium tosylate to their underarms for 4 weeks and 19 children treated with vehicle only. The children were enrolled in either of a pair of phase 3 pivotal trials that together randomized 697 patients. In November 2017, Dermira, the company developing this drug, submitted an application to the FDA for marketing approval of the agent for adults and children at least 9 years old. A statement from the company said an FDA decision is expected by mid-2018.
Getting approval from the FDA for an effective pediatric hyperhidrosis treatment would be an important advance because nothing now exists in that space, said Dr. Hebert, professor of dermatology and pediatrics and director of pediatric dermatology at the University of Texas Health Sciences Center at Houston.
Based on past FDA actions, safety data from 25 children should be adequate to support pediatric labeling, she said in an interview, though she added that confirmatory safety data from a phase 4 study in children would be a welcome future addition. Hyperhydrosis in adolescents is “underappreciated, underdiagnosed, and is very impactful,” and currently has limited treatment options that are readily available for children, especially effective options for more severe hyperhidrosis.
The pediatric data came from the phase 3, randomized, double-blind, vehicle-controlled ATMOS-1 (DRM04 in Subjects With Axillary Hyperhidrosis) trial. The trial ran at several U.S. and German centers, although only the U.S. centers enrolled pediatric patients.
The two trials enrolled patients with “intolerable or barely tolerable” primary, axillary hyperhidrosis of at least 6 months' duration. After 4 weeks, patients treated with glycopyrronium tosylate had improvements in their daily diary account of axillary sweating and in sweat production. Dr. Hebert and her associates reported overall results from the two trials at various prior dermatology meetings, and the company reported some of the results in a press release, but the results have not yet been published in a journal.
The new, pediatric analysis that Dr. Hebert reported showed that the responder rate based on a 4 point or greater improvement in daily sweat diary assessments occurred in 60% of the actively treated children and in 13% of the controls. A 50% or greater reduction in sweat production occurred in 80% of the treated children and in 55% of controls. Quality of life, measured using the Children’s Dermatology Life Quality Index improved by an average of 8 points among the treated children, compared with an average 2-point improvement among the controls. This level of improvement among the glycopyrronium-treated patients would have been enough to move patients from the moderate-effect category at baseline to a no- or small-effect category.
The treatment was generally well tolerated, with no serious adverse effects reported and with treatment effects that were primarily as expected from an anticholinergic agent, including dry mouth, pupil dilation, and blurred vision. One of the 25 treated children withdrew because of these effects, which then resolved. Blood testing showed no systemic absorption of the drug, Dr. Hebert said.
The ATMOS-1 and ATMOS-2 trials were sponsored by Dermira, the company developing glycopyrronium tosylate. Dr. Hebert has been a consultant to and has received research funding from Dermira, and some of the coauthors of the study are Dermira employees. Dr. Hebert is an advisor to the editorial board of Dermatology News.
SOURCE: Hebert A et al. Annual meeting of the American Academy of Dermatology Abstract 6659.
SAN DIEGO – A topical anticholinergic drug, glycopyrronium tosylate, was as safe and effective for treating hyperhidrosis in children 9-16 years old as it was in adults in two phase 3 trials that included 25 treated children, raising the prospect it could become the first drug to gain Food and Drug Administration approval for treating pediatric hyperhidrosis.
“Topical glycopyrronium tosylate treatment may provide a much needed treatment option for those with primary axillary hyperhidrosis, including pediatric patients,” Adelaide A. Hebert, MD, said at the annual meeting of the American Academy of Dermatology.
The data she reported from a post hoc analysis included 25 children. 9-16 years old, who received a daily, topical application of glycopyrronium tosylate to their underarms for 4 weeks and 19 children treated with vehicle only. The children were enrolled in either of a pair of phase 3 pivotal trials that together randomized 697 patients. In November 2017, Dermira, the company developing this drug, submitted an application to the FDA for marketing approval of the agent for adults and children at least 9 years old. A statement from the company said an FDA decision is expected by mid-2018.
Getting approval from the FDA for an effective pediatric hyperhidrosis treatment would be an important advance because nothing now exists in that space, said Dr. Hebert, professor of dermatology and pediatrics and director of pediatric dermatology at the University of Texas Health Sciences Center at Houston.
Based on past FDA actions, safety data from 25 children should be adequate to support pediatric labeling, she said in an interview, though she added that confirmatory safety data from a phase 4 study in children would be a welcome future addition. Hyperhydrosis in adolescents is “underappreciated, underdiagnosed, and is very impactful,” and currently has limited treatment options that are readily available for children, especially effective options for more severe hyperhidrosis.
The pediatric data came from the phase 3, randomized, double-blind, vehicle-controlled ATMOS-1 (DRM04 in Subjects With Axillary Hyperhidrosis) trial. The trial ran at several U.S. and German centers, although only the U.S. centers enrolled pediatric patients.
The two trials enrolled patients with “intolerable or barely tolerable” primary, axillary hyperhidrosis of at least 6 months' duration. After 4 weeks, patients treated with glycopyrronium tosylate had improvements in their daily diary account of axillary sweating and in sweat production. Dr. Hebert and her associates reported overall results from the two trials at various prior dermatology meetings, and the company reported some of the results in a press release, but the results have not yet been published in a journal.
The new, pediatric analysis that Dr. Hebert reported showed that the responder rate based on a 4 point or greater improvement in daily sweat diary assessments occurred in 60% of the actively treated children and in 13% of the controls. A 50% or greater reduction in sweat production occurred in 80% of the treated children and in 55% of controls. Quality of life, measured using the Children’s Dermatology Life Quality Index improved by an average of 8 points among the treated children, compared with an average 2-point improvement among the controls. This level of improvement among the glycopyrronium-treated patients would have been enough to move patients from the moderate-effect category at baseline to a no- or small-effect category.
The treatment was generally well tolerated, with no serious adverse effects reported and with treatment effects that were primarily as expected from an anticholinergic agent, including dry mouth, pupil dilation, and blurred vision. One of the 25 treated children withdrew because of these effects, which then resolved. Blood testing showed no systemic absorption of the drug, Dr. Hebert said.
The ATMOS-1 and ATMOS-2 trials were sponsored by Dermira, the company developing glycopyrronium tosylate. Dr. Hebert has been a consultant to and has received research funding from Dermira, and some of the coauthors of the study are Dermira employees. Dr. Hebert is an advisor to the editorial board of Dermatology News.
SOURCE: Hebert A et al. Annual meeting of the American Academy of Dermatology Abstract 6659.
SAN DIEGO – A topical anticholinergic drug, glycopyrronium tosylate, was as safe and effective for treating hyperhidrosis in children 9-16 years old as it was in adults in two phase 3 trials that included 25 treated children, raising the prospect it could become the first drug to gain Food and Drug Administration approval for treating pediatric hyperhidrosis.
“Topical glycopyrronium tosylate treatment may provide a much needed treatment option for those with primary axillary hyperhidrosis, including pediatric patients,” Adelaide A. Hebert, MD, said at the annual meeting of the American Academy of Dermatology.
The data she reported from a post hoc analysis included 25 children. 9-16 years old, who received a daily, topical application of glycopyrronium tosylate to their underarms for 4 weeks and 19 children treated with vehicle only. The children were enrolled in either of a pair of phase 3 pivotal trials that together randomized 697 patients. In November 2017, Dermira, the company developing this drug, submitted an application to the FDA for marketing approval of the agent for adults and children at least 9 years old. A statement from the company said an FDA decision is expected by mid-2018.
Getting approval from the FDA for an effective pediatric hyperhidrosis treatment would be an important advance because nothing now exists in that space, said Dr. Hebert, professor of dermatology and pediatrics and director of pediatric dermatology at the University of Texas Health Sciences Center at Houston.
Based on past FDA actions, safety data from 25 children should be adequate to support pediatric labeling, she said in an interview, though she added that confirmatory safety data from a phase 4 study in children would be a welcome future addition. Hyperhydrosis in adolescents is “underappreciated, underdiagnosed, and is very impactful,” and currently has limited treatment options that are readily available for children, especially effective options for more severe hyperhidrosis.
The pediatric data came from the phase 3, randomized, double-blind, vehicle-controlled ATMOS-1 (DRM04 in Subjects With Axillary Hyperhidrosis) trial. The trial ran at several U.S. and German centers, although only the U.S. centers enrolled pediatric patients.
The two trials enrolled patients with “intolerable or barely tolerable” primary, axillary hyperhidrosis of at least 6 months' duration. After 4 weeks, patients treated with glycopyrronium tosylate had improvements in their daily diary account of axillary sweating and in sweat production. Dr. Hebert and her associates reported overall results from the two trials at various prior dermatology meetings, and the company reported some of the results in a press release, but the results have not yet been published in a journal.
The new, pediatric analysis that Dr. Hebert reported showed that the responder rate based on a 4 point or greater improvement in daily sweat diary assessments occurred in 60% of the actively treated children and in 13% of the controls. A 50% or greater reduction in sweat production occurred in 80% of the treated children and in 55% of controls. Quality of life, measured using the Children’s Dermatology Life Quality Index improved by an average of 8 points among the treated children, compared with an average 2-point improvement among the controls. This level of improvement among the glycopyrronium-treated patients would have been enough to move patients from the moderate-effect category at baseline to a no- or small-effect category.
The treatment was generally well tolerated, with no serious adverse effects reported and with treatment effects that were primarily as expected from an anticholinergic agent, including dry mouth, pupil dilation, and blurred vision. One of the 25 treated children withdrew because of these effects, which then resolved. Blood testing showed no systemic absorption of the drug, Dr. Hebert said.
The ATMOS-1 and ATMOS-2 trials were sponsored by Dermira, the company developing glycopyrronium tosylate. Dr. Hebert has been a consultant to and has received research funding from Dermira, and some of the coauthors of the study are Dermira employees. Dr. Hebert is an advisor to the editorial board of Dermatology News.
SOURCE: Hebert A et al. Annual meeting of the American Academy of Dermatology Abstract 6659.
REPORTING FROM AAD 18
Key clinical point: Max. Daily, topical glycopyrronium tosylate safely controlled pediatric hyperhidrosis.
Major finding: At least a 4-point improvement in the axillary sweating daily diary score occurred in 60% of treated patients and in 13% of controls.
Study details: Post hoc analysis of data from 44 children enrolled in either of two pivotal trials, ATMOS-1 and ATMOS-2.
Disclosures: The ATMOS-1 and ATMOS-2 trials were sponsored by Dermira, the company developing glycopyrronium tosylate. Dr. Hebert has been a consultant to and has received research funding from Dermira, and some of the coauthors of the study are Dermira employees. Dr. Hebert is an adviser to the editorial board of Dermatology News.
Source: Hebert A et al. AAD 2018, Abstract 6659.
Refractory alopecia patients could consider a JAK inhibitor
SAN DIEGO – Treatment with a Janus kinase inhibitor such as tofacitinib is a reasonable option for patients with refractory alopecia who seek resolution of their hair loss and understand the adverse event risk from using this drug class, John E. Harris, MD, PhD, said at the annual meeting of the American Academy of Dermatology.
Using a Janus kinase (JAK) inhibitor to treat alopecia areata or totalis is a “highly successful, emerging therapy,” with efficacy rates for good responses of about a third or higher in a handful of published reports with experiences in more than 150 patients, said Dr. Harris, an associate professor of dermatology and director of the Vitiligo Clinic and Research Center at the University of Massachusetts Medical School in Worcester.
“Some clinicians may say ‘I’d never prescribe a JAK inhibitor for hair loss, it’s too dangerous,’ but several hundred alopecia patients have now received this with no serious adverse effects,” said Dr. Harris. He acknowledged, however, that eventually some patients treated this way will have serious adverse effects. He said that he is treating with tofacitinib a “handful” of alopecia patients who have been unresponsive to other treatments, are eager for an intervention that might regrow their hair, and who understand and accept the risk for developing an infection, shingles, or myelosuppression (with ruxolitinib treatment).
Roughly half of the alopecia patients prescribed tofacitinib (Xeljanz) by Dr. Harris have had their drug cost covered by health insurance, with the others paying for it themselves. Arranging for insurance coverage has usually involved filing an appeal, Dr. Harris said in an interview. The reported successful dosages have been 5 mg bid, with a boost to 10 mg bid for patients who don’t initially respond.
Insurance companies have not yet paid for treatment with ruxolitinib (Jakafi), which has been described in case reports in far fewer patients and which costs about $120,000 a year, he noted.
Dr. Harris said that JAK inhibitors also have great potential for treating vitiligo, a disorder he thinks shares many features in common with alopecia ( J Allergy Clin Immunol. 2017 Sept;140[3]:654-62).
“I think [JAK inhibitors] will have the same efficacy in vitiligo,” he predicted. He is particularly enthused about the possibility of administering ruxolitinib topically to patients with alopecia or vitiligo. Ruxolitinib is well suited to topical administration because of its good skin penetration, Dr. Harris said. Several trials now in progress are further studying JAK inhibitors for alopecia using oral or topical formulations.
Dr. Harris has been a consultant to and has received research funding from Pfizer, the company that markets tofacitinib (Xeljanz). He has also been a consultant to a dozen other companies, and has also received research support from Aclaris Therapeutics, Celgene, Dermavant, Genzyme, Sanofi, and Stiefel/GlaxoSmithKline.
SAN DIEGO – Treatment with a Janus kinase inhibitor such as tofacitinib is a reasonable option for patients with refractory alopecia who seek resolution of their hair loss and understand the adverse event risk from using this drug class, John E. Harris, MD, PhD, said at the annual meeting of the American Academy of Dermatology.
Using a Janus kinase (JAK) inhibitor to treat alopecia areata or totalis is a “highly successful, emerging therapy,” with efficacy rates for good responses of about a third or higher in a handful of published reports with experiences in more than 150 patients, said Dr. Harris, an associate professor of dermatology and director of the Vitiligo Clinic and Research Center at the University of Massachusetts Medical School in Worcester.
“Some clinicians may say ‘I’d never prescribe a JAK inhibitor for hair loss, it’s too dangerous,’ but several hundred alopecia patients have now received this with no serious adverse effects,” said Dr. Harris. He acknowledged, however, that eventually some patients treated this way will have serious adverse effects. He said that he is treating with tofacitinib a “handful” of alopecia patients who have been unresponsive to other treatments, are eager for an intervention that might regrow their hair, and who understand and accept the risk for developing an infection, shingles, or myelosuppression (with ruxolitinib treatment).
Roughly half of the alopecia patients prescribed tofacitinib (Xeljanz) by Dr. Harris have had their drug cost covered by health insurance, with the others paying for it themselves. Arranging for insurance coverage has usually involved filing an appeal, Dr. Harris said in an interview. The reported successful dosages have been 5 mg bid, with a boost to 10 mg bid for patients who don’t initially respond.
Insurance companies have not yet paid for treatment with ruxolitinib (Jakafi), which has been described in case reports in far fewer patients and which costs about $120,000 a year, he noted.
Dr. Harris said that JAK inhibitors also have great potential for treating vitiligo, a disorder he thinks shares many features in common with alopecia ( J Allergy Clin Immunol. 2017 Sept;140[3]:654-62).
“I think [JAK inhibitors] will have the same efficacy in vitiligo,” he predicted. He is particularly enthused about the possibility of administering ruxolitinib topically to patients with alopecia or vitiligo. Ruxolitinib is well suited to topical administration because of its good skin penetration, Dr. Harris said. Several trials now in progress are further studying JAK inhibitors for alopecia using oral or topical formulations.
Dr. Harris has been a consultant to and has received research funding from Pfizer, the company that markets tofacitinib (Xeljanz). He has also been a consultant to a dozen other companies, and has also received research support from Aclaris Therapeutics, Celgene, Dermavant, Genzyme, Sanofi, and Stiefel/GlaxoSmithKline.
SAN DIEGO – Treatment with a Janus kinase inhibitor such as tofacitinib is a reasonable option for patients with refractory alopecia who seek resolution of their hair loss and understand the adverse event risk from using this drug class, John E. Harris, MD, PhD, said at the annual meeting of the American Academy of Dermatology.
Using a Janus kinase (JAK) inhibitor to treat alopecia areata or totalis is a “highly successful, emerging therapy,” with efficacy rates for good responses of about a third or higher in a handful of published reports with experiences in more than 150 patients, said Dr. Harris, an associate professor of dermatology and director of the Vitiligo Clinic and Research Center at the University of Massachusetts Medical School in Worcester.
“Some clinicians may say ‘I’d never prescribe a JAK inhibitor for hair loss, it’s too dangerous,’ but several hundred alopecia patients have now received this with no serious adverse effects,” said Dr. Harris. He acknowledged, however, that eventually some patients treated this way will have serious adverse effects. He said that he is treating with tofacitinib a “handful” of alopecia patients who have been unresponsive to other treatments, are eager for an intervention that might regrow their hair, and who understand and accept the risk for developing an infection, shingles, or myelosuppression (with ruxolitinib treatment).
Roughly half of the alopecia patients prescribed tofacitinib (Xeljanz) by Dr. Harris have had their drug cost covered by health insurance, with the others paying for it themselves. Arranging for insurance coverage has usually involved filing an appeal, Dr. Harris said in an interview. The reported successful dosages have been 5 mg bid, with a boost to 10 mg bid for patients who don’t initially respond.
Insurance companies have not yet paid for treatment with ruxolitinib (Jakafi), which has been described in case reports in far fewer patients and which costs about $120,000 a year, he noted.
Dr. Harris said that JAK inhibitors also have great potential for treating vitiligo, a disorder he thinks shares many features in common with alopecia ( J Allergy Clin Immunol. 2017 Sept;140[3]:654-62).
“I think [JAK inhibitors] will have the same efficacy in vitiligo,” he predicted. He is particularly enthused about the possibility of administering ruxolitinib topically to patients with alopecia or vitiligo. Ruxolitinib is well suited to topical administration because of its good skin penetration, Dr. Harris said. Several trials now in progress are further studying JAK inhibitors for alopecia using oral or topical formulations.
Dr. Harris has been a consultant to and has received research funding from Pfizer, the company that markets tofacitinib (Xeljanz). He has also been a consultant to a dozen other companies, and has also received research support from Aclaris Therapeutics, Celgene, Dermavant, Genzyme, Sanofi, and Stiefel/GlaxoSmithKline.
EXPERT ANALYSIS AT AAD 18
