Photo by Steven Harbour

An investigative report has unearthed potential conflicts of interest among physicians who serve on advisory panels for the US Food and Drug Administration (FDA).

The investigation revealed that some FDA advisers are receiving significant post-hoc payments from the makers of drugs they reviewed.

The investigation also uncovered relationships between advisers and drug companies that predate drug reviews.

Journalist Charles Piller and his colleagues conducted this investigation and detailed the results in Science.

The report includes data—from the federal Open Payments website—on 107 physicians who voted on FDA advisory committees between 2013 and 2016.

Forty of these advisers received more than $10,000 in post-hoc earnings or research support from the makers of drugs they reviewed or from competing drug companies.

Twenty-six advisers received more than $100,000, and 7 advisers received more than $1 million.

The 17 top earners received more than $300,000 each. For these advisers, 94% of their earnings came from the makers of drugs they previ­ously reviewed or from those companies’ competitors.

The data also show that some advisers received funds from drug companies concurrent with or in the year before their advisory service.

Of the 17 top-earning advisers, 11 received financial sup­port from competing companies on one or more of the drugs they reviewed. Five advisers also received support from the makers of one or more of the drugs reviewed.

The FDA did not disclose this information to the public or issue waivers for these potential conflicts. The FDA can issue a waiver to allow the participation of an adviser with an active conflict or one that ended in the year before a vote, as long as the adviser in question can provide expertise that cannot be provided by someone else.

It is possible that the FDA dismissed the aforementioned financial ties that predated drug reviews, deciding these relationships were not conflicts and did not require a waiver. However, it is also possible that the FDA did not know about these potential conflicts.

Piller and his colleagues were unable to determine what the FDA knew, as the agency refused to release disclosure documents, discuss individual advisers, or explain what steps, if any, the FDA takes to validate advisers’ disclosures.

Photo by Steven Harbour

An investigative report has unearthed potential conflicts of interest among physicians who serve on advisory panels for the US Food and Drug Administration (FDA).

The investigation revealed that some FDA advisers are receiving significant post-hoc payments from the makers of drugs they reviewed.

The investigation also uncovered relationships between advisers and drug companies that predate drug reviews.

Journalist Charles Piller and his colleagues conducted this investigation and detailed the results in Science.

The report includes data—from the federal Open Payments website—on 107 physicians who voted on FDA advisory committees between 2013 and 2016.

Forty of these advisers received more than $10,000 in post-hoc earnings or research support from the makers of drugs they reviewed or from competing drug companies.

Twenty-six advisers received more than $100,000, and 7 advisers received more than $1 million.

The 17 top earners received more than $300,000 each. For these advisers, 94% of their earnings came from the makers of drugs they previ­ously reviewed or from those companies’ competitors.

The data also show that some advisers received funds from drug companies concurrent with or in the year before their advisory service.

Of the 17 top-earning advisers, 11 received financial sup­port from competing companies on one or more of the drugs they reviewed. Five advisers also received support from the makers of one or more of the drugs reviewed.

The FDA did not disclose this information to the public or issue waivers for these potential conflicts. The FDA can issue a waiver to allow the participation of an adviser with an active conflict or one that ended in the year before a vote, as long as the adviser in question can provide expertise that cannot be provided by someone else.

It is possible that the FDA dismissed the aforementioned financial ties that predated drug reviews, deciding these relationships were not conflicts and did not require a waiver. However, it is also possible that the FDA did not know about these potential conflicts.

Piller and his colleagues were unable to determine what the FDA knew, as the agency refused to release disclosure documents, discuss individual advisers, or explain what steps, if any, the FDA takes to validate advisers’ disclosures.

Photo by Steven Harbour

An investigative report has unearthed potential conflicts of interest among physicians who serve on advisory panels for the US Food and Drug Administration (FDA).

The investigation revealed that some FDA advisers are receiving significant post-hoc payments from the makers of drugs they reviewed.

The investigation also uncovered relationships between advisers and drug companies that predate drug reviews.

Journalist Charles Piller and his colleagues conducted this investigation and detailed the results in Science.

The report includes data—from the federal Open Payments website—on 107 physicians who voted on FDA advisory committees between 2013 and 2016.

Forty of these advisers received more than $10,000 in post-hoc earnings or research support from the makers of drugs they reviewed or from competing drug companies.

Twenty-six advisers received more than $100,000, and 7 advisers received more than $1 million.

The 17 top earners received more than $300,000 each. For these advisers, 94% of their earnings came from the makers of drugs they previ­ously reviewed or from those companies’ competitors.

The data also show that some advisers received funds from drug companies concurrent with or in the year before their advisory service.

Of the 17 top-earning advisers, 11 received financial sup­port from competing companies on one or more of the drugs they reviewed. Five advisers also received support from the makers of one or more of the drugs reviewed.

The FDA did not disclose this information to the public or issue waivers for these potential conflicts. The FDA can issue a waiver to allow the participation of an adviser with an active conflict or one that ended in the year before a vote, as long as the adviser in question can provide expertise that cannot be provided by someone else.

It is possible that the FDA dismissed the aforementioned financial ties that predated drug reviews, deciding these relationships were not conflicts and did not require a waiver. However, it is also possible that the FDA did not know about these potential conflicts.

Piller and his colleagues were unable to determine what the FDA knew, as the agency refused to release disclosure documents, discuss individual advisers, or explain what steps, if any, the FDA takes to validate advisers’ disclosures.

Clinical question: What is the expected clinical progression of patients with monoclonal gammopathy of undetermined significance (MGUS)?

Dr. Thota is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.

Clinical question: What is the expected clinical progression of patients with monoclonal gammopathy of undetermined significance (MGUS)?

Dr. Thota is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.

Clinical question: What is the expected clinical progression of patients with monoclonal gammopathy of undetermined significance (MGUS)?

Dr. Thota is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.

SAN DIEGO – More than 16% of emergency department sepsis patients are not admitted to the hospital, preliminary results from a large retrospective cohort study found.

Doug Brunk/MDedge News

“Nothing is really known about this topic,” lead study author Ithan D. Peltan, MD, said in an interview at an international conference of the American Thoracic Society. “In previous research, we’ve been focused on patients with sepsis who are admitted to the hospital. We have never thoroughly recognized that a fair number of patients who meet clinical criteria for sepsis in the emergency department are actually triaged to outpatient management. We don’t really know anything about these patients. What are their clinical characteristics and what are their outcomes like? And what are the factors that are leading them to be discharged from the ED rather than be admitted to the hospital?”

To find out, he and his associates retrospectively reviewed the medical records of 12,002 adult ED patients who met criteria for sepsis at two tertiary hospitals and two community hospitals in Utah between July 2013 and December 2016. They excluded trauma patients, those who left the ED against medical advice, those who were discharged to hospice or who died in the ED, and eligible patients’ repeat ED encounters. Patients transferred to another acute care facility were considered admitted, while transfers to non-acute care such as skilled nursing or psychiatric facilities were classified as discharges. Next, Dr. Peltan and his associates employed inverse probability weights using a propensity score for ED discharge based on age, sex, Charlson score, ED acuity score, initial ED vital signs, white blood cell count, lactate, sequential organ failure assessment (SOFA)score, busyness of the ED, and study hospital to compare 30-day mortality between patients admitted to the hospital versus those discharged from the ED.

Of the 12,002 patients included in the analysis, 10,032 (83.6%) were admitted, while 1,970 (16.4%) were discharged. Compared with admitted patients, discharged patients were younger (a mean of 53 vs. 60 years, respectively; P less than .001); more likely to be female (65% vs. 55%; P less than .001); more likely to be nonwhite or Hispanic (21% vs 17%; P less than .001), and had fewer comorbidities and physiologic derangements. In addition, crude mortality at 30 days was lower in discharged versus admitted patients (1.0% vs. 6.2%, respectively; P less than .001). After the propensity-adjusted analysis, there was no significant difference in 30-day mortality for discharged vs. admitted sepsis patients (adjusted odds ratio 1.0).

“We were worried that discharged ED sepsis patients were being mismanaged and weren’t going to do well as similar patients who were admitted to the hospital,” Dr. Peltan said. “This analysis is still a work in progress, but with that caveat, our findings so far suggest that physicians are making pretty good decisions overall.”

The researchers also found that, among 89 ED physicians who cared for 20 or more eligible patients, some did not discharge any of their sepsis patients, while others discharged 39% of their sepsis patients. “That was surprising,” Dr. Peltan said. “This could mean that some hospital sepsis admissions depend on physician practice style more than the patient’s condition or treatment needs.”

[email protected]

SOURCE: Peltan ID et al. ATS 2018, Abstract A5994/702.

SAN DIEGO – More than 16% of emergency department sepsis patients are not admitted to the hospital, preliminary results from a large retrospective cohort study found.

Doug Brunk/MDedge News

“Nothing is really known about this topic,” lead study author Ithan D. Peltan, MD, said in an interview at an international conference of the American Thoracic Society. “In previous research, we’ve been focused on patients with sepsis who are admitted to the hospital. We have never thoroughly recognized that a fair number of patients who meet clinical criteria for sepsis in the emergency department are actually triaged to outpatient management. We don’t really know anything about these patients. What are their clinical characteristics and what are their outcomes like? And what are the factors that are leading them to be discharged from the ED rather than be admitted to the hospital?”

To find out, he and his associates retrospectively reviewed the medical records of 12,002 adult ED patients who met criteria for sepsis at two tertiary hospitals and two community hospitals in Utah between July 2013 and December 2016. They excluded trauma patients, those who left the ED against medical advice, those who were discharged to hospice or who died in the ED, and eligible patients’ repeat ED encounters. Patients transferred to another acute care facility were considered admitted, while transfers to non-acute care such as skilled nursing or psychiatric facilities were classified as discharges. Next, Dr. Peltan and his associates employed inverse probability weights using a propensity score for ED discharge based on age, sex, Charlson score, ED acuity score, initial ED vital signs, white blood cell count, lactate, sequential organ failure assessment (SOFA)score, busyness of the ED, and study hospital to compare 30-day mortality between patients admitted to the hospital versus those discharged from the ED.

Of the 12,002 patients included in the analysis, 10,032 (83.6%) were admitted, while 1,970 (16.4%) were discharged. Compared with admitted patients, discharged patients were younger (a mean of 53 vs. 60 years, respectively; P less than .001); more likely to be female (65% vs. 55%; P less than .001); more likely to be nonwhite or Hispanic (21% vs 17%; P less than .001), and had fewer comorbidities and physiologic derangements. In addition, crude mortality at 30 days was lower in discharged versus admitted patients (1.0% vs. 6.2%, respectively; P less than .001). After the propensity-adjusted analysis, there was no significant difference in 30-day mortality for discharged vs. admitted sepsis patients (adjusted odds ratio 1.0).

“We were worried that discharged ED sepsis patients were being mismanaged and weren’t going to do well as similar patients who were admitted to the hospital,” Dr. Peltan said. “This analysis is still a work in progress, but with that caveat, our findings so far suggest that physicians are making pretty good decisions overall.”

The researchers also found that, among 89 ED physicians who cared for 20 or more eligible patients, some did not discharge any of their sepsis patients, while others discharged 39% of their sepsis patients. “That was surprising,” Dr. Peltan said. “This could mean that some hospital sepsis admissions depend on physician practice style more than the patient’s condition or treatment needs.”

[email protected]

SOURCE: Peltan ID et al. ATS 2018, Abstract A5994/702.

SAN DIEGO – More than 16% of emergency department sepsis patients are not admitted to the hospital, preliminary results from a large retrospective cohort study found.

Doug Brunk/MDedge News

“Nothing is really known about this topic,” lead study author Ithan D. Peltan, MD, said in an interview at an international conference of the American Thoracic Society. “In previous research, we’ve been focused on patients with sepsis who are admitted to the hospital. We have never thoroughly recognized that a fair number of patients who meet clinical criteria for sepsis in the emergency department are actually triaged to outpatient management. We don’t really know anything about these patients. What are their clinical characteristics and what are their outcomes like? And what are the factors that are leading them to be discharged from the ED rather than be admitted to the hospital?”

To find out, he and his associates retrospectively reviewed the medical records of 12,002 adult ED patients who met criteria for sepsis at two tertiary hospitals and two community hospitals in Utah between July 2013 and December 2016. They excluded trauma patients, those who left the ED against medical advice, those who were discharged to hospice or who died in the ED, and eligible patients’ repeat ED encounters. Patients transferred to another acute care facility were considered admitted, while transfers to non-acute care such as skilled nursing or psychiatric facilities were classified as discharges. Next, Dr. Peltan and his associates employed inverse probability weights using a propensity score for ED discharge based on age, sex, Charlson score, ED acuity score, initial ED vital signs, white blood cell count, lactate, sequential organ failure assessment (SOFA)score, busyness of the ED, and study hospital to compare 30-day mortality between patients admitted to the hospital versus those discharged from the ED.

Of the 12,002 patients included in the analysis, 10,032 (83.6%) were admitted, while 1,970 (16.4%) were discharged. Compared with admitted patients, discharged patients were younger (a mean of 53 vs. 60 years, respectively; P less than .001); more likely to be female (65% vs. 55%; P less than .001); more likely to be nonwhite or Hispanic (21% vs 17%; P less than .001), and had fewer comorbidities and physiologic derangements. In addition, crude mortality at 30 days was lower in discharged versus admitted patients (1.0% vs. 6.2%, respectively; P less than .001). After the propensity-adjusted analysis, there was no significant difference in 30-day mortality for discharged vs. admitted sepsis patients (adjusted odds ratio 1.0).

“We were worried that discharged ED sepsis patients were being mismanaged and weren’t going to do well as similar patients who were admitted to the hospital,” Dr. Peltan said. “This analysis is still a work in progress, but with that caveat, our findings so far suggest that physicians are making pretty good decisions overall.”

The researchers also found that, among 89 ED physicians who cared for 20 or more eligible patients, some did not discharge any of their sepsis patients, while others discharged 39% of their sepsis patients. “That was surprising,” Dr. Peltan said. “This could mean that some hospital sepsis admissions depend on physician practice style more than the patient’s condition or treatment needs.”

[email protected]

SOURCE: Peltan ID et al. ATS 2018, Abstract A5994/702.

LIVERPOOL, ENGLAND – Most patients with rheumatic diseases appear happy to switch from biologics to biosimilars and experience no issues, although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.

Sara Freeman/MDedgeNews

“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.

“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”

In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.

They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.

Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”

However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).

Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.

The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.

There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.

Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”

Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).

Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.

“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”

However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.

“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”

All authors had nothing to disclose.

SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
 

LIVERPOOL, ENGLAND – Most patients with rheumatic diseases appear happy to switch from biologics to biosimilars and experience no issues, although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.

Sara Freeman/MDedgeNews

“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.

“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”

In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.

They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.

Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”

However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).

Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.

The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.

There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.

Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”

Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).

Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.

“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”

However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.

“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”

All authors had nothing to disclose.

SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
 

LIVERPOOL, ENGLAND – Most patients with rheumatic diseases appear happy to switch from biologics to biosimilars and experience no issues, although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.

Sara Freeman/MDedgeNews

“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.

“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”

In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.

They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.

Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”

However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).

Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.

The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.

There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.

Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”

Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).

Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.

“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”

However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.

“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”

All authors had nothing to disclose.

SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
 

Direct oral anticoagulants were associated with decreased bleeding risk versus warfarin in a recent retrospective analysis of primary care databases.

Apixaban (Eliquis) was associated with decreased risk of major bleeding events versus warfarin both in patients with atrial fibrillation (AF) and those prescribed anticoagulants for other causes, according to study results.

Sebastian Kaulitzki/Thinkstock

Rivaroxaban (Xarelto) was associated with a decrease in risk of intracranial bleeding, compared with warfarin in patients without AF, as was dabigatran (Pradaxa), reported Yana Vinogradova, a research statistician in the division of primary care at the University of Nottingham, England, and her coauthors.

An increased risk of all-cause mortality was seen with both rivaroxaban and low-dose apixaban, possibly because more patients died of age-related causes while on these direct oral anticoagulants (DOACs), they reported.

“This large observational study, based on a general population in a primary care setting, provides reassurance about the safety of DOACs as an alternative to warfarin across all new incident users,” Ms. Vinogradova and her colleagues said in the BMJ.

Evidence establishing the noninferiority of DOACs to warfarin comes mostly from controlled trials in AF leaving “residual concerns” about the safety of these newer agents in real world settings, where a broader range of patients may receive them, they added.

Accordingly, they conducted an analysis based on patient data from two U.K. primary care databases that were representative of the national population, according to the researchers.

A total of 196,061 patients were represented in the study, including 103,270 (53%) with AF and 92,791 (47%) who received anticoagulants for other reasons.

A total of 67% of patients received warfarin, though its use declined from 98% in 2011, the beginning of the study period, to 23% in 2016, the end of the study period. Over that same time period, use of rivaroxaban rose from 1% to 42%, and use of apixaban rose from 0% to 31%, while dabigatran use peaked in 2013 at 10%, dropping to 3% by 2016.

Edoxaban was excluded from the study because it was not licensed in the United Kingdom until the end of 2015, investigators said.

For patients with AF, apixaban was linked to a lower major bleeding risk, both versus warfarin (adjusted hazard ratio, 0.66; 95% confidence interval, 0.54-0.79) and versus rivaroxaban, the published data show. Apixaban was associated with a lower risk of intracranial bleed versus warfarin in patients with AF (aHR, 0.40; 95% CI, 0.25-0.64) as was dabigatran (aHR, 0.45; 95% CI, 0.26-0.77).

For patients without AF, apixaban was again associated with a lower risk of major bleeding versus warfarin and versus rivaroxaban, while rivaroxaban was associated with lower intracranial bleeding risk versus warfarin, and apixaban with lower risks for gastrointestinal bleeds.

Compared with apixaban, rivaroxaban and dabigatran were associated with higher risks of certain bleeding events, further analyses show.

Rivaroxaban and lower-dose apixaban were both associated with increased all-cause mortality risk versus warfarin, both in the atrial fibrillation and non-AF groups, Ms. Vinogradova and her coinvestigators noted.

“A greater proportion of the older patients on apixaban and rivaroxaban may have died while still taking anticoagulants but from age-related causes other than ischemic stroke or venous thromboembolism,” they wrote.

Compared with patients on higher doses of DOACs, patients receiving lower doses were older and had more comorbidities and more previous events, they added.

Between DOACs, results of this particular analysis were most favorable for apixaban, according to investigators.

“Our study has shown that the risk of major bleeding is lower in patients taking apixaban regardless of the reason for prescribing,” they wrote. “This was most pronounced for intracranial bleeding in patients with atrial fibrillation and for gastrointestinal bleeding in patients without atrial fibrillation, appearing, in general, to show apixaban to be the safest drug.”

The study was supported by a grant from the National Institute for Health Research. The investigators had no relevant disclosures.
 

SOURCE: Vinogradova Y et al. BMJ 2018; 362:K2505.

Direct oral anticoagulants were associated with decreased bleeding risk versus warfarin in a recent retrospective analysis of primary care databases.

Apixaban (Eliquis) was associated with decreased risk of major bleeding events versus warfarin both in patients with atrial fibrillation (AF) and those prescribed anticoagulants for other causes, according to study results.

Sebastian Kaulitzki/Thinkstock

Rivaroxaban (Xarelto) was associated with a decrease in risk of intracranial bleeding, compared with warfarin in patients without AF, as was dabigatran (Pradaxa), reported Yana Vinogradova, a research statistician in the division of primary care at the University of Nottingham, England, and her coauthors.

An increased risk of all-cause mortality was seen with both rivaroxaban and low-dose apixaban, possibly because more patients died of age-related causes while on these direct oral anticoagulants (DOACs), they reported.

“This large observational study, based on a general population in a primary care setting, provides reassurance about the safety of DOACs as an alternative to warfarin across all new incident users,” Ms. Vinogradova and her colleagues said in the BMJ.

Evidence establishing the noninferiority of DOACs to warfarin comes mostly from controlled trials in AF leaving “residual concerns” about the safety of these newer agents in real world settings, where a broader range of patients may receive them, they added.

Accordingly, they conducted an analysis based on patient data from two U.K. primary care databases that were representative of the national population, according to the researchers.

A total of 196,061 patients were represented in the study, including 103,270 (53%) with AF and 92,791 (47%) who received anticoagulants for other reasons.

A total of 67% of patients received warfarin, though its use declined from 98% in 2011, the beginning of the study period, to 23% in 2016, the end of the study period. Over that same time period, use of rivaroxaban rose from 1% to 42%, and use of apixaban rose from 0% to 31%, while dabigatran use peaked in 2013 at 10%, dropping to 3% by 2016.

Edoxaban was excluded from the study because it was not licensed in the United Kingdom until the end of 2015, investigators said.

For patients with AF, apixaban was linked to a lower major bleeding risk, both versus warfarin (adjusted hazard ratio, 0.66; 95% confidence interval, 0.54-0.79) and versus rivaroxaban, the published data show. Apixaban was associated with a lower risk of intracranial bleed versus warfarin in patients with AF (aHR, 0.40; 95% CI, 0.25-0.64) as was dabigatran (aHR, 0.45; 95% CI, 0.26-0.77).

For patients without AF, apixaban was again associated with a lower risk of major bleeding versus warfarin and versus rivaroxaban, while rivaroxaban was associated with lower intracranial bleeding risk versus warfarin, and apixaban with lower risks for gastrointestinal bleeds.

Compared with apixaban, rivaroxaban and dabigatran were associated with higher risks of certain bleeding events, further analyses show.

Rivaroxaban and lower-dose apixaban were both associated with increased all-cause mortality risk versus warfarin, both in the atrial fibrillation and non-AF groups, Ms. Vinogradova and her coinvestigators noted.

“A greater proportion of the older patients on apixaban and rivaroxaban may have died while still taking anticoagulants but from age-related causes other than ischemic stroke or venous thromboembolism,” they wrote.

Compared with patients on higher doses of DOACs, patients receiving lower doses were older and had more comorbidities and more previous events, they added.

Between DOACs, results of this particular analysis were most favorable for apixaban, according to investigators.

“Our study has shown that the risk of major bleeding is lower in patients taking apixaban regardless of the reason for prescribing,” they wrote. “This was most pronounced for intracranial bleeding in patients with atrial fibrillation and for gastrointestinal bleeding in patients without atrial fibrillation, appearing, in general, to show apixaban to be the safest drug.”

The study was supported by a grant from the National Institute for Health Research. The investigators had no relevant disclosures.
 

SOURCE: Vinogradova Y et al. BMJ 2018; 362:K2505.

Direct oral anticoagulants were associated with decreased bleeding risk versus warfarin in a recent retrospective analysis of primary care databases.

Apixaban (Eliquis) was associated with decreased risk of major bleeding events versus warfarin both in patients with atrial fibrillation (AF) and those prescribed anticoagulants for other causes, according to study results.

Sebastian Kaulitzki/Thinkstock

Rivaroxaban (Xarelto) was associated with a decrease in risk of intracranial bleeding, compared with warfarin in patients without AF, as was dabigatran (Pradaxa), reported Yana Vinogradova, a research statistician in the division of primary care at the University of Nottingham, England, and her coauthors.

An increased risk of all-cause mortality was seen with both rivaroxaban and low-dose apixaban, possibly because more patients died of age-related causes while on these direct oral anticoagulants (DOACs), they reported.

“This large observational study, based on a general population in a primary care setting, provides reassurance about the safety of DOACs as an alternative to warfarin across all new incident users,” Ms. Vinogradova and her colleagues said in the BMJ.

Evidence establishing the noninferiority of DOACs to warfarin comes mostly from controlled trials in AF leaving “residual concerns” about the safety of these newer agents in real world settings, where a broader range of patients may receive them, they added.

Accordingly, they conducted an analysis based on patient data from two U.K. primary care databases that were representative of the national population, according to the researchers.

A total of 196,061 patients were represented in the study, including 103,270 (53%) with AF and 92,791 (47%) who received anticoagulants for other reasons.

A total of 67% of patients received warfarin, though its use declined from 98% in 2011, the beginning of the study period, to 23% in 2016, the end of the study period. Over that same time period, use of rivaroxaban rose from 1% to 42%, and use of apixaban rose from 0% to 31%, while dabigatran use peaked in 2013 at 10%, dropping to 3% by 2016.

Edoxaban was excluded from the study because it was not licensed in the United Kingdom until the end of 2015, investigators said.

For patients with AF, apixaban was linked to a lower major bleeding risk, both versus warfarin (adjusted hazard ratio, 0.66; 95% confidence interval, 0.54-0.79) and versus rivaroxaban, the published data show. Apixaban was associated with a lower risk of intracranial bleed versus warfarin in patients with AF (aHR, 0.40; 95% CI, 0.25-0.64) as was dabigatran (aHR, 0.45; 95% CI, 0.26-0.77).

For patients without AF, apixaban was again associated with a lower risk of major bleeding versus warfarin and versus rivaroxaban, while rivaroxaban was associated with lower intracranial bleeding risk versus warfarin, and apixaban with lower risks for gastrointestinal bleeds.

Compared with apixaban, rivaroxaban and dabigatran were associated with higher risks of certain bleeding events, further analyses show.

Rivaroxaban and lower-dose apixaban were both associated with increased all-cause mortality risk versus warfarin, both in the atrial fibrillation and non-AF groups, Ms. Vinogradova and her coinvestigators noted.

“A greater proportion of the older patients on apixaban and rivaroxaban may have died while still taking anticoagulants but from age-related causes other than ischemic stroke or venous thromboembolism,” they wrote.

Compared with patients on higher doses of DOACs, patients receiving lower doses were older and had more comorbidities and more previous events, they added.

Between DOACs, results of this particular analysis were most favorable for apixaban, according to investigators.

“Our study has shown that the risk of major bleeding is lower in patients taking apixaban regardless of the reason for prescribing,” they wrote. “This was most pronounced for intracranial bleeding in patients with atrial fibrillation and for gastrointestinal bleeding in patients without atrial fibrillation, appearing, in general, to show apixaban to be the safest drug.”

The study was supported by a grant from the National Institute for Health Research. The investigators had no relevant disclosures.
 

SOURCE: Vinogradova Y et al. BMJ 2018; 362:K2505.

Rosacea is a chronic skin condition that can be classified into 4 subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. Erythematotelangiectatic rosacea is characterized by redness of the face and excessive blushing. Papulopustular rosacea is a more severe form of disease that is characterized by papules and pustules of the central face. If left untreated, these subtypes may progress to phymatous rosacea, which is characterized by skin thickening, fibrosis, and cosmetic disfigurement. Ocular rosacea is characterized by redness and irritation of the eyes.¹ Rosacea patients often are burdened with embarrassment, social anxiety, and psychiatric comorbidities.

The Patient Health Questionnaire 9 (PHQ-9) is a validated and reliable self-administered tool for diagnosis of depression and designation of depression severity. This instrument could prove useful in screening for depression in rosacea patients given the high incidence of psychiatric comorbidities in this patient population.² The PHQ-9 consists of 9 questions that assess for criteria used to define depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition).³ The questionnaire is brief, easy to administer, and has 88% specificity and sensitivity.⁴

Other studies have evaluated the relationship between rosacea and psychiatric illness, but the PHQ-9 was not used as a screening tool.^7,8 Rosacea patients are at increased risk for having psychiatrist-diagnosed depression.⁵ In one assessment, a positive correlation between rosacea and psychiatric illness was noted using the Dermatology Life Quality Index, the rejection scale of the Questionnaire on Experience with Skin Complaints, and the German version of the Hospital Anxiety and Depression Scale.⁶ Interpretation of Rosacea Quality of Life and Dermatology Life Quality Index scores indicated that rosacea has a negative impact on quality of life.⁷

The purpose of this study was to examine the relationship between self-assessed rosacea severity scores and level of depression using the validated rosacea self-assessment tool and the PHQ-9 questionnaire, respectively.

Methods

Study Population
Study participants were adult patients from the Wake Forest Baptist Medical Center (Winston-Salem, North Carolina) dermatology clinic from January 2011 to December 2014 who had received a diagnosis of rosacea (International Classification of Diseases, Ninth Revision [ICD-9] code 695.3) from a Wake Forest dermatologist. Institutional review board approval was obtained prior to initiation of the study. Data collection occurred from October 2014 through February 2015. A total of 478 patients met criteria for participation in the study and were identified from the Wake Forest Baptist Hospital Transitional Data Warehouse and the electronic medical record. Because rosacea typically is not diagnosed in children and the data measures are not validated in children, this demographic group was excluded from participation.

Of 478 eligible patients who were invited to participate via mail or telephone, 46 completed the rosacea self-assessment tool and PHQ-9 survey in person. A total of 432 patients were mailed a presurvey recruitment letter notifying them that they would be receiving a survey in the mail unless they contacted the study team to decline participation. An email address and telephone number for the study team was provided. Twenty patients declined to participate in the study; surveys were then mailed to the remaining 412 patients. Sixteen of the mailed surveys were returned by the post office due to an incorrect address. A total of 195 surveys (149 through mail and 46 in person) were completed and analyzed. All survey respondents completed the validated rosacea self-assessment tool (Figure 1); of them, 183 completed the PHQ-9. Participants in this study received compensation for travel expenses and time.

Results

There is a direct relationship between rosacea severity and depression when comparing across the following levels of depression: nondepressed, minimal depression symptoms, minor depression, major depression (moderate), and major depression (severe)(P=.006; F=5.18; N=183)(Figures 2 and 3). There was no statistically significant difference in rosacea severity between the moderate and severe major depression groups.

Most patients reported they were nondepressed (68.9%). As measured by the PHQ-9, 31.1% of patients experienced some level of depression: 21.9% reported minimal depression symptoms, 7.1% reported minor depression, 1.1% reported major depression (moderate), and 1.1% reported major depression (severe)(Table).

Comment

There is a direct relationship between rosacea severity and level of depression. In our study, nearly one-third of patients reported some degree of depression. The reason for this correlation may be due to disease stigmatization and decreased quality of life due to the somatic symptoms of rosacea. Our study reinforced the results of other studies evaluating the psychosocial impact of rosacea.^8,9 Depression is associated with poor treatment adherence and poor outcomes in rosacea patients; therefore, depression may serve as an important outcome measure.¹⁰ The psychosocial impact of rosacea can be severe, but with disease improvement, there often is an improvement in the patient’s psychosocial status.⁷

There are several limitations to our study. The study population consisted of patients at a university dermatology clinic who may not be representative of patients in the general population; however, our hospital system does not require referral and provides care to a large percentage of the surrounding community.

Clinical implementation of the validated rosacea self-assessment tool and PHQ-9 may have several benefits. Patient-assessed rosacea severity and psychosocial impact obtained via use of these tools would provide physicians with information to fine-tune rosacea treatment regimens. Patients with the greatest social impact may require a more aggressive treatment approach. Early detection of depression in the rosacea population is important in informing treatment strategy and improving outcomes. Physicians should pay close attention to signs of depression in rosacea patients and determine if psychiatric treatment or referral for psychiatric evaluation is indicated. The correlation between rosacea and depression underscores the importance of treating this highly impactful disease; however, the low number of responders from the major depression (moderate) subgroup prevented us from making any strong conclusion about this specific subgroup.

Rosacea is a chronic skin condition that can be classified into 4 subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. Erythematotelangiectatic rosacea is characterized by redness of the face and excessive blushing. Papulopustular rosacea is a more severe form of disease that is characterized by papules and pustules of the central face. If left untreated, these subtypes may progress to phymatous rosacea, which is characterized by skin thickening, fibrosis, and cosmetic disfigurement. Ocular rosacea is characterized by redness and irritation of the eyes.¹ Rosacea patients often are burdened with embarrassment, social anxiety, and psychiatric comorbidities.

The Patient Health Questionnaire 9 (PHQ-9) is a validated and reliable self-administered tool for diagnosis of depression and designation of depression severity. This instrument could prove useful in screening for depression in rosacea patients given the high incidence of psychiatric comorbidities in this patient population.² The PHQ-9 consists of 9 questions that assess for criteria used to define depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition).³ The questionnaire is brief, easy to administer, and has 88% specificity and sensitivity.⁴

Other studies have evaluated the relationship between rosacea and psychiatric illness, but the PHQ-9 was not used as a screening tool.^7,8 Rosacea patients are at increased risk for having psychiatrist-diagnosed depression.⁵ In one assessment, a positive correlation between rosacea and psychiatric illness was noted using the Dermatology Life Quality Index, the rejection scale of the Questionnaire on Experience with Skin Complaints, and the German version of the Hospital Anxiety and Depression Scale.⁶ Interpretation of Rosacea Quality of Life and Dermatology Life Quality Index scores indicated that rosacea has a negative impact on quality of life.⁷

The purpose of this study was to examine the relationship between self-assessed rosacea severity scores and level of depression using the validated rosacea self-assessment tool and the PHQ-9 questionnaire, respectively.

Methods

Study Population
Study participants were adult patients from the Wake Forest Baptist Medical Center (Winston-Salem, North Carolina) dermatology clinic from January 2011 to December 2014 who had received a diagnosis of rosacea (International Classification of Diseases, Ninth Revision [ICD-9] code 695.3) from a Wake Forest dermatologist. Institutional review board approval was obtained prior to initiation of the study. Data collection occurred from October 2014 through February 2015. A total of 478 patients met criteria for participation in the study and were identified from the Wake Forest Baptist Hospital Transitional Data Warehouse and the electronic medical record. Because rosacea typically is not diagnosed in children and the data measures are not validated in children, this demographic group was excluded from participation.

Of 478 eligible patients who were invited to participate via mail or telephone, 46 completed the rosacea self-assessment tool and PHQ-9 survey in person. A total of 432 patients were mailed a presurvey recruitment letter notifying them that they would be receiving a survey in the mail unless they contacted the study team to decline participation. An email address and telephone number for the study team was provided. Twenty patients declined to participate in the study; surveys were then mailed to the remaining 412 patients. Sixteen of the mailed surveys were returned by the post office due to an incorrect address. A total of 195 surveys (149 through mail and 46 in person) were completed and analyzed. All survey respondents completed the validated rosacea self-assessment tool (Figure 1); of them, 183 completed the PHQ-9. Participants in this study received compensation for travel expenses and time.

Results

There is a direct relationship between rosacea severity and depression when comparing across the following levels of depression: nondepressed, minimal depression symptoms, minor depression, major depression (moderate), and major depression (severe)(P=.006; F=5.18; N=183)(Figures 2 and 3). There was no statistically significant difference in rosacea severity between the moderate and severe major depression groups.

Most patients reported they were nondepressed (68.9%). As measured by the PHQ-9, 31.1% of patients experienced some level of depression: 21.9% reported minimal depression symptoms, 7.1% reported minor depression, 1.1% reported major depression (moderate), and 1.1% reported major depression (severe)(Table).

Comment

There is a direct relationship between rosacea severity and level of depression. In our study, nearly one-third of patients reported some degree of depression. The reason for this correlation may be due to disease stigmatization and decreased quality of life due to the somatic symptoms of rosacea. Our study reinforced the results of other studies evaluating the psychosocial impact of rosacea.^8,9 Depression is associated with poor treatment adherence and poor outcomes in rosacea patients; therefore, depression may serve as an important outcome measure.¹⁰ The psychosocial impact of rosacea can be severe, but with disease improvement, there often is an improvement in the patient’s psychosocial status.⁷

There are several limitations to our study. The study population consisted of patients at a university dermatology clinic who may not be representative of patients in the general population; however, our hospital system does not require referral and provides care to a large percentage of the surrounding community.

Clinical implementation of the validated rosacea self-assessment tool and PHQ-9 may have several benefits. Patient-assessed rosacea severity and psychosocial impact obtained via use of these tools would provide physicians with information to fine-tune rosacea treatment regimens. Patients with the greatest social impact may require a more aggressive treatment approach. Early detection of depression in the rosacea population is important in informing treatment strategy and improving outcomes. Physicians should pay close attention to signs of depression in rosacea patients and determine if psychiatric treatment or referral for psychiatric evaluation is indicated. The correlation between rosacea and depression underscores the importance of treating this highly impactful disease; however, the low number of responders from the major depression (moderate) subgroup prevented us from making any strong conclusion about this specific subgroup.

Rosacea is a chronic skin condition that can be classified into 4 subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. Erythematotelangiectatic rosacea is characterized by redness of the face and excessive blushing. Papulopustular rosacea is a more severe form of disease that is characterized by papules and pustules of the central face. If left untreated, these subtypes may progress to phymatous rosacea, which is characterized by skin thickening, fibrosis, and cosmetic disfigurement. Ocular rosacea is characterized by redness and irritation of the eyes.¹ Rosacea patients often are burdened with embarrassment, social anxiety, and psychiatric comorbidities.

The Patient Health Questionnaire 9 (PHQ-9) is a validated and reliable self-administered tool for diagnosis of depression and designation of depression severity. This instrument could prove useful in screening for depression in rosacea patients given the high incidence of psychiatric comorbidities in this patient population.² The PHQ-9 consists of 9 questions that assess for criteria used to define depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition).³ The questionnaire is brief, easy to administer, and has 88% specificity and sensitivity.⁴

Other studies have evaluated the relationship between rosacea and psychiatric illness, but the PHQ-9 was not used as a screening tool.^7,8 Rosacea patients are at increased risk for having psychiatrist-diagnosed depression.⁵ In one assessment, a positive correlation between rosacea and psychiatric illness was noted using the Dermatology Life Quality Index, the rejection scale of the Questionnaire on Experience with Skin Complaints, and the German version of the Hospital Anxiety and Depression Scale.⁶ Interpretation of Rosacea Quality of Life and Dermatology Life Quality Index scores indicated that rosacea has a negative impact on quality of life.⁷

The purpose of this study was to examine the relationship between self-assessed rosacea severity scores and level of depression using the validated rosacea self-assessment tool and the PHQ-9 questionnaire, respectively.

Methods

Study Population
Study participants were adult patients from the Wake Forest Baptist Medical Center (Winston-Salem, North Carolina) dermatology clinic from January 2011 to December 2014 who had received a diagnosis of rosacea (International Classification of Diseases, Ninth Revision [ICD-9] code 695.3) from a Wake Forest dermatologist. Institutional review board approval was obtained prior to initiation of the study. Data collection occurred from October 2014 through February 2015. A total of 478 patients met criteria for participation in the study and were identified from the Wake Forest Baptist Hospital Transitional Data Warehouse and the electronic medical record. Because rosacea typically is not diagnosed in children and the data measures are not validated in children, this demographic group was excluded from participation.

Of 478 eligible patients who were invited to participate via mail or telephone, 46 completed the rosacea self-assessment tool and PHQ-9 survey in person. A total of 432 patients were mailed a presurvey recruitment letter notifying them that they would be receiving a survey in the mail unless they contacted the study team to decline participation. An email address and telephone number for the study team was provided. Twenty patients declined to participate in the study; surveys were then mailed to the remaining 412 patients. Sixteen of the mailed surveys were returned by the post office due to an incorrect address. A total of 195 surveys (149 through mail and 46 in person) were completed and analyzed. All survey respondents completed the validated rosacea self-assessment tool (Figure 1); of them, 183 completed the PHQ-9. Participants in this study received compensation for travel expenses and time.

Results

There is a direct relationship between rosacea severity and depression when comparing across the following levels of depression: nondepressed, minimal depression symptoms, minor depression, major depression (moderate), and major depression (severe)(P=.006; F=5.18; N=183)(Figures 2 and 3). There was no statistically significant difference in rosacea severity between the moderate and severe major depression groups.

Most patients reported they were nondepressed (68.9%). As measured by the PHQ-9, 31.1% of patients experienced some level of depression: 21.9% reported minimal depression symptoms, 7.1% reported minor depression, 1.1% reported major depression (moderate), and 1.1% reported major depression (severe)(Table).

Comment

There is a direct relationship between rosacea severity and level of depression. In our study, nearly one-third of patients reported some degree of depression. The reason for this correlation may be due to disease stigmatization and decreased quality of life due to the somatic symptoms of rosacea. Our study reinforced the results of other studies evaluating the psychosocial impact of rosacea.^8,9 Depression is associated with poor treatment adherence and poor outcomes in rosacea patients; therefore, depression may serve as an important outcome measure.¹⁰ The psychosocial impact of rosacea can be severe, but with disease improvement, there often is an improvement in the patient’s psychosocial status.⁷

There are several limitations to our study. The study population consisted of patients at a university dermatology clinic who may not be representative of patients in the general population; however, our hospital system does not require referral and provides care to a large percentage of the surrounding community.

Clinical implementation of the validated rosacea self-assessment tool and PHQ-9 may have several benefits. Patient-assessed rosacea severity and psychosocial impact obtained via use of these tools would provide physicians with information to fine-tune rosacea treatment regimens. Patients with the greatest social impact may require a more aggressive treatment approach. Early detection of depression in the rosacea population is important in informing treatment strategy and improving outcomes. Physicians should pay close attention to signs of depression in rosacea patients and determine if psychiatric treatment or referral for psychiatric evaluation is indicated. The correlation between rosacea and depression underscores the importance of treating this highly impactful disease; however, the low number of responders from the major depression (moderate) subgroup prevented us from making any strong conclusion about this specific subgroup.

STOCKHOLM – For fit, older patients with acute myeloid leukemia (AML), a combination of venetoclax and attenuated-dose induction chemotherapy is tolerable and associated with high response rates, results of the phase 1b CAVEAT trial have suggested.

There was one dose-limiting toxicity in a patient in cohort E (600 mg venetoclax). There were three deaths, all from sepsis, during the induction period (within 42 days) and one after 42 days. The deaths occurred in cohorts C, D, and E.

At the time of data cutoff, two patients had completed treatment, six were continuing, and 33 had discontinued. The primary reason for discontinuation was disease relapse, followed by refractory disease, adverse events, dose-limiting toxicity, or physician/patient decision.

Other adverse events included infections, including grade 3 infections in all 16 patients treated at the 400 mg and 600 mg levels, as well as sepsis, febrile neutropenia, and grade 3 rapid atrial fibrillation in two patients treated in the 400 mg and 600 mg venetoclax cohorts.“Overall, the impression from the investigators was that this is a very deliverable and well-tolerated regimen,” Dr. Wei said.

The overall combined CR/CRi rate was 71%, including CR/CRi in all 9 patients in the 200 mg venetoclax dose cohort.

“Even just with 1 week of monotherapy venetoclax exposure, 25% of patients had a 50% reduction in their bone marrow blasts,” Dr. Wei said.

Median overall survival among the 37 evaluable patients was 7.7 months. Among 12 patients who achieved a CR, the median overall survival was 18.5 months, and among the 12 patients with a CRi, the median overall survival was 7.7 months. For the remaining 13 patients, the median overall survival was 6.3 months.

Survival was significantly better for patients who were treatment-naive prior to venetoclax and chemotherapy, at a median of 18.6 months, compared with 3.8 months for patients who had previously received a hypomethylating agent and/or low-dose cytarabine (P = .0018).

Dose expansion of the 600-mg cohort is ongoing to provide better perspectives on efficacy.

The findings provide evidence that venetoclax monotherapy has cytoreductive potential and support future exploration of venetoclax in combination with 7+3 chemotherapy in younger, fit adults with AML, Dr. Wei said.

The study was supported by AbbVie/Genentech, the Victorian Cancer Agency, and the National Health and Medical Research Council of Australia. Dr. Wei reported research support and advisory board activities with AbbVie and other companies.

SOURCE: Wei AH et al. EHA Congress, Abstract S1564.

STOCKHOLM – For fit, older patients with acute myeloid leukemia (AML), a combination of venetoclax and attenuated-dose induction chemotherapy is tolerable and associated with high response rates, results of the phase 1b CAVEAT trial have suggested.

There was one dose-limiting toxicity in a patient in cohort E (600 mg venetoclax). There were three deaths, all from sepsis, during the induction period (within 42 days) and one after 42 days. The deaths occurred in cohorts C, D, and E.

At the time of data cutoff, two patients had completed treatment, six were continuing, and 33 had discontinued. The primary reason for discontinuation was disease relapse, followed by refractory disease, adverse events, dose-limiting toxicity, or physician/patient decision.

Other adverse events included infections, including grade 3 infections in all 16 patients treated at the 400 mg and 600 mg levels, as well as sepsis, febrile neutropenia, and grade 3 rapid atrial fibrillation in two patients treated in the 400 mg and 600 mg venetoclax cohorts.“Overall, the impression from the investigators was that this is a very deliverable and well-tolerated regimen,” Dr. Wei said.

The overall combined CR/CRi rate was 71%, including CR/CRi in all 9 patients in the 200 mg venetoclax dose cohort.

“Even just with 1 week of monotherapy venetoclax exposure, 25% of patients had a 50% reduction in their bone marrow blasts,” Dr. Wei said.

Median overall survival among the 37 evaluable patients was 7.7 months. Among 12 patients who achieved a CR, the median overall survival was 18.5 months, and among the 12 patients with a CRi, the median overall survival was 7.7 months. For the remaining 13 patients, the median overall survival was 6.3 months.

Survival was significantly better for patients who were treatment-naive prior to venetoclax and chemotherapy, at a median of 18.6 months, compared with 3.8 months for patients who had previously received a hypomethylating agent and/or low-dose cytarabine (P = .0018).

Dose expansion of the 600-mg cohort is ongoing to provide better perspectives on efficacy.

The findings provide evidence that venetoclax monotherapy has cytoreductive potential and support future exploration of venetoclax in combination with 7+3 chemotherapy in younger, fit adults with AML, Dr. Wei said.

The study was supported by AbbVie/Genentech, the Victorian Cancer Agency, and the National Health and Medical Research Council of Australia. Dr. Wei reported research support and advisory board activities with AbbVie and other companies.

SOURCE: Wei AH et al. EHA Congress, Abstract S1564.

STOCKHOLM – For fit, older patients with acute myeloid leukemia (AML), a combination of venetoclax and attenuated-dose induction chemotherapy is tolerable and associated with high response rates, results of the phase 1b CAVEAT trial have suggested.

There was one dose-limiting toxicity in a patient in cohort E (600 mg venetoclax). There were three deaths, all from sepsis, during the induction period (within 42 days) and one after 42 days. The deaths occurred in cohorts C, D, and E.

At the time of data cutoff, two patients had completed treatment, six were continuing, and 33 had discontinued. The primary reason for discontinuation was disease relapse, followed by refractory disease, adverse events, dose-limiting toxicity, or physician/patient decision.

Other adverse events included infections, including grade 3 infections in all 16 patients treated at the 400 mg and 600 mg levels, as well as sepsis, febrile neutropenia, and grade 3 rapid atrial fibrillation in two patients treated in the 400 mg and 600 mg venetoclax cohorts.“Overall, the impression from the investigators was that this is a very deliverable and well-tolerated regimen,” Dr. Wei said.

The overall combined CR/CRi rate was 71%, including CR/CRi in all 9 patients in the 200 mg venetoclax dose cohort.

“Even just with 1 week of monotherapy venetoclax exposure, 25% of patients had a 50% reduction in their bone marrow blasts,” Dr. Wei said.

Median overall survival among the 37 evaluable patients was 7.7 months. Among 12 patients who achieved a CR, the median overall survival was 18.5 months, and among the 12 patients with a CRi, the median overall survival was 7.7 months. For the remaining 13 patients, the median overall survival was 6.3 months.

Survival was significantly better for patients who were treatment-naive prior to venetoclax and chemotherapy, at a median of 18.6 months, compared with 3.8 months for patients who had previously received a hypomethylating agent and/or low-dose cytarabine (P = .0018).

Dose expansion of the 600-mg cohort is ongoing to provide better perspectives on efficacy.

The findings provide evidence that venetoclax monotherapy has cytoreductive potential and support future exploration of venetoclax in combination with 7+3 chemotherapy in younger, fit adults with AML, Dr. Wei said.

The study was supported by AbbVie/Genentech, the Victorian Cancer Agency, and the National Health and Medical Research Council of Australia. Dr. Wei reported research support and advisory board activities with AbbVie and other companies.

SOURCE: Wei AH et al. EHA Congress, Abstract S1564.

Germline mutations in patients with advanced renal cell carcinoma may be more common than previously suspected.

In a single-center cohort of 254 patients with advanced renal cell carcinoma (RCC) who received matched tumor-germline DNA sequencing, over a third (35.7%) of patients who had mutations in genes associated with RCC had not met current clinical criteria for testing.

In all, pathogenic germline mutations were identified in 41 patients (16.1%), with 14 patients’ mutations (5.5%) in genes known to be associated with RCC. For the remaining 27 patients (10.5%), the mutations were in non–RCC-associated genes, investigators reported in JAMA Oncology.

Of the non–RCC-associated mutations, CHEK2 was particularly common among patients with clear cell RCC (ccRCC), occurring in eight patients with ccRCC and two with non ccRCC (nccRCC). The overall odds ratio for this mutation among the study cohort was 3.0, compared with the general population (95% confidence interval 1.3-5.8; P = .003). “Although there are currently no RCC-specific screening recommendations for individuals with CHEK2 mutations, there may be incremental screening for other cancers, justifying including this gene on RCC panel tests,” wrote Maria Carlo, MD, and her coauthors.

Germline FH mutations were seen in seven patients, all with nccRCC. This higher rate of hereditary leiomyomatosis and RCC (HLRCC) was higher than previously reported in the literature, and clinical cues to the diagnosis were few among the study patients. Even though clues pointing to HLRCC were seen when tumor samples were submitted for histopathology to the genitourinary specialists at the study site, “it is unclear whether nonspecialist pathologists would be able to draw the same conclusions,” wrote Dr. Carlo and her colleagues.

Renal cell cancer–associated mutations were significantly more common in patients with nccRCC than in the ccRCC group: 9/74 (11.7%) nccRCC patients had an RCC-associated mutation, compared with 3/177 of the ccRCC group (P = .001).

The patient’s course of therapy could be guided by the mutation identified in 10% (eight) of the nccRCC patients, “none of which would have been identified with somatic-only sequencing,” wrote Dr. Carlo and associates. “Our results suggest that germline mutations in cancer-associated genes in patients with advanced RCC may be prevalent, and many of these mutations can be used to guide therapy.”

The 254 patients (median age 56 years, 70.5% male, 83.1% non-Hispanic white) were drawn from 267 patients with American Joint Committee on Cancer (AJCC) stage III or IV RCC participating in clinical trials at Memorial Sloan Kettering Cancer Center, New York, where Dr. Carlo practices as an oncologist. The patients included in the cohort were those who consented to germline sequencing and results disclosure.

To determine which pathogenic variants were identified by the study protocol that would have been missed by current testing standards, the investigators assumed that for those who met guidelines, the multigene test panel would probe for VHL, VH, FLCN, MET, SDHB, SDHD, BAP1, TSC1, TSC2, TP53, and MITF. If another mutation was picked up by the next-generation sequencing used in the study, or if a mutation was found in an individual who otherwise would not have been tested, the finding was considered incremental and attributable to the study protocol.

Implications of the additional mutations picked up by the tumor-germline sequencing approach go beyond the patient, said the researchers, who have seen several of the study participants’ family members receive positive test results for cancer-associated mutations as well. “Relatives who are also found to carry FH mutations should be considered for RCC screening. Early detection may increase the likelihood of cure and survivorship,” wrote Dr. Carlo and her coinvestigators.

Dr. Carlo reported serving as a consultant for Pfizer. Other authors reported multiple associations with pharmaceutical companies. The study was funded by the National Institutes of Health, the J. Randall and Kathleen L. MacDonald Kidney Cancer Research Fund, and the Robert and Kate Niehaus Center for Inherited Cancer Genomics at Memorial Sloan Kettering Cancer Center.

SOURCE: Carlo M et al. JAMA Oncol. 2018 Jul 5. doi: 10.1001/jamaoncol.2018.1986.

Germline mutations in patients with advanced renal cell carcinoma may be more common than previously suspected.

In a single-center cohort of 254 patients with advanced renal cell carcinoma (RCC) who received matched tumor-germline DNA sequencing, over a third (35.7%) of patients who had mutations in genes associated with RCC had not met current clinical criteria for testing.

In all, pathogenic germline mutations were identified in 41 patients (16.1%), with 14 patients’ mutations (5.5%) in genes known to be associated with RCC. For the remaining 27 patients (10.5%), the mutations were in non–RCC-associated genes, investigators reported in JAMA Oncology.

Of the non–RCC-associated mutations, CHEK2 was particularly common among patients with clear cell RCC (ccRCC), occurring in eight patients with ccRCC and two with non ccRCC (nccRCC). The overall odds ratio for this mutation among the study cohort was 3.0, compared with the general population (95% confidence interval 1.3-5.8; P = .003). “Although there are currently no RCC-specific screening recommendations for individuals with CHEK2 mutations, there may be incremental screening for other cancers, justifying including this gene on RCC panel tests,” wrote Maria Carlo, MD, and her coauthors.

Germline FH mutations were seen in seven patients, all with nccRCC. This higher rate of hereditary leiomyomatosis and RCC (HLRCC) was higher than previously reported in the literature, and clinical cues to the diagnosis were few among the study patients. Even though clues pointing to HLRCC were seen when tumor samples were submitted for histopathology to the genitourinary specialists at the study site, “it is unclear whether nonspecialist pathologists would be able to draw the same conclusions,” wrote Dr. Carlo and her colleagues.

Renal cell cancer–associated mutations were significantly more common in patients with nccRCC than in the ccRCC group: 9/74 (11.7%) nccRCC patients had an RCC-associated mutation, compared with 3/177 of the ccRCC group (P = .001).

The patient’s course of therapy could be guided by the mutation identified in 10% (eight) of the nccRCC patients, “none of which would have been identified with somatic-only sequencing,” wrote Dr. Carlo and associates. “Our results suggest that germline mutations in cancer-associated genes in patients with advanced RCC may be prevalent, and many of these mutations can be used to guide therapy.”

The 254 patients (median age 56 years, 70.5% male, 83.1% non-Hispanic white) were drawn from 267 patients with American Joint Committee on Cancer (AJCC) stage III or IV RCC participating in clinical trials at Memorial Sloan Kettering Cancer Center, New York, where Dr. Carlo practices as an oncologist. The patients included in the cohort were those who consented to germline sequencing and results disclosure.

To determine which pathogenic variants were identified by the study protocol that would have been missed by current testing standards, the investigators assumed that for those who met guidelines, the multigene test panel would probe for VHL, VH, FLCN, MET, SDHB, SDHD, BAP1, TSC1, TSC2, TP53, and MITF. If another mutation was picked up by the next-generation sequencing used in the study, or if a mutation was found in an individual who otherwise would not have been tested, the finding was considered incremental and attributable to the study protocol.

Implications of the additional mutations picked up by the tumor-germline sequencing approach go beyond the patient, said the researchers, who have seen several of the study participants’ family members receive positive test results for cancer-associated mutations as well. “Relatives who are also found to carry FH mutations should be considered for RCC screening. Early detection may increase the likelihood of cure and survivorship,” wrote Dr. Carlo and her coinvestigators.

Dr. Carlo reported serving as a consultant for Pfizer. Other authors reported multiple associations with pharmaceutical companies. The study was funded by the National Institutes of Health, the J. Randall and Kathleen L. MacDonald Kidney Cancer Research Fund, and the Robert and Kate Niehaus Center for Inherited Cancer Genomics at Memorial Sloan Kettering Cancer Center.

SOURCE: Carlo M et al. JAMA Oncol. 2018 Jul 5. doi: 10.1001/jamaoncol.2018.1986.

Germline mutations in patients with advanced renal cell carcinoma may be more common than previously suspected.

In a single-center cohort of 254 patients with advanced renal cell carcinoma (RCC) who received matched tumor-germline DNA sequencing, over a third (35.7%) of patients who had mutations in genes associated with RCC had not met current clinical criteria for testing.

In all, pathogenic germline mutations were identified in 41 patients (16.1%), with 14 patients’ mutations (5.5%) in genes known to be associated with RCC. For the remaining 27 patients (10.5%), the mutations were in non–RCC-associated genes, investigators reported in JAMA Oncology.

Of the non–RCC-associated mutations, CHEK2 was particularly common among patients with clear cell RCC (ccRCC), occurring in eight patients with ccRCC and two with non ccRCC (nccRCC). The overall odds ratio for this mutation among the study cohort was 3.0, compared with the general population (95% confidence interval 1.3-5.8; P = .003). “Although there are currently no RCC-specific screening recommendations for individuals with CHEK2 mutations, there may be incremental screening for other cancers, justifying including this gene on RCC panel tests,” wrote Maria Carlo, MD, and her coauthors.

Germline FH mutations were seen in seven patients, all with nccRCC. This higher rate of hereditary leiomyomatosis and RCC (HLRCC) was higher than previously reported in the literature, and clinical cues to the diagnosis were few among the study patients. Even though clues pointing to HLRCC were seen when tumor samples were submitted for histopathology to the genitourinary specialists at the study site, “it is unclear whether nonspecialist pathologists would be able to draw the same conclusions,” wrote Dr. Carlo and her colleagues.

Renal cell cancer–associated mutations were significantly more common in patients with nccRCC than in the ccRCC group: 9/74 (11.7%) nccRCC patients had an RCC-associated mutation, compared with 3/177 of the ccRCC group (P = .001).

The patient’s course of therapy could be guided by the mutation identified in 10% (eight) of the nccRCC patients, “none of which would have been identified with somatic-only sequencing,” wrote Dr. Carlo and associates. “Our results suggest that germline mutations in cancer-associated genes in patients with advanced RCC may be prevalent, and many of these mutations can be used to guide therapy.”

The 254 patients (median age 56 years, 70.5% male, 83.1% non-Hispanic white) were drawn from 267 patients with American Joint Committee on Cancer (AJCC) stage III or IV RCC participating in clinical trials at Memorial Sloan Kettering Cancer Center, New York, where Dr. Carlo practices as an oncologist. The patients included in the cohort were those who consented to germline sequencing and results disclosure.

To determine which pathogenic variants were identified by the study protocol that would have been missed by current testing standards, the investigators assumed that for those who met guidelines, the multigene test panel would probe for VHL, VH, FLCN, MET, SDHB, SDHD, BAP1, TSC1, TSC2, TP53, and MITF. If another mutation was picked up by the next-generation sequencing used in the study, or if a mutation was found in an individual who otherwise would not have been tested, the finding was considered incremental and attributable to the study protocol.

Implications of the additional mutations picked up by the tumor-germline sequencing approach go beyond the patient, said the researchers, who have seen several of the study participants’ family members receive positive test results for cancer-associated mutations as well. “Relatives who are also found to carry FH mutations should be considered for RCC screening. Early detection may increase the likelihood of cure and survivorship,” wrote Dr. Carlo and her coinvestigators.

Dr. Carlo reported serving as a consultant for Pfizer. Other authors reported multiple associations with pharmaceutical companies. The study was funded by the National Institutes of Health, the J. Randall and Kathleen L. MacDonald Kidney Cancer Research Fund, and the Robert and Kate Niehaus Center for Inherited Cancer Genomics at Memorial Sloan Kettering Cancer Center.

SOURCE: Carlo M et al. JAMA Oncol. 2018 Jul 5. doi: 10.1001/jamaoncol.2018.1986.

Acne vulgaris is prevalent in the general population, with 40 to 50 million affected individuals in the United States.¹ Severe inflammation and injury can lead to disfiguring scarring, which has a considerable impact on quality of life.² Numerous therapeutic options for acne scarring are available, including microneedling with and without platelet-rich plasma (PRP), lasers, chemical peels, and dermal fillers, with different modalities suited to individual patients and scar characteristics. This article reviews updates in treatment options for acne scarring.

Microneedling

Microneedling, also known as percutaneous collagen induction or collagen induction therapy, has been utilized for more than 2 decades.³ Dermatologic indications for microneedling include skin rejuvenation,^4-6 atrophic acne scarring,^7-9 and androgenic alopecia.^10,11 Microneedling also has been used to enhance skin penetration of topically applied drugs.^12-15 Fernandes¹⁶ described percutaneous collagen induction as the skin’s natural response to injury. Microneedling creates small wounds as fine needles puncture the epidermis and dermis, resulting in a cascade of growth factors that lead to tissue proliferation, regeneration, and a collagen remodeling phase that can last for several months.^8,16

Microneedling has gained popularity in the treatment of acne scarring.⁷ Alam et al⁹ conducted a split-face randomized clinical trial (RCT) to evaluate acne scarring after 3 microneedling sessions performed at 2-week intervals. Twenty participants with acne scarring on both sides of the face were enrolled in the study and one side of the face was randomized for treatment. Participants had at least two 5×5-cm areas of acne scarring graded as 2 (moderately atrophic scars) to 4 (hyperplastic or papular scars) on the quantitative Global Acne Scarring Classification system. A roller device with a 1.0-mm depth was used on participants with fine, less sebaceous skin and a 2.0-mm device for all others. Two blinded investigators assessed acne scars at baseline and at 3 and 6 months after treatment. Scar improvement was measured using the quantitative Goodman and Baron scale, which provides a score according to type and number of scars.¹⁷ Mean scar scores were significantly reduced at 6 months compared to baseline on the treatment side (P=.03) but not the control side. Participants experienced minimal pain associated with microneedling therapy, rated 1.08 of 10, and adverse effects were limited to mild transient erythema and edema.⁹ Several other clinical trials have demonstrated clinical improvements with microneedling.^18-20

The benefits of microneedling also have been observed on a histologic level. One group of investigators explored the effects of microneedling on dermal collagen in the treatment of various atrophic acne scars in 10 participants.⁷ After 6 treatment sessions performed at 2-week intervals, dermal collagen was assessed via punch biopsy. A roller device with a needle depth of 1.5 mm was used for all patients. At 1 month after treatment compared to baseline, mean (SD) levels of type I collagen were significantly increased (67.1% [4.2%] vs 70.4% [5.4%]; P=.01) as well as at 3 months after treatment compared to baseline for type III collagen (61.4% [3.6%] vs 74.3% [7.4%]; P=.01), type VII collagen (15.2% [2.1%] vs 21.3% [1.2%]; P=.03), and newly synthesized collagen (14.5% [5.8%] vs 19.5% [3.2%]; P=.02). Total elastin levels were significantly decreased at 3 months after treatment compared to baseline (51.3% [6.7%] vs 46.9% [4.3%]; P=.04). Adverse effects were limited to transient erythema and edema.⁷

Microneedling With Platelet-Rich Plasma

Microneedling has been combined with platelet-rich plasma (PRP) in the treatment of atrophic acne scars.²¹ In addition to inducing new collagen synthesis, microneedling aids in the absorption of PRP, an autologous concentrate of platelets that is obtained through peripheral venipuncture. The concentrate is centrifuged into 3 layers: (1) platelet-poor plasma, (2) PRP, and (3) erythrocytes.²² Platelet-rich plasma contains growth factors such as platelet-derived growth factor, transforming growth factor (TGF), and vascular endothelial growth factor, as well as cell adhesion molecules.^22,23 The application of PRP is thought to result in upregulated protein synthesis, greater collagen remodeling, and accelerated wound healing.²¹

Several studies have shown that the addition of PRP to microneedling can improve treatment outcome (Table 1).^24-27 Severity of acne scarring can be improved, such as reduced scar depth, by using both modalities synergistically (Figure).²⁴ Asif et al²⁶ compared microneedling with PRP to microneedling with distilled water in the treatment of 50 patients with atrophic acne scars graded 2 to 4 (mild to severe acne scarring) on the Goodman’s Qualitative classification and equal Goodman’s Qualitative and Quantitative scores on both halves of the face.^17,28 The right side of the face was treated with a 1.5-mm microneedling roller with intradermal and topical PRP, while the left side was treated with distilled water (placebo) delivered intradermally. Patients underwent 3 treatment sessions at 1-month intervals. The area treated with microneedling and PRP showed a 62.20% improvement from baseline after 3 treatments, while the placebo-treated area showed a 45.84% improvement on the Goodman and Baron quantitative scale.²⁶

Chawla²⁵ compared microneedling with topical PRP to microneedling with topical vitamin C in a split-face study of 30 participants with atrophic acne scarring graded 2 to 4 on the Goodman and Baron scale. A 1.5-mm roller device was used. Patients underwent 4 treatment sessions at 1-month intervals, and treatment efficacy was evaluated using the qualitative Goodman and Baron scale.²⁸ Participants experienced positive outcomes overall with both treatments. Notably, 18.5% (5/27) on the microneedling with PRP side demonstrated excellent response compared to 7.4% (2/27) on the microneedling with vitamin C side.²⁵

Laser Treatment

Laser skin resurfacing has shown to be efficacious in the treatment of both acne vulgaris and acne scarring. Various lasers have been utilized, including nonfractional CO₂ and erbium-doped:YAG (Er:YAG) lasers, as well as ablative fractional lasers (AFLs) and nonablative fractional lasers (NAFLs).²⁹

One retrospective study of 58 patients compared the use of 2 resurfacing lasers—10,600-nm nonfractional CO₂ and 2940-nm Er:YAG—and 2 fractional lasers—1550-nm NAFL and 10,600-nm AFL—in the treatment of atrophic acne scars.²⁹ A retrospective photographic analysis was performed by 6 blinded dermatologists to evaluate clinical improvement on a scale of 0 (no improvement) to 10 (excellent improvement). The mean improvement scores of the CO₂, Er:YAG, AFL, and NAFL groups were 6.0, 5.8, 2.2, and 5.2, respectively, and the mean number of treatments was 1.6, 1.1, 4.0, and 3.4, respectively. Thus, patients in the fractional laser groups required more treatments; however, those in the resurfacing laser groups had longer recovery times, pain, erythema, and postinflammatory hyperpigmentation. The investigators concluded that 3 consecutive AFL treatments could be as effective as a single resurfacing treatment with lower risk for complications.²⁹

A split-face RCT compared the use of the fractional Er:YAG laser on one side of the face to microneedling with a 2.0-mm needle on the other side for treatment of atrophic acne scars.³⁰ Thirty patients underwent 5 treatments at 1-month intervals. At 3-month follow-up, the areas treated with the Er:YAG laser showed 70% improvement from baseline compared to 30% improvement in the areas treated with microneedling (P<.001). Histologically, the Er:YAG laser showed a higher increase in dermal collagen than microneedling (P<.001). Furthermore, the Er:YAG laser yielded significantly lower pain scores (P<.001); however, patients reported higher rates of erythema, swelling, superficial crusting, and total downtime.³⁰

Lasers With PRP
More recent studies have examined the use of laser therapy in addition to PRP for the treatment of acne scars (Table 2).^31-34 Abdel Aal et al³³ examined the use of the ablative fractional CO₂ laser with and without intradermal PRP in a split-face study of 30 participants with various types of acne scarring (ie, boxcar, ice pick, and rolling scars). Participants underwent 2 treatments at 4-week intervals. Evaluations were performed by 2 blinded dermatologists 6 months after the final laser treatment using the qualitative Goodman and Baron scale.²⁸ Both treatments yielded improvement in scarring, but the PRP-treated side showed shorter durations of postprocedure erythema (P=.0052) as well as higher patient satisfaction scores (P<.001) than laser therapy alone.³³

In another split-face study, Gawdat et al³² examined combination treatment with the ablative fractional CO₂ laser and PRP in 30 participants with atrophic acne scars graded 2 to 4 on the qualitative Goodman and Baron scale.²⁸ Participants were randomized to 2 different treatment groups: In group 1, half of the face was treated with the fractional CO₂ laser and intradermal PRP, while the other half was treated with fractional CO₂ laser and intradermal saline. In group 2, half of the face was treated with fractional CO₂ laser and intradermal PRP, while the other half was treated with fractional CO₂ laser and topical PRP. All patients underwent 3 treatment sessions at 1-month intervals with assessment occurring a 6-month follow-up using the qualitative Goodman and Baron Scale.²⁸ In all participants, areas treated with the combined laser and PRP showed significant improvement in scarring (P=.03) and reduced recovery time (P=.02) compared to areas treated with laser therapy only. Patients receiving intradermal or topical PRP showed no statistically significant differences in improvement of scarring or recovery time; however, areas treated with topical PRP had significantly lower pain levels (P=.005).³²

Lee et al³¹ conducted a split-face study of 14 patients with moderate to severe acne scarring treated with an ablative fractional CO₂ laser followed by intradermal PRP or intradermal normal saline injections. Patients underwent 2 treatment sessions at 4-week intervals. Photographs taken at baseline and 4 months posttreatment were evaluated by 2 blinded dermatologists for clinical improvement using a quartile grading system. Erythema was assessed using a skin color measuring device. A blinded dermatologist assessed patients for adverse events. At 4-month follow-up, mean (SD) clinical improvement on the side receiving intradermal PRP was significantly better than the control side (2.7 [0.7] vs 2.3 [0.5]; P=.03). Erythema on posttreatment day 4 was significantly less on the side treated with PRP (P=.01). No adverse events were reported.³¹

Another split-face study compared the use of intradermal PRP to intradermal normal saline following fractional CO₂ laser treatment.³⁴ Twenty-five participants with moderate to severe acne scars completed 2 treatment sessions at 4-week intervals. Additionally, skin biopsies were collected to evaluate collagen production using immunohistochemistry, quantitative polymerase chain reaction, and western blot techniques. Experimental fibroblasts and keratinocytes were isolated and cultured. The cultures were irradiated with a fractional CO₂ laser and treated with PRP or platelet-poor plasma. Cultures were evaluated at 30 minutes, 24 hours, and 48 hours. Participants reported 75% improvement of acne scarring from baseline in the side treated with PRP compared to 50% improvement of acne scarring from baseline in the control group (P<.001). On days 7 and 84, participants reported greater improvement on the side treated with PRP (P=.03 and P=.02, respectively). On day 28, skin biopsy evaluation yielded higher levels of TGF-β1 (P=.02), TGF-β3 (P=.004), c-myc (P=.004), type I collagen (P=.03), and type III collagen (P=.03) on the PRP-treated side compared to the control side. Transforming growth factor β increases collagen and fibroblast production, while c-myc leads to cell cycle progression.^35-37 Similarly, TGF-β1, TGF-β3, types I andIII collagen, and p-Akt were increased in all cultures treated with PRP and platelet-poor plasma in a dose-dependent manner.³⁴ p-Akt is thought to regulate wound healing³⁸; however, PRP-treated keratinocytes yielded increased epidermal growth factor receptor and decreased keratin-16 at 48 hours, which suggests PRP plays a role in increasing epithelization and reducing laser-induced keratinocyte damage.³⁹ Adverse effects (eg, erythema, edema, oozing) were less frequent in the PRP-treated side.³⁴

Chemical Peels

Chemical peels are widely used in the treatment of acne scarring.⁴⁰ Peels improve scarring through destruction of the epidermal and/or dermal layers, leading to skin exfoliation, rejuvenation, and remodeling. Superficial peeling agents, which extend to the dermoepidermal junction, include resorcinol, tretinoin, glycolic acid, lactic acid, salicylic acid, and trichloroacetic acid (TCA) 10% to 35%.⁴¹ Medium-depth peeling agents extend to the upper reticular dermis and include phenol, TCA 35% to 50%, and Jessner solution (resorcinol, lactic acid, and salicylic acid in ethanol) followed by TCA 35%.⁴¹ Finally, the effects of deep peeling agents reach the mid reticular dermis and include the Baker-Gordon or Litton phenol formulas.⁴¹ Deep peels are associated with higher rates of adverse outcomes including infection, dyschromia, and scarring.^41,42

An RCT was performed to evaluate the use of a deep phenol 60% peel compared to microneedling with a 1.5-mm roller device plus a TCA 20% peel in the treatment of atrophic acne scars.⁴³ Twenty-four patients were randomly and evenly assigned to both treatment groups. The phenol group underwent a single treatment session, while the microneedling plus TCA group underwent 4 treatment sessions at 6-week intervals. Both groups were instructed to use daily topical tretinoin and hydroquinone 2% in the 2 weeks prior to treatment. Posttreatment results were evaluated using a quartile grading scale. Scarring improved from baseline by 75.12% (P<.001) in the phenol group and 69.43% (P<.001) in the microneedling plus TCA group, with no significant difference between groups. Adverse effects in the phenol group included erythema and hyperpigmentation, while adverse events in the microneedling plus TCA group included transient pain, edema, erythema, and desquamation.⁴³

Another study compared the use of a TCA 15% peel with microneedling to PRP with microneedling and microneedling alone in the treatment of atrophic acne scars.⁴⁴ Twenty-four patients were randomly assigned to the 3 treatment groups (8 to each group) and underwent 6 treatment sessions with 2-week intervals. A roller device with a 1.5-mm needle was used for microneedling. Microneedling plus TCA and microneedling plus PRP were significantly more effective than microneedling alone (P=.011 and P=.015, respectively); however, the TCA 15% peel with microneedling resulted in the largest increase in epidermal thickening. The investigators concluded that combined use of a TCA 15% peel and microneedling was the most effective in treating atrophic acne scarring.⁴⁴

Dermal Fillers

Dermal or subcutaneous fillers are used to increase volume in depressed scars and stimulate the skin’s natural production.⁴⁵ Tissue augmentation methods commonly are used for larger rolling acne scars. Options for filler materials include autologous fat, bovine, or human collagen derivatives; hyaluronic acid; and polymethyl methacrylate microspheres with collagen.⁴⁵ Newer fillers are formulated with lidocaine to decrease pain associated with the procedure.⁴⁶ Hyaluronic acid fillers provide natural volume correction and have limited potential to elicit an immune response due to their derivation from bacterial fermentation. Fillers using polymethyl methacrylate microspheres with collagen are permanent and effective, which may lead to reduced patient costs; however, they often are not a first choice for treatment.^45,46 Furthermore, if dermal fillers consist of bovine collagen, it is necessary to perform skin testing for allergy prior to use. Autologous fat transfer also has become popular for treatment of acne scarring, especially because there is no risk of allergic reaction, as the patient’s own fat is used for correction.⁴⁶ However, this method requires a high degree of skill, and results are unpredictable, generally lasting from 6 months to several years.

Therapies on the horizon include autologous cell therapy. A multicenter, double-blinded, placebo-controlled RCT examined the use of an autologous fibroblast filler in the treatment of bilateral, depressed, and distensible acne scars that were graded as moderate to severe.⁴⁷ Autologous fat fibroblasts were harvested from full-thickness postauricular punch biopsies. In this split-face study, 99 participants were treated with an intradermal autologous fibroblast filler on one cheek and a protein-free cell-culture medium on the contralateral cheek. Participants received an average of 5.9 mL of both autologous fat fibroblasts and cell-culture medium over 3 treatment sessions at 2-week intervals. The autologous fat fibroblasts were associated with greater improvement compared to cell-culture medium based on participant (43% vs 18%), evaluator (59% vs 42%), and independent photographic viewer’s assessment.⁴⁷

Conclusion

Acne scarring is a burden affecting millions of Americans. It often has a negative impact on quality of life and can lead to low self-esteem in patients. Numerous trials have indicated that microneedling is beneficial in the treatment of acne scarring, and emerging evidence indicates that the addition of PRP provides measurable benefits. Similarly, the addition of PRP to laser therapy may reduce recovery time as well as the commonly associated adverse events of erythema and pain. Chemical peels provide the advantage of being easily and efficiently performed in the office setting. Finally, the wide range of available dermal fillers can be tailored to treat specific types of acne scars. Autologous dermal fillers recently have been used and show promising benefits. It is important to consider desired outcome, cost, and adverse events when discussing therapeutic options for acne scarring with patients. The numerous therapeutic options warrant further research and well-designed RCTs to ensure optimal patient outcomes.

Acne vulgaris is prevalent in the general population, with 40 to 50 million affected individuals in the United States.¹ Severe inflammation and injury can lead to disfiguring scarring, which has a considerable impact on quality of life.² Numerous therapeutic options for acne scarring are available, including microneedling with and without platelet-rich plasma (PRP), lasers, chemical peels, and dermal fillers, with different modalities suited to individual patients and scar characteristics. This article reviews updates in treatment options for acne scarring.

Microneedling

Microneedling, also known as percutaneous collagen induction or collagen induction therapy, has been utilized for more than 2 decades.³ Dermatologic indications for microneedling include skin rejuvenation,^4-6 atrophic acne scarring,^7-9 and androgenic alopecia.^10,11 Microneedling also has been used to enhance skin penetration of topically applied drugs.^12-15 Fernandes¹⁶ described percutaneous collagen induction as the skin’s natural response to injury. Microneedling creates small wounds as fine needles puncture the epidermis and dermis, resulting in a cascade of growth factors that lead to tissue proliferation, regeneration, and a collagen remodeling phase that can last for several months.^8,16

Microneedling has gained popularity in the treatment of acne scarring.⁷ Alam et al⁹ conducted a split-face randomized clinical trial (RCT) to evaluate acne scarring after 3 microneedling sessions performed at 2-week intervals. Twenty participants with acne scarring on both sides of the face were enrolled in the study and one side of the face was randomized for treatment. Participants had at least two 5×5-cm areas of acne scarring graded as 2 (moderately atrophic scars) to 4 (hyperplastic or papular scars) on the quantitative Global Acne Scarring Classification system. A roller device with a 1.0-mm depth was used on participants with fine, less sebaceous skin and a 2.0-mm device for all others. Two blinded investigators assessed acne scars at baseline and at 3 and 6 months after treatment. Scar improvement was measured using the quantitative Goodman and Baron scale, which provides a score according to type and number of scars.¹⁷ Mean scar scores were significantly reduced at 6 months compared to baseline on the treatment side (P=.03) but not the control side. Participants experienced minimal pain associated with microneedling therapy, rated 1.08 of 10, and adverse effects were limited to mild transient erythema and edema.⁹ Several other clinical trials have demonstrated clinical improvements with microneedling.^18-20

The benefits of microneedling also have been observed on a histologic level. One group of investigators explored the effects of microneedling on dermal collagen in the treatment of various atrophic acne scars in 10 participants.⁷ After 6 treatment sessions performed at 2-week intervals, dermal collagen was assessed via punch biopsy. A roller device with a needle depth of 1.5 mm was used for all patients. At 1 month after treatment compared to baseline, mean (SD) levels of type I collagen were significantly increased (67.1% [4.2%] vs 70.4% [5.4%]; P=.01) as well as at 3 months after treatment compared to baseline for type III collagen (61.4% [3.6%] vs 74.3% [7.4%]; P=.01), type VII collagen (15.2% [2.1%] vs 21.3% [1.2%]; P=.03), and newly synthesized collagen (14.5% [5.8%] vs 19.5% [3.2%]; P=.02). Total elastin levels were significantly decreased at 3 months after treatment compared to baseline (51.3% [6.7%] vs 46.9% [4.3%]; P=.04). Adverse effects were limited to transient erythema and edema.⁷

Microneedling With Platelet-Rich Plasma

Microneedling has been combined with platelet-rich plasma (PRP) in the treatment of atrophic acne scars.²¹ In addition to inducing new collagen synthesis, microneedling aids in the absorption of PRP, an autologous concentrate of platelets that is obtained through peripheral venipuncture. The concentrate is centrifuged into 3 layers: (1) platelet-poor plasma, (2) PRP, and (3) erythrocytes.²² Platelet-rich plasma contains growth factors such as platelet-derived growth factor, transforming growth factor (TGF), and vascular endothelial growth factor, as well as cell adhesion molecules.^22,23 The application of PRP is thought to result in upregulated protein synthesis, greater collagen remodeling, and accelerated wound healing.²¹

Several studies have shown that the addition of PRP to microneedling can improve treatment outcome (Table 1).^24-27 Severity of acne scarring can be improved, such as reduced scar depth, by using both modalities synergistically (Figure).²⁴ Asif et al²⁶ compared microneedling with PRP to microneedling with distilled water in the treatment of 50 patients with atrophic acne scars graded 2 to 4 (mild to severe acne scarring) on the Goodman’s Qualitative classification and equal Goodman’s Qualitative and Quantitative scores on both halves of the face.^17,28 The right side of the face was treated with a 1.5-mm microneedling roller with intradermal and topical PRP, while the left side was treated with distilled water (placebo) delivered intradermally. Patients underwent 3 treatment sessions at 1-month intervals. The area treated with microneedling and PRP showed a 62.20% improvement from baseline after 3 treatments, while the placebo-treated area showed a 45.84% improvement on the Goodman and Baron quantitative scale.²⁶

Chawla²⁵ compared microneedling with topical PRP to microneedling with topical vitamin C in a split-face study of 30 participants with atrophic acne scarring graded 2 to 4 on the Goodman and Baron scale. A 1.5-mm roller device was used. Patients underwent 4 treatment sessions at 1-month intervals, and treatment efficacy was evaluated using the qualitative Goodman and Baron scale.²⁸ Participants experienced positive outcomes overall with both treatments. Notably, 18.5% (5/27) on the microneedling with PRP side demonstrated excellent response compared to 7.4% (2/27) on the microneedling with vitamin C side.²⁵

Laser Treatment

Laser skin resurfacing has shown to be efficacious in the treatment of both acne vulgaris and acne scarring. Various lasers have been utilized, including nonfractional CO₂ and erbium-doped:YAG (Er:YAG) lasers, as well as ablative fractional lasers (AFLs) and nonablative fractional lasers (NAFLs).²⁹

One retrospective study of 58 patients compared the use of 2 resurfacing lasers—10,600-nm nonfractional CO₂ and 2940-nm Er:YAG—and 2 fractional lasers—1550-nm NAFL and 10,600-nm AFL—in the treatment of atrophic acne scars.²⁹ A retrospective photographic analysis was performed by 6 blinded dermatologists to evaluate clinical improvement on a scale of 0 (no improvement) to 10 (excellent improvement). The mean improvement scores of the CO₂, Er:YAG, AFL, and NAFL groups were 6.0, 5.8, 2.2, and 5.2, respectively, and the mean number of treatments was 1.6, 1.1, 4.0, and 3.4, respectively. Thus, patients in the fractional laser groups required more treatments; however, those in the resurfacing laser groups had longer recovery times, pain, erythema, and postinflammatory hyperpigmentation. The investigators concluded that 3 consecutive AFL treatments could be as effective as a single resurfacing treatment with lower risk for complications.²⁹

A split-face RCT compared the use of the fractional Er:YAG laser on one side of the face to microneedling with a 2.0-mm needle on the other side for treatment of atrophic acne scars.³⁰ Thirty patients underwent 5 treatments at 1-month intervals. At 3-month follow-up, the areas treated with the Er:YAG laser showed 70% improvement from baseline compared to 30% improvement in the areas treated with microneedling (P<.001). Histologically, the Er:YAG laser showed a higher increase in dermal collagen than microneedling (P<.001). Furthermore, the Er:YAG laser yielded significantly lower pain scores (P<.001); however, patients reported higher rates of erythema, swelling, superficial crusting, and total downtime.³⁰

Lasers With PRP
More recent studies have examined the use of laser therapy in addition to PRP for the treatment of acne scars (Table 2).^31-34 Abdel Aal et al³³ examined the use of the ablative fractional CO₂ laser with and without intradermal PRP in a split-face study of 30 participants with various types of acne scarring (ie, boxcar, ice pick, and rolling scars). Participants underwent 2 treatments at 4-week intervals. Evaluations were performed by 2 blinded dermatologists 6 months after the final laser treatment using the qualitative Goodman and Baron scale.²⁸ Both treatments yielded improvement in scarring, but the PRP-treated side showed shorter durations of postprocedure erythema (P=.0052) as well as higher patient satisfaction scores (P<.001) than laser therapy alone.³³

In another split-face study, Gawdat et al³² examined combination treatment with the ablative fractional CO₂ laser and PRP in 30 participants with atrophic acne scars graded 2 to 4 on the qualitative Goodman and Baron scale.²⁸ Participants were randomized to 2 different treatment groups: In group 1, half of the face was treated with the fractional CO₂ laser and intradermal PRP, while the other half was treated with fractional CO₂ laser and intradermal saline. In group 2, half of the face was treated with fractional CO₂ laser and intradermal PRP, while the other half was treated with fractional CO₂ laser and topical PRP. All patients underwent 3 treatment sessions at 1-month intervals with assessment occurring a 6-month follow-up using the qualitative Goodman and Baron Scale.²⁸ In all participants, areas treated with the combined laser and PRP showed significant improvement in scarring (P=.03) and reduced recovery time (P=.02) compared to areas treated with laser therapy only. Patients receiving intradermal or topical PRP showed no statistically significant differences in improvement of scarring or recovery time; however, areas treated with topical PRP had significantly lower pain levels (P=.005).³²

Lee et al³¹ conducted a split-face study of 14 patients with moderate to severe acne scarring treated with an ablative fractional CO₂ laser followed by intradermal PRP or intradermal normal saline injections. Patients underwent 2 treatment sessions at 4-week intervals. Photographs taken at baseline and 4 months posttreatment were evaluated by 2 blinded dermatologists for clinical improvement using a quartile grading system. Erythema was assessed using a skin color measuring device. A blinded dermatologist assessed patients for adverse events. At 4-month follow-up, mean (SD) clinical improvement on the side receiving intradermal PRP was significantly better than the control side (2.7 [0.7] vs 2.3 [0.5]; P=.03). Erythema on posttreatment day 4 was significantly less on the side treated with PRP (P=.01). No adverse events were reported.³¹

Another split-face study compared the use of intradermal PRP to intradermal normal saline following fractional CO₂ laser treatment.³⁴ Twenty-five participants with moderate to severe acne scars completed 2 treatment sessions at 4-week intervals. Additionally, skin biopsies were collected to evaluate collagen production using immunohistochemistry, quantitative polymerase chain reaction, and western blot techniques. Experimental fibroblasts and keratinocytes were isolated and cultured. The cultures were irradiated with a fractional CO₂ laser and treated with PRP or platelet-poor plasma. Cultures were evaluated at 30 minutes, 24 hours, and 48 hours. Participants reported 75% improvement of acne scarring from baseline in the side treated with PRP compared to 50% improvement of acne scarring from baseline in the control group (P<.001). On days 7 and 84, participants reported greater improvement on the side treated with PRP (P=.03 and P=.02, respectively). On day 28, skin biopsy evaluation yielded higher levels of TGF-β1 (P=.02), TGF-β3 (P=.004), c-myc (P=.004), type I collagen (P=.03), and type III collagen (P=.03) on the PRP-treated side compared to the control side. Transforming growth factor β increases collagen and fibroblast production, while c-myc leads to cell cycle progression.^35-37 Similarly, TGF-β1, TGF-β3, types I andIII collagen, and p-Akt were increased in all cultures treated with PRP and platelet-poor plasma in a dose-dependent manner.³⁴ p-Akt is thought to regulate wound healing³⁸; however, PRP-treated keratinocytes yielded increased epidermal growth factor receptor and decreased keratin-16 at 48 hours, which suggests PRP plays a role in increasing epithelization and reducing laser-induced keratinocyte damage.³⁹ Adverse effects (eg, erythema, edema, oozing) were less frequent in the PRP-treated side.³⁴

Chemical Peels

Chemical peels are widely used in the treatment of acne scarring.⁴⁰ Peels improve scarring through destruction of the epidermal and/or dermal layers, leading to skin exfoliation, rejuvenation, and remodeling. Superficial peeling agents, which extend to the dermoepidermal junction, include resorcinol, tretinoin, glycolic acid, lactic acid, salicylic acid, and trichloroacetic acid (TCA) 10% to 35%.⁴¹ Medium-depth peeling agents extend to the upper reticular dermis and include phenol, TCA 35% to 50%, and Jessner solution (resorcinol, lactic acid, and salicylic acid in ethanol) followed by TCA 35%.⁴¹ Finally, the effects of deep peeling agents reach the mid reticular dermis and include the Baker-Gordon or Litton phenol formulas.⁴¹ Deep peels are associated with higher rates of adverse outcomes including infection, dyschromia, and scarring.^41,42

An RCT was performed to evaluate the use of a deep phenol 60% peel compared to microneedling with a 1.5-mm roller device plus a TCA 20% peel in the treatment of atrophic acne scars.⁴³ Twenty-four patients were randomly and evenly assigned to both treatment groups. The phenol group underwent a single treatment session, while the microneedling plus TCA group underwent 4 treatment sessions at 6-week intervals. Both groups were instructed to use daily topical tretinoin and hydroquinone 2% in the 2 weeks prior to treatment. Posttreatment results were evaluated using a quartile grading scale. Scarring improved from baseline by 75.12% (P<.001) in the phenol group and 69.43% (P<.001) in the microneedling plus TCA group, with no significant difference between groups. Adverse effects in the phenol group included erythema and hyperpigmentation, while adverse events in the microneedling plus TCA group included transient pain, edema, erythema, and desquamation.⁴³

Another study compared the use of a TCA 15% peel with microneedling to PRP with microneedling and microneedling alone in the treatment of atrophic acne scars.⁴⁴ Twenty-four patients were randomly assigned to the 3 treatment groups (8 to each group) and underwent 6 treatment sessions with 2-week intervals. A roller device with a 1.5-mm needle was used for microneedling. Microneedling plus TCA and microneedling plus PRP were significantly more effective than microneedling alone (P=.011 and P=.015, respectively); however, the TCA 15% peel with microneedling resulted in the largest increase in epidermal thickening. The investigators concluded that combined use of a TCA 15% peel and microneedling was the most effective in treating atrophic acne scarring.⁴⁴

Dermal Fillers

Dermal or subcutaneous fillers are used to increase volume in depressed scars and stimulate the skin’s natural production.⁴⁵ Tissue augmentation methods commonly are used for larger rolling acne scars. Options for filler materials include autologous fat, bovine, or human collagen derivatives; hyaluronic acid; and polymethyl methacrylate microspheres with collagen.⁴⁵ Newer fillers are formulated with lidocaine to decrease pain associated with the procedure.⁴⁶ Hyaluronic acid fillers provide natural volume correction and have limited potential to elicit an immune response due to their derivation from bacterial fermentation. Fillers using polymethyl methacrylate microspheres with collagen are permanent and effective, which may lead to reduced patient costs; however, they often are not a first choice for treatment.^45,46 Furthermore, if dermal fillers consist of bovine collagen, it is necessary to perform skin testing for allergy prior to use. Autologous fat transfer also has become popular for treatment of acne scarring, especially because there is no risk of allergic reaction, as the patient’s own fat is used for correction.⁴⁶ However, this method requires a high degree of skill, and results are unpredictable, generally lasting from 6 months to several years.

Therapies on the horizon include autologous cell therapy. A multicenter, double-blinded, placebo-controlled RCT examined the use of an autologous fibroblast filler in the treatment of bilateral, depressed, and distensible acne scars that were graded as moderate to severe.⁴⁷ Autologous fat fibroblasts were harvested from full-thickness postauricular punch biopsies. In this split-face study, 99 participants were treated with an intradermal autologous fibroblast filler on one cheek and a protein-free cell-culture medium on the contralateral cheek. Participants received an average of 5.9 mL of both autologous fat fibroblasts and cell-culture medium over 3 treatment sessions at 2-week intervals. The autologous fat fibroblasts were associated with greater improvement compared to cell-culture medium based on participant (43% vs 18%), evaluator (59% vs 42%), and independent photographic viewer’s assessment.⁴⁷

Conclusion

Acne scarring is a burden affecting millions of Americans. It often has a negative impact on quality of life and can lead to low self-esteem in patients. Numerous trials have indicated that microneedling is beneficial in the treatment of acne scarring, and emerging evidence indicates that the addition of PRP provides measurable benefits. Similarly, the addition of PRP to laser therapy may reduce recovery time as well as the commonly associated adverse events of erythema and pain. Chemical peels provide the advantage of being easily and efficiently performed in the office setting. Finally, the wide range of available dermal fillers can be tailored to treat specific types of acne scars. Autologous dermal fillers recently have been used and show promising benefits. It is important to consider desired outcome, cost, and adverse events when discussing therapeutic options for acne scarring with patients. The numerous therapeutic options warrant further research and well-designed RCTs to ensure optimal patient outcomes.

Acne vulgaris is prevalent in the general population, with 40 to 50 million affected individuals in the United States.¹ Severe inflammation and injury can lead to disfiguring scarring, which has a considerable impact on quality of life.² Numerous therapeutic options for acne scarring are available, including microneedling with and without platelet-rich plasma (PRP), lasers, chemical peels, and dermal fillers, with different modalities suited to individual patients and scar characteristics. This article reviews updates in treatment options for acne scarring.

Microneedling

Microneedling, also known as percutaneous collagen induction or collagen induction therapy, has been utilized for more than 2 decades.³ Dermatologic indications for microneedling include skin rejuvenation,^4-6 atrophic acne scarring,^7-9 and androgenic alopecia.^10,11 Microneedling also has been used to enhance skin penetration of topically applied drugs.^12-15 Fernandes¹⁶ described percutaneous collagen induction as the skin’s natural response to injury. Microneedling creates small wounds as fine needles puncture the epidermis and dermis, resulting in a cascade of growth factors that lead to tissue proliferation, regeneration, and a collagen remodeling phase that can last for several months.^8,16

Microneedling has gained popularity in the treatment of acne scarring.⁷ Alam et al⁹ conducted a split-face randomized clinical trial (RCT) to evaluate acne scarring after 3 microneedling sessions performed at 2-week intervals. Twenty participants with acne scarring on both sides of the face were enrolled in the study and one side of the face was randomized for treatment. Participants had at least two 5×5-cm areas of acne scarring graded as 2 (moderately atrophic scars) to 4 (hyperplastic or papular scars) on the quantitative Global Acne Scarring Classification system. A roller device with a 1.0-mm depth was used on participants with fine, less sebaceous skin and a 2.0-mm device for all others. Two blinded investigators assessed acne scars at baseline and at 3 and 6 months after treatment. Scar improvement was measured using the quantitative Goodman and Baron scale, which provides a score according to type and number of scars.¹⁷ Mean scar scores were significantly reduced at 6 months compared to baseline on the treatment side (P=.03) but not the control side. Participants experienced minimal pain associated with microneedling therapy, rated 1.08 of 10, and adverse effects were limited to mild transient erythema and edema.⁹ Several other clinical trials have demonstrated clinical improvements with microneedling.^18-20

The benefits of microneedling also have been observed on a histologic level. One group of investigators explored the effects of microneedling on dermal collagen in the treatment of various atrophic acne scars in 10 participants.⁷ After 6 treatment sessions performed at 2-week intervals, dermal collagen was assessed via punch biopsy. A roller device with a needle depth of 1.5 mm was used for all patients. At 1 month after treatment compared to baseline, mean (SD) levels of type I collagen were significantly increased (67.1% [4.2%] vs 70.4% [5.4%]; P=.01) as well as at 3 months after treatment compared to baseline for type III collagen (61.4% [3.6%] vs 74.3% [7.4%]; P=.01), type VII collagen (15.2% [2.1%] vs 21.3% [1.2%]; P=.03), and newly synthesized collagen (14.5% [5.8%] vs 19.5% [3.2%]; P=.02). Total elastin levels were significantly decreased at 3 months after treatment compared to baseline (51.3% [6.7%] vs 46.9% [4.3%]; P=.04). Adverse effects were limited to transient erythema and edema.⁷

Microneedling With Platelet-Rich Plasma

Microneedling has been combined with platelet-rich plasma (PRP) in the treatment of atrophic acne scars.²¹ In addition to inducing new collagen synthesis, microneedling aids in the absorption of PRP, an autologous concentrate of platelets that is obtained through peripheral venipuncture. The concentrate is centrifuged into 3 layers: (1) platelet-poor plasma, (2) PRP, and (3) erythrocytes.²² Platelet-rich plasma contains growth factors such as platelet-derived growth factor, transforming growth factor (TGF), and vascular endothelial growth factor, as well as cell adhesion molecules.^22,23 The application of PRP is thought to result in upregulated protein synthesis, greater collagen remodeling, and accelerated wound healing.²¹

Several studies have shown that the addition of PRP to microneedling can improve treatment outcome (Table 1).^24-27 Severity of acne scarring can be improved, such as reduced scar depth, by using both modalities synergistically (Figure).²⁴ Asif et al²⁶ compared microneedling with PRP to microneedling with distilled water in the treatment of 50 patients with atrophic acne scars graded 2 to 4 (mild to severe acne scarring) on the Goodman’s Qualitative classification and equal Goodman’s Qualitative and Quantitative scores on both halves of the face.^17,28 The right side of the face was treated with a 1.5-mm microneedling roller with intradermal and topical PRP, while the left side was treated with distilled water (placebo) delivered intradermally. Patients underwent 3 treatment sessions at 1-month intervals. The area treated with microneedling and PRP showed a 62.20% improvement from baseline after 3 treatments, while the placebo-treated area showed a 45.84% improvement on the Goodman and Baron quantitative scale.²⁶

Chawla²⁵ compared microneedling with topical PRP to microneedling with topical vitamin C in a split-face study of 30 participants with atrophic acne scarring graded 2 to 4 on the Goodman and Baron scale. A 1.5-mm roller device was used. Patients underwent 4 treatment sessions at 1-month intervals, and treatment efficacy was evaluated using the qualitative Goodman and Baron scale.²⁸ Participants experienced positive outcomes overall with both treatments. Notably, 18.5% (5/27) on the microneedling with PRP side demonstrated excellent response compared to 7.4% (2/27) on the microneedling with vitamin C side.²⁵

Laser Treatment

Laser skin resurfacing has shown to be efficacious in the treatment of both acne vulgaris and acne scarring. Various lasers have been utilized, including nonfractional CO₂ and erbium-doped:YAG (Er:YAG) lasers, as well as ablative fractional lasers (AFLs) and nonablative fractional lasers (NAFLs).²⁹

One retrospective study of 58 patients compared the use of 2 resurfacing lasers—10,600-nm nonfractional CO₂ and 2940-nm Er:YAG—and 2 fractional lasers—1550-nm NAFL and 10,600-nm AFL—in the treatment of atrophic acne scars.²⁹ A retrospective photographic analysis was performed by 6 blinded dermatologists to evaluate clinical improvement on a scale of 0 (no improvement) to 10 (excellent improvement). The mean improvement scores of the CO₂, Er:YAG, AFL, and NAFL groups were 6.0, 5.8, 2.2, and 5.2, respectively, and the mean number of treatments was 1.6, 1.1, 4.0, and 3.4, respectively. Thus, patients in the fractional laser groups required more treatments; however, those in the resurfacing laser groups had longer recovery times, pain, erythema, and postinflammatory hyperpigmentation. The investigators concluded that 3 consecutive AFL treatments could be as effective as a single resurfacing treatment with lower risk for complications.²⁹

A split-face RCT compared the use of the fractional Er:YAG laser on one side of the face to microneedling with a 2.0-mm needle on the other side for treatment of atrophic acne scars.³⁰ Thirty patients underwent 5 treatments at 1-month intervals. At 3-month follow-up, the areas treated with the Er:YAG laser showed 70% improvement from baseline compared to 30% improvement in the areas treated with microneedling (P<.001). Histologically, the Er:YAG laser showed a higher increase in dermal collagen than microneedling (P<.001). Furthermore, the Er:YAG laser yielded significantly lower pain scores (P<.001); however, patients reported higher rates of erythema, swelling, superficial crusting, and total downtime.³⁰

Lasers With PRP
More recent studies have examined the use of laser therapy in addition to PRP for the treatment of acne scars (Table 2).^31-34 Abdel Aal et al³³ examined the use of the ablative fractional CO₂ laser with and without intradermal PRP in a split-face study of 30 participants with various types of acne scarring (ie, boxcar, ice pick, and rolling scars). Participants underwent 2 treatments at 4-week intervals. Evaluations were performed by 2 blinded dermatologists 6 months after the final laser treatment using the qualitative Goodman and Baron scale.²⁸ Both treatments yielded improvement in scarring, but the PRP-treated side showed shorter durations of postprocedure erythema (P=.0052) as well as higher patient satisfaction scores (P<.001) than laser therapy alone.³³

In another split-face study, Gawdat et al³² examined combination treatment with the ablative fractional CO₂ laser and PRP in 30 participants with atrophic acne scars graded 2 to 4 on the qualitative Goodman and Baron scale.²⁸ Participants were randomized to 2 different treatment groups: In group 1, half of the face was treated with the fractional CO₂ laser and intradermal PRP, while the other half was treated with fractional CO₂ laser and intradermal saline. In group 2, half of the face was treated with fractional CO₂ laser and intradermal PRP, while the other half was treated with fractional CO₂ laser and topical PRP. All patients underwent 3 treatment sessions at 1-month intervals with assessment occurring a 6-month follow-up using the qualitative Goodman and Baron Scale.²⁸ In all participants, areas treated with the combined laser and PRP showed significant improvement in scarring (P=.03) and reduced recovery time (P=.02) compared to areas treated with laser therapy only. Patients receiving intradermal or topical PRP showed no statistically significant differences in improvement of scarring or recovery time; however, areas treated with topical PRP had significantly lower pain levels (P=.005).³²

Lee et al³¹ conducted a split-face study of 14 patients with moderate to severe acne scarring treated with an ablative fractional CO₂ laser followed by intradermal PRP or intradermal normal saline injections. Patients underwent 2 treatment sessions at 4-week intervals. Photographs taken at baseline and 4 months posttreatment were evaluated by 2 blinded dermatologists for clinical improvement using a quartile grading system. Erythema was assessed using a skin color measuring device. A blinded dermatologist assessed patients for adverse events. At 4-month follow-up, mean (SD) clinical improvement on the side receiving intradermal PRP was significantly better than the control side (2.7 [0.7] vs 2.3 [0.5]; P=.03). Erythema on posttreatment day 4 was significantly less on the side treated with PRP (P=.01). No adverse events were reported.³¹

Another split-face study compared the use of intradermal PRP to intradermal normal saline following fractional CO₂ laser treatment.³⁴ Twenty-five participants with moderate to severe acne scars completed 2 treatment sessions at 4-week intervals. Additionally, skin biopsies were collected to evaluate collagen production using immunohistochemistry, quantitative polymerase chain reaction, and western blot techniques. Experimental fibroblasts and keratinocytes were isolated and cultured. The cultures were irradiated with a fractional CO₂ laser and treated with PRP or platelet-poor plasma. Cultures were evaluated at 30 minutes, 24 hours, and 48 hours. Participants reported 75% improvement of acne scarring from baseline in the side treated with PRP compared to 50% improvement of acne scarring from baseline in the control group (P<.001). On days 7 and 84, participants reported greater improvement on the side treated with PRP (P=.03 and P=.02, respectively). On day 28, skin biopsy evaluation yielded higher levels of TGF-β1 (P=.02), TGF-β3 (P=.004), c-myc (P=.004), type I collagen (P=.03), and type III collagen (P=.03) on the PRP-treated side compared to the control side. Transforming growth factor β increases collagen and fibroblast production, while c-myc leads to cell cycle progression.^35-37 Similarly, TGF-β1, TGF-β3, types I andIII collagen, and p-Akt were increased in all cultures treated with PRP and platelet-poor plasma in a dose-dependent manner.³⁴ p-Akt is thought to regulate wound healing³⁸; however, PRP-treated keratinocytes yielded increased epidermal growth factor receptor and decreased keratin-16 at 48 hours, which suggests PRP plays a role in increasing epithelization and reducing laser-induced keratinocyte damage.³⁹ Adverse effects (eg, erythema, edema, oozing) were less frequent in the PRP-treated side.³⁴

Chemical Peels

Chemical peels are widely used in the treatment of acne scarring.⁴⁰ Peels improve scarring through destruction of the epidermal and/or dermal layers, leading to skin exfoliation, rejuvenation, and remodeling. Superficial peeling agents, which extend to the dermoepidermal junction, include resorcinol, tretinoin, glycolic acid, lactic acid, salicylic acid, and trichloroacetic acid (TCA) 10% to 35%.⁴¹ Medium-depth peeling agents extend to the upper reticular dermis and include phenol, TCA 35% to 50%, and Jessner solution (resorcinol, lactic acid, and salicylic acid in ethanol) followed by TCA 35%.⁴¹ Finally, the effects of deep peeling agents reach the mid reticular dermis and include the Baker-Gordon or Litton phenol formulas.⁴¹ Deep peels are associated with higher rates of adverse outcomes including infection, dyschromia, and scarring.^41,42

An RCT was performed to evaluate the use of a deep phenol 60% peel compared to microneedling with a 1.5-mm roller device plus a TCA 20% peel in the treatment of atrophic acne scars.⁴³ Twenty-four patients were randomly and evenly assigned to both treatment groups. The phenol group underwent a single treatment session, while the microneedling plus TCA group underwent 4 treatment sessions at 6-week intervals. Both groups were instructed to use daily topical tretinoin and hydroquinone 2% in the 2 weeks prior to treatment. Posttreatment results were evaluated using a quartile grading scale. Scarring improved from baseline by 75.12% (P<.001) in the phenol group and 69.43% (P<.001) in the microneedling plus TCA group, with no significant difference between groups. Adverse effects in the phenol group included erythema and hyperpigmentation, while adverse events in the microneedling plus TCA group included transient pain, edema, erythema, and desquamation.⁴³

Another study compared the use of a TCA 15% peel with microneedling to PRP with microneedling and microneedling alone in the treatment of atrophic acne scars.⁴⁴ Twenty-four patients were randomly assigned to the 3 treatment groups (8 to each group) and underwent 6 treatment sessions with 2-week intervals. A roller device with a 1.5-mm needle was used for microneedling. Microneedling plus TCA and microneedling plus PRP were significantly more effective than microneedling alone (P=.011 and P=.015, respectively); however, the TCA 15% peel with microneedling resulted in the largest increase in epidermal thickening. The investigators concluded that combined use of a TCA 15% peel and microneedling was the most effective in treating atrophic acne scarring.⁴⁴

Dermal Fillers

Dermal or subcutaneous fillers are used to increase volume in depressed scars and stimulate the skin’s natural production.⁴⁵ Tissue augmentation methods commonly are used for larger rolling acne scars. Options for filler materials include autologous fat, bovine, or human collagen derivatives; hyaluronic acid; and polymethyl methacrylate microspheres with collagen.⁴⁵ Newer fillers are formulated with lidocaine to decrease pain associated with the procedure.⁴⁶ Hyaluronic acid fillers provide natural volume correction and have limited potential to elicit an immune response due to their derivation from bacterial fermentation. Fillers using polymethyl methacrylate microspheres with collagen are permanent and effective, which may lead to reduced patient costs; however, they often are not a first choice for treatment.^45,46 Furthermore, if dermal fillers consist of bovine collagen, it is necessary to perform skin testing for allergy prior to use. Autologous fat transfer also has become popular for treatment of acne scarring, especially because there is no risk of allergic reaction, as the patient’s own fat is used for correction.⁴⁶ However, this method requires a high degree of skill, and results are unpredictable, generally lasting from 6 months to several years.

Therapies on the horizon include autologous cell therapy. A multicenter, double-blinded, placebo-controlled RCT examined the use of an autologous fibroblast filler in the treatment of bilateral, depressed, and distensible acne scars that were graded as moderate to severe.⁴⁷ Autologous fat fibroblasts were harvested from full-thickness postauricular punch biopsies. In this split-face study, 99 participants were treated with an intradermal autologous fibroblast filler on one cheek and a protein-free cell-culture medium on the contralateral cheek. Participants received an average of 5.9 mL of both autologous fat fibroblasts and cell-culture medium over 3 treatment sessions at 2-week intervals. The autologous fat fibroblasts were associated with greater improvement compared to cell-culture medium based on participant (43% vs 18%), evaluator (59% vs 42%), and independent photographic viewer’s assessment.⁴⁷

Conclusion

Acne scarring is a burden affecting millions of Americans. It often has a negative impact on quality of life and can lead to low self-esteem in patients. Numerous trials have indicated that microneedling is beneficial in the treatment of acne scarring, and emerging evidence indicates that the addition of PRP provides measurable benefits. Similarly, the addition of PRP to laser therapy may reduce recovery time as well as the commonly associated adverse events of erythema and pain. Chemical peels provide the advantage of being easily and efficiently performed in the office setting. Finally, the wide range of available dermal fillers can be tailored to treat specific types of acne scars. Autologous dermal fillers recently have been used and show promising benefits. It is important to consider desired outcome, cost, and adverse events when discussing therapeutic options for acne scarring with patients. The numerous therapeutic options warrant further research and well-designed RCTs to ensure optimal patient outcomes.

WASHINGTON – A majority of U.S. patients with presumed exocrine pancreatic insufficiency are likely going undiagnosed and untreated, and even those who get enzyme replacement therapy often receive too little, according to a recent analysis of insurance claims data from more than 48 million Americans.

Amid concerns that some people with nonspecific symptoms are overdiagnosed with exocrine pancreatic insufficiency (EPI) and hence getting unneeded treatment with pancreatic enzyme replacement therapy (PERT), it seems like substantial numbers of patients with legitimate pancreatic morbidity are often missed and are going untreated, Chris E. Forsmark, MD, said at the annual Digestive Disease Week^®. This includes patients with chronic pancreatitis, pancreatic cancer, and patients who underwent pancreatic resection surgery.

Mitchel L. Zoler/MDedge News

[email protected]

WASHINGTON – A majority of U.S. patients with presumed exocrine pancreatic insufficiency are likely going undiagnosed and untreated, and even those who get enzyme replacement therapy often receive too little, according to a recent analysis of insurance claims data from more than 48 million Americans.

Amid concerns that some people with nonspecific symptoms are overdiagnosed with exocrine pancreatic insufficiency (EPI) and hence getting unneeded treatment with pancreatic enzyme replacement therapy (PERT), it seems like substantial numbers of patients with legitimate pancreatic morbidity are often missed and are going untreated, Chris E. Forsmark, MD, said at the annual Digestive Disease Week^®. This includes patients with chronic pancreatitis, pancreatic cancer, and patients who underwent pancreatic resection surgery.

Mitchel L. Zoler/MDedge News

[email protected]

WASHINGTON – A majority of U.S. patients with presumed exocrine pancreatic insufficiency are likely going undiagnosed and untreated, and even those who get enzyme replacement therapy often receive too little, according to a recent analysis of insurance claims data from more than 48 million Americans.

Amid concerns that some people with nonspecific symptoms are overdiagnosed with exocrine pancreatic insufficiency (EPI) and hence getting unneeded treatment with pancreatic enzyme replacement therapy (PERT), it seems like substantial numbers of patients with legitimate pancreatic morbidity are often missed and are going untreated, Chris E. Forsmark, MD, said at the annual Digestive Disease Week^®. This includes patients with chronic pancreatitis, pancreatic cancer, and patients who underwent pancreatic resection surgery.

Mitchel L. Zoler/MDedge News

[email protected]