When I was in fellowship in the late 1990s, it was rare to see women at many of the big gastroenterology conferences. And in terms of presentations, there was maybe one session led by or for women at lunchtime. These conferences were the only events I had ever been to where the line for the men’s room was longer than the line for the women’s room.

Over the years, the lines for the women’s room have gotten longer, and the sessions led by female gastroenterologists have grown exponentially. However, women are still underrepresented in our field. Two out of five GI fellows are women, but women constitute less than 18% of practicing gastroenterologists. And the number of women in leadership positions is even lower.
 

Women in medicine face many challenges

According to a report in JAMA Network Open, women have lower starting salaries more than 90% of the time, which can create income disparities in earning potential throughout our entire careers.

Other studies suggest that female physicians also spend more time with patients and answering messages from patients and colleagues as well. This extra time, although it is done in small increments, adds up quickly and could suggest the pay gap between women and men is wider than we think.

Of course, female physicians still spend more time parenting children and doing household labor. A study found that female physicians spent 8.5 hours more per week on activities that support the family and household.

We’ve been discussing equity for women in medicine, and in the workplace, for decades. But events over the past several years – such as the killing of George Floyd and the formation of the #MeToo movement in response to workplace sexual harassment – have accelerated a paradigm shift in how organizations are focusing on diversity, equity, and inclusion (DEI) and creating cultures that support leadership development for women.

The Gastro Health Women’s Network

In 2020, the leadership of Gastro Health reiterated its commitment to fight discrimination and support equity by sending out a company-wide correspondence that encouraged us to be good stewards within our communities during these turbulent times.

This led to the development of the Gastro Health DEI Council and the Gastro Health Women’s Network, led by Dr. Asma Khapra and based on the framework developed by Dr. Dawn Sears. The programs developed by Dr. Sears are focused on facilitating authentic and supportive relationships, and they helped us create a network for women focused on recruitment, mentorship and retention, networking and social events, and leadership development.

Our network started with a meet & greet, inviting all women in Gastro Health to join a virtual call and get to know each other in an informal setting. This was a great way to introduce people to each other in our natural elements. It was wonderful to see how people are when they are at home and not working.
 

Recruiting female gastroenterologists

Even though about half of gastroenterology fellows choose independent GI, most fellowship programs don’t educate students about private practice careers or promote that path. In addition, a lot of the national GI conferences are geared toward the academic experience.

It’s incumbent on those of us in private practice to educate students about the benefits and challenges we face as members of independent GI groups, and Gastro Health set out to hold networking and recruitment events at different national conferences with GI fellows and residents.

We’re also working to develop partnerships with fellowship programs. This past year, we’ve held several educational dinners for fellows and residents. Most recently, Dr. Khapra and others took a road trip to New York for dinners with fellows from Mount Sinai, Westchester Medical Center, and the Albert Einstein College of Medicine.

While it was beneficial for Gastro Health to provide information about life as private practice gastroenterologists, it was also helpful for us to hear how the GI leaders of tomorrow are navigating their career choices and what is impacting their decisions about the future.
 

Mentorship and retention are vital to practice sustainability

Once you’ve recruited physicians to join your practice, how do you ensure their success? Many practices are rightly concerned about their long-term sustainability and are exploring ways to help early-career physicians maintain the clinical skills they need to treat patients and learn the business skills they need to succeed in private practice.

Sometimes it’s as simple as reaching out to new associates on the first day to let them know you’re glad they’ve joined the practice and to let them know you’re available if they need anything. But there’s also growing recognition that implementing a formal mentorship program can help people feel included and supported.

The Women’s Network worked to pair its members with Gastro Health partners as mentors, and we’ve learned some things along the way. Initially, we tried to pair people with similar lifestyles and interests. What we found is that while this sometimes works, we may have overcomplicated the process. We learned that sometimes people would prefer mentors who have backgrounds that are different from their own. We were reminded that mentorship has many faces, and letting those relationships develop naturally can sometimes be more effective.
 

Networking and social events deter isolation and keep people engaged

Private practice can be different from working within a hospital because oftentimes your colleagues are working in different offices or facilities. In the case of our organization, those offices may be in different states hundreds of miles away. Within a hospital, there might be more potential to interact with your colleagues, whether in clinical conferences or through a chance encounter in the cafeteria.

In private practice, you may need to be more intentional about creating opportunities for people to network and get to know each other outside of work. This year, we developed an email and WhatsApp group so that women throughout the network can connect with each other. We have used it to disseminate information about upcoming events, fellowship opportunities with the national GI societies, interesting articles, and anything important that we think other women within Gastro Health would like to know.

In March, Gastro Health sponsored five women to attend the Scrubs & Heels Summit, which was developed by Dr. Anita Afzali and Dr. Aline Charabaty to create opportunities for women in GI at different stages of their GI careers and help them succeed and achieve their professional goals. There were 2 days of educational talks, but it also included plenty of events for our colleagues to get to know each other and network with other amazing female GI leaders from across the nation.


 

Where’s the boardroom?

A recent study found that the percentage of women on the boards of the 1,000 largest public companies in America is a little more than 28%, even though research shows that S&P 500 companies headquartered in California with 30% or more women on their boards had 29% higher revenue.

We’re working to develop opportunities for women to be in leadership positions, within our practices and on the national stage in terms of representation, within our national GI societies. It’s very exciting that we have women in leadership within AGA and ASGE, and that Dr. Latha Alaparthi has made increasing the focus on leadership and pipeline development one of her main priorities as the president and board chair of the Digestive Health Physicians Association (DHPA).

Another way private practices can support women who are leaders is by making recommendations for committees within our national societies and by recognizing that time spent developing presentations and speaking at national conferences is beneficial to the practice in terms of thought leadership, branding, and recruitment of the next generation of practice leaders.

While we have a long way to go, we’re also making strides in the board room at the practice level. I’m the first woman, and notably a woman of color, to join the Gastro Health board of directors under the guidance of support of CEO Joseph Garcia. Dr. Aja McCutchen, who serves as the chair of the DHPA Diversity, Equity, and Inclusion committee, is similarly the first woman and woman of color on the board of directors for United Digestive in Atlanta.


 

What to look for in joining a practice

When determining which practice you might join, ask how committed the leadership of the organization is to supporting career development for women. Does the practice have a network, a committee or other internal group that supports female physicians? What steps does the practice leadership take to support women who are interested in executive opportunities?

If the practice does have an internal organization, how does it measure progress? For example, we’ve implemented focus groups to measure what is working and where we face the most challenges. Gastro Health partnered with a consultant to hold three confidential sessions with 10 women at a time. This will allow for us to collect depersonalized data that can be compiled into a report for the Gastro Health Board and leadership.

If you’re a woman who is considering a career in independent GI, seek out women in private practice and ask about their experiences. Ask about their path and what opportunities they sought out when starting their careers. They may know of some great opportunities that are available to build your leadership skills.

By creating a network for women, Gastro Health is hoping to make it easier to develop relationships and create productive partnerships. We are certain that working to address the specific challenges that female physicians face in their careers will strengthen our group, and ultimately independent gastroenterology overall.

Dr. Adams is a practicing gastroenterologist and partner at Gastro Health Fairfax in Virginia and serves on the Digestive Health Physicians Association’s Diversity, Equity, and Inclusion Committee. Dr. Adams has no conflicts to declare.

When I was in fellowship in the late 1990s, it was rare to see women at many of the big gastroenterology conferences. And in terms of presentations, there was maybe one session led by or for women at lunchtime. These conferences were the only events I had ever been to where the line for the men’s room was longer than the line for the women’s room.

Over the years, the lines for the women’s room have gotten longer, and the sessions led by female gastroenterologists have grown exponentially. However, women are still underrepresented in our field. Two out of five GI fellows are women, but women constitute less than 18% of practicing gastroenterologists. And the number of women in leadership positions is even lower.
 

Women in medicine face many challenges

According to a report in JAMA Network Open, women have lower starting salaries more than 90% of the time, which can create income disparities in earning potential throughout our entire careers.

Other studies suggest that female physicians also spend more time with patients and answering messages from patients and colleagues as well. This extra time, although it is done in small increments, adds up quickly and could suggest the pay gap between women and men is wider than we think.

Of course, female physicians still spend more time parenting children and doing household labor. A study found that female physicians spent 8.5 hours more per week on activities that support the family and household.

We’ve been discussing equity for women in medicine, and in the workplace, for decades. But events over the past several years – such as the killing of George Floyd and the formation of the #MeToo movement in response to workplace sexual harassment – have accelerated a paradigm shift in how organizations are focusing on diversity, equity, and inclusion (DEI) and creating cultures that support leadership development for women.

The Gastro Health Women’s Network

In 2020, the leadership of Gastro Health reiterated its commitment to fight discrimination and support equity by sending out a company-wide correspondence that encouraged us to be good stewards within our communities during these turbulent times.

This led to the development of the Gastro Health DEI Council and the Gastro Health Women’s Network, led by Dr. Asma Khapra and based on the framework developed by Dr. Dawn Sears. The programs developed by Dr. Sears are focused on facilitating authentic and supportive relationships, and they helped us create a network for women focused on recruitment, mentorship and retention, networking and social events, and leadership development.

Our network started with a meet & greet, inviting all women in Gastro Health to join a virtual call and get to know each other in an informal setting. This was a great way to introduce people to each other in our natural elements. It was wonderful to see how people are when they are at home and not working.
 

Recruiting female gastroenterologists

Even though about half of gastroenterology fellows choose independent GI, most fellowship programs don’t educate students about private practice careers or promote that path. In addition, a lot of the national GI conferences are geared toward the academic experience.

It’s incumbent on those of us in private practice to educate students about the benefits and challenges we face as members of independent GI groups, and Gastro Health set out to hold networking and recruitment events at different national conferences with GI fellows and residents.

We’re also working to develop partnerships with fellowship programs. This past year, we’ve held several educational dinners for fellows and residents. Most recently, Dr. Khapra and others took a road trip to New York for dinners with fellows from Mount Sinai, Westchester Medical Center, and the Albert Einstein College of Medicine.

While it was beneficial for Gastro Health to provide information about life as private practice gastroenterologists, it was also helpful for us to hear how the GI leaders of tomorrow are navigating their career choices and what is impacting their decisions about the future.
 

Mentorship and retention are vital to practice sustainability

Once you’ve recruited physicians to join your practice, how do you ensure their success? Many practices are rightly concerned about their long-term sustainability and are exploring ways to help early-career physicians maintain the clinical skills they need to treat patients and learn the business skills they need to succeed in private practice.

Sometimes it’s as simple as reaching out to new associates on the first day to let them know you’re glad they’ve joined the practice and to let them know you’re available if they need anything. But there’s also growing recognition that implementing a formal mentorship program can help people feel included and supported.

The Women’s Network worked to pair its members with Gastro Health partners as mentors, and we’ve learned some things along the way. Initially, we tried to pair people with similar lifestyles and interests. What we found is that while this sometimes works, we may have overcomplicated the process. We learned that sometimes people would prefer mentors who have backgrounds that are different from their own. We were reminded that mentorship has many faces, and letting those relationships develop naturally can sometimes be more effective.
 

Networking and social events deter isolation and keep people engaged

Private practice can be different from working within a hospital because oftentimes your colleagues are working in different offices or facilities. In the case of our organization, those offices may be in different states hundreds of miles away. Within a hospital, there might be more potential to interact with your colleagues, whether in clinical conferences or through a chance encounter in the cafeteria.

In private practice, you may need to be more intentional about creating opportunities for people to network and get to know each other outside of work. This year, we developed an email and WhatsApp group so that women throughout the network can connect with each other. We have used it to disseminate information about upcoming events, fellowship opportunities with the national GI societies, interesting articles, and anything important that we think other women within Gastro Health would like to know.

In March, Gastro Health sponsored five women to attend the Scrubs & Heels Summit, which was developed by Dr. Anita Afzali and Dr. Aline Charabaty to create opportunities for women in GI at different stages of their GI careers and help them succeed and achieve their professional goals. There were 2 days of educational talks, but it also included plenty of events for our colleagues to get to know each other and network with other amazing female GI leaders from across the nation.


 

Where’s the boardroom?

A recent study found that the percentage of women on the boards of the 1,000 largest public companies in America is a little more than 28%, even though research shows that S&P 500 companies headquartered in California with 30% or more women on their boards had 29% higher revenue.

We’re working to develop opportunities for women to be in leadership positions, within our practices and on the national stage in terms of representation, within our national GI societies. It’s very exciting that we have women in leadership within AGA and ASGE, and that Dr. Latha Alaparthi has made increasing the focus on leadership and pipeline development one of her main priorities as the president and board chair of the Digestive Health Physicians Association (DHPA).

Another way private practices can support women who are leaders is by making recommendations for committees within our national societies and by recognizing that time spent developing presentations and speaking at national conferences is beneficial to the practice in terms of thought leadership, branding, and recruitment of the next generation of practice leaders.

While we have a long way to go, we’re also making strides in the board room at the practice level. I’m the first woman, and notably a woman of color, to join the Gastro Health board of directors under the guidance of support of CEO Joseph Garcia. Dr. Aja McCutchen, who serves as the chair of the DHPA Diversity, Equity, and Inclusion committee, is similarly the first woman and woman of color on the board of directors for United Digestive in Atlanta.


 

What to look for in joining a practice

When determining which practice you might join, ask how committed the leadership of the organization is to supporting career development for women. Does the practice have a network, a committee or other internal group that supports female physicians? What steps does the practice leadership take to support women who are interested in executive opportunities?

If the practice does have an internal organization, how does it measure progress? For example, we’ve implemented focus groups to measure what is working and where we face the most challenges. Gastro Health partnered with a consultant to hold three confidential sessions with 10 women at a time. This will allow for us to collect depersonalized data that can be compiled into a report for the Gastro Health Board and leadership.

If you’re a woman who is considering a career in independent GI, seek out women in private practice and ask about their experiences. Ask about their path and what opportunities they sought out when starting their careers. They may know of some great opportunities that are available to build your leadership skills.

By creating a network for women, Gastro Health is hoping to make it easier to develop relationships and create productive partnerships. We are certain that working to address the specific challenges that female physicians face in their careers will strengthen our group, and ultimately independent gastroenterology overall.

Dr. Adams is a practicing gastroenterologist and partner at Gastro Health Fairfax in Virginia and serves on the Digestive Health Physicians Association’s Diversity, Equity, and Inclusion Committee. Dr. Adams has no conflicts to declare.

When I was in fellowship in the late 1990s, it was rare to see women at many of the big gastroenterology conferences. And in terms of presentations, there was maybe one session led by or for women at lunchtime. These conferences were the only events I had ever been to where the line for the men’s room was longer than the line for the women’s room.

Over the years, the lines for the women’s room have gotten longer, and the sessions led by female gastroenterologists have grown exponentially. However, women are still underrepresented in our field. Two out of five GI fellows are women, but women constitute less than 18% of practicing gastroenterologists. And the number of women in leadership positions is even lower.
 

Women in medicine face many challenges

According to a report in JAMA Network Open, women have lower starting salaries more than 90% of the time, which can create income disparities in earning potential throughout our entire careers.

Other studies suggest that female physicians also spend more time with patients and answering messages from patients and colleagues as well. This extra time, although it is done in small increments, adds up quickly and could suggest the pay gap between women and men is wider than we think.

Of course, female physicians still spend more time parenting children and doing household labor. A study found that female physicians spent 8.5 hours more per week on activities that support the family and household.

We’ve been discussing equity for women in medicine, and in the workplace, for decades. But events over the past several years – such as the killing of George Floyd and the formation of the #MeToo movement in response to workplace sexual harassment – have accelerated a paradigm shift in how organizations are focusing on diversity, equity, and inclusion (DEI) and creating cultures that support leadership development for women.

The Gastro Health Women’s Network

In 2020, the leadership of Gastro Health reiterated its commitment to fight discrimination and support equity by sending out a company-wide correspondence that encouraged us to be good stewards within our communities during these turbulent times.

This led to the development of the Gastro Health DEI Council and the Gastro Health Women’s Network, led by Dr. Asma Khapra and based on the framework developed by Dr. Dawn Sears. The programs developed by Dr. Sears are focused on facilitating authentic and supportive relationships, and they helped us create a network for women focused on recruitment, mentorship and retention, networking and social events, and leadership development.

Our network started with a meet & greet, inviting all women in Gastro Health to join a virtual call and get to know each other in an informal setting. This was a great way to introduce people to each other in our natural elements. It was wonderful to see how people are when they are at home and not working.
 

Recruiting female gastroenterologists

Even though about half of gastroenterology fellows choose independent GI, most fellowship programs don’t educate students about private practice careers or promote that path. In addition, a lot of the national GI conferences are geared toward the academic experience.

It’s incumbent on those of us in private practice to educate students about the benefits and challenges we face as members of independent GI groups, and Gastro Health set out to hold networking and recruitment events at different national conferences with GI fellows and residents.

We’re also working to develop partnerships with fellowship programs. This past year, we’ve held several educational dinners for fellows and residents. Most recently, Dr. Khapra and others took a road trip to New York for dinners with fellows from Mount Sinai, Westchester Medical Center, and the Albert Einstein College of Medicine.

While it was beneficial for Gastro Health to provide information about life as private practice gastroenterologists, it was also helpful for us to hear how the GI leaders of tomorrow are navigating their career choices and what is impacting their decisions about the future.
 

Mentorship and retention are vital to practice sustainability

Once you’ve recruited physicians to join your practice, how do you ensure their success? Many practices are rightly concerned about their long-term sustainability and are exploring ways to help early-career physicians maintain the clinical skills they need to treat patients and learn the business skills they need to succeed in private practice.

Sometimes it’s as simple as reaching out to new associates on the first day to let them know you’re glad they’ve joined the practice and to let them know you’re available if they need anything. But there’s also growing recognition that implementing a formal mentorship program can help people feel included and supported.

The Women’s Network worked to pair its members with Gastro Health partners as mentors, and we’ve learned some things along the way. Initially, we tried to pair people with similar lifestyles and interests. What we found is that while this sometimes works, we may have overcomplicated the process. We learned that sometimes people would prefer mentors who have backgrounds that are different from their own. We were reminded that mentorship has many faces, and letting those relationships develop naturally can sometimes be more effective.
 

Networking and social events deter isolation and keep people engaged

Private practice can be different from working within a hospital because oftentimes your colleagues are working in different offices or facilities. In the case of our organization, those offices may be in different states hundreds of miles away. Within a hospital, there might be more potential to interact with your colleagues, whether in clinical conferences or through a chance encounter in the cafeteria.

In private practice, you may need to be more intentional about creating opportunities for people to network and get to know each other outside of work. This year, we developed an email and WhatsApp group so that women throughout the network can connect with each other. We have used it to disseminate information about upcoming events, fellowship opportunities with the national GI societies, interesting articles, and anything important that we think other women within Gastro Health would like to know.

In March, Gastro Health sponsored five women to attend the Scrubs & Heels Summit, which was developed by Dr. Anita Afzali and Dr. Aline Charabaty to create opportunities for women in GI at different stages of their GI careers and help them succeed and achieve their professional goals. There were 2 days of educational talks, but it also included plenty of events for our colleagues to get to know each other and network with other amazing female GI leaders from across the nation.


 

Where’s the boardroom?

A recent study found that the percentage of women on the boards of the 1,000 largest public companies in America is a little more than 28%, even though research shows that S&P 500 companies headquartered in California with 30% or more women on their boards had 29% higher revenue.

We’re working to develop opportunities for women to be in leadership positions, within our practices and on the national stage in terms of representation, within our national GI societies. It’s very exciting that we have women in leadership within AGA and ASGE, and that Dr. Latha Alaparthi has made increasing the focus on leadership and pipeline development one of her main priorities as the president and board chair of the Digestive Health Physicians Association (DHPA).

Another way private practices can support women who are leaders is by making recommendations for committees within our national societies and by recognizing that time spent developing presentations and speaking at national conferences is beneficial to the practice in terms of thought leadership, branding, and recruitment of the next generation of practice leaders.

While we have a long way to go, we’re also making strides in the board room at the practice level. I’m the first woman, and notably a woman of color, to join the Gastro Health board of directors under the guidance of support of CEO Joseph Garcia. Dr. Aja McCutchen, who serves as the chair of the DHPA Diversity, Equity, and Inclusion committee, is similarly the first woman and woman of color on the board of directors for United Digestive in Atlanta.


 

What to look for in joining a practice

When determining which practice you might join, ask how committed the leadership of the organization is to supporting career development for women. Does the practice have a network, a committee or other internal group that supports female physicians? What steps does the practice leadership take to support women who are interested in executive opportunities?

If the practice does have an internal organization, how does it measure progress? For example, we’ve implemented focus groups to measure what is working and where we face the most challenges. Gastro Health partnered with a consultant to hold three confidential sessions with 10 women at a time. This will allow for us to collect depersonalized data that can be compiled into a report for the Gastro Health Board and leadership.

If you’re a woman who is considering a career in independent GI, seek out women in private practice and ask about their experiences. Ask about their path and what opportunities they sought out when starting their careers. They may know of some great opportunities that are available to build your leadership skills.

By creating a network for women, Gastro Health is hoping to make it easier to develop relationships and create productive partnerships. We are certain that working to address the specific challenges that female physicians face in their careers will strengthen our group, and ultimately independent gastroenterology overall.

Dr. Adams is a practicing gastroenterologist and partner at Gastro Health Fairfax in Virginia and serves on the Digestive Health Physicians Association’s Diversity, Equity, and Inclusion Committee. Dr. Adams has no conflicts to declare.

Efficacy of the investigational drug lebrikizumab is maintained in patients with moderate to severe atopic dermatitis for at least 1 year, according to new results from the phase 3 ADvocate1 and ADvocate2 trials.

“We’re focused on the responders,” said Andrew Blauvelt, MD, MBA, as he presented the positive findings at the annual congress of the European Academy of Dermatology and Venereology.

Responders were the 291 people whose atopic dermatitis greatly improved after an initial 16 weeks’ treatment with lebrikizumab in both trials and who were then randomly allocated to receive injections every 2 weeks (Q2W, n = 113) or every 4 weeks (Q4W, n = 118), or to receive placebo injections Q2W (n = 60).

“Very interestingly, for me, the Q4W maintenance dosing was just as good as the Q2W maintenance dosing,” said Dr. Blauvelt, president of Oregon Medical Research Center, Portland.

“Another highlight of these data is that the patients who went on to placebo, about 50% of the patients maintained good responses, despite no treatment from week 16 to week 52,” he added.

Most patients did not require topical steroids, and “there were no surprises here” in terms of the safety profile. Lebrikizumab, a monoclonal antibody, binds to soluble interleukin-13 and blocks IL-13 signaling.

“So, the study really shows that specific targeting of IL-13 with lebrikizumab, either Q2W or Q4W, has high maintenance of efficacy and is reasonably tolerated and safe in adolescents and adults with atopic dermatitis,” Dr. Blauvelt concluded.

“We know now that IL-13 is a critical cytokine in AD [atopic dermatitis] pathogenesis. The unique features of this drug I want to highlight is that it has high binding affinity for IL-13,” he said.

“It has a slow dissociation off rate, meaning it binds IL-13 tightly, very potently, and stays blocking and stays hold of IL-13 in a strong manner,” he added. The drug has a half-life of 25 days.

These features could be very important for long-term dosing of the drug, he argued.
 

Lebrikizumab phase 3 trials

ADvocate1 and ADvocate2 are two of several phase 3 trials evaluating the efficacy and safety of lebrikizumab for the treatment of atopic dermatitis.

These include the completed ADhere study, in which lebrikizumab was used in combination with topical steroids and showed positive results in skin improvement and relief of pruritus.

The ADore study, an open-label trial in adolescents, is yet to report. The ongoing ADjoin study, a long-term extension study, is actively recruiting.

ADvocate1 and ADvocate2 are two identically designed – multicenter, randomized, double-blind, placebo-controlled, parallel-group – monotherapy trials that initially pitched two dosing regimens of lebrikizumab (250 mg) against placebo with a double loading dose at baseline and week 2 and then one dose every 2 weeks. The pair of trials enrolled a total of 869 adolescents and adults.

After the 16-week induction period, all patients in the lebrikizumab arm who had responded to treatment were rerandomly assigned to receive lebrikizumab 250 mg Q2W or Q4W, or placebo Q2W during a 36-week long-term maintenance treatment period.

This brought the total treatment time to 52 weeks for those whose atopic dermatitis had initially responded to lebrikizumab, explained Blauvelt.

Responders were those who, at 16 weeks, had an Investigator’s Global Assessment score of 0 or 1 (IGA 0/1) with a 2-point improvement or who had a 75% improvement in the Eczema Area and Severity Index score (EASI 75) without the need for rescue medication, compared with baseline values.
 

Induction and maintenance phase results

At the end of the 16-week induction period, a greater proportion of patients who had been treated with lebrikizumab than placebo met a primary outcome of IGA 0/1 in each trial (43.1% vs. 12.7% in ADvocate1 and 33.2% vs. 10.8% in ADvocate2).

A similar result was seen for another primary outcome, EASI 75 (58.8% vs. 16.2% and 52.1% vs. 18.1%) and for a secondary outcome, improvement in pruritus using a numerical rating scale (45.9% vs. 13.0% and 39.8% vs. 11.5%).

In the maintenance phase, with respect to responders, Dr. Blauvelt reported “very similar results” between the QW2 and Q4W maintenance dosing, “and still a quite high response in [half] the patients who were randomized to placebo at week 16.”

In the ADvocate1 and ADvocate2 trials, respectively, an IGA 0/1 with at least a 2-point improvement was maintained at week 52 in 75.8% and 64.6% of patients treated with the Q2W lebrikizumab dose, 74.2% and 80.6% of those treated with the Q4W dose, and 46.5% and 49.8% of those given placebo.

EASI 75 was maintained at week 52 in a respective 79.2% and 77.4% of patients treated with the Q2W dose, 79.2% and 84.7% with the Q4W dose, and 61.3% and 72.0% with placebo.

As for maintenance of at least a 4-point improvement in pruritus score, results at 52 weeks were 81.2% and 90.3% for the 2-week dose, 80.4% and 88.1% for the 4-week dose, and 65.4% and 67.6% for placebo.

Although topical corticosteroid treatment was allowed during the maintenance phase, only about 15% of patients needed this, Dr. Blauvelt said.
 

Different dosing results questioned

During the discussion period, one delegate highlighted that the twice-weekly maintenance dosing schedule seemed to “do worse a little bit” than the 4-week dosing, with both “close to placebo,” although “the long-term effect is already very impressive.”

Dr. Blauvelt noted that a pooled analysis had been done and that “it’s very clear that being on lebrikizumab works better than not being on lebrikizumab.

“Now, Q2W versus Q4W. We believe that this may be due to the long half-life of the drug possibly. It could be due to the slow disassociation rate, it’s binding tightly,” he suggested.

“We also could talk about disease modification, right. So, it opens up the concept of hit hard, hit early for 16 weeks, and then maybe you can modify disease over time,” Dr. Blauvelt said.

He added: “That’s highly speculative, of course.”

Short-term safety data

The 52-week safety profile of lebrikizumab is consistent with previously published data at 16 weeks, Dr. Blauvelt said. The most common adverse events during the studies included atopic dermatitis, nasopharyngitis, conjunctivitis, conjunctivitis allergic, headache, and COVID-19.

“This drug has comparable efficacy with dupilumab and tralokinumab,” said Jashin J. Wu, MD, from the Dermatology Research and Education Foundation in Irvine, Calif., in an interview. He was not involved in the study.

“As it does not have any significant advantages with less long-term safety data, I do not see a place for it in my practice,” Dr. Wu said.

Dupilumab (Dupixent) and tralokinumab (Adbry) are monoclonal antibodies that also block IL-13. Both are already licensed for treating atopic dermatitis. Dupilumab was approved by the Food and Drug Administration in 2017, and tralokinumab was approved in 2021.

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly. Eli Lilly has exclusive rights for the development and commercialization of lebrikizumab in the United States and all countries outside Europe; European rights belong to Almirall for all dermatology indications, including atopic dermatitis. Dr. Blauvelt acts as an investigator and adviser to these companies as well as many other pharmaceutical companies that are involved in developing new dermatologic treatments. Dr. Wu has been an investigator, consultant, or speaker for multiple pharmaceutical companies.

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

Efficacy of the investigational drug lebrikizumab is maintained in patients with moderate to severe atopic dermatitis for at least 1 year, according to new results from the phase 3 ADvocate1 and ADvocate2 trials.

“We’re focused on the responders,” said Andrew Blauvelt, MD, MBA, as he presented the positive findings at the annual congress of the European Academy of Dermatology and Venereology.

Responders were the 291 people whose atopic dermatitis greatly improved after an initial 16 weeks’ treatment with lebrikizumab in both trials and who were then randomly allocated to receive injections every 2 weeks (Q2W, n = 113) or every 4 weeks (Q4W, n = 118), or to receive placebo injections Q2W (n = 60).

“Very interestingly, for me, the Q4W maintenance dosing was just as good as the Q2W maintenance dosing,” said Dr. Blauvelt, president of Oregon Medical Research Center, Portland.

“Another highlight of these data is that the patients who went on to placebo, about 50% of the patients maintained good responses, despite no treatment from week 16 to week 52,” he added.

Most patients did not require topical steroids, and “there were no surprises here” in terms of the safety profile. Lebrikizumab, a monoclonal antibody, binds to soluble interleukin-13 and blocks IL-13 signaling.

“So, the study really shows that specific targeting of IL-13 with lebrikizumab, either Q2W or Q4W, has high maintenance of efficacy and is reasonably tolerated and safe in adolescents and adults with atopic dermatitis,” Dr. Blauvelt concluded.

“We know now that IL-13 is a critical cytokine in AD [atopic dermatitis] pathogenesis. The unique features of this drug I want to highlight is that it has high binding affinity for IL-13,” he said.

“It has a slow dissociation off rate, meaning it binds IL-13 tightly, very potently, and stays blocking and stays hold of IL-13 in a strong manner,” he added. The drug has a half-life of 25 days.

These features could be very important for long-term dosing of the drug, he argued.
 

Lebrikizumab phase 3 trials

ADvocate1 and ADvocate2 are two of several phase 3 trials evaluating the efficacy and safety of lebrikizumab for the treatment of atopic dermatitis.

These include the completed ADhere study, in which lebrikizumab was used in combination with topical steroids and showed positive results in skin improvement and relief of pruritus.

The ADore study, an open-label trial in adolescents, is yet to report. The ongoing ADjoin study, a long-term extension study, is actively recruiting.

ADvocate1 and ADvocate2 are two identically designed – multicenter, randomized, double-blind, placebo-controlled, parallel-group – monotherapy trials that initially pitched two dosing regimens of lebrikizumab (250 mg) against placebo with a double loading dose at baseline and week 2 and then one dose every 2 weeks. The pair of trials enrolled a total of 869 adolescents and adults.

After the 16-week induction period, all patients in the lebrikizumab arm who had responded to treatment were rerandomly assigned to receive lebrikizumab 250 mg Q2W or Q4W, or placebo Q2W during a 36-week long-term maintenance treatment period.

This brought the total treatment time to 52 weeks for those whose atopic dermatitis had initially responded to lebrikizumab, explained Blauvelt.

Responders were those who, at 16 weeks, had an Investigator’s Global Assessment score of 0 or 1 (IGA 0/1) with a 2-point improvement or who had a 75% improvement in the Eczema Area and Severity Index score (EASI 75) without the need for rescue medication, compared with baseline values.
 

Induction and maintenance phase results

At the end of the 16-week induction period, a greater proportion of patients who had been treated with lebrikizumab than placebo met a primary outcome of IGA 0/1 in each trial (43.1% vs. 12.7% in ADvocate1 and 33.2% vs. 10.8% in ADvocate2).

A similar result was seen for another primary outcome, EASI 75 (58.8% vs. 16.2% and 52.1% vs. 18.1%) and for a secondary outcome, improvement in pruritus using a numerical rating scale (45.9% vs. 13.0% and 39.8% vs. 11.5%).

In the maintenance phase, with respect to responders, Dr. Blauvelt reported “very similar results” between the QW2 and Q4W maintenance dosing, “and still a quite high response in [half] the patients who were randomized to placebo at week 16.”

In the ADvocate1 and ADvocate2 trials, respectively, an IGA 0/1 with at least a 2-point improvement was maintained at week 52 in 75.8% and 64.6% of patients treated with the Q2W lebrikizumab dose, 74.2% and 80.6% of those treated with the Q4W dose, and 46.5% and 49.8% of those given placebo.

EASI 75 was maintained at week 52 in a respective 79.2% and 77.4% of patients treated with the Q2W dose, 79.2% and 84.7% with the Q4W dose, and 61.3% and 72.0% with placebo.

As for maintenance of at least a 4-point improvement in pruritus score, results at 52 weeks were 81.2% and 90.3% for the 2-week dose, 80.4% and 88.1% for the 4-week dose, and 65.4% and 67.6% for placebo.

Although topical corticosteroid treatment was allowed during the maintenance phase, only about 15% of patients needed this, Dr. Blauvelt said.
 

Different dosing results questioned

During the discussion period, one delegate highlighted that the twice-weekly maintenance dosing schedule seemed to “do worse a little bit” than the 4-week dosing, with both “close to placebo,” although “the long-term effect is already very impressive.”

Dr. Blauvelt noted that a pooled analysis had been done and that “it’s very clear that being on lebrikizumab works better than not being on lebrikizumab.

“Now, Q2W versus Q4W. We believe that this may be due to the long half-life of the drug possibly. It could be due to the slow disassociation rate, it’s binding tightly,” he suggested.

“We also could talk about disease modification, right. So, it opens up the concept of hit hard, hit early for 16 weeks, and then maybe you can modify disease over time,” Dr. Blauvelt said.

He added: “That’s highly speculative, of course.”

Short-term safety data

The 52-week safety profile of lebrikizumab is consistent with previously published data at 16 weeks, Dr. Blauvelt said. The most common adverse events during the studies included atopic dermatitis, nasopharyngitis, conjunctivitis, conjunctivitis allergic, headache, and COVID-19.

“This drug has comparable efficacy with dupilumab and tralokinumab,” said Jashin J. Wu, MD, from the Dermatology Research and Education Foundation in Irvine, Calif., in an interview. He was not involved in the study.

“As it does not have any significant advantages with less long-term safety data, I do not see a place for it in my practice,” Dr. Wu said.

Dupilumab (Dupixent) and tralokinumab (Adbry) are monoclonal antibodies that also block IL-13. Both are already licensed for treating atopic dermatitis. Dupilumab was approved by the Food and Drug Administration in 2017, and tralokinumab was approved in 2021.

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly. Eli Lilly has exclusive rights for the development and commercialization of lebrikizumab in the United States and all countries outside Europe; European rights belong to Almirall for all dermatology indications, including atopic dermatitis. Dr. Blauvelt acts as an investigator and adviser to these companies as well as many other pharmaceutical companies that are involved in developing new dermatologic treatments. Dr. Wu has been an investigator, consultant, or speaker for multiple pharmaceutical companies.

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

Efficacy of the investigational drug lebrikizumab is maintained in patients with moderate to severe atopic dermatitis for at least 1 year, according to new results from the phase 3 ADvocate1 and ADvocate2 trials.

“We’re focused on the responders,” said Andrew Blauvelt, MD, MBA, as he presented the positive findings at the annual congress of the European Academy of Dermatology and Venereology.

Responders were the 291 people whose atopic dermatitis greatly improved after an initial 16 weeks’ treatment with lebrikizumab in both trials and who were then randomly allocated to receive injections every 2 weeks (Q2W, n = 113) or every 4 weeks (Q4W, n = 118), or to receive placebo injections Q2W (n = 60).

“Very interestingly, for me, the Q4W maintenance dosing was just as good as the Q2W maintenance dosing,” said Dr. Blauvelt, president of Oregon Medical Research Center, Portland.

“Another highlight of these data is that the patients who went on to placebo, about 50% of the patients maintained good responses, despite no treatment from week 16 to week 52,” he added.

Most patients did not require topical steroids, and “there were no surprises here” in terms of the safety profile. Lebrikizumab, a monoclonal antibody, binds to soluble interleukin-13 and blocks IL-13 signaling.

“So, the study really shows that specific targeting of IL-13 with lebrikizumab, either Q2W or Q4W, has high maintenance of efficacy and is reasonably tolerated and safe in adolescents and adults with atopic dermatitis,” Dr. Blauvelt concluded.

“We know now that IL-13 is a critical cytokine in AD [atopic dermatitis] pathogenesis. The unique features of this drug I want to highlight is that it has high binding affinity for IL-13,” he said.

“It has a slow dissociation off rate, meaning it binds IL-13 tightly, very potently, and stays blocking and stays hold of IL-13 in a strong manner,” he added. The drug has a half-life of 25 days.

These features could be very important for long-term dosing of the drug, he argued.
 

Lebrikizumab phase 3 trials

ADvocate1 and ADvocate2 are two of several phase 3 trials evaluating the efficacy and safety of lebrikizumab for the treatment of atopic dermatitis.

These include the completed ADhere study, in which lebrikizumab was used in combination with topical steroids and showed positive results in skin improvement and relief of pruritus.

The ADore study, an open-label trial in adolescents, is yet to report. The ongoing ADjoin study, a long-term extension study, is actively recruiting.

ADvocate1 and ADvocate2 are two identically designed – multicenter, randomized, double-blind, placebo-controlled, parallel-group – monotherapy trials that initially pitched two dosing regimens of lebrikizumab (250 mg) against placebo with a double loading dose at baseline and week 2 and then one dose every 2 weeks. The pair of trials enrolled a total of 869 adolescents and adults.

After the 16-week induction period, all patients in the lebrikizumab arm who had responded to treatment were rerandomly assigned to receive lebrikizumab 250 mg Q2W or Q4W, or placebo Q2W during a 36-week long-term maintenance treatment period.

This brought the total treatment time to 52 weeks for those whose atopic dermatitis had initially responded to lebrikizumab, explained Blauvelt.

Responders were those who, at 16 weeks, had an Investigator’s Global Assessment score of 0 or 1 (IGA 0/1) with a 2-point improvement or who had a 75% improvement in the Eczema Area and Severity Index score (EASI 75) without the need for rescue medication, compared with baseline values.
 

Induction and maintenance phase results

At the end of the 16-week induction period, a greater proportion of patients who had been treated with lebrikizumab than placebo met a primary outcome of IGA 0/1 in each trial (43.1% vs. 12.7% in ADvocate1 and 33.2% vs. 10.8% in ADvocate2).

A similar result was seen for another primary outcome, EASI 75 (58.8% vs. 16.2% and 52.1% vs. 18.1%) and for a secondary outcome, improvement in pruritus using a numerical rating scale (45.9% vs. 13.0% and 39.8% vs. 11.5%).

In the maintenance phase, with respect to responders, Dr. Blauvelt reported “very similar results” between the QW2 and Q4W maintenance dosing, “and still a quite high response in [half] the patients who were randomized to placebo at week 16.”

In the ADvocate1 and ADvocate2 trials, respectively, an IGA 0/1 with at least a 2-point improvement was maintained at week 52 in 75.8% and 64.6% of patients treated with the Q2W lebrikizumab dose, 74.2% and 80.6% of those treated with the Q4W dose, and 46.5% and 49.8% of those given placebo.

EASI 75 was maintained at week 52 in a respective 79.2% and 77.4% of patients treated with the Q2W dose, 79.2% and 84.7% with the Q4W dose, and 61.3% and 72.0% with placebo.

As for maintenance of at least a 4-point improvement in pruritus score, results at 52 weeks were 81.2% and 90.3% for the 2-week dose, 80.4% and 88.1% for the 4-week dose, and 65.4% and 67.6% for placebo.

Although topical corticosteroid treatment was allowed during the maintenance phase, only about 15% of patients needed this, Dr. Blauvelt said.
 

Different dosing results questioned

During the discussion period, one delegate highlighted that the twice-weekly maintenance dosing schedule seemed to “do worse a little bit” than the 4-week dosing, with both “close to placebo,” although “the long-term effect is already very impressive.”

Dr. Blauvelt noted that a pooled analysis had been done and that “it’s very clear that being on lebrikizumab works better than not being on lebrikizumab.

“Now, Q2W versus Q4W. We believe that this may be due to the long half-life of the drug possibly. It could be due to the slow disassociation rate, it’s binding tightly,” he suggested.

“We also could talk about disease modification, right. So, it opens up the concept of hit hard, hit early for 16 weeks, and then maybe you can modify disease over time,” Dr. Blauvelt said.

He added: “That’s highly speculative, of course.”

Short-term safety data

The 52-week safety profile of lebrikizumab is consistent with previously published data at 16 weeks, Dr. Blauvelt said. The most common adverse events during the studies included atopic dermatitis, nasopharyngitis, conjunctivitis, conjunctivitis allergic, headache, and COVID-19.

“This drug has comparable efficacy with dupilumab and tralokinumab,” said Jashin J. Wu, MD, from the Dermatology Research and Education Foundation in Irvine, Calif., in an interview. He was not involved in the study.

“As it does not have any significant advantages with less long-term safety data, I do not see a place for it in my practice,” Dr. Wu said.

Dupilumab (Dupixent) and tralokinumab (Adbry) are monoclonal antibodies that also block IL-13. Both are already licensed for treating atopic dermatitis. Dupilumab was approved by the Food and Drug Administration in 2017, and tralokinumab was approved in 2021.

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly. Eli Lilly has exclusive rights for the development and commercialization of lebrikizumab in the United States and all countries outside Europe; European rights belong to Almirall for all dermatology indications, including atopic dermatitis. Dr. Blauvelt acts as an investigator and adviser to these companies as well as many other pharmaceutical companies that are involved in developing new dermatologic treatments. Dr. Wu has been an investigator, consultant, or speaker for multiple pharmaceutical companies.

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

Ruxolitinib cream can help repigment the skin in many body areas affected with vitiligo, researchers reported at the annual congress of the European Academy of Dermatology and Venereology.

Those difficult areas include the hands and feet, said Thierry Passeron, MD, PhD, of Université Côte d’Azur and Centre Hospitalier Universitaire de Nice (France).

Indeed, a 50% or greater improvement in the Vitiligo Area Scoring Index (VASI-50) of the hands and feet was achieved with ruxolitinib cream (Opzelura) in around one-third of patients after 52 weeks’ treatment, and more than half of patients showed improvement in the upper and lower extremities.

During one of the late-breaking news sessions, Dr. Passeron presented a pooled analysis of the Topical Ruxolitinib Evaluation in Vitiligo Study 1 (TRuE-V1) and Study 2 (TruE-V2), which assessed VASI-50 data by body regions.

Similarly positive results were seen on the head and neck and the trunk, with VASI-50 being reached in a respective 68% and 48% of patients after a full year of treatment.

“VASI-50 response rates rose steadily through 52 weeks for both the head and trunk,” said Dr. Passeron. He noted that the trials were initially double-blinded for 24 weeks and that there was a further open-label extension phase through week 52.

In the latter phase, all patients were treated with ruxolitinib; those who originally received a vehicle agent as placebo crossed over to the active treatment.
 

First FDA-approved treatment for adults and adolescents with vitiligo

Ruxolitinib is a Janus kinase 1/2 inhibitor that has been available for the treatment for atopic dermatitis for more than a year. It was recently approved by the U.S. Food and Drug Administration for the treatment of vitiligo in adults and pediatric patients aged 12 years and older.

This approval was based on the positive findings of the TRuE-V1 and TRuE-V2 studies, which showed that after 24 weeks, 30% of patients treated with ruxolitinib had at least 75% improvement in the facial VASI, compared with 10% of placebo-treated patients.

“These studies demonstrated very nice results, especially on the face, which is the easiest part to repigment in vitiligo,” Dr. Passeron said.

“We know that the location is very important when it comes to repigmentation of vitiligo,” he added. He noted that other body areas, “the extremities, for example, are much more difficult.”

The analysis he presented specifically assessed the effect of ruxolitinib cream on repigmentation in other areas.

Pooled analysis performed

Data from the two TRuE-V trials were pooled. The new analysis included a total of 661 individuals; of those patients, 443 had been treated with topical ruxolitinib, and 218 had received a vehicle cream as a placebo.

For the first 24 weeks, patients received twice-daily 1.5% ruxolitinib cream or vehicle cream. This was followed by a 28-week extension phase in which everyone was treated with ruxolitinib cream, after which there was a 30-day final follow-up period.

Dr. Passeron reported data by body region for weeks 12, 24, and 52, which showed an increasing percentage of patients with VASI-50.

“We didn’t look at the face; that we know well, that is a very good result,” he said.

The best results were seen for the head and neck. VASI-50 was reached by 28.3%, 45.3%, and 68.1% of patients treated with ruxolitinib cream at weeks 12, 24, and 52, respectively. Corresponding rates for the placebo-crossover group were 19.8%, 23.8%, and 51%.

Repigmentation rates of the hand, upper extremities, trunk, lower extremities, and feet were about 9%-15% for both ruxolitinib and placebo at 12 weeks, but by 24 weeks, there was a clear increase in repigmentation rates in the ruxolitinib group for all body areas.

The 24-week VASI-50 rates for hand repigmentation were 24.9% for ruxolitinib cream and 14.4% for placebo. Corresponding rates for upper extremity repigmentation were 33.2% and 8.2%; for the trunk, 26.4% and 12.2%; for the lower extremities, 29.5% and 12.2%; and for the feet, 18.5% and 12.5%.

“The results are quite poor at 12 weeks,” Dr. Passeron said. “It’s very important to keep this in mind; it takes time to repigment vitiligo, it takes to 6-24 months. We have to explain to our patients that they will have to wait to see the results.”
 

Steady improvements, no new safety concerns

Regarding VASI-50 over time, there was a steady increase in total body scores; 47.7% of patients who received ruxolitinib and 23.3% of placebo-treated patients hit this target at 52 weeks.

“And what is also very important to see is that we didn’t reach the plateau,” Dr. Passeron reported.

Similar patterns were seen for all the other body areas. Again there was a suggestion that rates may continue to rise with continued long-term treatment.

“About one-third of the patients reached at least 50% repigmentation after 1 year of treatment in the hands and feet,” Dr. Passeron said. He noted that certain areas, such as the back of the hand or tips of the fingers, may be unresponsive.

“So, we have to also to warn the patient that probably on these areas we have to combine it with other treatment because it remains very, very difficult to treat.”

There were no new safety concerns regarding treatment-emergent adverse events, which were reported in 52% of patients who received ruxolitinib and in 36% of placebo-treated patients.

The most common adverse reactions included COVID-19 (6.1% vs. 3.1%), acne at the application site (5.3% vs. 1.3%), and pruritus at the application site (3.9% vs. 2.7%), although cases were “mild or moderate,” said Dr. Passeron.
 

An expert’s take-home

“The results of TRuE-V phase 3 studies are encouraging and exciting,” Viktoria Eleftheriadou, MD, MRCP(UK), SCE(Derm), PhD, said in providing an independent comment for this news organization.

“Although ruxolitinib cream is applied on the skin, this novel treatment for vitiligo is not without risks; therefore, careful monitoring of patients who are started on this topical treatment would be prudent,” said Dr. Eleftheriadou, who is a consultant dermatologist for Walsall Healthcare NHS Trust and the Royal Wolverhampton NHS Trust, Birmingham, United Kingdom.

“I would like to see how many patients achieved VASI-75 or VASI-80 score, which from patients’ perspectives is a more meaningful outcome, as well as how long these results will last for,” she added.

The study was funded by Incyte Corporation. Dr. Passeron has received grants, honoraria, or both from AbbVie, ACM Pharma, Almirall, Amgen, Astellas, Bristol-Myers Squibb, Celgene, Galderma, Genzyme/Sanofi, GlaxoSmithKline, Incyte Corporation, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Sun Pharmaceuticals, and UCB. Dr. Passeron is the cofounder of YUKIN Therapeutics and has patents on WNT agonists or GSK2b antagonist for repigmentation of vitiligo and on the use of CXCR3B blockers in vitiligo. Dr. Eleftheriadou is an investigator and trial development group member on the HI-Light Vitiligo Trial (specific), a lead investigator on the pilot HI-Light Vitiligo Trial, and a medical advisory panel member of the Vitiligo Society UK. Dr. Eleftheriadou also provides consultancy services to Incyte and Pfizer.

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

Ruxolitinib cream can help repigment the skin in many body areas affected with vitiligo, researchers reported at the annual congress of the European Academy of Dermatology and Venereology.

Those difficult areas include the hands and feet, said Thierry Passeron, MD, PhD, of Université Côte d’Azur and Centre Hospitalier Universitaire de Nice (France).

Indeed, a 50% or greater improvement in the Vitiligo Area Scoring Index (VASI-50) of the hands and feet was achieved with ruxolitinib cream (Opzelura) in around one-third of patients after 52 weeks’ treatment, and more than half of patients showed improvement in the upper and lower extremities.

During one of the late-breaking news sessions, Dr. Passeron presented a pooled analysis of the Topical Ruxolitinib Evaluation in Vitiligo Study 1 (TRuE-V1) and Study 2 (TruE-V2), which assessed VASI-50 data by body regions.

Similarly positive results were seen on the head and neck and the trunk, with VASI-50 being reached in a respective 68% and 48% of patients after a full year of treatment.

“VASI-50 response rates rose steadily through 52 weeks for both the head and trunk,” said Dr. Passeron. He noted that the trials were initially double-blinded for 24 weeks and that there was a further open-label extension phase through week 52.

In the latter phase, all patients were treated with ruxolitinib; those who originally received a vehicle agent as placebo crossed over to the active treatment.
 

First FDA-approved treatment for adults and adolescents with vitiligo

Ruxolitinib is a Janus kinase 1/2 inhibitor that has been available for the treatment for atopic dermatitis for more than a year. It was recently approved by the U.S. Food and Drug Administration for the treatment of vitiligo in adults and pediatric patients aged 12 years and older.

This approval was based on the positive findings of the TRuE-V1 and TRuE-V2 studies, which showed that after 24 weeks, 30% of patients treated with ruxolitinib had at least 75% improvement in the facial VASI, compared with 10% of placebo-treated patients.

“These studies demonstrated very nice results, especially on the face, which is the easiest part to repigment in vitiligo,” Dr. Passeron said.

“We know that the location is very important when it comes to repigmentation of vitiligo,” he added. He noted that other body areas, “the extremities, for example, are much more difficult.”

The analysis he presented specifically assessed the effect of ruxolitinib cream on repigmentation in other areas.

Pooled analysis performed

Data from the two TRuE-V trials were pooled. The new analysis included a total of 661 individuals; of those patients, 443 had been treated with topical ruxolitinib, and 218 had received a vehicle cream as a placebo.

For the first 24 weeks, patients received twice-daily 1.5% ruxolitinib cream or vehicle cream. This was followed by a 28-week extension phase in which everyone was treated with ruxolitinib cream, after which there was a 30-day final follow-up period.

Dr. Passeron reported data by body region for weeks 12, 24, and 52, which showed an increasing percentage of patients with VASI-50.

“We didn’t look at the face; that we know well, that is a very good result,” he said.

The best results were seen for the head and neck. VASI-50 was reached by 28.3%, 45.3%, and 68.1% of patients treated with ruxolitinib cream at weeks 12, 24, and 52, respectively. Corresponding rates for the placebo-crossover group were 19.8%, 23.8%, and 51%.

Repigmentation rates of the hand, upper extremities, trunk, lower extremities, and feet were about 9%-15% for both ruxolitinib and placebo at 12 weeks, but by 24 weeks, there was a clear increase in repigmentation rates in the ruxolitinib group for all body areas.

The 24-week VASI-50 rates for hand repigmentation were 24.9% for ruxolitinib cream and 14.4% for placebo. Corresponding rates for upper extremity repigmentation were 33.2% and 8.2%; for the trunk, 26.4% and 12.2%; for the lower extremities, 29.5% and 12.2%; and for the feet, 18.5% and 12.5%.

“The results are quite poor at 12 weeks,” Dr. Passeron said. “It’s very important to keep this in mind; it takes time to repigment vitiligo, it takes to 6-24 months. We have to explain to our patients that they will have to wait to see the results.”
 

Steady improvements, no new safety concerns

Regarding VASI-50 over time, there was a steady increase in total body scores; 47.7% of patients who received ruxolitinib and 23.3% of placebo-treated patients hit this target at 52 weeks.

“And what is also very important to see is that we didn’t reach the plateau,” Dr. Passeron reported.

Similar patterns were seen for all the other body areas. Again there was a suggestion that rates may continue to rise with continued long-term treatment.

“About one-third of the patients reached at least 50% repigmentation after 1 year of treatment in the hands and feet,” Dr. Passeron said. He noted that certain areas, such as the back of the hand or tips of the fingers, may be unresponsive.

“So, we have to also to warn the patient that probably on these areas we have to combine it with other treatment because it remains very, very difficult to treat.”

There were no new safety concerns regarding treatment-emergent adverse events, which were reported in 52% of patients who received ruxolitinib and in 36% of placebo-treated patients.

The most common adverse reactions included COVID-19 (6.1% vs. 3.1%), acne at the application site (5.3% vs. 1.3%), and pruritus at the application site (3.9% vs. 2.7%), although cases were “mild or moderate,” said Dr. Passeron.
 

An expert’s take-home

“The results of TRuE-V phase 3 studies are encouraging and exciting,” Viktoria Eleftheriadou, MD, MRCP(UK), SCE(Derm), PhD, said in providing an independent comment for this news organization.

“Although ruxolitinib cream is applied on the skin, this novel treatment for vitiligo is not without risks; therefore, careful monitoring of patients who are started on this topical treatment would be prudent,” said Dr. Eleftheriadou, who is a consultant dermatologist for Walsall Healthcare NHS Trust and the Royal Wolverhampton NHS Trust, Birmingham, United Kingdom.

“I would like to see how many patients achieved VASI-75 or VASI-80 score, which from patients’ perspectives is a more meaningful outcome, as well as how long these results will last for,” she added.

The study was funded by Incyte Corporation. Dr. Passeron has received grants, honoraria, or both from AbbVie, ACM Pharma, Almirall, Amgen, Astellas, Bristol-Myers Squibb, Celgene, Galderma, Genzyme/Sanofi, GlaxoSmithKline, Incyte Corporation, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Sun Pharmaceuticals, and UCB. Dr. Passeron is the cofounder of YUKIN Therapeutics and has patents on WNT agonists or GSK2b antagonist for repigmentation of vitiligo and on the use of CXCR3B blockers in vitiligo. Dr. Eleftheriadou is an investigator and trial development group member on the HI-Light Vitiligo Trial (specific), a lead investigator on the pilot HI-Light Vitiligo Trial, and a medical advisory panel member of the Vitiligo Society UK. Dr. Eleftheriadou also provides consultancy services to Incyte and Pfizer.

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

Ruxolitinib cream can help repigment the skin in many body areas affected with vitiligo, researchers reported at the annual congress of the European Academy of Dermatology and Venereology.

Those difficult areas include the hands and feet, said Thierry Passeron, MD, PhD, of Université Côte d’Azur and Centre Hospitalier Universitaire de Nice (France).

Indeed, a 50% or greater improvement in the Vitiligo Area Scoring Index (VASI-50) of the hands and feet was achieved with ruxolitinib cream (Opzelura) in around one-third of patients after 52 weeks’ treatment, and more than half of patients showed improvement in the upper and lower extremities.

During one of the late-breaking news sessions, Dr. Passeron presented a pooled analysis of the Topical Ruxolitinib Evaluation in Vitiligo Study 1 (TRuE-V1) and Study 2 (TruE-V2), which assessed VASI-50 data by body regions.

Similarly positive results were seen on the head and neck and the trunk, with VASI-50 being reached in a respective 68% and 48% of patients after a full year of treatment.

“VASI-50 response rates rose steadily through 52 weeks for both the head and trunk,” said Dr. Passeron. He noted that the trials were initially double-blinded for 24 weeks and that there was a further open-label extension phase through week 52.

In the latter phase, all patients were treated with ruxolitinib; those who originally received a vehicle agent as placebo crossed over to the active treatment.
 

First FDA-approved treatment for adults and adolescents with vitiligo

Ruxolitinib is a Janus kinase 1/2 inhibitor that has been available for the treatment for atopic dermatitis for more than a year. It was recently approved by the U.S. Food and Drug Administration for the treatment of vitiligo in adults and pediatric patients aged 12 years and older.

This approval was based on the positive findings of the TRuE-V1 and TRuE-V2 studies, which showed that after 24 weeks, 30% of patients treated with ruxolitinib had at least 75% improvement in the facial VASI, compared with 10% of placebo-treated patients.

“These studies demonstrated very nice results, especially on the face, which is the easiest part to repigment in vitiligo,” Dr. Passeron said.

“We know that the location is very important when it comes to repigmentation of vitiligo,” he added. He noted that other body areas, “the extremities, for example, are much more difficult.”

The analysis he presented specifically assessed the effect of ruxolitinib cream on repigmentation in other areas.

Pooled analysis performed

Data from the two TRuE-V trials were pooled. The new analysis included a total of 661 individuals; of those patients, 443 had been treated with topical ruxolitinib, and 218 had received a vehicle cream as a placebo.

For the first 24 weeks, patients received twice-daily 1.5% ruxolitinib cream or vehicle cream. This was followed by a 28-week extension phase in which everyone was treated with ruxolitinib cream, after which there was a 30-day final follow-up period.

Dr. Passeron reported data by body region for weeks 12, 24, and 52, which showed an increasing percentage of patients with VASI-50.

“We didn’t look at the face; that we know well, that is a very good result,” he said.

The best results were seen for the head and neck. VASI-50 was reached by 28.3%, 45.3%, and 68.1% of patients treated with ruxolitinib cream at weeks 12, 24, and 52, respectively. Corresponding rates for the placebo-crossover group were 19.8%, 23.8%, and 51%.

Repigmentation rates of the hand, upper extremities, trunk, lower extremities, and feet were about 9%-15% for both ruxolitinib and placebo at 12 weeks, but by 24 weeks, there was a clear increase in repigmentation rates in the ruxolitinib group for all body areas.

The 24-week VASI-50 rates for hand repigmentation were 24.9% for ruxolitinib cream and 14.4% for placebo. Corresponding rates for upper extremity repigmentation were 33.2% and 8.2%; for the trunk, 26.4% and 12.2%; for the lower extremities, 29.5% and 12.2%; and for the feet, 18.5% and 12.5%.

“The results are quite poor at 12 weeks,” Dr. Passeron said. “It’s very important to keep this in mind; it takes time to repigment vitiligo, it takes to 6-24 months. We have to explain to our patients that they will have to wait to see the results.”
 

Steady improvements, no new safety concerns

Regarding VASI-50 over time, there was a steady increase in total body scores; 47.7% of patients who received ruxolitinib and 23.3% of placebo-treated patients hit this target at 52 weeks.

“And what is also very important to see is that we didn’t reach the plateau,” Dr. Passeron reported.

Similar patterns were seen for all the other body areas. Again there was a suggestion that rates may continue to rise with continued long-term treatment.

“About one-third of the patients reached at least 50% repigmentation after 1 year of treatment in the hands and feet,” Dr. Passeron said. He noted that certain areas, such as the back of the hand or tips of the fingers, may be unresponsive.

“So, we have to also to warn the patient that probably on these areas we have to combine it with other treatment because it remains very, very difficult to treat.”

There were no new safety concerns regarding treatment-emergent adverse events, which were reported in 52% of patients who received ruxolitinib and in 36% of placebo-treated patients.

The most common adverse reactions included COVID-19 (6.1% vs. 3.1%), acne at the application site (5.3% vs. 1.3%), and pruritus at the application site (3.9% vs. 2.7%), although cases were “mild or moderate,” said Dr. Passeron.
 

An expert’s take-home

“The results of TRuE-V phase 3 studies are encouraging and exciting,” Viktoria Eleftheriadou, MD, MRCP(UK), SCE(Derm), PhD, said in providing an independent comment for this news organization.

“Although ruxolitinib cream is applied on the skin, this novel treatment for vitiligo is not without risks; therefore, careful monitoring of patients who are started on this topical treatment would be prudent,” said Dr. Eleftheriadou, who is a consultant dermatologist for Walsall Healthcare NHS Trust and the Royal Wolverhampton NHS Trust, Birmingham, United Kingdom.

“I would like to see how many patients achieved VASI-75 or VASI-80 score, which from patients’ perspectives is a more meaningful outcome, as well as how long these results will last for,” she added.

The study was funded by Incyte Corporation. Dr. Passeron has received grants, honoraria, or both from AbbVie, ACM Pharma, Almirall, Amgen, Astellas, Bristol-Myers Squibb, Celgene, Galderma, Genzyme/Sanofi, GlaxoSmithKline, Incyte Corporation, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Sun Pharmaceuticals, and UCB. Dr. Passeron is the cofounder of YUKIN Therapeutics and has patents on WNT agonists or GSK2b antagonist for repigmentation of vitiligo and on the use of CXCR3B blockers in vitiligo. Dr. Eleftheriadou is an investigator and trial development group member on the HI-Light Vitiligo Trial (specific), a lead investigator on the pilot HI-Light Vitiligo Trial, and a medical advisory panel member of the Vitiligo Society UK. Dr. Eleftheriadou also provides consultancy services to Incyte and Pfizer.

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

French children with peanut allergy tend to have reactions to other legumes, including soy, lentil, pea, bean, lupin, and fenugreek, and those other allergies often lead to anaphylactic reactions, a retrospective study from France reports.

“Among children allergic to peanut, at least two-thirds were sensitized to one other legume, and legume allergy was diagnosed in one-quarter of the sensitized patients,” wrote senior study author Amandine Divaret-Chauveau, MD, of Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, and colleagues. The report is in Pediatric Allergy and Immunology.

People worldwide are eating more legumes these days, the authors noted. High in protein, low in unsaturated fats, with low production costs, legumes are important components of increasingly vegetarian, healthy, sustainable diets.

Food allergens are the most common childhood triggers of allergic reactions. Among children in France, legumes cause 14.6% of food-related anaphylactic reactions, with peanut as the main allergen, they added.

Dr. Divaret-Chauveau and colleagues assessed the prevalence and relevance of sensitization to legumes among all children and adolescents aged 1-17 years who had peanut allergy and had been admitted to one academic pediatric allergy department over roughly 3 years, beginning in early 2017. For the 195 study participants, peanut allergy had been confirmed, and they had been documented to have consumed or to have sensitization to at least one non-peanut legume; 69.7% were boys.

The researchers analyzed data on consumption history, skin prick tests, specific immunoglobulin E status, prior allergic reactions, and oral food challenges for each legume. They found the following:

• Among the 195 children with peanut allergy, 98.4% had at least one other atopic disease.
• Of the 195 children with peanut allergy, 122 (63.9%) were sensitized to at least one other legume. Of these 122 children, 66.3% were sensitized to fenugreek, 42.2% to lentil, 39.9% to soy, and 34.2% to lupin.
• Allergy to one or more legumes was confirmed for 27.9% of the 122 sensitized children, including 4.9% who had multiple legume allergies. Lentil, lupin, and pea were the main allergens.
• Of the 118 children also having a non-legume food allergy, the main food allergens were egg (57.6%), cow’s milk (33.0%), cashew (39.0%), pistachio (23.7%), and hazelnut (30.5%).
• Fifty percent of allergic reactions to non-peanut legumes were severe, often showing as asthma. Atopic comorbidities, including asthma, in most participants may have contributed to the severity of allergic reactions, the authors noted.

Allergy awareness needs to grow with plant-based diets

“The high prevalence of legume sensitization reported in our study highlights the need to explore legume consumption in children with PA [peanut allergy], and the need to investigate sensitization in the absence of consumption,” they added.

Jodi A. Shroba, MSN, APRN, CPNP, coordinator for the Food Allergy Program at Children’s Mercy Kansas City, in Missouri, told this news organization that few data are available in the literature regarding allergies to legumes other than peanut.

“It was interesting that these authors found such a high legume sensitization in their peanut-allergic patients,” Ms. Shroba, who was not involved in the study, said by email. “As more people are starting to eat plant-based diets, it is important that we better understand their allergenicity and cross-reactivity so we can better help guide patient management and education.”

Deborah Albright, MD, assistant professor of pediatrics at the University of Pittsburgh, agreed.

“As plant-based protein consumption broadens worldwide, awareness of the potential for cross-reactivity and co-allergy amongst legumes will become increasingly important,” she said by email.

“However, positive allergy tests do not reliably correlate with true food allergy; therefore, the diagnosis of legume co-allergy should be confirmed by the individual patient’s history, a formal food challenge, or both,” advised Dr. Albright. She was not involved in the study.

“Cross-sensitization to other legumes in patients with a single legume allergy is common; however, true clinical reactivity is often not present,” she added. “Also, legume allergy test sensitization rates and objective reactivity on food challenge can vary by region, depending on diet and pollen aeroallergen exposure.

“Systematic exploration of tolerance versus co-allergy to other legumes should be considered in patients allergic to peanut or other legumes,” Dr. Albright said.

The authors recommend further research and registry data collection of legume anaphylaxis.

Details regarding funding for the study were not provided. The authors, Ms. Shroba, and Dr. Albright report no relevant financial relationships.

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

French children with peanut allergy tend to have reactions to other legumes, including soy, lentil, pea, bean, lupin, and fenugreek, and those other allergies often lead to anaphylactic reactions, a retrospective study from France reports.

“Among children allergic to peanut, at least two-thirds were sensitized to one other legume, and legume allergy was diagnosed in one-quarter of the sensitized patients,” wrote senior study author Amandine Divaret-Chauveau, MD, of Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, and colleagues. The report is in Pediatric Allergy and Immunology.

People worldwide are eating more legumes these days, the authors noted. High in protein, low in unsaturated fats, with low production costs, legumes are important components of increasingly vegetarian, healthy, sustainable diets.

Food allergens are the most common childhood triggers of allergic reactions. Among children in France, legumes cause 14.6% of food-related anaphylactic reactions, with peanut as the main allergen, they added.

Dr. Divaret-Chauveau and colleagues assessed the prevalence and relevance of sensitization to legumes among all children and adolescents aged 1-17 years who had peanut allergy and had been admitted to one academic pediatric allergy department over roughly 3 years, beginning in early 2017. For the 195 study participants, peanut allergy had been confirmed, and they had been documented to have consumed or to have sensitization to at least one non-peanut legume; 69.7% were boys.

The researchers analyzed data on consumption history, skin prick tests, specific immunoglobulin E status, prior allergic reactions, and oral food challenges for each legume. They found the following:

• Among the 195 children with peanut allergy, 98.4% had at least one other atopic disease.
• Of the 195 children with peanut allergy, 122 (63.9%) were sensitized to at least one other legume. Of these 122 children, 66.3% were sensitized to fenugreek, 42.2% to lentil, 39.9% to soy, and 34.2% to lupin.
• Allergy to one or more legumes was confirmed for 27.9% of the 122 sensitized children, including 4.9% who had multiple legume allergies. Lentil, lupin, and pea were the main allergens.
• Of the 118 children also having a non-legume food allergy, the main food allergens were egg (57.6%), cow’s milk (33.0%), cashew (39.0%), pistachio (23.7%), and hazelnut (30.5%).
• Fifty percent of allergic reactions to non-peanut legumes were severe, often showing as asthma. Atopic comorbidities, including asthma, in most participants may have contributed to the severity of allergic reactions, the authors noted.

Allergy awareness needs to grow with plant-based diets

“The high prevalence of legume sensitization reported in our study highlights the need to explore legume consumption in children with PA [peanut allergy], and the need to investigate sensitization in the absence of consumption,” they added.

Jodi A. Shroba, MSN, APRN, CPNP, coordinator for the Food Allergy Program at Children’s Mercy Kansas City, in Missouri, told this news organization that few data are available in the literature regarding allergies to legumes other than peanut.

“It was interesting that these authors found such a high legume sensitization in their peanut-allergic patients,” Ms. Shroba, who was not involved in the study, said by email. “As more people are starting to eat plant-based diets, it is important that we better understand their allergenicity and cross-reactivity so we can better help guide patient management and education.”

Deborah Albright, MD, assistant professor of pediatrics at the University of Pittsburgh, agreed.

“As plant-based protein consumption broadens worldwide, awareness of the potential for cross-reactivity and co-allergy amongst legumes will become increasingly important,” she said by email.

“However, positive allergy tests do not reliably correlate with true food allergy; therefore, the diagnosis of legume co-allergy should be confirmed by the individual patient’s history, a formal food challenge, or both,” advised Dr. Albright. She was not involved in the study.

“Cross-sensitization to other legumes in patients with a single legume allergy is common; however, true clinical reactivity is often not present,” she added. “Also, legume allergy test sensitization rates and objective reactivity on food challenge can vary by region, depending on diet and pollen aeroallergen exposure.

“Systematic exploration of tolerance versus co-allergy to other legumes should be considered in patients allergic to peanut or other legumes,” Dr. Albright said.

The authors recommend further research and registry data collection of legume anaphylaxis.

Details regarding funding for the study were not provided. The authors, Ms. Shroba, and Dr. Albright report no relevant financial relationships.

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

French children with peanut allergy tend to have reactions to other legumes, including soy, lentil, pea, bean, lupin, and fenugreek, and those other allergies often lead to anaphylactic reactions, a retrospective study from France reports.

“Among children allergic to peanut, at least two-thirds were sensitized to one other legume, and legume allergy was diagnosed in one-quarter of the sensitized patients,” wrote senior study author Amandine Divaret-Chauveau, MD, of Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, and colleagues. The report is in Pediatric Allergy and Immunology.

People worldwide are eating more legumes these days, the authors noted. High in protein, low in unsaturated fats, with low production costs, legumes are important components of increasingly vegetarian, healthy, sustainable diets.

Food allergens are the most common childhood triggers of allergic reactions. Among children in France, legumes cause 14.6% of food-related anaphylactic reactions, with peanut as the main allergen, they added.

Dr. Divaret-Chauveau and colleagues assessed the prevalence and relevance of sensitization to legumes among all children and adolescents aged 1-17 years who had peanut allergy and had been admitted to one academic pediatric allergy department over roughly 3 years, beginning in early 2017. For the 195 study participants, peanut allergy had been confirmed, and they had been documented to have consumed or to have sensitization to at least one non-peanut legume; 69.7% were boys.

The researchers analyzed data on consumption history, skin prick tests, specific immunoglobulin E status, prior allergic reactions, and oral food challenges for each legume. They found the following:

• Among the 195 children with peanut allergy, 98.4% had at least one other atopic disease.
• Of the 195 children with peanut allergy, 122 (63.9%) were sensitized to at least one other legume. Of these 122 children, 66.3% were sensitized to fenugreek, 42.2% to lentil, 39.9% to soy, and 34.2% to lupin.
• Allergy to one or more legumes was confirmed for 27.9% of the 122 sensitized children, including 4.9% who had multiple legume allergies. Lentil, lupin, and pea were the main allergens.
• Of the 118 children also having a non-legume food allergy, the main food allergens were egg (57.6%), cow’s milk (33.0%), cashew (39.0%), pistachio (23.7%), and hazelnut (30.5%).
• Fifty percent of allergic reactions to non-peanut legumes were severe, often showing as asthma. Atopic comorbidities, including asthma, in most participants may have contributed to the severity of allergic reactions, the authors noted.

Allergy awareness needs to grow with plant-based diets

“The high prevalence of legume sensitization reported in our study highlights the need to explore legume consumption in children with PA [peanut allergy], and the need to investigate sensitization in the absence of consumption,” they added.

Jodi A. Shroba, MSN, APRN, CPNP, coordinator for the Food Allergy Program at Children’s Mercy Kansas City, in Missouri, told this news organization that few data are available in the literature regarding allergies to legumes other than peanut.

“It was interesting that these authors found such a high legume sensitization in their peanut-allergic patients,” Ms. Shroba, who was not involved in the study, said by email. “As more people are starting to eat plant-based diets, it is important that we better understand their allergenicity and cross-reactivity so we can better help guide patient management and education.”

Deborah Albright, MD, assistant professor of pediatrics at the University of Pittsburgh, agreed.

“As plant-based protein consumption broadens worldwide, awareness of the potential for cross-reactivity and co-allergy amongst legumes will become increasingly important,” she said by email.

“However, positive allergy tests do not reliably correlate with true food allergy; therefore, the diagnosis of legume co-allergy should be confirmed by the individual patient’s history, a formal food challenge, or both,” advised Dr. Albright. She was not involved in the study.

“Cross-sensitization to other legumes in patients with a single legume allergy is common; however, true clinical reactivity is often not present,” she added. “Also, legume allergy test sensitization rates and objective reactivity on food challenge can vary by region, depending on diet and pollen aeroallergen exposure.

“Systematic exploration of tolerance versus co-allergy to other legumes should be considered in patients allergic to peanut or other legumes,” Dr. Albright said.

The authors recommend further research and registry data collection of legume anaphylaxis.

Details regarding funding for the study were not provided. The authors, Ms. Shroba, and Dr. Albright report no relevant financial relationships.

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

Several leading medical groups on Oct. 3 called on U.S. Attorney General Merrick Garland to investigate and prosecute those responsible for a recent spate of threats and attacks against hospitals and physicians who are providing gender-affirming care.

In an Oct. 3 letter, the American Academy of Pediatrics (AAP), the American Medical Association (AMA), and the Children’s Hospital Association detailed the risk posed by these threats to physicians, patients, and the federally protected right to health care.

The letter comes during a campaign of intimidation and misinformation that has disrupted gender-related care in Seattle, Akron, Ohio, Nashville, Tenn., and Boston in the past few weeks. Hospitals across the country and their ambulatory sites have been forced to substantially increase protection, and “some providers have needed 24/7 security,” according to the letter.

Not only do the threats bully physicians providing gender-affirming care and the patients who receive that care, but “they have also disrupted many other services to families seeking care,” the letter claims.

According to STAT, many hospitals that provide gender-affirming care have responded to the threats by removing information about the treatment from their websites.

At one hospital, a new mother was separated from her preterm infant because the facility’s neonatal intensive care unit was locked down as the result of a bomb threat. (It’s not clear whether that incident is the same as a similar threat that led to the arrest of a 37-year-old Massachusetts woman, who is facing criminal charges in the episode.)

“The attacks are rooted in an intentional campaign of disinformation” by high-profile social media users, according to the letter. The medical organizations have also called on major tech companies, including TikTok, Twitter, and Meta, to do more to prevent the coordination of disinformation campaigns and violence against health care providers and patients.

“We now urge your office to take swift action to investigate and prosecute all organizations, individuals, and entities responsible,” the letter states.

“We cannot stand by as threats of violence against our members and their patients proliferate with little consequence. We call on the Department of Justice to investigate these attacks and social media platforms to reduce the spread of the misinformation enabling them,” AAP President Moira Szilagyi, MD, PhD, FAAP, said in a press release.

In addition to physical threats at their workplace, providers face threats on their personal social media accounts and harassment via phone and email. The letter notes that these unchecked attacks are coming after health care workers spent 3 years working on the front lines of a pandemic.

“Individuals in all workplaces have the right to a safe environment, out of harm’s way and free of intimidation or reprisal,” AMA President Jack Resneck Jr, MD, said in a statement. “The AMA will continue to work with federal, state, and local law enforcement officials to develop and implement strategies that protect hard-working, law-abiding physicians and other health care workers from senseless acts of violence, abuse, and intimidation.”

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

Several leading medical groups on Oct. 3 called on U.S. Attorney General Merrick Garland to investigate and prosecute those responsible for a recent spate of threats and attacks against hospitals and physicians who are providing gender-affirming care.

In an Oct. 3 letter, the American Academy of Pediatrics (AAP), the American Medical Association (AMA), and the Children’s Hospital Association detailed the risk posed by these threats to physicians, patients, and the federally protected right to health care.

The letter comes during a campaign of intimidation and misinformation that has disrupted gender-related care in Seattle, Akron, Ohio, Nashville, Tenn., and Boston in the past few weeks. Hospitals across the country and their ambulatory sites have been forced to substantially increase protection, and “some providers have needed 24/7 security,” according to the letter.

Not only do the threats bully physicians providing gender-affirming care and the patients who receive that care, but “they have also disrupted many other services to families seeking care,” the letter claims.

According to STAT, many hospitals that provide gender-affirming care have responded to the threats by removing information about the treatment from their websites.

At one hospital, a new mother was separated from her preterm infant because the facility’s neonatal intensive care unit was locked down as the result of a bomb threat. (It’s not clear whether that incident is the same as a similar threat that led to the arrest of a 37-year-old Massachusetts woman, who is facing criminal charges in the episode.)

“The attacks are rooted in an intentional campaign of disinformation” by high-profile social media users, according to the letter. The medical organizations have also called on major tech companies, including TikTok, Twitter, and Meta, to do more to prevent the coordination of disinformation campaigns and violence against health care providers and patients.

“We now urge your office to take swift action to investigate and prosecute all organizations, individuals, and entities responsible,” the letter states.

“We cannot stand by as threats of violence against our members and their patients proliferate with little consequence. We call on the Department of Justice to investigate these attacks and social media platforms to reduce the spread of the misinformation enabling them,” AAP President Moira Szilagyi, MD, PhD, FAAP, said in a press release.

In addition to physical threats at their workplace, providers face threats on their personal social media accounts and harassment via phone and email. The letter notes that these unchecked attacks are coming after health care workers spent 3 years working on the front lines of a pandemic.

“Individuals in all workplaces have the right to a safe environment, out of harm’s way and free of intimidation or reprisal,” AMA President Jack Resneck Jr, MD, said in a statement. “The AMA will continue to work with federal, state, and local law enforcement officials to develop and implement strategies that protect hard-working, law-abiding physicians and other health care workers from senseless acts of violence, abuse, and intimidation.”

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

Several leading medical groups on Oct. 3 called on U.S. Attorney General Merrick Garland to investigate and prosecute those responsible for a recent spate of threats and attacks against hospitals and physicians who are providing gender-affirming care.

In an Oct. 3 letter, the American Academy of Pediatrics (AAP), the American Medical Association (AMA), and the Children’s Hospital Association detailed the risk posed by these threats to physicians, patients, and the federally protected right to health care.

The letter comes during a campaign of intimidation and misinformation that has disrupted gender-related care in Seattle, Akron, Ohio, Nashville, Tenn., and Boston in the past few weeks. Hospitals across the country and their ambulatory sites have been forced to substantially increase protection, and “some providers have needed 24/7 security,” according to the letter.

Not only do the threats bully physicians providing gender-affirming care and the patients who receive that care, but “they have also disrupted many other services to families seeking care,” the letter claims.

According to STAT, many hospitals that provide gender-affirming care have responded to the threats by removing information about the treatment from their websites.

At one hospital, a new mother was separated from her preterm infant because the facility’s neonatal intensive care unit was locked down as the result of a bomb threat. (It’s not clear whether that incident is the same as a similar threat that led to the arrest of a 37-year-old Massachusetts woman, who is facing criminal charges in the episode.)

“The attacks are rooted in an intentional campaign of disinformation” by high-profile social media users, according to the letter. The medical organizations have also called on major tech companies, including TikTok, Twitter, and Meta, to do more to prevent the coordination of disinformation campaigns and violence against health care providers and patients.

“We now urge your office to take swift action to investigate and prosecute all organizations, individuals, and entities responsible,” the letter states.

“We cannot stand by as threats of violence against our members and their patients proliferate with little consequence. We call on the Department of Justice to investigate these attacks and social media platforms to reduce the spread of the misinformation enabling them,” AAP President Moira Szilagyi, MD, PhD, FAAP, said in a press release.

In addition to physical threats at their workplace, providers face threats on their personal social media accounts and harassment via phone and email. The letter notes that these unchecked attacks are coming after health care workers spent 3 years working on the front lines of a pandemic.

“Individuals in all workplaces have the right to a safe environment, out of harm’s way and free of intimidation or reprisal,” AMA President Jack Resneck Jr, MD, said in a statement. “The AMA will continue to work with federal, state, and local law enforcement officials to develop and implement strategies that protect hard-working, law-abiding physicians and other health care workers from senseless acts of violence, abuse, and intimidation.”

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

Lasmiditan—the first migraine treatment in the new ditan class— is a serotonin receptor agonist, similar to triptan medications. However, it is specific for the 5HT_1F receptor rather than the 5HT_1B/1D receptor. The main purpose of this specificity is that it leads to less vascular risk; specifically, this medication should be safer for populations at higher risk for vascular events, such as myocardial infarction and stroke.

Only one triptan, naratriptan, had previously been studied for the treatment of menstrual migraine, at a recommended dose of 2.5 mg twice daily as a bridge. A new study by MacGregor and colleagues looked at taking 50, 100, or 200 mg of lasmiditan vs placebo for an individual premenstrual attack.

The participants in the study were recruited from the intention-to-treat population of two prior studies for this drug, a phase 2 trial and a phase 3 trial. The menstrual calendars of the female participants were reviewed, followed by randomization into one of the four groups. Patients with chronic migraine were excluded from the study. The primary outcome was freedom from pain at 2 hours; secondary outcomes were freedom from the most bothersome symptom and reduction in pain severity.

Of the four populations followed, all three intervention groups noted significant results in freedom from pain at 2 hours compared with placebo. The 2-hour responder rate was 33.6% for the 200 mg group, 16.7% for the 50 mg and 100 mg groups, and 7.6% for the placebo group. Freedom from the most bothersome symptom and pain reduction were also significant in these populations.

Menstruation-associated migraine and worsening headache attacks due to patients' hormonal fluctuations are some of the most common issues and triggers that neurologists and headache specialists confront. Although the responder rates for freedom from pain at 2 hours were not very robust, lasmiditan does appear to be significantly effective in this population, and in those with menstrual triggers specifically. The field of headache medicine would be even better served by additional studies on both preventive and more acute medications in association with hormonal triggers.

Another very common trigger for migraine is changes in sleep patterns. An astute headache specialist will always ask about sleep quantity and quality during an initial assessment of a patient. Many headache centers have sleep-specific questionnaires that patients fill out during intake. The precise association between migraine and sleep deserves more elucidation. Duan and colleagues specifically set out to reveal whether differences in sleep quality affect migraine frequency; whether this is the same among different gender and age groups; and whether headache disability, severity, mood, and quality of life are related to underlying sleep changes independent of other factors.

A total of 134 participants with migraine and 70 without migraine or any other headache disorder were enrolled in the study. Sleep quality was assessed through The Pittsburgh Sleep Quality Index (PSQI) questionnaire. This is a commonly used self-reported questionnaire for assessing quality and quantity of sleep over the past month and is considered the standard of care in most sleep centers. The investigators here sought to determine the predictive value of the PSQI in regard to migraine. Migraine disability was assessed via the Migraine Disability Assessment (MIDAS) scale as well as the Headache Impact Test (HIT-6). Statistical analysis was performed with logistical regression, t test, and χ² squared test.

There strongest correlations between poor sleep quality and risk of migraine were found in women, patients over 35 years old, and those with lower education levels. The results revealed that the migraine group had poorer sleep quality, as well as higher anxiety and depression scores, compared with the control group. A low PSQI score (eg, poorer sleep quality) was associated with higher migraine frequency; this was independent of body mass index (BMI), weekly exercise time, and smoking or drinking history. After participants were divided into good and poor sleep quality subgroups, the PSQI score was found to increase the odds ratio of migraine by a factor of 6.

The investigators were able to show the predictive quality of the PSQI score. Worse sleep quality was found to be associated with a higher MIDAS score and HIT-6 score as well as total pain burden, pain severity, decreased quality of life, depression, and anxiety. Although most headache specialists spend a significant amount of time discussing sleep as it relates to migraine, it may be worth considering following a sleep quality scale, such as the PSQI, over time as we monitor our patients. This may allow us to take a more proactive role and be able to prognosticate our patients' migraine journey somewhat better. Although sleep triggers and associations with migraine can be very difficult to discuss and treat, this study very clearly argues for the importance of focusing on sleep with our patients.

Although the most common aura our patients with migraine experience is visual, many patients with migraine will also experience non-aura visual changes. These can range from short-lasting episodes of blurred vision, such as transient visual obscurations, or other transient visual disturbances that do not fit the criteria of aura as defined by the International Classification of Headache Disorders (ICHD).

A prior study by Tsao and colleagues had revealed that almost half of headache patients experienced some headache-related visual change, the most common of which were short-lasting flickering lights or a movable, monochromatic scotoma. As opposed to visual aura, these transient disturbances were shorter in onset and duration and typically occurred during the headache phase of a migraine attack. In the current study, Tsao and colleagues sought to determine whether the presence of these findings was associated with a different headache burden from that typically found in migraine with aura.

The participants in this study were enrolled over a 10-year period from May 2010 to July 2020. They initially underwent a visual phenomenon questionnaire and then a thorough clinical interview to determine their headache diagnosis per ICHD criteria — specifically whether they had an underlying diagnosis of migraine with aura or migraine without aura. Participants were also separately diagnosed with chronic migraine or medication overuse headache. A visual rating scale was used in the initial questionnaires. This scale posed questions about the duration of symptoms; whether the symptoms develop gradually or suddenly; and whether the visual change was a scotoma, zigzag lines, or in a unilateral or bilateral visual field. A prior study by these investigators determined this visual rating scale to be highly sensitive and specific for diagnosing migraine with aura.

Participants were also given the MIDAS questionnaire and were assessed with the HIT-6 scale, a migraine photophobia score, and the Beck Depression Inventory. A total of 12,255 patients were enrolled, 9946 with migraine, who were subdivided on the basis of diagnosis of migraine with or without aura. Blurred vision was the most common visual complaint among all migraine patients. Patients who had transient visual disturbances that did not fit the criteria of migraine with aura were noted to have a statistically significant higher headache frequency, more severe headache-related disability, a higher likelihood of developing medication overuse headache, and a greater incidence of anxiety and depression.

An important distinction that all headache specialists make is whether their patients experience migraine with or without aura. The primary purpose for this distinction is to determine the appropriateness of specific medications (estrogen or vasoconstrictive medications), as migraine aura relates to vascular risk. We usually delve deeply into whether the visual symptoms that our patients experience do or do not fit into the ICHD criteria of migraine aura. We should not discard or think less of non-aura visual disturbances; these authors argue very clearly that these kinds of visual changes can be very relevant prognostically.

Lasmiditan—the first migraine treatment in the new ditan class— is a serotonin receptor agonist, similar to triptan medications. However, it is specific for the 5HT_1F receptor rather than the 5HT_1B/1D receptor. The main purpose of this specificity is that it leads to less vascular risk; specifically, this medication should be safer for populations at higher risk for vascular events, such as myocardial infarction and stroke.

Only one triptan, naratriptan, had previously been studied for the treatment of menstrual migraine, at a recommended dose of 2.5 mg twice daily as a bridge. A new study by MacGregor and colleagues looked at taking 50, 100, or 200 mg of lasmiditan vs placebo for an individual premenstrual attack.

The participants in the study were recruited from the intention-to-treat population of two prior studies for this drug, a phase 2 trial and a phase 3 trial. The menstrual calendars of the female participants were reviewed, followed by randomization into one of the four groups. Patients with chronic migraine were excluded from the study. The primary outcome was freedom from pain at 2 hours; secondary outcomes were freedom from the most bothersome symptom and reduction in pain severity.

Of the four populations followed, all three intervention groups noted significant results in freedom from pain at 2 hours compared with placebo. The 2-hour responder rate was 33.6% for the 200 mg group, 16.7% for the 50 mg and 100 mg groups, and 7.6% for the placebo group. Freedom from the most bothersome symptom and pain reduction were also significant in these populations.

Menstruation-associated migraine and worsening headache attacks due to patients' hormonal fluctuations are some of the most common issues and triggers that neurologists and headache specialists confront. Although the responder rates for freedom from pain at 2 hours were not very robust, lasmiditan does appear to be significantly effective in this population, and in those with menstrual triggers specifically. The field of headache medicine would be even better served by additional studies on both preventive and more acute medications in association with hormonal triggers.

Another very common trigger for migraine is changes in sleep patterns. An astute headache specialist will always ask about sleep quantity and quality during an initial assessment of a patient. Many headache centers have sleep-specific questionnaires that patients fill out during intake. The precise association between migraine and sleep deserves more elucidation. Duan and colleagues specifically set out to reveal whether differences in sleep quality affect migraine frequency; whether this is the same among different gender and age groups; and whether headache disability, severity, mood, and quality of life are related to underlying sleep changes independent of other factors.

A total of 134 participants with migraine and 70 without migraine or any other headache disorder were enrolled in the study. Sleep quality was assessed through The Pittsburgh Sleep Quality Index (PSQI) questionnaire. This is a commonly used self-reported questionnaire for assessing quality and quantity of sleep over the past month and is considered the standard of care in most sleep centers. The investigators here sought to determine the predictive value of the PSQI in regard to migraine. Migraine disability was assessed via the Migraine Disability Assessment (MIDAS) scale as well as the Headache Impact Test (HIT-6). Statistical analysis was performed with logistical regression, t test, and χ² squared test.

There strongest correlations between poor sleep quality and risk of migraine were found in women, patients over 35 years old, and those with lower education levels. The results revealed that the migraine group had poorer sleep quality, as well as higher anxiety and depression scores, compared with the control group. A low PSQI score (eg, poorer sleep quality) was associated with higher migraine frequency; this was independent of body mass index (BMI), weekly exercise time, and smoking or drinking history. After participants were divided into good and poor sleep quality subgroups, the PSQI score was found to increase the odds ratio of migraine by a factor of 6.

The investigators were able to show the predictive quality of the PSQI score. Worse sleep quality was found to be associated with a higher MIDAS score and HIT-6 score as well as total pain burden, pain severity, decreased quality of life, depression, and anxiety. Although most headache specialists spend a significant amount of time discussing sleep as it relates to migraine, it may be worth considering following a sleep quality scale, such as the PSQI, over time as we monitor our patients. This may allow us to take a more proactive role and be able to prognosticate our patients' migraine journey somewhat better. Although sleep triggers and associations with migraine can be very difficult to discuss and treat, this study very clearly argues for the importance of focusing on sleep with our patients.

Although the most common aura our patients with migraine experience is visual, many patients with migraine will also experience non-aura visual changes. These can range from short-lasting episodes of blurred vision, such as transient visual obscurations, or other transient visual disturbances that do not fit the criteria of aura as defined by the International Classification of Headache Disorders (ICHD).

A prior study by Tsao and colleagues had revealed that almost half of headache patients experienced some headache-related visual change, the most common of which were short-lasting flickering lights or a movable, monochromatic scotoma. As opposed to visual aura, these transient disturbances were shorter in onset and duration and typically occurred during the headache phase of a migraine attack. In the current study, Tsao and colleagues sought to determine whether the presence of these findings was associated with a different headache burden from that typically found in migraine with aura.

The participants in this study were enrolled over a 10-year period from May 2010 to July 2020. They initially underwent a visual phenomenon questionnaire and then a thorough clinical interview to determine their headache diagnosis per ICHD criteria — specifically whether they had an underlying diagnosis of migraine with aura or migraine without aura. Participants were also separately diagnosed with chronic migraine or medication overuse headache. A visual rating scale was used in the initial questionnaires. This scale posed questions about the duration of symptoms; whether the symptoms develop gradually or suddenly; and whether the visual change was a scotoma, zigzag lines, or in a unilateral or bilateral visual field. A prior study by these investigators determined this visual rating scale to be highly sensitive and specific for diagnosing migraine with aura.

Participants were also given the MIDAS questionnaire and were assessed with the HIT-6 scale, a migraine photophobia score, and the Beck Depression Inventory. A total of 12,255 patients were enrolled, 9946 with migraine, who were subdivided on the basis of diagnosis of migraine with or without aura. Blurred vision was the most common visual complaint among all migraine patients. Patients who had transient visual disturbances that did not fit the criteria of migraine with aura were noted to have a statistically significant higher headache frequency, more severe headache-related disability, a higher likelihood of developing medication overuse headache, and a greater incidence of anxiety and depression.

An important distinction that all headache specialists make is whether their patients experience migraine with or without aura. The primary purpose for this distinction is to determine the appropriateness of specific medications (estrogen or vasoconstrictive medications), as migraine aura relates to vascular risk. We usually delve deeply into whether the visual symptoms that our patients experience do or do not fit into the ICHD criteria of migraine aura. We should not discard or think less of non-aura visual disturbances; these authors argue very clearly that these kinds of visual changes can be very relevant prognostically.

Lasmiditan—the first migraine treatment in the new ditan class— is a serotonin receptor agonist, similar to triptan medications. However, it is specific for the 5HT_1F receptor rather than the 5HT_1B/1D receptor. The main purpose of this specificity is that it leads to less vascular risk; specifically, this medication should be safer for populations at higher risk for vascular events, such as myocardial infarction and stroke.

Only one triptan, naratriptan, had previously been studied for the treatment of menstrual migraine, at a recommended dose of 2.5 mg twice daily as a bridge. A new study by MacGregor and colleagues looked at taking 50, 100, or 200 mg of lasmiditan vs placebo for an individual premenstrual attack.

The participants in the study were recruited from the intention-to-treat population of two prior studies for this drug, a phase 2 trial and a phase 3 trial. The menstrual calendars of the female participants were reviewed, followed by randomization into one of the four groups. Patients with chronic migraine were excluded from the study. The primary outcome was freedom from pain at 2 hours; secondary outcomes were freedom from the most bothersome symptom and reduction in pain severity.

Of the four populations followed, all three intervention groups noted significant results in freedom from pain at 2 hours compared with placebo. The 2-hour responder rate was 33.6% for the 200 mg group, 16.7% for the 50 mg and 100 mg groups, and 7.6% for the placebo group. Freedom from the most bothersome symptom and pain reduction were also significant in these populations.

Menstruation-associated migraine and worsening headache attacks due to patients' hormonal fluctuations are some of the most common issues and triggers that neurologists and headache specialists confront. Although the responder rates for freedom from pain at 2 hours were not very robust, lasmiditan does appear to be significantly effective in this population, and in those with menstrual triggers specifically. The field of headache medicine would be even better served by additional studies on both preventive and more acute medications in association with hormonal triggers.

Another very common trigger for migraine is changes in sleep patterns. An astute headache specialist will always ask about sleep quantity and quality during an initial assessment of a patient. Many headache centers have sleep-specific questionnaires that patients fill out during intake. The precise association between migraine and sleep deserves more elucidation. Duan and colleagues specifically set out to reveal whether differences in sleep quality affect migraine frequency; whether this is the same among different gender and age groups; and whether headache disability, severity, mood, and quality of life are related to underlying sleep changes independent of other factors.

A total of 134 participants with migraine and 70 without migraine or any other headache disorder were enrolled in the study. Sleep quality was assessed through The Pittsburgh Sleep Quality Index (PSQI) questionnaire. This is a commonly used self-reported questionnaire for assessing quality and quantity of sleep over the past month and is considered the standard of care in most sleep centers. The investigators here sought to determine the predictive value of the PSQI in regard to migraine. Migraine disability was assessed via the Migraine Disability Assessment (MIDAS) scale as well as the Headache Impact Test (HIT-6). Statistical analysis was performed with logistical regression, t test, and χ² squared test.

There strongest correlations between poor sleep quality and risk of migraine were found in women, patients over 35 years old, and those with lower education levels. The results revealed that the migraine group had poorer sleep quality, as well as higher anxiety and depression scores, compared with the control group. A low PSQI score (eg, poorer sleep quality) was associated with higher migraine frequency; this was independent of body mass index (BMI), weekly exercise time, and smoking or drinking history. After participants were divided into good and poor sleep quality subgroups, the PSQI score was found to increase the odds ratio of migraine by a factor of 6.

The investigators were able to show the predictive quality of the PSQI score. Worse sleep quality was found to be associated with a higher MIDAS score and HIT-6 score as well as total pain burden, pain severity, decreased quality of life, depression, and anxiety. Although most headache specialists spend a significant amount of time discussing sleep as it relates to migraine, it may be worth considering following a sleep quality scale, such as the PSQI, over time as we monitor our patients. This may allow us to take a more proactive role and be able to prognosticate our patients' migraine journey somewhat better. Although sleep triggers and associations with migraine can be very difficult to discuss and treat, this study very clearly argues for the importance of focusing on sleep with our patients.

Although the most common aura our patients with migraine experience is visual, many patients with migraine will also experience non-aura visual changes. These can range from short-lasting episodes of blurred vision, such as transient visual obscurations, or other transient visual disturbances that do not fit the criteria of aura as defined by the International Classification of Headache Disorders (ICHD).

A prior study by Tsao and colleagues had revealed that almost half of headache patients experienced some headache-related visual change, the most common of which were short-lasting flickering lights or a movable, monochromatic scotoma. As opposed to visual aura, these transient disturbances were shorter in onset and duration and typically occurred during the headache phase of a migraine attack. In the current study, Tsao and colleagues sought to determine whether the presence of these findings was associated with a different headache burden from that typically found in migraine with aura.

The participants in this study were enrolled over a 10-year period from May 2010 to July 2020. They initially underwent a visual phenomenon questionnaire and then a thorough clinical interview to determine their headache diagnosis per ICHD criteria — specifically whether they had an underlying diagnosis of migraine with aura or migraine without aura. Participants were also separately diagnosed with chronic migraine or medication overuse headache. A visual rating scale was used in the initial questionnaires. This scale posed questions about the duration of symptoms; whether the symptoms develop gradually or suddenly; and whether the visual change was a scotoma, zigzag lines, or in a unilateral or bilateral visual field. A prior study by these investigators determined this visual rating scale to be highly sensitive and specific for diagnosing migraine with aura.

Participants were also given the MIDAS questionnaire and were assessed with the HIT-6 scale, a migraine photophobia score, and the Beck Depression Inventory. A total of 12,255 patients were enrolled, 9946 with migraine, who were subdivided on the basis of diagnosis of migraine with or without aura. Blurred vision was the most common visual complaint among all migraine patients. Patients who had transient visual disturbances that did not fit the criteria of migraine with aura were noted to have a statistically significant higher headache frequency, more severe headache-related disability, a higher likelihood of developing medication overuse headache, and a greater incidence of anxiety and depression.

An important distinction that all headache specialists make is whether their patients experience migraine with or without aura. The primary purpose for this distinction is to determine the appropriateness of specific medications (estrogen or vasoconstrictive medications), as migraine aura relates to vascular risk. We usually delve deeply into whether the visual symptoms that our patients experience do or do not fit into the ICHD criteria of migraine aura. We should not discard or think less of non-aura visual disturbances; these authors argue very clearly that these kinds of visual changes can be very relevant prognostically.

PARIS – New disappointing results from a trial of adjuvant immunotherapy for patients with renal cell carcinoma who underwent nephrectomy contrast with those from a previous trial that showed benefit with another agent.

The new results, from CheckMate 914, show that adjuvant treatment with the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) did not improve disease-free survival (DFS), compared with placebo.

The finding was presented at the annual meeting of the European Society for Medical Oncology.

CheckMate 914 “did not meet the primary endpoint,” study presenter Robert J. Motzer, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York, said at a press conference.

The results contrast with those seen with pembrolizumab (Keytruda) in the same setting, where the drug achieved a 32% reduction in risk of recurrence or death over placebo in KEYNOTE-564. This led to the U.S. Food and Drug Administration granting approval for the drug as adjuvant treatment following surgery in patients with renal cell carcinoma at intermediate or high risk for recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.

Another trial of adjuvant immunotherapy in renal cell carcinoma, also presented at ESMO 2022, the IMmotion010 trial with adjuvant atezolizumab (Tecentriq), also did not show any clinical benefit over placebo.

However, Dr. Motzer said that despite both of these new trials showing no benefit, “I don’t think it takes away from standard of care pembrolizumab” in this setting.

There is a great need for adjuvant therapy for patients who undergo surgery, Dr. Motzer commented. The standard treatment for stage I-III localized nonmetastatic renal cell carcinoma is radical or partial nephrectomy, but there remains a “substantial risk” of relapse after surgery, occurring in up to 50% of patients.

In the past, the standard of care for these patients would be watching and waiting and “hoping that the patient doesn’t relapse,” he said, and if they did, then “we would treat accordingly for metastatic disease.”
 

Differences between trials

When asked about the contrast between the latest trial with the adjuvant nivolumab-ipilimumab combination and the earlier trial with adjuvant pembrolizumab, Dr. Motzer told this news organization that there are differences in the designs of the two studies. “Although they are both global phase 2 trials ... [there are] some differences in the patient population.”

However, the “main differences” are the duration, intensity, and tolerability of the treatment regimens. “I suspect that’s impacted on the outcome of our trial,” he said, as “many of our patients didn’t complete even that 6 months of the more toxic immunotherapy [nivolumab-ipilimumab combination].”

Dr. Motzer also noted that, compared with the metastatic setting, patients “do not tolerate therapy as well” in the adjuvant setting. Consequently, the risk-benefit of a drug is “slightly different ... as we have to be much more concerned about toxicity.”

In addition, he said, “our trial also used these kind-of gross clinical features that were developed years ago” to select patients, but now “there’s other much more refined techniques” that look at the underlying biological signatures “to identify who responds to immunotherapy.”

“So I think we have to do a deep dive into the biology in this trial and in the Merck trial [of pembrolizumab] to see if we can better define who is going to relapse and who is going to benefit,” he said.

Commenting on the new results, Dominik Berthold, MD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, also wondered whether differences in trial design and study populations could explain the divergent results between the CheckMate and KEYNOTE trials.

“Investigators will need to look in detail at subpopulations and biomarkers to guide treatment decisions and trial design for current and future patients,” he added.

Dr. Berthold said he agrees that pembrolizumab remains standard of care, but “I’m not really sure that we have really to offer all patients” the drug.

He explained that, on the one hand, there is the risk of over-treating many patients, depending on their stage, and on the other hand, “many patients who get pembrolizumab actually do progress.”

In addition, there is the question of the treatment sequence in patients who are already exposed to immunotherapy and when to start tyrosine kinase inhibitors, as well as the much broader issue of the lack of long-term overall survival data with pembrolizumab.

Dr. Berthold noted the issue of whether the high treatment discontinuation rate in CheckMate 914 affected the efficacy of nivolumab plus ipilimumab raises the question of whether, from an immunological point of view, 1 year of pembrolizumab is more effective than 3 months of the combination therapy.

“I think it might be one of the explanations,” he said, adding, however, that these are just “hypotheses” at this stage.
 

Details of the new results

Previous results with the nivolumab-ipilimumab combination, from the CheckMate 214 trial in patients with advanced renal cell carcinoma, had demonstrated that upfront nivolumab plus ipilimumab offered significantly longer treatment-free survival than the VEGF inhibitor sunitinib. The “striking results” from that trial indicated the combination was not only associated with a survival benefit, but also “high response rates, durable responses, complete responses, and even treatment responses that continue after treatment is discontinued,” Dr. Motzer commented.

So his team set out to test the combination in the adjuvant setting in the CheckMate 914 trial, designed in two parts: Part A, comparing nivolumab plus ipilimumab with placebo, and Part B, adding nivolumab monotherapy as another comparator.

Reporting on Part A of the trial, Dr. Motzer explained that they included 816 patients with renal cell carcinoma who had undergone radical or partial nephrectomy with negative surgical margins and had a predominantly clear cell histology.

They also selected patients based on their pathologic TNM staging, choosing “high-risk” individuals, Dr. Motzer explained, but who nevertheless had no evidence of residual disease or distant metastases following nephrectomy.

Between 4 and 12 weeks after surgery, patients were randomized to receive 12 doses of nivolumab plus four doses of ipilimumab or matched placebos for an expected treatment duration of 24 weeks.

The median age of patients was 58-59 years, and approximately 71% were men. By far the most common type of surgery was radical nephrectomy, with 93%, and Dr. Motzer noted that most patients (77%-78%) had pT3 disease without nodal involvement.

After a median follow-up of 37.0 months, there was no significant difference between groups in the primary endpoint of DFS, as assessed by blinded independent central review.

Median DFS was not reached for nivolumab plus ipilimumab versus 50.7 months for placebo, at a hazard ratio of 0.92 (P = .5347). At 24 months, DFS was 76.4% with the combination therapy versus 74.0% for placebo.

Subgroup analysis did not reveal any patient groups that significantly benefitted from the combination therapy, although there was a signal of greater benefit in those with other than pT3 disease.

While tumors with sarcomatoid features appeared to have a significant benefit from nivolumab plus ipilimumab therapy, they represented only 5% of the study population.

During his presentation, Dr. Motzer showed the median duration of therapy was 5.1 months in both groups, but only 57% of nivolumab plus ipilimumab patients completed all doses versus 89% of those assigned to placebo.

In addition, 33% of patients given nivolumab plus ipilimumab discontinued due to study drug toxicity and 29% had a treatment-related adverse event that led to treatment discontinuation. This compared with only 1% of patients for both outcomes with placebo.

The most common treatment-related adverse events in the combination therapy group were pruritus (27%), fatigue (25%), diarrhea (20%), rash (19%), hyperthyroidism (16%), and hypothyroidism (16%), and the vast majority of events were grade 1-2.

Dr. Motzer said that, following these negative results, they are “certainly digging deeper into the details to see which particular groups may have benefited and when toxicity occurred.

Then, more importantly, the team will look out for the results of Part B of the trial to assess the impact of nivolumab monotherapy. “I’m hoping it’s better tolerated,” he said.

Discussant James Larkin, MD, PhD, a consultant medical oncologist at The Royal Marsden, London, said the results from CheckMate 914 came “as a bit of a surprise.”

As did Dr. Motzer, Dr. Larkin singled out the high number of patients who could not complete the full dosing schedule and discontinued treatment.

He added that, while one has to be “cautious” when comparing trials, KEYNOTE-564 was “relatively similar” in design, and it’s “unlikely there’s any significant difference in activity” between the two drugs.

Dr. Larkin also believes data from Part B of CheckMate 914 will be “illuminating.”

There are nevertheless a number of outstanding questions about the results from Part A, he said, the main one being how to better select patients who might respond to the combination, which currently is not possible due to the lack of clinically relevant biomarkers.

The study was funded by Bristol Myers Squibb. Dr. Motzer has disclosed relationships with AstraZeneca, Aveo Pharmaceuticals, Bristol Myers Squibb, Eisai, EMD Serono, Exelixis, Genentech/Roche, Incyte, Lilly Oncology, Merck, Novartis, and Pfizer.

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

PARIS – New disappointing results from a trial of adjuvant immunotherapy for patients with renal cell carcinoma who underwent nephrectomy contrast with those from a previous trial that showed benefit with another agent.

The new results, from CheckMate 914, show that adjuvant treatment with the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) did not improve disease-free survival (DFS), compared with placebo.

The finding was presented at the annual meeting of the European Society for Medical Oncology.

CheckMate 914 “did not meet the primary endpoint,” study presenter Robert J. Motzer, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York, said at a press conference.

The results contrast with those seen with pembrolizumab (Keytruda) in the same setting, where the drug achieved a 32% reduction in risk of recurrence or death over placebo in KEYNOTE-564. This led to the U.S. Food and Drug Administration granting approval for the drug as adjuvant treatment following surgery in patients with renal cell carcinoma at intermediate or high risk for recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.

Another trial of adjuvant immunotherapy in renal cell carcinoma, also presented at ESMO 2022, the IMmotion010 trial with adjuvant atezolizumab (Tecentriq), also did not show any clinical benefit over placebo.

However, Dr. Motzer said that despite both of these new trials showing no benefit, “I don’t think it takes away from standard of care pembrolizumab” in this setting.

There is a great need for adjuvant therapy for patients who undergo surgery, Dr. Motzer commented. The standard treatment for stage I-III localized nonmetastatic renal cell carcinoma is radical or partial nephrectomy, but there remains a “substantial risk” of relapse after surgery, occurring in up to 50% of patients.

In the past, the standard of care for these patients would be watching and waiting and “hoping that the patient doesn’t relapse,” he said, and if they did, then “we would treat accordingly for metastatic disease.”
 

Differences between trials

When asked about the contrast between the latest trial with the adjuvant nivolumab-ipilimumab combination and the earlier trial with adjuvant pembrolizumab, Dr. Motzer told this news organization that there are differences in the designs of the two studies. “Although they are both global phase 2 trials ... [there are] some differences in the patient population.”

However, the “main differences” are the duration, intensity, and tolerability of the treatment regimens. “I suspect that’s impacted on the outcome of our trial,” he said, as “many of our patients didn’t complete even that 6 months of the more toxic immunotherapy [nivolumab-ipilimumab combination].”

Dr. Motzer also noted that, compared with the metastatic setting, patients “do not tolerate therapy as well” in the adjuvant setting. Consequently, the risk-benefit of a drug is “slightly different ... as we have to be much more concerned about toxicity.”

In addition, he said, “our trial also used these kind-of gross clinical features that were developed years ago” to select patients, but now “there’s other much more refined techniques” that look at the underlying biological signatures “to identify who responds to immunotherapy.”

“So I think we have to do a deep dive into the biology in this trial and in the Merck trial [of pembrolizumab] to see if we can better define who is going to relapse and who is going to benefit,” he said.

Commenting on the new results, Dominik Berthold, MD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, also wondered whether differences in trial design and study populations could explain the divergent results between the CheckMate and KEYNOTE trials.

“Investigators will need to look in detail at subpopulations and biomarkers to guide treatment decisions and trial design for current and future patients,” he added.

Dr. Berthold said he agrees that pembrolizumab remains standard of care, but “I’m not really sure that we have really to offer all patients” the drug.

He explained that, on the one hand, there is the risk of over-treating many patients, depending on their stage, and on the other hand, “many patients who get pembrolizumab actually do progress.”

In addition, there is the question of the treatment sequence in patients who are already exposed to immunotherapy and when to start tyrosine kinase inhibitors, as well as the much broader issue of the lack of long-term overall survival data with pembrolizumab.

Dr. Berthold noted the issue of whether the high treatment discontinuation rate in CheckMate 914 affected the efficacy of nivolumab plus ipilimumab raises the question of whether, from an immunological point of view, 1 year of pembrolizumab is more effective than 3 months of the combination therapy.

“I think it might be one of the explanations,” he said, adding, however, that these are just “hypotheses” at this stage.
 

Details of the new results

Previous results with the nivolumab-ipilimumab combination, from the CheckMate 214 trial in patients with advanced renal cell carcinoma, had demonstrated that upfront nivolumab plus ipilimumab offered significantly longer treatment-free survival than the VEGF inhibitor sunitinib. The “striking results” from that trial indicated the combination was not only associated with a survival benefit, but also “high response rates, durable responses, complete responses, and even treatment responses that continue after treatment is discontinued,” Dr. Motzer commented.

So his team set out to test the combination in the adjuvant setting in the CheckMate 914 trial, designed in two parts: Part A, comparing nivolumab plus ipilimumab with placebo, and Part B, adding nivolumab monotherapy as another comparator.

Reporting on Part A of the trial, Dr. Motzer explained that they included 816 patients with renal cell carcinoma who had undergone radical or partial nephrectomy with negative surgical margins and had a predominantly clear cell histology.

They also selected patients based on their pathologic TNM staging, choosing “high-risk” individuals, Dr. Motzer explained, but who nevertheless had no evidence of residual disease or distant metastases following nephrectomy.

Between 4 and 12 weeks after surgery, patients were randomized to receive 12 doses of nivolumab plus four doses of ipilimumab or matched placebos for an expected treatment duration of 24 weeks.

The median age of patients was 58-59 years, and approximately 71% were men. By far the most common type of surgery was radical nephrectomy, with 93%, and Dr. Motzer noted that most patients (77%-78%) had pT3 disease without nodal involvement.

After a median follow-up of 37.0 months, there was no significant difference between groups in the primary endpoint of DFS, as assessed by blinded independent central review.

Median DFS was not reached for nivolumab plus ipilimumab versus 50.7 months for placebo, at a hazard ratio of 0.92 (P = .5347). At 24 months, DFS was 76.4% with the combination therapy versus 74.0% for placebo.

Subgroup analysis did not reveal any patient groups that significantly benefitted from the combination therapy, although there was a signal of greater benefit in those with other than pT3 disease.

While tumors with sarcomatoid features appeared to have a significant benefit from nivolumab plus ipilimumab therapy, they represented only 5% of the study population.

During his presentation, Dr. Motzer showed the median duration of therapy was 5.1 months in both groups, but only 57% of nivolumab plus ipilimumab patients completed all doses versus 89% of those assigned to placebo.

In addition, 33% of patients given nivolumab plus ipilimumab discontinued due to study drug toxicity and 29% had a treatment-related adverse event that led to treatment discontinuation. This compared with only 1% of patients for both outcomes with placebo.

The most common treatment-related adverse events in the combination therapy group were pruritus (27%), fatigue (25%), diarrhea (20%), rash (19%), hyperthyroidism (16%), and hypothyroidism (16%), and the vast majority of events were grade 1-2.

Dr. Motzer said that, following these negative results, they are “certainly digging deeper into the details to see which particular groups may have benefited and when toxicity occurred.

Then, more importantly, the team will look out for the results of Part B of the trial to assess the impact of nivolumab monotherapy. “I’m hoping it’s better tolerated,” he said.

Discussant James Larkin, MD, PhD, a consultant medical oncologist at The Royal Marsden, London, said the results from CheckMate 914 came “as a bit of a surprise.”

As did Dr. Motzer, Dr. Larkin singled out the high number of patients who could not complete the full dosing schedule and discontinued treatment.

He added that, while one has to be “cautious” when comparing trials, KEYNOTE-564 was “relatively similar” in design, and it’s “unlikely there’s any significant difference in activity” between the two drugs.

Dr. Larkin also believes data from Part B of CheckMate 914 will be “illuminating.”

There are nevertheless a number of outstanding questions about the results from Part A, he said, the main one being how to better select patients who might respond to the combination, which currently is not possible due to the lack of clinically relevant biomarkers.

The study was funded by Bristol Myers Squibb. Dr. Motzer has disclosed relationships with AstraZeneca, Aveo Pharmaceuticals, Bristol Myers Squibb, Eisai, EMD Serono, Exelixis, Genentech/Roche, Incyte, Lilly Oncology, Merck, Novartis, and Pfizer.

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

PARIS – New disappointing results from a trial of adjuvant immunotherapy for patients with renal cell carcinoma who underwent nephrectomy contrast with those from a previous trial that showed benefit with another agent.

The new results, from CheckMate 914, show that adjuvant treatment with the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) did not improve disease-free survival (DFS), compared with placebo.

The finding was presented at the annual meeting of the European Society for Medical Oncology.

CheckMate 914 “did not meet the primary endpoint,” study presenter Robert J. Motzer, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York, said at a press conference.

The results contrast with those seen with pembrolizumab (Keytruda) in the same setting, where the drug achieved a 32% reduction in risk of recurrence or death over placebo in KEYNOTE-564. This led to the U.S. Food and Drug Administration granting approval for the drug as adjuvant treatment following surgery in patients with renal cell carcinoma at intermediate or high risk for recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.

Another trial of adjuvant immunotherapy in renal cell carcinoma, also presented at ESMO 2022, the IMmotion010 trial with adjuvant atezolizumab (Tecentriq), also did not show any clinical benefit over placebo.

However, Dr. Motzer said that despite both of these new trials showing no benefit, “I don’t think it takes away from standard of care pembrolizumab” in this setting.

There is a great need for adjuvant therapy for patients who undergo surgery, Dr. Motzer commented. The standard treatment for stage I-III localized nonmetastatic renal cell carcinoma is radical or partial nephrectomy, but there remains a “substantial risk” of relapse after surgery, occurring in up to 50% of patients.

In the past, the standard of care for these patients would be watching and waiting and “hoping that the patient doesn’t relapse,” he said, and if they did, then “we would treat accordingly for metastatic disease.”
 

Differences between trials

When asked about the contrast between the latest trial with the adjuvant nivolumab-ipilimumab combination and the earlier trial with adjuvant pembrolizumab, Dr. Motzer told this news organization that there are differences in the designs of the two studies. “Although they are both global phase 2 trials ... [there are] some differences in the patient population.”

However, the “main differences” are the duration, intensity, and tolerability of the treatment regimens. “I suspect that’s impacted on the outcome of our trial,” he said, as “many of our patients didn’t complete even that 6 months of the more toxic immunotherapy [nivolumab-ipilimumab combination].”

Dr. Motzer also noted that, compared with the metastatic setting, patients “do not tolerate therapy as well” in the adjuvant setting. Consequently, the risk-benefit of a drug is “slightly different ... as we have to be much more concerned about toxicity.”

In addition, he said, “our trial also used these kind-of gross clinical features that were developed years ago” to select patients, but now “there’s other much more refined techniques” that look at the underlying biological signatures “to identify who responds to immunotherapy.”

“So I think we have to do a deep dive into the biology in this trial and in the Merck trial [of pembrolizumab] to see if we can better define who is going to relapse and who is going to benefit,” he said.

Commenting on the new results, Dominik Berthold, MD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, also wondered whether differences in trial design and study populations could explain the divergent results between the CheckMate and KEYNOTE trials.

“Investigators will need to look in detail at subpopulations and biomarkers to guide treatment decisions and trial design for current and future patients,” he added.

Dr. Berthold said he agrees that pembrolizumab remains standard of care, but “I’m not really sure that we have really to offer all patients” the drug.

He explained that, on the one hand, there is the risk of over-treating many patients, depending on their stage, and on the other hand, “many patients who get pembrolizumab actually do progress.”

In addition, there is the question of the treatment sequence in patients who are already exposed to immunotherapy and when to start tyrosine kinase inhibitors, as well as the much broader issue of the lack of long-term overall survival data with pembrolizumab.

Dr. Berthold noted the issue of whether the high treatment discontinuation rate in CheckMate 914 affected the efficacy of nivolumab plus ipilimumab raises the question of whether, from an immunological point of view, 1 year of pembrolizumab is more effective than 3 months of the combination therapy.

“I think it might be one of the explanations,” he said, adding, however, that these are just “hypotheses” at this stage.
 

Details of the new results

Previous results with the nivolumab-ipilimumab combination, from the CheckMate 214 trial in patients with advanced renal cell carcinoma, had demonstrated that upfront nivolumab plus ipilimumab offered significantly longer treatment-free survival than the VEGF inhibitor sunitinib. The “striking results” from that trial indicated the combination was not only associated with a survival benefit, but also “high response rates, durable responses, complete responses, and even treatment responses that continue after treatment is discontinued,” Dr. Motzer commented.

So his team set out to test the combination in the adjuvant setting in the CheckMate 914 trial, designed in two parts: Part A, comparing nivolumab plus ipilimumab with placebo, and Part B, adding nivolumab monotherapy as another comparator.

Reporting on Part A of the trial, Dr. Motzer explained that they included 816 patients with renal cell carcinoma who had undergone radical or partial nephrectomy with negative surgical margins and had a predominantly clear cell histology.

They also selected patients based on their pathologic TNM staging, choosing “high-risk” individuals, Dr. Motzer explained, but who nevertheless had no evidence of residual disease or distant metastases following nephrectomy.

Between 4 and 12 weeks after surgery, patients were randomized to receive 12 doses of nivolumab plus four doses of ipilimumab or matched placebos for an expected treatment duration of 24 weeks.

The median age of patients was 58-59 years, and approximately 71% were men. By far the most common type of surgery was radical nephrectomy, with 93%, and Dr. Motzer noted that most patients (77%-78%) had pT3 disease without nodal involvement.

After a median follow-up of 37.0 months, there was no significant difference between groups in the primary endpoint of DFS, as assessed by blinded independent central review.

Median DFS was not reached for nivolumab plus ipilimumab versus 50.7 months for placebo, at a hazard ratio of 0.92 (P = .5347). At 24 months, DFS was 76.4% with the combination therapy versus 74.0% for placebo.

Subgroup analysis did not reveal any patient groups that significantly benefitted from the combination therapy, although there was a signal of greater benefit in those with other than pT3 disease.

While tumors with sarcomatoid features appeared to have a significant benefit from nivolumab plus ipilimumab therapy, they represented only 5% of the study population.

During his presentation, Dr. Motzer showed the median duration of therapy was 5.1 months in both groups, but only 57% of nivolumab plus ipilimumab patients completed all doses versus 89% of those assigned to placebo.

In addition, 33% of patients given nivolumab plus ipilimumab discontinued due to study drug toxicity and 29% had a treatment-related adverse event that led to treatment discontinuation. This compared with only 1% of patients for both outcomes with placebo.

The most common treatment-related adverse events in the combination therapy group were pruritus (27%), fatigue (25%), diarrhea (20%), rash (19%), hyperthyroidism (16%), and hypothyroidism (16%), and the vast majority of events were grade 1-2.

Dr. Motzer said that, following these negative results, they are “certainly digging deeper into the details to see which particular groups may have benefited and when toxicity occurred.

Then, more importantly, the team will look out for the results of Part B of the trial to assess the impact of nivolumab monotherapy. “I’m hoping it’s better tolerated,” he said.

Discussant James Larkin, MD, PhD, a consultant medical oncologist at The Royal Marsden, London, said the results from CheckMate 914 came “as a bit of a surprise.”

As did Dr. Motzer, Dr. Larkin singled out the high number of patients who could not complete the full dosing schedule and discontinued treatment.

He added that, while one has to be “cautious” when comparing trials, KEYNOTE-564 was “relatively similar” in design, and it’s “unlikely there’s any significant difference in activity” between the two drugs.

Dr. Larkin also believes data from Part B of CheckMate 914 will be “illuminating.”

There are nevertheless a number of outstanding questions about the results from Part A, he said, the main one being how to better select patients who might respond to the combination, which currently is not possible due to the lack of clinically relevant biomarkers.

The study was funded by Bristol Myers Squibb. Dr. Motzer has disclosed relationships with AstraZeneca, Aveo Pharmaceuticals, Bristol Myers Squibb, Eisai, EMD Serono, Exelixis, Genentech/Roche, Incyte, Lilly Oncology, Merck, Novartis, and Pfizer.

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

Bariatric surgery may raise the risk of developing epilepsy, new research suggests. Analyzing health records, investigators compared almost 17,000 patients who had undergone bariatric surgery with more than 620,000 individuals with obesity who had not undergone the surgery.

During a minimum 3-year follow-up period, the surgery group had a 45% higher risk of developing epilepsy than the nonsurgery group. Moreover, patients who had a stroke after their bariatric surgery were 14 times more likely to develop epilepsy than those who did not have a stroke.

“When considering having bariatric surgery, people should talk to their doctors about the benefits and risks,” senior investigator Jorge Burneo, MD, professor of neurology, biostatistics, and epidemiology and endowed chair in epilepsy at Western University, London, told this news organization.

“While there are many health benefits of weight loss, our findings suggest that epilepsy is a long-term risk of bariatric surgery for weight loss,” Dr. Burneo said.

The findings were published online in Neurology.
 

Unrecognized risk factor?

Bariatric surgery has become more common as global rates of obesity have increased. The surgery has been shown to reduce the risk for serious obesity-related conditions, the researchers note.

However, “in addition to the positive outcomes of bariatric surgery, several long-term neurological complications have also been identified,” they write.

One previous study reported increased epilepsy risk following gastric bypass. Those findings “suggest that bariatric surgery may be an unrecognized epilepsy risk factor; however, this possible association has not been thoroughly explored,” write the investigators.

Dr. Burneo said he conducted the study because he has seen patients with epilepsy in his clinic who were “without risk factors, with normal MRIs, who shared the history of having bariatric surgery before the development of epilepsy.”

The researchers’ primary objective was to “assess whether epilepsy risk is elevated following bariatric surgery for weight loss relative to a nonsurgical cohort of patients who are obese,” he noted.

The study used linked administrative health databases in Ontario, Canada. Patients were accrued from July 1, 2010, to Dec. 31, 2016, and were followed until Dec. 31, 2019. The analysis included 639,472 participants, 2.7% of whom had undergone bariatric surgery.

The “exposed” cohort consisted of all Ontario residents aged 18 years or older who had undergone bariatric surgery during the 6-year period (n = 16,958; 65.1% women; mean age, 47.4 years), while the “unexposed” cohort consisted of patients hospitalized with a diagnosis of obesity who had not undergone bariatric surgery (n = 622,514; 62.8% women; mean age, 47.6 years).

Patients with a history of seizures, epilepsy, epilepsy risk factors, prior brain surgery, psychiatric disorders, or drug or alcohol abuse/dependence were excluded from the analysis.

The researchers collected data on patients’ sociodemographic characteristics at the index date, as well as Charlson Comorbidity Index scores during the 2 years prior to index, and data regarding several specific comorbidities, such as diabetes mellitus, hypertension, sleep apnea, depression/anxiety, and cardiovascular factors.

The exposed and unexposed cohorts were followed for a median period of 5.8 and 5.9 person-years, respectively.
 

‘Unclear’ mechanisms

Before weighting, 0.4% of participants in the exposed cohort (n = 73) developed epilepsy, versus 0.2% of participants in the unexposed cohort (n = 1,260) by the end of the follow-up period.

In the weighted cohorts, there were 50.1 epilepsy diagnoses per 100,000 person-years, versus 34.1 per 100,000 person-years (rate difference, 16 per 100,000 person-years).

The multivariable analysis of the weighted cohort showed the hazard ratio for epilepsy cases that were associated with bariatric surgery was 1.45 (95% confidence interval, 1.35-1.56), after adjusting for sleep apnea and including stroke as a time-varying covariate.

Having a stroke during the follow-up period increased epilepsy 14-fold in the exposed cohort (HR, 14.03; 95% CI, 4.25-46.25).

The investigators note that they were unable to measure obesity status or body mass index throughout the study and that some obesity-related comorbidities “may affect epilepsy risk.”

In addition, Dr. Burneo reported that the study did not investigate potential causes and mechanisms of the association between bariatric surgery and epilepsy risk.

Hypotheses “include potential nutritional deficiencies, receipt of general anesthesia, or other unclear causes,” he said.

“Future research should investigate epilepsy as a potential long-term complication of bariatric surgery, exploring the possible effects of this procedure,” Dr. Burneo added.
 

Risk-benefit discussion

In a comment, Jacqueline French, MD, professor of neurology at NYU Grossman School of Medicine, and director of NYU’s Epilepsy Study Consortium, said she was “not 100% surprised by the findings” because she has seen in her clinical practice “a number of patients who developed epilepsy after bariatric surgery or had a history of bariatric surgery at the time they developed epilepsy.”

On the other hand, she has also seen patients who did not have a history of bariatric surgery and who developed epilepsy.

“I’m unable to tell if there is an association, although I’ve had it at the back of my head as a thought and wondered about it,” said Dr. French, who is also the chief medical and innovation officer at the Epilepsy Foundation. She was not involved with the study.

She noted that possible mechanisms underlying the association are that gastric bypass surgery leads to a “significant alteration” in nutrient absorption. Moreover, “we now know that the microbiome is associated with epilepsy” and that changes occur in the gut microbiome after bariatric surgery, Dr. French said.

There are two take-home messages for practicing clinicians, she added.

“Although the risk [of developing epilepsy] is very low, it should be presented as part of the risks and benefits to patients considering bariatric surgery,” she said.

“It’s equally important to follow up on the potential differences in these patients who go on to develop epilepsy following bariatric surgery,” said Dr. French. “Is there a certain metabolic profile or some nutrient previously absorbed that now is not absorbed that might predispose people to risk?”

This would be “enormously important to know because it might not just pertain to these people but to a whole other cohort of people who develop epilepsy,” Dr. French concluded.

The study was funded by the Ontario Ministry of Health and Ministry of Long-Term Care and by the Jack Cowin Endowed Chair in Epilepsy Research at Western University. Dr. Burneo holds the Jack Cowin Endowed Chair in Epilepsy Research at Western University. The other investigators and Dr. French have reported no relevant financial relationships.

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

Bariatric surgery may raise the risk of developing epilepsy, new research suggests. Analyzing health records, investigators compared almost 17,000 patients who had undergone bariatric surgery with more than 620,000 individuals with obesity who had not undergone the surgery.

During a minimum 3-year follow-up period, the surgery group had a 45% higher risk of developing epilepsy than the nonsurgery group. Moreover, patients who had a stroke after their bariatric surgery were 14 times more likely to develop epilepsy than those who did not have a stroke.

“When considering having bariatric surgery, people should talk to their doctors about the benefits and risks,” senior investigator Jorge Burneo, MD, professor of neurology, biostatistics, and epidemiology and endowed chair in epilepsy at Western University, London, told this news organization.

“While there are many health benefits of weight loss, our findings suggest that epilepsy is a long-term risk of bariatric surgery for weight loss,” Dr. Burneo said.

The findings were published online in Neurology.
 

Unrecognized risk factor?

Bariatric surgery has become more common as global rates of obesity have increased. The surgery has been shown to reduce the risk for serious obesity-related conditions, the researchers note.

However, “in addition to the positive outcomes of bariatric surgery, several long-term neurological complications have also been identified,” they write.

One previous study reported increased epilepsy risk following gastric bypass. Those findings “suggest that bariatric surgery may be an unrecognized epilepsy risk factor; however, this possible association has not been thoroughly explored,” write the investigators.

Dr. Burneo said he conducted the study because he has seen patients with epilepsy in his clinic who were “without risk factors, with normal MRIs, who shared the history of having bariatric surgery before the development of epilepsy.”

The researchers’ primary objective was to “assess whether epilepsy risk is elevated following bariatric surgery for weight loss relative to a nonsurgical cohort of patients who are obese,” he noted.

The study used linked administrative health databases in Ontario, Canada. Patients were accrued from July 1, 2010, to Dec. 31, 2016, and were followed until Dec. 31, 2019. The analysis included 639,472 participants, 2.7% of whom had undergone bariatric surgery.

The “exposed” cohort consisted of all Ontario residents aged 18 years or older who had undergone bariatric surgery during the 6-year period (n = 16,958; 65.1% women; mean age, 47.4 years), while the “unexposed” cohort consisted of patients hospitalized with a diagnosis of obesity who had not undergone bariatric surgery (n = 622,514; 62.8% women; mean age, 47.6 years).

Patients with a history of seizures, epilepsy, epilepsy risk factors, prior brain surgery, psychiatric disorders, or drug or alcohol abuse/dependence were excluded from the analysis.

The researchers collected data on patients’ sociodemographic characteristics at the index date, as well as Charlson Comorbidity Index scores during the 2 years prior to index, and data regarding several specific comorbidities, such as diabetes mellitus, hypertension, sleep apnea, depression/anxiety, and cardiovascular factors.

The exposed and unexposed cohorts were followed for a median period of 5.8 and 5.9 person-years, respectively.
 

‘Unclear’ mechanisms

Before weighting, 0.4% of participants in the exposed cohort (n = 73) developed epilepsy, versus 0.2% of participants in the unexposed cohort (n = 1,260) by the end of the follow-up period.

In the weighted cohorts, there were 50.1 epilepsy diagnoses per 100,000 person-years, versus 34.1 per 100,000 person-years (rate difference, 16 per 100,000 person-years).

The multivariable analysis of the weighted cohort showed the hazard ratio for epilepsy cases that were associated with bariatric surgery was 1.45 (95% confidence interval, 1.35-1.56), after adjusting for sleep apnea and including stroke as a time-varying covariate.

Having a stroke during the follow-up period increased epilepsy 14-fold in the exposed cohort (HR, 14.03; 95% CI, 4.25-46.25).

The investigators note that they were unable to measure obesity status or body mass index throughout the study and that some obesity-related comorbidities “may affect epilepsy risk.”

In addition, Dr. Burneo reported that the study did not investigate potential causes and mechanisms of the association between bariatric surgery and epilepsy risk.

Hypotheses “include potential nutritional deficiencies, receipt of general anesthesia, or other unclear causes,” he said.

“Future research should investigate epilepsy as a potential long-term complication of bariatric surgery, exploring the possible effects of this procedure,” Dr. Burneo added.
 

Risk-benefit discussion

In a comment, Jacqueline French, MD, professor of neurology at NYU Grossman School of Medicine, and director of NYU’s Epilepsy Study Consortium, said she was “not 100% surprised by the findings” because she has seen in her clinical practice “a number of patients who developed epilepsy after bariatric surgery or had a history of bariatric surgery at the time they developed epilepsy.”

On the other hand, she has also seen patients who did not have a history of bariatric surgery and who developed epilepsy.

“I’m unable to tell if there is an association, although I’ve had it at the back of my head as a thought and wondered about it,” said Dr. French, who is also the chief medical and innovation officer at the Epilepsy Foundation. She was not involved with the study.

She noted that possible mechanisms underlying the association are that gastric bypass surgery leads to a “significant alteration” in nutrient absorption. Moreover, “we now know that the microbiome is associated with epilepsy” and that changes occur in the gut microbiome after bariatric surgery, Dr. French said.

There are two take-home messages for practicing clinicians, she added.

“Although the risk [of developing epilepsy] is very low, it should be presented as part of the risks and benefits to patients considering bariatric surgery,” she said.

“It’s equally important to follow up on the potential differences in these patients who go on to develop epilepsy following bariatric surgery,” said Dr. French. “Is there a certain metabolic profile or some nutrient previously absorbed that now is not absorbed that might predispose people to risk?”

This would be “enormously important to know because it might not just pertain to these people but to a whole other cohort of people who develop epilepsy,” Dr. French concluded.

The study was funded by the Ontario Ministry of Health and Ministry of Long-Term Care and by the Jack Cowin Endowed Chair in Epilepsy Research at Western University. Dr. Burneo holds the Jack Cowin Endowed Chair in Epilepsy Research at Western University. The other investigators and Dr. French have reported no relevant financial relationships.

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

Bariatric surgery may raise the risk of developing epilepsy, new research suggests. Analyzing health records, investigators compared almost 17,000 patients who had undergone bariatric surgery with more than 620,000 individuals with obesity who had not undergone the surgery.

During a minimum 3-year follow-up period, the surgery group had a 45% higher risk of developing epilepsy than the nonsurgery group. Moreover, patients who had a stroke after their bariatric surgery were 14 times more likely to develop epilepsy than those who did not have a stroke.

“When considering having bariatric surgery, people should talk to their doctors about the benefits and risks,” senior investigator Jorge Burneo, MD, professor of neurology, biostatistics, and epidemiology and endowed chair in epilepsy at Western University, London, told this news organization.

“While there are many health benefits of weight loss, our findings suggest that epilepsy is a long-term risk of bariatric surgery for weight loss,” Dr. Burneo said.

The findings were published online in Neurology.
 

Unrecognized risk factor?

Bariatric surgery has become more common as global rates of obesity have increased. The surgery has been shown to reduce the risk for serious obesity-related conditions, the researchers note.

However, “in addition to the positive outcomes of bariatric surgery, several long-term neurological complications have also been identified,” they write.

One previous study reported increased epilepsy risk following gastric bypass. Those findings “suggest that bariatric surgery may be an unrecognized epilepsy risk factor; however, this possible association has not been thoroughly explored,” write the investigators.

Dr. Burneo said he conducted the study because he has seen patients with epilepsy in his clinic who were “without risk factors, with normal MRIs, who shared the history of having bariatric surgery before the development of epilepsy.”

The researchers’ primary objective was to “assess whether epilepsy risk is elevated following bariatric surgery for weight loss relative to a nonsurgical cohort of patients who are obese,” he noted.

The study used linked administrative health databases in Ontario, Canada. Patients were accrued from July 1, 2010, to Dec. 31, 2016, and were followed until Dec. 31, 2019. The analysis included 639,472 participants, 2.7% of whom had undergone bariatric surgery.

The “exposed” cohort consisted of all Ontario residents aged 18 years or older who had undergone bariatric surgery during the 6-year period (n = 16,958; 65.1% women; mean age, 47.4 years), while the “unexposed” cohort consisted of patients hospitalized with a diagnosis of obesity who had not undergone bariatric surgery (n = 622,514; 62.8% women; mean age, 47.6 years).

Patients with a history of seizures, epilepsy, epilepsy risk factors, prior brain surgery, psychiatric disorders, or drug or alcohol abuse/dependence were excluded from the analysis.

The researchers collected data on patients’ sociodemographic characteristics at the index date, as well as Charlson Comorbidity Index scores during the 2 years prior to index, and data regarding several specific comorbidities, such as diabetes mellitus, hypertension, sleep apnea, depression/anxiety, and cardiovascular factors.

The exposed and unexposed cohorts were followed for a median period of 5.8 and 5.9 person-years, respectively.
 

‘Unclear’ mechanisms

Before weighting, 0.4% of participants in the exposed cohort (n = 73) developed epilepsy, versus 0.2% of participants in the unexposed cohort (n = 1,260) by the end of the follow-up period.

In the weighted cohorts, there were 50.1 epilepsy diagnoses per 100,000 person-years, versus 34.1 per 100,000 person-years (rate difference, 16 per 100,000 person-years).

The multivariable analysis of the weighted cohort showed the hazard ratio for epilepsy cases that were associated with bariatric surgery was 1.45 (95% confidence interval, 1.35-1.56), after adjusting for sleep apnea and including stroke as a time-varying covariate.

Having a stroke during the follow-up period increased epilepsy 14-fold in the exposed cohort (HR, 14.03; 95% CI, 4.25-46.25).

The investigators note that they were unable to measure obesity status or body mass index throughout the study and that some obesity-related comorbidities “may affect epilepsy risk.”

In addition, Dr. Burneo reported that the study did not investigate potential causes and mechanisms of the association between bariatric surgery and epilepsy risk.

Hypotheses “include potential nutritional deficiencies, receipt of general anesthesia, or other unclear causes,” he said.

“Future research should investigate epilepsy as a potential long-term complication of bariatric surgery, exploring the possible effects of this procedure,” Dr. Burneo added.
 

Risk-benefit discussion

In a comment, Jacqueline French, MD, professor of neurology at NYU Grossman School of Medicine, and director of NYU’s Epilepsy Study Consortium, said she was “not 100% surprised by the findings” because she has seen in her clinical practice “a number of patients who developed epilepsy after bariatric surgery or had a history of bariatric surgery at the time they developed epilepsy.”

On the other hand, she has also seen patients who did not have a history of bariatric surgery and who developed epilepsy.

“I’m unable to tell if there is an association, although I’ve had it at the back of my head as a thought and wondered about it,” said Dr. French, who is also the chief medical and innovation officer at the Epilepsy Foundation. She was not involved with the study.

She noted that possible mechanisms underlying the association are that gastric bypass surgery leads to a “significant alteration” in nutrient absorption. Moreover, “we now know that the microbiome is associated with epilepsy” and that changes occur in the gut microbiome after bariatric surgery, Dr. French said.

There are two take-home messages for practicing clinicians, she added.

“Although the risk [of developing epilepsy] is very low, it should be presented as part of the risks and benefits to patients considering bariatric surgery,” she said.

“It’s equally important to follow up on the potential differences in these patients who go on to develop epilepsy following bariatric surgery,” said Dr. French. “Is there a certain metabolic profile or some nutrient previously absorbed that now is not absorbed that might predispose people to risk?”

This would be “enormously important to know because it might not just pertain to these people but to a whole other cohort of people who develop epilepsy,” Dr. French concluded.

The study was funded by the Ontario Ministry of Health and Ministry of Long-Term Care and by the Jack Cowin Endowed Chair in Epilepsy Research at Western University. Dr. Burneo holds the Jack Cowin Endowed Chair in Epilepsy Research at Western University. The other investigators and Dr. French have reported no relevant financial relationships.

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

Some pediatricians believe that molluscum contagiosum (MC) should not be treated because they usually self-resolve in 6-18 months, but Rebecca Smith, MD, sees things differently.

“If you don’t treat them, they’re going to spread,” Dr. Smith, who practices dermatology in Fort Mill, S.C., said at Medscape Live’s annual Coastal Dermatology Symposium. “They’re going to be itchy, they can spread on the patient themselves and then to others, and they can cause scarring. The prevalence is anywhere from 5% to 11%. That means there are 6 million patients out there, just waiting to come into your clinics.”

To date, no treatment has been approved by the Food and Drug Administration for MC, although a laundry list of agents have been tried, including cantharidin; cryotherapy; curettage with and without imiquimod; sinecatechins ointment, 15%; imiquimod; and retinoids. And there are several treatments that are being investigated.

A 2017 Cochrane review of 22 studies involving 1,650 patients demonstrated that no single intervention has been consistently effective in treating MC. “Most of the studies were actually very low quality,” said Dr. Smith, who was not involved with the analysis. “The one high quality study showed that imiquimod did not work any better than its vehicle.”
 

Investigational treatments

One of the products in the pipeline is VP-102, a proprietary drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, which has been evaluated in phase 3 studies of patients with molluscum aged 2 years and older. It features a visualization agent so that the person applying the drug can see which lesions have been treated. It also contains a bittering agent to mitigate oral ingestion by children.

Courtesy Dr. Sarah Cipriano

VP-102, which is being developed by Verrica Pharmaceuticals, is applied once every 21 days in up to 4 applications, and multiple lesions can be treated with one applicator. “It’s a stable concentration with a good shelf life, and two phase 3 randomized studies have shown about a 50% complete clearance of new and existing lesions at day 84,” Dr. Smith said. Those studies enrolled children and adults.

A separate analysis of the same data presented at a meeting in 2019 showed that 77% of patients treated with VP-102 achieved greater than 75% clearance, while 65.8% achieved more than 90% clearance.

The new kid on the block is a gel formulation of a nitric oxide–releasing medication, berdazimer 10.3%, a first-in-class topical treatment being developed by Novan, which can be applied at home. In a multicenter study published in JAMA Dermatology, researchers randomized 444 patients to berdazimer gel 10.3% and 447 to a placebo gel, applied once daily in a thin layer on all MC lesions for 12 weeks. The study was conducted at 55 clinics across the United States between Sept. 1, 2020, and July 21, 2021. The mean age of the patients was about 6.5 years and participants had 3-70 raised MC lesions; those with sexually transmitted MC or MC in the periocular area were excluded. The primary endpoint was complete clearance of MC lesions after 12 weeks of treatment.

At 12 weeks, significantly more patients treated with berdazimer gel achieved complete clearance than those on vehicle (32.4% vs. 19.7%; P < .001). A total of 64 (14.4%) patients in the berdazimer group discontinued treatment because of MC clearance, compared with 40 patients (8.9%) in the vehicle group.

More recently, investigators evaluated autoinoculation vs. 35% trichloroacetic acid (TCA) for the treatment of MC. Autoinoculation involves puncturing the perilesional and lesional skin 5-7 times with an insulin syringe. “This gets a little bit of the virus into the dermis, and you hope to elicit an immune response,” explained Dr. Smith, who was not involved with the study. At 3 months, 80% of patients in the autoinoculation group achieved complete clearance, compared with 62% of those in the TCA group, while recurrence at 6 months was 3% vs. 40%, respectively.

Manual extraction of MC lesions is another option. “I love to pop the cores out with my thumbs,” Dr. Smith said. “You have to pick the patients who can tolerate this, and the MC lesions need to be ripe and ready.”

For ophthalmic lesions, watchful waiting is advisable unless the MC lesions are symptomatic or bothersome or large lesions form on the lid margin, which may cause ocular irritation or even a corneal abrasion. “If a patient presents with a multisite infection that includes ocular lesions, treat lesions on other parts of the body and keep your fingers crossed that a systemic immune response occurs,” she said.

The desired immune response is known as the “BOTE” sign (the beginning of the end), which heralds the clearance of the molluscum infection. This often appears as reddening of all the MC lesions and occasionally as a granulomatous “id-like” reaction especially on the extensor elbows and knees. “When this happens, it often scares the patients,” Dr. Smith said. But she explains that this is a positive development, and that “this means that the lesions are about to self-resolve.”

Dr. Smith disclosed that she serves as a speaker or a member of the speakers bureau for Amgen, CeraVe, EPI, Galderma, InCyte, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Sun. She also serves as an advisor or consultant for Janssen, Lilly, Regeneron, and Sanofi Genzyme.

Medscape Live and this news organization are owned by the same parent company.

Some pediatricians believe that molluscum contagiosum (MC) should not be treated because they usually self-resolve in 6-18 months, but Rebecca Smith, MD, sees things differently.

“If you don’t treat them, they’re going to spread,” Dr. Smith, who practices dermatology in Fort Mill, S.C., said at Medscape Live’s annual Coastal Dermatology Symposium. “They’re going to be itchy, they can spread on the patient themselves and then to others, and they can cause scarring. The prevalence is anywhere from 5% to 11%. That means there are 6 million patients out there, just waiting to come into your clinics.”

To date, no treatment has been approved by the Food and Drug Administration for MC, although a laundry list of agents have been tried, including cantharidin; cryotherapy; curettage with and without imiquimod; sinecatechins ointment, 15%; imiquimod; and retinoids. And there are several treatments that are being investigated.

A 2017 Cochrane review of 22 studies involving 1,650 patients demonstrated that no single intervention has been consistently effective in treating MC. “Most of the studies were actually very low quality,” said Dr. Smith, who was not involved with the analysis. “The one high quality study showed that imiquimod did not work any better than its vehicle.”
 

Investigational treatments

One of the products in the pipeline is VP-102, a proprietary drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, which has been evaluated in phase 3 studies of patients with molluscum aged 2 years and older. It features a visualization agent so that the person applying the drug can see which lesions have been treated. It also contains a bittering agent to mitigate oral ingestion by children.

Courtesy Dr. Sarah Cipriano

VP-102, which is being developed by Verrica Pharmaceuticals, is applied once every 21 days in up to 4 applications, and multiple lesions can be treated with one applicator. “It’s a stable concentration with a good shelf life, and two phase 3 randomized studies have shown about a 50% complete clearance of new and existing lesions at day 84,” Dr. Smith said. Those studies enrolled children and adults.

A separate analysis of the same data presented at a meeting in 2019 showed that 77% of patients treated with VP-102 achieved greater than 75% clearance, while 65.8% achieved more than 90% clearance.

The new kid on the block is a gel formulation of a nitric oxide–releasing medication, berdazimer 10.3%, a first-in-class topical treatment being developed by Novan, which can be applied at home. In a multicenter study published in JAMA Dermatology, researchers randomized 444 patients to berdazimer gel 10.3% and 447 to a placebo gel, applied once daily in a thin layer on all MC lesions for 12 weeks. The study was conducted at 55 clinics across the United States between Sept. 1, 2020, and July 21, 2021. The mean age of the patients was about 6.5 years and participants had 3-70 raised MC lesions; those with sexually transmitted MC or MC in the periocular area were excluded. The primary endpoint was complete clearance of MC lesions after 12 weeks of treatment.

At 12 weeks, significantly more patients treated with berdazimer gel achieved complete clearance than those on vehicle (32.4% vs. 19.7%; P < .001). A total of 64 (14.4%) patients in the berdazimer group discontinued treatment because of MC clearance, compared with 40 patients (8.9%) in the vehicle group.

More recently, investigators evaluated autoinoculation vs. 35% trichloroacetic acid (TCA) for the treatment of MC. Autoinoculation involves puncturing the perilesional and lesional skin 5-7 times with an insulin syringe. “This gets a little bit of the virus into the dermis, and you hope to elicit an immune response,” explained Dr. Smith, who was not involved with the study. At 3 months, 80% of patients in the autoinoculation group achieved complete clearance, compared with 62% of those in the TCA group, while recurrence at 6 months was 3% vs. 40%, respectively.

Manual extraction of MC lesions is another option. “I love to pop the cores out with my thumbs,” Dr. Smith said. “You have to pick the patients who can tolerate this, and the MC lesions need to be ripe and ready.”

For ophthalmic lesions, watchful waiting is advisable unless the MC lesions are symptomatic or bothersome or large lesions form on the lid margin, which may cause ocular irritation or even a corneal abrasion. “If a patient presents with a multisite infection that includes ocular lesions, treat lesions on other parts of the body and keep your fingers crossed that a systemic immune response occurs,” she said.

The desired immune response is known as the “BOTE” sign (the beginning of the end), which heralds the clearance of the molluscum infection. This often appears as reddening of all the MC lesions and occasionally as a granulomatous “id-like” reaction especially on the extensor elbows and knees. “When this happens, it often scares the patients,” Dr. Smith said. But she explains that this is a positive development, and that “this means that the lesions are about to self-resolve.”

Dr. Smith disclosed that she serves as a speaker or a member of the speakers bureau for Amgen, CeraVe, EPI, Galderma, InCyte, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Sun. She also serves as an advisor or consultant for Janssen, Lilly, Regeneron, and Sanofi Genzyme.

Medscape Live and this news organization are owned by the same parent company.

Some pediatricians believe that molluscum contagiosum (MC) should not be treated because they usually self-resolve in 6-18 months, but Rebecca Smith, MD, sees things differently.

“If you don’t treat them, they’re going to spread,” Dr. Smith, who practices dermatology in Fort Mill, S.C., said at Medscape Live’s annual Coastal Dermatology Symposium. “They’re going to be itchy, they can spread on the patient themselves and then to others, and they can cause scarring. The prevalence is anywhere from 5% to 11%. That means there are 6 million patients out there, just waiting to come into your clinics.”

To date, no treatment has been approved by the Food and Drug Administration for MC, although a laundry list of agents have been tried, including cantharidin; cryotherapy; curettage with and without imiquimod; sinecatechins ointment, 15%; imiquimod; and retinoids. And there are several treatments that are being investigated.

A 2017 Cochrane review of 22 studies involving 1,650 patients demonstrated that no single intervention has been consistently effective in treating MC. “Most of the studies were actually very low quality,” said Dr. Smith, who was not involved with the analysis. “The one high quality study showed that imiquimod did not work any better than its vehicle.”
 

Investigational treatments

One of the products in the pipeline is VP-102, a proprietary drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, which has been evaluated in phase 3 studies of patients with molluscum aged 2 years and older. It features a visualization agent so that the person applying the drug can see which lesions have been treated. It also contains a bittering agent to mitigate oral ingestion by children.

Courtesy Dr. Sarah Cipriano

VP-102, which is being developed by Verrica Pharmaceuticals, is applied once every 21 days in up to 4 applications, and multiple lesions can be treated with one applicator. “It’s a stable concentration with a good shelf life, and two phase 3 randomized studies have shown about a 50% complete clearance of new and existing lesions at day 84,” Dr. Smith said. Those studies enrolled children and adults.

A separate analysis of the same data presented at a meeting in 2019 showed that 77% of patients treated with VP-102 achieved greater than 75% clearance, while 65.8% achieved more than 90% clearance.

The new kid on the block is a gel formulation of a nitric oxide–releasing medication, berdazimer 10.3%, a first-in-class topical treatment being developed by Novan, which can be applied at home. In a multicenter study published in JAMA Dermatology, researchers randomized 444 patients to berdazimer gel 10.3% and 447 to a placebo gel, applied once daily in a thin layer on all MC lesions for 12 weeks. The study was conducted at 55 clinics across the United States between Sept. 1, 2020, and July 21, 2021. The mean age of the patients was about 6.5 years and participants had 3-70 raised MC lesions; those with sexually transmitted MC or MC in the periocular area were excluded. The primary endpoint was complete clearance of MC lesions after 12 weeks of treatment.

At 12 weeks, significantly more patients treated with berdazimer gel achieved complete clearance than those on vehicle (32.4% vs. 19.7%; P < .001). A total of 64 (14.4%) patients in the berdazimer group discontinued treatment because of MC clearance, compared with 40 patients (8.9%) in the vehicle group.

More recently, investigators evaluated autoinoculation vs. 35% trichloroacetic acid (TCA) for the treatment of MC. Autoinoculation involves puncturing the perilesional and lesional skin 5-7 times with an insulin syringe. “This gets a little bit of the virus into the dermis, and you hope to elicit an immune response,” explained Dr. Smith, who was not involved with the study. At 3 months, 80% of patients in the autoinoculation group achieved complete clearance, compared with 62% of those in the TCA group, while recurrence at 6 months was 3% vs. 40%, respectively.

Manual extraction of MC lesions is another option. “I love to pop the cores out with my thumbs,” Dr. Smith said. “You have to pick the patients who can tolerate this, and the MC lesions need to be ripe and ready.”

For ophthalmic lesions, watchful waiting is advisable unless the MC lesions are symptomatic or bothersome or large lesions form on the lid margin, which may cause ocular irritation or even a corneal abrasion. “If a patient presents with a multisite infection that includes ocular lesions, treat lesions on other parts of the body and keep your fingers crossed that a systemic immune response occurs,” she said.

The desired immune response is known as the “BOTE” sign (the beginning of the end), which heralds the clearance of the molluscum infection. This often appears as reddening of all the MC lesions and occasionally as a granulomatous “id-like” reaction especially on the extensor elbows and knees. “When this happens, it often scares the patients,” Dr. Smith said. But she explains that this is a positive development, and that “this means that the lesions are about to self-resolve.”

Dr. Smith disclosed that she serves as a speaker or a member of the speakers bureau for Amgen, CeraVe, EPI, Galderma, InCyte, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Sun. She also serves as an advisor or consultant for Janssen, Lilly, Regeneron, and Sanofi Genzyme.

Medscape Live and this news organization are owned by the same parent company.