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Frustration over iPLEDGE evident at FDA meeting
During 2 days of after the chaotic rollout of the new REMS platform at the end of 2021.
On March 29, at the end of the FDA’s joint meeting of two advisory committees that addressed ways to improve the iPLEDGE program, most panelists voted to change the 19-day lockout period for patients who can become pregnant, and the requirement that every month, providers must document counseling of those who cannot get pregnant and are taking the drug for acne.
However, there was no consensus on whether there should be a lockout at all or for how long, and what an appropriate interval for counseling those who cannot get pregnant would be, if not monthly. Those voting on the questions repeatedly cited a lack of data to make well-informed decisions.
The meeting of the two panels, the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee, was held March 28-29, to discuss proposed changes to iPLEDGE requirements, to minimize the program’s burden on patients, prescribers, and pharmacies – while maintaining safe use of the highly teratogenic drug.
Lockout based on outdated reasoning
John S. Barbieri, MD, a dermatologist and epidemiologist, and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital in Boston, speaking as deputy chair of the American Academy of Dermatology Association (AADA) iPLEDGE work group, described the burden of getting the drug to patients. He was not on the panel, but spoke during the open public hearing.
“Compared to other acne medications, the time it takes to successfully go from prescribed (isotretinoin) to when the patient actually has it in their hands is 5- to 10-fold higher,” he said.
Among the barriers is the 19-day lockout period for people who can get pregnant and miss the 7-day window for picking up their prescriptions. They must then wait 19 days to get a pregnancy test to clear them for receiving the medication.
Gregory Wedin, PharmD, pharmacovigilance and risk management director of Upsher-Smith Laboratories, who spoke on behalf of the Isotretinoin Products Manufacturer Group (IPMG), which manages iPLEDGE, said, “The rationale for the 19-day wait is to ensure the next confirmatory pregnancy test is completed after the most fertile period of the menstrual cycle is passed.”
Many don’t have a monthly cycle
But Dr. Barbieri said that reasoning is outdated.
“The current program’s focus on the menstrual cycle is really an antiquated approach,” he said. “Many patients do not have a monthly cycle due to medical conditions like polycystic ovarian syndrome, or due to [certain kinds of] contraception.”
He added, “By removing this 19-day lockout and, really, the archaic timing around the menstrual cycle in general in this program, we can simplify the program, improve it, and better align it with the real-world biology of our patients.” He added that patients are often missing the 7-day window for picking up their prescriptions through no fault of their own. Speakers at the hearing also mentioned insurance hassles and ordering delays.
Communication with IPMG
Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and outgoing chair of the AADA iPLEDGE work group, cited difficulty in working with IPMG on modifications as another barrier. She also spoke during the open public hearing.
“Despite many, many attempts to work with the IPMG, we are not aware of any organizational structure or key leaders to communicate with. Instead we have been given repeatedly a generic email address for trying to establish a working relationship and we believe this may explain the inaction of the IPMG since our proposals 4 years ago in 2019.”
Among those proposals, she said, were allowing telemedicine visits as part of the iPLEDGE REMS program and reducing counseling attestation to every 6 months instead of monthly for those who cannot become pregnant.
She pointed to the chaotic rollout of modifications to the iPLEDGE program on a new website at the end of 2021.
In 2021, she said, “despite 6 months of notification, no prescriber input was solicited before revamping the website. This lack of transparency and accountability has been a major hurdle in improving iPLEDGE.”
Dr. Barbieri called the rollout “a debacle” that could have been mitigated with communication with IPMG. “We warned about every issue that happened and talked about ways to mitigate it and were largely ignored,” he said.
“By including dermatologists and key stakeholders in these discussions, as we move forward with changes to improve this program, we can make sure that it’s patient-centered.”
IPMG did not address the specific complaints about the working relationship with the AADA workgroup at the meeting.
Monthly attestation for counseling patients who cannot get pregnant
Dr. Barbieri said the monthly requirement to counsel patients who cannot get pregnant and document that counseling unfairly burdens clinicians and patients. “We’re essentially asking patients to come in monthly just to tell them not to share their drugs [or] donate blood,” he said.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among the panel members voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
IPMG representative Dr. Wedin, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”
He said that while an extension to 120 days would reduce burden on prescribers, it comes with the risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.
“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Dr. Wedin said.
Home pregnancy testing
The advisory groups were also tasked with discussing whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most committee members and those in the public hearing who spoke on the issue agreed that home tests should continue in an effort to increase access and decrease burden.
During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory.
Lindsey Crist, PharmD, a risk management analyst at the FDA, who presented the FDA review committee’s analysis, said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.
“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” Dr. Crist said.
Dr. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
Workaround to avoid falsification
Advisory committee member Brian P. Green, DO, associate professor of dermatology at Penn State University, Hershey, Pa., spoke in support of home pregnancy tests.
“What we have people do for telemedicine is take the stick, write their name, write the date on it, and send a picture of that the same day as their visit,” he said. “That way we have the pregnancy test the same day. Allowing this to continue to happen at home is important. Bringing people in is burdensome and costly.”
Emmy Graber, MD, a dermatologist who practices in Boston, and a director of the American Acne and Rosacea Society (AARS), relayed an example of the burden for a patient using isotretinoin who lives 1.5 hours away from the dermatology office. She is able to meet the requirements of iPLEDGE only through telehealth.
“Home pregnancy tests are highly sensitive, equal to the ones done in CLIA-certified labs, and highly accurate when interpreted by a dermatology provider,” said Dr. Graber, who spoke on behalf of the AARS during the open public hearing.
“Notably, CLIA [Clinical Laboratory Improvement Amendments] certification is not required by other REMS programs” for teratogenic drugs, she added.
Dr. Graber said it’s important to note that in the time the pandemic exceptions have been made for isotretinoin patients, “there has been no reported spike in pregnancy in the past three years.
“We do have some data to show that it is not imposing additional harms,” she said.
Suggestions for improvement
At the end of the hearing, advisory committee members were asked to propose improvements to the iPLEDGE REMS program.
Dr. Green advocated for the addition of an iPLEDGE mobile app.
“Most people go to their phones rather than their computers, particularly teenagers and younger people,” he noted.
Advisory committee member Megha M. Tollefson, MD, professor of dermatology and pediatric and adolescent medicine at Mayo Clinic in Rochester, Minn., echoed the need for an iPLEDGE app.
The young patients getting isotretinoin “don’t respond to email, they don’t necessarily go onto web pages. If we’re going to be as effective as possible, it’s going to have to be through an app-based system.”
Dr. Tollefson said she would like to see patient counseling standardized through the app. “I think there’s a lot of variability in what counseling is given when it’s left to the individual prescriber or practice,” she said.
Exceptions for long-acting contraceptives?
Advisory committee member Abbey B. Berenson, MD, PhD, professor of obstetrics and gynecology at University of Texas Medical Branch in Galveston, said that patients taking long-acting reversible contraceptives (LARCs) may need to be considered differently when deciding the intervals for attestation or whether to have a lockout period.
“LARC methods’ rate of failure is extremely low,” she said. “While it is true, as it has been pointed out, that all methods can fail, when they’re over 99% effective, I think that we can treat those methods differently than we treat methods such as birth control pills or abstinence that fail far more often. That is one way we could minimize burden on the providers and the patients.”
She also suggested using members of the health care team other than physicians to complete counseling, such as a nurse or pharmacist.
Prescriptions for emergency contraception
Advisory committee member Sascha Dublin, MD, PhD, senior scientific investigator for Kaiser Permanente Washington Health Research Institute in Seattle, said most patients taking the drug who can get pregnant should get a prescription for emergency contraception at the time of the first isotretinoin prescription.
“They don’t have to buy it, but to make it available at the very beginning sets the expectation that it would be good to have in your medicine cabinet, particularly if the [contraception] choice is abstinence or birth control pills.”
Dr. Dublin also called for better transparency surrounding the role of IPMG.
She said IPMG should be expected to collect data in a way that allows examination of health disparities, including by race and ethnicity and insurance status. Dr. Dublin added that she was concerned about the poor communication between dermatological societies and IPMG.
“The FDA should really require that IPMG hold periodic, regularly scheduled stakeholder forums,” she said. “There has to be a mechanism in place for IPMG to listen to those concerns in real time and respond.”
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
During 2 days of after the chaotic rollout of the new REMS platform at the end of 2021.
On March 29, at the end of the FDA’s joint meeting of two advisory committees that addressed ways to improve the iPLEDGE program, most panelists voted to change the 19-day lockout period for patients who can become pregnant, and the requirement that every month, providers must document counseling of those who cannot get pregnant and are taking the drug for acne.
However, there was no consensus on whether there should be a lockout at all or for how long, and what an appropriate interval for counseling those who cannot get pregnant would be, if not monthly. Those voting on the questions repeatedly cited a lack of data to make well-informed decisions.
The meeting of the two panels, the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee, was held March 28-29, to discuss proposed changes to iPLEDGE requirements, to minimize the program’s burden on patients, prescribers, and pharmacies – while maintaining safe use of the highly teratogenic drug.
Lockout based on outdated reasoning
John S. Barbieri, MD, a dermatologist and epidemiologist, and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital in Boston, speaking as deputy chair of the American Academy of Dermatology Association (AADA) iPLEDGE work group, described the burden of getting the drug to patients. He was not on the panel, but spoke during the open public hearing.
“Compared to other acne medications, the time it takes to successfully go from prescribed (isotretinoin) to when the patient actually has it in their hands is 5- to 10-fold higher,” he said.
Among the barriers is the 19-day lockout period for people who can get pregnant and miss the 7-day window for picking up their prescriptions. They must then wait 19 days to get a pregnancy test to clear them for receiving the medication.
Gregory Wedin, PharmD, pharmacovigilance and risk management director of Upsher-Smith Laboratories, who spoke on behalf of the Isotretinoin Products Manufacturer Group (IPMG), which manages iPLEDGE, said, “The rationale for the 19-day wait is to ensure the next confirmatory pregnancy test is completed after the most fertile period of the menstrual cycle is passed.”
Many don’t have a monthly cycle
But Dr. Barbieri said that reasoning is outdated.
“The current program’s focus on the menstrual cycle is really an antiquated approach,” he said. “Many patients do not have a monthly cycle due to medical conditions like polycystic ovarian syndrome, or due to [certain kinds of] contraception.”
He added, “By removing this 19-day lockout and, really, the archaic timing around the menstrual cycle in general in this program, we can simplify the program, improve it, and better align it with the real-world biology of our patients.” He added that patients are often missing the 7-day window for picking up their prescriptions through no fault of their own. Speakers at the hearing also mentioned insurance hassles and ordering delays.
Communication with IPMG
Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and outgoing chair of the AADA iPLEDGE work group, cited difficulty in working with IPMG on modifications as another barrier. She also spoke during the open public hearing.
“Despite many, many attempts to work with the IPMG, we are not aware of any organizational structure or key leaders to communicate with. Instead we have been given repeatedly a generic email address for trying to establish a working relationship and we believe this may explain the inaction of the IPMG since our proposals 4 years ago in 2019.”
Among those proposals, she said, were allowing telemedicine visits as part of the iPLEDGE REMS program and reducing counseling attestation to every 6 months instead of monthly for those who cannot become pregnant.
She pointed to the chaotic rollout of modifications to the iPLEDGE program on a new website at the end of 2021.
In 2021, she said, “despite 6 months of notification, no prescriber input was solicited before revamping the website. This lack of transparency and accountability has been a major hurdle in improving iPLEDGE.”
Dr. Barbieri called the rollout “a debacle” that could have been mitigated with communication with IPMG. “We warned about every issue that happened and talked about ways to mitigate it and were largely ignored,” he said.
“By including dermatologists and key stakeholders in these discussions, as we move forward with changes to improve this program, we can make sure that it’s patient-centered.”
IPMG did not address the specific complaints about the working relationship with the AADA workgroup at the meeting.
Monthly attestation for counseling patients who cannot get pregnant
Dr. Barbieri said the monthly requirement to counsel patients who cannot get pregnant and document that counseling unfairly burdens clinicians and patients. “We’re essentially asking patients to come in monthly just to tell them not to share their drugs [or] donate blood,” he said.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among the panel members voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
IPMG representative Dr. Wedin, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”
He said that while an extension to 120 days would reduce burden on prescribers, it comes with the risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.
“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Dr. Wedin said.
Home pregnancy testing
The advisory groups were also tasked with discussing whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most committee members and those in the public hearing who spoke on the issue agreed that home tests should continue in an effort to increase access and decrease burden.
During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory.
Lindsey Crist, PharmD, a risk management analyst at the FDA, who presented the FDA review committee’s analysis, said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.
“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” Dr. Crist said.
Dr. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
Workaround to avoid falsification
Advisory committee member Brian P. Green, DO, associate professor of dermatology at Penn State University, Hershey, Pa., spoke in support of home pregnancy tests.
“What we have people do for telemedicine is take the stick, write their name, write the date on it, and send a picture of that the same day as their visit,” he said. “That way we have the pregnancy test the same day. Allowing this to continue to happen at home is important. Bringing people in is burdensome and costly.”
Emmy Graber, MD, a dermatologist who practices in Boston, and a director of the American Acne and Rosacea Society (AARS), relayed an example of the burden for a patient using isotretinoin who lives 1.5 hours away from the dermatology office. She is able to meet the requirements of iPLEDGE only through telehealth.
“Home pregnancy tests are highly sensitive, equal to the ones done in CLIA-certified labs, and highly accurate when interpreted by a dermatology provider,” said Dr. Graber, who spoke on behalf of the AARS during the open public hearing.
“Notably, CLIA [Clinical Laboratory Improvement Amendments] certification is not required by other REMS programs” for teratogenic drugs, she added.
Dr. Graber said it’s important to note that in the time the pandemic exceptions have been made for isotretinoin patients, “there has been no reported spike in pregnancy in the past three years.
“We do have some data to show that it is not imposing additional harms,” she said.
Suggestions for improvement
At the end of the hearing, advisory committee members were asked to propose improvements to the iPLEDGE REMS program.
Dr. Green advocated for the addition of an iPLEDGE mobile app.
“Most people go to their phones rather than their computers, particularly teenagers and younger people,” he noted.
Advisory committee member Megha M. Tollefson, MD, professor of dermatology and pediatric and adolescent medicine at Mayo Clinic in Rochester, Minn., echoed the need for an iPLEDGE app.
The young patients getting isotretinoin “don’t respond to email, they don’t necessarily go onto web pages. If we’re going to be as effective as possible, it’s going to have to be through an app-based system.”
Dr. Tollefson said she would like to see patient counseling standardized through the app. “I think there’s a lot of variability in what counseling is given when it’s left to the individual prescriber or practice,” she said.
Exceptions for long-acting contraceptives?
Advisory committee member Abbey B. Berenson, MD, PhD, professor of obstetrics and gynecology at University of Texas Medical Branch in Galveston, said that patients taking long-acting reversible contraceptives (LARCs) may need to be considered differently when deciding the intervals for attestation or whether to have a lockout period.
“LARC methods’ rate of failure is extremely low,” she said. “While it is true, as it has been pointed out, that all methods can fail, when they’re over 99% effective, I think that we can treat those methods differently than we treat methods such as birth control pills or abstinence that fail far more often. That is one way we could minimize burden on the providers and the patients.”
She also suggested using members of the health care team other than physicians to complete counseling, such as a nurse or pharmacist.
Prescriptions for emergency contraception
Advisory committee member Sascha Dublin, MD, PhD, senior scientific investigator for Kaiser Permanente Washington Health Research Institute in Seattle, said most patients taking the drug who can get pregnant should get a prescription for emergency contraception at the time of the first isotretinoin prescription.
“They don’t have to buy it, but to make it available at the very beginning sets the expectation that it would be good to have in your medicine cabinet, particularly if the [contraception] choice is abstinence or birth control pills.”
Dr. Dublin also called for better transparency surrounding the role of IPMG.
She said IPMG should be expected to collect data in a way that allows examination of health disparities, including by race and ethnicity and insurance status. Dr. Dublin added that she was concerned about the poor communication between dermatological societies and IPMG.
“The FDA should really require that IPMG hold periodic, regularly scheduled stakeholder forums,” she said. “There has to be a mechanism in place for IPMG to listen to those concerns in real time and respond.”
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
During 2 days of after the chaotic rollout of the new REMS platform at the end of 2021.
On March 29, at the end of the FDA’s joint meeting of two advisory committees that addressed ways to improve the iPLEDGE program, most panelists voted to change the 19-day lockout period for patients who can become pregnant, and the requirement that every month, providers must document counseling of those who cannot get pregnant and are taking the drug for acne.
However, there was no consensus on whether there should be a lockout at all or for how long, and what an appropriate interval for counseling those who cannot get pregnant would be, if not monthly. Those voting on the questions repeatedly cited a lack of data to make well-informed decisions.
The meeting of the two panels, the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee, was held March 28-29, to discuss proposed changes to iPLEDGE requirements, to minimize the program’s burden on patients, prescribers, and pharmacies – while maintaining safe use of the highly teratogenic drug.
Lockout based on outdated reasoning
John S. Barbieri, MD, a dermatologist and epidemiologist, and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital in Boston, speaking as deputy chair of the American Academy of Dermatology Association (AADA) iPLEDGE work group, described the burden of getting the drug to patients. He was not on the panel, but spoke during the open public hearing.
“Compared to other acne medications, the time it takes to successfully go from prescribed (isotretinoin) to when the patient actually has it in their hands is 5- to 10-fold higher,” he said.
Among the barriers is the 19-day lockout period for people who can get pregnant and miss the 7-day window for picking up their prescriptions. They must then wait 19 days to get a pregnancy test to clear them for receiving the medication.
Gregory Wedin, PharmD, pharmacovigilance and risk management director of Upsher-Smith Laboratories, who spoke on behalf of the Isotretinoin Products Manufacturer Group (IPMG), which manages iPLEDGE, said, “The rationale for the 19-day wait is to ensure the next confirmatory pregnancy test is completed after the most fertile period of the menstrual cycle is passed.”
Many don’t have a monthly cycle
But Dr. Barbieri said that reasoning is outdated.
“The current program’s focus on the menstrual cycle is really an antiquated approach,” he said. “Many patients do not have a monthly cycle due to medical conditions like polycystic ovarian syndrome, or due to [certain kinds of] contraception.”
He added, “By removing this 19-day lockout and, really, the archaic timing around the menstrual cycle in general in this program, we can simplify the program, improve it, and better align it with the real-world biology of our patients.” He added that patients are often missing the 7-day window for picking up their prescriptions through no fault of their own. Speakers at the hearing also mentioned insurance hassles and ordering delays.
Communication with IPMG
Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and outgoing chair of the AADA iPLEDGE work group, cited difficulty in working with IPMG on modifications as another barrier. She also spoke during the open public hearing.
“Despite many, many attempts to work with the IPMG, we are not aware of any organizational structure or key leaders to communicate with. Instead we have been given repeatedly a generic email address for trying to establish a working relationship and we believe this may explain the inaction of the IPMG since our proposals 4 years ago in 2019.”
Among those proposals, she said, were allowing telemedicine visits as part of the iPLEDGE REMS program and reducing counseling attestation to every 6 months instead of monthly for those who cannot become pregnant.
She pointed to the chaotic rollout of modifications to the iPLEDGE program on a new website at the end of 2021.
In 2021, she said, “despite 6 months of notification, no prescriber input was solicited before revamping the website. This lack of transparency and accountability has been a major hurdle in improving iPLEDGE.”
Dr. Barbieri called the rollout “a debacle” that could have been mitigated with communication with IPMG. “We warned about every issue that happened and talked about ways to mitigate it and were largely ignored,” he said.
“By including dermatologists and key stakeholders in these discussions, as we move forward with changes to improve this program, we can make sure that it’s patient-centered.”
IPMG did not address the specific complaints about the working relationship with the AADA workgroup at the meeting.
Monthly attestation for counseling patients who cannot get pregnant
Dr. Barbieri said the monthly requirement to counsel patients who cannot get pregnant and document that counseling unfairly burdens clinicians and patients. “We’re essentially asking patients to come in monthly just to tell them not to share their drugs [or] donate blood,” he said.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among the panel members voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
IPMG representative Dr. Wedin, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”
He said that while an extension to 120 days would reduce burden on prescribers, it comes with the risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.
“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Dr. Wedin said.
Home pregnancy testing
The advisory groups were also tasked with discussing whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most committee members and those in the public hearing who spoke on the issue agreed that home tests should continue in an effort to increase access and decrease burden.
During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory.
Lindsey Crist, PharmD, a risk management analyst at the FDA, who presented the FDA review committee’s analysis, said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.
“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” Dr. Crist said.
Dr. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
Workaround to avoid falsification
Advisory committee member Brian P. Green, DO, associate professor of dermatology at Penn State University, Hershey, Pa., spoke in support of home pregnancy tests.
“What we have people do for telemedicine is take the stick, write their name, write the date on it, and send a picture of that the same day as their visit,” he said. “That way we have the pregnancy test the same day. Allowing this to continue to happen at home is important. Bringing people in is burdensome and costly.”
Emmy Graber, MD, a dermatologist who practices in Boston, and a director of the American Acne and Rosacea Society (AARS), relayed an example of the burden for a patient using isotretinoin who lives 1.5 hours away from the dermatology office. She is able to meet the requirements of iPLEDGE only through telehealth.
“Home pregnancy tests are highly sensitive, equal to the ones done in CLIA-certified labs, and highly accurate when interpreted by a dermatology provider,” said Dr. Graber, who spoke on behalf of the AARS during the open public hearing.
“Notably, CLIA [Clinical Laboratory Improvement Amendments] certification is not required by other REMS programs” for teratogenic drugs, she added.
Dr. Graber said it’s important to note that in the time the pandemic exceptions have been made for isotretinoin patients, “there has been no reported spike in pregnancy in the past three years.
“We do have some data to show that it is not imposing additional harms,” she said.
Suggestions for improvement
At the end of the hearing, advisory committee members were asked to propose improvements to the iPLEDGE REMS program.
Dr. Green advocated for the addition of an iPLEDGE mobile app.
“Most people go to their phones rather than their computers, particularly teenagers and younger people,” he noted.
Advisory committee member Megha M. Tollefson, MD, professor of dermatology and pediatric and adolescent medicine at Mayo Clinic in Rochester, Minn., echoed the need for an iPLEDGE app.
The young patients getting isotretinoin “don’t respond to email, they don’t necessarily go onto web pages. If we’re going to be as effective as possible, it’s going to have to be through an app-based system.”
Dr. Tollefson said she would like to see patient counseling standardized through the app. “I think there’s a lot of variability in what counseling is given when it’s left to the individual prescriber or practice,” she said.
Exceptions for long-acting contraceptives?
Advisory committee member Abbey B. Berenson, MD, PhD, professor of obstetrics and gynecology at University of Texas Medical Branch in Galveston, said that patients taking long-acting reversible contraceptives (LARCs) may need to be considered differently when deciding the intervals for attestation or whether to have a lockout period.
“LARC methods’ rate of failure is extremely low,” she said. “While it is true, as it has been pointed out, that all methods can fail, when they’re over 99% effective, I think that we can treat those methods differently than we treat methods such as birth control pills or abstinence that fail far more often. That is one way we could minimize burden on the providers and the patients.”
She also suggested using members of the health care team other than physicians to complete counseling, such as a nurse or pharmacist.
Prescriptions for emergency contraception
Advisory committee member Sascha Dublin, MD, PhD, senior scientific investigator for Kaiser Permanente Washington Health Research Institute in Seattle, said most patients taking the drug who can get pregnant should get a prescription for emergency contraception at the time of the first isotretinoin prescription.
“They don’t have to buy it, but to make it available at the very beginning sets the expectation that it would be good to have in your medicine cabinet, particularly if the [contraception] choice is abstinence or birth control pills.”
Dr. Dublin also called for better transparency surrounding the role of IPMG.
She said IPMG should be expected to collect data in a way that allows examination of health disparities, including by race and ethnicity and insurance status. Dr. Dublin added that she was concerned about the poor communication between dermatological societies and IPMG.
“The FDA should really require that IPMG hold periodic, regularly scheduled stakeholder forums,” she said. “There has to be a mechanism in place for IPMG to listen to those concerns in real time and respond.”
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
FDA panels vote to modify isotretinoin iPLEDGE REMS
At a joint meeting of a drug for severe, nodular acne that is highly teratogenic.
The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.
Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.
Listed options and the number of votes for each were:
- Only with the first prescription as part of patient enrollment (10)
- Monthly (1)
- Every 120 days (6)
- Some other frequency (5)
For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.
Lack of data
On both questions, several advisory committee members cited a lack of data on which they could base their decision.
On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.
“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”
The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.
The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.
They were also tasked with discussing other REMS requirements without taking a vote on each topic.
Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.
The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
A version of this article first appeared on Medscape.com.
At a joint meeting of a drug for severe, nodular acne that is highly teratogenic.
The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.
Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.
Listed options and the number of votes for each were:
- Only with the first prescription as part of patient enrollment (10)
- Monthly (1)
- Every 120 days (6)
- Some other frequency (5)
For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.
Lack of data
On both questions, several advisory committee members cited a lack of data on which they could base their decision.
On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.
“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”
The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.
The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.
They were also tasked with discussing other REMS requirements without taking a vote on each topic.
Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.
The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
A version of this article first appeared on Medscape.com.
At a joint meeting of a drug for severe, nodular acne that is highly teratogenic.
The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.
Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.
Listed options and the number of votes for each were:
- Only with the first prescription as part of patient enrollment (10)
- Monthly (1)
- Every 120 days (6)
- Some other frequency (5)
For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.
Lack of data
On both questions, several advisory committee members cited a lack of data on which they could base their decision.
On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.
“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”
The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.
The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.
They were also tasked with discussing other REMS requirements without taking a vote on each topic.
Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.
The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
A version of this article first appeared on Medscape.com.
FDA Advisory panels consider easing isotretinoin requirements
for patients, pharmacies, and prescribers.
Isotretinoin, previously called Accutane, is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane.
In a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee, experts addressed ways to improve the modified iPLEDGE Risk Evaluation and Mitigation Strategy (iPLEDGE REMS) for isotretinoin that caused chaos after its rollout at the end of 2021.
In January 2022, problems were multiplying with the program for clinicians, pharmacists, and patients, causing extensive delays and prescription denials. In response, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve problems.
March 28 was the first day of a 2-day meeting addressing what can be done to reduce burden with the iPLEDGE REMS while maintaining safety and preventing fetal exposure to the drug.
Key areas of concern
The meeting focused on several key areas.
The 19-day lockout period
The lockout is a current restriction for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the specified 7-day prescription window. Currently, those who miss the window must wait 19 days from the date of the first pregnancy test to take an additional pregnancy test to be eligible to receive the drug.
Lindsey Crist, PharmD, a risk management analyst for the FDA, who presented the FDA review committee’s analysis, acknowledged that the lockout period causes delays in treatment and adds frustration and costs.
She said it’s important to remember that the lockout applies only to the first prescription. “It’s intended as an additional layer of screening to detect pregnancy,” she said.
“At least 12 pregnancies have been identified during the 19-day lockout from March 2017–September of 2022,” she noted.
The FDA is looking to the advisory committee to provide recommendations on whether the lockout period should be changed.
Home testing
During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory and home pregnancy tests have been allowed. The question now is whether home tests should continue to be allowed.
Ms. Crist said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.
“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” she said.
Ms. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
Documenting counseling patients who cannot get pregnant
Currently, this documentation must be done monthly, primarily to counsel patients against drug sharing or giving blood. Proposed changes include extending the intervals for attestation or eliminating it to reduce burden on clinicians.
IPMG representative Gregory Wedin, PharmD, pharmacovigilance and risk management director for Upsher-Smith Laboratories, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”
He said that while extending to 120 days would reduce burden on prescribers, it comes with risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.
“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Mr. Wedin said.
On March 29, the panel will hear more recommendations for and against modifications to iPLEDGE REMS and will vote on select modifications at the end of the meeting.
A version of this article first appeared on Medscape.com.
for patients, pharmacies, and prescribers.
Isotretinoin, previously called Accutane, is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane.
In a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee, experts addressed ways to improve the modified iPLEDGE Risk Evaluation and Mitigation Strategy (iPLEDGE REMS) for isotretinoin that caused chaos after its rollout at the end of 2021.
In January 2022, problems were multiplying with the program for clinicians, pharmacists, and patients, causing extensive delays and prescription denials. In response, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve problems.
March 28 was the first day of a 2-day meeting addressing what can be done to reduce burden with the iPLEDGE REMS while maintaining safety and preventing fetal exposure to the drug.
Key areas of concern
The meeting focused on several key areas.
The 19-day lockout period
The lockout is a current restriction for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the specified 7-day prescription window. Currently, those who miss the window must wait 19 days from the date of the first pregnancy test to take an additional pregnancy test to be eligible to receive the drug.
Lindsey Crist, PharmD, a risk management analyst for the FDA, who presented the FDA review committee’s analysis, acknowledged that the lockout period causes delays in treatment and adds frustration and costs.
She said it’s important to remember that the lockout applies only to the first prescription. “It’s intended as an additional layer of screening to detect pregnancy,” she said.
“At least 12 pregnancies have been identified during the 19-day lockout from March 2017–September of 2022,” she noted.
The FDA is looking to the advisory committee to provide recommendations on whether the lockout period should be changed.
Home testing
During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory and home pregnancy tests have been allowed. The question now is whether home tests should continue to be allowed.
Ms. Crist said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.
“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” she said.
Ms. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
Documenting counseling patients who cannot get pregnant
Currently, this documentation must be done monthly, primarily to counsel patients against drug sharing or giving blood. Proposed changes include extending the intervals for attestation or eliminating it to reduce burden on clinicians.
IPMG representative Gregory Wedin, PharmD, pharmacovigilance and risk management director for Upsher-Smith Laboratories, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”
He said that while extending to 120 days would reduce burden on prescribers, it comes with risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.
“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Mr. Wedin said.
On March 29, the panel will hear more recommendations for and against modifications to iPLEDGE REMS and will vote on select modifications at the end of the meeting.
A version of this article first appeared on Medscape.com.
for patients, pharmacies, and prescribers.
Isotretinoin, previously called Accutane, is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane.
In a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee, experts addressed ways to improve the modified iPLEDGE Risk Evaluation and Mitigation Strategy (iPLEDGE REMS) for isotretinoin that caused chaos after its rollout at the end of 2021.
In January 2022, problems were multiplying with the program for clinicians, pharmacists, and patients, causing extensive delays and prescription denials. In response, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve problems.
March 28 was the first day of a 2-day meeting addressing what can be done to reduce burden with the iPLEDGE REMS while maintaining safety and preventing fetal exposure to the drug.
Key areas of concern
The meeting focused on several key areas.
The 19-day lockout period
The lockout is a current restriction for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the specified 7-day prescription window. Currently, those who miss the window must wait 19 days from the date of the first pregnancy test to take an additional pregnancy test to be eligible to receive the drug.
Lindsey Crist, PharmD, a risk management analyst for the FDA, who presented the FDA review committee’s analysis, acknowledged that the lockout period causes delays in treatment and adds frustration and costs.
She said it’s important to remember that the lockout applies only to the first prescription. “It’s intended as an additional layer of screening to detect pregnancy,” she said.
“At least 12 pregnancies have been identified during the 19-day lockout from March 2017–September of 2022,” she noted.
The FDA is looking to the advisory committee to provide recommendations on whether the lockout period should be changed.
Home testing
During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory and home pregnancy tests have been allowed. The question now is whether home tests should continue to be allowed.
Ms. Crist said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.
“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” she said.
Ms. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
Documenting counseling patients who cannot get pregnant
Currently, this documentation must be done monthly, primarily to counsel patients against drug sharing or giving blood. Proposed changes include extending the intervals for attestation or eliminating it to reduce burden on clinicians.
IPMG representative Gregory Wedin, PharmD, pharmacovigilance and risk management director for Upsher-Smith Laboratories, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”
He said that while extending to 120 days would reduce burden on prescribers, it comes with risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.
“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Mr. Wedin said.
On March 29, the panel will hear more recommendations for and against modifications to iPLEDGE REMS and will vote on select modifications at the end of the meeting.
A version of this article first appeared on Medscape.com.
Spironolactone: an ‘inexpensive, effective’ option for acne in women
HONOLULU – In the clinical experience of Julie C. Harper, MD, an increasing number of women with acne are turning to off-label, long-term treatment with spironolactone.
“Spironolactone is fairly accessible, inexpensive, and effective for our patients,” Dr. Harper, a dermatologist who practices in Birmingham, Ala., said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!
An aldosterone receptor antagonist commonly used to treat high blood pressure and heart failure, spironolactone also has antiandrogenic properties with a proven track record for treating acne and hirsutism. It reduces androgen production, inhibits 5-alpha reductase, and increases sex hormone binding globulin. The dosing range for treating acne is 25 mg to 200 mg per day, but Dr. Harper prefers a maximum dose of 100 mg per day.
According to a systematic review of its use for acne in adult women, the most common side effect is menstrual irregularity, while other common side effects include breast tenderness/swelling, fatigue, and headaches.
“The higher the dose, the higher the rate of side effects,” she said. Concomitant use of an oral contraceptive lessens menstrual irregularities and prevents pregnancies, to avoid exposure during pregnancy and the hypothetical risk of feminization of the male fetus with exposure late in the first trimester. “Early in my career, I used to say if you’re going to be on spironolactone you’re also going to be on an oral contraceptive. But the longer I’ve practiced, I’ve learned that women who have a contraindication to birth control pills or who don’t want to take it can still benefit from an oral antiandrogen by being on spironolactone.”
A large retrospective analysis of 14-year data concluded that routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. “If you’re between the ages of 18 and 45, healthy, and not taking other medications where I’m worried about potassium levels, I’m not checking those levels at all,” Dr. Harper said.
Spironolactone labeling includes a boxed warning regarding the potential for tumorigenicity based on rat studies, but the dosages used in those studies were 25-250 times higher than the exposure dose in humans, Dr. Harper said.
Results from a systematic review and meta-analysis of seven studies in the medical literature found no evidence of an increased risk of breast cancer in women with exposure to spironolactone. “However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism,” the study authors wrote.
In a separate study, researchers drew from patients in the Humana Insurance database from 2005 to 2017 to address whether spironolactone is associated with an increased risk of recurrence of breast cancer. Recurrent breast cancer was examined in 29,146 women with continuous health insurance for 2 years after a diagnosis of breast cancer. Of these, 746 were prescribed spironolactone, and the remainder were not. The researchers found that 123 women (16.5%) who were prescribed spironolactone had a breast cancer recurrence, compared with 3,649 women (12.8%) with a breast cancer recurrence who had not been prescribed spironolactone (P = .004). Adjusted Cox regression analysis following propensity matching showed no association between spironolactone and increased breast cancer recurrence (adjusted hazard ratio, 0.966; P = .953).
According to Dr. Harper, spironolactone may take about 3 months to kick in. “Likely this is a long-term treatment, and most of the time we’re going to be using it in combination with other acne treatments such as topical retinoids or topical benzoyl peroxide, oral antibiotics, or even isotretinoin.”
A study of long-term spironolactone use in 403 women found that the most common dose prescribed was 100 mg/day, and 68% of the women were concurrently prescribed a topical retinoid, 2.2% an oral antibiotic, and 40.7% an oral contraceptive.
The study population included 32 patients with a history of polycystic ovarian syndrome, 1 with a history of breast cancer, and 5 were hypercoagulable. Patients took the drug for a mean of 471 days. “As opposed to our antibiotics, where the course for patients is generally 3-4 months, when you start someone on spironolactone, they may end up staying on it,” Dr. Harper said.
Dr. Harper disclosed that she serves as an advisor or consultant for Almirall, Cassiopeia, Cutera, EPI, Galderma, L’Oreal, Ortho Dermatologics, Sol Gel, and Vyne. She also serves as a speaker or member of a speaker’s bureau for Almirall, Cassiopeia, Cutera, EPI, Galderma, Journey Almirall, L’Oreal, Ortho Dermatologics, Sun Pharmaceutical Industries, and Vyne.
Medscape and this news organization are owned by the same parent company.
HONOLULU – In the clinical experience of Julie C. Harper, MD, an increasing number of women with acne are turning to off-label, long-term treatment with spironolactone.
“Spironolactone is fairly accessible, inexpensive, and effective for our patients,” Dr. Harper, a dermatologist who practices in Birmingham, Ala., said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!
An aldosterone receptor antagonist commonly used to treat high blood pressure and heart failure, spironolactone also has antiandrogenic properties with a proven track record for treating acne and hirsutism. It reduces androgen production, inhibits 5-alpha reductase, and increases sex hormone binding globulin. The dosing range for treating acne is 25 mg to 200 mg per day, but Dr. Harper prefers a maximum dose of 100 mg per day.
According to a systematic review of its use for acne in adult women, the most common side effect is menstrual irregularity, while other common side effects include breast tenderness/swelling, fatigue, and headaches.
“The higher the dose, the higher the rate of side effects,” she said. Concomitant use of an oral contraceptive lessens menstrual irregularities and prevents pregnancies, to avoid exposure during pregnancy and the hypothetical risk of feminization of the male fetus with exposure late in the first trimester. “Early in my career, I used to say if you’re going to be on spironolactone you’re also going to be on an oral contraceptive. But the longer I’ve practiced, I’ve learned that women who have a contraindication to birth control pills or who don’t want to take it can still benefit from an oral antiandrogen by being on spironolactone.”
A large retrospective analysis of 14-year data concluded that routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. “If you’re between the ages of 18 and 45, healthy, and not taking other medications where I’m worried about potassium levels, I’m not checking those levels at all,” Dr. Harper said.
Spironolactone labeling includes a boxed warning regarding the potential for tumorigenicity based on rat studies, but the dosages used in those studies were 25-250 times higher than the exposure dose in humans, Dr. Harper said.
Results from a systematic review and meta-analysis of seven studies in the medical literature found no evidence of an increased risk of breast cancer in women with exposure to spironolactone. “However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism,” the study authors wrote.
In a separate study, researchers drew from patients in the Humana Insurance database from 2005 to 2017 to address whether spironolactone is associated with an increased risk of recurrence of breast cancer. Recurrent breast cancer was examined in 29,146 women with continuous health insurance for 2 years after a diagnosis of breast cancer. Of these, 746 were prescribed spironolactone, and the remainder were not. The researchers found that 123 women (16.5%) who were prescribed spironolactone had a breast cancer recurrence, compared with 3,649 women (12.8%) with a breast cancer recurrence who had not been prescribed spironolactone (P = .004). Adjusted Cox regression analysis following propensity matching showed no association between spironolactone and increased breast cancer recurrence (adjusted hazard ratio, 0.966; P = .953).
According to Dr. Harper, spironolactone may take about 3 months to kick in. “Likely this is a long-term treatment, and most of the time we’re going to be using it in combination with other acne treatments such as topical retinoids or topical benzoyl peroxide, oral antibiotics, or even isotretinoin.”
A study of long-term spironolactone use in 403 women found that the most common dose prescribed was 100 mg/day, and 68% of the women were concurrently prescribed a topical retinoid, 2.2% an oral antibiotic, and 40.7% an oral contraceptive.
The study population included 32 patients with a history of polycystic ovarian syndrome, 1 with a history of breast cancer, and 5 were hypercoagulable. Patients took the drug for a mean of 471 days. “As opposed to our antibiotics, where the course for patients is generally 3-4 months, when you start someone on spironolactone, they may end up staying on it,” Dr. Harper said.
Dr. Harper disclosed that she serves as an advisor or consultant for Almirall, Cassiopeia, Cutera, EPI, Galderma, L’Oreal, Ortho Dermatologics, Sol Gel, and Vyne. She also serves as a speaker or member of a speaker’s bureau for Almirall, Cassiopeia, Cutera, EPI, Galderma, Journey Almirall, L’Oreal, Ortho Dermatologics, Sun Pharmaceutical Industries, and Vyne.
Medscape and this news organization are owned by the same parent company.
HONOLULU – In the clinical experience of Julie C. Harper, MD, an increasing number of women with acne are turning to off-label, long-term treatment with spironolactone.
“Spironolactone is fairly accessible, inexpensive, and effective for our patients,” Dr. Harper, a dermatologist who practices in Birmingham, Ala., said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!
An aldosterone receptor antagonist commonly used to treat high blood pressure and heart failure, spironolactone also has antiandrogenic properties with a proven track record for treating acne and hirsutism. It reduces androgen production, inhibits 5-alpha reductase, and increases sex hormone binding globulin. The dosing range for treating acne is 25 mg to 200 mg per day, but Dr. Harper prefers a maximum dose of 100 mg per day.
According to a systematic review of its use for acne in adult women, the most common side effect is menstrual irregularity, while other common side effects include breast tenderness/swelling, fatigue, and headaches.
“The higher the dose, the higher the rate of side effects,” she said. Concomitant use of an oral contraceptive lessens menstrual irregularities and prevents pregnancies, to avoid exposure during pregnancy and the hypothetical risk of feminization of the male fetus with exposure late in the first trimester. “Early in my career, I used to say if you’re going to be on spironolactone you’re also going to be on an oral contraceptive. But the longer I’ve practiced, I’ve learned that women who have a contraindication to birth control pills or who don’t want to take it can still benefit from an oral antiandrogen by being on spironolactone.”
A large retrospective analysis of 14-year data concluded that routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. “If you’re between the ages of 18 and 45, healthy, and not taking other medications where I’m worried about potassium levels, I’m not checking those levels at all,” Dr. Harper said.
Spironolactone labeling includes a boxed warning regarding the potential for tumorigenicity based on rat studies, but the dosages used in those studies were 25-250 times higher than the exposure dose in humans, Dr. Harper said.
Results from a systematic review and meta-analysis of seven studies in the medical literature found no evidence of an increased risk of breast cancer in women with exposure to spironolactone. “However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism,” the study authors wrote.
In a separate study, researchers drew from patients in the Humana Insurance database from 2005 to 2017 to address whether spironolactone is associated with an increased risk of recurrence of breast cancer. Recurrent breast cancer was examined in 29,146 women with continuous health insurance for 2 years after a diagnosis of breast cancer. Of these, 746 were prescribed spironolactone, and the remainder were not. The researchers found that 123 women (16.5%) who were prescribed spironolactone had a breast cancer recurrence, compared with 3,649 women (12.8%) with a breast cancer recurrence who had not been prescribed spironolactone (P = .004). Adjusted Cox regression analysis following propensity matching showed no association between spironolactone and increased breast cancer recurrence (adjusted hazard ratio, 0.966; P = .953).
According to Dr. Harper, spironolactone may take about 3 months to kick in. “Likely this is a long-term treatment, and most of the time we’re going to be using it in combination with other acne treatments such as topical retinoids or topical benzoyl peroxide, oral antibiotics, or even isotretinoin.”
A study of long-term spironolactone use in 403 women found that the most common dose prescribed was 100 mg/day, and 68% of the women were concurrently prescribed a topical retinoid, 2.2% an oral antibiotic, and 40.7% an oral contraceptive.
The study population included 32 patients with a history of polycystic ovarian syndrome, 1 with a history of breast cancer, and 5 were hypercoagulable. Patients took the drug for a mean of 471 days. “As opposed to our antibiotics, where the course for patients is generally 3-4 months, when you start someone on spironolactone, they may end up staying on it,” Dr. Harper said.
Dr. Harper disclosed that she serves as an advisor or consultant for Almirall, Cassiopeia, Cutera, EPI, Galderma, L’Oreal, Ortho Dermatologics, Sol Gel, and Vyne. She also serves as a speaker or member of a speaker’s bureau for Almirall, Cassiopeia, Cutera, EPI, Galderma, Journey Almirall, L’Oreal, Ortho Dermatologics, Sun Pharmaceutical Industries, and Vyne.
Medscape and this news organization are owned by the same parent company.
AT THE MEDSCAPELIVE! HAWAII DERMATOLOGY SEMINAR
Bridging the Digital Divide in Teledermatology Usage: A Retrospective Review of Patient Visits
Teledermatology is an effective patient care model for the delivery of high-quality dermatologic care.1 Teledermatology can occur using synchronous, asynchronous, and hybrid models of care. In asynchronous visits (AVs), patients or health professionals submit photographs and information for dermatologists to review and provide treatment recommendations. With synchronous visits (SVs), patients have a visit with a dermatology health professional in real time via live video conferencing software. Hybrid models incorporate asynchronous strategies for patient intake forms and skin photograph submissions as well as synchronous methods for live video consultation in a single visit.1 However, remarkable inequities in internet access limit telemedicine usage among medically marginalized patient populations, including racialized, elderly, and low socioeconomic status groups.2
Synchronous visits, a relatively newer teledermatology format, allow for communication with dermatology professionals from the convenience of a patient’s selected location. The live interaction of SVs allows dermatology professionals to answer questions, provide treatment recommendations, and build therapeutic relationships with patients. Concerns for dermatologist reimbursement, malpractice/liability, and technological challenges stalled large-scale uptake of teledermatology platforms.3 The COVID-19 pandemic led to a drastic increase in teledermatology usage of approximately 587.2%, largely due to public safety measures and Medicaid reimbursement parity between SV and in-office visits (IVs).3,4
With the implementation of SVs as a patient care model, we investigated the demographics of patients who utilized SVs, AVs, or IVs, and we propose strategies to promote equity in dermatologic care access.
Methods
This study was approved by the University of Pittsburgh institutional review board (STUDY20110043). We performed a retrospective electronic medical record review of deidentified data from the University of Pittsburgh Medical Center, a tertiary care center in Allegheny County, Pennsylvania, with an established asynchronous teledermatology program. Hybrid SVs were integrated into the University of Pittsburgh Medical Center patient care visit options in March 2020. Patients were instructed to upload photographs of their skin conditions prior to SV appointments. The study included visits occurring between July and December 2020. Visit types included SVs, AVs, and IVs.
We analyzed the initial dermatology visits of 17,130 patients aged 17.5 years and older. Recorded data included diagnosis, age, sex, race, ethnicity, and insurance type for each visit type. Patients without a reported race (990 patients) or ethnicity (1712 patients) were excluded from analysis of race/ethnicity data. Patient zip codes were compared with the zip codes of Allegheny County municipalities as reported by the Allegheny County Elections Division.
Statistical Analysis—Descriptive statistics were calculated; frequency with percentage was used to report categorical variables, and the mean (SD) was used for normally distributed continuous variables. Univariate analysis was performed using the χ2 test for categorical variables. One-way analysis of variance was used to compare age among visit types. Statistical significance was defined as P<.05. IBM SPSS Statistics for Windows, Version 24 (IBM Corp) was used for all statistical analyses.
Results
In our study population, 81.2% (13,916) of patients were residents of Allegheny County, where 51.6% of residents are female and 81.4% are older than 18 years according to data from 2020.5 The racial and ethnic demographics of Allegheny County were 13.4% African American/Black, 0.2% American Indian/Alaska Native, 4.2% Asian, 2.3% Hispanic/Latino, and 79.6% White. The percentage of residents who identified as Native Hawaiian/Pacific Islander was reported to be greater than 0% but less than 0.5%.5
In our analysis, IVs were the most utilized visit type, accounting for 71.5% (12,240) of visits, followed by 15.0% (2577) for SVs and 13.5% (2313) for AVs. The mean age (SD) of IV patients was 51.0 (18.8) years compared with 39.9 (16.9) years for SV patients and 37.5 (14.3) years for AV patients (eTable). The majority of patients for all visits were female: 62.1% (7599) for IVs, 71.4% (1652) for AVs, and 72.8% (1877) for SVs. The largest racial or ethnic group for all visit types included White patients (83.8% [13,524] of all patients), followed by Black (12.4% [2007]), Hispanic/Latino (1.4% [209]), Asian (3.4% [555]), American Indian/Alaska Native (0.2% [35]), and Native Hawaiian/Other Pacific Islander patients (0.1% [19]).
Asian patients, who comprised 4.2% of Allegheny County residents,5 accounted for 2.7% (334) of IVs, 4.9% (113) of AVs, and 4.2% (108) of SVs. Black patients, who were reported as 13.4% of the Allegheny County population,5 were more likely to utilize SVs (19% [490])compared with AVs (7.5% [174]) and IVs (11% [1343]). Hispanic/Latino patients had a disproportionally lower utilization of dermatologic care in all settings, comprising 1.4% (209) of all patients in our study compared with 2.3% of Allegheny County residents.5 White patients, who comprised 79.6% of Allegheny County residents, accounted for 81.1% (9928) of IVs, 67.4% (1737) of SVs, and 80.4% (1859) of AVs. There was no significant difference in the percentage of American Indian/Alaska Native and Native Hawaiian/Other Pacific Islander patients among visit types.
The 3 most common diagnoses for IVs were skin cancer screening, seborrheic keratosis, and melanocytic nevus (Table 1). Skin cancer screening was the most common diagnosis, accounting for 12.2% (8530) of 69,812 IVs. The 3 most common diagnoses for SVs were acne vulgaris, dermatitis, and psoriasis. The 3 most common diagnoses for AVs were acne vulgaris, dermatitis, and perioral dermatitis.
Private insurance was the most common insurance type among all patients (71.4% [12,224])(Table 2). A higher percentage of patients with Medicaid insurance (17.9% [461]) utilized SVs compared with AVs (10.1% [233]) and IVs (11.3% 1385]). Similarly, a higher percentage of patients with no insurance or no insurance listed were seen via SVs (12.5% [322]) compared with AVs (5.1% [117]) and IVs (1.7% [203]). Patients with Medicare insurance used IVs (15.4% [1886]) more than SVs (6.0% [155]) or AVs (2.6% [60]). There was no significant difference among visit type usage for patients with public insurance.
Comment
Teledermatology Benefits—In this retrospective review of medical records of patients who obtained dermatologic care after the implementation of SVs at our institution, we found a proportionally higher use of SVs among Black patients, patients with Medicaid, and patients who are underinsured. Benefits of teledermatology include decreases in patient transportation and associated costs, time away from work or home, and need for childcare.6 The SV format provides the additional advantage of direct live interaction and the development of a patient-physician or patient–physician assistant relationship. Although the prerequisite technology, internet, and broadband connectivity preclude use of teledermatology for many vulnerable patients,2 its convenience ultimately may reduce inequities in access.
Disparities in Dermatologic Care—Hispanic ethnicity and male sex are among described patient demographics associated with decreased rates of outpatient dermatologic care.7 We reported disparities in dermatologic care utilization across all visit types among Hispanic patients and males. Patients identifying as Hispanic/Latino composed only 1.4% (n=209) of our study population compared with 2.3% of Allegheny County residents.5 During our study period, most patients seen were female, accounting for 62.1% to 72.8% of visits, compared with 51.6% of Allegheny County residents.5 These disparities in dermatologic care use may have implications for increased skin-associated morbidity and provide impetus for dermatologists to increase engagement with these patient groups.
Characteristics of Patients Using Teledermatology—Patients using SVs and AVs were significantly younger (mean age [SD], 39.9 [16.9] years and 37.5 [14.3] years, respectively) compared with those using IVs (51.0 [18.8] years). This finding reflects known digital knowledge barriers among older patients.8,9 The synchronous communication format of SVs simulates the traditional visit style of IVs, which may be preferable for some patients. Continued patient education and advocacy for broadband access may increase teledermatology use among older patients and patients with limited technology resources.8
Teledermatology visits were used most frequently for acne and dermatitis, while IVs were used for skin cancer screenings and examination of concerning lesions. This usage pattern is consistent with a previously described consensus among dermatologists on the conditions most amenable to teledermatology evaluation.3
Medicaid reimbursement parity for SVs is in effect nationally until the end of the COVID-19 public health emergency declaration in the United States.10 As of February 2023, the public health emergency declaration has been renewed 12 times since January 2020, with the most recent renewal on January 11, 2023.11 As of January 2023, 21 states have enacted legislation providing permanent reimbursement parity for SV services. Six additional states have some payment parity in place, each with its own qualifying criteria, and 23 states have no payment parity.12 Only 25 Medicaid programs currently provide reimbursement for AV services.13
Study Limitations—Our study was limited by lack of data on patients who are multiracial and those who identify as nonbinary and transgender. Because of the low numbers of Hispanic patients associated with each race category and a high number of patients who did not report an ethnicity or race, race and ethnicity data were analyzed separately. For SVs, patients were instructed to upload photographs prior to their visit; however, the percentage of patients who uploaded photographs was not analyzed.
Conclusion
Expansion of teledermatology services, including SVs and AVs, patient outreach and education, advocacy for broadband access, and Medicaid payment parity, may improve dermatologic care access for medically marginalized groups. Teledermatology has the potential to serve as an effective health care option for patients who are racially minoritized, older, and underinsured. To further assess the effectiveness of teledermatology, we plan to analyze the number of SVs and AVs that were referred to IVs. Future studies also will investigate the impact of implementing patient education and patient-reported outcomes of teledermatology visits.
- Lee JJ, English JC. Teledermatology: a review and update. Am J Clin Dermatol. 2018;19:253-260.
- Bakhtiar M, Elbuluk N, Lipoff JB. The digital divide: how COVID-19’s telemedicine expansion could exacerbate disparities. J Am Acad Dermatol. 2020;83:E345-E346.
- Kennedy J, Arey S, Hopkins Z, et al. dermatologist perceptions of teledermatology implementation and future use after COVID-19: demographics, barriers, and insights. JAMA Dermatol. 2021;157:595-597.
- Centers for Disease Control and Prevention. Using telehealth to expand access to essential health services during the COVID-19 pandemic. Updated June 10, 2020. Accessed February 10, 2023. https://www.cdc.gov/coronavirus/2019-ncov/hcp/telehealth.html
- United States Census Bureau. QuickFacts: Allegheny County, Pennsylvania. Accessed August 12, 2021. https://www.census.gov/quickfacts/alleghenycountypennsylvania
- Moore HW. Teledermatology—access to specialized care via a different model. Dermatology Advisor. November 12, 2019. Accessed February 10, 2023. https://www.dermatologyadvisor.com/home/topics/practice-management/teledermatology-access-to-specialized-care-via-a-different-model/
- Tripathi R, Knusel KD, Ezaldein HH, et al. Association of demographic and socioeconomic characteristics with differences in use of outpatient dermatology services in the United States. JAMA Dermatol. 2018;154:1286-1291.
- Nouri S, Khoong EC, Lyles CR, et al. Addressing equity in telemedicine for chronic disease management during the COVID-19 pandemic [published online May 4, 2020]. NEJM Catal Innov Care Deliv. doi:10.1056/CAT.20.0123
- Swenson K, Ghertner R. People in low-income households have less access to internet services—2019 update. Office of the Assistant Secretary for Planning and Evaluation; US Department of Health and Human Services. March 2021. Accessed February 10, 2023. https://aspe.hhs.gov/sites/default/files/private/pdf/263601/internet-access-among-low-income-2019.pdf
- Centers for Medicare and Medicaid Services. COVID-19 frequently asked questions (FAQs) on Medicare fee-for-service (FFS) billing. Updated August 16, 2022. Accessed February 10, 2023. https://www.cms.gov/files/document/03092020-covid-19-faqs-508.pdf
- US Department of Health and Human Services. Renewal of determination that a public health emergency exists. Updated February 9, 2023. Accessed February 20, 2023. https://aspr.hhs.gov/legal/PHE/Pages/COVID19-9Feb2023.aspx?
- Augenstein J, Smith JM. Executive summary: tracking telehealth changes state-by-state in response to COVID-19. Updated January 27, 2023. Accessed February 10, 2023. https://www.manatt.com/insights/newsletters/covid-19-update/executive-summary-tracking-telehealth-changes-stat
- Center for Connected Health Policy. Policy trend maps: store and forward Medicaid reimbursement. Accessed June 23, 2022. https://www.cchpca.org/policy-trends/
Teledermatology is an effective patient care model for the delivery of high-quality dermatologic care.1 Teledermatology can occur using synchronous, asynchronous, and hybrid models of care. In asynchronous visits (AVs), patients or health professionals submit photographs and information for dermatologists to review and provide treatment recommendations. With synchronous visits (SVs), patients have a visit with a dermatology health professional in real time via live video conferencing software. Hybrid models incorporate asynchronous strategies for patient intake forms and skin photograph submissions as well as synchronous methods for live video consultation in a single visit.1 However, remarkable inequities in internet access limit telemedicine usage among medically marginalized patient populations, including racialized, elderly, and low socioeconomic status groups.2
Synchronous visits, a relatively newer teledermatology format, allow for communication with dermatology professionals from the convenience of a patient’s selected location. The live interaction of SVs allows dermatology professionals to answer questions, provide treatment recommendations, and build therapeutic relationships with patients. Concerns for dermatologist reimbursement, malpractice/liability, and technological challenges stalled large-scale uptake of teledermatology platforms.3 The COVID-19 pandemic led to a drastic increase in teledermatology usage of approximately 587.2%, largely due to public safety measures and Medicaid reimbursement parity between SV and in-office visits (IVs).3,4
With the implementation of SVs as a patient care model, we investigated the demographics of patients who utilized SVs, AVs, or IVs, and we propose strategies to promote equity in dermatologic care access.
Methods
This study was approved by the University of Pittsburgh institutional review board (STUDY20110043). We performed a retrospective electronic medical record review of deidentified data from the University of Pittsburgh Medical Center, a tertiary care center in Allegheny County, Pennsylvania, with an established asynchronous teledermatology program. Hybrid SVs were integrated into the University of Pittsburgh Medical Center patient care visit options in March 2020. Patients were instructed to upload photographs of their skin conditions prior to SV appointments. The study included visits occurring between July and December 2020. Visit types included SVs, AVs, and IVs.
We analyzed the initial dermatology visits of 17,130 patients aged 17.5 years and older. Recorded data included diagnosis, age, sex, race, ethnicity, and insurance type for each visit type. Patients without a reported race (990 patients) or ethnicity (1712 patients) were excluded from analysis of race/ethnicity data. Patient zip codes were compared with the zip codes of Allegheny County municipalities as reported by the Allegheny County Elections Division.
Statistical Analysis—Descriptive statistics were calculated; frequency with percentage was used to report categorical variables, and the mean (SD) was used for normally distributed continuous variables. Univariate analysis was performed using the χ2 test for categorical variables. One-way analysis of variance was used to compare age among visit types. Statistical significance was defined as P<.05. IBM SPSS Statistics for Windows, Version 24 (IBM Corp) was used for all statistical analyses.
Results
In our study population, 81.2% (13,916) of patients were residents of Allegheny County, where 51.6% of residents are female and 81.4% are older than 18 years according to data from 2020.5 The racial and ethnic demographics of Allegheny County were 13.4% African American/Black, 0.2% American Indian/Alaska Native, 4.2% Asian, 2.3% Hispanic/Latino, and 79.6% White. The percentage of residents who identified as Native Hawaiian/Pacific Islander was reported to be greater than 0% but less than 0.5%.5
In our analysis, IVs were the most utilized visit type, accounting for 71.5% (12,240) of visits, followed by 15.0% (2577) for SVs and 13.5% (2313) for AVs. The mean age (SD) of IV patients was 51.0 (18.8) years compared with 39.9 (16.9) years for SV patients and 37.5 (14.3) years for AV patients (eTable). The majority of patients for all visits were female: 62.1% (7599) for IVs, 71.4% (1652) for AVs, and 72.8% (1877) for SVs. The largest racial or ethnic group for all visit types included White patients (83.8% [13,524] of all patients), followed by Black (12.4% [2007]), Hispanic/Latino (1.4% [209]), Asian (3.4% [555]), American Indian/Alaska Native (0.2% [35]), and Native Hawaiian/Other Pacific Islander patients (0.1% [19]).
Asian patients, who comprised 4.2% of Allegheny County residents,5 accounted for 2.7% (334) of IVs, 4.9% (113) of AVs, and 4.2% (108) of SVs. Black patients, who were reported as 13.4% of the Allegheny County population,5 were more likely to utilize SVs (19% [490])compared with AVs (7.5% [174]) and IVs (11% [1343]). Hispanic/Latino patients had a disproportionally lower utilization of dermatologic care in all settings, comprising 1.4% (209) of all patients in our study compared with 2.3% of Allegheny County residents.5 White patients, who comprised 79.6% of Allegheny County residents, accounted for 81.1% (9928) of IVs, 67.4% (1737) of SVs, and 80.4% (1859) of AVs. There was no significant difference in the percentage of American Indian/Alaska Native and Native Hawaiian/Other Pacific Islander patients among visit types.
The 3 most common diagnoses for IVs were skin cancer screening, seborrheic keratosis, and melanocytic nevus (Table 1). Skin cancer screening was the most common diagnosis, accounting for 12.2% (8530) of 69,812 IVs. The 3 most common diagnoses for SVs were acne vulgaris, dermatitis, and psoriasis. The 3 most common diagnoses for AVs were acne vulgaris, dermatitis, and perioral dermatitis.
Private insurance was the most common insurance type among all patients (71.4% [12,224])(Table 2). A higher percentage of patients with Medicaid insurance (17.9% [461]) utilized SVs compared with AVs (10.1% [233]) and IVs (11.3% 1385]). Similarly, a higher percentage of patients with no insurance or no insurance listed were seen via SVs (12.5% [322]) compared with AVs (5.1% [117]) and IVs (1.7% [203]). Patients with Medicare insurance used IVs (15.4% [1886]) more than SVs (6.0% [155]) or AVs (2.6% [60]). There was no significant difference among visit type usage for patients with public insurance.
Comment
Teledermatology Benefits—In this retrospective review of medical records of patients who obtained dermatologic care after the implementation of SVs at our institution, we found a proportionally higher use of SVs among Black patients, patients with Medicaid, and patients who are underinsured. Benefits of teledermatology include decreases in patient transportation and associated costs, time away from work or home, and need for childcare.6 The SV format provides the additional advantage of direct live interaction and the development of a patient-physician or patient–physician assistant relationship. Although the prerequisite technology, internet, and broadband connectivity preclude use of teledermatology for many vulnerable patients,2 its convenience ultimately may reduce inequities in access.
Disparities in Dermatologic Care—Hispanic ethnicity and male sex are among described patient demographics associated with decreased rates of outpatient dermatologic care.7 We reported disparities in dermatologic care utilization across all visit types among Hispanic patients and males. Patients identifying as Hispanic/Latino composed only 1.4% (n=209) of our study population compared with 2.3% of Allegheny County residents.5 During our study period, most patients seen were female, accounting for 62.1% to 72.8% of visits, compared with 51.6% of Allegheny County residents.5 These disparities in dermatologic care use may have implications for increased skin-associated morbidity and provide impetus for dermatologists to increase engagement with these patient groups.
Characteristics of Patients Using Teledermatology—Patients using SVs and AVs were significantly younger (mean age [SD], 39.9 [16.9] years and 37.5 [14.3] years, respectively) compared with those using IVs (51.0 [18.8] years). This finding reflects known digital knowledge barriers among older patients.8,9 The synchronous communication format of SVs simulates the traditional visit style of IVs, which may be preferable for some patients. Continued patient education and advocacy for broadband access may increase teledermatology use among older patients and patients with limited technology resources.8
Teledermatology visits were used most frequently for acne and dermatitis, while IVs were used for skin cancer screenings and examination of concerning lesions. This usage pattern is consistent with a previously described consensus among dermatologists on the conditions most amenable to teledermatology evaluation.3
Medicaid reimbursement parity for SVs is in effect nationally until the end of the COVID-19 public health emergency declaration in the United States.10 As of February 2023, the public health emergency declaration has been renewed 12 times since January 2020, with the most recent renewal on January 11, 2023.11 As of January 2023, 21 states have enacted legislation providing permanent reimbursement parity for SV services. Six additional states have some payment parity in place, each with its own qualifying criteria, and 23 states have no payment parity.12 Only 25 Medicaid programs currently provide reimbursement for AV services.13
Study Limitations—Our study was limited by lack of data on patients who are multiracial and those who identify as nonbinary and transgender. Because of the low numbers of Hispanic patients associated with each race category and a high number of patients who did not report an ethnicity or race, race and ethnicity data were analyzed separately. For SVs, patients were instructed to upload photographs prior to their visit; however, the percentage of patients who uploaded photographs was not analyzed.
Conclusion
Expansion of teledermatology services, including SVs and AVs, patient outreach and education, advocacy for broadband access, and Medicaid payment parity, may improve dermatologic care access for medically marginalized groups. Teledermatology has the potential to serve as an effective health care option for patients who are racially minoritized, older, and underinsured. To further assess the effectiveness of teledermatology, we plan to analyze the number of SVs and AVs that were referred to IVs. Future studies also will investigate the impact of implementing patient education and patient-reported outcomes of teledermatology visits.
Teledermatology is an effective patient care model for the delivery of high-quality dermatologic care.1 Teledermatology can occur using synchronous, asynchronous, and hybrid models of care. In asynchronous visits (AVs), patients or health professionals submit photographs and information for dermatologists to review and provide treatment recommendations. With synchronous visits (SVs), patients have a visit with a dermatology health professional in real time via live video conferencing software. Hybrid models incorporate asynchronous strategies for patient intake forms and skin photograph submissions as well as synchronous methods for live video consultation in a single visit.1 However, remarkable inequities in internet access limit telemedicine usage among medically marginalized patient populations, including racialized, elderly, and low socioeconomic status groups.2
Synchronous visits, a relatively newer teledermatology format, allow for communication with dermatology professionals from the convenience of a patient’s selected location. The live interaction of SVs allows dermatology professionals to answer questions, provide treatment recommendations, and build therapeutic relationships with patients. Concerns for dermatologist reimbursement, malpractice/liability, and technological challenges stalled large-scale uptake of teledermatology platforms.3 The COVID-19 pandemic led to a drastic increase in teledermatology usage of approximately 587.2%, largely due to public safety measures and Medicaid reimbursement parity between SV and in-office visits (IVs).3,4
With the implementation of SVs as a patient care model, we investigated the demographics of patients who utilized SVs, AVs, or IVs, and we propose strategies to promote equity in dermatologic care access.
Methods
This study was approved by the University of Pittsburgh institutional review board (STUDY20110043). We performed a retrospective electronic medical record review of deidentified data from the University of Pittsburgh Medical Center, a tertiary care center in Allegheny County, Pennsylvania, with an established asynchronous teledermatology program. Hybrid SVs were integrated into the University of Pittsburgh Medical Center patient care visit options in March 2020. Patients were instructed to upload photographs of their skin conditions prior to SV appointments. The study included visits occurring between July and December 2020. Visit types included SVs, AVs, and IVs.
We analyzed the initial dermatology visits of 17,130 patients aged 17.5 years and older. Recorded data included diagnosis, age, sex, race, ethnicity, and insurance type for each visit type. Patients without a reported race (990 patients) or ethnicity (1712 patients) were excluded from analysis of race/ethnicity data. Patient zip codes were compared with the zip codes of Allegheny County municipalities as reported by the Allegheny County Elections Division.
Statistical Analysis—Descriptive statistics were calculated; frequency with percentage was used to report categorical variables, and the mean (SD) was used for normally distributed continuous variables. Univariate analysis was performed using the χ2 test for categorical variables. One-way analysis of variance was used to compare age among visit types. Statistical significance was defined as P<.05. IBM SPSS Statistics for Windows, Version 24 (IBM Corp) was used for all statistical analyses.
Results
In our study population, 81.2% (13,916) of patients were residents of Allegheny County, where 51.6% of residents are female and 81.4% are older than 18 years according to data from 2020.5 The racial and ethnic demographics of Allegheny County were 13.4% African American/Black, 0.2% American Indian/Alaska Native, 4.2% Asian, 2.3% Hispanic/Latino, and 79.6% White. The percentage of residents who identified as Native Hawaiian/Pacific Islander was reported to be greater than 0% but less than 0.5%.5
In our analysis, IVs were the most utilized visit type, accounting for 71.5% (12,240) of visits, followed by 15.0% (2577) for SVs and 13.5% (2313) for AVs. The mean age (SD) of IV patients was 51.0 (18.8) years compared with 39.9 (16.9) years for SV patients and 37.5 (14.3) years for AV patients (eTable). The majority of patients for all visits were female: 62.1% (7599) for IVs, 71.4% (1652) for AVs, and 72.8% (1877) for SVs. The largest racial or ethnic group for all visit types included White patients (83.8% [13,524] of all patients), followed by Black (12.4% [2007]), Hispanic/Latino (1.4% [209]), Asian (3.4% [555]), American Indian/Alaska Native (0.2% [35]), and Native Hawaiian/Other Pacific Islander patients (0.1% [19]).
Asian patients, who comprised 4.2% of Allegheny County residents,5 accounted for 2.7% (334) of IVs, 4.9% (113) of AVs, and 4.2% (108) of SVs. Black patients, who were reported as 13.4% of the Allegheny County population,5 were more likely to utilize SVs (19% [490])compared with AVs (7.5% [174]) and IVs (11% [1343]). Hispanic/Latino patients had a disproportionally lower utilization of dermatologic care in all settings, comprising 1.4% (209) of all patients in our study compared with 2.3% of Allegheny County residents.5 White patients, who comprised 79.6% of Allegheny County residents, accounted for 81.1% (9928) of IVs, 67.4% (1737) of SVs, and 80.4% (1859) of AVs. There was no significant difference in the percentage of American Indian/Alaska Native and Native Hawaiian/Other Pacific Islander patients among visit types.
The 3 most common diagnoses for IVs were skin cancer screening, seborrheic keratosis, and melanocytic nevus (Table 1). Skin cancer screening was the most common diagnosis, accounting for 12.2% (8530) of 69,812 IVs. The 3 most common diagnoses for SVs were acne vulgaris, dermatitis, and psoriasis. The 3 most common diagnoses for AVs were acne vulgaris, dermatitis, and perioral dermatitis.
Private insurance was the most common insurance type among all patients (71.4% [12,224])(Table 2). A higher percentage of patients with Medicaid insurance (17.9% [461]) utilized SVs compared with AVs (10.1% [233]) and IVs (11.3% 1385]). Similarly, a higher percentage of patients with no insurance or no insurance listed were seen via SVs (12.5% [322]) compared with AVs (5.1% [117]) and IVs (1.7% [203]). Patients with Medicare insurance used IVs (15.4% [1886]) more than SVs (6.0% [155]) or AVs (2.6% [60]). There was no significant difference among visit type usage for patients with public insurance.
Comment
Teledermatology Benefits—In this retrospective review of medical records of patients who obtained dermatologic care after the implementation of SVs at our institution, we found a proportionally higher use of SVs among Black patients, patients with Medicaid, and patients who are underinsured. Benefits of teledermatology include decreases in patient transportation and associated costs, time away from work or home, and need for childcare.6 The SV format provides the additional advantage of direct live interaction and the development of a patient-physician or patient–physician assistant relationship. Although the prerequisite technology, internet, and broadband connectivity preclude use of teledermatology for many vulnerable patients,2 its convenience ultimately may reduce inequities in access.
Disparities in Dermatologic Care—Hispanic ethnicity and male sex are among described patient demographics associated with decreased rates of outpatient dermatologic care.7 We reported disparities in dermatologic care utilization across all visit types among Hispanic patients and males. Patients identifying as Hispanic/Latino composed only 1.4% (n=209) of our study population compared with 2.3% of Allegheny County residents.5 During our study period, most patients seen were female, accounting for 62.1% to 72.8% of visits, compared with 51.6% of Allegheny County residents.5 These disparities in dermatologic care use may have implications for increased skin-associated morbidity and provide impetus for dermatologists to increase engagement with these patient groups.
Characteristics of Patients Using Teledermatology—Patients using SVs and AVs were significantly younger (mean age [SD], 39.9 [16.9] years and 37.5 [14.3] years, respectively) compared with those using IVs (51.0 [18.8] years). This finding reflects known digital knowledge barriers among older patients.8,9 The synchronous communication format of SVs simulates the traditional visit style of IVs, which may be preferable for some patients. Continued patient education and advocacy for broadband access may increase teledermatology use among older patients and patients with limited technology resources.8
Teledermatology visits were used most frequently for acne and dermatitis, while IVs were used for skin cancer screenings and examination of concerning lesions. This usage pattern is consistent with a previously described consensus among dermatologists on the conditions most amenable to teledermatology evaluation.3
Medicaid reimbursement parity for SVs is in effect nationally until the end of the COVID-19 public health emergency declaration in the United States.10 As of February 2023, the public health emergency declaration has been renewed 12 times since January 2020, with the most recent renewal on January 11, 2023.11 As of January 2023, 21 states have enacted legislation providing permanent reimbursement parity for SV services. Six additional states have some payment parity in place, each with its own qualifying criteria, and 23 states have no payment parity.12 Only 25 Medicaid programs currently provide reimbursement for AV services.13
Study Limitations—Our study was limited by lack of data on patients who are multiracial and those who identify as nonbinary and transgender. Because of the low numbers of Hispanic patients associated with each race category and a high number of patients who did not report an ethnicity or race, race and ethnicity data were analyzed separately. For SVs, patients were instructed to upload photographs prior to their visit; however, the percentage of patients who uploaded photographs was not analyzed.
Conclusion
Expansion of teledermatology services, including SVs and AVs, patient outreach and education, advocacy for broadband access, and Medicaid payment parity, may improve dermatologic care access for medically marginalized groups. Teledermatology has the potential to serve as an effective health care option for patients who are racially minoritized, older, and underinsured. To further assess the effectiveness of teledermatology, we plan to analyze the number of SVs and AVs that were referred to IVs. Future studies also will investigate the impact of implementing patient education and patient-reported outcomes of teledermatology visits.
- Lee JJ, English JC. Teledermatology: a review and update. Am J Clin Dermatol. 2018;19:253-260.
- Bakhtiar M, Elbuluk N, Lipoff JB. The digital divide: how COVID-19’s telemedicine expansion could exacerbate disparities. J Am Acad Dermatol. 2020;83:E345-E346.
- Kennedy J, Arey S, Hopkins Z, et al. dermatologist perceptions of teledermatology implementation and future use after COVID-19: demographics, barriers, and insights. JAMA Dermatol. 2021;157:595-597.
- Centers for Disease Control and Prevention. Using telehealth to expand access to essential health services during the COVID-19 pandemic. Updated June 10, 2020. Accessed February 10, 2023. https://www.cdc.gov/coronavirus/2019-ncov/hcp/telehealth.html
- United States Census Bureau. QuickFacts: Allegheny County, Pennsylvania. Accessed August 12, 2021. https://www.census.gov/quickfacts/alleghenycountypennsylvania
- Moore HW. Teledermatology—access to specialized care via a different model. Dermatology Advisor. November 12, 2019. Accessed February 10, 2023. https://www.dermatologyadvisor.com/home/topics/practice-management/teledermatology-access-to-specialized-care-via-a-different-model/
- Tripathi R, Knusel KD, Ezaldein HH, et al. Association of demographic and socioeconomic characteristics with differences in use of outpatient dermatology services in the United States. JAMA Dermatol. 2018;154:1286-1291.
- Nouri S, Khoong EC, Lyles CR, et al. Addressing equity in telemedicine for chronic disease management during the COVID-19 pandemic [published online May 4, 2020]. NEJM Catal Innov Care Deliv. doi:10.1056/CAT.20.0123
- Swenson K, Ghertner R. People in low-income households have less access to internet services—2019 update. Office of the Assistant Secretary for Planning and Evaluation; US Department of Health and Human Services. March 2021. Accessed February 10, 2023. https://aspe.hhs.gov/sites/default/files/private/pdf/263601/internet-access-among-low-income-2019.pdf
- Centers for Medicare and Medicaid Services. COVID-19 frequently asked questions (FAQs) on Medicare fee-for-service (FFS) billing. Updated August 16, 2022. Accessed February 10, 2023. https://www.cms.gov/files/document/03092020-covid-19-faqs-508.pdf
- US Department of Health and Human Services. Renewal of determination that a public health emergency exists. Updated February 9, 2023. Accessed February 20, 2023. https://aspr.hhs.gov/legal/PHE/Pages/COVID19-9Feb2023.aspx?
- Augenstein J, Smith JM. Executive summary: tracking telehealth changes state-by-state in response to COVID-19. Updated January 27, 2023. Accessed February 10, 2023. https://www.manatt.com/insights/newsletters/covid-19-update/executive-summary-tracking-telehealth-changes-stat
- Center for Connected Health Policy. Policy trend maps: store and forward Medicaid reimbursement. Accessed June 23, 2022. https://www.cchpca.org/policy-trends/
- Lee JJ, English JC. Teledermatology: a review and update. Am J Clin Dermatol. 2018;19:253-260.
- Bakhtiar M, Elbuluk N, Lipoff JB. The digital divide: how COVID-19’s telemedicine expansion could exacerbate disparities. J Am Acad Dermatol. 2020;83:E345-E346.
- Kennedy J, Arey S, Hopkins Z, et al. dermatologist perceptions of teledermatology implementation and future use after COVID-19: demographics, barriers, and insights. JAMA Dermatol. 2021;157:595-597.
- Centers for Disease Control and Prevention. Using telehealth to expand access to essential health services during the COVID-19 pandemic. Updated June 10, 2020. Accessed February 10, 2023. https://www.cdc.gov/coronavirus/2019-ncov/hcp/telehealth.html
- United States Census Bureau. QuickFacts: Allegheny County, Pennsylvania. Accessed August 12, 2021. https://www.census.gov/quickfacts/alleghenycountypennsylvania
- Moore HW. Teledermatology—access to specialized care via a different model. Dermatology Advisor. November 12, 2019. Accessed February 10, 2023. https://www.dermatologyadvisor.com/home/topics/practice-management/teledermatology-access-to-specialized-care-via-a-different-model/
- Tripathi R, Knusel KD, Ezaldein HH, et al. Association of demographic and socioeconomic characteristics with differences in use of outpatient dermatology services in the United States. JAMA Dermatol. 2018;154:1286-1291.
- Nouri S, Khoong EC, Lyles CR, et al. Addressing equity in telemedicine for chronic disease management during the COVID-19 pandemic [published online May 4, 2020]. NEJM Catal Innov Care Deliv. doi:10.1056/CAT.20.0123
- Swenson K, Ghertner R. People in low-income households have less access to internet services—2019 update. Office of the Assistant Secretary for Planning and Evaluation; US Department of Health and Human Services. March 2021. Accessed February 10, 2023. https://aspe.hhs.gov/sites/default/files/private/pdf/263601/internet-access-among-low-income-2019.pdf
- Centers for Medicare and Medicaid Services. COVID-19 frequently asked questions (FAQs) on Medicare fee-for-service (FFS) billing. Updated August 16, 2022. Accessed February 10, 2023. https://www.cms.gov/files/document/03092020-covid-19-faqs-508.pdf
- US Department of Health and Human Services. Renewal of determination that a public health emergency exists. Updated February 9, 2023. Accessed February 20, 2023. https://aspr.hhs.gov/legal/PHE/Pages/COVID19-9Feb2023.aspx?
- Augenstein J, Smith JM. Executive summary: tracking telehealth changes state-by-state in response to COVID-19. Updated January 27, 2023. Accessed February 10, 2023. https://www.manatt.com/insights/newsletters/covid-19-update/executive-summary-tracking-telehealth-changes-stat
- Center for Connected Health Policy. Policy trend maps: store and forward Medicaid reimbursement. Accessed June 23, 2022. https://www.cchpca.org/policy-trends/
Practice Points
- There is increased use of synchronous video visits (SVs) among Black patients, patients with Medicaid, and patients who are underinsured.
- Synchronous video visits may increase dermatologic care utilization for medically marginalized groups.
- Efforts are needed to increase engagement with dermatologic care for Hispanic and male patients.
How to manage isotretinoin’s bothersome mucocutaneous side effects
HONOLULU –
“If they don’t have dry lips, you have to wonder if they’re even absorbing isotretinoin,” Dr. Barbieri, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “Everyone is going to get dry lips.”
According to a retrospective review of 1,743 patients started on isotretinoin, other common mucocutaneous side effects include eczema, nose bleeds, and eye problems. Emerging research suggests that there may be a role for oral omega-3 in decreasing such side effects of the drug. In a case control study, 118 patients were randomized to isotretinoin alone or isotretinoin plus 1 g/day of oral omega-3 for 16 weeks. At week 16, the rate of dry lips was 26% in the isoretinoin only group compared with 14% in the combination group; similar trends were seen with dry nose (11% vs. 0 %, respectively) and dry skin (11% vs. 2%).
“Omega-3 is a simple thing that we can think about recommending for patients,” Dr. Barbieri said. “It’s very safe, inexpensive, and it may help us manage these common sides effect we run into.”
Another potential side effect of isotretinoin that he characterized as underappreciated is chronic dry eye and other ocular changes. One retrospective cohort study of 14,682 adolescents and young adults in Israel found that use of the drug resulted in reduced tear production and reduced tear quality. In another study, a review and meta-analysis of 21 publications involving 1,105 eyes of 842 patients, isotretinoin use was associated with increased conjunctival fluorescein staining, decreased corneal thickness, and worse patient-reported ocular surface disease index scores.
“These changes may be mediated by meibomian gland dysfunction and atrophy,” Dr. Barbieri said. “Fortunately, many of these tear film changes appear to resolve after treatment. Those changes in corneal thickness do seem to get better. That’s reassuring.”
In a study of 54 patients treated with isotretinoin, tear production and quality returned to baseline within 6 months of treatment completion. “But some changes in the meibomian gland may be persistent,” Dr. Barbieri said. “At 6 and 12 months after the end of treatment, you can still see changes in the meibomian glands of patients who were treated with a standard course of 120 to 150 mg/kg isotretinoin,” he said, referring to the results of a study of 88 patients .
One study investigated the effects of omega-3 fatty acids and punctal plugs on tear film and ocular surface parameters in 90 patients receiving systemic isotretinoin therapy. They were divided into three groups: Those who received a soft preloaded silicone plug that was inserted in the inferior punctum of both eyes and received oral omega-3 fatty acid capsules twice daily for a total dose of 1,040 mg/day for 6 months; those who received a soft preloaded silicone plug and oral placebo, and those who received isotretinoin alone. At 6 months’ follow-up, those who were treated with omega-3 combined with the preloaded silicone plug had better meibomian gland function than did those who received isotretinoin alone or isotretinoin with the preloaded silicone plug.
Dr. Barbieri also noted that antihistamines may play a role in enhancing the effect of isotretinoin. In one study, 20 patients were treated with isotretinoin 0.4 mg/kg per day and 20 patients were also treated with an antihistamine, desloratadine 5 mg/day for 12 weeks. At week 12, patients in the group treated with isotretinoin and the antihistamine showed a more statistically significant decrease in acne lesion counts, compared with the isotretinoin-only group (reductions of 44.8% vs. 17.8%, respectively, in noninflammatory lesions; 55.8% vs. 22.9% in inflammatory lesions, and 45.6% vs. 18.7% in total lesions (P < .05 for all associations).
A subsequent larger study yielded similar findings. There were also lower rates of initial flaring and higher rates of patient satisfaction in the antihistamine groups in both studies.
In an interview at the meeting, Lawrence F. Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, described Dr. Barbieri as “a leader in taking a comprehensive view on what the history and latest information is on isotretinoin. His fresh approach is something everyone should consider and figure out what they can use in their practice.”
Dr. Barbieri disclosed that he receives consulting fees from Dexcel for work unrelated to his presentation. Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics. Medscape and this news organization are owned by the same parent company.
HONOLULU –
“If they don’t have dry lips, you have to wonder if they’re even absorbing isotretinoin,” Dr. Barbieri, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “Everyone is going to get dry lips.”
According to a retrospective review of 1,743 patients started on isotretinoin, other common mucocutaneous side effects include eczema, nose bleeds, and eye problems. Emerging research suggests that there may be a role for oral omega-3 in decreasing such side effects of the drug. In a case control study, 118 patients were randomized to isotretinoin alone or isotretinoin plus 1 g/day of oral omega-3 for 16 weeks. At week 16, the rate of dry lips was 26% in the isoretinoin only group compared with 14% in the combination group; similar trends were seen with dry nose (11% vs. 0 %, respectively) and dry skin (11% vs. 2%).
“Omega-3 is a simple thing that we can think about recommending for patients,” Dr. Barbieri said. “It’s very safe, inexpensive, and it may help us manage these common sides effect we run into.”
Another potential side effect of isotretinoin that he characterized as underappreciated is chronic dry eye and other ocular changes. One retrospective cohort study of 14,682 adolescents and young adults in Israel found that use of the drug resulted in reduced tear production and reduced tear quality. In another study, a review and meta-analysis of 21 publications involving 1,105 eyes of 842 patients, isotretinoin use was associated with increased conjunctival fluorescein staining, decreased corneal thickness, and worse patient-reported ocular surface disease index scores.
“These changes may be mediated by meibomian gland dysfunction and atrophy,” Dr. Barbieri said. “Fortunately, many of these tear film changes appear to resolve after treatment. Those changes in corneal thickness do seem to get better. That’s reassuring.”
In a study of 54 patients treated with isotretinoin, tear production and quality returned to baseline within 6 months of treatment completion. “But some changes in the meibomian gland may be persistent,” Dr. Barbieri said. “At 6 and 12 months after the end of treatment, you can still see changes in the meibomian glands of patients who were treated with a standard course of 120 to 150 mg/kg isotretinoin,” he said, referring to the results of a study of 88 patients .
One study investigated the effects of omega-3 fatty acids and punctal plugs on tear film and ocular surface parameters in 90 patients receiving systemic isotretinoin therapy. They were divided into three groups: Those who received a soft preloaded silicone plug that was inserted in the inferior punctum of both eyes and received oral omega-3 fatty acid capsules twice daily for a total dose of 1,040 mg/day for 6 months; those who received a soft preloaded silicone plug and oral placebo, and those who received isotretinoin alone. At 6 months’ follow-up, those who were treated with omega-3 combined with the preloaded silicone plug had better meibomian gland function than did those who received isotretinoin alone or isotretinoin with the preloaded silicone plug.
Dr. Barbieri also noted that antihistamines may play a role in enhancing the effect of isotretinoin. In one study, 20 patients were treated with isotretinoin 0.4 mg/kg per day and 20 patients were also treated with an antihistamine, desloratadine 5 mg/day for 12 weeks. At week 12, patients in the group treated with isotretinoin and the antihistamine showed a more statistically significant decrease in acne lesion counts, compared with the isotretinoin-only group (reductions of 44.8% vs. 17.8%, respectively, in noninflammatory lesions; 55.8% vs. 22.9% in inflammatory lesions, and 45.6% vs. 18.7% in total lesions (P < .05 for all associations).
A subsequent larger study yielded similar findings. There were also lower rates of initial flaring and higher rates of patient satisfaction in the antihistamine groups in both studies.
In an interview at the meeting, Lawrence F. Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, described Dr. Barbieri as “a leader in taking a comprehensive view on what the history and latest information is on isotretinoin. His fresh approach is something everyone should consider and figure out what they can use in their practice.”
Dr. Barbieri disclosed that he receives consulting fees from Dexcel for work unrelated to his presentation. Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics. Medscape and this news organization are owned by the same parent company.
HONOLULU –
“If they don’t have dry lips, you have to wonder if they’re even absorbing isotretinoin,” Dr. Barbieri, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “Everyone is going to get dry lips.”
According to a retrospective review of 1,743 patients started on isotretinoin, other common mucocutaneous side effects include eczema, nose bleeds, and eye problems. Emerging research suggests that there may be a role for oral omega-3 in decreasing such side effects of the drug. In a case control study, 118 patients were randomized to isotretinoin alone or isotretinoin plus 1 g/day of oral omega-3 for 16 weeks. At week 16, the rate of dry lips was 26% in the isoretinoin only group compared with 14% in the combination group; similar trends were seen with dry nose (11% vs. 0 %, respectively) and dry skin (11% vs. 2%).
“Omega-3 is a simple thing that we can think about recommending for patients,” Dr. Barbieri said. “It’s very safe, inexpensive, and it may help us manage these common sides effect we run into.”
Another potential side effect of isotretinoin that he characterized as underappreciated is chronic dry eye and other ocular changes. One retrospective cohort study of 14,682 adolescents and young adults in Israel found that use of the drug resulted in reduced tear production and reduced tear quality. In another study, a review and meta-analysis of 21 publications involving 1,105 eyes of 842 patients, isotretinoin use was associated with increased conjunctival fluorescein staining, decreased corneal thickness, and worse patient-reported ocular surface disease index scores.
“These changes may be mediated by meibomian gland dysfunction and atrophy,” Dr. Barbieri said. “Fortunately, many of these tear film changes appear to resolve after treatment. Those changes in corneal thickness do seem to get better. That’s reassuring.”
In a study of 54 patients treated with isotretinoin, tear production and quality returned to baseline within 6 months of treatment completion. “But some changes in the meibomian gland may be persistent,” Dr. Barbieri said. “At 6 and 12 months after the end of treatment, you can still see changes in the meibomian glands of patients who were treated with a standard course of 120 to 150 mg/kg isotretinoin,” he said, referring to the results of a study of 88 patients .
One study investigated the effects of omega-3 fatty acids and punctal plugs on tear film and ocular surface parameters in 90 patients receiving systemic isotretinoin therapy. They were divided into three groups: Those who received a soft preloaded silicone plug that was inserted in the inferior punctum of both eyes and received oral omega-3 fatty acid capsules twice daily for a total dose of 1,040 mg/day for 6 months; those who received a soft preloaded silicone plug and oral placebo, and those who received isotretinoin alone. At 6 months’ follow-up, those who were treated with omega-3 combined with the preloaded silicone plug had better meibomian gland function than did those who received isotretinoin alone or isotretinoin with the preloaded silicone plug.
Dr. Barbieri also noted that antihistamines may play a role in enhancing the effect of isotretinoin. In one study, 20 patients were treated with isotretinoin 0.4 mg/kg per day and 20 patients were also treated with an antihistamine, desloratadine 5 mg/day for 12 weeks. At week 12, patients in the group treated with isotretinoin and the antihistamine showed a more statistically significant decrease in acne lesion counts, compared with the isotretinoin-only group (reductions of 44.8% vs. 17.8%, respectively, in noninflammatory lesions; 55.8% vs. 22.9% in inflammatory lesions, and 45.6% vs. 18.7% in total lesions (P < .05 for all associations).
A subsequent larger study yielded similar findings. There were also lower rates of initial flaring and higher rates of patient satisfaction in the antihistamine groups in both studies.
In an interview at the meeting, Lawrence F. Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, described Dr. Barbieri as “a leader in taking a comprehensive view on what the history and latest information is on isotretinoin. His fresh approach is something everyone should consider and figure out what they can use in their practice.”
Dr. Barbieri disclosed that he receives consulting fees from Dexcel for work unrelated to his presentation. Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics. Medscape and this news organization are owned by the same parent company.
AT THE MEDSCAPE LIVE! HAWAII DERMATOLOGY SEMINAR
Embattled iPLEDGE program: Changes ahead?
In December 2021, major changes took effect in the iPLEDGE program, the Food and Drug Administration–required safety program for managing the risks of isotretinoin’s teratogenicity and preventing exposure during pregnancy. Now, more modifications may be coming to the acne drug’s safety program.
The risk evaluation and mitigation strategy (REMS) requirements. The aim, according to the FDA meeting announcement, is “to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of isotretinoin oral capsules for patients.”
Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane. Its former brand name was Accutane.
Problems began to surface days after a new, gender-neutral approach to the risk mitigation program was launched on Dec. 13, 2021. That program had been approved earlier by the FDA.
However, the problems that were encountered were a result of glitches in changes in the platform that had been planned, and were not related to the gender-neutral changes. The iPLEDGE program had transitioned to the new platform, and the rollout was far from smooth. Dermatologists, pharmacists, patients, parents of patients, and others were frustrated and angry that they could not access the new platform and obtain the medication promptly. Reaching the help line to sort out problems was another exercise in frustration. Wait times while on hold were unbearably long, or problems were not resolved over the phone.
(The new gender-neutral approach, which advocates said was needed to preserve inclusiveness of their patients, including transgender patients, places potential patients into two categories: those who can become pregnant, and those who cannot. Previously, there were three categories into which patients were classified: females who have reproductive potential, females who do not have reproductive potential, and males.)
Before pharmacists can fill a prescription for isotretinoin, a medical provider must confirm a patient’s negative pregnancy test and inform a patient with reproductive potential of the risks of the medication.
In January 2022, to deal with the chaotic launch and subsequent problems, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve the problems reported by clinicians, pharmacists, and patients.
The American Academy of Dermatology Association formed an iPLEDGE work group to address the issues and suggest solutions. It has made several requests of and suggestions for the IPMG, which manages the program, according to Andrea L. Zaenglein, MD, professor of dermatology and pediatrics at Penn State Hershey (Pa.) Medical Center, and a member of the work group.
“We are asking them to eliminate the monthly attestation for patients who can’t get pregnant and to review and modify restrictive and punitive waiting and lockout periods for all patients,” she told this news organization.
As of February 2023, most of the platform glitches had been smoothed out, Dr. Zaenglein said. Still, “improvements to the design of the website could improve the user interface,” she added.
The FDA has established a docket for the public to submit comments before the meeting. The docket number is FDA-2022-N-3071. The electronic filing system will accept comments until 11:59 p.m. Eastern time on March 27. Background material and a link to the live webcast of the panel meeting will be available to the public no later than 2 days before the meeting and will be posted on the FDA web page or at the time of the meeting.
A version of this article first appeared on Medscape.com.
In December 2021, major changes took effect in the iPLEDGE program, the Food and Drug Administration–required safety program for managing the risks of isotretinoin’s teratogenicity and preventing exposure during pregnancy. Now, more modifications may be coming to the acne drug’s safety program.
The risk evaluation and mitigation strategy (REMS) requirements. The aim, according to the FDA meeting announcement, is “to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of isotretinoin oral capsules for patients.”
Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane. Its former brand name was Accutane.
Problems began to surface days after a new, gender-neutral approach to the risk mitigation program was launched on Dec. 13, 2021. That program had been approved earlier by the FDA.
However, the problems that were encountered were a result of glitches in changes in the platform that had been planned, and were not related to the gender-neutral changes. The iPLEDGE program had transitioned to the new platform, and the rollout was far from smooth. Dermatologists, pharmacists, patients, parents of patients, and others were frustrated and angry that they could not access the new platform and obtain the medication promptly. Reaching the help line to sort out problems was another exercise in frustration. Wait times while on hold were unbearably long, or problems were not resolved over the phone.
(The new gender-neutral approach, which advocates said was needed to preserve inclusiveness of their patients, including transgender patients, places potential patients into two categories: those who can become pregnant, and those who cannot. Previously, there were three categories into which patients were classified: females who have reproductive potential, females who do not have reproductive potential, and males.)
Before pharmacists can fill a prescription for isotretinoin, a medical provider must confirm a patient’s negative pregnancy test and inform a patient with reproductive potential of the risks of the medication.
In January 2022, to deal with the chaotic launch and subsequent problems, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve the problems reported by clinicians, pharmacists, and patients.
The American Academy of Dermatology Association formed an iPLEDGE work group to address the issues and suggest solutions. It has made several requests of and suggestions for the IPMG, which manages the program, according to Andrea L. Zaenglein, MD, professor of dermatology and pediatrics at Penn State Hershey (Pa.) Medical Center, and a member of the work group.
“We are asking them to eliminate the monthly attestation for patients who can’t get pregnant and to review and modify restrictive and punitive waiting and lockout periods for all patients,” she told this news organization.
As of February 2023, most of the platform glitches had been smoothed out, Dr. Zaenglein said. Still, “improvements to the design of the website could improve the user interface,” she added.
The FDA has established a docket for the public to submit comments before the meeting. The docket number is FDA-2022-N-3071. The electronic filing system will accept comments until 11:59 p.m. Eastern time on March 27. Background material and a link to the live webcast of the panel meeting will be available to the public no later than 2 days before the meeting and will be posted on the FDA web page or at the time of the meeting.
A version of this article first appeared on Medscape.com.
In December 2021, major changes took effect in the iPLEDGE program, the Food and Drug Administration–required safety program for managing the risks of isotretinoin’s teratogenicity and preventing exposure during pregnancy. Now, more modifications may be coming to the acne drug’s safety program.
The risk evaluation and mitigation strategy (REMS) requirements. The aim, according to the FDA meeting announcement, is “to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of isotretinoin oral capsules for patients.”
Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane. Its former brand name was Accutane.
Problems began to surface days after a new, gender-neutral approach to the risk mitigation program was launched on Dec. 13, 2021. That program had been approved earlier by the FDA.
However, the problems that were encountered were a result of glitches in changes in the platform that had been planned, and were not related to the gender-neutral changes. The iPLEDGE program had transitioned to the new platform, and the rollout was far from smooth. Dermatologists, pharmacists, patients, parents of patients, and others were frustrated and angry that they could not access the new platform and obtain the medication promptly. Reaching the help line to sort out problems was another exercise in frustration. Wait times while on hold were unbearably long, or problems were not resolved over the phone.
(The new gender-neutral approach, which advocates said was needed to preserve inclusiveness of their patients, including transgender patients, places potential patients into two categories: those who can become pregnant, and those who cannot. Previously, there were three categories into which patients were classified: females who have reproductive potential, females who do not have reproductive potential, and males.)
Before pharmacists can fill a prescription for isotretinoin, a medical provider must confirm a patient’s negative pregnancy test and inform a patient with reproductive potential of the risks of the medication.
In January 2022, to deal with the chaotic launch and subsequent problems, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve the problems reported by clinicians, pharmacists, and patients.
The American Academy of Dermatology Association formed an iPLEDGE work group to address the issues and suggest solutions. It has made several requests of and suggestions for the IPMG, which manages the program, according to Andrea L. Zaenglein, MD, professor of dermatology and pediatrics at Penn State Hershey (Pa.) Medical Center, and a member of the work group.
“We are asking them to eliminate the monthly attestation for patients who can’t get pregnant and to review and modify restrictive and punitive waiting and lockout periods for all patients,” she told this news organization.
As of February 2023, most of the platform glitches had been smoothed out, Dr. Zaenglein said. Still, “improvements to the design of the website could improve the user interface,” she added.
The FDA has established a docket for the public to submit comments before the meeting. The docket number is FDA-2022-N-3071. The electronic filing system will accept comments until 11:59 p.m. Eastern time on March 27. Background material and a link to the live webcast of the panel meeting will be available to the public no later than 2 days before the meeting and will be posted on the FDA web page or at the time of the meeting.
A version of this article first appeared on Medscape.com.
Study documents link between preadolescent acne and elevated BMI
The that used age- and sex-matched controls.
The investigators also identified “a potential association” with precocious puberty that they said “should be considered, especially among those presenting [with acne] under 8 or 9 years old.” The study was published in Pediatric Dermatology .
Senior author Megha M. Tollefson, MD, and coauthors used resources of the Rochester Epidemiology Project to identify all residents of Olmstead County, Minn., who were diagnosed with acne between the ages of 7 and 12 years during 2010-2018. They then randomly selected two age and sex-matched community controls in order to evaluate the relationship of preadolescent acne and BMI.
They confirmed 643 acne cases, and calculated an annual age- and sex-adjusted incidence rate for ages 7-12 of 58 per 10,000 person-years (95% confidence interval, 53.5-62.5). The incidence rate was significantly higher in females than males (89.2 vs. 28.2 per 10,000 person-years; P < .001), and it significantly increased with age (incidence rates of 4.3, 24.4, and 144.3 per 10,000 person-years among those ages 7-8, 9-10, and 11-12 years, respectively).
The median BMI percentile among children with acne was significantly higher than those without an acne diagnosis (75.0 vs. 65.0; P <.001). They also were much more likely to be obese: 16.7% of the children with acne had a BMI in at least the 95th percentile, compared with 12.2% among controls with no acne diagnosis (P = .01). (The qualifying 581 acne cases for this analysis had BMIs recorded within 8 months of the index data, in addition to not having pre-existing acne-relevant endocrine disorders.)
“High BMI is a strong risk factor for acne development and severity in adults, but until now pediatric studies have revealed mixed information ... [and have been] largely retrospective reviews without controls,” Dr. Tollefson, professor of pediatrics and dermatology at the Mayo Clinic, Rochester, Minn., and colleagues wrote.
‘Valuable’ data
Leah Lalor, MD, a pediatric dermatologist not involved with the research, said she is happy to see it. “It’s really valuable,” she said in an interview. “It’s actually the first study that gives us incidence data for preadolescent acne. We all have [had our estimates], but this study quantifies it ... and it will set the stage for further studies of preadolescents in the future.”
The study also documents that “girls are more likely to present to the clinic with acne, and to do so at younger ages, which we’ve suspected and which makes physiologic sense since girls tend to go through puberty earlier than boys,” said Dr. Lalor, assistant professor of dermatology and pediatrics at the Medical College of Wisconsin and the Children’s Wisconsin Clinics, both in Milwaukee. “And most interestingly, it really reveals that BMI is higher among preadolescents with acne than those without.”
The important caveat, she emphasized, is that the study population in Olmstead County, Minn. has a relatively higher level of education, wealth, and employment than the rest of the United States.
The investigators also found that use of systemic acne medications increased with increasing BMI (odds ratio, 1.43 per 5 kg/m2 increase in BMI; 95% CI, 1.07-1.92; P = .015). Approximately 5% of underweight or normal children were prescribed systemic acne medications, compared with 8.1% of overweight children, and 10.3% of those who were obese – data that suggest that most preadolescents with acne had mild to moderate disease and that more severe acne may be associated with increasing BMI percentiles, the authors wrote.
Approximately 4% of the 643 preadolescents with acne were diagnosed with an acne-relevant endocrine disorder prior to or at the time of acne diagnosis – most commonly precocious puberty. Of the 24 diagnoses of precocious puberty, 22 were in females, with a mean age at diagnosis of 7.3 years.
Puberty before age 8 in girls and 9 in boys is classified as precocious puberty. “Thus, a thorough review of systems and exam should be done in this population [with acne] to look for precocious puberty with a low threshold for systemic evaluation if indicated,” the authors wrote, also noting that 19 or the 482 female patients with acne were subsequently diagnosed with polycystic ovary syndrome.
Dr. Lalor said she “automatically” refers children with acne who are younger than 7 for an endocrine workup, but not necessarily children ages 7, 8, or 9 because “that’s considered within the normal realm of starting to get some acne.” Acne in the context of other symptoms such as body odor, hair, or thelarche may prompt referral in these ages, however, she said.
Future research
Obesity may influence preadolescent acne development through its effect on puberty, as overweight and obese girls achieve puberty earlier than those with normal BMI. And “insulin resistance, which may be related to obesity, has been implicated with inducing or worsening acne potentially related to shifts in IGF-1 [insulin-like growth factor 1] signaling and hyperandrogenemia,” Dr. Tollefson and colleagues wrote. Nutrition is also a possible confounder in the study.
“Patients and families have long felt that certain foods or practices contribute to acne, though this has been difficult to prove,” Dr. Lalor said. “We know that excess skim milk seems to contribute ... and there’s a correlation between high glycemic load diets [and acne].”
Assessing dietary habits in conjunction with BMI, and acne incidence and severity, would be valuable. So would research to determine “if decreasing the BMI percentile [in children with acne] would improve or prevent acne, without doing any acne treatments,” she said.
The study was supported by the National Institute on Aging and the Rochester Epidemiology Project. The authors reported no conflicts of interest. Dr. Lalor also reported no conflicts of interest.
The that used age- and sex-matched controls.
The investigators also identified “a potential association” with precocious puberty that they said “should be considered, especially among those presenting [with acne] under 8 or 9 years old.” The study was published in Pediatric Dermatology .
Senior author Megha M. Tollefson, MD, and coauthors used resources of the Rochester Epidemiology Project to identify all residents of Olmstead County, Minn., who were diagnosed with acne between the ages of 7 and 12 years during 2010-2018. They then randomly selected two age and sex-matched community controls in order to evaluate the relationship of preadolescent acne and BMI.
They confirmed 643 acne cases, and calculated an annual age- and sex-adjusted incidence rate for ages 7-12 of 58 per 10,000 person-years (95% confidence interval, 53.5-62.5). The incidence rate was significantly higher in females than males (89.2 vs. 28.2 per 10,000 person-years; P < .001), and it significantly increased with age (incidence rates of 4.3, 24.4, and 144.3 per 10,000 person-years among those ages 7-8, 9-10, and 11-12 years, respectively).
The median BMI percentile among children with acne was significantly higher than those without an acne diagnosis (75.0 vs. 65.0; P <.001). They also were much more likely to be obese: 16.7% of the children with acne had a BMI in at least the 95th percentile, compared with 12.2% among controls with no acne diagnosis (P = .01). (The qualifying 581 acne cases for this analysis had BMIs recorded within 8 months of the index data, in addition to not having pre-existing acne-relevant endocrine disorders.)
“High BMI is a strong risk factor for acne development and severity in adults, but until now pediatric studies have revealed mixed information ... [and have been] largely retrospective reviews without controls,” Dr. Tollefson, professor of pediatrics and dermatology at the Mayo Clinic, Rochester, Minn., and colleagues wrote.
‘Valuable’ data
Leah Lalor, MD, a pediatric dermatologist not involved with the research, said she is happy to see it. “It’s really valuable,” she said in an interview. “It’s actually the first study that gives us incidence data for preadolescent acne. We all have [had our estimates], but this study quantifies it ... and it will set the stage for further studies of preadolescents in the future.”
The study also documents that “girls are more likely to present to the clinic with acne, and to do so at younger ages, which we’ve suspected and which makes physiologic sense since girls tend to go through puberty earlier than boys,” said Dr. Lalor, assistant professor of dermatology and pediatrics at the Medical College of Wisconsin and the Children’s Wisconsin Clinics, both in Milwaukee. “And most interestingly, it really reveals that BMI is higher among preadolescents with acne than those without.”
The important caveat, she emphasized, is that the study population in Olmstead County, Minn. has a relatively higher level of education, wealth, and employment than the rest of the United States.
The investigators also found that use of systemic acne medications increased with increasing BMI (odds ratio, 1.43 per 5 kg/m2 increase in BMI; 95% CI, 1.07-1.92; P = .015). Approximately 5% of underweight or normal children were prescribed systemic acne medications, compared with 8.1% of overweight children, and 10.3% of those who were obese – data that suggest that most preadolescents with acne had mild to moderate disease and that more severe acne may be associated with increasing BMI percentiles, the authors wrote.
Approximately 4% of the 643 preadolescents with acne were diagnosed with an acne-relevant endocrine disorder prior to or at the time of acne diagnosis – most commonly precocious puberty. Of the 24 diagnoses of precocious puberty, 22 were in females, with a mean age at diagnosis of 7.3 years.
Puberty before age 8 in girls and 9 in boys is classified as precocious puberty. “Thus, a thorough review of systems and exam should be done in this population [with acne] to look for precocious puberty with a low threshold for systemic evaluation if indicated,” the authors wrote, also noting that 19 or the 482 female patients with acne were subsequently diagnosed with polycystic ovary syndrome.
Dr. Lalor said she “automatically” refers children with acne who are younger than 7 for an endocrine workup, but not necessarily children ages 7, 8, or 9 because “that’s considered within the normal realm of starting to get some acne.” Acne in the context of other symptoms such as body odor, hair, or thelarche may prompt referral in these ages, however, she said.
Future research
Obesity may influence preadolescent acne development through its effect on puberty, as overweight and obese girls achieve puberty earlier than those with normal BMI. And “insulin resistance, which may be related to obesity, has been implicated with inducing or worsening acne potentially related to shifts in IGF-1 [insulin-like growth factor 1] signaling and hyperandrogenemia,” Dr. Tollefson and colleagues wrote. Nutrition is also a possible confounder in the study.
“Patients and families have long felt that certain foods or practices contribute to acne, though this has been difficult to prove,” Dr. Lalor said. “We know that excess skim milk seems to contribute ... and there’s a correlation between high glycemic load diets [and acne].”
Assessing dietary habits in conjunction with BMI, and acne incidence and severity, would be valuable. So would research to determine “if decreasing the BMI percentile [in children with acne] would improve or prevent acne, without doing any acne treatments,” she said.
The study was supported by the National Institute on Aging and the Rochester Epidemiology Project. The authors reported no conflicts of interest. Dr. Lalor also reported no conflicts of interest.
The that used age- and sex-matched controls.
The investigators also identified “a potential association” with precocious puberty that they said “should be considered, especially among those presenting [with acne] under 8 or 9 years old.” The study was published in Pediatric Dermatology .
Senior author Megha M. Tollefson, MD, and coauthors used resources of the Rochester Epidemiology Project to identify all residents of Olmstead County, Minn., who were diagnosed with acne between the ages of 7 and 12 years during 2010-2018. They then randomly selected two age and sex-matched community controls in order to evaluate the relationship of preadolescent acne and BMI.
They confirmed 643 acne cases, and calculated an annual age- and sex-adjusted incidence rate for ages 7-12 of 58 per 10,000 person-years (95% confidence interval, 53.5-62.5). The incidence rate was significantly higher in females than males (89.2 vs. 28.2 per 10,000 person-years; P < .001), and it significantly increased with age (incidence rates of 4.3, 24.4, and 144.3 per 10,000 person-years among those ages 7-8, 9-10, and 11-12 years, respectively).
The median BMI percentile among children with acne was significantly higher than those without an acne diagnosis (75.0 vs. 65.0; P <.001). They also were much more likely to be obese: 16.7% of the children with acne had a BMI in at least the 95th percentile, compared with 12.2% among controls with no acne diagnosis (P = .01). (The qualifying 581 acne cases for this analysis had BMIs recorded within 8 months of the index data, in addition to not having pre-existing acne-relevant endocrine disorders.)
“High BMI is a strong risk factor for acne development and severity in adults, but until now pediatric studies have revealed mixed information ... [and have been] largely retrospective reviews without controls,” Dr. Tollefson, professor of pediatrics and dermatology at the Mayo Clinic, Rochester, Minn., and colleagues wrote.
‘Valuable’ data
Leah Lalor, MD, a pediatric dermatologist not involved with the research, said she is happy to see it. “It’s really valuable,” she said in an interview. “It’s actually the first study that gives us incidence data for preadolescent acne. We all have [had our estimates], but this study quantifies it ... and it will set the stage for further studies of preadolescents in the future.”
The study also documents that “girls are more likely to present to the clinic with acne, and to do so at younger ages, which we’ve suspected and which makes physiologic sense since girls tend to go through puberty earlier than boys,” said Dr. Lalor, assistant professor of dermatology and pediatrics at the Medical College of Wisconsin and the Children’s Wisconsin Clinics, both in Milwaukee. “And most interestingly, it really reveals that BMI is higher among preadolescents with acne than those without.”
The important caveat, she emphasized, is that the study population in Olmstead County, Minn. has a relatively higher level of education, wealth, and employment than the rest of the United States.
The investigators also found that use of systemic acne medications increased with increasing BMI (odds ratio, 1.43 per 5 kg/m2 increase in BMI; 95% CI, 1.07-1.92; P = .015). Approximately 5% of underweight or normal children were prescribed systemic acne medications, compared with 8.1% of overweight children, and 10.3% of those who were obese – data that suggest that most preadolescents with acne had mild to moderate disease and that more severe acne may be associated with increasing BMI percentiles, the authors wrote.
Approximately 4% of the 643 preadolescents with acne were diagnosed with an acne-relevant endocrine disorder prior to or at the time of acne diagnosis – most commonly precocious puberty. Of the 24 diagnoses of precocious puberty, 22 were in females, with a mean age at diagnosis of 7.3 years.
Puberty before age 8 in girls and 9 in boys is classified as precocious puberty. “Thus, a thorough review of systems and exam should be done in this population [with acne] to look for precocious puberty with a low threshold for systemic evaluation if indicated,” the authors wrote, also noting that 19 or the 482 female patients with acne were subsequently diagnosed with polycystic ovary syndrome.
Dr. Lalor said she “automatically” refers children with acne who are younger than 7 for an endocrine workup, but not necessarily children ages 7, 8, or 9 because “that’s considered within the normal realm of starting to get some acne.” Acne in the context of other symptoms such as body odor, hair, or thelarche may prompt referral in these ages, however, she said.
Future research
Obesity may influence preadolescent acne development through its effect on puberty, as overweight and obese girls achieve puberty earlier than those with normal BMI. And “insulin resistance, which may be related to obesity, has been implicated with inducing or worsening acne potentially related to shifts in IGF-1 [insulin-like growth factor 1] signaling and hyperandrogenemia,” Dr. Tollefson and colleagues wrote. Nutrition is also a possible confounder in the study.
“Patients and families have long felt that certain foods or practices contribute to acne, though this has been difficult to prove,” Dr. Lalor said. “We know that excess skim milk seems to contribute ... and there’s a correlation between high glycemic load diets [and acne].”
Assessing dietary habits in conjunction with BMI, and acne incidence and severity, would be valuable. So would research to determine “if decreasing the BMI percentile [in children with acne] would improve or prevent acne, without doing any acne treatments,” she said.
The study was supported by the National Institute on Aging and the Rochester Epidemiology Project. The authors reported no conflicts of interest. Dr. Lalor also reported no conflicts of interest.
FROM PEDIATRIC DERMATOLOGY
Large cohort study finds isotretinoin not associated with IBD
that also found no significant association of oral tetracycline-class antibiotics with IBD – and a small but statistically significant association of acne itself with the inflammatory disorders that make up IBD.
For the study, senior author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, and his colleagues used data from the TriNetX global research platform, which mines patient-level electronic medical record data from dozens of health care organizations, mainly in the United States. The network includes over 106 million patients. They looked at four cohorts: Patients without acne; those with acne but no current or prior use of systemic medications; those with acne managed with isotretinoin (and no prior use of oral tetracycline-class antibiotics); and those with acne managed with oral tetracycline-class antibiotics (and no exposure to isotretinoin).
For the acne cohorts, the investigators captured first encounters with a diagnosis of acne and first prescriptions of interest. And studywide, they used propensity score matching to balance cohorts for age, sex, race, ethnicity, and combined oral contraceptive use.
“These data should provide more reassurance to patients and prescribers that isotretinoin does not appear to result in a meaningfully increased risk of inflammatory bowel disease,” they wrote in the study, published online in the Journal of the American Academy of Dermatology.
“These are important findings as isotretinoin is a valuable treatment for acne that can result in a durable remission of disease activity, prevent acne scarring, and reduce our overreliance on oral antibiotics for acne,” they added.
Indeed, dermatologist Jonathan S. Weiss, MD, who was not involved in the research and was asked to comment on the study, said that the findings “are reassuring given the large numbers of patients evaluated and treated.” The smallest cohort – the isotretinoin group – had over 11,000 patients, and the other cohorts had over 100,000 patients each, he said in an interview.
“At this point, I’m not sure we need any other immediate information to feel comfortable using isotretinoin with respect to a potential to cause IBD, but it would be nice to see some longitudinal follow-up data for longer-term reassurance,” added Dr. Weiss, who practices in Snellville, Georgia, and is on the board of the directors of the American Acne and Rosacea Society.
The findings: Risk with acne
To assess the potential association between acne and IBD, the researchers identified more than 350,000 patients with acne managed without systemic medications, and propensity score matched them with patients who did not have acne. Altogether, their mean age was 22; 32.1% were male, and 59.6% were White.
Compared with the controls who did not have acne, they found a statistically significant association between acne and risk of incident IBD (odds ratio, 1.42; 95% confidence interval, 1.23-1.65) and an absolute risk difference of .04%. Separated into Crohn’s disease (CD) and ulcerative colitis (UC), ORs were 1.56 and 1.62, respectively.
Tetracyclines
To assess the association of oral tetracycline use and IBD, they compared more than 144,000 patients whose acne was managed with antibiotics with patients whose acne was managed without systemic medications. The patients had a mean age of 24.4; 34.7% were male, and 68.2% were White.
Compared with the patients who were not on systemic medications, there were no significant associations among those on oral tetracyclines, with an OR for incident IBD of 1 (95% CI, 0.82-1.22), an OR for incident CD of 1.09 (95% CI, 0.86-1.38), and an OR for UC of 0.78 (95% CI, 0.61-1.00).
Isotretinoin
To evaluate the association of isotretinoin and IBD, the researchers compared more than 11,000 patients treated with isotretinoin with two matched groups: patients with acne managed without systemic medications, and patients with acne managed with oral tetracyclines. The latter comparison was made to minimize potential confounding by acne severity. These patients had a mean age of 21.1; 49.5% were male, and 75.3% were White.
In the first comparison, compared with patients not treated with systemic medications, the OR for 1-year incidence of IBD among patients treated with isotretinoin was 1.29 (95% CI, 0.64-2.59), with an absolute risk difference of .036%. The ORs for CD and UC were 1.00 (95% CI, 0.45-2.23) and 1.27 (95% CI, .58-2.80), respectively.
And compared with the antibiotic-managed group, the OR for incident IBD among those on isotretinoin was 1.13 (95% CI, 0.57-2.21), with an absolute risk difference of .018%. The OR for CD was 1.00 (95% CI, 0.45-2.23). The OR for UC could not be accurately estimated because of an insufficient number of events in the tetracycline-treated group.
‘Challenging’ area of research
Researching acne treatments and the potential risk of IBD has been a methodologically “challenging topic to study” because of possible confounding and surveillance bias depending on study designs, Dr. Barbieri, director of the Brigham and Women’s Advanced Acne Therapeutics Clinic, said in an interview.
Studies that have identified a potential association between isotretinoin and IBD often have not adequately controlled for prior antibiotic exposure, for instance. And other studies, including a retrospective cohort study also published recently in JAAD using the same TriNetX database, have found 6-month isotretinoin-related risks of IBD but no increased risk at 1 year or more of follow-up – a finding that suggests a role of surveillance bias, Dr. Barbieri said.
The follow-up period of 1 year in their new study was chosen to minimize the risk of such bias. “Since patients on isotretinoin are seen more often, and since there are historical concerns about isotretinoin and IBD, patients on isotretinoin may be more likely to be screened earlier and thus could be diagnosed sooner than those not on [the medication],” he said.
He and his coauthors considered similar potential bias in designing the no-acne cohort, choosing patients who had routine primary care visits without abnormal findings in order to “reduce potential for bias due to frequency of interaction with the health care system,” they noted in their paper. (Patients had no prior encounters for acne and no history of acne treatments.)
Antibiotics, acne itself
Research on antibiotic use for acne and risk of IBD is scant, and the few studies that have been published show conflicting findings, Dr. Barbieri noted. In the meantime, studies and meta-analyses in the general medical literature – not involving acne – have identified an association between lifetime oral antibiotic exposure and IBD, he said.
While the results of the new study “are reassuring that oral tetracycline-class exposure for acne may not be associated with a significant absolute risk of inflammatory bowel disease, given the potential for antibiotic resistance and other antibiotic-associated complications, it remains important to be judicious” with their use in acne management, he and his coauthors wrote in the study.
The potential association between antibiotics for acne and IBD needs further study, preferably with longer follow-up duration, Dr. Barbieri said in the interview, but researchers are challenged by the lack of datasets with high-quality longitudinal data “beyond a few years of follow-up.”
The extent to which acne itself is associated with IBD is another area ripe for more research. Thus far, it seems that IBD and acne – and other chronic inflammatory skin diseases such as psoriasis – involve similar pathogenic pathways. “We know that in IBD Th17 and TNF immunologic pathways are important, so it’s not surprising that there may be associations,” he said.
In their paper, Dr. Barbieri and his coauthors emphasize, however, that the absolute risk difference between acne and IBD is small. It’s “unlikely that population level screening is warranted among patients with acne,” they wrote.
A second new study
The other study, also published recently in JAAD, used the same TriNetX research platform to identify approximately 77,000 patients with acne starting isotretinoin and matched them with patients starting oral antibiotics.
The investigators, Khalaf Kridin MD, PhD, and Ralf J. Ludwig, MD, of the Lübeck Institute of Experimental Dermatology, University of Lübeck (Germany), found that the lifetime risks (greater than 6 months) for patients on isotretinoin were not significantly elevated, compared with those on oral antibiotics for either CD (hazard ratio 1.05; 95% CI, 0.89-1.24, P = .583) or UC (HR, 1.13; 95% CI, 0.95-1.34; P = .162) They also looked at the risk of irritable bowel syndrome (IBS) and found a lower lifetime risk in the isotretinoin group.
In the short term, during the first 6 months after drug initiation, there was a significant, but slight increase in UC in the isotretinoin group. But this risk decreased to the level of the antibiotic group with longer follow up. “The absolute incidence rates [of IBD] and the risk difference of UC within the first 6 months are of limited clinical significance,” they wrote.
It may be, Dr. Weiss said in commenting on this study, “that isotretinoin unmasks an already-existing genetic tendency to UC early on in the course of treatment, but that it does not truly cause an increased incidence of any type of IBD.”
Both studies, said Dr. Barbieri, “add to an extensive body of literature that supports that isotretinoin is not associated with IBD.”
Dr. Barbieri had no disclosures for the study, for which Matthew T. Taylor served as first author. Coauthor Shawn Kwatra, MD, disclosed that he is an advisory board member/consultant for numerous pharmaceutical companies and has served as an investigator for several. Both are supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The other authors had no disclosures. Dr. Kridin and Dr. Ludwig had no disclosures for their study. Dr. Weiss had no disclosures.
that also found no significant association of oral tetracycline-class antibiotics with IBD – and a small but statistically significant association of acne itself with the inflammatory disorders that make up IBD.
For the study, senior author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, and his colleagues used data from the TriNetX global research platform, which mines patient-level electronic medical record data from dozens of health care organizations, mainly in the United States. The network includes over 106 million patients. They looked at four cohorts: Patients without acne; those with acne but no current or prior use of systemic medications; those with acne managed with isotretinoin (and no prior use of oral tetracycline-class antibiotics); and those with acne managed with oral tetracycline-class antibiotics (and no exposure to isotretinoin).
For the acne cohorts, the investigators captured first encounters with a diagnosis of acne and first prescriptions of interest. And studywide, they used propensity score matching to balance cohorts for age, sex, race, ethnicity, and combined oral contraceptive use.
“These data should provide more reassurance to patients and prescribers that isotretinoin does not appear to result in a meaningfully increased risk of inflammatory bowel disease,” they wrote in the study, published online in the Journal of the American Academy of Dermatology.
“These are important findings as isotretinoin is a valuable treatment for acne that can result in a durable remission of disease activity, prevent acne scarring, and reduce our overreliance on oral antibiotics for acne,” they added.
Indeed, dermatologist Jonathan S. Weiss, MD, who was not involved in the research and was asked to comment on the study, said that the findings “are reassuring given the large numbers of patients evaluated and treated.” The smallest cohort – the isotretinoin group – had over 11,000 patients, and the other cohorts had over 100,000 patients each, he said in an interview.
“At this point, I’m not sure we need any other immediate information to feel comfortable using isotretinoin with respect to a potential to cause IBD, but it would be nice to see some longitudinal follow-up data for longer-term reassurance,” added Dr. Weiss, who practices in Snellville, Georgia, and is on the board of the directors of the American Acne and Rosacea Society.
The findings: Risk with acne
To assess the potential association between acne and IBD, the researchers identified more than 350,000 patients with acne managed without systemic medications, and propensity score matched them with patients who did not have acne. Altogether, their mean age was 22; 32.1% were male, and 59.6% were White.
Compared with the controls who did not have acne, they found a statistically significant association between acne and risk of incident IBD (odds ratio, 1.42; 95% confidence interval, 1.23-1.65) and an absolute risk difference of .04%. Separated into Crohn’s disease (CD) and ulcerative colitis (UC), ORs were 1.56 and 1.62, respectively.
Tetracyclines
To assess the association of oral tetracycline use and IBD, they compared more than 144,000 patients whose acne was managed with antibiotics with patients whose acne was managed without systemic medications. The patients had a mean age of 24.4; 34.7% were male, and 68.2% were White.
Compared with the patients who were not on systemic medications, there were no significant associations among those on oral tetracyclines, with an OR for incident IBD of 1 (95% CI, 0.82-1.22), an OR for incident CD of 1.09 (95% CI, 0.86-1.38), and an OR for UC of 0.78 (95% CI, 0.61-1.00).
Isotretinoin
To evaluate the association of isotretinoin and IBD, the researchers compared more than 11,000 patients treated with isotretinoin with two matched groups: patients with acne managed without systemic medications, and patients with acne managed with oral tetracyclines. The latter comparison was made to minimize potential confounding by acne severity. These patients had a mean age of 21.1; 49.5% were male, and 75.3% were White.
In the first comparison, compared with patients not treated with systemic medications, the OR for 1-year incidence of IBD among patients treated with isotretinoin was 1.29 (95% CI, 0.64-2.59), with an absolute risk difference of .036%. The ORs for CD and UC were 1.00 (95% CI, 0.45-2.23) and 1.27 (95% CI, .58-2.80), respectively.
And compared with the antibiotic-managed group, the OR for incident IBD among those on isotretinoin was 1.13 (95% CI, 0.57-2.21), with an absolute risk difference of .018%. The OR for CD was 1.00 (95% CI, 0.45-2.23). The OR for UC could not be accurately estimated because of an insufficient number of events in the tetracycline-treated group.
‘Challenging’ area of research
Researching acne treatments and the potential risk of IBD has been a methodologically “challenging topic to study” because of possible confounding and surveillance bias depending on study designs, Dr. Barbieri, director of the Brigham and Women’s Advanced Acne Therapeutics Clinic, said in an interview.
Studies that have identified a potential association between isotretinoin and IBD often have not adequately controlled for prior antibiotic exposure, for instance. And other studies, including a retrospective cohort study also published recently in JAAD using the same TriNetX database, have found 6-month isotretinoin-related risks of IBD but no increased risk at 1 year or more of follow-up – a finding that suggests a role of surveillance bias, Dr. Barbieri said.
The follow-up period of 1 year in their new study was chosen to minimize the risk of such bias. “Since patients on isotretinoin are seen more often, and since there are historical concerns about isotretinoin and IBD, patients on isotretinoin may be more likely to be screened earlier and thus could be diagnosed sooner than those not on [the medication],” he said.
He and his coauthors considered similar potential bias in designing the no-acne cohort, choosing patients who had routine primary care visits without abnormal findings in order to “reduce potential for bias due to frequency of interaction with the health care system,” they noted in their paper. (Patients had no prior encounters for acne and no history of acne treatments.)
Antibiotics, acne itself
Research on antibiotic use for acne and risk of IBD is scant, and the few studies that have been published show conflicting findings, Dr. Barbieri noted. In the meantime, studies and meta-analyses in the general medical literature – not involving acne – have identified an association between lifetime oral antibiotic exposure and IBD, he said.
While the results of the new study “are reassuring that oral tetracycline-class exposure for acne may not be associated with a significant absolute risk of inflammatory bowel disease, given the potential for antibiotic resistance and other antibiotic-associated complications, it remains important to be judicious” with their use in acne management, he and his coauthors wrote in the study.
The potential association between antibiotics for acne and IBD needs further study, preferably with longer follow-up duration, Dr. Barbieri said in the interview, but researchers are challenged by the lack of datasets with high-quality longitudinal data “beyond a few years of follow-up.”
The extent to which acne itself is associated with IBD is another area ripe for more research. Thus far, it seems that IBD and acne – and other chronic inflammatory skin diseases such as psoriasis – involve similar pathogenic pathways. “We know that in IBD Th17 and TNF immunologic pathways are important, so it’s not surprising that there may be associations,” he said.
In their paper, Dr. Barbieri and his coauthors emphasize, however, that the absolute risk difference between acne and IBD is small. It’s “unlikely that population level screening is warranted among patients with acne,” they wrote.
A second new study
The other study, also published recently in JAAD, used the same TriNetX research platform to identify approximately 77,000 patients with acne starting isotretinoin and matched them with patients starting oral antibiotics.
The investigators, Khalaf Kridin MD, PhD, and Ralf J. Ludwig, MD, of the Lübeck Institute of Experimental Dermatology, University of Lübeck (Germany), found that the lifetime risks (greater than 6 months) for patients on isotretinoin were not significantly elevated, compared with those on oral antibiotics for either CD (hazard ratio 1.05; 95% CI, 0.89-1.24, P = .583) or UC (HR, 1.13; 95% CI, 0.95-1.34; P = .162) They also looked at the risk of irritable bowel syndrome (IBS) and found a lower lifetime risk in the isotretinoin group.
In the short term, during the first 6 months after drug initiation, there was a significant, but slight increase in UC in the isotretinoin group. But this risk decreased to the level of the antibiotic group with longer follow up. “The absolute incidence rates [of IBD] and the risk difference of UC within the first 6 months are of limited clinical significance,” they wrote.
It may be, Dr. Weiss said in commenting on this study, “that isotretinoin unmasks an already-existing genetic tendency to UC early on in the course of treatment, but that it does not truly cause an increased incidence of any type of IBD.”
Both studies, said Dr. Barbieri, “add to an extensive body of literature that supports that isotretinoin is not associated with IBD.”
Dr. Barbieri had no disclosures for the study, for which Matthew T. Taylor served as first author. Coauthor Shawn Kwatra, MD, disclosed that he is an advisory board member/consultant for numerous pharmaceutical companies and has served as an investigator for several. Both are supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The other authors had no disclosures. Dr. Kridin and Dr. Ludwig had no disclosures for their study. Dr. Weiss had no disclosures.
that also found no significant association of oral tetracycline-class antibiotics with IBD – and a small but statistically significant association of acne itself with the inflammatory disorders that make up IBD.
For the study, senior author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, and his colleagues used data from the TriNetX global research platform, which mines patient-level electronic medical record data from dozens of health care organizations, mainly in the United States. The network includes over 106 million patients. They looked at four cohorts: Patients without acne; those with acne but no current or prior use of systemic medications; those with acne managed with isotretinoin (and no prior use of oral tetracycline-class antibiotics); and those with acne managed with oral tetracycline-class antibiotics (and no exposure to isotretinoin).
For the acne cohorts, the investigators captured first encounters with a diagnosis of acne and first prescriptions of interest. And studywide, they used propensity score matching to balance cohorts for age, sex, race, ethnicity, and combined oral contraceptive use.
“These data should provide more reassurance to patients and prescribers that isotretinoin does not appear to result in a meaningfully increased risk of inflammatory bowel disease,” they wrote in the study, published online in the Journal of the American Academy of Dermatology.
“These are important findings as isotretinoin is a valuable treatment for acne that can result in a durable remission of disease activity, prevent acne scarring, and reduce our overreliance on oral antibiotics for acne,” they added.
Indeed, dermatologist Jonathan S. Weiss, MD, who was not involved in the research and was asked to comment on the study, said that the findings “are reassuring given the large numbers of patients evaluated and treated.” The smallest cohort – the isotretinoin group – had over 11,000 patients, and the other cohorts had over 100,000 patients each, he said in an interview.
“At this point, I’m not sure we need any other immediate information to feel comfortable using isotretinoin with respect to a potential to cause IBD, but it would be nice to see some longitudinal follow-up data for longer-term reassurance,” added Dr. Weiss, who practices in Snellville, Georgia, and is on the board of the directors of the American Acne and Rosacea Society.
The findings: Risk with acne
To assess the potential association between acne and IBD, the researchers identified more than 350,000 patients with acne managed without systemic medications, and propensity score matched them with patients who did not have acne. Altogether, their mean age was 22; 32.1% were male, and 59.6% were White.
Compared with the controls who did not have acne, they found a statistically significant association between acne and risk of incident IBD (odds ratio, 1.42; 95% confidence interval, 1.23-1.65) and an absolute risk difference of .04%. Separated into Crohn’s disease (CD) and ulcerative colitis (UC), ORs were 1.56 and 1.62, respectively.
Tetracyclines
To assess the association of oral tetracycline use and IBD, they compared more than 144,000 patients whose acne was managed with antibiotics with patients whose acne was managed without systemic medications. The patients had a mean age of 24.4; 34.7% were male, and 68.2% were White.
Compared with the patients who were not on systemic medications, there were no significant associations among those on oral tetracyclines, with an OR for incident IBD of 1 (95% CI, 0.82-1.22), an OR for incident CD of 1.09 (95% CI, 0.86-1.38), and an OR for UC of 0.78 (95% CI, 0.61-1.00).
Isotretinoin
To evaluate the association of isotretinoin and IBD, the researchers compared more than 11,000 patients treated with isotretinoin with two matched groups: patients with acne managed without systemic medications, and patients with acne managed with oral tetracyclines. The latter comparison was made to minimize potential confounding by acne severity. These patients had a mean age of 21.1; 49.5% were male, and 75.3% were White.
In the first comparison, compared with patients not treated with systemic medications, the OR for 1-year incidence of IBD among patients treated with isotretinoin was 1.29 (95% CI, 0.64-2.59), with an absolute risk difference of .036%. The ORs for CD and UC were 1.00 (95% CI, 0.45-2.23) and 1.27 (95% CI, .58-2.80), respectively.
And compared with the antibiotic-managed group, the OR for incident IBD among those on isotretinoin was 1.13 (95% CI, 0.57-2.21), with an absolute risk difference of .018%. The OR for CD was 1.00 (95% CI, 0.45-2.23). The OR for UC could not be accurately estimated because of an insufficient number of events in the tetracycline-treated group.
‘Challenging’ area of research
Researching acne treatments and the potential risk of IBD has been a methodologically “challenging topic to study” because of possible confounding and surveillance bias depending on study designs, Dr. Barbieri, director of the Brigham and Women’s Advanced Acne Therapeutics Clinic, said in an interview.
Studies that have identified a potential association between isotretinoin and IBD often have not adequately controlled for prior antibiotic exposure, for instance. And other studies, including a retrospective cohort study also published recently in JAAD using the same TriNetX database, have found 6-month isotretinoin-related risks of IBD but no increased risk at 1 year or more of follow-up – a finding that suggests a role of surveillance bias, Dr. Barbieri said.
The follow-up period of 1 year in their new study was chosen to minimize the risk of such bias. “Since patients on isotretinoin are seen more often, and since there are historical concerns about isotretinoin and IBD, patients on isotretinoin may be more likely to be screened earlier and thus could be diagnosed sooner than those not on [the medication],” he said.
He and his coauthors considered similar potential bias in designing the no-acne cohort, choosing patients who had routine primary care visits without abnormal findings in order to “reduce potential for bias due to frequency of interaction with the health care system,” they noted in their paper. (Patients had no prior encounters for acne and no history of acne treatments.)
Antibiotics, acne itself
Research on antibiotic use for acne and risk of IBD is scant, and the few studies that have been published show conflicting findings, Dr. Barbieri noted. In the meantime, studies and meta-analyses in the general medical literature – not involving acne – have identified an association between lifetime oral antibiotic exposure and IBD, he said.
While the results of the new study “are reassuring that oral tetracycline-class exposure for acne may not be associated with a significant absolute risk of inflammatory bowel disease, given the potential for antibiotic resistance and other antibiotic-associated complications, it remains important to be judicious” with their use in acne management, he and his coauthors wrote in the study.
The potential association between antibiotics for acne and IBD needs further study, preferably with longer follow-up duration, Dr. Barbieri said in the interview, but researchers are challenged by the lack of datasets with high-quality longitudinal data “beyond a few years of follow-up.”
The extent to which acne itself is associated with IBD is another area ripe for more research. Thus far, it seems that IBD and acne – and other chronic inflammatory skin diseases such as psoriasis – involve similar pathogenic pathways. “We know that in IBD Th17 and TNF immunologic pathways are important, so it’s not surprising that there may be associations,” he said.
In their paper, Dr. Barbieri and his coauthors emphasize, however, that the absolute risk difference between acne and IBD is small. It’s “unlikely that population level screening is warranted among patients with acne,” they wrote.
A second new study
The other study, also published recently in JAAD, used the same TriNetX research platform to identify approximately 77,000 patients with acne starting isotretinoin and matched them with patients starting oral antibiotics.
The investigators, Khalaf Kridin MD, PhD, and Ralf J. Ludwig, MD, of the Lübeck Institute of Experimental Dermatology, University of Lübeck (Germany), found that the lifetime risks (greater than 6 months) for patients on isotretinoin were not significantly elevated, compared with those on oral antibiotics for either CD (hazard ratio 1.05; 95% CI, 0.89-1.24, P = .583) or UC (HR, 1.13; 95% CI, 0.95-1.34; P = .162) They also looked at the risk of irritable bowel syndrome (IBS) and found a lower lifetime risk in the isotretinoin group.
In the short term, during the first 6 months after drug initiation, there was a significant, but slight increase in UC in the isotretinoin group. But this risk decreased to the level of the antibiotic group with longer follow up. “The absolute incidence rates [of IBD] and the risk difference of UC within the first 6 months are of limited clinical significance,” they wrote.
It may be, Dr. Weiss said in commenting on this study, “that isotretinoin unmasks an already-existing genetic tendency to UC early on in the course of treatment, but that it does not truly cause an increased incidence of any type of IBD.”
Both studies, said Dr. Barbieri, “add to an extensive body of literature that supports that isotretinoin is not associated with IBD.”
Dr. Barbieri had no disclosures for the study, for which Matthew T. Taylor served as first author. Coauthor Shawn Kwatra, MD, disclosed that he is an advisory board member/consultant for numerous pharmaceutical companies and has served as an investigator for several. Both are supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The other authors had no disclosures. Dr. Kridin and Dr. Ludwig had no disclosures for their study. Dr. Weiss had no disclosures.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Berdazimer gel under review at FDA for treating molluscum contagiosum
, the manufacturer announced.
If the submission is accepted by the FDA, the topical product could be approved in the first quarter of 2024, according to a press release from Novan, the manufacturer. If approved, it would be the first-in-class topical treatment for MC, the common, contagious viral skin infection that affects approximately six million individuals in the United States each year, most of them children aged 1-14 years, the statement noted. No FDA-approved therapies currently exist for the condition, which causes unsightly lesions on the face, trunk, limbs, and axillae that may persist untreated for a period of years.
The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a nitric oxide–releasing agent. A 3.4% formulation is in development for the topical treatment of acne, according to the company.
The submission for FDA approval is based on data from the B-SIMPLE4 study, a phase 3 randomized trial of nearly 900 individuals with MC aged 6 months and older (mean age, 6.6 years), with 3-70 raised lesions. Participants were randomized to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily for 12 weeks. The results were published in JAMA Dermatology.
The primary outcome was complete clearance of all lesions. At 12 weeks, 32.4% of patients in the berdazimer group achieved this outcome vs. 19.7% of those in the vehicle group (P < .001). Overall adverse event rates were low in both groups; 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events across both groups were application-site pain and erythema, and most of these were mild or moderate.
, the manufacturer announced.
If the submission is accepted by the FDA, the topical product could be approved in the first quarter of 2024, according to a press release from Novan, the manufacturer. If approved, it would be the first-in-class topical treatment for MC, the common, contagious viral skin infection that affects approximately six million individuals in the United States each year, most of them children aged 1-14 years, the statement noted. No FDA-approved therapies currently exist for the condition, which causes unsightly lesions on the face, trunk, limbs, and axillae that may persist untreated for a period of years.
The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a nitric oxide–releasing agent. A 3.4% formulation is in development for the topical treatment of acne, according to the company.
The submission for FDA approval is based on data from the B-SIMPLE4 study, a phase 3 randomized trial of nearly 900 individuals with MC aged 6 months and older (mean age, 6.6 years), with 3-70 raised lesions. Participants were randomized to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily for 12 weeks. The results were published in JAMA Dermatology.
The primary outcome was complete clearance of all lesions. At 12 weeks, 32.4% of patients in the berdazimer group achieved this outcome vs. 19.7% of those in the vehicle group (P < .001). Overall adverse event rates were low in both groups; 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events across both groups were application-site pain and erythema, and most of these were mild or moderate.
, the manufacturer announced.
If the submission is accepted by the FDA, the topical product could be approved in the first quarter of 2024, according to a press release from Novan, the manufacturer. If approved, it would be the first-in-class topical treatment for MC, the common, contagious viral skin infection that affects approximately six million individuals in the United States each year, most of them children aged 1-14 years, the statement noted. No FDA-approved therapies currently exist for the condition, which causes unsightly lesions on the face, trunk, limbs, and axillae that may persist untreated for a period of years.
The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a nitric oxide–releasing agent. A 3.4% formulation is in development for the topical treatment of acne, according to the company.
The submission for FDA approval is based on data from the B-SIMPLE4 study, a phase 3 randomized trial of nearly 900 individuals with MC aged 6 months and older (mean age, 6.6 years), with 3-70 raised lesions. Participants were randomized to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily for 12 weeks. The results were published in JAMA Dermatology.
The primary outcome was complete clearance of all lesions. At 12 weeks, 32.4% of patients in the berdazimer group achieved this outcome vs. 19.7% of those in the vehicle group (P < .001). Overall adverse event rates were low in both groups; 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events across both groups were application-site pain and erythema, and most of these were mild or moderate.