Conference Coverage

With the strong likelihood that dermatologists in the United States will have to resolve dermatologic issues created by cultural cosmetic practices originating elsewhere, strategies for an open nonjudgmental approach are instrumental, according to a dermatologist with expertise in these types of cases who spoke at the Skin of Color Update 2021.

“Instead of avoiding the discussion of cultural practices, we should discuss them and be open about them. It fosters a comfortable environment, trust, and better compliance,” reported Neelam Ajit Vashi, MD, founding director of the Boston University Center for Ethnic Skin.

Out of fear of causing offense, a desire to be discreet, or of personal discomfort with foreign cultural practices, some clinicians might elect to limit themselves to the information that the patient volunteers, which is a mistake, according to Dr. Vashi.

“The avoidance of topics around culture actually limits the ability to have a successful relationship,” she maintained.

Successful encounters are not just based on a willingness to listen, Dr. Vashi said. Clinicians should be seeking a base of knowledge. With growing globalization and widespread immigration, “it is increasingly important for dermatologists in the U.S. to understand the role of cultural practices [in creating skin problems] and recognize the sequelae,” Dr. Vashi said.

Taking some common examples of dermatologic complaints created by cosmetic practices originating elsewhere, Dr. Vashi described key clinical points in addressing complications related to henna, hair removal through threading, and placement of decorative adornments on the forehead, called bindi. In addition, she pointed out common issues with facial and body marking created with kumkum powder, hair oils, and skin lightening agents.
 

Black henna

For cosmetic enhancement, henna is relatively benign. It is also no longer confined to the south Asian communities where it originated. However, Dr. Vashi pointed out that patients of south Asian origin or descent might be more likely to use black henna, a variety with more risks.

Black henna contains additives, such as diaminobenzenes and p-phenylenediamine (PPD), to darken the tone of the product as well as provide other desired characteristics, such as an accelerated drying time. While some patients do develop reactions to conventional henna, the risks of black henna are greater.

“The acute contact dermatitis reactions can include dyspigmentation, leukoderma, and keloids,” Dr. Vashi said. Other complications include erythema multiforme, temporary hypertrichosis, and systemic allergic reactions, such as angioedema.

While those who have had a reaction to henna should avoid further contact, Dr. Vashi warned that sequelae can include cross reactions with latex and rubber as well as some pharmaceutical agents, such as sulfonamides. When taking a patient history, she noted, be aware that risks of henna extend to the hairdressers and cosmeticians who sometimes apply these products on others.

Hair threading, bindi, and kumkum

Hair threading, another practice popularized in south Asia and now growing in popularity globally, involves capturing hairs between cotton threads for removal of both the hair and its follicle. It is a relatively rapid and efficient method of permanent depilation. In addition to pain and erythema, Dr. Vashi reported that the complications associated with hair threading include pigmentary changes, infections such as bullous impetigo, and lesions of koebnerization – such as vitiligo and lichen planus.

Bindi, a Hindi tradition that involves placing adornments between the eyebrows, and kumkum, a powder typically made from turmeric to be employed for decorative markings, have also spread to use outside of their cultural context, according to Dr. Vashi. She said that the complications of these two cosmetic practices are shared, and stem largely from contact dermatitis.

Veena Nair/Moment/Getty Images

Hair oils, skin-lightening agents

Culturally-linked hair oils among patients from south Asia or Africa – or descendants from these areas – can damage hair in a variety of ways as well as cause contact dermatitis. The oils can also exacerbate existing skin diseases.

“Oils with high oleic acid, such as coconut or olive oils or shea butter, can worsen seborrheic dermatitis,” Dr. Vashi cautioned.

Of this list of dermatologic issues induced by culturally linked cosmetic practices, skin lightening agents might pose the most risk for permanent and irreversible complications. Dr. Vashi said that up to 70% of patients using lighteners develop complications, and there is a relationship between the severity of side effects as duration of use increases.

“The problem is that ingredients of many of these products, which are imported illegally and sold on the black market, are often not disclosed,” Dr. Vashi said. Some contain a high content of metals such as lead, copper, and iron, whether they are added intentionally or end up in the product because of poor quality control. For those developing adverse events associated with the products, the obvious treatment is discontinuation.

When patients are unwilling to discontinue any of the products that have led to dermatologic issues, Dr. Vashi encouraged physicians “to take a middle ground.” Simple avoidance can be challenging for practices that are culturally meaningful. In respecting cultural differences, she encouraged tolerance and compromise.

“Often these patients will be doing an alternative medication or intervention, but this does not mean that they are not accepting what we have to offer,” she said. She indicated that mutual respect will lead to better solutions.

The awareness of common cultural practices that can have a harmful impact on the skin is an area of practice that deserves more attention, Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology at Weill Cornell Medical Center, New York, said in an interview.

With the strong likelihood that dermatologists in the United States will have to resolve dermatologic issues created by cultural cosmetic practices originating elsewhere, strategies for an open nonjudgmental approach are instrumental, according to a dermatologist with expertise in these types of cases who spoke at the Skin of Color Update 2021.

“Instead of avoiding the discussion of cultural practices, we should discuss them and be open about them. It fosters a comfortable environment, trust, and better compliance,” reported Neelam Ajit Vashi, MD, founding director of the Boston University Center for Ethnic Skin.

Out of fear of causing offense, a desire to be discreet, or of personal discomfort with foreign cultural practices, some clinicians might elect to limit themselves to the information that the patient volunteers, which is a mistake, according to Dr. Vashi.

“The avoidance of topics around culture actually limits the ability to have a successful relationship,” she maintained.

Successful encounters are not just based on a willingness to listen, Dr. Vashi said. Clinicians should be seeking a base of knowledge. With growing globalization and widespread immigration, “it is increasingly important for dermatologists in the U.S. to understand the role of cultural practices [in creating skin problems] and recognize the sequelae,” Dr. Vashi said.

Taking some common examples of dermatologic complaints created by cosmetic practices originating elsewhere, Dr. Vashi described key clinical points in addressing complications related to henna, hair removal through threading, and placement of decorative adornments on the forehead, called bindi. In addition, she pointed out common issues with facial and body marking created with kumkum powder, hair oils, and skin lightening agents.
 

Black henna

For cosmetic enhancement, henna is relatively benign. It is also no longer confined to the south Asian communities where it originated. However, Dr. Vashi pointed out that patients of south Asian origin or descent might be more likely to use black henna, a variety with more risks.

Black henna contains additives, such as diaminobenzenes and p-phenylenediamine (PPD), to darken the tone of the product as well as provide other desired characteristics, such as an accelerated drying time. While some patients do develop reactions to conventional henna, the risks of black henna are greater.

“The acute contact dermatitis reactions can include dyspigmentation, leukoderma, and keloids,” Dr. Vashi said. Other complications include erythema multiforme, temporary hypertrichosis, and systemic allergic reactions, such as angioedema.

While those who have had a reaction to henna should avoid further contact, Dr. Vashi warned that sequelae can include cross reactions with latex and rubber as well as some pharmaceutical agents, such as sulfonamides. When taking a patient history, she noted, be aware that risks of henna extend to the hairdressers and cosmeticians who sometimes apply these products on others.

Hair threading, bindi, and kumkum

Hair threading, another practice popularized in south Asia and now growing in popularity globally, involves capturing hairs between cotton threads for removal of both the hair and its follicle. It is a relatively rapid and efficient method of permanent depilation. In addition to pain and erythema, Dr. Vashi reported that the complications associated with hair threading include pigmentary changes, infections such as bullous impetigo, and lesions of koebnerization – such as vitiligo and lichen planus.

Bindi, a Hindi tradition that involves placing adornments between the eyebrows, and kumkum, a powder typically made from turmeric to be employed for decorative markings, have also spread to use outside of their cultural context, according to Dr. Vashi. She said that the complications of these two cosmetic practices are shared, and stem largely from contact dermatitis.

Veena Nair/Moment/Getty Images

Hair oils, skin-lightening agents

Culturally-linked hair oils among patients from south Asia or Africa – or descendants from these areas – can damage hair in a variety of ways as well as cause contact dermatitis. The oils can also exacerbate existing skin diseases.

“Oils with high oleic acid, such as coconut or olive oils or shea butter, can worsen seborrheic dermatitis,” Dr. Vashi cautioned.

Of this list of dermatologic issues induced by culturally linked cosmetic practices, skin lightening agents might pose the most risk for permanent and irreversible complications. Dr. Vashi said that up to 70% of patients using lighteners develop complications, and there is a relationship between the severity of side effects as duration of use increases.

“The problem is that ingredients of many of these products, which are imported illegally and sold on the black market, are often not disclosed,” Dr. Vashi said. Some contain a high content of metals such as lead, copper, and iron, whether they are added intentionally or end up in the product because of poor quality control. For those developing adverse events associated with the products, the obvious treatment is discontinuation.

When patients are unwilling to discontinue any of the products that have led to dermatologic issues, Dr. Vashi encouraged physicians “to take a middle ground.” Simple avoidance can be challenging for practices that are culturally meaningful. In respecting cultural differences, she encouraged tolerance and compromise.

“Often these patients will be doing an alternative medication or intervention, but this does not mean that they are not accepting what we have to offer,” she said. She indicated that mutual respect will lead to better solutions.

The awareness of common cultural practices that can have a harmful impact on the skin is an area of practice that deserves more attention, Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology at Weill Cornell Medical Center, New York, said in an interview.

With the strong likelihood that dermatologists in the United States will have to resolve dermatologic issues created by cultural cosmetic practices originating elsewhere, strategies for an open nonjudgmental approach are instrumental, according to a dermatologist with expertise in these types of cases who spoke at the Skin of Color Update 2021.

“Instead of avoiding the discussion of cultural practices, we should discuss them and be open about them. It fosters a comfortable environment, trust, and better compliance,” reported Neelam Ajit Vashi, MD, founding director of the Boston University Center for Ethnic Skin.

Out of fear of causing offense, a desire to be discreet, or of personal discomfort with foreign cultural practices, some clinicians might elect to limit themselves to the information that the patient volunteers, which is a mistake, according to Dr. Vashi.

“The avoidance of topics around culture actually limits the ability to have a successful relationship,” she maintained.

Successful encounters are not just based on a willingness to listen, Dr. Vashi said. Clinicians should be seeking a base of knowledge. With growing globalization and widespread immigration, “it is increasingly important for dermatologists in the U.S. to understand the role of cultural practices [in creating skin problems] and recognize the sequelae,” Dr. Vashi said.

Taking some common examples of dermatologic complaints created by cosmetic practices originating elsewhere, Dr. Vashi described key clinical points in addressing complications related to henna, hair removal through threading, and placement of decorative adornments on the forehead, called bindi. In addition, she pointed out common issues with facial and body marking created with kumkum powder, hair oils, and skin lightening agents.
 

Black henna

For cosmetic enhancement, henna is relatively benign. It is also no longer confined to the south Asian communities where it originated. However, Dr. Vashi pointed out that patients of south Asian origin or descent might be more likely to use black henna, a variety with more risks.

Black henna contains additives, such as diaminobenzenes and p-phenylenediamine (PPD), to darken the tone of the product as well as provide other desired characteristics, such as an accelerated drying time. While some patients do develop reactions to conventional henna, the risks of black henna are greater.

“The acute contact dermatitis reactions can include dyspigmentation, leukoderma, and keloids,” Dr. Vashi said. Other complications include erythema multiforme, temporary hypertrichosis, and systemic allergic reactions, such as angioedema.

While those who have had a reaction to henna should avoid further contact, Dr. Vashi warned that sequelae can include cross reactions with latex and rubber as well as some pharmaceutical agents, such as sulfonamides. When taking a patient history, she noted, be aware that risks of henna extend to the hairdressers and cosmeticians who sometimes apply these products on others.

Hair threading, bindi, and kumkum

Hair threading, another practice popularized in south Asia and now growing in popularity globally, involves capturing hairs between cotton threads for removal of both the hair and its follicle. It is a relatively rapid and efficient method of permanent depilation. In addition to pain and erythema, Dr. Vashi reported that the complications associated with hair threading include pigmentary changes, infections such as bullous impetigo, and lesions of koebnerization – such as vitiligo and lichen planus.

Bindi, a Hindi tradition that involves placing adornments between the eyebrows, and kumkum, a powder typically made from turmeric to be employed for decorative markings, have also spread to use outside of their cultural context, according to Dr. Vashi. She said that the complications of these two cosmetic practices are shared, and stem largely from contact dermatitis.

Veena Nair/Moment/Getty Images

Hair oils, skin-lightening agents

Culturally-linked hair oils among patients from south Asia or Africa – or descendants from these areas – can damage hair in a variety of ways as well as cause contact dermatitis. The oils can also exacerbate existing skin diseases.

“Oils with high oleic acid, such as coconut or olive oils or shea butter, can worsen seborrheic dermatitis,” Dr. Vashi cautioned.

Of this list of dermatologic issues induced by culturally linked cosmetic practices, skin lightening agents might pose the most risk for permanent and irreversible complications. Dr. Vashi said that up to 70% of patients using lighteners develop complications, and there is a relationship between the severity of side effects as duration of use increases.

“The problem is that ingredients of many of these products, which are imported illegally and sold on the black market, are often not disclosed,” Dr. Vashi said. Some contain a high content of metals such as lead, copper, and iron, whether they are added intentionally or end up in the product because of poor quality control. For those developing adverse events associated with the products, the obvious treatment is discontinuation.

When patients are unwilling to discontinue any of the products that have led to dermatologic issues, Dr. Vashi encouraged physicians “to take a middle ground.” Simple avoidance can be challenging for practices that are culturally meaningful. In respecting cultural differences, she encouraged tolerance and compromise.

“Often these patients will be doing an alternative medication or intervention, but this does not mean that they are not accepting what we have to offer,” she said. She indicated that mutual respect will lead to better solutions.

The awareness of common cultural practices that can have a harmful impact on the skin is an area of practice that deserves more attention, Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology at Weill Cornell Medical Center, New York, said in an interview.

Any pause in taking the osteoporosis drug risedronate (Actonel) should last no longer than 2 years rather than the 2-3 years currently recommended for bisphosphonates, new research suggests.

BananaStock/thinkstockphotos.com

In a cohort of patients aged 66 and older in Ontario, Canada, those who had been taking risedronate had a 34% greater risk of a hip fracture during year 2 to year 3 of a pause in taking the drug – a drug holiday – compared with those who had been taking alendronate (Fosamax). 

The study showed that “risedronate, which has a shorter half-life, confers relatively less hip fracture protection than alendronate during drug holidays longer than 2 years and careful monitoring and follow-up after 2 years is likely warranted,” Kaley (Kaleen) N. Hayes, Pharm D, PhD, summarized in an oral presentation at the annual meeting of the American Society for Bone and Mineral Research. Dr. Hayes is an assistant professor in the department of health services, policy, and practice at Brown University School of Public Health, Providence, R.I.

“Although alendronate and risedronate have similar effectiveness for preventing fractures on treatment, our findings suggest that older patients on a risedronate drug holiday may benefit from assessment to consider resuming therapy after 2 years to prevent hip fractures,” she elaborated in an email.

Juliet Compston, MD, identified this study as one of the meeting’s clinical science highlights.

“This is the first study to directly compare fracture incidence during a drug holiday after treatment with the two most commonly prescribed oral bisphosphonates, alendronate and risedronate,” she told this news organization in an email.

The difference in fracture incidence during the 3-year drug holiday is “consistent with the known difference in pharmacokinetic properties of the two drugs,” noted Dr. Compston, professor of bone medicine and honorary consultant physician at the University of Cambridge (England) School of Clinical Medicine.

Since the increased risk of fracture after stopping risedronate vs. alendronate was seen by 2 years, “reevaluation of risk in risedronate-treated patients should therefore be considered earlier than the recommended period of 2-3 years after discontinuation,” she said.

“The study does not provide information about the optimal duration of drug holiday for either risedronate or alendronate, but it supports a shorter duration for the former of up to 2 years,” according to Dr. Compston.

Study rationale and findings

“The question of whether people treated for osteoporosis with oral bisphosphonates should have drug holidays is controversial,” Dr. Compston noted, “but many guidelines recommend that in lower-risk individuals who have received bisphosphonates for 5 years, a break from treatment of 2-3 years should be considered.”

Five or more years of bisphosphonate treatment for osteoporosis has been associated with rare adverse effects such as atypical femoral fractures, and these drugs appear to have fracture protection effects that linger for a while, so a drug holiday is recommended for most patients, Dr. Hayes added.

Guidelines such as the 2016 ASBMR task force report on long-term bisphosphonates for osteoporosis, she continued, “acknowledge that evidence for this recommendation comes primarily from the extension trial for alendronate, and patients undergoing a risedronate drug holiday may need to be reassessed earlier because of risedronate’s shorter half-life.”

Compared with alendronate, risedronate accumulates less in the bone and is eliminated more quickly from the body, so its fracture protection during drug holidays may be shorter.

The researchers aimed to estimate the 3-year fracture risk after discontinuing long-term (3 or more years) risedronate vs. alendronate therapy among older adults in Ontario.

From health care administrative data, they identified 120,368 patients aged 66 years and older who had started taking risedronate or alendronate as initial therapy for osteoporosis during the period 2000-2016. They had taken the therapy for 3 or more years (with at least 80% adherence) before stopping it for 120 days or longer.

The researchers found that 45% of patients were taking risedronate and 55% were taking alendronate, which are the main bisphosphonates used in Ontario, Dr. Hayes noted. Etidronate (Didronel) is recommended as second-line therapy and accounts for less than 2% of patients starting oral bisphosphonate therapy. 

In an earlier study, the researchers identified a shift toward greater use of risedronate than alendronate since 2008, likely related to newer formulations (for example, monthly and weekly delayed-release formulations of risedronate vs. only weekly alendronate formulations).

The researchers matched 25,077 patients taking alendronate with 25,077 patients taking risedronate, based on fracture risk–related characteristics, including demographics, diagnoses, medication use, and health care use.

The patients had a mean age of 74 when they started taking an oral bisphosphonate; 82% were women and most were White.  

Most patients (78%) had received a prescription from a general practitioner and, on average, they took the bisphosphonate therapy for 5.9 years before the drug holiday.  

The primary outcome of incident hip fracture during a 3-year drug holiday occurred in 915 patients. There were 12.4 events per 1,000 patients in the risedronate group vs. 10.6 events per 1,000 patients in the alendronate group (hazard ratio, 1.18; 95% confidence interval, 1.04-1.34).

The risks were not significantly higher during year 1 or year 2 of the drug holiday, but the curves began to diverge after 2 years, coauthor Suzanne Cadarette, PhD, of the Leslie Dan Faculty of Pharmacy at the University of Toronto, explained when replying to a question after the presentation. Dr. Cadarette supervised this PhD dissertation research by Dr. Hayes.

The researchers acknowledged that the limitations of their study include a lack of information about race or bone mineral density, and the findings may not apply to a younger, more racially diverse population.

The research was supported by the University of Toronto Dalla Lana School of Public Health and the Leslie Dan Faculty of Pharmacy, a Canadian Institutes of Health Research grant, and a doctoral research award. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Any pause in taking the osteoporosis drug risedronate (Actonel) should last no longer than 2 years rather than the 2-3 years currently recommended for bisphosphonates, new research suggests.

BananaStock/thinkstockphotos.com

In a cohort of patients aged 66 and older in Ontario, Canada, those who had been taking risedronate had a 34% greater risk of a hip fracture during year 2 to year 3 of a pause in taking the drug – a drug holiday – compared with those who had been taking alendronate (Fosamax). 

The study showed that “risedronate, which has a shorter half-life, confers relatively less hip fracture protection than alendronate during drug holidays longer than 2 years and careful monitoring and follow-up after 2 years is likely warranted,” Kaley (Kaleen) N. Hayes, Pharm D, PhD, summarized in an oral presentation at the annual meeting of the American Society for Bone and Mineral Research. Dr. Hayes is an assistant professor in the department of health services, policy, and practice at Brown University School of Public Health, Providence, R.I.

“Although alendronate and risedronate have similar effectiveness for preventing fractures on treatment, our findings suggest that older patients on a risedronate drug holiday may benefit from assessment to consider resuming therapy after 2 years to prevent hip fractures,” she elaborated in an email.

Juliet Compston, MD, identified this study as one of the meeting’s clinical science highlights.

“This is the first study to directly compare fracture incidence during a drug holiday after treatment with the two most commonly prescribed oral bisphosphonates, alendronate and risedronate,” she told this news organization in an email.

The difference in fracture incidence during the 3-year drug holiday is “consistent with the known difference in pharmacokinetic properties of the two drugs,” noted Dr. Compston, professor of bone medicine and honorary consultant physician at the University of Cambridge (England) School of Clinical Medicine.

Since the increased risk of fracture after stopping risedronate vs. alendronate was seen by 2 years, “reevaluation of risk in risedronate-treated patients should therefore be considered earlier than the recommended period of 2-3 years after discontinuation,” she said.

“The study does not provide information about the optimal duration of drug holiday for either risedronate or alendronate, but it supports a shorter duration for the former of up to 2 years,” according to Dr. Compston.

Study rationale and findings

“The question of whether people treated for osteoporosis with oral bisphosphonates should have drug holidays is controversial,” Dr. Compston noted, “but many guidelines recommend that in lower-risk individuals who have received bisphosphonates for 5 years, a break from treatment of 2-3 years should be considered.”

Five or more years of bisphosphonate treatment for osteoporosis has been associated with rare adverse effects such as atypical femoral fractures, and these drugs appear to have fracture protection effects that linger for a while, so a drug holiday is recommended for most patients, Dr. Hayes added.

Guidelines such as the 2016 ASBMR task force report on long-term bisphosphonates for osteoporosis, she continued, “acknowledge that evidence for this recommendation comes primarily from the extension trial for alendronate, and patients undergoing a risedronate drug holiday may need to be reassessed earlier because of risedronate’s shorter half-life.”

Compared with alendronate, risedronate accumulates less in the bone and is eliminated more quickly from the body, so its fracture protection during drug holidays may be shorter.

The researchers aimed to estimate the 3-year fracture risk after discontinuing long-term (3 or more years) risedronate vs. alendronate therapy among older adults in Ontario.

From health care administrative data, they identified 120,368 patients aged 66 years and older who had started taking risedronate or alendronate as initial therapy for osteoporosis during the period 2000-2016. They had taken the therapy for 3 or more years (with at least 80% adherence) before stopping it for 120 days or longer.

The researchers found that 45% of patients were taking risedronate and 55% were taking alendronate, which are the main bisphosphonates used in Ontario, Dr. Hayes noted. Etidronate (Didronel) is recommended as second-line therapy and accounts for less than 2% of patients starting oral bisphosphonate therapy. 

In an earlier study, the researchers identified a shift toward greater use of risedronate than alendronate since 2008, likely related to newer formulations (for example, monthly and weekly delayed-release formulations of risedronate vs. only weekly alendronate formulations).

The researchers matched 25,077 patients taking alendronate with 25,077 patients taking risedronate, based on fracture risk–related characteristics, including demographics, diagnoses, medication use, and health care use.

The patients had a mean age of 74 when they started taking an oral bisphosphonate; 82% were women and most were White.  

Most patients (78%) had received a prescription from a general practitioner and, on average, they took the bisphosphonate therapy for 5.9 years before the drug holiday.  

The primary outcome of incident hip fracture during a 3-year drug holiday occurred in 915 patients. There were 12.4 events per 1,000 patients in the risedronate group vs. 10.6 events per 1,000 patients in the alendronate group (hazard ratio, 1.18; 95% confidence interval, 1.04-1.34).

The risks were not significantly higher during year 1 or year 2 of the drug holiday, but the curves began to diverge after 2 years, coauthor Suzanne Cadarette, PhD, of the Leslie Dan Faculty of Pharmacy at the University of Toronto, explained when replying to a question after the presentation. Dr. Cadarette supervised this PhD dissertation research by Dr. Hayes.

The researchers acknowledged that the limitations of their study include a lack of information about race or bone mineral density, and the findings may not apply to a younger, more racially diverse population.

The research was supported by the University of Toronto Dalla Lana School of Public Health and the Leslie Dan Faculty of Pharmacy, a Canadian Institutes of Health Research grant, and a doctoral research award. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Any pause in taking the osteoporosis drug risedronate (Actonel) should last no longer than 2 years rather than the 2-3 years currently recommended for bisphosphonates, new research suggests.

BananaStock/thinkstockphotos.com

In a cohort of patients aged 66 and older in Ontario, Canada, those who had been taking risedronate had a 34% greater risk of a hip fracture during year 2 to year 3 of a pause in taking the drug – a drug holiday – compared with those who had been taking alendronate (Fosamax). 

The study showed that “risedronate, which has a shorter half-life, confers relatively less hip fracture protection than alendronate during drug holidays longer than 2 years and careful monitoring and follow-up after 2 years is likely warranted,” Kaley (Kaleen) N. Hayes, Pharm D, PhD, summarized in an oral presentation at the annual meeting of the American Society for Bone and Mineral Research. Dr. Hayes is an assistant professor in the department of health services, policy, and practice at Brown University School of Public Health, Providence, R.I.

“Although alendronate and risedronate have similar effectiveness for preventing fractures on treatment, our findings suggest that older patients on a risedronate drug holiday may benefit from assessment to consider resuming therapy after 2 years to prevent hip fractures,” she elaborated in an email.

Juliet Compston, MD, identified this study as one of the meeting’s clinical science highlights.

“This is the first study to directly compare fracture incidence during a drug holiday after treatment with the two most commonly prescribed oral bisphosphonates, alendronate and risedronate,” she told this news organization in an email.

The difference in fracture incidence during the 3-year drug holiday is “consistent with the known difference in pharmacokinetic properties of the two drugs,” noted Dr. Compston, professor of bone medicine and honorary consultant physician at the University of Cambridge (England) School of Clinical Medicine.

Since the increased risk of fracture after stopping risedronate vs. alendronate was seen by 2 years, “reevaluation of risk in risedronate-treated patients should therefore be considered earlier than the recommended period of 2-3 years after discontinuation,” she said.

“The study does not provide information about the optimal duration of drug holiday for either risedronate or alendronate, but it supports a shorter duration for the former of up to 2 years,” according to Dr. Compston.

Study rationale and findings

“The question of whether people treated for osteoporosis with oral bisphosphonates should have drug holidays is controversial,” Dr. Compston noted, “but many guidelines recommend that in lower-risk individuals who have received bisphosphonates for 5 years, a break from treatment of 2-3 years should be considered.”

Five or more years of bisphosphonate treatment for osteoporosis has been associated with rare adverse effects such as atypical femoral fractures, and these drugs appear to have fracture protection effects that linger for a while, so a drug holiday is recommended for most patients, Dr. Hayes added.

Guidelines such as the 2016 ASBMR task force report on long-term bisphosphonates for osteoporosis, she continued, “acknowledge that evidence for this recommendation comes primarily from the extension trial for alendronate, and patients undergoing a risedronate drug holiday may need to be reassessed earlier because of risedronate’s shorter half-life.”

Compared with alendronate, risedronate accumulates less in the bone and is eliminated more quickly from the body, so its fracture protection during drug holidays may be shorter.

The researchers aimed to estimate the 3-year fracture risk after discontinuing long-term (3 or more years) risedronate vs. alendronate therapy among older adults in Ontario.

From health care administrative data, they identified 120,368 patients aged 66 years and older who had started taking risedronate or alendronate as initial therapy for osteoporosis during the period 2000-2016. They had taken the therapy for 3 or more years (with at least 80% adherence) before stopping it for 120 days or longer.

The researchers found that 45% of patients were taking risedronate and 55% were taking alendronate, which are the main bisphosphonates used in Ontario, Dr. Hayes noted. Etidronate (Didronel) is recommended as second-line therapy and accounts for less than 2% of patients starting oral bisphosphonate therapy. 

In an earlier study, the researchers identified a shift toward greater use of risedronate than alendronate since 2008, likely related to newer formulations (for example, monthly and weekly delayed-release formulations of risedronate vs. only weekly alendronate formulations).

The researchers matched 25,077 patients taking alendronate with 25,077 patients taking risedronate, based on fracture risk–related characteristics, including demographics, diagnoses, medication use, and health care use.

The patients had a mean age of 74 when they started taking an oral bisphosphonate; 82% were women and most were White.  

Most patients (78%) had received a prescription from a general practitioner and, on average, they took the bisphosphonate therapy for 5.9 years before the drug holiday.  

The primary outcome of incident hip fracture during a 3-year drug holiday occurred in 915 patients. There were 12.4 events per 1,000 patients in the risedronate group vs. 10.6 events per 1,000 patients in the alendronate group (hazard ratio, 1.18; 95% confidence interval, 1.04-1.34).

The risks were not significantly higher during year 1 or year 2 of the drug holiday, but the curves began to diverge after 2 years, coauthor Suzanne Cadarette, PhD, of the Leslie Dan Faculty of Pharmacy at the University of Toronto, explained when replying to a question after the presentation. Dr. Cadarette supervised this PhD dissertation research by Dr. Hayes.

The researchers acknowledged that the limitations of their study include a lack of information about race or bone mineral density, and the findings may not apply to a younger, more racially diverse population.

The research was supported by the University of Toronto Dalla Lana School of Public Health and the Leslie Dan Faculty of Pharmacy, a Canadian Institutes of Health Research grant, and a doctoral research award. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

“Postmenopausal women with low bone mass should obtain adequate calcium and vitamin D and participate in bone-loading exercises,” researchers noted in a recent study published in Osteoporosis International.

sbm Hotting/Fotolia.com

“Additional use of bisphosphonates will increase bone mineral density (BMD), especially at the spine,” wrote Nancy Waltman, PhD, College of Nursing, University of Nebraska Medical Center, Omaha, and colleagues.

The findings are partial results from the Heartland Osteoporosis Prevention Study (HOPS), which randomized women who had entered menopause within the previous 6 months and had osteopenia (low bone mass, T score –1.0 to –2.49) to receive one of three treatments for 12 months:

• Bone-loading and resistance exercise plus calcium and vitamin D supplements.
• Risedronate plus calcium and vitamin D supplements.
• Calcium and vitamin D supplements alone (control).

At 1 year, “risedronate significantly increased BMD at the spine, compared to exercise and control, and serum biomarkers of bone turnover also significantly reduced in the risedronate group,” Laura Bilek, PT, PhD, said during an oral presentation of the research at the annual meeting of the American Society for Bone and Mineral Research.

However, the results also showed that, importantly, “in postmenopausal women, exercise appears to improve strength at the hip through changes in structure, not BMD,” stressed Dr. Bilek, of the College of Allied Health Professionals, University of Nebraska Medical Center.
 

Bone health is about more than just bone mineral density

“The key takeaway for clinicians is that bone health is about more than just density!” she noted in an email.

Current guidelines don’t recommend prescribing risedronate until a woman has overt osteoporosis, she said.

On the other hand, many studies have shown that, to be most effective, bone-loading exercises should be a lifelong habit and women should begin to do them at least during menopause and should not wait until bone loss occurs.

Other studies have shown that exercise changes bone structure (size or geometry), which improves bone strength. The current study supports both prior observations.

And exercise also improves muscle strength and decreases the risk of falls and fractures, Dr. Bilek noted.

Invited to comment, Pauline M. Camacho, MD, cochair of the task force for the American Association of Clinical Endocrinologists (AACE) guidelines for osteoporosis, noted that all three measures – pharmacotherapy, exercise, and calcium/vitamin D – are important in the successful management of osteoporosis.

This study showed that risedronate is superior to calcium/vitamin D supplementation as well as exercise for BMD and for bone turnover in these women with osteopenia, said Dr. Camacho, professor of medicine and director of the Osteoporosis and Metabolic Bone Disease Center, Loyola University Medical Center, Chicago.

“Most women with osteopenia do not receive pharmacologic therapy,” she noted, and receive it only “if there is a history of fractures or they have other features that change that diagnosis to osteoporosis.

“There is no downside to exercise, and this needs to be advised to all patients,” she said. “The other aspect of exercise that was not assessed in this study is its effect on balance. Patients who exercise will have improved balance, which should translate into fewer falls, and thus fewer fractures.”
 

How can women with osteopenia maintain bone health?

In their article, Dr. Waltman and colleagues say the Lifting Intervention for Training Muscle and Osteoporosis Rehabilitation (LIFTMOR) clinical trial is one of the first to address clinician concerns about the safety and effectiveness of exercise to improve bone health.

In that trial of 101 postmenopausal women with low bone mass, 8 months of 30-minute, twice-weekly, supervised high-intensity resistance and impact training was safe and BMD increased by 2.9% at the lumbar spine and 0.3% at the femoral neck.

“Our [HOPS] study,” Dr. Waltman and colleagues explained, “builds on the LIFTMOR clinical trial and adds further data to inform whether postmenopausal women with low bone mass can effectively maintain or even improve BMD with bone-loading exercises prior to prescriptions for medication.

“Our long-term goal is to contribute to the development of clinical practice guidelines for the prevention of fractures in postmenopausal women with low bone mass,” they said.

They randomized 276 postmenopausal women who were a mean age of 54 (range, 44-63); most were White (78%) or Hispanic (6%).

Women were excluded from the study if they had a diagnosis of osteoporosis (T-score < −2.5); had an increased risk of a major fracture or hip fracture; had been on bisphosphonates within the last 6 months; were currently on estrogen, tamoxifen, or aromatase inhibitors; had a serum vitamin D level < 10 mg/mL or > 100 mg/mL; had any conditions that prohibited prescriptions for calcium and vitamin D supplements, risedronate, or exercise; or weighed more than 300 pounds.

All women received 1,200 mg/day of calcium (from supplements or diet) and 1,000-3,000 IU/day of vitamin D supplements, based on their serum 25(OH) vitamin D levels.  

The exercise program consisted of visiting a gym three times a week for 45 minutes of bone-loading exercise – jogging with a weighted vest – and resistance exercises, which were supervised by a trainer for the first 2 weeks.

Women in the risedronate group received a 150-mg tablet of risedronate every 4 weeks.  

At baseline, 6 months, and 12 months, the women had DXA scans to determine BMD and hip structure, and had blood tests to determine levels of serum markers for bone formation (bone specific alkaline phosphatase [Alkphase B]) and bone resorption (N-terminal telopeptide [NTx]).

Compared with baseline, at 12 months, the women had the following changes in BMD at the following sites:

• Spine: +1.9%, +0.9%, and –0.4%, in the risedronate, exercise, and control groups.
• Total hip: +0.9%, +0.5%, and +0.5%, in the risedronate, exercise, and control groups.
• Femoral neck: +0.09%, –0.4%, and –0.5%, in the risedronate, exercise, and control groups.

These improvements in BMD were significantly greater in the risedronate group than in the exercise or control groups (P < .01 for both).

The decreases in serum levels of NtX and Alkphase B were also greater with risedronate than in the exercise or control groups (P < .01 for all).

The most frequent adverse effect with the calcium supplement was constipation (n = 4). Some women taking risedronate had gastrointestinal disturbances (n = 4), muscle or joint pain (n = 11), or chest pain and dizziness (n = 2). None of the women had adverse effects from vitamin D. A few women had muscle soreness from exercise that went away after the exercises were adapted. None of the women had a serious injury or fracture from exercise.

More women in the exercise group withdrew from the study (n = 20), with most citing lack of time as the reason; 13 women withdrew from the risedronate group, and 16 withdrew from the control group.

Of the 276 participants who completed the 12-month study, treatment adherence was 92% for calcium, 94% for vitamin D, 75% for risedronate, and 59% for exercise.

Exercise was associated with positive changes in intertrochanter hip structural analysis measures, which will be described in an upcoming study, Dr. Bilek said.

The study was funded by the National Institute of Nursing Research of the National Institutes of Health. The researchers have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

“Postmenopausal women with low bone mass should obtain adequate calcium and vitamin D and participate in bone-loading exercises,” researchers noted in a recent study published in Osteoporosis International.

sbm Hotting/Fotolia.com

“Additional use of bisphosphonates will increase bone mineral density (BMD), especially at the spine,” wrote Nancy Waltman, PhD, College of Nursing, University of Nebraska Medical Center, Omaha, and colleagues.

The findings are partial results from the Heartland Osteoporosis Prevention Study (HOPS), which randomized women who had entered menopause within the previous 6 months and had osteopenia (low bone mass, T score –1.0 to –2.49) to receive one of three treatments for 12 months:

• Bone-loading and resistance exercise plus calcium and vitamin D supplements.
• Risedronate plus calcium and vitamin D supplements.
• Calcium and vitamin D supplements alone (control).

At 1 year, “risedronate significantly increased BMD at the spine, compared to exercise and control, and serum biomarkers of bone turnover also significantly reduced in the risedronate group,” Laura Bilek, PT, PhD, said during an oral presentation of the research at the annual meeting of the American Society for Bone and Mineral Research.

However, the results also showed that, importantly, “in postmenopausal women, exercise appears to improve strength at the hip through changes in structure, not BMD,” stressed Dr. Bilek, of the College of Allied Health Professionals, University of Nebraska Medical Center.
 

Bone health is about more than just bone mineral density

“The key takeaway for clinicians is that bone health is about more than just density!” she noted in an email.

Current guidelines don’t recommend prescribing risedronate until a woman has overt osteoporosis, she said.

On the other hand, many studies have shown that, to be most effective, bone-loading exercises should be a lifelong habit and women should begin to do them at least during menopause and should not wait until bone loss occurs.

Other studies have shown that exercise changes bone structure (size or geometry), which improves bone strength. The current study supports both prior observations.

And exercise also improves muscle strength and decreases the risk of falls and fractures, Dr. Bilek noted.

Invited to comment, Pauline M. Camacho, MD, cochair of the task force for the American Association of Clinical Endocrinologists (AACE) guidelines for osteoporosis, noted that all three measures – pharmacotherapy, exercise, and calcium/vitamin D – are important in the successful management of osteoporosis.

This study showed that risedronate is superior to calcium/vitamin D supplementation as well as exercise for BMD and for bone turnover in these women with osteopenia, said Dr. Camacho, professor of medicine and director of the Osteoporosis and Metabolic Bone Disease Center, Loyola University Medical Center, Chicago.

“Most women with osteopenia do not receive pharmacologic therapy,” she noted, and receive it only “if there is a history of fractures or they have other features that change that diagnosis to osteoporosis.

“There is no downside to exercise, and this needs to be advised to all patients,” she said. “The other aspect of exercise that was not assessed in this study is its effect on balance. Patients who exercise will have improved balance, which should translate into fewer falls, and thus fewer fractures.”
 

How can women with osteopenia maintain bone health?

In their article, Dr. Waltman and colleagues say the Lifting Intervention for Training Muscle and Osteoporosis Rehabilitation (LIFTMOR) clinical trial is one of the first to address clinician concerns about the safety and effectiveness of exercise to improve bone health.

In that trial of 101 postmenopausal women with low bone mass, 8 months of 30-minute, twice-weekly, supervised high-intensity resistance and impact training was safe and BMD increased by 2.9% at the lumbar spine and 0.3% at the femoral neck.

“Our [HOPS] study,” Dr. Waltman and colleagues explained, “builds on the LIFTMOR clinical trial and adds further data to inform whether postmenopausal women with low bone mass can effectively maintain or even improve BMD with bone-loading exercises prior to prescriptions for medication.

“Our long-term goal is to contribute to the development of clinical practice guidelines for the prevention of fractures in postmenopausal women with low bone mass,” they said.

They randomized 276 postmenopausal women who were a mean age of 54 (range, 44-63); most were White (78%) or Hispanic (6%).

Women were excluded from the study if they had a diagnosis of osteoporosis (T-score < −2.5); had an increased risk of a major fracture or hip fracture; had been on bisphosphonates within the last 6 months; were currently on estrogen, tamoxifen, or aromatase inhibitors; had a serum vitamin D level < 10 mg/mL or > 100 mg/mL; had any conditions that prohibited prescriptions for calcium and vitamin D supplements, risedronate, or exercise; or weighed more than 300 pounds.

All women received 1,200 mg/day of calcium (from supplements or diet) and 1,000-3,000 IU/day of vitamin D supplements, based on their serum 25(OH) vitamin D levels.  

The exercise program consisted of visiting a gym three times a week for 45 minutes of bone-loading exercise – jogging with a weighted vest – and resistance exercises, which were supervised by a trainer for the first 2 weeks.

Women in the risedronate group received a 150-mg tablet of risedronate every 4 weeks.  

At baseline, 6 months, and 12 months, the women had DXA scans to determine BMD and hip structure, and had blood tests to determine levels of serum markers for bone formation (bone specific alkaline phosphatase [Alkphase B]) and bone resorption (N-terminal telopeptide [NTx]).

Compared with baseline, at 12 months, the women had the following changes in BMD at the following sites:

• Spine: +1.9%, +0.9%, and –0.4%, in the risedronate, exercise, and control groups.
• Total hip: +0.9%, +0.5%, and +0.5%, in the risedronate, exercise, and control groups.
• Femoral neck: +0.09%, –0.4%, and –0.5%, in the risedronate, exercise, and control groups.

These improvements in BMD were significantly greater in the risedronate group than in the exercise or control groups (P < .01 for both).

The decreases in serum levels of NtX and Alkphase B were also greater with risedronate than in the exercise or control groups (P < .01 for all).

The most frequent adverse effect with the calcium supplement was constipation (n = 4). Some women taking risedronate had gastrointestinal disturbances (n = 4), muscle or joint pain (n = 11), or chest pain and dizziness (n = 2). None of the women had adverse effects from vitamin D. A few women had muscle soreness from exercise that went away after the exercises were adapted. None of the women had a serious injury or fracture from exercise.

More women in the exercise group withdrew from the study (n = 20), with most citing lack of time as the reason; 13 women withdrew from the risedronate group, and 16 withdrew from the control group.

Of the 276 participants who completed the 12-month study, treatment adherence was 92% for calcium, 94% for vitamin D, 75% for risedronate, and 59% for exercise.

Exercise was associated with positive changes in intertrochanter hip structural analysis measures, which will be described in an upcoming study, Dr. Bilek said.

The study was funded by the National Institute of Nursing Research of the National Institutes of Health. The researchers have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

“Postmenopausal women with low bone mass should obtain adequate calcium and vitamin D and participate in bone-loading exercises,” researchers noted in a recent study published in Osteoporosis International.

sbm Hotting/Fotolia.com

“Additional use of bisphosphonates will increase bone mineral density (BMD), especially at the spine,” wrote Nancy Waltman, PhD, College of Nursing, University of Nebraska Medical Center, Omaha, and colleagues.

The findings are partial results from the Heartland Osteoporosis Prevention Study (HOPS), which randomized women who had entered menopause within the previous 6 months and had osteopenia (low bone mass, T score –1.0 to –2.49) to receive one of three treatments for 12 months:

• Bone-loading and resistance exercise plus calcium and vitamin D supplements.
• Risedronate plus calcium and vitamin D supplements.
• Calcium and vitamin D supplements alone (control).

At 1 year, “risedronate significantly increased BMD at the spine, compared to exercise and control, and serum biomarkers of bone turnover also significantly reduced in the risedronate group,” Laura Bilek, PT, PhD, said during an oral presentation of the research at the annual meeting of the American Society for Bone and Mineral Research.

However, the results also showed that, importantly, “in postmenopausal women, exercise appears to improve strength at the hip through changes in structure, not BMD,” stressed Dr. Bilek, of the College of Allied Health Professionals, University of Nebraska Medical Center.
 

Bone health is about more than just bone mineral density

“The key takeaway for clinicians is that bone health is about more than just density!” she noted in an email.

Current guidelines don’t recommend prescribing risedronate until a woman has overt osteoporosis, she said.

On the other hand, many studies have shown that, to be most effective, bone-loading exercises should be a lifelong habit and women should begin to do them at least during menopause and should not wait until bone loss occurs.

Other studies have shown that exercise changes bone structure (size or geometry), which improves bone strength. The current study supports both prior observations.

And exercise also improves muscle strength and decreases the risk of falls and fractures, Dr. Bilek noted.

Invited to comment, Pauline M. Camacho, MD, cochair of the task force for the American Association of Clinical Endocrinologists (AACE) guidelines for osteoporosis, noted that all three measures – pharmacotherapy, exercise, and calcium/vitamin D – are important in the successful management of osteoporosis.

This study showed that risedronate is superior to calcium/vitamin D supplementation as well as exercise for BMD and for bone turnover in these women with osteopenia, said Dr. Camacho, professor of medicine and director of the Osteoporosis and Metabolic Bone Disease Center, Loyola University Medical Center, Chicago.

“Most women with osteopenia do not receive pharmacologic therapy,” she noted, and receive it only “if there is a history of fractures or they have other features that change that diagnosis to osteoporosis.

“There is no downside to exercise, and this needs to be advised to all patients,” she said. “The other aspect of exercise that was not assessed in this study is its effect on balance. Patients who exercise will have improved balance, which should translate into fewer falls, and thus fewer fractures.”
 

How can women with osteopenia maintain bone health?

In their article, Dr. Waltman and colleagues say the Lifting Intervention for Training Muscle and Osteoporosis Rehabilitation (LIFTMOR) clinical trial is one of the first to address clinician concerns about the safety and effectiveness of exercise to improve bone health.

In that trial of 101 postmenopausal women with low bone mass, 8 months of 30-minute, twice-weekly, supervised high-intensity resistance and impact training was safe and BMD increased by 2.9% at the lumbar spine and 0.3% at the femoral neck.

“Our [HOPS] study,” Dr. Waltman and colleagues explained, “builds on the LIFTMOR clinical trial and adds further data to inform whether postmenopausal women with low bone mass can effectively maintain or even improve BMD with bone-loading exercises prior to prescriptions for medication.

“Our long-term goal is to contribute to the development of clinical practice guidelines for the prevention of fractures in postmenopausal women with low bone mass,” they said.

They randomized 276 postmenopausal women who were a mean age of 54 (range, 44-63); most were White (78%) or Hispanic (6%).

Women were excluded from the study if they had a diagnosis of osteoporosis (T-score < −2.5); had an increased risk of a major fracture or hip fracture; had been on bisphosphonates within the last 6 months; were currently on estrogen, tamoxifen, or aromatase inhibitors; had a serum vitamin D level < 10 mg/mL or > 100 mg/mL; had any conditions that prohibited prescriptions for calcium and vitamin D supplements, risedronate, or exercise; or weighed more than 300 pounds.

All women received 1,200 mg/day of calcium (from supplements or diet) and 1,000-3,000 IU/day of vitamin D supplements, based on their serum 25(OH) vitamin D levels.  

The exercise program consisted of visiting a gym three times a week for 45 minutes of bone-loading exercise – jogging with a weighted vest – and resistance exercises, which were supervised by a trainer for the first 2 weeks.

Women in the risedronate group received a 150-mg tablet of risedronate every 4 weeks.  

At baseline, 6 months, and 12 months, the women had DXA scans to determine BMD and hip structure, and had blood tests to determine levels of serum markers for bone formation (bone specific alkaline phosphatase [Alkphase B]) and bone resorption (N-terminal telopeptide [NTx]).

Compared with baseline, at 12 months, the women had the following changes in BMD at the following sites:

• Spine: +1.9%, +0.9%, and –0.4%, in the risedronate, exercise, and control groups.
• Total hip: +0.9%, +0.5%, and +0.5%, in the risedronate, exercise, and control groups.
• Femoral neck: +0.09%, –0.4%, and –0.5%, in the risedronate, exercise, and control groups.

These improvements in BMD were significantly greater in the risedronate group than in the exercise or control groups (P < .01 for both).

The decreases in serum levels of NtX and Alkphase B were also greater with risedronate than in the exercise or control groups (P < .01 for all).

The most frequent adverse effect with the calcium supplement was constipation (n = 4). Some women taking risedronate had gastrointestinal disturbances (n = 4), muscle or joint pain (n = 11), or chest pain and dizziness (n = 2). None of the women had adverse effects from vitamin D. A few women had muscle soreness from exercise that went away after the exercises were adapted. None of the women had a serious injury or fracture from exercise.

More women in the exercise group withdrew from the study (n = 20), with most citing lack of time as the reason; 13 women withdrew from the risedronate group, and 16 withdrew from the control group.

Of the 276 participants who completed the 12-month study, treatment adherence was 92% for calcium, 94% for vitamin D, 75% for risedronate, and 59% for exercise.

Exercise was associated with positive changes in intertrochanter hip structural analysis measures, which will be described in an upcoming study, Dr. Bilek said.

The study was funded by the National Institute of Nursing Research of the National Institutes of Health. The researchers have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People with insulin-treated type 1 diabetes who had problems avoiding hypoglycemic episodes despite optimal care were helped significantly by a new psychoeducational program called HARPdoc, it was reported at the annual meeting of the European Association for the Study of Diabetes.

In a randomized controlled trial (RCT), both HARPdoc and the more established Blood Glucose Awareness Training (BGAT) were effective at reducing the number of severe hypoglycemia episodes seen, from five episodes at baseline to one at 1 year in both groups, and one and none at 2-years’ follow-up, respectively.

“HARPdoc is not superior to BGAT in its ability to restore hypoglycemia awareness and reduce severe hypoglycemia,” said Stephanie Amiel, MD, FRCP, the chief investigator for the trial. However, “it does reduce cognitive barriers to hypoglycemia avoidance, so it achieves what it set out to do.”

Dr. Amiel, professor of diabetes research at Kings College London, added that it was important to note that HARPdoc was better than BGAT at improving participants’ mental health, “producing a clinically important and sustainable reduction in diabetes distress, anxiety, and depression.”
 

What’s HARPdoc?

The Hypoglycaemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycaemia persisting despite optimised self-care (HARPdoc) was designed to specifically address why some people with type 1 diabetes find it difficult to avoid recurrent hypoglycemia.

“It’s a psychoeducational program with clinical knowledge about hypoglycemia and group learning, but also explicit topics on mindset and behavior change,” explained Nicole de Zoysa, DClinPsych, one of the clinical psychologists involved in the trial.

Over the course of the 6-week program, there are four group sessions (weeks 1-3, and week 6) and two individual sessions (weeks 4 and 5) ­that address important “cognitive barriers” or “thinking traps” to avoiding hypoglycemia that were identified during prior qualitative research.

HARPdoc is thus “an attempt to make sense of people’s reluctance or seeming reluctance to take action around hypoglycemia, Dr. de Zoysa said. The intervention draws on both cognitive behavioral theory “to work with the beliefs” and motivational interviewing “to work with the resistance.”
 

The HARPdoc RCT

Starting in 2017 and ending earlier this year, the HARPdoc RCT was a parallel group study conducted at three specialist diabetes centers in the United Kingdom and one in the United States.

A total of 99 adults with insulin-treated type 1 diabetes and impaired hypoglycemia awareness were enrolled – with 49 randomized to the HARPdoc arm and 50 to the BGAT arm. All had been offered technologies to help them potentially bring their hypoglycemia under better control, such as continuous glucose monitoring, insulin pumps, or closed loop systems, and received structured education on flexible insulin dosing.

The aim was to show superiority of the HARPdoc program over BGAT, in helping people avoid episodes of severe hypoglycemia, defined as episodes that needed other people’s intervention to help resolve.

BGAT is also a psychoeducation program that has been around since the 1980s but barely used in the United Kingdom, Dr. Amiel noted.

Baseline demographic characteristics were similar for the HARPdoc and BGAT arms: The mean age was 57 versus 52 years, there was a long (30+ years) duration of diabetes, over half of the participants were male, and almost all were White.
 

Primary endpoint not met, but still ‘impressive’

Although the primary endpoint of the trial was not met, the reductions in severe hypoglycemia seen are still “impressive,” said Ramzi Ajjan, MD, FRCP, of Leeds (England) University and Leeds Teaching Hospitals Trust.

“I was really blown away,” by the improvement in both study arms, said Dr. Ajjan, who was not involved in the trial. “These people have had proper clinical input,” he stressed, noting that both interventions worked, with no difference between them in terms of severe hypoglycemia.

Dr. Ajjan was not surprised by the better cognition scores measured using the A2A questionnaire seen with HARPdoc versus BGAT, as “this is what the intervention was designed to address.”

In terms of the mental health benefits seen, HARPdoc significantly reduced the level of diabetes distress as measured using the Problem Areas In Diabetes (PAID) questionnaire versus the BGAT intervention.

The PAID score was around 30 in both groups at baseline, this fell to about 26 at 1 year, and around 20 at 2 years in the HARPdoc group, which was significantly lower than the score seen in the BGAT group which rose slightly then fell back to baseline levels.

A similar pattern was seen in the levels of depression and anxiety, which were measured by the HADS-D and HADS-A instruments. So HARPdoc was more effective at improving psychological and mental health outcomes than BGAT, Dr. Ajjan observed.

The HARPdoc project is funded by the Juvenile Diabetes Research Foundation with additional support from the UK’s National Institute of Health Research. The HARPdoc RCT was jointly sponsored by King’s College London and King’s College Hospital NHS Foundation Trust. Dr. Amiel has served on advisory panels for Roche, Medtronic, and Novo Nordisk. Dr. de Zoysa did not state having any conflicts of interest. Dr. Ajjan disclosed that he has financial relationships with multiple pharmaceutical companies.

People with insulin-treated type 1 diabetes who had problems avoiding hypoglycemic episodes despite optimal care were helped significantly by a new psychoeducational program called HARPdoc, it was reported at the annual meeting of the European Association for the Study of Diabetes.

In a randomized controlled trial (RCT), both HARPdoc and the more established Blood Glucose Awareness Training (BGAT) were effective at reducing the number of severe hypoglycemia episodes seen, from five episodes at baseline to one at 1 year in both groups, and one and none at 2-years’ follow-up, respectively.

“HARPdoc is not superior to BGAT in its ability to restore hypoglycemia awareness and reduce severe hypoglycemia,” said Stephanie Amiel, MD, FRCP, the chief investigator for the trial. However, “it does reduce cognitive barriers to hypoglycemia avoidance, so it achieves what it set out to do.”

Dr. Amiel, professor of diabetes research at Kings College London, added that it was important to note that HARPdoc was better than BGAT at improving participants’ mental health, “producing a clinically important and sustainable reduction in diabetes distress, anxiety, and depression.”
 

What’s HARPdoc?

The Hypoglycaemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycaemia persisting despite optimised self-care (HARPdoc) was designed to specifically address why some people with type 1 diabetes find it difficult to avoid recurrent hypoglycemia.

“It’s a psychoeducational program with clinical knowledge about hypoglycemia and group learning, but also explicit topics on mindset and behavior change,” explained Nicole de Zoysa, DClinPsych, one of the clinical psychologists involved in the trial.

Over the course of the 6-week program, there are four group sessions (weeks 1-3, and week 6) and two individual sessions (weeks 4 and 5) ­that address important “cognitive barriers” or “thinking traps” to avoiding hypoglycemia that were identified during prior qualitative research.

HARPdoc is thus “an attempt to make sense of people’s reluctance or seeming reluctance to take action around hypoglycemia, Dr. de Zoysa said. The intervention draws on both cognitive behavioral theory “to work with the beliefs” and motivational interviewing “to work with the resistance.”
 

The HARPdoc RCT

Starting in 2017 and ending earlier this year, the HARPdoc RCT was a parallel group study conducted at three specialist diabetes centers in the United Kingdom and one in the United States.

A total of 99 adults with insulin-treated type 1 diabetes and impaired hypoglycemia awareness were enrolled – with 49 randomized to the HARPdoc arm and 50 to the BGAT arm. All had been offered technologies to help them potentially bring their hypoglycemia under better control, such as continuous glucose monitoring, insulin pumps, or closed loop systems, and received structured education on flexible insulin dosing.

The aim was to show superiority of the HARPdoc program over BGAT, in helping people avoid episodes of severe hypoglycemia, defined as episodes that needed other people’s intervention to help resolve.

BGAT is also a psychoeducation program that has been around since the 1980s but barely used in the United Kingdom, Dr. Amiel noted.

Baseline demographic characteristics were similar for the HARPdoc and BGAT arms: The mean age was 57 versus 52 years, there was a long (30+ years) duration of diabetes, over half of the participants were male, and almost all were White.
 

Primary endpoint not met, but still ‘impressive’

Although the primary endpoint of the trial was not met, the reductions in severe hypoglycemia seen are still “impressive,” said Ramzi Ajjan, MD, FRCP, of Leeds (England) University and Leeds Teaching Hospitals Trust.

“I was really blown away,” by the improvement in both study arms, said Dr. Ajjan, who was not involved in the trial. “These people have had proper clinical input,” he stressed, noting that both interventions worked, with no difference between them in terms of severe hypoglycemia.

Dr. Ajjan was not surprised by the better cognition scores measured using the A2A questionnaire seen with HARPdoc versus BGAT, as “this is what the intervention was designed to address.”

In terms of the mental health benefits seen, HARPdoc significantly reduced the level of diabetes distress as measured using the Problem Areas In Diabetes (PAID) questionnaire versus the BGAT intervention.

The PAID score was around 30 in both groups at baseline, this fell to about 26 at 1 year, and around 20 at 2 years in the HARPdoc group, which was significantly lower than the score seen in the BGAT group which rose slightly then fell back to baseline levels.

A similar pattern was seen in the levels of depression and anxiety, which were measured by the HADS-D and HADS-A instruments. So HARPdoc was more effective at improving psychological and mental health outcomes than BGAT, Dr. Ajjan observed.

The HARPdoc project is funded by the Juvenile Diabetes Research Foundation with additional support from the UK’s National Institute of Health Research. The HARPdoc RCT was jointly sponsored by King’s College London and King’s College Hospital NHS Foundation Trust. Dr. Amiel has served on advisory panels for Roche, Medtronic, and Novo Nordisk. Dr. de Zoysa did not state having any conflicts of interest. Dr. Ajjan disclosed that he has financial relationships with multiple pharmaceutical companies.

People with insulin-treated type 1 diabetes who had problems avoiding hypoglycemic episodes despite optimal care were helped significantly by a new psychoeducational program called HARPdoc, it was reported at the annual meeting of the European Association for the Study of Diabetes.

In a randomized controlled trial (RCT), both HARPdoc and the more established Blood Glucose Awareness Training (BGAT) were effective at reducing the number of severe hypoglycemia episodes seen, from five episodes at baseline to one at 1 year in both groups, and one and none at 2-years’ follow-up, respectively.

“HARPdoc is not superior to BGAT in its ability to restore hypoglycemia awareness and reduce severe hypoglycemia,” said Stephanie Amiel, MD, FRCP, the chief investigator for the trial. However, “it does reduce cognitive barriers to hypoglycemia avoidance, so it achieves what it set out to do.”

Dr. Amiel, professor of diabetes research at Kings College London, added that it was important to note that HARPdoc was better than BGAT at improving participants’ mental health, “producing a clinically important and sustainable reduction in diabetes distress, anxiety, and depression.”
 

What’s HARPdoc?

The Hypoglycaemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycaemia persisting despite optimised self-care (HARPdoc) was designed to specifically address why some people with type 1 diabetes find it difficult to avoid recurrent hypoglycemia.

“It’s a psychoeducational program with clinical knowledge about hypoglycemia and group learning, but also explicit topics on mindset and behavior change,” explained Nicole de Zoysa, DClinPsych, one of the clinical psychologists involved in the trial.

Over the course of the 6-week program, there are four group sessions (weeks 1-3, and week 6) and two individual sessions (weeks 4 and 5) ­that address important “cognitive barriers” or “thinking traps” to avoiding hypoglycemia that were identified during prior qualitative research.

HARPdoc is thus “an attempt to make sense of people’s reluctance or seeming reluctance to take action around hypoglycemia, Dr. de Zoysa said. The intervention draws on both cognitive behavioral theory “to work with the beliefs” and motivational interviewing “to work with the resistance.”
 

The HARPdoc RCT

Starting in 2017 and ending earlier this year, the HARPdoc RCT was a parallel group study conducted at three specialist diabetes centers in the United Kingdom and one in the United States.

A total of 99 adults with insulin-treated type 1 diabetes and impaired hypoglycemia awareness were enrolled – with 49 randomized to the HARPdoc arm and 50 to the BGAT arm. All had been offered technologies to help them potentially bring their hypoglycemia under better control, such as continuous glucose monitoring, insulin pumps, or closed loop systems, and received structured education on flexible insulin dosing.

The aim was to show superiority of the HARPdoc program over BGAT, in helping people avoid episodes of severe hypoglycemia, defined as episodes that needed other people’s intervention to help resolve.

BGAT is also a psychoeducation program that has been around since the 1980s but barely used in the United Kingdom, Dr. Amiel noted.

Baseline demographic characteristics were similar for the HARPdoc and BGAT arms: The mean age was 57 versus 52 years, there was a long (30+ years) duration of diabetes, over half of the participants were male, and almost all were White.
 

Primary endpoint not met, but still ‘impressive’

Although the primary endpoint of the trial was not met, the reductions in severe hypoglycemia seen are still “impressive,” said Ramzi Ajjan, MD, FRCP, of Leeds (England) University and Leeds Teaching Hospitals Trust.

“I was really blown away,” by the improvement in both study arms, said Dr. Ajjan, who was not involved in the trial. “These people have had proper clinical input,” he stressed, noting that both interventions worked, with no difference between them in terms of severe hypoglycemia.

Dr. Ajjan was not surprised by the better cognition scores measured using the A2A questionnaire seen with HARPdoc versus BGAT, as “this is what the intervention was designed to address.”

In terms of the mental health benefits seen, HARPdoc significantly reduced the level of diabetes distress as measured using the Problem Areas In Diabetes (PAID) questionnaire versus the BGAT intervention.

The PAID score was around 30 in both groups at baseline, this fell to about 26 at 1 year, and around 20 at 2 years in the HARPdoc group, which was significantly lower than the score seen in the BGAT group which rose slightly then fell back to baseline levels.

A similar pattern was seen in the levels of depression and anxiety, which were measured by the HADS-D and HADS-A instruments. So HARPdoc was more effective at improving psychological and mental health outcomes than BGAT, Dr. Ajjan observed.

The HARPdoc project is funded by the Juvenile Diabetes Research Foundation with additional support from the UK’s National Institute of Health Research. The HARPdoc RCT was jointly sponsored by King’s College London and King’s College Hospital NHS Foundation Trust. Dr. Amiel has served on advisory panels for Roche, Medtronic, and Novo Nordisk. Dr. de Zoysa did not state having any conflicts of interest. Dr. Ajjan disclosed that he has financial relationships with multiple pharmaceutical companies.

Baricitinib, an oral inhibitor of Janus kinase (JAK) types 1 and 2, produced substantial rates of hair growth with acceptable tolerability for patients with alopecia areata, according to the results of two phase 3 trials presented at the European Academy of Dermatology and Venereology (EADV) 2021 Annual Meeting.

In both trials, severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of greater than or equal to 50, was an enrollment requirement. The primary endpoint was a SALT score of less than or equal to 20, signifying 80% scalp coverage.

“The mean SALT score at entry was 85,” reported Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn. He explained that the SALT scale extends from 0 (no hair loss) to 100 (complete hair loss). About 45% of patients in the phase 3 trials had alopecia universalis.

In both trials, called BRAVE-AA1 and BRAVE-AA2, a response was seen with baricitinib after about 4 weeks. Response increased steadily through the entire 36 weeks of treatment. At the end of 36 weeks, when response curves still had an upward trajectory, the proportion of those treated with the 4-mg dose of baricitinib who had achieved a SALT score of less than or equal to 20 had reached 35.2% in BRAVE-AA1 and 32.5% in BRAVE-AA2.

The nearly identical BRAVE-AA1 and BRAVE-AA2 trials enrolled 654 and 546 patients, respectively. The patients were randomly assigned in a 3:2:2 ratio to receive baricitinib 4 mg, baricitinib 2 mg, or placebo. All treatments were taken once daily. Regrowth of eyebrow and eyelash hair were secondary outcomes.

There was a clear dose effect; hair growth increased more quickly with the 4-mg dose of baricitinib than with the 2-mg dose. The difference between the active therapy and placebo was significant by 16 weeks with the 4-mg dose. By 24 weeks, the advantage of the 2-mg dose over placebo also reached significance. The response rate with the 4-mg dose was nearly twice as great.

At the end of the 36-week trials, the proportion of patients treated with baricitinib 2 mg who achieved the primary endpoint was 21.7% and 17.3% in the BRAVE-AA1 and BRAVE-AA2 trials, respectively. Among patients taking placebo, the primary endpoint was met by 5.3% and 2.6%, respectively, at the end of the two trials.

The differences in responses with the 4-mg and the 2-mg doses were significantly higher compared with placebo (P ≤ .001 for both doses vs. placebo).

Using a scoring system for eyebrow and eyelash hair loss, the proportion of patients who achieved a score of 0 (full coverage) or 1 (minimal gaps) was again superior in both trials for patients taking the higher dose of baricitinib. This level of response was reached by about 31% to 35% of those taking the 4-mg dose in BRAVE-AA1 and BRAVE-AA2 (P ≤ .001 vs. placebo). With the lower dose, the rates were 19.1% and 13.5%, respectively. This endpoint was reached in only about 3% of patients who took placebo.

Rates of adverse events were modestly higher in the two active treatment groups in comparison with the group taking placebo. The most commonly occurring adverse events with baricitinib included upper respiratory tract infections, nasopharyngitis, urinary tract infections, and headache, according to Dr. King.

“Most of the adverse events were mild to moderate,” he said. He also reported that none of these adverse events occurred in more than 10% of patients, and there were no cases of other opportunistic infections, thromboembolic events, or gastrointestinal perforations. The discontinuation rates because of adverse events with active therapy were less than 3% in both trials.

JAK inhibitors are currently employed in the treatment of a variety of inflammatory diseases. Baricitinib is currently approved for the treatment of rheumatoid arthritis. Because specificity differs markedly for their inhibition of JAK kinases (JAK1, JAK2, JAK3, and Tyk2), these drugs do not appear to be interchangeable with regard to clinical effect.

Several case reports of hair regrowth with baricitinib led to a phase 2 trial, which was recently published in the Journal of the American Academy of Dermatology. In this trial, the therapy also yielded substantial benefit for patients with alopecia areata. The benefit of baricitinib is attributed to inhibition of JAK1 and JAK2 signaling, which has been implicated in cytokine-mediated immune dysfunction leading to damage of hair follicles.

Alopecia areata is a common disorder that can have a large adverse impact on quality of life, Dr. King noted. There is no approved therapy for this condition, so there is a large unmet need. Although longer follow-up is needed to gauge sustained efficacy and safety, he considers these results promising for a therapy with clinically meaningful benefit.

This point was reiterated by Yolanda Gilaberte Calzada, MD, PhD, head of the Dermatology Service, University Hospital Miguel Servet, Zaragoza, Spain, who was moderator of the session in which Dr. King presented these data. She expressed excitement about the promise of baricitinib, particularly with regard to the substantial proportion of patients who achieved meaningful degrees of hair regrowth.

“All of us will be happy to have options for alopecia areata,” said Dr. Calzada, who predicted that the higher dose of baricitinib will be selected for clinical development, given its greater efficacy with little increase in safety concerns.

Eli Lilly provided funding for the BRAVE-AA1 and -AA2 trials. Dr. King has financial relationships with Arena, Aclaris, Bristol-Myers Squibb, Concert, Pfizer, Regeneron, Sanofi Genzyme, and Eli Lilly. Dr. Calzada has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Baricitinib, an oral inhibitor of Janus kinase (JAK) types 1 and 2, produced substantial rates of hair growth with acceptable tolerability for patients with alopecia areata, according to the results of two phase 3 trials presented at the European Academy of Dermatology and Venereology (EADV) 2021 Annual Meeting.

In both trials, severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of greater than or equal to 50, was an enrollment requirement. The primary endpoint was a SALT score of less than or equal to 20, signifying 80% scalp coverage.

“The mean SALT score at entry was 85,” reported Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn. He explained that the SALT scale extends from 0 (no hair loss) to 100 (complete hair loss). About 45% of patients in the phase 3 trials had alopecia universalis.

In both trials, called BRAVE-AA1 and BRAVE-AA2, a response was seen with baricitinib after about 4 weeks. Response increased steadily through the entire 36 weeks of treatment. At the end of 36 weeks, when response curves still had an upward trajectory, the proportion of those treated with the 4-mg dose of baricitinib who had achieved a SALT score of less than or equal to 20 had reached 35.2% in BRAVE-AA1 and 32.5% in BRAVE-AA2.

The nearly identical BRAVE-AA1 and BRAVE-AA2 trials enrolled 654 and 546 patients, respectively. The patients were randomly assigned in a 3:2:2 ratio to receive baricitinib 4 mg, baricitinib 2 mg, or placebo. All treatments were taken once daily. Regrowth of eyebrow and eyelash hair were secondary outcomes.

There was a clear dose effect; hair growth increased more quickly with the 4-mg dose of baricitinib than with the 2-mg dose. The difference between the active therapy and placebo was significant by 16 weeks with the 4-mg dose. By 24 weeks, the advantage of the 2-mg dose over placebo also reached significance. The response rate with the 4-mg dose was nearly twice as great.

At the end of the 36-week trials, the proportion of patients treated with baricitinib 2 mg who achieved the primary endpoint was 21.7% and 17.3% in the BRAVE-AA1 and BRAVE-AA2 trials, respectively. Among patients taking placebo, the primary endpoint was met by 5.3% and 2.6%, respectively, at the end of the two trials.

The differences in responses with the 4-mg and the 2-mg doses were significantly higher compared with placebo (P ≤ .001 for both doses vs. placebo).

Using a scoring system for eyebrow and eyelash hair loss, the proportion of patients who achieved a score of 0 (full coverage) or 1 (minimal gaps) was again superior in both trials for patients taking the higher dose of baricitinib. This level of response was reached by about 31% to 35% of those taking the 4-mg dose in BRAVE-AA1 and BRAVE-AA2 (P ≤ .001 vs. placebo). With the lower dose, the rates were 19.1% and 13.5%, respectively. This endpoint was reached in only about 3% of patients who took placebo.

Rates of adverse events were modestly higher in the two active treatment groups in comparison with the group taking placebo. The most commonly occurring adverse events with baricitinib included upper respiratory tract infections, nasopharyngitis, urinary tract infections, and headache, according to Dr. King.

“Most of the adverse events were mild to moderate,” he said. He also reported that none of these adverse events occurred in more than 10% of patients, and there were no cases of other opportunistic infections, thromboembolic events, or gastrointestinal perforations. The discontinuation rates because of adverse events with active therapy were less than 3% in both trials.

JAK inhibitors are currently employed in the treatment of a variety of inflammatory diseases. Baricitinib is currently approved for the treatment of rheumatoid arthritis. Because specificity differs markedly for their inhibition of JAK kinases (JAK1, JAK2, JAK3, and Tyk2), these drugs do not appear to be interchangeable with regard to clinical effect.

Several case reports of hair regrowth with baricitinib led to a phase 2 trial, which was recently published in the Journal of the American Academy of Dermatology. In this trial, the therapy also yielded substantial benefit for patients with alopecia areata. The benefit of baricitinib is attributed to inhibition of JAK1 and JAK2 signaling, which has been implicated in cytokine-mediated immune dysfunction leading to damage of hair follicles.

Alopecia areata is a common disorder that can have a large adverse impact on quality of life, Dr. King noted. There is no approved therapy for this condition, so there is a large unmet need. Although longer follow-up is needed to gauge sustained efficacy and safety, he considers these results promising for a therapy with clinically meaningful benefit.

This point was reiterated by Yolanda Gilaberte Calzada, MD, PhD, head of the Dermatology Service, University Hospital Miguel Servet, Zaragoza, Spain, who was moderator of the session in which Dr. King presented these data. She expressed excitement about the promise of baricitinib, particularly with regard to the substantial proportion of patients who achieved meaningful degrees of hair regrowth.

“All of us will be happy to have options for alopecia areata,” said Dr. Calzada, who predicted that the higher dose of baricitinib will be selected for clinical development, given its greater efficacy with little increase in safety concerns.

Eli Lilly provided funding for the BRAVE-AA1 and -AA2 trials. Dr. King has financial relationships with Arena, Aclaris, Bristol-Myers Squibb, Concert, Pfizer, Regeneron, Sanofi Genzyme, and Eli Lilly. Dr. Calzada has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Baricitinib, an oral inhibitor of Janus kinase (JAK) types 1 and 2, produced substantial rates of hair growth with acceptable tolerability for patients with alopecia areata, according to the results of two phase 3 trials presented at the European Academy of Dermatology and Venereology (EADV) 2021 Annual Meeting.

In both trials, severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of greater than or equal to 50, was an enrollment requirement. The primary endpoint was a SALT score of less than or equal to 20, signifying 80% scalp coverage.

“The mean SALT score at entry was 85,” reported Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn. He explained that the SALT scale extends from 0 (no hair loss) to 100 (complete hair loss). About 45% of patients in the phase 3 trials had alopecia universalis.

In both trials, called BRAVE-AA1 and BRAVE-AA2, a response was seen with baricitinib after about 4 weeks. Response increased steadily through the entire 36 weeks of treatment. At the end of 36 weeks, when response curves still had an upward trajectory, the proportion of those treated with the 4-mg dose of baricitinib who had achieved a SALT score of less than or equal to 20 had reached 35.2% in BRAVE-AA1 and 32.5% in BRAVE-AA2.

The nearly identical BRAVE-AA1 and BRAVE-AA2 trials enrolled 654 and 546 patients, respectively. The patients were randomly assigned in a 3:2:2 ratio to receive baricitinib 4 mg, baricitinib 2 mg, or placebo. All treatments were taken once daily. Regrowth of eyebrow and eyelash hair were secondary outcomes.

There was a clear dose effect; hair growth increased more quickly with the 4-mg dose of baricitinib than with the 2-mg dose. The difference between the active therapy and placebo was significant by 16 weeks with the 4-mg dose. By 24 weeks, the advantage of the 2-mg dose over placebo also reached significance. The response rate with the 4-mg dose was nearly twice as great.

At the end of the 36-week trials, the proportion of patients treated with baricitinib 2 mg who achieved the primary endpoint was 21.7% and 17.3% in the BRAVE-AA1 and BRAVE-AA2 trials, respectively. Among patients taking placebo, the primary endpoint was met by 5.3% and 2.6%, respectively, at the end of the two trials.

The differences in responses with the 4-mg and the 2-mg doses were significantly higher compared with placebo (P ≤ .001 for both doses vs. placebo).

Using a scoring system for eyebrow and eyelash hair loss, the proportion of patients who achieved a score of 0 (full coverage) or 1 (minimal gaps) was again superior in both trials for patients taking the higher dose of baricitinib. This level of response was reached by about 31% to 35% of those taking the 4-mg dose in BRAVE-AA1 and BRAVE-AA2 (P ≤ .001 vs. placebo). With the lower dose, the rates were 19.1% and 13.5%, respectively. This endpoint was reached in only about 3% of patients who took placebo.

Rates of adverse events were modestly higher in the two active treatment groups in comparison with the group taking placebo. The most commonly occurring adverse events with baricitinib included upper respiratory tract infections, nasopharyngitis, urinary tract infections, and headache, according to Dr. King.

“Most of the adverse events were mild to moderate,” he said. He also reported that none of these adverse events occurred in more than 10% of patients, and there were no cases of other opportunistic infections, thromboembolic events, or gastrointestinal perforations. The discontinuation rates because of adverse events with active therapy were less than 3% in both trials.

JAK inhibitors are currently employed in the treatment of a variety of inflammatory diseases. Baricitinib is currently approved for the treatment of rheumatoid arthritis. Because specificity differs markedly for their inhibition of JAK kinases (JAK1, JAK2, JAK3, and Tyk2), these drugs do not appear to be interchangeable with regard to clinical effect.

Several case reports of hair regrowth with baricitinib led to a phase 2 trial, which was recently published in the Journal of the American Academy of Dermatology. In this trial, the therapy also yielded substantial benefit for patients with alopecia areata. The benefit of baricitinib is attributed to inhibition of JAK1 and JAK2 signaling, which has been implicated in cytokine-mediated immune dysfunction leading to damage of hair follicles.

Alopecia areata is a common disorder that can have a large adverse impact on quality of life, Dr. King noted. There is no approved therapy for this condition, so there is a large unmet need. Although longer follow-up is needed to gauge sustained efficacy and safety, he considers these results promising for a therapy with clinically meaningful benefit.

This point was reiterated by Yolanda Gilaberte Calzada, MD, PhD, head of the Dermatology Service, University Hospital Miguel Servet, Zaragoza, Spain, who was moderator of the session in which Dr. King presented these data. She expressed excitement about the promise of baricitinib, particularly with regard to the substantial proportion of patients who achieved meaningful degrees of hair regrowth.

“All of us will be happy to have options for alopecia areata,” said Dr. Calzada, who predicted that the higher dose of baricitinib will be selected for clinical development, given its greater efficacy with little increase in safety concerns.

Eli Lilly provided funding for the BRAVE-AA1 and -AA2 trials. Dr. King has financial relationships with Arena, Aclaris, Bristol-Myers Squibb, Concert, Pfizer, Regeneron, Sanofi Genzyme, and Eli Lilly. Dr. Calzada has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Weight loss of at least 15% of body weight should become the “initial principal treatment goal” for many patients with type 2 diabetes, according to a new review and proposal published by an international quartet of diabetologists.

Although this proposition currently has formal backing from just the four authors of the article published in the Lancet, their recommendation to elevate substantial weight loss to the front line of management for many patients with type 2 diabetes drew quick support from leaders of several diabetes organizations, albeit with some caveats.

“Our main message is that treatment of obesity should be the future of diabetes treatment,” summed up Ildiko Lingvay, MD, lead author of the new review and proposal, at the annual meeting of the European Association for the Study of Diabetes.

“Right now, a relatively small percentage of clinicians [who treat patients with type 2 diabetes] address obesity and know how to treat it. That has to change. Every clinician who treats diabetes needs to know how to treat obesity,” said Dr. Lingvay, a professor in the division of endocrinology at the University of Texas Southwestern Medical Center, Dallas.

This requires a sea change in the way clinicians approach treating patients with type 2 diabetes, which until now has generally involved “exclusive focus on glycemic control,” the authors wrote. “Practice management should refocus to effectively incorporate weight management to treat patients with type 2 diabetes.”

Successfully implementing their new, proposed change in focus “will take fundamental change,” noted Dr. Lingvay, who expressed hope that international guidelines will soon endorse this approach, an action that would be “a huge step in the right direction.”
 

Target weight-loss drugs to the right patients.

Initial reactions from representatives of several diabetes and obesity groups suggested that official endorsements of this management strategy for at least a subset of patients with type 2 diabetes may be forthcoming.

“The American Diabetes Association’s standards of care is aligned with this approach in focusing on obesity as a target of management in people with type 2 diabetes,” commented Nuha A. El Sayed, MD, vice president for health care improvement for the ADA. An “area of discussion” is the specific weight-loss target of at least 15%, because patients benefit from more modest weight losses of 5%-7%, and a target loss of 15% may not be achievable for some patients, she noted in a statement.

The ADA’s leadership and its professional practice committee will “carefully consider” the new, published proposal, added Dr. El Sayed, a diabetologist at the Joslin Diabetes Center in Boston.

Similar caution over generalizability of the 15% loss target came from Stefano Del Prato, MD, president of the European Society for the Study of Diabetes.

“Not everyone responds to the same extent” to the newest pharmaceuticals for facilitating weight loss, such as the glucagonlike peptide-1 receptor agonists, so the ideal would be to try to “identify patients who respond better to weight loss and can lose at least 15% of their weight. We need to improve our ability to identify patients who respond better,” said Dr. Del Prato, a professor of endocrinology and metabolism at the University of Pisa (Italy).

Despite this, he agreed in an interview that “a significant reduction in body weight should be seen as a target for treatment of type 2 diabetes,”

“Appropriate training for obesity management is essential for those working on type 2 diabetes prevention or management,” commented Jason C.G. Halford, PhD, a professor of biological psychology at the University Of Leeds (England), and president of the European Association for the Study of Obesity.

For some patients with type 2 diabetes “losing 10%-15% of body weight can mean their diabetes goes into remission,” and “losing even a small amount of weight can be life changing, it can help people better manage their blood sugars and blood pressure, and reduce their risk for developing diabetes complications like heart disease and sight loss,” commented Lucy Chambers, PhD, head of research communications for Diabetes UK.

15% loss is a ‘reachable’ goal

Dr. Lingvay and coauthors acknowledged that weight loss of less than 15% can benefit many patients with type 2 diabetes, but they felt that a loss of at least 15% gives patients a realistic and potentially potent goal to strive for.

At least 15% loss “is a goal that is beneficial and reachable for many patients. Not everyone will get there, but the closer that patients get to this, or beyond, the bigger their benefit,” she explained. “There is no magic number” for exactly how much weight a patient needs to lose to improve their health. Dr. Lingvay also highlighted that weight loss is a better target for patients than remission of their diabetes because remission may no longer be possible in patients with longstanding type 2 diabetes.

The review divides patients with type 2 diabetes into three subgroups: those with adiposity-related disease, which includes about 40%-70% of patients with type 2 diabetes; patients with cardiovascular disease as their most prominent comorbidity, a subgroup that includes about a third of patients with type 2 diabetes; and the remaining patients with primarily beta-cell dysfunction with a principle morbidity of hyperglycemia, comprising about 10%-20% of patients with type 2 diabetes. Patients in the adiposity-related diabetes subgroup form the primary target group for interventions focused on weight loss.

Incretin-based weight-loss agents propel change.

The review also links the timing of the new recommendations to recent evidence that treatment with relatively new medications from classes such as the GLP-1 receptor agonists can produce weight loss of at least 15% in most patients with type 2 diabetes, especially those with the adiposity-related form of the disease.

“The number of patients who can achieve and maintain weight loss with lifestyle alone is limited, and while bariatric surgery is very effective [for producing substantial weight loss], only a minority of patients have access to it,” and the necessary scalability of surgery is doubtful, said Priya Sumithran, MBBS, PhD, an endocrinologist and leader of the obesity research group at the University of Melbourne, and a coauthor on the new review. Compelling evidence now exists that the gap between lifestyle interventions and bariatric surgery can now be filled by a new generation of incretin-based agents that can safely produce substantial weight loss.

New agents that work as GLP-1 receptor agonists and on related incretin pathways “have changed how we think about treating type 2 diabetes,” Dr. Lingvay declared.

Dr. Lingvay and Dr. Del Prato have each been consultants to numerous drug companies. Dr. Sumithran has been an adviser to and speaker on behalf of Novo Nordisk. Dr. El Sayed, Dr. Halford, and Dr. Chambers had no relevant disclosures.

mzoler@mdedge.com

Weight loss of at least 15% of body weight should become the “initial principal treatment goal” for many patients with type 2 diabetes, according to a new review and proposal published by an international quartet of diabetologists.

Although this proposition currently has formal backing from just the four authors of the article published in the Lancet, their recommendation to elevate substantial weight loss to the front line of management for many patients with type 2 diabetes drew quick support from leaders of several diabetes organizations, albeit with some caveats.

“Our main message is that treatment of obesity should be the future of diabetes treatment,” summed up Ildiko Lingvay, MD, lead author of the new review and proposal, at the annual meeting of the European Association for the Study of Diabetes.

“Right now, a relatively small percentage of clinicians [who treat patients with type 2 diabetes] address obesity and know how to treat it. That has to change. Every clinician who treats diabetes needs to know how to treat obesity,” said Dr. Lingvay, a professor in the division of endocrinology at the University of Texas Southwestern Medical Center, Dallas.

This requires a sea change in the way clinicians approach treating patients with type 2 diabetes, which until now has generally involved “exclusive focus on glycemic control,” the authors wrote. “Practice management should refocus to effectively incorporate weight management to treat patients with type 2 diabetes.”

Successfully implementing their new, proposed change in focus “will take fundamental change,” noted Dr. Lingvay, who expressed hope that international guidelines will soon endorse this approach, an action that would be “a huge step in the right direction.”
 

Target weight-loss drugs to the right patients.

Initial reactions from representatives of several diabetes and obesity groups suggested that official endorsements of this management strategy for at least a subset of patients with type 2 diabetes may be forthcoming.

“The American Diabetes Association’s standards of care is aligned with this approach in focusing on obesity as a target of management in people with type 2 diabetes,” commented Nuha A. El Sayed, MD, vice president for health care improvement for the ADA. An “area of discussion” is the specific weight-loss target of at least 15%, because patients benefit from more modest weight losses of 5%-7%, and a target loss of 15% may not be achievable for some patients, she noted in a statement.

The ADA’s leadership and its professional practice committee will “carefully consider” the new, published proposal, added Dr. El Sayed, a diabetologist at the Joslin Diabetes Center in Boston.

Similar caution over generalizability of the 15% loss target came from Stefano Del Prato, MD, president of the European Society for the Study of Diabetes.

“Not everyone responds to the same extent” to the newest pharmaceuticals for facilitating weight loss, such as the glucagonlike peptide-1 receptor agonists, so the ideal would be to try to “identify patients who respond better to weight loss and can lose at least 15% of their weight. We need to improve our ability to identify patients who respond better,” said Dr. Del Prato, a professor of endocrinology and metabolism at the University of Pisa (Italy).

Despite this, he agreed in an interview that “a significant reduction in body weight should be seen as a target for treatment of type 2 diabetes,”

“Appropriate training for obesity management is essential for those working on type 2 diabetes prevention or management,” commented Jason C.G. Halford, PhD, a professor of biological psychology at the University Of Leeds (England), and president of the European Association for the Study of Obesity.

For some patients with type 2 diabetes “losing 10%-15% of body weight can mean their diabetes goes into remission,” and “losing even a small amount of weight can be life changing, it can help people better manage their blood sugars and blood pressure, and reduce their risk for developing diabetes complications like heart disease and sight loss,” commented Lucy Chambers, PhD, head of research communications for Diabetes UK.

15% loss is a ‘reachable’ goal

Dr. Lingvay and coauthors acknowledged that weight loss of less than 15% can benefit many patients with type 2 diabetes, but they felt that a loss of at least 15% gives patients a realistic and potentially potent goal to strive for.

At least 15% loss “is a goal that is beneficial and reachable for many patients. Not everyone will get there, but the closer that patients get to this, or beyond, the bigger their benefit,” she explained. “There is no magic number” for exactly how much weight a patient needs to lose to improve their health. Dr. Lingvay also highlighted that weight loss is a better target for patients than remission of their diabetes because remission may no longer be possible in patients with longstanding type 2 diabetes.

The review divides patients with type 2 diabetes into three subgroups: those with adiposity-related disease, which includes about 40%-70% of patients with type 2 diabetes; patients with cardiovascular disease as their most prominent comorbidity, a subgroup that includes about a third of patients with type 2 diabetes; and the remaining patients with primarily beta-cell dysfunction with a principle morbidity of hyperglycemia, comprising about 10%-20% of patients with type 2 diabetes. Patients in the adiposity-related diabetes subgroup form the primary target group for interventions focused on weight loss.

Incretin-based weight-loss agents propel change.

The review also links the timing of the new recommendations to recent evidence that treatment with relatively new medications from classes such as the GLP-1 receptor agonists can produce weight loss of at least 15% in most patients with type 2 diabetes, especially those with the adiposity-related form of the disease.

“The number of patients who can achieve and maintain weight loss with lifestyle alone is limited, and while bariatric surgery is very effective [for producing substantial weight loss], only a minority of patients have access to it,” and the necessary scalability of surgery is doubtful, said Priya Sumithran, MBBS, PhD, an endocrinologist and leader of the obesity research group at the University of Melbourne, and a coauthor on the new review. Compelling evidence now exists that the gap between lifestyle interventions and bariatric surgery can now be filled by a new generation of incretin-based agents that can safely produce substantial weight loss.

New agents that work as GLP-1 receptor agonists and on related incretin pathways “have changed how we think about treating type 2 diabetes,” Dr. Lingvay declared.

Dr. Lingvay and Dr. Del Prato have each been consultants to numerous drug companies. Dr. Sumithran has been an adviser to and speaker on behalf of Novo Nordisk. Dr. El Sayed, Dr. Halford, and Dr. Chambers had no relevant disclosures.

mzoler@mdedge.com

Weight loss of at least 15% of body weight should become the “initial principal treatment goal” for many patients with type 2 diabetes, according to a new review and proposal published by an international quartet of diabetologists.

Although this proposition currently has formal backing from just the four authors of the article published in the Lancet, their recommendation to elevate substantial weight loss to the front line of management for many patients with type 2 diabetes drew quick support from leaders of several diabetes organizations, albeit with some caveats.

“Our main message is that treatment of obesity should be the future of diabetes treatment,” summed up Ildiko Lingvay, MD, lead author of the new review and proposal, at the annual meeting of the European Association for the Study of Diabetes.

“Right now, a relatively small percentage of clinicians [who treat patients with type 2 diabetes] address obesity and know how to treat it. That has to change. Every clinician who treats diabetes needs to know how to treat obesity,” said Dr. Lingvay, a professor in the division of endocrinology at the University of Texas Southwestern Medical Center, Dallas.

This requires a sea change in the way clinicians approach treating patients with type 2 diabetes, which until now has generally involved “exclusive focus on glycemic control,” the authors wrote. “Practice management should refocus to effectively incorporate weight management to treat patients with type 2 diabetes.”

Successfully implementing their new, proposed change in focus “will take fundamental change,” noted Dr. Lingvay, who expressed hope that international guidelines will soon endorse this approach, an action that would be “a huge step in the right direction.”
 

Target weight-loss drugs to the right patients.

Initial reactions from representatives of several diabetes and obesity groups suggested that official endorsements of this management strategy for at least a subset of patients with type 2 diabetes may be forthcoming.

“The American Diabetes Association’s standards of care is aligned with this approach in focusing on obesity as a target of management in people with type 2 diabetes,” commented Nuha A. El Sayed, MD, vice president for health care improvement for the ADA. An “area of discussion” is the specific weight-loss target of at least 15%, because patients benefit from more modest weight losses of 5%-7%, and a target loss of 15% may not be achievable for some patients, she noted in a statement.

The ADA’s leadership and its professional practice committee will “carefully consider” the new, published proposal, added Dr. El Sayed, a diabetologist at the Joslin Diabetes Center in Boston.

Similar caution over generalizability of the 15% loss target came from Stefano Del Prato, MD, president of the European Society for the Study of Diabetes.

“Not everyone responds to the same extent” to the newest pharmaceuticals for facilitating weight loss, such as the glucagonlike peptide-1 receptor agonists, so the ideal would be to try to “identify patients who respond better to weight loss and can lose at least 15% of their weight. We need to improve our ability to identify patients who respond better,” said Dr. Del Prato, a professor of endocrinology and metabolism at the University of Pisa (Italy).

Despite this, he agreed in an interview that “a significant reduction in body weight should be seen as a target for treatment of type 2 diabetes,”

“Appropriate training for obesity management is essential for those working on type 2 diabetes prevention or management,” commented Jason C.G. Halford, PhD, a professor of biological psychology at the University Of Leeds (England), and president of the European Association for the Study of Obesity.

For some patients with type 2 diabetes “losing 10%-15% of body weight can mean their diabetes goes into remission,” and “losing even a small amount of weight can be life changing, it can help people better manage their blood sugars and blood pressure, and reduce their risk for developing diabetes complications like heart disease and sight loss,” commented Lucy Chambers, PhD, head of research communications for Diabetes UK.

15% loss is a ‘reachable’ goal

Dr. Lingvay and coauthors acknowledged that weight loss of less than 15% can benefit many patients with type 2 diabetes, but they felt that a loss of at least 15% gives patients a realistic and potentially potent goal to strive for.

At least 15% loss “is a goal that is beneficial and reachable for many patients. Not everyone will get there, but the closer that patients get to this, or beyond, the bigger their benefit,” she explained. “There is no magic number” for exactly how much weight a patient needs to lose to improve their health. Dr. Lingvay also highlighted that weight loss is a better target for patients than remission of their diabetes because remission may no longer be possible in patients with longstanding type 2 diabetes.

The review divides patients with type 2 diabetes into three subgroups: those with adiposity-related disease, which includes about 40%-70% of patients with type 2 diabetes; patients with cardiovascular disease as their most prominent comorbidity, a subgroup that includes about a third of patients with type 2 diabetes; and the remaining patients with primarily beta-cell dysfunction with a principle morbidity of hyperglycemia, comprising about 10%-20% of patients with type 2 diabetes. Patients in the adiposity-related diabetes subgroup form the primary target group for interventions focused on weight loss.

Incretin-based weight-loss agents propel change.

The review also links the timing of the new recommendations to recent evidence that treatment with relatively new medications from classes such as the GLP-1 receptor agonists can produce weight loss of at least 15% in most patients with type 2 diabetes, especially those with the adiposity-related form of the disease.

“The number of patients who can achieve and maintain weight loss with lifestyle alone is limited, and while bariatric surgery is very effective [for producing substantial weight loss], only a minority of patients have access to it,” and the necessary scalability of surgery is doubtful, said Priya Sumithran, MBBS, PhD, an endocrinologist and leader of the obesity research group at the University of Melbourne, and a coauthor on the new review. Compelling evidence now exists that the gap between lifestyle interventions and bariatric surgery can now be filled by a new generation of incretin-based agents that can safely produce substantial weight loss.

New agents that work as GLP-1 receptor agonists and on related incretin pathways “have changed how we think about treating type 2 diabetes,” Dr. Lingvay declared.

Dr. Lingvay and Dr. Del Prato have each been consultants to numerous drug companies. Dr. Sumithran has been an adviser to and speaker on behalf of Novo Nordisk. Dr. El Sayed, Dr. Halford, and Dr. Chambers had no relevant disclosures.

mzoler@mdedge.com

A topical cream formulation of the Janus kinase inhibitor ruxolitinib was superior to its vehicle for treating vitiligo across all primary and secondary endpoints in two multicenter phase 3 trials presented together at the annual meeting of the European Academy of Dermatology and Venereology.

On the primary endpoint of F-VASI 75 (75% improvement in the Facial and Vitiligo Scoring Index), rates were nearly four times higher at 24 weeks in one trial (29.9% vs. 7.5%; P < .0001) and more than twice as great in the other (29.9% vs. 12.9%; P < .01).

“The larger phase 3 trials confirm the previous phase 2 findings,” reported David Rosmarin, MD, vice chairman for research and education, department of dermatology, Tufts Medical Center, Boston. These findings not only include substantial clinical efficacy but good tolerability with “no serious treatment-related adverse events,” he noted.
 

600 patients randomized

In one of the trials, called TRuE-V1, 330 patients with vitiligo were randomly assigned in a 2:1 ratio to 1.5% ruxolitinib or vehicle applied twice daily. In the other trial, called TRuE-V2, 344 patients were randomly assigned. The participating centers were in Europe and North America.

Patients aged 12 years or older with nonsegmental vitiligo and depigmentation covering no more than 10% of the total body surface area were eligible. The mean baseline F-VASI values were 1.0. The mean total VASI (T-FASI) values were 6.5. On those enrolled, half were female, 11% were adolescents, and 73% had Fitzpatrick skin phototypes III-VI.

Ruxolitinib cream provided near-complete vitiligo clearance (F-VASI 90) on the face at 24 weeks in only about 15% of patients, but this was several times higher than the 2% achieved on vehicle in the TRuE-V1 (P < .01) and the TRuE-V2 trials (P < .05), respectively.

F-VASI 50 response rates greater than 50%

For F-VASI 50, the response rate with ruxolitinib in both studies was approximately 51%. Relative to the 17.2% response on vehicle in TRuE-v1 and 23.4% in TRuE-V2 (both P < .0001 vs. active therapy), the advantage of the topical JAK inhibitor was considered to be a clinically meaningful, not just significant from a statistical standpoint.

In fact, improvement on the 5-point Vitiligo Noticeability Scale “also supported a clinically meaningful benefit,” Dr. Rosmarin reported. When those achieving a score of 4 (much less noticeable) or 5 (no longer noticeable), the response rates at 24 weeks were 24.5% and 21.6% in the TRuE-V1 and TRuE-V2 trials, respectively. Again, these response rates were several times greater than the 3.3% (P < .001) and 6.6% (P < .01) observed in the vehicle arms of TRuE-V1 and TRuE-V2 (P < .01), respectively.

Treatment-related adverse events were infrequent. The most common were acne at the application site, which occurred in about 5% of patients receiving ruxolitinib (vs. 2% or fewer of those receiving vehicle) and pruritus, which also occurred in about 5% of patients. However, the rates of pruritus among those on placebo reached 4% in TRuE-V1 and 2% in TRuE-V2 trials.

In vitiligo, where there has been recent progress in understanding the pathophysiology, loss of melanocytes in immune dysregulation has been linked to activation of the JAK signaling pathway, according to Dr. Rosmarin. In the 52-week phase 2 trial with 205 patients, ruxolitinib was associated with a sustained response and no serious treatment-related adverse events.
 

52-week data might show more benefit

Patients are continuing to be followed in the TRuE-V1 and TRuE-V-2 trials. Based on the phase 2 data and on the progressive improvement still being observed at the end of 24 weeks in the phase 3 trials, Dr. Rosmarin expects 52-week results be valuable in understanding the clinical role of ruxolitinib.

“We will be looking for further improvement in response as we follow these patients out to 1 year,” he said.

This further follow-up is important, agreed Iltefat Hamzavi, MD, senior staff physician, department of dermatology, Henry Ford Hospital, Detroit.

Despite the promise of perhaps other JAK inhibitors, “we still need to understand how long it will take for the drug to offer optimal results. We already know that is more than 24 weeks,” said Dr. Hamzavi, who has been involved in the clinical trials with this drug but was not involved with the TRuE-V1 or -V2 trials.

He also said more follow-up is needed to understand the duration of effect. He is, however, optimistic about the clinical role of this mechanism for treatment of vitiligo.

“I do think that JAK inhibitors show a lot of promise [in vitiligo] for certain locations of the body,” he said.

Given the limited treatment options for effective and prolonged improvement in vitiligo, both Dr. Hamzavi and Dr. Rosmarin indicated an effective topical cream is likely to be considered by physicians and patients to be a substantial advance.

On Sept. 21, ruxolitinib (Opzelura) 1.5% cream was approved by the Food and Drug Administration for the short-term treatment of mild to moderate atopic dermatitis in children and adults ages 12 years and older – the first FDA approval of this product.

Dr. Rosmarin reported financial relationships with more than 20 pharmaceutical companies, including Incyte, which provided funding for the TRuE-V1 and -V2 trials. Dr. Hamzavi reported financial relationships with more than 15 companies with pharmaceutical or cosmetic products, including Incyte.

A version of this article first appeared on Medscape.com.

A topical cream formulation of the Janus kinase inhibitor ruxolitinib was superior to its vehicle for treating vitiligo across all primary and secondary endpoints in two multicenter phase 3 trials presented together at the annual meeting of the European Academy of Dermatology and Venereology.

On the primary endpoint of F-VASI 75 (75% improvement in the Facial and Vitiligo Scoring Index), rates were nearly four times higher at 24 weeks in one trial (29.9% vs. 7.5%; P < .0001) and more than twice as great in the other (29.9% vs. 12.9%; P < .01).

“The larger phase 3 trials confirm the previous phase 2 findings,” reported David Rosmarin, MD, vice chairman for research and education, department of dermatology, Tufts Medical Center, Boston. These findings not only include substantial clinical efficacy but good tolerability with “no serious treatment-related adverse events,” he noted.
 

600 patients randomized

In one of the trials, called TRuE-V1, 330 patients with vitiligo were randomly assigned in a 2:1 ratio to 1.5% ruxolitinib or vehicle applied twice daily. In the other trial, called TRuE-V2, 344 patients were randomly assigned. The participating centers were in Europe and North America.

Patients aged 12 years or older with nonsegmental vitiligo and depigmentation covering no more than 10% of the total body surface area were eligible. The mean baseline F-VASI values were 1.0. The mean total VASI (T-FASI) values were 6.5. On those enrolled, half were female, 11% were adolescents, and 73% had Fitzpatrick skin phototypes III-VI.

Ruxolitinib cream provided near-complete vitiligo clearance (F-VASI 90) on the face at 24 weeks in only about 15% of patients, but this was several times higher than the 2% achieved on vehicle in the TRuE-V1 (P < .01) and the TRuE-V2 trials (P < .05), respectively.

F-VASI 50 response rates greater than 50%

For F-VASI 50, the response rate with ruxolitinib in both studies was approximately 51%. Relative to the 17.2% response on vehicle in TRuE-v1 and 23.4% in TRuE-V2 (both P < .0001 vs. active therapy), the advantage of the topical JAK inhibitor was considered to be a clinically meaningful, not just significant from a statistical standpoint.

In fact, improvement on the 5-point Vitiligo Noticeability Scale “also supported a clinically meaningful benefit,” Dr. Rosmarin reported. When those achieving a score of 4 (much less noticeable) or 5 (no longer noticeable), the response rates at 24 weeks were 24.5% and 21.6% in the TRuE-V1 and TRuE-V2 trials, respectively. Again, these response rates were several times greater than the 3.3% (P < .001) and 6.6% (P < .01) observed in the vehicle arms of TRuE-V1 and TRuE-V2 (P < .01), respectively.

Treatment-related adverse events were infrequent. The most common were acne at the application site, which occurred in about 5% of patients receiving ruxolitinib (vs. 2% or fewer of those receiving vehicle) and pruritus, which also occurred in about 5% of patients. However, the rates of pruritus among those on placebo reached 4% in TRuE-V1 and 2% in TRuE-V2 trials.

In vitiligo, where there has been recent progress in understanding the pathophysiology, loss of melanocytes in immune dysregulation has been linked to activation of the JAK signaling pathway, according to Dr. Rosmarin. In the 52-week phase 2 trial with 205 patients, ruxolitinib was associated with a sustained response and no serious treatment-related adverse events.
 

52-week data might show more benefit

Patients are continuing to be followed in the TRuE-V1 and TRuE-V-2 trials. Based on the phase 2 data and on the progressive improvement still being observed at the end of 24 weeks in the phase 3 trials, Dr. Rosmarin expects 52-week results be valuable in understanding the clinical role of ruxolitinib.

“We will be looking for further improvement in response as we follow these patients out to 1 year,” he said.

This further follow-up is important, agreed Iltefat Hamzavi, MD, senior staff physician, department of dermatology, Henry Ford Hospital, Detroit.

Despite the promise of perhaps other JAK inhibitors, “we still need to understand how long it will take for the drug to offer optimal results. We already know that is more than 24 weeks,” said Dr. Hamzavi, who has been involved in the clinical trials with this drug but was not involved with the TRuE-V1 or -V2 trials.

He also said more follow-up is needed to understand the duration of effect. He is, however, optimistic about the clinical role of this mechanism for treatment of vitiligo.

“I do think that JAK inhibitors show a lot of promise [in vitiligo] for certain locations of the body,” he said.

Given the limited treatment options for effective and prolonged improvement in vitiligo, both Dr. Hamzavi and Dr. Rosmarin indicated an effective topical cream is likely to be considered by physicians and patients to be a substantial advance.

On Sept. 21, ruxolitinib (Opzelura) 1.5% cream was approved by the Food and Drug Administration for the short-term treatment of mild to moderate atopic dermatitis in children and adults ages 12 years and older – the first FDA approval of this product.

Dr. Rosmarin reported financial relationships with more than 20 pharmaceutical companies, including Incyte, which provided funding for the TRuE-V1 and -V2 trials. Dr. Hamzavi reported financial relationships with more than 15 companies with pharmaceutical or cosmetic products, including Incyte.

A version of this article first appeared on Medscape.com.

A topical cream formulation of the Janus kinase inhibitor ruxolitinib was superior to its vehicle for treating vitiligo across all primary and secondary endpoints in two multicenter phase 3 trials presented together at the annual meeting of the European Academy of Dermatology and Venereology.

On the primary endpoint of F-VASI 75 (75% improvement in the Facial and Vitiligo Scoring Index), rates were nearly four times higher at 24 weeks in one trial (29.9% vs. 7.5%; P < .0001) and more than twice as great in the other (29.9% vs. 12.9%; P < .01).

“The larger phase 3 trials confirm the previous phase 2 findings,” reported David Rosmarin, MD, vice chairman for research and education, department of dermatology, Tufts Medical Center, Boston. These findings not only include substantial clinical efficacy but good tolerability with “no serious treatment-related adverse events,” he noted.
 

600 patients randomized

In one of the trials, called TRuE-V1, 330 patients with vitiligo were randomly assigned in a 2:1 ratio to 1.5% ruxolitinib or vehicle applied twice daily. In the other trial, called TRuE-V2, 344 patients were randomly assigned. The participating centers were in Europe and North America.

Patients aged 12 years or older with nonsegmental vitiligo and depigmentation covering no more than 10% of the total body surface area were eligible. The mean baseline F-VASI values were 1.0. The mean total VASI (T-FASI) values were 6.5. On those enrolled, half were female, 11% were adolescents, and 73% had Fitzpatrick skin phototypes III-VI.

Ruxolitinib cream provided near-complete vitiligo clearance (F-VASI 90) on the face at 24 weeks in only about 15% of patients, but this was several times higher than the 2% achieved on vehicle in the TRuE-V1 (P < .01) and the TRuE-V2 trials (P < .05), respectively.

F-VASI 50 response rates greater than 50%

For F-VASI 50, the response rate with ruxolitinib in both studies was approximately 51%. Relative to the 17.2% response on vehicle in TRuE-v1 and 23.4% in TRuE-V2 (both P < .0001 vs. active therapy), the advantage of the topical JAK inhibitor was considered to be a clinically meaningful, not just significant from a statistical standpoint.

In fact, improvement on the 5-point Vitiligo Noticeability Scale “also supported a clinically meaningful benefit,” Dr. Rosmarin reported. When those achieving a score of 4 (much less noticeable) or 5 (no longer noticeable), the response rates at 24 weeks were 24.5% and 21.6% in the TRuE-V1 and TRuE-V2 trials, respectively. Again, these response rates were several times greater than the 3.3% (P < .001) and 6.6% (P < .01) observed in the vehicle arms of TRuE-V1 and TRuE-V2 (P < .01), respectively.

Treatment-related adverse events were infrequent. The most common were acne at the application site, which occurred in about 5% of patients receiving ruxolitinib (vs. 2% or fewer of those receiving vehicle) and pruritus, which also occurred in about 5% of patients. However, the rates of pruritus among those on placebo reached 4% in TRuE-V1 and 2% in TRuE-V2 trials.

In vitiligo, where there has been recent progress in understanding the pathophysiology, loss of melanocytes in immune dysregulation has been linked to activation of the JAK signaling pathway, according to Dr. Rosmarin. In the 52-week phase 2 trial with 205 patients, ruxolitinib was associated with a sustained response and no serious treatment-related adverse events.
 

52-week data might show more benefit

Patients are continuing to be followed in the TRuE-V1 and TRuE-V-2 trials. Based on the phase 2 data and on the progressive improvement still being observed at the end of 24 weeks in the phase 3 trials, Dr. Rosmarin expects 52-week results be valuable in understanding the clinical role of ruxolitinib.

“We will be looking for further improvement in response as we follow these patients out to 1 year,” he said.

This further follow-up is important, agreed Iltefat Hamzavi, MD, senior staff physician, department of dermatology, Henry Ford Hospital, Detroit.

Despite the promise of perhaps other JAK inhibitors, “we still need to understand how long it will take for the drug to offer optimal results. We already know that is more than 24 weeks,” said Dr. Hamzavi, who has been involved in the clinical trials with this drug but was not involved with the TRuE-V1 or -V2 trials.

He also said more follow-up is needed to understand the duration of effect. He is, however, optimistic about the clinical role of this mechanism for treatment of vitiligo.

“I do think that JAK inhibitors show a lot of promise [in vitiligo] for certain locations of the body,” he said.

Given the limited treatment options for effective and prolonged improvement in vitiligo, both Dr. Hamzavi and Dr. Rosmarin indicated an effective topical cream is likely to be considered by physicians and patients to be a substantial advance.

On Sept. 21, ruxolitinib (Opzelura) 1.5% cream was approved by the Food and Drug Administration for the short-term treatment of mild to moderate atopic dermatitis in children and adults ages 12 years and older – the first FDA approval of this product.

Dr. Rosmarin reported financial relationships with more than 20 pharmaceutical companies, including Incyte, which provided funding for the TRuE-V1 and -V2 trials. Dr. Hamzavi reported financial relationships with more than 15 companies with pharmaceutical or cosmetic products, including Incyte.

A version of this article first appeared on Medscape.com.

Irish dermatologists are reporting two more cases of a rare skin ulcer known as reactive infectious mucocutaneous eruption (RIME) in teenage males who were infected with COVID-19. A similar case in an adolescent, also with ulcers affecting the mouth and penis, was reported earlier in 2021 in the United States.

“Our cases show that a swab for COVID-19 can be added to the list of investigations for mucosal and cutaneous rashes in children and probably adults,” said dermatologist Stephanie Bowe, MD, of South Infirmary-Victoria University Hospital in Cork, Ireland, in an interview. “Our patients seemed to improve with IV steroids, but there is not enough data to recommend them to all patients or for use in the different cutaneous presentations associated with COVID-19.”

The new case reports were presented at the 2021 meeting of the World Congress of Pediatric Dermatology and published in Pediatric Dermatology.

Researchers have noted that skin disorders linked to COVID-19 infection are different than those in adults. In children, the conditions include morbilliform rash, pernio-like acral lesions, urticaria, macular erythema, vesicular eruption, papulosquamous eruption, and retiform purpura. “The pathogenesis of each is not fully understood but likely related to the inflammatory response to COVID-19 and the various pathways within the body, which become activated,” Dr. Bowe said.

The first patient, a 17-year-old boy, presented at clinic 6 days after he’d been confirmed to be infected with COVID-19 and 8 days after developing fever and cough. “He had a 2-day history of conjunctivitis and ulceration of his oral mucosa, erythematous circumferential erosions of the glans penis with no other cutaneous findings,” the authors write in the report.

The boy “was distressed and embarrassed about his genital ulceration and also found eating very painful due to his oral ulceration,” Dr. Bowe said.

The second patient, a 14-year-old boy, was hospitalized 7 days after a positive COVID-19 test and 9 days after developing cough and fever. “He had a 5-day history of ulceration of the oral mucosa with mild conjunctivitis,” the authors wrote. “Ulceration of the glans penis developed on day 2 of admission.”

The 14-year-old was sicker than the 17-year-old boy, Dr. Bowe said. “He was unable to tolerate an oral diet for several days and had exquisite pain and vomiting with his coughing fits.”

This patient had a history of recurrent herpes labialis, but it’s unclear whether herpes simplex virus (HSV) played a role in the COVID-19–related case. “There is a possibility that the patient was more susceptible to viral cutaneous reactions during COVID-19 infection, but we didn’t have any definite history of HSV infection at the time of mucositis,” Dr. Bowe said. “We also didn’t have any swabs positive for HSV even though several were done at the time.”

Both patients received IV steroids – hydrocortisone at 100 mg 3 times daily for 3 days. This treatment was used “because of deterioration in symptoms and COVID-19 infection,” Dr. Bowe said. “IV steroids were used for respiratory symptoms of COVID-19, so we felt these cutaneous symptoms may have also been caused by an inflammatory response and might benefit from steroids. There was very little literature about this specific situation, though.”

She added that intravenous steroids wouldn’t be appropriate for most pediatric patients, and noted that “their use is controversial in the literature for erythema multiforme and RIME.”

In addition, the patients received betamethasone valerate 0.1% ointment once daily, hydrocortisone 2.5 mg buccal tablets 4 times daily, analgesia with acetaminophen and ibuprofen, and intravenous hydration. The first patient also received prednisolone 1% eye drops, while the second patient was given lidocaine hydrochloride mouthwash and total parenteral nutrition for 5 days.

The patients were discharged after 4 and 14 days, respectively.

Dermatologists in Massachusetts reported a similar case earlier in 2021 in a 17-year-old boy who was positive for COVID-19 and presented with “shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities.”

The patient received betamethasone valerate 0.1% ointment for the lips and penis, intraoral dexamethasone solution, viscous lidocaine, acetaminophen, and ibuprofen. He also received oral prednisone at approximately 1 mg/kg daily for 4 consecutive days after worsening oral pain. A recurrence of oral pain 3 months later was resolved with a higher and longer treatment with oral prednisone.

Dermatologists have also reported cases of erythema multiforme lesions of the mucosa in adults with COVID-19. One case was reported in Iran, and the other in France.

The authors report no study funding and disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Irish dermatologists are reporting two more cases of a rare skin ulcer known as reactive infectious mucocutaneous eruption (RIME) in teenage males who were infected with COVID-19. A similar case in an adolescent, also with ulcers affecting the mouth and penis, was reported earlier in 2021 in the United States.

“Our cases show that a swab for COVID-19 can be added to the list of investigations for mucosal and cutaneous rashes in children and probably adults,” said dermatologist Stephanie Bowe, MD, of South Infirmary-Victoria University Hospital in Cork, Ireland, in an interview. “Our patients seemed to improve with IV steroids, but there is not enough data to recommend them to all patients or for use in the different cutaneous presentations associated with COVID-19.”

The new case reports were presented at the 2021 meeting of the World Congress of Pediatric Dermatology and published in Pediatric Dermatology.

Researchers have noted that skin disorders linked to COVID-19 infection are different than those in adults. In children, the conditions include morbilliform rash, pernio-like acral lesions, urticaria, macular erythema, vesicular eruption, papulosquamous eruption, and retiform purpura. “The pathogenesis of each is not fully understood but likely related to the inflammatory response to COVID-19 and the various pathways within the body, which become activated,” Dr. Bowe said.

The first patient, a 17-year-old boy, presented at clinic 6 days after he’d been confirmed to be infected with COVID-19 and 8 days after developing fever and cough. “He had a 2-day history of conjunctivitis and ulceration of his oral mucosa, erythematous circumferential erosions of the glans penis with no other cutaneous findings,” the authors write in the report.

The boy “was distressed and embarrassed about his genital ulceration and also found eating very painful due to his oral ulceration,” Dr. Bowe said.

The second patient, a 14-year-old boy, was hospitalized 7 days after a positive COVID-19 test and 9 days after developing cough and fever. “He had a 5-day history of ulceration of the oral mucosa with mild conjunctivitis,” the authors wrote. “Ulceration of the glans penis developed on day 2 of admission.”

The 14-year-old was sicker than the 17-year-old boy, Dr. Bowe said. “He was unable to tolerate an oral diet for several days and had exquisite pain and vomiting with his coughing fits.”

This patient had a history of recurrent herpes labialis, but it’s unclear whether herpes simplex virus (HSV) played a role in the COVID-19–related case. “There is a possibility that the patient was more susceptible to viral cutaneous reactions during COVID-19 infection, but we didn’t have any definite history of HSV infection at the time of mucositis,” Dr. Bowe said. “We also didn’t have any swabs positive for HSV even though several were done at the time.”

Both patients received IV steroids – hydrocortisone at 100 mg 3 times daily for 3 days. This treatment was used “because of deterioration in symptoms and COVID-19 infection,” Dr. Bowe said. “IV steroids were used for respiratory symptoms of COVID-19, so we felt these cutaneous symptoms may have also been caused by an inflammatory response and might benefit from steroids. There was very little literature about this specific situation, though.”

She added that intravenous steroids wouldn’t be appropriate for most pediatric patients, and noted that “their use is controversial in the literature for erythema multiforme and RIME.”

In addition, the patients received betamethasone valerate 0.1% ointment once daily, hydrocortisone 2.5 mg buccal tablets 4 times daily, analgesia with acetaminophen and ibuprofen, and intravenous hydration. The first patient also received prednisolone 1% eye drops, while the second patient was given lidocaine hydrochloride mouthwash and total parenteral nutrition for 5 days.

The patients were discharged after 4 and 14 days, respectively.

Dermatologists in Massachusetts reported a similar case earlier in 2021 in a 17-year-old boy who was positive for COVID-19 and presented with “shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities.”

The patient received betamethasone valerate 0.1% ointment for the lips and penis, intraoral dexamethasone solution, viscous lidocaine, acetaminophen, and ibuprofen. He also received oral prednisone at approximately 1 mg/kg daily for 4 consecutive days after worsening oral pain. A recurrence of oral pain 3 months later was resolved with a higher and longer treatment with oral prednisone.

Dermatologists have also reported cases of erythema multiforme lesions of the mucosa in adults with COVID-19. One case was reported in Iran, and the other in France.

The authors report no study funding and disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Irish dermatologists are reporting two more cases of a rare skin ulcer known as reactive infectious mucocutaneous eruption (RIME) in teenage males who were infected with COVID-19. A similar case in an adolescent, also with ulcers affecting the mouth and penis, was reported earlier in 2021 in the United States.

“Our cases show that a swab for COVID-19 can be added to the list of investigations for mucosal and cutaneous rashes in children and probably adults,” said dermatologist Stephanie Bowe, MD, of South Infirmary-Victoria University Hospital in Cork, Ireland, in an interview. “Our patients seemed to improve with IV steroids, but there is not enough data to recommend them to all patients or for use in the different cutaneous presentations associated with COVID-19.”

The new case reports were presented at the 2021 meeting of the World Congress of Pediatric Dermatology and published in Pediatric Dermatology.

Researchers have noted that skin disorders linked to COVID-19 infection are different than those in adults. In children, the conditions include morbilliform rash, pernio-like acral lesions, urticaria, macular erythema, vesicular eruption, papulosquamous eruption, and retiform purpura. “The pathogenesis of each is not fully understood but likely related to the inflammatory response to COVID-19 and the various pathways within the body, which become activated,” Dr. Bowe said.

The first patient, a 17-year-old boy, presented at clinic 6 days after he’d been confirmed to be infected with COVID-19 and 8 days after developing fever and cough. “He had a 2-day history of conjunctivitis and ulceration of his oral mucosa, erythematous circumferential erosions of the glans penis with no other cutaneous findings,” the authors write in the report.

The boy “was distressed and embarrassed about his genital ulceration and also found eating very painful due to his oral ulceration,” Dr. Bowe said.

The second patient, a 14-year-old boy, was hospitalized 7 days after a positive COVID-19 test and 9 days after developing cough and fever. “He had a 5-day history of ulceration of the oral mucosa with mild conjunctivitis,” the authors wrote. “Ulceration of the glans penis developed on day 2 of admission.”

The 14-year-old was sicker than the 17-year-old boy, Dr. Bowe said. “He was unable to tolerate an oral diet for several days and had exquisite pain and vomiting with his coughing fits.”

This patient had a history of recurrent herpes labialis, but it’s unclear whether herpes simplex virus (HSV) played a role in the COVID-19–related case. “There is a possibility that the patient was more susceptible to viral cutaneous reactions during COVID-19 infection, but we didn’t have any definite history of HSV infection at the time of mucositis,” Dr. Bowe said. “We also didn’t have any swabs positive for HSV even though several were done at the time.”

Both patients received IV steroids – hydrocortisone at 100 mg 3 times daily for 3 days. This treatment was used “because of deterioration in symptoms and COVID-19 infection,” Dr. Bowe said. “IV steroids were used for respiratory symptoms of COVID-19, so we felt these cutaneous symptoms may have also been caused by an inflammatory response and might benefit from steroids. There was very little literature about this specific situation, though.”

She added that intravenous steroids wouldn’t be appropriate for most pediatric patients, and noted that “their use is controversial in the literature for erythema multiforme and RIME.”

In addition, the patients received betamethasone valerate 0.1% ointment once daily, hydrocortisone 2.5 mg buccal tablets 4 times daily, analgesia with acetaminophen and ibuprofen, and intravenous hydration. The first patient also received prednisolone 1% eye drops, while the second patient was given lidocaine hydrochloride mouthwash and total parenteral nutrition for 5 days.

The patients were discharged after 4 and 14 days, respectively.

Dermatologists in Massachusetts reported a similar case earlier in 2021 in a 17-year-old boy who was positive for COVID-19 and presented with “shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities.”

The patient received betamethasone valerate 0.1% ointment for the lips and penis, intraoral dexamethasone solution, viscous lidocaine, acetaminophen, and ibuprofen. He also received oral prednisone at approximately 1 mg/kg daily for 4 consecutive days after worsening oral pain. A recurrence of oral pain 3 months later was resolved with a higher and longer treatment with oral prednisone.

Dermatologists have also reported cases of erythema multiforme lesions of the mucosa in adults with COVID-19. One case was reported in Iran, and the other in France.

The authors report no study funding and disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Serious adverse events remained rare and skin remained largely clear in adolescents treated with dupilumab for moderate to severe atopic dermatitis (AD) for up to 52 weeks in a phase 3, open-label extension trial, researchers reported.

At 1 year, 86% of 50 remaining patients with weights under 60 kg (132 lb) had achieved 75% improvement on the Eczema Area and Severity Index (EASI-75, and 77% of 51 remaining patients with weights over 60 kg reached that level of clearance. Only 5 (1.7%) of 294 patients had serious treatment-emergent adverse events (TEAEs).

The findings back up a perception that patients can stay on dupilumab for some time instead of having to switch from one biologic to another after a few years, study coauthor Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, said in an interview. He added that the drug’s long-term safety profile is “very reassuring.”

The industry-funded findings of the study were released in a poster at the 2021 meeting of the World Congress of Pediatric Dermatology.

The FDA approved dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, for treating AD in adults in 2017; it is now approved for treating patients ages 6 years and older with moderate to severe atopic dermatitis whose disease is not adequately controlled with topicals.

The new study tracked patients who received at least 300 mg dupilumab subcutaneously every 4 weeks. The dose could be increased if needed to improve clinical response to once every 2 weeks (200 mg if baseline weight was <60 kg; 300 mg if ≥60 kg).

At 52 weeks, 37% of 52 patients with weights under 60 kg reached an Investigator Global Assessment (IGA) of 0/1, a level that had been fairly steady since week 16 (n = 146). Among 51 heavier patients, 49% reached an IGA of 0/1 at 52 weeks; this percentage grew steadily since baseline.

The mean percentage change in EASI was –87% in the lower-weight group (n = 50) at 52 weeks and –80.1% in the larger-weight group (n = 51). The majority of the reduction in EASI occurred in the first 4 weeks of treatment.

At 52 weeks, the mean Children’s Dermatology Life Quality Index level, which judges the effect of AD on life, was judged as “small” (low) in 71 patients. At baseline, the mean level among 189 patients was “moderate.” The levels dipped below “moderate” at week 4 and never rose above “small” after that.

“Treatment-emergent adverse events reported in ≥5% of patients were nasopharyngitis (21.1%), AD (19.4%), upper respiratory tract infection (12.4%), headache (9.4%), and oropharyngeal pain (5.7%),” the investigators wrote in the poster. They add that 6.7% of patients experienced injection-site reactions, and 8.7% of patients experienced treatment-emergent “narrow conjunctivitis,” which includes conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, and atopic keratoconjunctivitis.

Dr. Simpson noted that cases of conjunctivitis fell over time. It’s not clear why this adverse effect appears, he said.

He said that the findings reflect his own experience in clinic. Many of his adolescent patients took part in early dupilumab trials, he said, and dozens have been taking the drug for more than 5 years. “They just seem to get better and better,” he said.

University of Minnesota, Minneapolis, dermatologist Sheilagh Maguiness, MD, who wasn’t involved with the study, said in an interview that dupilumab remains “the safest, most effective and evidence-based therapy we had for children with moderate to severe atopic dermatitis.”

The new study’s findings are “very reassuring,” she said, and similar to those in a 2021 report that tracked long-term use of the drug in children aged 6-11.

Like Dr. Simpson, Dr. Maguiness said many pediatric patients at her clinic have stayed on the drug for more than 5 years. They still have “sustained improvement in skin disease and in their quality of life as well”

There are, however, still questions about dupilumab treatment. “For children who have responded well, when could we consider dose reduction or discontinuation? I have done this successfully just a handful of times, but I would love to see data about what percentage of pediatric patients experience rebound disease after coming off the drug and after what duration of treatment,” she said. “Another mystery that will be very interesting to unravel is the question as to whether or not early treatment with dupilumab may attenuate other atopic diseases.”

Dr. Maguiness added that “another issue specific to pediatric use of dupilumab is the recommendation surrounding vaccinations. This is an issue that should be studied in terms of antibody response and safety surrounding vaccinations, particularly as we are eagerly awaiting a pediatric FDA approval for the COVID-19 vaccine in children.”

She also urged colleagues to push back against insurers who resist paying for dupilumab. “Whether prescribing this medication on or off label, insurance companies are often requiring patients to try and fail other traditional immunosuppressive medications such as methotrexate, cyclosporine, or to pursue phototherapy,” she said. “Oftentimes, these are not practical or even safe options for children for a multitude of reasons. Don’t be shy about advocating for your patients by second- or even third-level appeals to try and gain approval for children who are in need of treatment.”

The study was funded by Sanofi Genzyme and Regeneron Pharmaceuticals. The study authors reported various disclosures. Dr. Simpson reported investigator and consultant fee relationships from various pharmaceutical companies. Dr. Maguiness was an investigator for one of the initial pediatric dupilumab trials.

A version of this article first appeared on Medscape.com.

Serious adverse events remained rare and skin remained largely clear in adolescents treated with dupilumab for moderate to severe atopic dermatitis (AD) for up to 52 weeks in a phase 3, open-label extension trial, researchers reported.

At 1 year, 86% of 50 remaining patients with weights under 60 kg (132 lb) had achieved 75% improvement on the Eczema Area and Severity Index (EASI-75, and 77% of 51 remaining patients with weights over 60 kg reached that level of clearance. Only 5 (1.7%) of 294 patients had serious treatment-emergent adverse events (TEAEs).

The findings back up a perception that patients can stay on dupilumab for some time instead of having to switch from one biologic to another after a few years, study coauthor Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, said in an interview. He added that the drug’s long-term safety profile is “very reassuring.”

The industry-funded findings of the study were released in a poster at the 2021 meeting of the World Congress of Pediatric Dermatology.

The FDA approved dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, for treating AD in adults in 2017; it is now approved for treating patients ages 6 years and older with moderate to severe atopic dermatitis whose disease is not adequately controlled with topicals.

The new study tracked patients who received at least 300 mg dupilumab subcutaneously every 4 weeks. The dose could be increased if needed to improve clinical response to once every 2 weeks (200 mg if baseline weight was <60 kg; 300 mg if ≥60 kg).

At 52 weeks, 37% of 52 patients with weights under 60 kg reached an Investigator Global Assessment (IGA) of 0/1, a level that had been fairly steady since week 16 (n = 146). Among 51 heavier patients, 49% reached an IGA of 0/1 at 52 weeks; this percentage grew steadily since baseline.

The mean percentage change in EASI was –87% in the lower-weight group (n = 50) at 52 weeks and –80.1% in the larger-weight group (n = 51). The majority of the reduction in EASI occurred in the first 4 weeks of treatment.

At 52 weeks, the mean Children’s Dermatology Life Quality Index level, which judges the effect of AD on life, was judged as “small” (low) in 71 patients. At baseline, the mean level among 189 patients was “moderate.” The levels dipped below “moderate” at week 4 and never rose above “small” after that.

“Treatment-emergent adverse events reported in ≥5% of patients were nasopharyngitis (21.1%), AD (19.4%), upper respiratory tract infection (12.4%), headache (9.4%), and oropharyngeal pain (5.7%),” the investigators wrote in the poster. They add that 6.7% of patients experienced injection-site reactions, and 8.7% of patients experienced treatment-emergent “narrow conjunctivitis,” which includes conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, and atopic keratoconjunctivitis.

Dr. Simpson noted that cases of conjunctivitis fell over time. It’s not clear why this adverse effect appears, he said.

He said that the findings reflect his own experience in clinic. Many of his adolescent patients took part in early dupilumab trials, he said, and dozens have been taking the drug for more than 5 years. “They just seem to get better and better,” he said.

University of Minnesota, Minneapolis, dermatologist Sheilagh Maguiness, MD, who wasn’t involved with the study, said in an interview that dupilumab remains “the safest, most effective and evidence-based therapy we had for children with moderate to severe atopic dermatitis.”

The new study’s findings are “very reassuring,” she said, and similar to those in a 2021 report that tracked long-term use of the drug in children aged 6-11.

Like Dr. Simpson, Dr. Maguiness said many pediatric patients at her clinic have stayed on the drug for more than 5 years. They still have “sustained improvement in skin disease and in their quality of life as well”

There are, however, still questions about dupilumab treatment. “For children who have responded well, when could we consider dose reduction or discontinuation? I have done this successfully just a handful of times, but I would love to see data about what percentage of pediatric patients experience rebound disease after coming off the drug and after what duration of treatment,” she said. “Another mystery that will be very interesting to unravel is the question as to whether or not early treatment with dupilumab may attenuate other atopic diseases.”

Dr. Maguiness added that “another issue specific to pediatric use of dupilumab is the recommendation surrounding vaccinations. This is an issue that should be studied in terms of antibody response and safety surrounding vaccinations, particularly as we are eagerly awaiting a pediatric FDA approval for the COVID-19 vaccine in children.”

She also urged colleagues to push back against insurers who resist paying for dupilumab. “Whether prescribing this medication on or off label, insurance companies are often requiring patients to try and fail other traditional immunosuppressive medications such as methotrexate, cyclosporine, or to pursue phototherapy,” she said. “Oftentimes, these are not practical or even safe options for children for a multitude of reasons. Don’t be shy about advocating for your patients by second- or even third-level appeals to try and gain approval for children who are in need of treatment.”

The study was funded by Sanofi Genzyme and Regeneron Pharmaceuticals. The study authors reported various disclosures. Dr. Simpson reported investigator and consultant fee relationships from various pharmaceutical companies. Dr. Maguiness was an investigator for one of the initial pediatric dupilumab trials.

A version of this article first appeared on Medscape.com.

Serious adverse events remained rare and skin remained largely clear in adolescents treated with dupilumab for moderate to severe atopic dermatitis (AD) for up to 52 weeks in a phase 3, open-label extension trial, researchers reported.

At 1 year, 86% of 50 remaining patients with weights under 60 kg (132 lb) had achieved 75% improvement on the Eczema Area and Severity Index (EASI-75, and 77% of 51 remaining patients with weights over 60 kg reached that level of clearance. Only 5 (1.7%) of 294 patients had serious treatment-emergent adverse events (TEAEs).

The findings back up a perception that patients can stay on dupilumab for some time instead of having to switch from one biologic to another after a few years, study coauthor Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, said in an interview. He added that the drug’s long-term safety profile is “very reassuring.”

The industry-funded findings of the study were released in a poster at the 2021 meeting of the World Congress of Pediatric Dermatology.

The FDA approved dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, for treating AD in adults in 2017; it is now approved for treating patients ages 6 years and older with moderate to severe atopic dermatitis whose disease is not adequately controlled with topicals.

The new study tracked patients who received at least 300 mg dupilumab subcutaneously every 4 weeks. The dose could be increased if needed to improve clinical response to once every 2 weeks (200 mg if baseline weight was <60 kg; 300 mg if ≥60 kg).

At 52 weeks, 37% of 52 patients with weights under 60 kg reached an Investigator Global Assessment (IGA) of 0/1, a level that had been fairly steady since week 16 (n = 146). Among 51 heavier patients, 49% reached an IGA of 0/1 at 52 weeks; this percentage grew steadily since baseline.

The mean percentage change in EASI was –87% in the lower-weight group (n = 50) at 52 weeks and –80.1% in the larger-weight group (n = 51). The majority of the reduction in EASI occurred in the first 4 weeks of treatment.

At 52 weeks, the mean Children’s Dermatology Life Quality Index level, which judges the effect of AD on life, was judged as “small” (low) in 71 patients. At baseline, the mean level among 189 patients was “moderate.” The levels dipped below “moderate” at week 4 and never rose above “small” after that.

“Treatment-emergent adverse events reported in ≥5% of patients were nasopharyngitis (21.1%), AD (19.4%), upper respiratory tract infection (12.4%), headache (9.4%), and oropharyngeal pain (5.7%),” the investigators wrote in the poster. They add that 6.7% of patients experienced injection-site reactions, and 8.7% of patients experienced treatment-emergent “narrow conjunctivitis,” which includes conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, and atopic keratoconjunctivitis.

Dr. Simpson noted that cases of conjunctivitis fell over time. It’s not clear why this adverse effect appears, he said.

He said that the findings reflect his own experience in clinic. Many of his adolescent patients took part in early dupilumab trials, he said, and dozens have been taking the drug for more than 5 years. “They just seem to get better and better,” he said.

University of Minnesota, Minneapolis, dermatologist Sheilagh Maguiness, MD, who wasn’t involved with the study, said in an interview that dupilumab remains “the safest, most effective and evidence-based therapy we had for children with moderate to severe atopic dermatitis.”

The new study’s findings are “very reassuring,” she said, and similar to those in a 2021 report that tracked long-term use of the drug in children aged 6-11.

Like Dr. Simpson, Dr. Maguiness said many pediatric patients at her clinic have stayed on the drug for more than 5 years. They still have “sustained improvement in skin disease and in their quality of life as well”

There are, however, still questions about dupilumab treatment. “For children who have responded well, when could we consider dose reduction or discontinuation? I have done this successfully just a handful of times, but I would love to see data about what percentage of pediatric patients experience rebound disease after coming off the drug and after what duration of treatment,” she said. “Another mystery that will be very interesting to unravel is the question as to whether or not early treatment with dupilumab may attenuate other atopic diseases.”

Dr. Maguiness added that “another issue specific to pediatric use of dupilumab is the recommendation surrounding vaccinations. This is an issue that should be studied in terms of antibody response and safety surrounding vaccinations, particularly as we are eagerly awaiting a pediatric FDA approval for the COVID-19 vaccine in children.”

She also urged colleagues to push back against insurers who resist paying for dupilumab. “Whether prescribing this medication on or off label, insurance companies are often requiring patients to try and fail other traditional immunosuppressive medications such as methotrexate, cyclosporine, or to pursue phototherapy,” she said. “Oftentimes, these are not practical or even safe options for children for a multitude of reasons. Don’t be shy about advocating for your patients by second- or even third-level appeals to try and gain approval for children who are in need of treatment.”

The study was funded by Sanofi Genzyme and Regeneron Pharmaceuticals. The study authors reported various disclosures. Dr. Simpson reported investigator and consultant fee relationships from various pharmaceutical companies. Dr. Maguiness was an investigator for one of the initial pediatric dupilumab trials.

A version of this article first appeared on Medscape.com.

Although any adverse event from an elective procedure is reasonably considered a bad outcome, some adverse events associated with cosmetic filler injections risk being catastrophic if not promptly addressed, according to an expert explaining the signs of an impending disaster at the Skin of Color Update 2021.

The most serious of the adverse events stem from vascular compromise, which is often signaled immediately by sharp pain and blanching of the skin, according to Hassan Galadari, MD, assistant professor of dermatology at the United Arab Emirates University, Dubai.

“Swift and aggressive treatment is required to avoid irreversible changes,” said Dr. Galadari, warning that blindness and vision impairment can be permanent, and that other events associated with vascular compromise include stroke and other types of embolism, as well as tissue necrosis.

To be swift, Dr. Galadari advised an immediate halt of injections and then a series of steps to abort the vascular insult. The goal is to encourage blood flow to prevent clotting and dissipate the filler.

“Massage the area like crazy. Keep on massaging. The more you massage the better. You are recruiting blood into that area so it remains viable,” Dr. Galadari said.
 

Hyaluronidase injections helpful

Warm compresses should also be applied for periods ranging from 5 minutes up to an hour, he added. In patients treated with hyaluronic acid, he also commonly introduces hyaluronidase injections of 200-500 IU diluted in lidocaine or saline. The injections are placed 2-3 cm apart and repeated every hour until signs and symptoms improve.

“Flush all of the filler out,” he said, emphasizing the urgency for reversing risk of vascular adverse events.

To sustain blood flow and avoid clots, he also recommends initiating aspirin with maintenance doses sustained over several days. Sildenafil to further improve conditions of blood perfusion can be “considered.”

The risks of vascular compromise, like other complications from filler injections, are low, but they are not zero, and the opportunity to prevent irreversible changes depends on acting quickly, according to Dr. Galadari.

“To prevent embolism, recognize the danger zones,” he advised, identifying the glabella region as the site of highest risk. The risk of vascular compromise from injections into the nasal region is lower but higher than injections of the nasolabial fold and forehead, which are associated with a relatively low risk.

Slow injections reduce risks

Some basic strategies he recommended for preventing vascular compromise included slow injections while keeping pressure low and using small volumes of filler per shot. Fractionated treatment and microdroplet techniques can be appropriate depending on the site of injection.

“Delivery of the filler by cannulas rather than by needles is preferable,” according to Dr. Galadari, who noted that a task force from the American Society for Dermatologic Surgery recently endorsed this approach as part of other recommendations to avoid complications of injectable fillers.

The Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database suggests that adverse events of any substantial severity from filler injections, not just those involving vascular compromise, occur at a rate of 1 per 3,600 cases. However, MAUDE is a passive surveillance system dependent on reports provided by clinicians and others, so this event rate might be an underrepresentation.

In the MAUDE database, complication rates are listed for each of the available filler products and show a variation in rates not just overall but also for each of the major types of complications, which include skin-specific complications such as nodules, discoloration, and inflammation, as well as neurologic adverse events, infection, and vascular compromise, Dr. Galadari reported.
 

Filler products are not interchangeable

Again, because of passive data collection, it is not clear whether the differences between products is a true representation of relative risk. Nevertheless, Dr. Galadari cautioned that these products are not necessarily interchangeable, advising clinicians to avoid products without an established safety track record.

There are a wide variety of fillers, including biostimulatory products, such as poly-L-lactic acid and calcium hydroxyapatite, and permanent fillers, such as silicone, in addition to collagen and hyaluronic acid, which function as temporary fillers, according to Dr. Galadari. He emphasized that the specific risks of each filler vary, but clinicians should always respond quickly whenever there is an adverse reaction or evidence of vascular compromise.

In flushing out filler, Cheryl M. Burgess, MD, of the Center for Dermatology and Dermatologic Surgery, Washington, who spoke at the meeting, also emphasized a prompt response. She too employs hyaluronidase injections to break down excess hyaluronic acid in the event of complications related to this filler.

Importantly, Dr. Burgess pointed out that hyaluronic acid can be considered safe for darker skin types, including Fitzpatrick skin types IV, V, and VI, but she added that speed of injection might be a particularly important variable for cosmetic procedures in skin of color.

“There is less postinflammatory hyperpigmentation with slower injection times and more with serial or multiple puncture injection technique,” she cautioned.

She further concurred with the value of cannulas over needles in most instances for facial contouring applications with filler, but she encouraged clinicians not to be overly ambitious and to move gradually toward goals.

“The desired outcome may require multiple sessions with conservative measures,” she said, indicating that conservative measures also represent a strategy to avoid adverse events.

Although any adverse event from an elective procedure is reasonably considered a bad outcome, some adverse events associated with cosmetic filler injections risk being catastrophic if not promptly addressed, according to an expert explaining the signs of an impending disaster at the Skin of Color Update 2021.

The most serious of the adverse events stem from vascular compromise, which is often signaled immediately by sharp pain and blanching of the skin, according to Hassan Galadari, MD, assistant professor of dermatology at the United Arab Emirates University, Dubai.

“Swift and aggressive treatment is required to avoid irreversible changes,” said Dr. Galadari, warning that blindness and vision impairment can be permanent, and that other events associated with vascular compromise include stroke and other types of embolism, as well as tissue necrosis.

To be swift, Dr. Galadari advised an immediate halt of injections and then a series of steps to abort the vascular insult. The goal is to encourage blood flow to prevent clotting and dissipate the filler.

“Massage the area like crazy. Keep on massaging. The more you massage the better. You are recruiting blood into that area so it remains viable,” Dr. Galadari said.
 

Hyaluronidase injections helpful

Warm compresses should also be applied for periods ranging from 5 minutes up to an hour, he added. In patients treated with hyaluronic acid, he also commonly introduces hyaluronidase injections of 200-500 IU diluted in lidocaine or saline. The injections are placed 2-3 cm apart and repeated every hour until signs and symptoms improve.

“Flush all of the filler out,” he said, emphasizing the urgency for reversing risk of vascular adverse events.

To sustain blood flow and avoid clots, he also recommends initiating aspirin with maintenance doses sustained over several days. Sildenafil to further improve conditions of blood perfusion can be “considered.”

The risks of vascular compromise, like other complications from filler injections, are low, but they are not zero, and the opportunity to prevent irreversible changes depends on acting quickly, according to Dr. Galadari.

“To prevent embolism, recognize the danger zones,” he advised, identifying the glabella region as the site of highest risk. The risk of vascular compromise from injections into the nasal region is lower but higher than injections of the nasolabial fold and forehead, which are associated with a relatively low risk.

Slow injections reduce risks

Some basic strategies he recommended for preventing vascular compromise included slow injections while keeping pressure low and using small volumes of filler per shot. Fractionated treatment and microdroplet techniques can be appropriate depending on the site of injection.

“Delivery of the filler by cannulas rather than by needles is preferable,” according to Dr. Galadari, who noted that a task force from the American Society for Dermatologic Surgery recently endorsed this approach as part of other recommendations to avoid complications of injectable fillers.

The Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database suggests that adverse events of any substantial severity from filler injections, not just those involving vascular compromise, occur at a rate of 1 per 3,600 cases. However, MAUDE is a passive surveillance system dependent on reports provided by clinicians and others, so this event rate might be an underrepresentation.

In the MAUDE database, complication rates are listed for each of the available filler products and show a variation in rates not just overall but also for each of the major types of complications, which include skin-specific complications such as nodules, discoloration, and inflammation, as well as neurologic adverse events, infection, and vascular compromise, Dr. Galadari reported.
 

Filler products are not interchangeable

Again, because of passive data collection, it is not clear whether the differences between products is a true representation of relative risk. Nevertheless, Dr. Galadari cautioned that these products are not necessarily interchangeable, advising clinicians to avoid products without an established safety track record.

There are a wide variety of fillers, including biostimulatory products, such as poly-L-lactic acid and calcium hydroxyapatite, and permanent fillers, such as silicone, in addition to collagen and hyaluronic acid, which function as temporary fillers, according to Dr. Galadari. He emphasized that the specific risks of each filler vary, but clinicians should always respond quickly whenever there is an adverse reaction or evidence of vascular compromise.

In flushing out filler, Cheryl M. Burgess, MD, of the Center for Dermatology and Dermatologic Surgery, Washington, who spoke at the meeting, also emphasized a prompt response. She too employs hyaluronidase injections to break down excess hyaluronic acid in the event of complications related to this filler.

Importantly, Dr. Burgess pointed out that hyaluronic acid can be considered safe for darker skin types, including Fitzpatrick skin types IV, V, and VI, but she added that speed of injection might be a particularly important variable for cosmetic procedures in skin of color.

“There is less postinflammatory hyperpigmentation with slower injection times and more with serial or multiple puncture injection technique,” she cautioned.

She further concurred with the value of cannulas over needles in most instances for facial contouring applications with filler, but she encouraged clinicians not to be overly ambitious and to move gradually toward goals.

“The desired outcome may require multiple sessions with conservative measures,” she said, indicating that conservative measures also represent a strategy to avoid adverse events.

Although any adverse event from an elective procedure is reasonably considered a bad outcome, some adverse events associated with cosmetic filler injections risk being catastrophic if not promptly addressed, according to an expert explaining the signs of an impending disaster at the Skin of Color Update 2021.

The most serious of the adverse events stem from vascular compromise, which is often signaled immediately by sharp pain and blanching of the skin, according to Hassan Galadari, MD, assistant professor of dermatology at the United Arab Emirates University, Dubai.

“Swift and aggressive treatment is required to avoid irreversible changes,” said Dr. Galadari, warning that blindness and vision impairment can be permanent, and that other events associated with vascular compromise include stroke and other types of embolism, as well as tissue necrosis.

To be swift, Dr. Galadari advised an immediate halt of injections and then a series of steps to abort the vascular insult. The goal is to encourage blood flow to prevent clotting and dissipate the filler.

“Massage the area like crazy. Keep on massaging. The more you massage the better. You are recruiting blood into that area so it remains viable,” Dr. Galadari said.
 

Hyaluronidase injections helpful

Warm compresses should also be applied for periods ranging from 5 minutes up to an hour, he added. In patients treated with hyaluronic acid, he also commonly introduces hyaluronidase injections of 200-500 IU diluted in lidocaine or saline. The injections are placed 2-3 cm apart and repeated every hour until signs and symptoms improve.

“Flush all of the filler out,” he said, emphasizing the urgency for reversing risk of vascular adverse events.

To sustain blood flow and avoid clots, he also recommends initiating aspirin with maintenance doses sustained over several days. Sildenafil to further improve conditions of blood perfusion can be “considered.”

The risks of vascular compromise, like other complications from filler injections, are low, but they are not zero, and the opportunity to prevent irreversible changes depends on acting quickly, according to Dr. Galadari.

“To prevent embolism, recognize the danger zones,” he advised, identifying the glabella region as the site of highest risk. The risk of vascular compromise from injections into the nasal region is lower but higher than injections of the nasolabial fold and forehead, which are associated with a relatively low risk.

Slow injections reduce risks

Some basic strategies he recommended for preventing vascular compromise included slow injections while keeping pressure low and using small volumes of filler per shot. Fractionated treatment and microdroplet techniques can be appropriate depending on the site of injection.

“Delivery of the filler by cannulas rather than by needles is preferable,” according to Dr. Galadari, who noted that a task force from the American Society for Dermatologic Surgery recently endorsed this approach as part of other recommendations to avoid complications of injectable fillers.

The Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database suggests that adverse events of any substantial severity from filler injections, not just those involving vascular compromise, occur at a rate of 1 per 3,600 cases. However, MAUDE is a passive surveillance system dependent on reports provided by clinicians and others, so this event rate might be an underrepresentation.

In the MAUDE database, complication rates are listed for each of the available filler products and show a variation in rates not just overall but also for each of the major types of complications, which include skin-specific complications such as nodules, discoloration, and inflammation, as well as neurologic adverse events, infection, and vascular compromise, Dr. Galadari reported.
 

Filler products are not interchangeable

Again, because of passive data collection, it is not clear whether the differences between products is a true representation of relative risk. Nevertheless, Dr. Galadari cautioned that these products are not necessarily interchangeable, advising clinicians to avoid products without an established safety track record.

There are a wide variety of fillers, including biostimulatory products, such as poly-L-lactic acid and calcium hydroxyapatite, and permanent fillers, such as silicone, in addition to collagen and hyaluronic acid, which function as temporary fillers, according to Dr. Galadari. He emphasized that the specific risks of each filler vary, but clinicians should always respond quickly whenever there is an adverse reaction or evidence of vascular compromise.

In flushing out filler, Cheryl M. Burgess, MD, of the Center for Dermatology and Dermatologic Surgery, Washington, who spoke at the meeting, also emphasized a prompt response. She too employs hyaluronidase injections to break down excess hyaluronic acid in the event of complications related to this filler.

Importantly, Dr. Burgess pointed out that hyaluronic acid can be considered safe for darker skin types, including Fitzpatrick skin types IV, V, and VI, but she added that speed of injection might be a particularly important variable for cosmetic procedures in skin of color.

“There is less postinflammatory hyperpigmentation with slower injection times and more with serial or multiple puncture injection technique,” she cautioned.

She further concurred with the value of cannulas over needles in most instances for facial contouring applications with filler, but she encouraged clinicians not to be overly ambitious and to move gradually toward goals.

“The desired outcome may require multiple sessions with conservative measures,” she said, indicating that conservative measures also represent a strategy to avoid adverse events.