This transcript has been edited for clarity. 

Rachel S. Rubin, MD: As a sexual medicine specialist, I treat a lot of menopause. Why? Because menopausal complaints are not just hot flashes and night sweats; we see so many sexual health problems: genital urinary syndrome of menopause (GUSM), low libido, pain with sex, arousal disorders, orgasm disorders. I am joined today with a superstar in the menopause field, Dr. Stephanie Faubion. Introduce yourself to our amazing listeners.

Stephanie S. Faubion, MD, MBA: I am Stephanie Faubion, director of the Mayo Clinic Center for Women’s Health and medical director for the Menopause Society.

Dr. Rubin: That is a very short introduction for a very impressive person who really is an authority, if you’ve ever read an article about menopause. I asked Dr. Faubion if she spends all her time talking to reporters. But it’s very important because menopause is having a moment. We can’t go a day without seeing a headline, an Instagram story, or something; my feed is full of menopause information. Why do you think menopause is having a moment right now?

Dr. Faubion: It’s a well-deserved moment and should have happened a long time ago. It’s having a moment for several reasons. The generation of women experiencing perimenopause and menopause is different now; they are less willing to suffer in silence, which is a great thing. We’ve also created a little bit of a care vacuum. The Women’s Health Initiative (WHI) study came out in 2002, and after that, we really left women with few choices about what to take to manage their symptoms. That created a vacuum. 

After that, clinicians decided they no longer needed to worry about being educated about menopause because there was really nothing to do for menopause if we weren’t going to use hormone therapy. Where we’ve come to now is women are having symptoms; they’re having a problem. It’s affecting all aspects of their lives: their relationships, their quality of life, their ability to work. And they’re saying, “Hey, this isn’t right. We need to do something about this.” There’s still very little research in this area. We have a lot more to do. They’re demanding answers, as they should. 

Dr. Rubin: We have quite a lot of tools in our toolbox that are evidence based, that really work and help people. I always say to my patients, “You have a generation of clinicians who were not taught how to do this well. Hormones are not all good or all bad, all right or all wrong, but they require some understanding of when to use them and how to safely use them.” That way, you can avoid your patients going to the snake oil salesmen down the street selling non–evidence-based treatments. 

One article that came out this year that I thought was really fascinating was about what we are calling NFLM: not feeling like myself. I will tell you, I think it’s brilliant because there is not a woman aged 40 or above who doesn’t deeply connect with the idea of NFLM. Can you speak to the symptoms of perimenopause and menopause beyond hot flashes and night sweats? I named a few sexual symptoms earlier. We’re really learning about all these new areas to understand, what is perimenopause? 

Dr. Faubion: Very rarely does a woman come in and say, “I have hot flashes” and I say, “Well, is that all you have?” “Yep. That’s all I have. I just have a couple of hot flashes.” That almost never happens, as you know. Menopause is not just about hot flashes, although that’s one of the most common symptoms. Hot flashes also occur at night. We call them night sweats when that happens. But there’s the sleep disturbance, which is probably not just related to night sweats but a lot of other things as well. Mood symptoms can be crazy. A lot of women come in with descriptions of irritability, just not feeling right, or feeling anxious. Another common symptom that we’re learning about is joint aches. 

It’s important to remember when we’re talking about these symptoms that estrogen affects every tissue and organ system in the body. And when you lose it, you have effects in pretty much every tissue and organ system in the body. So, it’s not just about hot flashes and night sweats. We’ve also learned recently that women in perimenopause can have the same symptoms that women have after menopause. It’s not just that it starts at menopause. 

Dr. Rubin: This is really important because we are speaking to the primary care world. The way medicine is set up, you’re allowed to have one problem. If you have more than one problem, I don’t know what to do. You go in the crazy bucket of we’re not interested or we don’t have time to take care of you. But menopause is never one problem. So, the disaster here is that these women are getting diagnosed with a mental health condition, with fibromyalgia, with dry eye, with sexual dysfunction, with depression or anxiety. They’re getting 10 diagnoses for what is actually one underlying hypogonadal problem. 

Dr. Faubion: That’s exactly right. I’ve seen a woman at the Mayo Clinic, who came to me as a general internist, not even knowing I did menopause. She traveled across the country to see me. She’s gaining weight, she’s losing her hair, she’s sweating. She thinks there is something horribly wrong with her, like she must have cancer or something. When you put it all together — the palpitations and the rest — it was all menopause. Think of the expense to come to the Mayo Clinic and be evaluated for that. But no one, including her, had put together the fact that all of these symptoms were related to menopause. You’re exactly right. Sometimes women don’t even recognize that it’s all related. 

Dr. Rubin: For the primary care viewers, we were raised on the idea that hormones cause cancer. Can you speak to that? What are the data in 2024? Am I going to die if I take hormone therapy? Am I going to risk blood clots and horrible cancers? 

Dr. Faubion: To be brief, we now know who the best candidates are for hormone therapy, and we can really minimize risk. We also know that there are differences between the formulations that we use, the route of delivery, and the dose. We can really individualize this for the woman. 

When it comes down to cancer risk, the WHI found that if you have a uterus and you’re taking both an estrogen and a progestogen (specifically conjugated equine estrogen and medroxyprogesterone acetate), the risk for breast cancer was increased slightly. When I say “slightly,” I’m talking the same as the increase in breast cancer risk of drinking one to two glasses of wine a night, or being overweight, or being inactive. We are really talking about less than one case per thousand women per year after about 5 years of hormone therapy. So, it’s a very small increased risk.

In contrast, the data showed that the risk for breast cancer did not appear to be increased in women who did not have a uterus and were using conjugated equine estrogen alone, either during the study or in the 18-year follow-up. The blood clot risk associated with estrogen-containing hormone therapy can be minimized with transdermal preparations of estrogen, particularly with lower doses. Overall, we don’t see that these risks are prohibitive for most women, and if they are having bothersome symptoms, they can use an estrogen-containing product safely. 

Dr. Rubin: We can learn new things, right? For example, the new GLP-1 drugs, which is also very fascinating — using those in perimenopause and menopause. A GLP-1 deficiency may be increased as you go to perimenopause and menopause. By adding back hormones, maybe we can help keep muscle around, keep mental health better, and keep bones stronger, because osteoporosis and fractures kill more people than breast cancer does. 

So, as a primary care clinician, how do we learn to write prescriptions for hormone therapy? How do we learn how to counsel patients properly? Do we have to go back and take a fellowship? How do I learn how to integrate the evidence into my practice? 

Dr. Faubion: An easy thing to do to gain confidence is take a course. The North American Menopause Society has an annual meeting in Chicago in September, and we do a Menopause 101 course for clinicians there. It’s also available online. There are ways to get this information in a digestible way to where you can learn the basics: Here’s where I start; here’s how I need to follow it up. It’s really not that difficult to get into this. 

As to your point about the GLP-1 drugs, we all have to learn new things every day because treatments change, drugs change, etc. Although hormones have been out there for a long time, many clinicians haven’t had the experience of treating menopausal women. I would put a plea out to my primary care colleagues in internal medicine and family medicine that you need to be doing this. Think about it — you already are the expert on brain health and bone health and heart health. You should be the most comfortable in dealing with hormone therapy that has effects throughout the entire body. It’s important for us as primary care providers to really have a handle on this and to be the owners of managing menopause for women in midlife. 

Dr. Rubin: I couldn’t agree more. As a sexual medicine doctor, treating menopausal women is actually what fuels my soul and stops all burnout because they get better. My clinic is full of a fifty-something-year-old people who come back and they say sex is good. “My relationship is good.” “I’m kicking butt at work.” I have a patient who just started law school because she feels good, and she says, “I’m keeping up with the 20-year-olds.” It is incredible to see people who feel terrible and then watch them blossom and get better. There’s nothing that fuels my soul more than these patients. 

What is exciting you in the menopause world? What are you hopeful for down the road with some of these new initiatives coming out? 

Dr. Faubion: The fact that we have a president of the United States and a National Institutes of Health who are more interested in looking at menopause is amazing. It’s an exciting time; there’s more interest, and more research funding seems to be available for the United States. 

In terms of clinical management, we now have so many options available to women. We’ve been talking about hormone therapy, but we now have nonhormonal medications out there as well that are on the market, such as fezolinetant, a neurokinin 3 inhibitor that came out last year. There’s probably another one coming out in the next year or so. So, women have lots of options, and for the first time, we can really individualize treatment for women and look at what symptoms are bothering them, and how best to get them back to where they should be. 

We’re also starting a menopause-in-the-workplace initiative with the Menopause Society and really kind of tackling that one. We know that a lot of women are missing work, not taking a promotion, or avoiding a leadership role because of their menopause symptoms. Women should never be in the position of compromising their work lives because of menopause symptoms. This is something we can help women with. 

Dr. Rubin: Our big takeaway today is: Believe your patients when they come to you, and they’ve driven and parked and arranged childcare, and showed up to your office and waited to see you. When they’re telling you that they have all these symptoms and they’re not feeling like themselves, maybe before you jump straight to the SSRI or just say, “Do some yoga and deep breathing,” maybe really dive into the menopause literature and understand the pros and cons, and the risks and benefits of hormone therapy. We do it with so many other things. We can do it with hormone therapy as well. It is not a one-size-fits-all. We do need to talk to our patients, customize their care, and really figure out what they care about and what they want. Patients are able to understand risks and benefits and can make good decisions for themselves.

Dr. Rubin is an assistant clinical professor, Department of Urology, at Georgetown University, Washington, DC. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

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

This transcript has been edited for clarity. 

Rachel S. Rubin, MD: As a sexual medicine specialist, I treat a lot of menopause. Why? Because menopausal complaints are not just hot flashes and night sweats; we see so many sexual health problems: genital urinary syndrome of menopause (GUSM), low libido, pain with sex, arousal disorders, orgasm disorders. I am joined today with a superstar in the menopause field, Dr. Stephanie Faubion. Introduce yourself to our amazing listeners.

Stephanie S. Faubion, MD, MBA: I am Stephanie Faubion, director of the Mayo Clinic Center for Women’s Health and medical director for the Menopause Society.

Dr. Rubin: That is a very short introduction for a very impressive person who really is an authority, if you’ve ever read an article about menopause. I asked Dr. Faubion if she spends all her time talking to reporters. But it’s very important because menopause is having a moment. We can’t go a day without seeing a headline, an Instagram story, or something; my feed is full of menopause information. Why do you think menopause is having a moment right now?

Dr. Faubion: It’s a well-deserved moment and should have happened a long time ago. It’s having a moment for several reasons. The generation of women experiencing perimenopause and menopause is different now; they are less willing to suffer in silence, which is a great thing. We’ve also created a little bit of a care vacuum. The Women’s Health Initiative (WHI) study came out in 2002, and after that, we really left women with few choices about what to take to manage their symptoms. That created a vacuum. 

After that, clinicians decided they no longer needed to worry about being educated about menopause because there was really nothing to do for menopause if we weren’t going to use hormone therapy. Where we’ve come to now is women are having symptoms; they’re having a problem. It’s affecting all aspects of their lives: their relationships, their quality of life, their ability to work. And they’re saying, “Hey, this isn’t right. We need to do something about this.” There’s still very little research in this area. We have a lot more to do. They’re demanding answers, as they should. 

Dr. Rubin: We have quite a lot of tools in our toolbox that are evidence based, that really work and help people. I always say to my patients, “You have a generation of clinicians who were not taught how to do this well. Hormones are not all good or all bad, all right or all wrong, but they require some understanding of when to use them and how to safely use them.” That way, you can avoid your patients going to the snake oil salesmen down the street selling non–evidence-based treatments. 

One article that came out this year that I thought was really fascinating was about what we are calling NFLM: not feeling like myself. I will tell you, I think it’s brilliant because there is not a woman aged 40 or above who doesn’t deeply connect with the idea of NFLM. Can you speak to the symptoms of perimenopause and menopause beyond hot flashes and night sweats? I named a few sexual symptoms earlier. We’re really learning about all these new areas to understand, what is perimenopause? 

Dr. Faubion: Very rarely does a woman come in and say, “I have hot flashes” and I say, “Well, is that all you have?” “Yep. That’s all I have. I just have a couple of hot flashes.” That almost never happens, as you know. Menopause is not just about hot flashes, although that’s one of the most common symptoms. Hot flashes also occur at night. We call them night sweats when that happens. But there’s the sleep disturbance, which is probably not just related to night sweats but a lot of other things as well. Mood symptoms can be crazy. A lot of women come in with descriptions of irritability, just not feeling right, or feeling anxious. Another common symptom that we’re learning about is joint aches. 

It’s important to remember when we’re talking about these symptoms that estrogen affects every tissue and organ system in the body. And when you lose it, you have effects in pretty much every tissue and organ system in the body. So, it’s not just about hot flashes and night sweats. We’ve also learned recently that women in perimenopause can have the same symptoms that women have after menopause. It’s not just that it starts at menopause. 

Dr. Rubin: This is really important because we are speaking to the primary care world. The way medicine is set up, you’re allowed to have one problem. If you have more than one problem, I don’t know what to do. You go in the crazy bucket of we’re not interested or we don’t have time to take care of you. But menopause is never one problem. So, the disaster here is that these women are getting diagnosed with a mental health condition, with fibromyalgia, with dry eye, with sexual dysfunction, with depression or anxiety. They’re getting 10 diagnoses for what is actually one underlying hypogonadal problem. 

Dr. Faubion: That’s exactly right. I’ve seen a woman at the Mayo Clinic, who came to me as a general internist, not even knowing I did menopause. She traveled across the country to see me. She’s gaining weight, she’s losing her hair, she’s sweating. She thinks there is something horribly wrong with her, like she must have cancer or something. When you put it all together — the palpitations and the rest — it was all menopause. Think of the expense to come to the Mayo Clinic and be evaluated for that. But no one, including her, had put together the fact that all of these symptoms were related to menopause. You’re exactly right. Sometimes women don’t even recognize that it’s all related. 

Dr. Rubin: For the primary care viewers, we were raised on the idea that hormones cause cancer. Can you speak to that? What are the data in 2024? Am I going to die if I take hormone therapy? Am I going to risk blood clots and horrible cancers? 

Dr. Faubion: To be brief, we now know who the best candidates are for hormone therapy, and we can really minimize risk. We also know that there are differences between the formulations that we use, the route of delivery, and the dose. We can really individualize this for the woman. 

When it comes down to cancer risk, the WHI found that if you have a uterus and you’re taking both an estrogen and a progestogen (specifically conjugated equine estrogen and medroxyprogesterone acetate), the risk for breast cancer was increased slightly. When I say “slightly,” I’m talking the same as the increase in breast cancer risk of drinking one to two glasses of wine a night, or being overweight, or being inactive. We are really talking about less than one case per thousand women per year after about 5 years of hormone therapy. So, it’s a very small increased risk.

In contrast, the data showed that the risk for breast cancer did not appear to be increased in women who did not have a uterus and were using conjugated equine estrogen alone, either during the study or in the 18-year follow-up. The blood clot risk associated with estrogen-containing hormone therapy can be minimized with transdermal preparations of estrogen, particularly with lower doses. Overall, we don’t see that these risks are prohibitive for most women, and if they are having bothersome symptoms, they can use an estrogen-containing product safely. 

Dr. Rubin: We can learn new things, right? For example, the new GLP-1 drugs, which is also very fascinating — using those in perimenopause and menopause. A GLP-1 deficiency may be increased as you go to perimenopause and menopause. By adding back hormones, maybe we can help keep muscle around, keep mental health better, and keep bones stronger, because osteoporosis and fractures kill more people than breast cancer does. 

So, as a primary care clinician, how do we learn to write prescriptions for hormone therapy? How do we learn how to counsel patients properly? Do we have to go back and take a fellowship? How do I learn how to integrate the evidence into my practice? 

Dr. Faubion: An easy thing to do to gain confidence is take a course. The North American Menopause Society has an annual meeting in Chicago in September, and we do a Menopause 101 course for clinicians there. It’s also available online. There are ways to get this information in a digestible way to where you can learn the basics: Here’s where I start; here’s how I need to follow it up. It’s really not that difficult to get into this. 

As to your point about the GLP-1 drugs, we all have to learn new things every day because treatments change, drugs change, etc. Although hormones have been out there for a long time, many clinicians haven’t had the experience of treating menopausal women. I would put a plea out to my primary care colleagues in internal medicine and family medicine that you need to be doing this. Think about it — you already are the expert on brain health and bone health and heart health. You should be the most comfortable in dealing with hormone therapy that has effects throughout the entire body. It’s important for us as primary care providers to really have a handle on this and to be the owners of managing menopause for women in midlife. 

Dr. Rubin: I couldn’t agree more. As a sexual medicine doctor, treating menopausal women is actually what fuels my soul and stops all burnout because they get better. My clinic is full of a fifty-something-year-old people who come back and they say sex is good. “My relationship is good.” “I’m kicking butt at work.” I have a patient who just started law school because she feels good, and she says, “I’m keeping up with the 20-year-olds.” It is incredible to see people who feel terrible and then watch them blossom and get better. There’s nothing that fuels my soul more than these patients. 

What is exciting you in the menopause world? What are you hopeful for down the road with some of these new initiatives coming out? 

Dr. Faubion: The fact that we have a president of the United States and a National Institutes of Health who are more interested in looking at menopause is amazing. It’s an exciting time; there’s more interest, and more research funding seems to be available for the United States. 

In terms of clinical management, we now have so many options available to women. We’ve been talking about hormone therapy, but we now have nonhormonal medications out there as well that are on the market, such as fezolinetant, a neurokinin 3 inhibitor that came out last year. There’s probably another one coming out in the next year or so. So, women have lots of options, and for the first time, we can really individualize treatment for women and look at what symptoms are bothering them, and how best to get them back to where they should be. 

We’re also starting a menopause-in-the-workplace initiative with the Menopause Society and really kind of tackling that one. We know that a lot of women are missing work, not taking a promotion, or avoiding a leadership role because of their menopause symptoms. Women should never be in the position of compromising their work lives because of menopause symptoms. This is something we can help women with. 

Dr. Rubin: Our big takeaway today is: Believe your patients when they come to you, and they’ve driven and parked and arranged childcare, and showed up to your office and waited to see you. When they’re telling you that they have all these symptoms and they’re not feeling like themselves, maybe before you jump straight to the SSRI or just say, “Do some yoga and deep breathing,” maybe really dive into the menopause literature and understand the pros and cons, and the risks and benefits of hormone therapy. We do it with so many other things. We can do it with hormone therapy as well. It is not a one-size-fits-all. We do need to talk to our patients, customize their care, and really figure out what they care about and what they want. Patients are able to understand risks and benefits and can make good decisions for themselves.

Dr. Rubin is an assistant clinical professor, Department of Urology, at Georgetown University, Washington, DC. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

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

This transcript has been edited for clarity. 

Rachel S. Rubin, MD: As a sexual medicine specialist, I treat a lot of menopause. Why? Because menopausal complaints are not just hot flashes and night sweats; we see so many sexual health problems: genital urinary syndrome of menopause (GUSM), low libido, pain with sex, arousal disorders, orgasm disorders. I am joined today with a superstar in the menopause field, Dr. Stephanie Faubion. Introduce yourself to our amazing listeners.

Stephanie S. Faubion, MD, MBA: I am Stephanie Faubion, director of the Mayo Clinic Center for Women’s Health and medical director for the Menopause Society.

Dr. Rubin: That is a very short introduction for a very impressive person who really is an authority, if you’ve ever read an article about menopause. I asked Dr. Faubion if she spends all her time talking to reporters. But it’s very important because menopause is having a moment. We can’t go a day without seeing a headline, an Instagram story, or something; my feed is full of menopause information. Why do you think menopause is having a moment right now?

Dr. Faubion: It’s a well-deserved moment and should have happened a long time ago. It’s having a moment for several reasons. The generation of women experiencing perimenopause and menopause is different now; they are less willing to suffer in silence, which is a great thing. We’ve also created a little bit of a care vacuum. The Women’s Health Initiative (WHI) study came out in 2002, and after that, we really left women with few choices about what to take to manage their symptoms. That created a vacuum. 

After that, clinicians decided they no longer needed to worry about being educated about menopause because there was really nothing to do for menopause if we weren’t going to use hormone therapy. Where we’ve come to now is women are having symptoms; they’re having a problem. It’s affecting all aspects of their lives: their relationships, their quality of life, their ability to work. And they’re saying, “Hey, this isn’t right. We need to do something about this.” There’s still very little research in this area. We have a lot more to do. They’re demanding answers, as they should. 

Dr. Rubin: We have quite a lot of tools in our toolbox that are evidence based, that really work and help people. I always say to my patients, “You have a generation of clinicians who were not taught how to do this well. Hormones are not all good or all bad, all right or all wrong, but they require some understanding of when to use them and how to safely use them.” That way, you can avoid your patients going to the snake oil salesmen down the street selling non–evidence-based treatments. 

One article that came out this year that I thought was really fascinating was about what we are calling NFLM: not feeling like myself. I will tell you, I think it’s brilliant because there is not a woman aged 40 or above who doesn’t deeply connect with the idea of NFLM. Can you speak to the symptoms of perimenopause and menopause beyond hot flashes and night sweats? I named a few sexual symptoms earlier. We’re really learning about all these new areas to understand, what is perimenopause? 

Dr. Faubion: Very rarely does a woman come in and say, “I have hot flashes” and I say, “Well, is that all you have?” “Yep. That’s all I have. I just have a couple of hot flashes.” That almost never happens, as you know. Menopause is not just about hot flashes, although that’s one of the most common symptoms. Hot flashes also occur at night. We call them night sweats when that happens. But there’s the sleep disturbance, which is probably not just related to night sweats but a lot of other things as well. Mood symptoms can be crazy. A lot of women come in with descriptions of irritability, just not feeling right, or feeling anxious. Another common symptom that we’re learning about is joint aches. 

It’s important to remember when we’re talking about these symptoms that estrogen affects every tissue and organ system in the body. And when you lose it, you have effects in pretty much every tissue and organ system in the body. So, it’s not just about hot flashes and night sweats. We’ve also learned recently that women in perimenopause can have the same symptoms that women have after menopause. It’s not just that it starts at menopause. 

Dr. Rubin: This is really important because we are speaking to the primary care world. The way medicine is set up, you’re allowed to have one problem. If you have more than one problem, I don’t know what to do. You go in the crazy bucket of we’re not interested or we don’t have time to take care of you. But menopause is never one problem. So, the disaster here is that these women are getting diagnosed with a mental health condition, with fibromyalgia, with dry eye, with sexual dysfunction, with depression or anxiety. They’re getting 10 diagnoses for what is actually one underlying hypogonadal problem. 

Dr. Faubion: That’s exactly right. I’ve seen a woman at the Mayo Clinic, who came to me as a general internist, not even knowing I did menopause. She traveled across the country to see me. She’s gaining weight, she’s losing her hair, she’s sweating. She thinks there is something horribly wrong with her, like she must have cancer or something. When you put it all together — the palpitations and the rest — it was all menopause. Think of the expense to come to the Mayo Clinic and be evaluated for that. But no one, including her, had put together the fact that all of these symptoms were related to menopause. You’re exactly right. Sometimes women don’t even recognize that it’s all related. 

Dr. Rubin: For the primary care viewers, we were raised on the idea that hormones cause cancer. Can you speak to that? What are the data in 2024? Am I going to die if I take hormone therapy? Am I going to risk blood clots and horrible cancers? 

Dr. Faubion: To be brief, we now know who the best candidates are for hormone therapy, and we can really minimize risk. We also know that there are differences between the formulations that we use, the route of delivery, and the dose. We can really individualize this for the woman. 

When it comes down to cancer risk, the WHI found that if you have a uterus and you’re taking both an estrogen and a progestogen (specifically conjugated equine estrogen and medroxyprogesterone acetate), the risk for breast cancer was increased slightly. When I say “slightly,” I’m talking the same as the increase in breast cancer risk of drinking one to two glasses of wine a night, or being overweight, or being inactive. We are really talking about less than one case per thousand women per year after about 5 years of hormone therapy. So, it’s a very small increased risk.

In contrast, the data showed that the risk for breast cancer did not appear to be increased in women who did not have a uterus and were using conjugated equine estrogen alone, either during the study or in the 18-year follow-up. The blood clot risk associated with estrogen-containing hormone therapy can be minimized with transdermal preparations of estrogen, particularly with lower doses. Overall, we don’t see that these risks are prohibitive for most women, and if they are having bothersome symptoms, they can use an estrogen-containing product safely. 

Dr. Rubin: We can learn new things, right? For example, the new GLP-1 drugs, which is also very fascinating — using those in perimenopause and menopause. A GLP-1 deficiency may be increased as you go to perimenopause and menopause. By adding back hormones, maybe we can help keep muscle around, keep mental health better, and keep bones stronger, because osteoporosis and fractures kill more people than breast cancer does. 

So, as a primary care clinician, how do we learn to write prescriptions for hormone therapy? How do we learn how to counsel patients properly? Do we have to go back and take a fellowship? How do I learn how to integrate the evidence into my practice? 

Dr. Faubion: An easy thing to do to gain confidence is take a course. The North American Menopause Society has an annual meeting in Chicago in September, and we do a Menopause 101 course for clinicians there. It’s also available online. There are ways to get this information in a digestible way to where you can learn the basics: Here’s where I start; here’s how I need to follow it up. It’s really not that difficult to get into this. 

As to your point about the GLP-1 drugs, we all have to learn new things every day because treatments change, drugs change, etc. Although hormones have been out there for a long time, many clinicians haven’t had the experience of treating menopausal women. I would put a plea out to my primary care colleagues in internal medicine and family medicine that you need to be doing this. Think about it — you already are the expert on brain health and bone health and heart health. You should be the most comfortable in dealing with hormone therapy that has effects throughout the entire body. It’s important for us as primary care providers to really have a handle on this and to be the owners of managing menopause for women in midlife. 

Dr. Rubin: I couldn’t agree more. As a sexual medicine doctor, treating menopausal women is actually what fuels my soul and stops all burnout because they get better. My clinic is full of a fifty-something-year-old people who come back and they say sex is good. “My relationship is good.” “I’m kicking butt at work.” I have a patient who just started law school because she feels good, and she says, “I’m keeping up with the 20-year-olds.” It is incredible to see people who feel terrible and then watch them blossom and get better. There’s nothing that fuels my soul more than these patients. 

What is exciting you in the menopause world? What are you hopeful for down the road with some of these new initiatives coming out? 

Dr. Faubion: The fact that we have a president of the United States and a National Institutes of Health who are more interested in looking at menopause is amazing. It’s an exciting time; there’s more interest, and more research funding seems to be available for the United States. 

In terms of clinical management, we now have so many options available to women. We’ve been talking about hormone therapy, but we now have nonhormonal medications out there as well that are on the market, such as fezolinetant, a neurokinin 3 inhibitor that came out last year. There’s probably another one coming out in the next year or so. So, women have lots of options, and for the first time, we can really individualize treatment for women and look at what symptoms are bothering them, and how best to get them back to where they should be. 

We’re also starting a menopause-in-the-workplace initiative with the Menopause Society and really kind of tackling that one. We know that a lot of women are missing work, not taking a promotion, or avoiding a leadership role because of their menopause symptoms. Women should never be in the position of compromising their work lives because of menopause symptoms. This is something we can help women with. 

Dr. Rubin: Our big takeaway today is: Believe your patients when they come to you, and they’ve driven and parked and arranged childcare, and showed up to your office and waited to see you. When they’re telling you that they have all these symptoms and they’re not feeling like themselves, maybe before you jump straight to the SSRI or just say, “Do some yoga and deep breathing,” maybe really dive into the menopause literature and understand the pros and cons, and the risks and benefits of hormone therapy. We do it with so many other things. We can do it with hormone therapy as well. It is not a one-size-fits-all. We do need to talk to our patients, customize their care, and really figure out what they care about and what they want. Patients are able to understand risks and benefits and can make good decisions for themselves.

Dr. Rubin is an assistant clinical professor, Department of Urology, at Georgetown University, Washington, DC. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

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

This transcript has been edited for clarity. 

There has been a large amount of news lately about dating online and dating apps. Probably the most common way younger people find potential partners is to go online and see who’s there that they might want to meet. 

Online dating is also notorious for being full of scammers. There are all kinds of people out there that you have to be careful of, who are trying to rip you off by saying, “Send me money, I’m in trouble,” or “Now that we have a relationship, will you support my particular entrepreneurial idea?” Certainly, dangers are there. 

Another danger we don’t talk much about is meeting people who have sexually transmitted diseases. That’s been a problem before websites and before dating apps. I think the opportunity of meeting more people — strangers, people you don’t really know — who may not tell you the truth about their health, and particularly their sexual health, is really out there. 

It’s always good medical advice to tell people to practice safe sex, and that often involves a man wearing a condom. It certainly is the case that we want to attend not just to the prevention of unwanted pregnancy but also to the transmission of diseases. I think it’s very important to tell women of reproductive age to get their HPV shot to try to reduce cancers in their reproductive systems, or sometimes in men — anal cancers, or even being a transmitter of disease. 

Even then, certainly one wants to recommend that, in an age where some people are going to meet many partners that they don’t know well or don’t have much background with, it’s wise to try to prevent diseases using the vaccines we’ve got, using the contraceptive methods that will prevent disease transmission, and reminding people to ask about sex life. 

I did come across a website that just startled me. It’s called HeHealth, and basically it says to men, if you are conscientious about your sex life, take a picture of your penis, send it to us, and we have doctors — I presume they’re US doctors but I don’t know — who will diagnose venereal diseases based on that picture. I presume women could also say, “Before we have sex, or now that we’re approaching that possibility, I want you to send a picture to this company on this website.” 

Now, a couple of reminders. I think we all know this, but just because you’re not manifesting symptoms on your reproductive organs doesn’t mean you don’t have a sexual disease. It’s not a reliable measure. Yes, maybe you could have somebody say: “Oh, that looks nasty. I’m not sure you ought to have sex right now, and maybe you should go get some treatment.” This is going to miss many cases and is not a reliable indicator that your partner is safe in terms of not transmitting diseases to you. 

It also isn’t clear what they do with these images. Do they keep them? Who can see them? Could they resell them? What sort of privacy protection have you got if you decide to use this? 

There’s another issue here, which is, if they misdiagnose someone and you do catch a sexual disease, who’s liable? Can you go after them for using doctors who weren’t competent or transmitting images that weren’t really adequate because you didn’t know how to take that picture properly when you sent that off to them? There are many unknowns. 

The bottom line is that we’re in a different world, I think, of romance. We’re in a world where some people are going to meet more partners. Some people are going to meet more strangers. One approach is to have us take pictures of ourselves, send them off to who knows where, and ask for a green light to go ahead and have sexual relations. I don’t think we’re anywhere close to being able to rely on that as a way to avoid the risks of unprotected sexual behavior. 

We do know what to do in dealing with patients who are sexually active. First, we have to ask them. Then we’ve got to recommend available vaccinations to prevent the transmission of some cancers, the HPV vaccine. Then they need that reminder about safe sexual practices not only to protect against unwanted pregnancy, but still, in this day and age, to protect against syphilis, which is on the rise, plus HIV, gonorrhea, chlamydia, and other sexually transmissible diseases. 

I’m not going to rely on the penis picture to make the world safe for sex. I think we have to still use the old-fashioned techniques of education and prevention to do the best we can.

Dr. Caplan is director of the Division of Medical Ethics at New York University Langone Medical Center, New York City. He reported conflicts of interest with Johnson & Johnson’s Panel for Compassionate Drug Use and Medscape.

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

This transcript has been edited for clarity. 

There has been a large amount of news lately about dating online and dating apps. Probably the most common way younger people find potential partners is to go online and see who’s there that they might want to meet. 

Online dating is also notorious for being full of scammers. There are all kinds of people out there that you have to be careful of, who are trying to rip you off by saying, “Send me money, I’m in trouble,” or “Now that we have a relationship, will you support my particular entrepreneurial idea?” Certainly, dangers are there. 

Another danger we don’t talk much about is meeting people who have sexually transmitted diseases. That’s been a problem before websites and before dating apps. I think the opportunity of meeting more people — strangers, people you don’t really know — who may not tell you the truth about their health, and particularly their sexual health, is really out there. 

It’s always good medical advice to tell people to practice safe sex, and that often involves a man wearing a condom. It certainly is the case that we want to attend not just to the prevention of unwanted pregnancy but also to the transmission of diseases. I think it’s very important to tell women of reproductive age to get their HPV shot to try to reduce cancers in their reproductive systems, or sometimes in men — anal cancers, or even being a transmitter of disease. 

Even then, certainly one wants to recommend that, in an age where some people are going to meet many partners that they don’t know well or don’t have much background with, it’s wise to try to prevent diseases using the vaccines we’ve got, using the contraceptive methods that will prevent disease transmission, and reminding people to ask about sex life. 

I did come across a website that just startled me. It’s called HeHealth, and basically it says to men, if you are conscientious about your sex life, take a picture of your penis, send it to us, and we have doctors — I presume they’re US doctors but I don’t know — who will diagnose venereal diseases based on that picture. I presume women could also say, “Before we have sex, or now that we’re approaching that possibility, I want you to send a picture to this company on this website.” 

Now, a couple of reminders. I think we all know this, but just because you’re not manifesting symptoms on your reproductive organs doesn’t mean you don’t have a sexual disease. It’s not a reliable measure. Yes, maybe you could have somebody say: “Oh, that looks nasty. I’m not sure you ought to have sex right now, and maybe you should go get some treatment.” This is going to miss many cases and is not a reliable indicator that your partner is safe in terms of not transmitting diseases to you. 

It also isn’t clear what they do with these images. Do they keep them? Who can see them? Could they resell them? What sort of privacy protection have you got if you decide to use this? 

There’s another issue here, which is, if they misdiagnose someone and you do catch a sexual disease, who’s liable? Can you go after them for using doctors who weren’t competent or transmitting images that weren’t really adequate because you didn’t know how to take that picture properly when you sent that off to them? There are many unknowns. 

The bottom line is that we’re in a different world, I think, of romance. We’re in a world where some people are going to meet more partners. Some people are going to meet more strangers. One approach is to have us take pictures of ourselves, send them off to who knows where, and ask for a green light to go ahead and have sexual relations. I don’t think we’re anywhere close to being able to rely on that as a way to avoid the risks of unprotected sexual behavior. 

We do know what to do in dealing with patients who are sexually active. First, we have to ask them. Then we’ve got to recommend available vaccinations to prevent the transmission of some cancers, the HPV vaccine. Then they need that reminder about safe sexual practices not only to protect against unwanted pregnancy, but still, in this day and age, to protect against syphilis, which is on the rise, plus HIV, gonorrhea, chlamydia, and other sexually transmissible diseases. 

I’m not going to rely on the penis picture to make the world safe for sex. I think we have to still use the old-fashioned techniques of education and prevention to do the best we can.

Dr. Caplan is director of the Division of Medical Ethics at New York University Langone Medical Center, New York City. He reported conflicts of interest with Johnson & Johnson’s Panel for Compassionate Drug Use and Medscape.

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

This transcript has been edited for clarity. 

There has been a large amount of news lately about dating online and dating apps. Probably the most common way younger people find potential partners is to go online and see who’s there that they might want to meet. 

Online dating is also notorious for being full of scammers. There are all kinds of people out there that you have to be careful of, who are trying to rip you off by saying, “Send me money, I’m in trouble,” or “Now that we have a relationship, will you support my particular entrepreneurial idea?” Certainly, dangers are there. 

Another danger we don’t talk much about is meeting people who have sexually transmitted diseases. That’s been a problem before websites and before dating apps. I think the opportunity of meeting more people — strangers, people you don’t really know — who may not tell you the truth about their health, and particularly their sexual health, is really out there. 

It’s always good medical advice to tell people to practice safe sex, and that often involves a man wearing a condom. It certainly is the case that we want to attend not just to the prevention of unwanted pregnancy but also to the transmission of diseases. I think it’s very important to tell women of reproductive age to get their HPV shot to try to reduce cancers in their reproductive systems, or sometimes in men — anal cancers, or even being a transmitter of disease. 

Even then, certainly one wants to recommend that, in an age where some people are going to meet many partners that they don’t know well or don’t have much background with, it’s wise to try to prevent diseases using the vaccines we’ve got, using the contraceptive methods that will prevent disease transmission, and reminding people to ask about sex life. 

I did come across a website that just startled me. It’s called HeHealth, and basically it says to men, if you are conscientious about your sex life, take a picture of your penis, send it to us, and we have doctors — I presume they’re US doctors but I don’t know — who will diagnose venereal diseases based on that picture. I presume women could also say, “Before we have sex, or now that we’re approaching that possibility, I want you to send a picture to this company on this website.” 

Now, a couple of reminders. I think we all know this, but just because you’re not manifesting symptoms on your reproductive organs doesn’t mean you don’t have a sexual disease. It’s not a reliable measure. Yes, maybe you could have somebody say: “Oh, that looks nasty. I’m not sure you ought to have sex right now, and maybe you should go get some treatment.” This is going to miss many cases and is not a reliable indicator that your partner is safe in terms of not transmitting diseases to you. 

It also isn’t clear what they do with these images. Do they keep them? Who can see them? Could they resell them? What sort of privacy protection have you got if you decide to use this? 

There’s another issue here, which is, if they misdiagnose someone and you do catch a sexual disease, who’s liable? Can you go after them for using doctors who weren’t competent or transmitting images that weren’t really adequate because you didn’t know how to take that picture properly when you sent that off to them? There are many unknowns. 

The bottom line is that we’re in a different world, I think, of romance. We’re in a world where some people are going to meet more partners. Some people are going to meet more strangers. One approach is to have us take pictures of ourselves, send them off to who knows where, and ask for a green light to go ahead and have sexual relations. I don’t think we’re anywhere close to being able to rely on that as a way to avoid the risks of unprotected sexual behavior. 

We do know what to do in dealing with patients who are sexually active. First, we have to ask them. Then we’ve got to recommend available vaccinations to prevent the transmission of some cancers, the HPV vaccine. Then they need that reminder about safe sexual practices not only to protect against unwanted pregnancy, but still, in this day and age, to protect against syphilis, which is on the rise, plus HIV, gonorrhea, chlamydia, and other sexually transmissible diseases. 

I’m not going to rely on the penis picture to make the world safe for sex. I think we have to still use the old-fashioned techniques of education and prevention to do the best we can.

Dr. Caplan is director of the Division of Medical Ethics at New York University Langone Medical Center, New York City. He reported conflicts of interest with Johnson & Johnson’s Panel for Compassionate Drug Use and Medscape.

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

The US Food and Drug Administration (FDA) has granted accelerated approval to adagrasib (Krazati, Mirati Therapeutics) with cetuximab for certain patients with KRAS G12C–mutated colorectal cancer (CRC).

More specifically, the highly selective and potent small-molecule KRAS G12C inhibitor is now indicated for patients with locally advanced or metastatic KRAS G12C–mutated CRC — as determined by an FDA-approved test — who previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and, if eligible, a vascular endothelial growth factor inhibitor, according to an FDA press release.

The agent is the first KRAS inhibitor approved for CRC. Adagrasib was previously granted accelerated approval for KRAS G12C–mutated non–small cell lung cancer, based on findings from the KRYSTAL-12 trial.

The CRC approval was based on findings from the KRYSTAL-1 multicenter, single-arm expansion cohort trial, which reported an overall response rate of 34% among 94 enrolled patients. 

All responses were partial responses, and the median duration of response was 5.8 months, with 31% of responding patients experiencing a duration of response of at least 6 months.

Patients received 600 mg of adagrasib twice daily plus cetuximab administered in either a biweekly 500 mg/m² dose or an initial dose of 400 mg/m² followed by weekly doses of 250 mg/m². Those who discontinued adagrasib also had to discontinue cetuximab, but adagrasib could be continued if cetuximab was discontinued.

The recommended adagrasib dose is 600 mg given orally twice daily until disease progression or unacceptable toxicity, according to the prescribing information. 

Adverse reactions occurring in at least 20% of treated patients included rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, cough, dizziness, constipation, and peripheral neuropathy.

“Patients with KRAS G12C–mutated colorectal cancer have historically faced poor prognoses and remain in need of additional treatment options,” Scott Kopetz, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, stated earlier this year in a press release announcing the FDA’s decision to accept the drug application for priority review.

“Although KRAS had previously been considered ‘undruggable,’ these data from KRYSTAL-1 reinforce the potential benefit of adagrasib for these specific patients,” Dr. Kopetz said in the statement from Bristol Myers Squibb, which acquired Mirati Therapeutics in 2023.

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

The US Food and Drug Administration (FDA) has granted accelerated approval to adagrasib (Krazati, Mirati Therapeutics) with cetuximab for certain patients with KRAS G12C–mutated colorectal cancer (CRC).

More specifically, the highly selective and potent small-molecule KRAS G12C inhibitor is now indicated for patients with locally advanced or metastatic KRAS G12C–mutated CRC — as determined by an FDA-approved test — who previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and, if eligible, a vascular endothelial growth factor inhibitor, according to an FDA press release.

The agent is the first KRAS inhibitor approved for CRC. Adagrasib was previously granted accelerated approval for KRAS G12C–mutated non–small cell lung cancer, based on findings from the KRYSTAL-12 trial.

The CRC approval was based on findings from the KRYSTAL-1 multicenter, single-arm expansion cohort trial, which reported an overall response rate of 34% among 94 enrolled patients. 

All responses were partial responses, and the median duration of response was 5.8 months, with 31% of responding patients experiencing a duration of response of at least 6 months.

Patients received 600 mg of adagrasib twice daily plus cetuximab administered in either a biweekly 500 mg/m² dose or an initial dose of 400 mg/m² followed by weekly doses of 250 mg/m². Those who discontinued adagrasib also had to discontinue cetuximab, but adagrasib could be continued if cetuximab was discontinued.

The recommended adagrasib dose is 600 mg given orally twice daily until disease progression or unacceptable toxicity, according to the prescribing information. 

Adverse reactions occurring in at least 20% of treated patients included rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, cough, dizziness, constipation, and peripheral neuropathy.

“Patients with KRAS G12C–mutated colorectal cancer have historically faced poor prognoses and remain in need of additional treatment options,” Scott Kopetz, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, stated earlier this year in a press release announcing the FDA’s decision to accept the drug application for priority review.

“Although KRAS had previously been considered ‘undruggable,’ these data from KRYSTAL-1 reinforce the potential benefit of adagrasib for these specific patients,” Dr. Kopetz said in the statement from Bristol Myers Squibb, which acquired Mirati Therapeutics in 2023.

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

The US Food and Drug Administration (FDA) has granted accelerated approval to adagrasib (Krazati, Mirati Therapeutics) with cetuximab for certain patients with KRAS G12C–mutated colorectal cancer (CRC).

More specifically, the highly selective and potent small-molecule KRAS G12C inhibitor is now indicated for patients with locally advanced or metastatic KRAS G12C–mutated CRC — as determined by an FDA-approved test — who previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and, if eligible, a vascular endothelial growth factor inhibitor, according to an FDA press release.

The agent is the first KRAS inhibitor approved for CRC. Adagrasib was previously granted accelerated approval for KRAS G12C–mutated non–small cell lung cancer, based on findings from the KRYSTAL-12 trial.

The CRC approval was based on findings from the KRYSTAL-1 multicenter, single-arm expansion cohort trial, which reported an overall response rate of 34% among 94 enrolled patients. 

All responses were partial responses, and the median duration of response was 5.8 months, with 31% of responding patients experiencing a duration of response of at least 6 months.

Patients received 600 mg of adagrasib twice daily plus cetuximab administered in either a biweekly 500 mg/m² dose or an initial dose of 400 mg/m² followed by weekly doses of 250 mg/m². Those who discontinued adagrasib also had to discontinue cetuximab, but adagrasib could be continued if cetuximab was discontinued.

The recommended adagrasib dose is 600 mg given orally twice daily until disease progression or unacceptable toxicity, according to the prescribing information. 

Adverse reactions occurring in at least 20% of treated patients included rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, cough, dizziness, constipation, and peripheral neuropathy.

“Patients with KRAS G12C–mutated colorectal cancer have historically faced poor prognoses and remain in need of additional treatment options,” Scott Kopetz, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, stated earlier this year in a press release announcing the FDA’s decision to accept the drug application for priority review.

“Although KRAS had previously been considered ‘undruggable,’ these data from KRYSTAL-1 reinforce the potential benefit of adagrasib for these specific patients,” Dr. Kopetz said in the statement from Bristol Myers Squibb, which acquired Mirati Therapeutics in 2023.

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

The Food and Drug Administration has approved a topical anticholinergic, sofpironium topical gel, 12.45%, for the treatment of primary axillary hyperhidrosis in adults and children aged ≥ 9 years.

According to a press release from Botanix Pharmaceuticals, which developed the product and will market it under the brand name Sofdra, approval was based on results from two phase 3 studies that enrolled 710 patients with primary axillary hyperhidrosis. In the trials, patients treated with sofpironium topical gel, 12.45%, experienced “clinically and statistically meaningful changes” from baseline in the Gravimetric Sweat Production and the Hyperhidrosis Disease Severity Measure–Axillary seven-item score, according to the company.

Botanix plans to enable qualified patients to gain early access to the product in the third quarter of 2024, with commercial sales expected in the fourth quarter of 2024.
 

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

The Food and Drug Administration has approved a topical anticholinergic, sofpironium topical gel, 12.45%, for the treatment of primary axillary hyperhidrosis in adults and children aged ≥ 9 years.

According to a press release from Botanix Pharmaceuticals, which developed the product and will market it under the brand name Sofdra, approval was based on results from two phase 3 studies that enrolled 710 patients with primary axillary hyperhidrosis. In the trials, patients treated with sofpironium topical gel, 12.45%, experienced “clinically and statistically meaningful changes” from baseline in the Gravimetric Sweat Production and the Hyperhidrosis Disease Severity Measure–Axillary seven-item score, according to the company.

Botanix plans to enable qualified patients to gain early access to the product in the third quarter of 2024, with commercial sales expected in the fourth quarter of 2024.
 

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

The Food and Drug Administration has approved a topical anticholinergic, sofpironium topical gel, 12.45%, for the treatment of primary axillary hyperhidrosis in adults and children aged ≥ 9 years.

According to a press release from Botanix Pharmaceuticals, which developed the product and will market it under the brand name Sofdra, approval was based on results from two phase 3 studies that enrolled 710 patients with primary axillary hyperhidrosis. In the trials, patients treated with sofpironium topical gel, 12.45%, experienced “clinically and statistically meaningful changes” from baseline in the Gravimetric Sweat Production and the Hyperhidrosis Disease Severity Measure–Axillary seven-item score, according to the company.

Botanix plans to enable qualified patients to gain early access to the product in the third quarter of 2024, with commercial sales expected in the fourth quarter of 2024.
 

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

CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.

Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.

However, ctDNA’s role in guiding clinical decisions is still being defined. Australian investigators presented research showing that a negative ctDNA finding can be used to avoid unnecessary chemotherapy in postoperative stage II colon cancer patients without affecting survival outcomes, at the annual meeting of the American Society of Clinical Oncology (ASCO), in Chicago.

The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
 

DYNAMIC Trial Results

Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.

Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.

At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.

Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).

Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).

“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
 

DYNAMIC-Pancreas Study Results

In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.

At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.

Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.

In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.

“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”

The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.

“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”

But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.

Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”

Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.

Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”

Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.

Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.

CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.

Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.

However, ctDNA’s role in guiding clinical decisions is still being defined. Australian investigators presented research showing that a negative ctDNA finding can be used to avoid unnecessary chemotherapy in postoperative stage II colon cancer patients without affecting survival outcomes, at the annual meeting of the American Society of Clinical Oncology (ASCO), in Chicago.

The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
 

DYNAMIC Trial Results

Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.

Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.

At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.

Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).

Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).

“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
 

DYNAMIC-Pancreas Study Results

In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.

At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.

Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.

In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.

“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”

The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.

“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”

But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.

Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”

Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.

Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”

Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.

Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.

CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.

Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.

However, ctDNA’s role in guiding clinical decisions is still being defined. Australian investigators presented research showing that a negative ctDNA finding can be used to avoid unnecessary chemotherapy in postoperative stage II colon cancer patients without affecting survival outcomes, at the annual meeting of the American Society of Clinical Oncology (ASCO), in Chicago.

The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
 

DYNAMIC Trial Results

Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.

Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.

At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.

Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).

Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).

“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
 

DYNAMIC-Pancreas Study Results

In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.

At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.

Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.

In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.

“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”

The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.

“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”

But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.

Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”

Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.

Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”

Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.

Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.

WASHINGTON — In 2013, Vishal A. Patel, MD, was completing a fellowship in Mohs surgery and cutaneous oncology at Columbia University Irving Medical Center, New York City, when a study was published showing that most nonmelanoma skin cancers (NMSCs) were treated with surgery, regardless of the patient’s life expectancy. Life expectancy “should enter into treatment decisions,” the authors concluded.

“The article got a lot of pushback from the Mohs surgeons,” and the value of surgery in older adults and particularly those with limited life expectancy “became a hot topic,” Dr. Patel recalled at the ElderDerm conference hosted by the Department of Dermatology at George Washington University, Washington, DC, and described as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Christine Kilgore

Today, however, more than a decade later, guidelines still promote surgical therapy as the gold standard across the board, and questions raised by the study are still unaddressed, Dr. Patel, associate professor of dermatology and medicine/oncology at George Washington University, said at the meeting. These questions are becoming increasingly urgent as the incidence of skin cancer, especially NMSC, rises in the older adult population, especially in patients older than 85 years. “It’s a function of our training and our treatment guidelines that we reach for the most definitive treatment, which happens to be the most aggressive, in these patients,” added Dr. Patel, who is also director of the cutaneous oncology program at the GW Cancer Center.

“Sometimes we lose track of what ... we need to do” to provide care that reflects the best interests of the older patient, he continued. “Surgery may be the gold standard for treating the majority of NMSCs ... but is it the [best option] for what our older patients and patients with limited life expectancy need?”

Learning about what truly matters to the patient is a key element of the “age-friendly, whole-person care” that dermatologists must embrace as older adults become an increasingly large subset of their patient population, Christina Prather, MD, director and associate professor of geriatrics and palliative medicine at George Washington University, said at the meeting.

By 2040, projections are that the number of adults aged 85 years and older in the United States will be nearly quadruple the number in 2000, according to one estimate.

“We know that there are less than 6000 practicing geriatricians in the country ... [so the healthcare system] needs more of you who know how to bring an age-friendly approach to care,” Dr. Prather said. Dermatology is among the specialties that need to be “geriatricized.”
 

NMSC Increasing in the Older Population

The incidence of skin cancer is rising faster than that of any other cancer, Dr. Patel said. One window into the epidemiology, he said, comes from recently published data showing that an average of 6.1 million adults were treated each year for skin cancer during 2016-2018 (5.2 million of them for NMSC) — an increase from an average of 5.8 million annually in the 2012-2015 period. The data come from the Medical Expenditure Panel Survey (MEPS), which is conducted by the US Public Health Service through the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention.

As a frame of reference, the average number of adults treated each year for nonskin cancers during these periods rose from 10.8 to 11.9 million, according to the 2023 MEPS data. “Skin cancer is about one-third of all cancers combined,” Dr. Patel said.

Not only is the incidence of NMSC significantly higher than that of melanoma but it also shows a more prominent aging trend. This was documented recently in a long-term observational study from Japan, in which researchers looked at the change in the median age of patients with NMSC and melanoma, compared with cancers of other organs, from 1991 to 2020 and found that NMSC had by far the greatest rise in median age, to a median age of 80 years in 2021.

Even more notable, Dr. Patel said, was a particularly marked increase in the number of patients with skin cancer aged 90 years and older. In 2021, this group of older adults accounted for 17% of patients receiving treatment for skin cancer at the Japanese hospital where the data were collected.

The 2013 study that stirred Dr. Patel as a fellow was of 1536 consecutive patients diagnosed with NMSC at two dermatology clinics (a University of California San Francisco–based private clinic and a Veterans Affairs Medical Center clinic) and followed for 6 years. “What’s interesting and worth thinking about is that, regardless of patients’ life expectancy, NMSCs were treated aggressively and surgically, and the choice of surgery was not influenced by the patient’s poor prognosis in a multivariate model” adjusted for tumor and patient characteristics, he said at the meeting.

The researchers defined limited life expectancy as either 85 years or older or having a Charleston Comorbidity Index ≥ 3. Approximately half of the patients with limited life expectancy died within 5 years, none of NMSC. Most patients with limited life expectancy were not often bothered by their tumors, and approximately one in five reported a treatment complication within 2 years. The 5-year tumor recurrence rate was 3.7%.

A more recent study looked at 1181 patients older than 85 years with NMSC referred for Mohs surgery. Almost all patients in the multicenter, prospective cohort study (91.3%) were treated with Mohs.

Treated patients were more likely to have facial tumors and higher functional status than those not treated with Mohs surgery, and the most common reasons provided by surgeons for proceeding with the surgery were a patient desire for a high cure rate (66%), higher functional status for age (57%), and high-risk tumor type (40%). Almost 42% of the referred patients were 89 years or older.

“Granted, [the reasons] are justified indications for surgery,” Dr. Patel said. Yet the study brings up the question of “whether we need to do Mohs surgery this frequently in elderly patients?” In an email after the meeting, he added, “it’s a question we may need to reconsider as the elderly population continues to increase and median age of NMSC rises.”
 

Underutilized Management Options for NMSC

In his practice, discussions of treatment options are preceded by a thorough discussion of the disease itself. Many lesions are low risk, and helping patients understand risks, as well as understanding what is important to the patient — especially those with limited life expectancy — will guide shared decision-making to choose the best treatment, Dr. Patel said at the meeting.

The dermatologist’s risk assessment — both staging and stratifying risk as it relates to specific outcomes such as recurrence, metastases, or death — takes on added importance in the older patient, he emphasized. “I think we underutilize the risk assessment.”

Also underutilized is the option of shave removal for low-risk squamous cell carcinomas and basal cell carcinomas, Dr. Patel said, noting that, in the National Comprehensive Cancer Network guidelines, “there’s an option for shave removal and nothing more if you have clear margins.”

Alternatively, disc excision with the initial biopsy can often be considered. “Having that intent to treat at the time of biopsy may be all that needs to be done” in older patients with obvious or highly suspicious lesions, he said.

Systemic immunotherapy has joined the treatment armamentarium for advanced basal cell carcinoma and advanced cutaneous squamous cell carcinoma, and if early, ongoing research of intralesional programmed cell death protein 1 inhibitor treatment advances, this could be another option for older adults in the future, Dr. Patel said. Targeting drug delivery directly to the tumor would lower the total dose, decrease systemic exposure, and could be used to avoid surgery for some groups of patients, such as those with limited life expectancy.

A Personal Story, a Word on Melanoma

Dr. Prather recalled when her 97-year-old grandfather had a skin lesion on his forehead removed, and a conversation he had with her mother about whether he really needed to have the procedure because he had cognitive impairment and was on oral anticoagulants.

The clinician “said it absolutely had to go. ... I can’t tell you how much his doctors’ visits and wound care consumed my family’s life for the next few years — for this thing that never quite healed,” she said.

“Was it necessary? The more I’ve learned over time is that it wasn’t,” Dr. Prather added. “We have to take time [with our older patients] and think critically. What is feasible? What makes the most sense? What is the most important thing I need to know about the patient?”

Also important, Dr. Patel noted, is the big-picture consideration of skin cancer treatment costs. The MEPS survey data showing the rising prevalence of skin cancer treatment also documented the economic burden: A nearly 30% increase in the average annual cost of treating NMSC from $5 billion in 2012-2015 to $6.5 billion in 2016-2018. (The average annual costs of treating melanoma decreased slightly.) “Skin cancer is a big drain on our limited resources,” he said.

With melanoma as well, dermatologists must think critically and holistically about the individual patient — and not have “a single view lens of the disease and how we treat the disease,” said Dr. Patel, urging the audience to read a “Sounding Board” article published in The New England Journal of Medicine in 2021. The article argued that there is overdiagnosis of cutaneous melanoma stemming from increased screening, falling clinical thresholds for biopsy, and falling pathological thresholds for labeling morphologic changes as cancer.

“There’s a diagnostic disconnect and a problem of overdiagnosis ... because we’re afraid to miss or make a mistake,” he said. “It leads to the question, do all lesions denoted as skin cancers need aggressive treatment? What does it mean for the patient in front of you?”

Dr. Patel reported receiving honoraria from Regeneron, Almirall, Biofrontera, Sun Pharma, and SkylineDx and serving on the speaker bureau of Regeneron and Almirall. He is chief medical officer for Lazarus AI and is cofounder of the Skin Cancer Outcomes consortium. Dr. Prather disclosed relationships with the National Institutes of Health, AHRQ, The Washington Home Foundation, and the Alzheimer’s Association.

A version of this article appeared on Medscape.com.

WASHINGTON — In 2013, Vishal A. Patel, MD, was completing a fellowship in Mohs surgery and cutaneous oncology at Columbia University Irving Medical Center, New York City, when a study was published showing that most nonmelanoma skin cancers (NMSCs) were treated with surgery, regardless of the patient’s life expectancy. Life expectancy “should enter into treatment decisions,” the authors concluded.

“The article got a lot of pushback from the Mohs surgeons,” and the value of surgery in older adults and particularly those with limited life expectancy “became a hot topic,” Dr. Patel recalled at the ElderDerm conference hosted by the Department of Dermatology at George Washington University, Washington, DC, and described as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Christine Kilgore

Today, however, more than a decade later, guidelines still promote surgical therapy as the gold standard across the board, and questions raised by the study are still unaddressed, Dr. Patel, associate professor of dermatology and medicine/oncology at George Washington University, said at the meeting. These questions are becoming increasingly urgent as the incidence of skin cancer, especially NMSC, rises in the older adult population, especially in patients older than 85 years. “It’s a function of our training and our treatment guidelines that we reach for the most definitive treatment, which happens to be the most aggressive, in these patients,” added Dr. Patel, who is also director of the cutaneous oncology program at the GW Cancer Center.

“Sometimes we lose track of what ... we need to do” to provide care that reflects the best interests of the older patient, he continued. “Surgery may be the gold standard for treating the majority of NMSCs ... but is it the [best option] for what our older patients and patients with limited life expectancy need?”

Learning about what truly matters to the patient is a key element of the “age-friendly, whole-person care” that dermatologists must embrace as older adults become an increasingly large subset of their patient population, Christina Prather, MD, director and associate professor of geriatrics and palliative medicine at George Washington University, said at the meeting.

By 2040, projections are that the number of adults aged 85 years and older in the United States will be nearly quadruple the number in 2000, according to one estimate.

“We know that there are less than 6000 practicing geriatricians in the country ... [so the healthcare system] needs more of you who know how to bring an age-friendly approach to care,” Dr. Prather said. Dermatology is among the specialties that need to be “geriatricized.”
 

NMSC Increasing in the Older Population

The incidence of skin cancer is rising faster than that of any other cancer, Dr. Patel said. One window into the epidemiology, he said, comes from recently published data showing that an average of 6.1 million adults were treated each year for skin cancer during 2016-2018 (5.2 million of them for NMSC) — an increase from an average of 5.8 million annually in the 2012-2015 period. The data come from the Medical Expenditure Panel Survey (MEPS), which is conducted by the US Public Health Service through the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention.

As a frame of reference, the average number of adults treated each year for nonskin cancers during these periods rose from 10.8 to 11.9 million, according to the 2023 MEPS data. “Skin cancer is about one-third of all cancers combined,” Dr. Patel said.

Not only is the incidence of NMSC significantly higher than that of melanoma but it also shows a more prominent aging trend. This was documented recently in a long-term observational study from Japan, in which researchers looked at the change in the median age of patients with NMSC and melanoma, compared with cancers of other organs, from 1991 to 2020 and found that NMSC had by far the greatest rise in median age, to a median age of 80 years in 2021.

Even more notable, Dr. Patel said, was a particularly marked increase in the number of patients with skin cancer aged 90 years and older. In 2021, this group of older adults accounted for 17% of patients receiving treatment for skin cancer at the Japanese hospital where the data were collected.

The 2013 study that stirred Dr. Patel as a fellow was of 1536 consecutive patients diagnosed with NMSC at two dermatology clinics (a University of California San Francisco–based private clinic and a Veterans Affairs Medical Center clinic) and followed for 6 years. “What’s interesting and worth thinking about is that, regardless of patients’ life expectancy, NMSCs were treated aggressively and surgically, and the choice of surgery was not influenced by the patient’s poor prognosis in a multivariate model” adjusted for tumor and patient characteristics, he said at the meeting.

The researchers defined limited life expectancy as either 85 years or older or having a Charleston Comorbidity Index ≥ 3. Approximately half of the patients with limited life expectancy died within 5 years, none of NMSC. Most patients with limited life expectancy were not often bothered by their tumors, and approximately one in five reported a treatment complication within 2 years. The 5-year tumor recurrence rate was 3.7%.

A more recent study looked at 1181 patients older than 85 years with NMSC referred for Mohs surgery. Almost all patients in the multicenter, prospective cohort study (91.3%) were treated with Mohs.

Treated patients were more likely to have facial tumors and higher functional status than those not treated with Mohs surgery, and the most common reasons provided by surgeons for proceeding with the surgery were a patient desire for a high cure rate (66%), higher functional status for age (57%), and high-risk tumor type (40%). Almost 42% of the referred patients were 89 years or older.

“Granted, [the reasons] are justified indications for surgery,” Dr. Patel said. Yet the study brings up the question of “whether we need to do Mohs surgery this frequently in elderly patients?” In an email after the meeting, he added, “it’s a question we may need to reconsider as the elderly population continues to increase and median age of NMSC rises.”
 

Underutilized Management Options for NMSC

In his practice, discussions of treatment options are preceded by a thorough discussion of the disease itself. Many lesions are low risk, and helping patients understand risks, as well as understanding what is important to the patient — especially those with limited life expectancy — will guide shared decision-making to choose the best treatment, Dr. Patel said at the meeting.

The dermatologist’s risk assessment — both staging and stratifying risk as it relates to specific outcomes such as recurrence, metastases, or death — takes on added importance in the older patient, he emphasized. “I think we underutilize the risk assessment.”

Also underutilized is the option of shave removal for low-risk squamous cell carcinomas and basal cell carcinomas, Dr. Patel said, noting that, in the National Comprehensive Cancer Network guidelines, “there’s an option for shave removal and nothing more if you have clear margins.”

Alternatively, disc excision with the initial biopsy can often be considered. “Having that intent to treat at the time of biopsy may be all that needs to be done” in older patients with obvious or highly suspicious lesions, he said.

Systemic immunotherapy has joined the treatment armamentarium for advanced basal cell carcinoma and advanced cutaneous squamous cell carcinoma, and if early, ongoing research of intralesional programmed cell death protein 1 inhibitor treatment advances, this could be another option for older adults in the future, Dr. Patel said. Targeting drug delivery directly to the tumor would lower the total dose, decrease systemic exposure, and could be used to avoid surgery for some groups of patients, such as those with limited life expectancy.

A Personal Story, a Word on Melanoma

Dr. Prather recalled when her 97-year-old grandfather had a skin lesion on his forehead removed, and a conversation he had with her mother about whether he really needed to have the procedure because he had cognitive impairment and was on oral anticoagulants.

The clinician “said it absolutely had to go. ... I can’t tell you how much his doctors’ visits and wound care consumed my family’s life for the next few years — for this thing that never quite healed,” she said.

“Was it necessary? The more I’ve learned over time is that it wasn’t,” Dr. Prather added. “We have to take time [with our older patients] and think critically. What is feasible? What makes the most sense? What is the most important thing I need to know about the patient?”

Also important, Dr. Patel noted, is the big-picture consideration of skin cancer treatment costs. The MEPS survey data showing the rising prevalence of skin cancer treatment also documented the economic burden: A nearly 30% increase in the average annual cost of treating NMSC from $5 billion in 2012-2015 to $6.5 billion in 2016-2018. (The average annual costs of treating melanoma decreased slightly.) “Skin cancer is a big drain on our limited resources,” he said.

With melanoma as well, dermatologists must think critically and holistically about the individual patient — and not have “a single view lens of the disease and how we treat the disease,” said Dr. Patel, urging the audience to read a “Sounding Board” article published in The New England Journal of Medicine in 2021. The article argued that there is overdiagnosis of cutaneous melanoma stemming from increased screening, falling clinical thresholds for biopsy, and falling pathological thresholds for labeling morphologic changes as cancer.

“There’s a diagnostic disconnect and a problem of overdiagnosis ... because we’re afraid to miss or make a mistake,” he said. “It leads to the question, do all lesions denoted as skin cancers need aggressive treatment? What does it mean for the patient in front of you?”

Dr. Patel reported receiving honoraria from Regeneron, Almirall, Biofrontera, Sun Pharma, and SkylineDx and serving on the speaker bureau of Regeneron and Almirall. He is chief medical officer for Lazarus AI and is cofounder of the Skin Cancer Outcomes consortium. Dr. Prather disclosed relationships with the National Institutes of Health, AHRQ, The Washington Home Foundation, and the Alzheimer’s Association.

A version of this article appeared on Medscape.com.

WASHINGTON — In 2013, Vishal A. Patel, MD, was completing a fellowship in Mohs surgery and cutaneous oncology at Columbia University Irving Medical Center, New York City, when a study was published showing that most nonmelanoma skin cancers (NMSCs) were treated with surgery, regardless of the patient’s life expectancy. Life expectancy “should enter into treatment decisions,” the authors concluded.

“The article got a lot of pushback from the Mohs surgeons,” and the value of surgery in older adults and particularly those with limited life expectancy “became a hot topic,” Dr. Patel recalled at the ElderDerm conference hosted by the Department of Dermatology at George Washington University, Washington, DC, and described as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Christine Kilgore

Today, however, more than a decade later, guidelines still promote surgical therapy as the gold standard across the board, and questions raised by the study are still unaddressed, Dr. Patel, associate professor of dermatology and medicine/oncology at George Washington University, said at the meeting. These questions are becoming increasingly urgent as the incidence of skin cancer, especially NMSC, rises in the older adult population, especially in patients older than 85 years. “It’s a function of our training and our treatment guidelines that we reach for the most definitive treatment, which happens to be the most aggressive, in these patients,” added Dr. Patel, who is also director of the cutaneous oncology program at the GW Cancer Center.

“Sometimes we lose track of what ... we need to do” to provide care that reflects the best interests of the older patient, he continued. “Surgery may be the gold standard for treating the majority of NMSCs ... but is it the [best option] for what our older patients and patients with limited life expectancy need?”

Learning about what truly matters to the patient is a key element of the “age-friendly, whole-person care” that dermatologists must embrace as older adults become an increasingly large subset of their patient population, Christina Prather, MD, director and associate professor of geriatrics and palliative medicine at George Washington University, said at the meeting.

By 2040, projections are that the number of adults aged 85 years and older in the United States will be nearly quadruple the number in 2000, according to one estimate.

“We know that there are less than 6000 practicing geriatricians in the country ... [so the healthcare system] needs more of you who know how to bring an age-friendly approach to care,” Dr. Prather said. Dermatology is among the specialties that need to be “geriatricized.”
 

NMSC Increasing in the Older Population

The incidence of skin cancer is rising faster than that of any other cancer, Dr. Patel said. One window into the epidemiology, he said, comes from recently published data showing that an average of 6.1 million adults were treated each year for skin cancer during 2016-2018 (5.2 million of them for NMSC) — an increase from an average of 5.8 million annually in the 2012-2015 period. The data come from the Medical Expenditure Panel Survey (MEPS), which is conducted by the US Public Health Service through the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention.

As a frame of reference, the average number of adults treated each year for nonskin cancers during these periods rose from 10.8 to 11.9 million, according to the 2023 MEPS data. “Skin cancer is about one-third of all cancers combined,” Dr. Patel said.

Not only is the incidence of NMSC significantly higher than that of melanoma but it also shows a more prominent aging trend. This was documented recently in a long-term observational study from Japan, in which researchers looked at the change in the median age of patients with NMSC and melanoma, compared with cancers of other organs, from 1991 to 2020 and found that NMSC had by far the greatest rise in median age, to a median age of 80 years in 2021.

Even more notable, Dr. Patel said, was a particularly marked increase in the number of patients with skin cancer aged 90 years and older. In 2021, this group of older adults accounted for 17% of patients receiving treatment for skin cancer at the Japanese hospital where the data were collected.

The 2013 study that stirred Dr. Patel as a fellow was of 1536 consecutive patients diagnosed with NMSC at two dermatology clinics (a University of California San Francisco–based private clinic and a Veterans Affairs Medical Center clinic) and followed for 6 years. “What’s interesting and worth thinking about is that, regardless of patients’ life expectancy, NMSCs were treated aggressively and surgically, and the choice of surgery was not influenced by the patient’s poor prognosis in a multivariate model” adjusted for tumor and patient characteristics, he said at the meeting.

The researchers defined limited life expectancy as either 85 years or older or having a Charleston Comorbidity Index ≥ 3. Approximately half of the patients with limited life expectancy died within 5 years, none of NMSC. Most patients with limited life expectancy were not often bothered by their tumors, and approximately one in five reported a treatment complication within 2 years. The 5-year tumor recurrence rate was 3.7%.

A more recent study looked at 1181 patients older than 85 years with NMSC referred for Mohs surgery. Almost all patients in the multicenter, prospective cohort study (91.3%) were treated with Mohs.

Treated patients were more likely to have facial tumors and higher functional status than those not treated with Mohs surgery, and the most common reasons provided by surgeons for proceeding with the surgery were a patient desire for a high cure rate (66%), higher functional status for age (57%), and high-risk tumor type (40%). Almost 42% of the referred patients were 89 years or older.

“Granted, [the reasons] are justified indications for surgery,” Dr. Patel said. Yet the study brings up the question of “whether we need to do Mohs surgery this frequently in elderly patients?” In an email after the meeting, he added, “it’s a question we may need to reconsider as the elderly population continues to increase and median age of NMSC rises.”
 

Underutilized Management Options for NMSC

In his practice, discussions of treatment options are preceded by a thorough discussion of the disease itself. Many lesions are low risk, and helping patients understand risks, as well as understanding what is important to the patient — especially those with limited life expectancy — will guide shared decision-making to choose the best treatment, Dr. Patel said at the meeting.

The dermatologist’s risk assessment — both staging and stratifying risk as it relates to specific outcomes such as recurrence, metastases, or death — takes on added importance in the older patient, he emphasized. “I think we underutilize the risk assessment.”

Also underutilized is the option of shave removal for low-risk squamous cell carcinomas and basal cell carcinomas, Dr. Patel said, noting that, in the National Comprehensive Cancer Network guidelines, “there’s an option for shave removal and nothing more if you have clear margins.”

Alternatively, disc excision with the initial biopsy can often be considered. “Having that intent to treat at the time of biopsy may be all that needs to be done” in older patients with obvious or highly suspicious lesions, he said.

Systemic immunotherapy has joined the treatment armamentarium for advanced basal cell carcinoma and advanced cutaneous squamous cell carcinoma, and if early, ongoing research of intralesional programmed cell death protein 1 inhibitor treatment advances, this could be another option for older adults in the future, Dr. Patel said. Targeting drug delivery directly to the tumor would lower the total dose, decrease systemic exposure, and could be used to avoid surgery for some groups of patients, such as those with limited life expectancy.

A Personal Story, a Word on Melanoma

Dr. Prather recalled when her 97-year-old grandfather had a skin lesion on his forehead removed, and a conversation he had with her mother about whether he really needed to have the procedure because he had cognitive impairment and was on oral anticoagulants.

The clinician “said it absolutely had to go. ... I can’t tell you how much his doctors’ visits and wound care consumed my family’s life for the next few years — for this thing that never quite healed,” she said.

“Was it necessary? The more I’ve learned over time is that it wasn’t,” Dr. Prather added. “We have to take time [with our older patients] and think critically. What is feasible? What makes the most sense? What is the most important thing I need to know about the patient?”

Also important, Dr. Patel noted, is the big-picture consideration of skin cancer treatment costs. The MEPS survey data showing the rising prevalence of skin cancer treatment also documented the economic burden: A nearly 30% increase in the average annual cost of treating NMSC from $5 billion in 2012-2015 to $6.5 billion in 2016-2018. (The average annual costs of treating melanoma decreased slightly.) “Skin cancer is a big drain on our limited resources,” he said.

With melanoma as well, dermatologists must think critically and holistically about the individual patient — and not have “a single view lens of the disease and how we treat the disease,” said Dr. Patel, urging the audience to read a “Sounding Board” article published in The New England Journal of Medicine in 2021. The article argued that there is overdiagnosis of cutaneous melanoma stemming from increased screening, falling clinical thresholds for biopsy, and falling pathological thresholds for labeling morphologic changes as cancer.

“There’s a diagnostic disconnect and a problem of overdiagnosis ... because we’re afraid to miss or make a mistake,” he said. “It leads to the question, do all lesions denoted as skin cancers need aggressive treatment? What does it mean for the patient in front of you?”

Dr. Patel reported receiving honoraria from Regeneron, Almirall, Biofrontera, Sun Pharma, and SkylineDx and serving on the speaker bureau of Regeneron and Almirall. He is chief medical officer for Lazarus AI and is cofounder of the Skin Cancer Outcomes consortium. Dr. Prather disclosed relationships with the National Institutes of Health, AHRQ, The Washington Home Foundation, and the Alzheimer’s Association.

A version of this article appeared on Medscape.com.

VIENNA — To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.

“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.

The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.

The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.

“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.

A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.

Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.

Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.

At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.

At 2 years, the proportion of patients maintained at the target sUA was almost twice as great in the nurse-led arm (83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m² (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).

The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.

Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.

The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).

Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
 

Potential Advantages of Nurse-Led Care

Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.

“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.

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

VIENNA — To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.

“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.

The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.

The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.

“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.

A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.

Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.

Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.

At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.

At 2 years, the proportion of patients maintained at the target sUA was almost twice as great in the nurse-led arm (83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m² (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).

The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.

Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.

The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).

Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
 

Potential Advantages of Nurse-Led Care

Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.

“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.

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

VIENNA — To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.

“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.

The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.

The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.

“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.

A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.

Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.

Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.

At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.

At 2 years, the proportion of patients maintained at the target sUA was almost twice as great in the nurse-led arm (83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m² (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).

The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.

Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.

The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).

Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
 

Potential Advantages of Nurse-Led Care

Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.

“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.

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

TOPLINE:

A study reveals that hydroxychloroquine levels during the first trimester in pregnant women with systemic lupus erythematosus (SLE) are linked to severe maternal flares but not to adverse pregnancy outcomes.

METHODOLOGY:

• Researchers included pregnant women with SLE (median age, 32.1 years; median duration of disease, 8.3 years) who were enrolled in an ongoing French prospective observational study and were receiving hydroxychloroquine.
• The study assessed hydroxychloroquine blood levels during the first trimester. It defined severe nonadherence as having levels < 200 ng/mL and classified levels < 500 ng/mL as subtherapeutic.
• Primary outcomes were maternal flares during pregnancy and adverse pregnancy outcomes, including fetal/neonatal death and preterm delivery.

TAKEAWAY:

• Overall, 32 women experienced at least one flare during the second and third trimester; four had severe flares.
• The rates of severe maternal SLE flares were significantly associated with hydroxychloroquine levels in the first trimester that were classified as subtherapeutic (8.8% vs 0.7% with above subtherapeutic levels, P = .02) and severely nonadherent (13.3% vs 1.3% with above severely nonadherent levels, P = .04).
• There was no significant difference in adverse pregnancy outcomes by hydroxychloroquine level, suggesting its specific effect on maternal health rather than fetal health.

IN PRACTICE:

According to the authors, “this study supports hydroxychloroquine blood level assessment in pregnant women with SLE, as a predictor of severe maternal disease activity in pregnancy.”

SOURCE:

The study was led by Gelsomina Alle, MD, Assistance Publique-Hôpitaux de Paris, Paris, France. It was published online in Rheumatology.

LIMITATIONS:

The study’s sample size limited the ability to perform multivariate analyses for severe flares. Patients had to have an ongoing pregnancy at 12 weeks to be included, potentially excluding those with early pregnancy loss. The study only observed first-trimester hydroxychloroquine levels, not accounting for adherence variations throughout pregnancy.

DISCLOSURES:

The study funding source was not disclosed. Several authors declared financial relationships with pharmaceutical companies, including research support and consulting fees.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

A study reveals that hydroxychloroquine levels during the first trimester in pregnant women with systemic lupus erythematosus (SLE) are linked to severe maternal flares but not to adverse pregnancy outcomes.

METHODOLOGY:

• Researchers included pregnant women with SLE (median age, 32.1 years; median duration of disease, 8.3 years) who were enrolled in an ongoing French prospective observational study and were receiving hydroxychloroquine.
• The study assessed hydroxychloroquine blood levels during the first trimester. It defined severe nonadherence as having levels < 200 ng/mL and classified levels < 500 ng/mL as subtherapeutic.
• Primary outcomes were maternal flares during pregnancy and adverse pregnancy outcomes, including fetal/neonatal death and preterm delivery.

TAKEAWAY:

• Overall, 32 women experienced at least one flare during the second and third trimester; four had severe flares.
• The rates of severe maternal SLE flares were significantly associated with hydroxychloroquine levels in the first trimester that were classified as subtherapeutic (8.8% vs 0.7% with above subtherapeutic levels, P = .02) and severely nonadherent (13.3% vs 1.3% with above severely nonadherent levels, P = .04).
• There was no significant difference in adverse pregnancy outcomes by hydroxychloroquine level, suggesting its specific effect on maternal health rather than fetal health.

IN PRACTICE:

According to the authors, “this study supports hydroxychloroquine blood level assessment in pregnant women with SLE, as a predictor of severe maternal disease activity in pregnancy.”

SOURCE:

The study was led by Gelsomina Alle, MD, Assistance Publique-Hôpitaux de Paris, Paris, France. It was published online in Rheumatology.

LIMITATIONS:

The study’s sample size limited the ability to perform multivariate analyses for severe flares. Patients had to have an ongoing pregnancy at 12 weeks to be included, potentially excluding those with early pregnancy loss. The study only observed first-trimester hydroxychloroquine levels, not accounting for adherence variations throughout pregnancy.

DISCLOSURES:

The study funding source was not disclosed. Several authors declared financial relationships with pharmaceutical companies, including research support and consulting fees.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

A study reveals that hydroxychloroquine levels during the first trimester in pregnant women with systemic lupus erythematosus (SLE) are linked to severe maternal flares but not to adverse pregnancy outcomes.

METHODOLOGY:

• Researchers included pregnant women with SLE (median age, 32.1 years; median duration of disease, 8.3 years) who were enrolled in an ongoing French prospective observational study and were receiving hydroxychloroquine.
• The study assessed hydroxychloroquine blood levels during the first trimester. It defined severe nonadherence as having levels < 200 ng/mL and classified levels < 500 ng/mL as subtherapeutic.
• Primary outcomes were maternal flares during pregnancy and adverse pregnancy outcomes, including fetal/neonatal death and preterm delivery.

TAKEAWAY:

• Overall, 32 women experienced at least one flare during the second and third trimester; four had severe flares.
• The rates of severe maternal SLE flares were significantly associated with hydroxychloroquine levels in the first trimester that were classified as subtherapeutic (8.8% vs 0.7% with above subtherapeutic levels, P = .02) and severely nonadherent (13.3% vs 1.3% with above severely nonadherent levels, P = .04).
• There was no significant difference in adverse pregnancy outcomes by hydroxychloroquine level, suggesting its specific effect on maternal health rather than fetal health.

IN PRACTICE:

According to the authors, “this study supports hydroxychloroquine blood level assessment in pregnant women with SLE, as a predictor of severe maternal disease activity in pregnancy.”

SOURCE:

The study was led by Gelsomina Alle, MD, Assistance Publique-Hôpitaux de Paris, Paris, France. It was published online in Rheumatology.

LIMITATIONS:

The study’s sample size limited the ability to perform multivariate analyses for severe flares. Patients had to have an ongoing pregnancy at 12 weeks to be included, potentially excluding those with early pregnancy loss. The study only observed first-trimester hydroxychloroquine levels, not accounting for adherence variations throughout pregnancy.

DISCLOSURES:

The study funding source was not disclosed. Several authors declared financial relationships with pharmaceutical companies, including research support and consulting fees.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Men with immunoglobulin G4 (IgG4)-related disease exhibit significantly lower serum lipase levels and a greater likelihood of organ involvement than women, highlighting significant sex-dependent differences in disease manifestations.

METHODOLOGY:

• Researchers conducted a retrospective study of 328 patients (69% men) diagnosed with IgG4-related disease at the Massachusetts General Hospital – Rheumatology Clinic, Boston, who met the American College of Rheumatology–European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria between January 2008 and May 2023.
• Among the 328 patients, 69% were men and 31% were women, with a significant male-to-female ratio of 2.2:1.0. Men were typically older at diagnosis (median age, 63.7 vs 58.2 years).
• Data on serum lipase levels, renal involvement, and other clinical and laboratory parameters were collected.

TAKEAWAY:

• Men had higher baseline ACR-EULAR scores, indicating more severe disease (median score of 35.0 vs 29.5; P = .0010).
• Male patients demonstrated a median baseline serum lipase concentration of 24.5 U/L, significantly lower than the 33.5 U/L observed in women.
• Pancreatic (50% vs 26%) or renal (36% vs 18%) involvement was more common in men.
• Men exhibited higher IgG4 levels (P = .0050) and active B-cell responses in the blood (P = .0095).

IN PRACTICE:

According to the authors, this work confirms “the impression of an important sex disparity among patients with IgG4-related disease, with most patients being male, and male patients demonstrating strong tendencies toward more severe disease than female patients.”

SOURCE:

The study was led by Isha Jha, MD, Massachusetts General Hospital, Boston. It was published online on May 30, 2024, in The Lancet Rheumatology. 

LIMITATIONS:

The study’s retrospective design may limit the ability to establish causality between sex differences and IgG4-related disease manifestations. A relatively small percentage of patients were assessed before receiving any immunosuppressive treatment, potentially influencing the observed clinical parameters.

DISCLOSURES:

This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors declared financial ties outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Men with immunoglobulin G4 (IgG4)-related disease exhibit significantly lower serum lipase levels and a greater likelihood of organ involvement than women, highlighting significant sex-dependent differences in disease manifestations.

METHODOLOGY:

• Researchers conducted a retrospective study of 328 patients (69% men) diagnosed with IgG4-related disease at the Massachusetts General Hospital – Rheumatology Clinic, Boston, who met the American College of Rheumatology–European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria between January 2008 and May 2023.
• Among the 328 patients, 69% were men and 31% were women, with a significant male-to-female ratio of 2.2:1.0. Men were typically older at diagnosis (median age, 63.7 vs 58.2 years).
• Data on serum lipase levels, renal involvement, and other clinical and laboratory parameters were collected.

TAKEAWAY:

• Men had higher baseline ACR-EULAR scores, indicating more severe disease (median score of 35.0 vs 29.5; P = .0010).
• Male patients demonstrated a median baseline serum lipase concentration of 24.5 U/L, significantly lower than the 33.5 U/L observed in women.
• Pancreatic (50% vs 26%) or renal (36% vs 18%) involvement was more common in men.
• Men exhibited higher IgG4 levels (P = .0050) and active B-cell responses in the blood (P = .0095).

IN PRACTICE:

According to the authors, this work confirms “the impression of an important sex disparity among patients with IgG4-related disease, with most patients being male, and male patients demonstrating strong tendencies toward more severe disease than female patients.”

SOURCE:

The study was led by Isha Jha, MD, Massachusetts General Hospital, Boston. It was published online on May 30, 2024, in The Lancet Rheumatology. 

LIMITATIONS:

The study’s retrospective design may limit the ability to establish causality between sex differences and IgG4-related disease manifestations. A relatively small percentage of patients were assessed before receiving any immunosuppressive treatment, potentially influencing the observed clinical parameters.

DISCLOSURES:

This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors declared financial ties outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Men with immunoglobulin G4 (IgG4)-related disease exhibit significantly lower serum lipase levels and a greater likelihood of organ involvement than women, highlighting significant sex-dependent differences in disease manifestations.

METHODOLOGY:

• Researchers conducted a retrospective study of 328 patients (69% men) diagnosed with IgG4-related disease at the Massachusetts General Hospital – Rheumatology Clinic, Boston, who met the American College of Rheumatology–European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria between January 2008 and May 2023.
• Among the 328 patients, 69% were men and 31% were women, with a significant male-to-female ratio of 2.2:1.0. Men were typically older at diagnosis (median age, 63.7 vs 58.2 years).
• Data on serum lipase levels, renal involvement, and other clinical and laboratory parameters were collected.

TAKEAWAY:

• Men had higher baseline ACR-EULAR scores, indicating more severe disease (median score of 35.0 vs 29.5; P = .0010).
• Male patients demonstrated a median baseline serum lipase concentration of 24.5 U/L, significantly lower than the 33.5 U/L observed in women.
• Pancreatic (50% vs 26%) or renal (36% vs 18%) involvement was more common in men.
• Men exhibited higher IgG4 levels (P = .0050) and active B-cell responses in the blood (P = .0095).

IN PRACTICE:

According to the authors, this work confirms “the impression of an important sex disparity among patients with IgG4-related disease, with most patients being male, and male patients demonstrating strong tendencies toward more severe disease than female patients.”

SOURCE:

The study was led by Isha Jha, MD, Massachusetts General Hospital, Boston. It was published online on May 30, 2024, in The Lancet Rheumatology. 

LIMITATIONS:

The study’s retrospective design may limit the ability to establish causality between sex differences and IgG4-related disease manifestations. A relatively small percentage of patients were assessed before receiving any immunosuppressive treatment, potentially influencing the observed clinical parameters.

DISCLOSURES:

This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors declared financial ties outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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