A low-sodium diet was not associated with a reduction in future clinical events in a new study in ambulatory patients with heart failure. But there was a moderate benefit on quality of life and New York Heart Association (NYHA) functional class.

“The guidelines used to strongly recommend a reduction in sodium intake in heart failure patients, but this advice has backed off in recent years because of the lack of data. Most heart failure guidelines now do not make any recommendations on dietary sodium,” he said.

SODIUM-HF was a pragmatic, multinational, open-label, randomized trial conducted in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand), which included 809 patients (median age, 67 years) with chronic heart failure (NYHA functional class II–III) who were receiving optimally tolerated guideline-directed medical treatment. They were randomly assigned to usual care according to local guidelines or a low-sodium diet of less than 100 mmol (<1,500 mg/day). Patients with a baseline sodium intake of less than 1,500 mg/day were excluded.

In the intervention group, patients were asked to follow low-sodium menus developed by dietitians localized to each region. They also received behavioral counseling by trained dietitians or physicians or nurses.

Dietary sodium intake was assessed by using a 3-day food record (including 1 weekend day) at baseline, 6 months, and 12 months in both groups and, for the intervention group, also at 3 and 9 months to monitor and support dietary adherence.

Dr. Ezekowitz explained that although the best method for measuring sodium levels would normally be a 24-hour urine sodium, this would be impractical in a large clinical trial. In addition, he pointed out that urinary sodium is not an accurate measure of actual sodium levels in patients taking diuretics, so it is not a good measure to use in a heart failure population.

“The food record method of assessing sodium levels has been well validated; I think we measured it as accurately as we could have done,” he added.

Results showed that between baseline and 12 months, the median sodium intake decreased from 2,286 mg/day to 1,658 mg/day in the low-sodium group and from 2,119 mg/day to 2,073 mg/day in the usual care group. The median difference between groups was 415 mg/day at 12 months.

By 12 months, events comprising the primary outcome (hospitalization or emergency department visits due to cardiovascular causes or all-cause death) had occurred in 15% of patients in the low-sodium diet group and 17% of those in the usual care group (hazard ratio [HR], 0.89 [95% CI, 0.63 - 1.26]; P = .53).

All-cause death occurred in 6% of patients in the low-sodium diet group and 4% of those in the usual care group (HR, 1.38; P = .32). Cardiovascular-related hospitalization occurred in 10% of the low-sodium group and 12% of the usual care group (HR, 0.82; P = .36), and cardiovascular-related emergency department visits occurred in 4% of both groups (HR, 1.21; P = .60).

The absence of treatment effect for the primary outcome was consistent across most prespecified subgroups, including those with higher vs lower baseline sodium intake. But there was a suggestion of a greater reduction in the primary outcome in individuals younger than age 65 years than in those age 65 years and older.

Quality-of-life measures on the Kansas City Cardiomyopathy Questionnaire (KCCQ) suggested a benefit in the low-sodium group, with mean between-group differences in the change from baseline to 12 months of 3.38 points in the overall summary score, 3.29 points in the clinical summary score, and 3.77 points in the physical limitation score (all differences were statistically significant).

There was no significant difference in 6-minute-walk distance at 12 months between the low-sodium diet group and the usual care group.

NYHA functional class at 12 months differed significantly between groups; the low-sodium diet group had a greater likelihood of improving by one NYHA class than the usual care group (odds ratio, 0.59; P = .0061).

No safety events related to the study treatment were reported in either group.

Dr. Ezekowitz said that to investigate whether longer follow-up may show a difference in events, further analyses are planned at 2 years and 5 years.

Questions on food recall and blinding

Commenting on the findings at the late-breaking clinical trials session at the ACC meeting, Biykem Bozkurt, MD, professor of medicine at Baylor College of Medicine, Houston, congratulated Dr. Ezekowitz on conducting this trial.

“We have been chasing the holy grail of sodium reduction in heart failure for a very long time, so I have to commend you and your team for taking on this challenge, especially during the pandemic,” she said.

But Dr. Bozkurt questioned whether the intervention group actually had a meaningful sodium reduction given that this was measured by food recall and this may have been accounted for by under-reporting of certain food intakes.

Dr. Ezekowitz responded that patients acted as their own controls in that calorie intake, fluid intake, and weight were also assessed and did not change. “So I think we did have a meaningful reduction in sodium,” he said.

Dr. Bozkurt also queried whether the improvements in quality of life and functional status were reliable given that this was an unblinded study.

To this point, Dr. Ezekowitz pointed out that the KCCQ quality-of-life measure was a highly validated instrument and that improvements were seen in these measures at 3, 6, and 12 months. “It is not like these were spurious findings, so I think we have to look at this as a real result,” he argued.

Commenting on the study at an ACC press conference, Mary Norine Walsh, MD, director of the heart failure and cardiac transplantation programs at St. Vincent Heart Center in Indianapolis, said the trial had answered two important questions: that sodium reduction in heart failure may not reduce heart failure hospitalization/death but that patients feel better.

“I think we can safely tell patients that if they slip up a bit they may not end up in hospital,” she added.

This study was funded by the Canadian Institutes of Health Research and the University Hospital Foundation (Edmonton, Alberta, Canada) and the Health Research Council of New Zealand. Dr. Ezekowitz reports research grants from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, eko.ai, US2.ai, Merck, Novartis, Otsuka, Sanofi, and Servier and consulting fees from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Merck, Novartis, Otsuka, Sanofi, and Servier.

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

A low-sodium diet was not associated with a reduction in future clinical events in a new study in ambulatory patients with heart failure. But there was a moderate benefit on quality of life and New York Heart Association (NYHA) functional class.

“The guidelines used to strongly recommend a reduction in sodium intake in heart failure patients, but this advice has backed off in recent years because of the lack of data. Most heart failure guidelines now do not make any recommendations on dietary sodium,” he said.

SODIUM-HF was a pragmatic, multinational, open-label, randomized trial conducted in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand), which included 809 patients (median age, 67 years) with chronic heart failure (NYHA functional class II–III) who were receiving optimally tolerated guideline-directed medical treatment. They were randomly assigned to usual care according to local guidelines or a low-sodium diet of less than 100 mmol (<1,500 mg/day). Patients with a baseline sodium intake of less than 1,500 mg/day were excluded.

In the intervention group, patients were asked to follow low-sodium menus developed by dietitians localized to each region. They also received behavioral counseling by trained dietitians or physicians or nurses.

Dietary sodium intake was assessed by using a 3-day food record (including 1 weekend day) at baseline, 6 months, and 12 months in both groups and, for the intervention group, also at 3 and 9 months to monitor and support dietary adherence.

Dr. Ezekowitz explained that although the best method for measuring sodium levels would normally be a 24-hour urine sodium, this would be impractical in a large clinical trial. In addition, he pointed out that urinary sodium is not an accurate measure of actual sodium levels in patients taking diuretics, so it is not a good measure to use in a heart failure population.

“The food record method of assessing sodium levels has been well validated; I think we measured it as accurately as we could have done,” he added.

Results showed that between baseline and 12 months, the median sodium intake decreased from 2,286 mg/day to 1,658 mg/day in the low-sodium group and from 2,119 mg/day to 2,073 mg/day in the usual care group. The median difference between groups was 415 mg/day at 12 months.

By 12 months, events comprising the primary outcome (hospitalization or emergency department visits due to cardiovascular causes or all-cause death) had occurred in 15% of patients in the low-sodium diet group and 17% of those in the usual care group (hazard ratio [HR], 0.89 [95% CI, 0.63 - 1.26]; P = .53).

All-cause death occurred in 6% of patients in the low-sodium diet group and 4% of those in the usual care group (HR, 1.38; P = .32). Cardiovascular-related hospitalization occurred in 10% of the low-sodium group and 12% of the usual care group (HR, 0.82; P = .36), and cardiovascular-related emergency department visits occurred in 4% of both groups (HR, 1.21; P = .60).

The absence of treatment effect for the primary outcome was consistent across most prespecified subgroups, including those with higher vs lower baseline sodium intake. But there was a suggestion of a greater reduction in the primary outcome in individuals younger than age 65 years than in those age 65 years and older.

Quality-of-life measures on the Kansas City Cardiomyopathy Questionnaire (KCCQ) suggested a benefit in the low-sodium group, with mean between-group differences in the change from baseline to 12 months of 3.38 points in the overall summary score, 3.29 points in the clinical summary score, and 3.77 points in the physical limitation score (all differences were statistically significant).

There was no significant difference in 6-minute-walk distance at 12 months between the low-sodium diet group and the usual care group.

NYHA functional class at 12 months differed significantly between groups; the low-sodium diet group had a greater likelihood of improving by one NYHA class than the usual care group (odds ratio, 0.59; P = .0061).

No safety events related to the study treatment were reported in either group.

Dr. Ezekowitz said that to investigate whether longer follow-up may show a difference in events, further analyses are planned at 2 years and 5 years.

Questions on food recall and blinding

Commenting on the findings at the late-breaking clinical trials session at the ACC meeting, Biykem Bozkurt, MD, professor of medicine at Baylor College of Medicine, Houston, congratulated Dr. Ezekowitz on conducting this trial.

“We have been chasing the holy grail of sodium reduction in heart failure for a very long time, so I have to commend you and your team for taking on this challenge, especially during the pandemic,” she said.

But Dr. Bozkurt questioned whether the intervention group actually had a meaningful sodium reduction given that this was measured by food recall and this may have been accounted for by under-reporting of certain food intakes.

Dr. Ezekowitz responded that patients acted as their own controls in that calorie intake, fluid intake, and weight were also assessed and did not change. “So I think we did have a meaningful reduction in sodium,” he said.

Dr. Bozkurt also queried whether the improvements in quality of life and functional status were reliable given that this was an unblinded study.

To this point, Dr. Ezekowitz pointed out that the KCCQ quality-of-life measure was a highly validated instrument and that improvements were seen in these measures at 3, 6, and 12 months. “It is not like these were spurious findings, so I think we have to look at this as a real result,” he argued.

Commenting on the study at an ACC press conference, Mary Norine Walsh, MD, director of the heart failure and cardiac transplantation programs at St. Vincent Heart Center in Indianapolis, said the trial had answered two important questions: that sodium reduction in heart failure may not reduce heart failure hospitalization/death but that patients feel better.

“I think we can safely tell patients that if they slip up a bit they may not end up in hospital,” she added.

This study was funded by the Canadian Institutes of Health Research and the University Hospital Foundation (Edmonton, Alberta, Canada) and the Health Research Council of New Zealand. Dr. Ezekowitz reports research grants from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, eko.ai, US2.ai, Merck, Novartis, Otsuka, Sanofi, and Servier and consulting fees from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Merck, Novartis, Otsuka, Sanofi, and Servier.

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

A low-sodium diet was not associated with a reduction in future clinical events in a new study in ambulatory patients with heart failure. But there was a moderate benefit on quality of life and New York Heart Association (NYHA) functional class.

“The guidelines used to strongly recommend a reduction in sodium intake in heart failure patients, but this advice has backed off in recent years because of the lack of data. Most heart failure guidelines now do not make any recommendations on dietary sodium,” he said.

SODIUM-HF was a pragmatic, multinational, open-label, randomized trial conducted in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand), which included 809 patients (median age, 67 years) with chronic heart failure (NYHA functional class II–III) who were receiving optimally tolerated guideline-directed medical treatment. They were randomly assigned to usual care according to local guidelines or a low-sodium diet of less than 100 mmol (<1,500 mg/day). Patients with a baseline sodium intake of less than 1,500 mg/day were excluded.

In the intervention group, patients were asked to follow low-sodium menus developed by dietitians localized to each region. They also received behavioral counseling by trained dietitians or physicians or nurses.

Dietary sodium intake was assessed by using a 3-day food record (including 1 weekend day) at baseline, 6 months, and 12 months in both groups and, for the intervention group, also at 3 and 9 months to monitor and support dietary adherence.

Dr. Ezekowitz explained that although the best method for measuring sodium levels would normally be a 24-hour urine sodium, this would be impractical in a large clinical trial. In addition, he pointed out that urinary sodium is not an accurate measure of actual sodium levels in patients taking diuretics, so it is not a good measure to use in a heart failure population.

“The food record method of assessing sodium levels has been well validated; I think we measured it as accurately as we could have done,” he added.

Results showed that between baseline and 12 months, the median sodium intake decreased from 2,286 mg/day to 1,658 mg/day in the low-sodium group and from 2,119 mg/day to 2,073 mg/day in the usual care group. The median difference between groups was 415 mg/day at 12 months.

By 12 months, events comprising the primary outcome (hospitalization or emergency department visits due to cardiovascular causes or all-cause death) had occurred in 15% of patients in the low-sodium diet group and 17% of those in the usual care group (hazard ratio [HR], 0.89 [95% CI, 0.63 - 1.26]; P = .53).

All-cause death occurred in 6% of patients in the low-sodium diet group and 4% of those in the usual care group (HR, 1.38; P = .32). Cardiovascular-related hospitalization occurred in 10% of the low-sodium group and 12% of the usual care group (HR, 0.82; P = .36), and cardiovascular-related emergency department visits occurred in 4% of both groups (HR, 1.21; P = .60).

The absence of treatment effect for the primary outcome was consistent across most prespecified subgroups, including those with higher vs lower baseline sodium intake. But there was a suggestion of a greater reduction in the primary outcome in individuals younger than age 65 years than in those age 65 years and older.

Quality-of-life measures on the Kansas City Cardiomyopathy Questionnaire (KCCQ) suggested a benefit in the low-sodium group, with mean between-group differences in the change from baseline to 12 months of 3.38 points in the overall summary score, 3.29 points in the clinical summary score, and 3.77 points in the physical limitation score (all differences were statistically significant).

There was no significant difference in 6-minute-walk distance at 12 months between the low-sodium diet group and the usual care group.

NYHA functional class at 12 months differed significantly between groups; the low-sodium diet group had a greater likelihood of improving by one NYHA class than the usual care group (odds ratio, 0.59; P = .0061).

No safety events related to the study treatment were reported in either group.

Dr. Ezekowitz said that to investigate whether longer follow-up may show a difference in events, further analyses are planned at 2 years and 5 years.

Questions on food recall and blinding

Commenting on the findings at the late-breaking clinical trials session at the ACC meeting, Biykem Bozkurt, MD, professor of medicine at Baylor College of Medicine, Houston, congratulated Dr. Ezekowitz on conducting this trial.

“We have been chasing the holy grail of sodium reduction in heart failure for a very long time, so I have to commend you and your team for taking on this challenge, especially during the pandemic,” she said.

But Dr. Bozkurt questioned whether the intervention group actually had a meaningful sodium reduction given that this was measured by food recall and this may have been accounted for by under-reporting of certain food intakes.

Dr. Ezekowitz responded that patients acted as their own controls in that calorie intake, fluid intake, and weight were also assessed and did not change. “So I think we did have a meaningful reduction in sodium,” he said.

Dr. Bozkurt also queried whether the improvements in quality of life and functional status were reliable given that this was an unblinded study.

To this point, Dr. Ezekowitz pointed out that the KCCQ quality-of-life measure was a highly validated instrument and that improvements were seen in these measures at 3, 6, and 12 months. “It is not like these were spurious findings, so I think we have to look at this as a real result,” he argued.

Commenting on the study at an ACC press conference, Mary Norine Walsh, MD, director of the heart failure and cardiac transplantation programs at St. Vincent Heart Center in Indianapolis, said the trial had answered two important questions: that sodium reduction in heart failure may not reduce heart failure hospitalization/death but that patients feel better.

“I think we can safely tell patients that if they slip up a bit they may not end up in hospital,” she added.

This study was funded by the Canadian Institutes of Health Research and the University Hospital Foundation (Edmonton, Alberta, Canada) and the Health Research Council of New Zealand. Dr. Ezekowitz reports research grants from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, eko.ai, US2.ai, Merck, Novartis, Otsuka, Sanofi, and Servier and consulting fees from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Merck, Novartis, Otsuka, Sanofi, and Servier.

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

This transcript of a video roundtable, which is available on Medscape.com, has been edited for clarity.

Hope S. Rugo, MD: Hello. I’m Hope Rugo, a breast medical oncologist from the University of California, San Francisco. I’m joined here by three of my friends and colleagues to discuss the toxicity of new agents in the treatment of breast cancer. Fatima, do you want to start by introducing yourself?

Fatima F. Cardoso, MD: Sure. Hello, everyone. I’m Fatima Cardoso, a breast medical oncologist in Lisbon, Portugal.

Dr. Rugo: Sheila.

Sheila Pettiford: Hi, I’m Sheila Pettiford. I am a metastatic [breast cancer] patient and have been for almost 8 years in April. I used to live in Philadelphia, Pennsylvania, but moved to Delaware in the last couple of years during the pandemic. I’m happy to be here.

Dr. Rugo: Julia.

Julia Maués: Hi, everyone. I also am a person living with metastatic breast cancer. I was diagnosed in 2013, so it’s going to be 9 years, also in April.
 

Effective monitoring and management of side effects: A team effort

Dr. Rugo: We have an amazing group and an international representation, which is also really nice because we get different perspectives. What we’re going to talk about is important to providers and patients across the board. With the host of new agents for the treatment of breast cancer – most of which have really moved us forward in terms of having effective treatment options – we’ve also been faced with a lot of new toxicities or side effects that we haven’t seen before or that we might not have expected from the specific agent.

Those toxicities across the board include side effects that are quite familiar to us, like low blood counts, but we may not advise people well enough about other side effects such as mouth sores, inflammation of the lungs, immune toxicities, and skin toxicities.

Fatima, do you want to start and talk about how we can think about these toxicities and address them?

Dr. Cardoso: Sure. Thank you. From the health care provider point of view, what I would highlight is to educate. Educate before we start the treatment. It’s very important to inform the patient but in a balanced way, so we don’t overexaggerate certain types of side effects or underestimate certain types of side effects.

It’s very important because an informed patient will be attentive to the types of side effects that can happen. Also, teach the patient when it is a [cause for] alarm or something for which they might need to contact their health care team and when that’s not the case. I think this is one crucial topic.

The other one is to monitor. Find ways how to best communicate between the patient and the health care team but in a way that you can monitor, so you can act very early on. Most of these new side effects, if you act early on, will not become severe. It is very important to know about them and to act early on.

I believe there is something important that we don’t think about all the time, and that is prophylaxis. Do not be shy about using prophylactic measures, be it for the mouth sores, nausea and vomiting, diarrhea, and other things that really impact the quality of life of patients. Those, to start, are my three major points of attention for health care professionals.

Dr. Rugo: I think that’s so incredibly important – the comments that you’ve made – and also that prevention and prophylaxis are so important. You don’t want to have a patient have diarrhea in the middle of the night and not have any antipropulsive agents at home. Just as a very straightforward example, it’s really important.

Also, the ability to know what you should be looking for and how you can manage it [is important]. There are many examples of times when, even with some education, providers may not have communicated well to the patient. Then the patient is surprised and unhappy with the situation and unable to manage it.
 

The importance of education

Sheila, your comments on this from the patient perspective are so important. How important is the education piece, and how do you manage the fear of side effects vs actually managing the side effects that might be caused by the treatment you’re taking?

Ms. Pettiford: Thank you for that question. I really think it’s a dance. It’s a dance between the patient and the health care team. Yes, education is absolutely important. However, the health care professionals have to establish a relationship of trust with the patient. My own circumstances were that – and I was very fortunate in that my oncologist, who I chose just by looking and not by a recommendation – I did find an oncologist who listened to me.

When it came time for me to deal with a new medication, the education she provided me was sufficient because of the fact that there was a lot of listening that had gone on prior to the new medicine being given to me. I trusted what I was hearing, and it felt like there was a balanced situation that came about from what I was being told. I could look it up, too.

There still is that part of the patient who will be participating in the process, as well. They can still look up things, and that’s one of the downfalls of the information age we are in. It is a dance. I just want to go back to that. There’s a dance between the patient and the health care providers.

Dr. Rugo: Julia, from the patient’s side, how do you balance the benefits you might get from a treatment versus the side effects and how best to manage them?

Ms. Maués: I think it’s interesting that when we talk with our doctors, and especially when we read about a certain treatment, the attention is focused on the very severe and unlikely side effects that a drug has. We don’t talk as much about the side effects that are most likely to happen and will affect us but may not be life threatening.

Especially for those of us with metastatic cancer who are going to ideally be on a drug for a very long time, we’re then faced with low-grade nausea for the rest of our lives. That’s not okay either, right? I think it’s important to talk about all of the levels of toxicities and everything that can be done to avoid this.
 

Communication is key

Ms. Pettiford: I just want to add something that Dr. Cardoso said about monitoring that is absolutely important. We’re in a day and time when it’s very difficult to get someone on the telephone, but we do have digital charts and other ways that monitoring can take place. I was at a large teaching university, and I had to go monthly for my treatments. Every month, there were questions that were asked about my life and my condition. I could always get in contact with somebody through the digital chart.

Dr. Rugo: That’s an incredibly important comment, Sheila, about communication and how patients can feel like they have someone to go to in real time who can help manage things. Fatima, I’m interested in your comment on that.

Also, just to go to the next step, which is that when we see data reported on clinical trials and how the agent we’ve added or substituted is better than the standard, the toxicity tables are side effects that occur in at least 10% or more patients and sometimes even 20%. Then they’re graded, where often the division is grade 3 or greater. That may not actually reflect much about what the individual patient experience is. How do we interpret these data? Communication and interpretation?

Dr. Cardoso: Absolutely. I always call attention that perhaps, since we focus so much on grade 3 and 4 [side effects], that is the reason why we don’t see in the usual reporting differences quality of life between treatments. Quality of life is affected also significantly by grade 2 side effects. Or, like Julia was mentioning, even grade 1, if they are persistent, will eventually affect your quality of life.

Sometimes, like I was saying, don’t underestimate – it’s a little bit like that. We focus on explaining, “Look, this new immunotherapy can give you all these different side effects.” But then we forget to say: “Oh, by the way, it may also give you some nausea.” Actually, the nausea will affect the patient’s quality of life. I think that’s why it is so important to balance the way we provide the information.

I would like also to take on what Sheila said that sometimes too much information is not very helpful. That’s why sometimes we have to go stepwise. The first time you’re about to start the treatment, advise [the patient] on the most frequent side effects. Later on, you have time to say: “Okay, by the way, this can also give a rare side effect. This is what you should look for. If you have it, please contact your health care team.”

I think the most difficult part, at least from my experience, is for patients to understand what is really a sign of a severe side effect and what is normal for that type of treatment. Some of the new ways of communicating, like using some patient-reported outcome (PRO) apps, actually help the patient by saying, “This that you are feeling is normal. It can wait for your next appointment. This that you are feeling, it’s better if you try to reach your health care team right away. Or, this is an urgent thing and go to the emergency room near you.”

For this kind of triage, there are now new apps that can help. I think this is the most difficult part because when you are a patient, you don’t know if what you are feeling is actually a sign of something very severe or if it’s normal for the type of treatment you are receiving.

Dr. Rugo: I think that’s so important, and these new PRO apps may help with this. Of course, nothing substitutes for talking in the end if you’re confused or it doesn’t fit into whatever’s in that paradigm. I think it’s important.
 

Best practices in focusing on the individual patient

Julia, what do you think the best way of educating the patient is when you’re going to start a new treatment? You might be newly diagnosed with cancer or you might have had cancer for a number of years. You’re going to start a new treatment. What’s the best way to know what to look for and how to manage it?

Ms. Maués: I think the key here is that everyone’s different, so have that conversation, the doctor and the patient, about what the best way [of education] is for that specific person. Do they want a flyer listing all of the side effects? Do they want a link to a video they can watch and understand? Do they want someone to come in and give an extra explanation about things? Everyone learns so differently, and I think it’s really hard to assume there’s one way that all patients will understand.

I think the PRO apps are great, and also another benefit is that you keep track of your side effects. Sometimes we don’t even remember well. When did you have nausea? Was it in the morning? Was it in the evening? Is it every day? If you track it with these apps, then you will have the data stored there in the form to answer those questions.

Dr. Cardoso: There was recently a publication – I found it quite interesting – from Lesley Fallowfield’s group saying that the majority of patients would better absorb the information if it is not just text, but if it somehow has a video component, an image, or an infographic that would help them memorize a little bit more information.

Dr. Rugo: There’s been a move toward trying to make videos because the amount of education that’s needed on the providers’ side from our nurses and advanced practice providers may be overwhelming, so things might get missed. The idea of having videos to get everybody on the same page is very popular right now for this reason, and Lesley’s work is really groundbreaking.

Sheila, what do you think is the best way to communicate information?

Ms. Pettiford: Well, I definitely think it’s important for the doctors to recognize, as Julia said, that everyone is different, and all their patients are different. They could come with the same exact subtype of whatever cancer they have – in this situation, breast cancer – and still have so many different reactions. It’s so important for everybody on the health care team to listen to what the patient says because the patient is the one who is living with the illness and knows their body, hopefully.

It’s just one of those things. It’s not a one-size-fits-all situation. You give the standards, but I think it’s important to offer various ways of communicating to a patient because some people are visual. Some people want an overwhelming amount of information so they can sort through it. Then, you have some people who just want the bullet points. Again, it is important not to try to do it as a one-size-fits-all type thing.

Dr. Rugo: Yes, that’s such a good point. I’m always struck by the fact that some patients are totally on top of it and listen to it all, and then other people, we just can’t get them to even call in regarding their side effects. In some ways, it’s frightening for people to call in with issues. Maybe they’re afraid they won’t get the treatment, or that it is related to their cancer progressing, too. Trying to meet people on their own level is a real challenge and an important one.

We talked about education for providers. Fatima, how should we be best educating for these new drugs and new side effects? So many different manifestations can occur, and as we talked about, they might be quite uncommon. We just want people to keep their ears up for any kind of unusual toxicity we see. We all know that the presentation of efficacy data is not adequate for education.

Dr. Cardoso: When we present a new treatment, we focus usually on efficacy, right? Then we say a few things about safety, particularly if there is a new or a severe side effect, but we don’t go through details on how to best manage this in clinical practice.

Anecdotally, I remember that I contacted you because I was going to start using a new treatment and you had some experience. I asked, “What about nausea and vomiting? What do you do for prophylaxis?” I couldn’t find it anywhere in the manuscripts or the presentations. I think we need to focus a little bit more on practical tips. If you are about to start this new treatment, what you should think about and not just the very severe and rare side effects?

Of course, as health care professionals, we need to keep this in our minds. For example, with immunotherapy, side effects can often occur even after stopping the treatment. For other types of new treatments, we need to gain knowledge about endocrinology, for example, which is something that oncologists wouldn’t have to deal with that often in the past. Now, new skills are needed.

It’s also what makes our profession so exciting. There’s always something new to learn, and I like to look at it from that perspective. It’s not boring at all. We are always learning new things.

Dr. Rugo: Indeed. Certainly, you and I have worked together on trying to encourage our pharmaceutical colleagues to publish these papers alongside their urgency of distributing the efficacy data and publishing the papers on efficacy, and also to do a nitty-gritty review of safety and talk about management strategies. I’m really pleased that there seems to be a little more focus on that earlier now in the drug process – although still not early enough – but it’s getting there. That’s a good thing.

Ms. Pettiford: Julia, you mentioned earlier how important it is for the individual patient’s quality of life to understand how these side effects can affect them. It really is one of those things in which we have to make personal decisions. What might be good for one person in terms of what happens with side effects, and their ability to function might not work with someone else.

If you are a person who’s dealing with metastatic disease who has children, a household, a dog, and a cat to take care of, what I can handle being that I’m a single person is not what they can handle. That’s all a part of the education piece. That’s all part of the teamwork. That’s all part of the communication process. It all comes into play.

Dr. Rugo: That’s such an incredibly important point. As we’re wrapping up, it would be great if everybody had some points to make that pulled together some of our conversation. Julia, do you want to start?

Ms. Maués: Yes, I was going to add specifically about the topic you were just discussing, with all that an oncologist’s team has to know and all the different areas of our health being affected by these new treatments. One tip for patients and their teams is that the other providers around the patients may not be as informed about the disease and the treatments they are on. Sometimes we patients end up getting information that isn’t up to date with the latest drugs and things like that.

When we do talk with someone about our issues, make sure they are informed about the new drugs. For example, we often have skin issues. There are dermatologists that work with cancer patients often, and they’re very informed about the side effects that come with these drugs. There are others who never see these sorts of issues and may assume it’s something completely different.

I usually just go to doctors that my oncologist’s team collaborates with and gets referrals from because they send their patients to these doctors often. These are doctors that see cancer patients. We’re a very unique group.

Dr. Rugo: That’s a really good point. I have the same thing. We all have a little stable of people we refer to for various issues that we can reach on speed dial.
 

The importance of diversity in clinical trials to obtain the most useful outcomes

Fatima, there’s recently been, appropriately so, more of a push to try and evaluate side effects by racial and ethnic subgroups. I think we’re still pretty crummy at it, but we are making some progress. How important is that to you when you think about patients and managing them?

Dr. Cardoso: I think this is quite important. One area of research that is underused, really, is all the new genomics and sequencing technologies to understand why people react differently to the same treatment. Why is it that for some people, either for ethnic or other reasons, you have a different metabolism or something else that justifies a very high rate of side effects from a certain treatment, whereas in other regions of the world this doesn’t happen?

Not to go into these new drugs, but when using a very old drug like a taxane, I found a difference in reaction between the Portuguese patients and the Belgian patients, the two countries where I’ve worked. I even found that the cause might be genetic because the Portuguese living in Belgium reacted differently than the Belgians themselves.

Maybe there is something in the genetics that justifies the type of side effects that you have. I make a plea also for us to dedicate research to understanding why certain side effects are related to race and others are related to maybe some other types of genetic alterations that will lead to an increased side effect.

Dr. Rugo: Sheila, comments?

Ms. Pettiford: That is just excellent. It’s excellent to even consider it because it is so obvious. To me, it’s an obvious situation because there are things that are underneath the skin that we don’t understand. We have to take that into consideration when we are dealing with all these wonderful – I call them miracle – drugs that have come about in the last 20 years.

There still is much more to be done, and I try to participate in any type of organization that’s encouraging diversity in clinical trials because you need to have people of all different ethnicities in order for us to get to these answers. It’s fascinating that you found this out, doctor.
 

The patient-centered dosing initiative

Ms. Maués: I have the pleasure of being a member of a patient-led initiative called the Patient-Centered Dosing Initiative (PCDI). We are highlighting the discussion around dosages of drugs, especially in the metastatic setting. Metastatic breast cancer is what we’re focusing on, although it could apply to any type of cancer. We are advised by a number of wonderful, world-renowned physicians, Dr. Rugo being one of them. Anne Loeser, the leader of our group, has spoken at ASCO about this topic of dosage. What we’re seeing is that the dosage determination for oncology drugs is still done in the same way it used to be done decades ago and mostly with the curative intent of early-stage disease — metastatic cancer patients back then really didn’t live long at all. What we’re seeing right now is people with metastatic breast cancer that are able to, in some cases, live a long life managing their disease.

Patients are put on doses that are too high for them to be able to manage the side effects, and then they end up having to go off the drug, which means they have lost one of the tools in their toolbox. So, what we like to say about dosing is that, for metastatic cancer patients, it’s a marathon and not a sprint. If we throw all the poison at the patient from the very beginning, they won’t be able to take this for a very long time. And in the metastatic setting, the goal is to stay on each therapy for as long as possible. If we burn one of the cards early on, you have to move on to the next one. This is finite because at some point, there are not enough drugs that can help a particular patient. The PCDI is really getting a lot of visibility with the FDA and experts. People are talking more about dosages, and the FDA is now providing guidance for pharmaceutical companies to study different dosages in the clinical trials from the very beginning. This initiative is almost 3 years old, and we have made a tremendous impact since then.

Dr. Rugo: I think this is an incredibly important area moving forward, and thankfully, there’s so much interest now in not only promoting diversity, enrollment in trials, and education to promote diversity but also in looking at differences in efficacy and side effects.

I’ll just thank everybody for your contributions and amazing perspectives in this incredibly important area. As we move forward with better agents, we need to also make sure we’re understanding what the side effects are, managing them, and hearing the voices of our patients. Thanks very much.

Ms. Pettiford: Thank you so much.

Dr. Cardoso: Thank you.

Ms. Maués: Thank you.
 

Editor’s note: Our panelists would like to highlight these points:

• The patient and the health care team must build trust with each other. 
• African Americans have historical reasons for not trusting the health care industry. Much outreach is still needed. 
• Inform and educate before the start of treatment and during the treatment.
• Be balanced and do not underestimate common side effects or overestimate rare ones. Adapt the amount and the detail of the information to the wishes of the individual patient. Offer various methods of delivery (e.g., videos, pamphlets, fact sheets).
• Patients will research their condition and treatments online. Instead of trying to stop this, help them find the best sources.
• Patients will connect with others in the patient community and learn from each other’s experiences. Keep in mind that everyone is different, and decisions should always be made together with the medical team.
• Monitor patients regularly, especially during the first few treatment cycles.
• Use different forms of communication between the patient and health care providers (e.g., apps, digital charts, oncology nurses/nurse navigators, responsive oncologists, different forms of telemedicine), but don’t forget to speak directly with the patient.
• The use of new PRO apps can be very useful to help patients differentiate between urgent and nonurgent signs and symptoms.
• As much as possible, use preventive/prophylactic measures, namely for nausea, vomiting, diarrhea/constipation, and mucositis.
• Be aware of late side effects, especially with immunotherapy.
• Don’t forget that grade 1-2 side effects can substantially impact quality of life, particularly if they are persistent.
• Consider quality-of-life issues for each patient. What is acceptable for one patient may not be for another.
• Learn how to manage new and specific side effects (e.g., endocrine, skin related, pneumonitis).
• Keep an open dialogue about treatment and side effects. Things can change, and there are different ways to address issues such as medications for side effects and dosing changes.
• Listen to your patient and respond in a timely fashion.
• Ethnicity and genetics should be studied as a factor for individual side effects. Standard industry dosages of a new anticancer medication might not be as effective in one ethnic group as another due to the lack of diversity in clinical trials.
• Medications with hard-to-manage or dangerous side effects may be counterproductive regardless of effectiveness.
• Cancer treatment varies vastly depending on region and type of treatment facility. There are many unmet needs in rural areas because of lack of oncology personnel, finances, transportation, etc.

Dr. Rugo is a professor in the department of medicine, University of California San Francisco Comprehensive Cancer Center; director, Breast Oncology and Clinical Trials Education, Cancer Infusion Services, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco. Dr. Cardoso is director, breast unit, Champalimaud Clinical Centre, Lisbon. Financial disclosures for both Dr. Rugo and Dr. Cardoso are available on Medscape.com, where this article first appeared. Julia Maués is a patient in Washington. She has disclosed no relevant financial relationships. Sheila Pettiford is a patient in Middletown, Del. She has disclosed no relevant financial relationships.

This transcript of a video roundtable, which is available on Medscape.com, has been edited for clarity.

Hope S. Rugo, MD: Hello. I’m Hope Rugo, a breast medical oncologist from the University of California, San Francisco. I’m joined here by three of my friends and colleagues to discuss the toxicity of new agents in the treatment of breast cancer. Fatima, do you want to start by introducing yourself?

Fatima F. Cardoso, MD: Sure. Hello, everyone. I’m Fatima Cardoso, a breast medical oncologist in Lisbon, Portugal.

Dr. Rugo: Sheila.

Sheila Pettiford: Hi, I’m Sheila Pettiford. I am a metastatic [breast cancer] patient and have been for almost 8 years in April. I used to live in Philadelphia, Pennsylvania, but moved to Delaware in the last couple of years during the pandemic. I’m happy to be here.

Dr. Rugo: Julia.

Julia Maués: Hi, everyone. I also am a person living with metastatic breast cancer. I was diagnosed in 2013, so it’s going to be 9 years, also in April.
 

Effective monitoring and management of side effects: A team effort

Dr. Rugo: We have an amazing group and an international representation, which is also really nice because we get different perspectives. What we’re going to talk about is important to providers and patients across the board. With the host of new agents for the treatment of breast cancer – most of which have really moved us forward in terms of having effective treatment options – we’ve also been faced with a lot of new toxicities or side effects that we haven’t seen before or that we might not have expected from the specific agent.

Those toxicities across the board include side effects that are quite familiar to us, like low blood counts, but we may not advise people well enough about other side effects such as mouth sores, inflammation of the lungs, immune toxicities, and skin toxicities.

Fatima, do you want to start and talk about how we can think about these toxicities and address them?

Dr. Cardoso: Sure. Thank you. From the health care provider point of view, what I would highlight is to educate. Educate before we start the treatment. It’s very important to inform the patient but in a balanced way, so we don’t overexaggerate certain types of side effects or underestimate certain types of side effects.

It’s very important because an informed patient will be attentive to the types of side effects that can happen. Also, teach the patient when it is a [cause for] alarm or something for which they might need to contact their health care team and when that’s not the case. I think this is one crucial topic.

The other one is to monitor. Find ways how to best communicate between the patient and the health care team but in a way that you can monitor, so you can act very early on. Most of these new side effects, if you act early on, will not become severe. It is very important to know about them and to act early on.

I believe there is something important that we don’t think about all the time, and that is prophylaxis. Do not be shy about using prophylactic measures, be it for the mouth sores, nausea and vomiting, diarrhea, and other things that really impact the quality of life of patients. Those, to start, are my three major points of attention for health care professionals.

Dr. Rugo: I think that’s so incredibly important – the comments that you’ve made – and also that prevention and prophylaxis are so important. You don’t want to have a patient have diarrhea in the middle of the night and not have any antipropulsive agents at home. Just as a very straightforward example, it’s really important.

Also, the ability to know what you should be looking for and how you can manage it [is important]. There are many examples of times when, even with some education, providers may not have communicated well to the patient. Then the patient is surprised and unhappy with the situation and unable to manage it.
 

The importance of education

Sheila, your comments on this from the patient perspective are so important. How important is the education piece, and how do you manage the fear of side effects vs actually managing the side effects that might be caused by the treatment you’re taking?

Ms. Pettiford: Thank you for that question. I really think it’s a dance. It’s a dance between the patient and the health care team. Yes, education is absolutely important. However, the health care professionals have to establish a relationship of trust with the patient. My own circumstances were that – and I was very fortunate in that my oncologist, who I chose just by looking and not by a recommendation – I did find an oncologist who listened to me.

When it came time for me to deal with a new medication, the education she provided me was sufficient because of the fact that there was a lot of listening that had gone on prior to the new medicine being given to me. I trusted what I was hearing, and it felt like there was a balanced situation that came about from what I was being told. I could look it up, too.

There still is that part of the patient who will be participating in the process, as well. They can still look up things, and that’s one of the downfalls of the information age we are in. It is a dance. I just want to go back to that. There’s a dance between the patient and the health care providers.

Dr. Rugo: Julia, from the patient’s side, how do you balance the benefits you might get from a treatment versus the side effects and how best to manage them?

Ms. Maués: I think it’s interesting that when we talk with our doctors, and especially when we read about a certain treatment, the attention is focused on the very severe and unlikely side effects that a drug has. We don’t talk as much about the side effects that are most likely to happen and will affect us but may not be life threatening.

Especially for those of us with metastatic cancer who are going to ideally be on a drug for a very long time, we’re then faced with low-grade nausea for the rest of our lives. That’s not okay either, right? I think it’s important to talk about all of the levels of toxicities and everything that can be done to avoid this.
 

Communication is key

Ms. Pettiford: I just want to add something that Dr. Cardoso said about monitoring that is absolutely important. We’re in a day and time when it’s very difficult to get someone on the telephone, but we do have digital charts and other ways that monitoring can take place. I was at a large teaching university, and I had to go monthly for my treatments. Every month, there were questions that were asked about my life and my condition. I could always get in contact with somebody through the digital chart.

Dr. Rugo: That’s an incredibly important comment, Sheila, about communication and how patients can feel like they have someone to go to in real time who can help manage things. Fatima, I’m interested in your comment on that.

Also, just to go to the next step, which is that when we see data reported on clinical trials and how the agent we’ve added or substituted is better than the standard, the toxicity tables are side effects that occur in at least 10% or more patients and sometimes even 20%. Then they’re graded, where often the division is grade 3 or greater. That may not actually reflect much about what the individual patient experience is. How do we interpret these data? Communication and interpretation?

Dr. Cardoso: Absolutely. I always call attention that perhaps, since we focus so much on grade 3 and 4 [side effects], that is the reason why we don’t see in the usual reporting differences quality of life between treatments. Quality of life is affected also significantly by grade 2 side effects. Or, like Julia was mentioning, even grade 1, if they are persistent, will eventually affect your quality of life.

Sometimes, like I was saying, don’t underestimate – it’s a little bit like that. We focus on explaining, “Look, this new immunotherapy can give you all these different side effects.” But then we forget to say: “Oh, by the way, it may also give you some nausea.” Actually, the nausea will affect the patient’s quality of life. I think that’s why it is so important to balance the way we provide the information.

I would like also to take on what Sheila said that sometimes too much information is not very helpful. That’s why sometimes we have to go stepwise. The first time you’re about to start the treatment, advise [the patient] on the most frequent side effects. Later on, you have time to say: “Okay, by the way, this can also give a rare side effect. This is what you should look for. If you have it, please contact your health care team.”

I think the most difficult part, at least from my experience, is for patients to understand what is really a sign of a severe side effect and what is normal for that type of treatment. Some of the new ways of communicating, like using some patient-reported outcome (PRO) apps, actually help the patient by saying, “This that you are feeling is normal. It can wait for your next appointment. This that you are feeling, it’s better if you try to reach your health care team right away. Or, this is an urgent thing and go to the emergency room near you.”

For this kind of triage, there are now new apps that can help. I think this is the most difficult part because when you are a patient, you don’t know if what you are feeling is actually a sign of something very severe or if it’s normal for the type of treatment you are receiving.

Dr. Rugo: I think that’s so important, and these new PRO apps may help with this. Of course, nothing substitutes for talking in the end if you’re confused or it doesn’t fit into whatever’s in that paradigm. I think it’s important.
 

Best practices in focusing on the individual patient

Julia, what do you think the best way of educating the patient is when you’re going to start a new treatment? You might be newly diagnosed with cancer or you might have had cancer for a number of years. You’re going to start a new treatment. What’s the best way to know what to look for and how to manage it?

Ms. Maués: I think the key here is that everyone’s different, so have that conversation, the doctor and the patient, about what the best way [of education] is for that specific person. Do they want a flyer listing all of the side effects? Do they want a link to a video they can watch and understand? Do they want someone to come in and give an extra explanation about things? Everyone learns so differently, and I think it’s really hard to assume there’s one way that all patients will understand.

I think the PRO apps are great, and also another benefit is that you keep track of your side effects. Sometimes we don’t even remember well. When did you have nausea? Was it in the morning? Was it in the evening? Is it every day? If you track it with these apps, then you will have the data stored there in the form to answer those questions.

Dr. Cardoso: There was recently a publication – I found it quite interesting – from Lesley Fallowfield’s group saying that the majority of patients would better absorb the information if it is not just text, but if it somehow has a video component, an image, or an infographic that would help them memorize a little bit more information.

Dr. Rugo: There’s been a move toward trying to make videos because the amount of education that’s needed on the providers’ side from our nurses and advanced practice providers may be overwhelming, so things might get missed. The idea of having videos to get everybody on the same page is very popular right now for this reason, and Lesley’s work is really groundbreaking.

Sheila, what do you think is the best way to communicate information?

Ms. Pettiford: Well, I definitely think it’s important for the doctors to recognize, as Julia said, that everyone is different, and all their patients are different. They could come with the same exact subtype of whatever cancer they have – in this situation, breast cancer – and still have so many different reactions. It’s so important for everybody on the health care team to listen to what the patient says because the patient is the one who is living with the illness and knows their body, hopefully.

It’s just one of those things. It’s not a one-size-fits-all situation. You give the standards, but I think it’s important to offer various ways of communicating to a patient because some people are visual. Some people want an overwhelming amount of information so they can sort through it. Then, you have some people who just want the bullet points. Again, it is important not to try to do it as a one-size-fits-all type thing.

Dr. Rugo: Yes, that’s such a good point. I’m always struck by the fact that some patients are totally on top of it and listen to it all, and then other people, we just can’t get them to even call in regarding their side effects. In some ways, it’s frightening for people to call in with issues. Maybe they’re afraid they won’t get the treatment, or that it is related to their cancer progressing, too. Trying to meet people on their own level is a real challenge and an important one.

We talked about education for providers. Fatima, how should we be best educating for these new drugs and new side effects? So many different manifestations can occur, and as we talked about, they might be quite uncommon. We just want people to keep their ears up for any kind of unusual toxicity we see. We all know that the presentation of efficacy data is not adequate for education.

Dr. Cardoso: When we present a new treatment, we focus usually on efficacy, right? Then we say a few things about safety, particularly if there is a new or a severe side effect, but we don’t go through details on how to best manage this in clinical practice.

Anecdotally, I remember that I contacted you because I was going to start using a new treatment and you had some experience. I asked, “What about nausea and vomiting? What do you do for prophylaxis?” I couldn’t find it anywhere in the manuscripts or the presentations. I think we need to focus a little bit more on practical tips. If you are about to start this new treatment, what you should think about and not just the very severe and rare side effects?

Of course, as health care professionals, we need to keep this in our minds. For example, with immunotherapy, side effects can often occur even after stopping the treatment. For other types of new treatments, we need to gain knowledge about endocrinology, for example, which is something that oncologists wouldn’t have to deal with that often in the past. Now, new skills are needed.

It’s also what makes our profession so exciting. There’s always something new to learn, and I like to look at it from that perspective. It’s not boring at all. We are always learning new things.

Dr. Rugo: Indeed. Certainly, you and I have worked together on trying to encourage our pharmaceutical colleagues to publish these papers alongside their urgency of distributing the efficacy data and publishing the papers on efficacy, and also to do a nitty-gritty review of safety and talk about management strategies. I’m really pleased that there seems to be a little more focus on that earlier now in the drug process – although still not early enough – but it’s getting there. That’s a good thing.

Ms. Pettiford: Julia, you mentioned earlier how important it is for the individual patient’s quality of life to understand how these side effects can affect them. It really is one of those things in which we have to make personal decisions. What might be good for one person in terms of what happens with side effects, and their ability to function might not work with someone else.

If you are a person who’s dealing with metastatic disease who has children, a household, a dog, and a cat to take care of, what I can handle being that I’m a single person is not what they can handle. That’s all a part of the education piece. That’s all part of the teamwork. That’s all part of the communication process. It all comes into play.

Dr. Rugo: That’s such an incredibly important point. As we’re wrapping up, it would be great if everybody had some points to make that pulled together some of our conversation. Julia, do you want to start?

Ms. Maués: Yes, I was going to add specifically about the topic you were just discussing, with all that an oncologist’s team has to know and all the different areas of our health being affected by these new treatments. One tip for patients and their teams is that the other providers around the patients may not be as informed about the disease and the treatments they are on. Sometimes we patients end up getting information that isn’t up to date with the latest drugs and things like that.

When we do talk with someone about our issues, make sure they are informed about the new drugs. For example, we often have skin issues. There are dermatologists that work with cancer patients often, and they’re very informed about the side effects that come with these drugs. There are others who never see these sorts of issues and may assume it’s something completely different.

I usually just go to doctors that my oncologist’s team collaborates with and gets referrals from because they send their patients to these doctors often. These are doctors that see cancer patients. We’re a very unique group.

Dr. Rugo: That’s a really good point. I have the same thing. We all have a little stable of people we refer to for various issues that we can reach on speed dial.
 

The importance of diversity in clinical trials to obtain the most useful outcomes

Fatima, there’s recently been, appropriately so, more of a push to try and evaluate side effects by racial and ethnic subgroups. I think we’re still pretty crummy at it, but we are making some progress. How important is that to you when you think about patients and managing them?

Dr. Cardoso: I think this is quite important. One area of research that is underused, really, is all the new genomics and sequencing technologies to understand why people react differently to the same treatment. Why is it that for some people, either for ethnic or other reasons, you have a different metabolism or something else that justifies a very high rate of side effects from a certain treatment, whereas in other regions of the world this doesn’t happen?

Not to go into these new drugs, but when using a very old drug like a taxane, I found a difference in reaction between the Portuguese patients and the Belgian patients, the two countries where I’ve worked. I even found that the cause might be genetic because the Portuguese living in Belgium reacted differently than the Belgians themselves.

Maybe there is something in the genetics that justifies the type of side effects that you have. I make a plea also for us to dedicate research to understanding why certain side effects are related to race and others are related to maybe some other types of genetic alterations that will lead to an increased side effect.

Dr. Rugo: Sheila, comments?

Ms. Pettiford: That is just excellent. It’s excellent to even consider it because it is so obvious. To me, it’s an obvious situation because there are things that are underneath the skin that we don’t understand. We have to take that into consideration when we are dealing with all these wonderful – I call them miracle – drugs that have come about in the last 20 years.

There still is much more to be done, and I try to participate in any type of organization that’s encouraging diversity in clinical trials because you need to have people of all different ethnicities in order for us to get to these answers. It’s fascinating that you found this out, doctor.
 

The patient-centered dosing initiative

Ms. Maués: I have the pleasure of being a member of a patient-led initiative called the Patient-Centered Dosing Initiative (PCDI). We are highlighting the discussion around dosages of drugs, especially in the metastatic setting. Metastatic breast cancer is what we’re focusing on, although it could apply to any type of cancer. We are advised by a number of wonderful, world-renowned physicians, Dr. Rugo being one of them. Anne Loeser, the leader of our group, has spoken at ASCO about this topic of dosage. What we’re seeing is that the dosage determination for oncology drugs is still done in the same way it used to be done decades ago and mostly with the curative intent of early-stage disease — metastatic cancer patients back then really didn’t live long at all. What we’re seeing right now is people with metastatic breast cancer that are able to, in some cases, live a long life managing their disease.

Patients are put on doses that are too high for them to be able to manage the side effects, and then they end up having to go off the drug, which means they have lost one of the tools in their toolbox. So, what we like to say about dosing is that, for metastatic cancer patients, it’s a marathon and not a sprint. If we throw all the poison at the patient from the very beginning, they won’t be able to take this for a very long time. And in the metastatic setting, the goal is to stay on each therapy for as long as possible. If we burn one of the cards early on, you have to move on to the next one. This is finite because at some point, there are not enough drugs that can help a particular patient. The PCDI is really getting a lot of visibility with the FDA and experts. People are talking more about dosages, and the FDA is now providing guidance for pharmaceutical companies to study different dosages in the clinical trials from the very beginning. This initiative is almost 3 years old, and we have made a tremendous impact since then.

Dr. Rugo: I think this is an incredibly important area moving forward, and thankfully, there’s so much interest now in not only promoting diversity, enrollment in trials, and education to promote diversity but also in looking at differences in efficacy and side effects.

I’ll just thank everybody for your contributions and amazing perspectives in this incredibly important area. As we move forward with better agents, we need to also make sure we’re understanding what the side effects are, managing them, and hearing the voices of our patients. Thanks very much.

Ms. Pettiford: Thank you so much.

Dr. Cardoso: Thank you.

Ms. Maués: Thank you.
 

Editor’s note: Our panelists would like to highlight these points:

• The patient and the health care team must build trust with each other. 
• African Americans have historical reasons for not trusting the health care industry. Much outreach is still needed. 
• Inform and educate before the start of treatment and during the treatment.
• Be balanced and do not underestimate common side effects or overestimate rare ones. Adapt the amount and the detail of the information to the wishes of the individual patient. Offer various methods of delivery (e.g., videos, pamphlets, fact sheets).
• Patients will research their condition and treatments online. Instead of trying to stop this, help them find the best sources.
• Patients will connect with others in the patient community and learn from each other’s experiences. Keep in mind that everyone is different, and decisions should always be made together with the medical team.
• Monitor patients regularly, especially during the first few treatment cycles.
• Use different forms of communication between the patient and health care providers (e.g., apps, digital charts, oncology nurses/nurse navigators, responsive oncologists, different forms of telemedicine), but don’t forget to speak directly with the patient.
• The use of new PRO apps can be very useful to help patients differentiate between urgent and nonurgent signs and symptoms.
• As much as possible, use preventive/prophylactic measures, namely for nausea, vomiting, diarrhea/constipation, and mucositis.
• Be aware of late side effects, especially with immunotherapy.
• Don’t forget that grade 1-2 side effects can substantially impact quality of life, particularly if they are persistent.
• Consider quality-of-life issues for each patient. What is acceptable for one patient may not be for another.
• Learn how to manage new and specific side effects (e.g., endocrine, skin related, pneumonitis).
• Keep an open dialogue about treatment and side effects. Things can change, and there are different ways to address issues such as medications for side effects and dosing changes.
• Listen to your patient and respond in a timely fashion.
• Ethnicity and genetics should be studied as a factor for individual side effects. Standard industry dosages of a new anticancer medication might not be as effective in one ethnic group as another due to the lack of diversity in clinical trials.
• Medications with hard-to-manage or dangerous side effects may be counterproductive regardless of effectiveness.
• Cancer treatment varies vastly depending on region and type of treatment facility. There are many unmet needs in rural areas because of lack of oncology personnel, finances, transportation, etc.

Dr. Rugo is a professor in the department of medicine, University of California San Francisco Comprehensive Cancer Center; director, Breast Oncology and Clinical Trials Education, Cancer Infusion Services, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco. Dr. Cardoso is director, breast unit, Champalimaud Clinical Centre, Lisbon. Financial disclosures for both Dr. Rugo and Dr. Cardoso are available on Medscape.com, where this article first appeared. Julia Maués is a patient in Washington. She has disclosed no relevant financial relationships. Sheila Pettiford is a patient in Middletown, Del. She has disclosed no relevant financial relationships.

This transcript of a video roundtable, which is available on Medscape.com, has been edited for clarity.

Hope S. Rugo, MD: Hello. I’m Hope Rugo, a breast medical oncologist from the University of California, San Francisco. I’m joined here by three of my friends and colleagues to discuss the toxicity of new agents in the treatment of breast cancer. Fatima, do you want to start by introducing yourself?

Fatima F. Cardoso, MD: Sure. Hello, everyone. I’m Fatima Cardoso, a breast medical oncologist in Lisbon, Portugal.

Dr. Rugo: Sheila.

Sheila Pettiford: Hi, I’m Sheila Pettiford. I am a metastatic [breast cancer] patient and have been for almost 8 years in April. I used to live in Philadelphia, Pennsylvania, but moved to Delaware in the last couple of years during the pandemic. I’m happy to be here.

Dr. Rugo: Julia.

Julia Maués: Hi, everyone. I also am a person living with metastatic breast cancer. I was diagnosed in 2013, so it’s going to be 9 years, also in April.
 

Effective monitoring and management of side effects: A team effort

Dr. Rugo: We have an amazing group and an international representation, which is also really nice because we get different perspectives. What we’re going to talk about is important to providers and patients across the board. With the host of new agents for the treatment of breast cancer – most of which have really moved us forward in terms of having effective treatment options – we’ve also been faced with a lot of new toxicities or side effects that we haven’t seen before or that we might not have expected from the specific agent.

Those toxicities across the board include side effects that are quite familiar to us, like low blood counts, but we may not advise people well enough about other side effects such as mouth sores, inflammation of the lungs, immune toxicities, and skin toxicities.

Fatima, do you want to start and talk about how we can think about these toxicities and address them?

Dr. Cardoso: Sure. Thank you. From the health care provider point of view, what I would highlight is to educate. Educate before we start the treatment. It’s very important to inform the patient but in a balanced way, so we don’t overexaggerate certain types of side effects or underestimate certain types of side effects.

It’s very important because an informed patient will be attentive to the types of side effects that can happen. Also, teach the patient when it is a [cause for] alarm or something for which they might need to contact their health care team and when that’s not the case. I think this is one crucial topic.

The other one is to monitor. Find ways how to best communicate between the patient and the health care team but in a way that you can monitor, so you can act very early on. Most of these new side effects, if you act early on, will not become severe. It is very important to know about them and to act early on.

I believe there is something important that we don’t think about all the time, and that is prophylaxis. Do not be shy about using prophylactic measures, be it for the mouth sores, nausea and vomiting, diarrhea, and other things that really impact the quality of life of patients. Those, to start, are my three major points of attention for health care professionals.

Dr. Rugo: I think that’s so incredibly important – the comments that you’ve made – and also that prevention and prophylaxis are so important. You don’t want to have a patient have diarrhea in the middle of the night and not have any antipropulsive agents at home. Just as a very straightforward example, it’s really important.

Also, the ability to know what you should be looking for and how you can manage it [is important]. There are many examples of times when, even with some education, providers may not have communicated well to the patient. Then the patient is surprised and unhappy with the situation and unable to manage it.
 

The importance of education

Sheila, your comments on this from the patient perspective are so important. How important is the education piece, and how do you manage the fear of side effects vs actually managing the side effects that might be caused by the treatment you’re taking?

Ms. Pettiford: Thank you for that question. I really think it’s a dance. It’s a dance between the patient and the health care team. Yes, education is absolutely important. However, the health care professionals have to establish a relationship of trust with the patient. My own circumstances were that – and I was very fortunate in that my oncologist, who I chose just by looking and not by a recommendation – I did find an oncologist who listened to me.

When it came time for me to deal with a new medication, the education she provided me was sufficient because of the fact that there was a lot of listening that had gone on prior to the new medicine being given to me. I trusted what I was hearing, and it felt like there was a balanced situation that came about from what I was being told. I could look it up, too.

There still is that part of the patient who will be participating in the process, as well. They can still look up things, and that’s one of the downfalls of the information age we are in. It is a dance. I just want to go back to that. There’s a dance between the patient and the health care providers.

Dr. Rugo: Julia, from the patient’s side, how do you balance the benefits you might get from a treatment versus the side effects and how best to manage them?

Ms. Maués: I think it’s interesting that when we talk with our doctors, and especially when we read about a certain treatment, the attention is focused on the very severe and unlikely side effects that a drug has. We don’t talk as much about the side effects that are most likely to happen and will affect us but may not be life threatening.

Especially for those of us with metastatic cancer who are going to ideally be on a drug for a very long time, we’re then faced with low-grade nausea for the rest of our lives. That’s not okay either, right? I think it’s important to talk about all of the levels of toxicities and everything that can be done to avoid this.
 

Communication is key

Ms. Pettiford: I just want to add something that Dr. Cardoso said about monitoring that is absolutely important. We’re in a day and time when it’s very difficult to get someone on the telephone, but we do have digital charts and other ways that monitoring can take place. I was at a large teaching university, and I had to go monthly for my treatments. Every month, there were questions that were asked about my life and my condition. I could always get in contact with somebody through the digital chart.

Dr. Rugo: That’s an incredibly important comment, Sheila, about communication and how patients can feel like they have someone to go to in real time who can help manage things. Fatima, I’m interested in your comment on that.

Also, just to go to the next step, which is that when we see data reported on clinical trials and how the agent we’ve added or substituted is better than the standard, the toxicity tables are side effects that occur in at least 10% or more patients and sometimes even 20%. Then they’re graded, where often the division is grade 3 or greater. That may not actually reflect much about what the individual patient experience is. How do we interpret these data? Communication and interpretation?

Dr. Cardoso: Absolutely. I always call attention that perhaps, since we focus so much on grade 3 and 4 [side effects], that is the reason why we don’t see in the usual reporting differences quality of life between treatments. Quality of life is affected also significantly by grade 2 side effects. Or, like Julia was mentioning, even grade 1, if they are persistent, will eventually affect your quality of life.

Sometimes, like I was saying, don’t underestimate – it’s a little bit like that. We focus on explaining, “Look, this new immunotherapy can give you all these different side effects.” But then we forget to say: “Oh, by the way, it may also give you some nausea.” Actually, the nausea will affect the patient’s quality of life. I think that’s why it is so important to balance the way we provide the information.

I would like also to take on what Sheila said that sometimes too much information is not very helpful. That’s why sometimes we have to go stepwise. The first time you’re about to start the treatment, advise [the patient] on the most frequent side effects. Later on, you have time to say: “Okay, by the way, this can also give a rare side effect. This is what you should look for. If you have it, please contact your health care team.”

I think the most difficult part, at least from my experience, is for patients to understand what is really a sign of a severe side effect and what is normal for that type of treatment. Some of the new ways of communicating, like using some patient-reported outcome (PRO) apps, actually help the patient by saying, “This that you are feeling is normal. It can wait for your next appointment. This that you are feeling, it’s better if you try to reach your health care team right away. Or, this is an urgent thing and go to the emergency room near you.”

For this kind of triage, there are now new apps that can help. I think this is the most difficult part because when you are a patient, you don’t know if what you are feeling is actually a sign of something very severe or if it’s normal for the type of treatment you are receiving.

Dr. Rugo: I think that’s so important, and these new PRO apps may help with this. Of course, nothing substitutes for talking in the end if you’re confused or it doesn’t fit into whatever’s in that paradigm. I think it’s important.
 

Best practices in focusing on the individual patient

Julia, what do you think the best way of educating the patient is when you’re going to start a new treatment? You might be newly diagnosed with cancer or you might have had cancer for a number of years. You’re going to start a new treatment. What’s the best way to know what to look for and how to manage it?

Ms. Maués: I think the key here is that everyone’s different, so have that conversation, the doctor and the patient, about what the best way [of education] is for that specific person. Do they want a flyer listing all of the side effects? Do they want a link to a video they can watch and understand? Do they want someone to come in and give an extra explanation about things? Everyone learns so differently, and I think it’s really hard to assume there’s one way that all patients will understand.

I think the PRO apps are great, and also another benefit is that you keep track of your side effects. Sometimes we don’t even remember well. When did you have nausea? Was it in the morning? Was it in the evening? Is it every day? If you track it with these apps, then you will have the data stored there in the form to answer those questions.

Dr. Cardoso: There was recently a publication – I found it quite interesting – from Lesley Fallowfield’s group saying that the majority of patients would better absorb the information if it is not just text, but if it somehow has a video component, an image, or an infographic that would help them memorize a little bit more information.

Dr. Rugo: There’s been a move toward trying to make videos because the amount of education that’s needed on the providers’ side from our nurses and advanced practice providers may be overwhelming, so things might get missed. The idea of having videos to get everybody on the same page is very popular right now for this reason, and Lesley’s work is really groundbreaking.

Sheila, what do you think is the best way to communicate information?

Ms. Pettiford: Well, I definitely think it’s important for the doctors to recognize, as Julia said, that everyone is different, and all their patients are different. They could come with the same exact subtype of whatever cancer they have – in this situation, breast cancer – and still have so many different reactions. It’s so important for everybody on the health care team to listen to what the patient says because the patient is the one who is living with the illness and knows their body, hopefully.

It’s just one of those things. It’s not a one-size-fits-all situation. You give the standards, but I think it’s important to offer various ways of communicating to a patient because some people are visual. Some people want an overwhelming amount of information so they can sort through it. Then, you have some people who just want the bullet points. Again, it is important not to try to do it as a one-size-fits-all type thing.

Dr. Rugo: Yes, that’s such a good point. I’m always struck by the fact that some patients are totally on top of it and listen to it all, and then other people, we just can’t get them to even call in regarding their side effects. In some ways, it’s frightening for people to call in with issues. Maybe they’re afraid they won’t get the treatment, or that it is related to their cancer progressing, too. Trying to meet people on their own level is a real challenge and an important one.

We talked about education for providers. Fatima, how should we be best educating for these new drugs and new side effects? So many different manifestations can occur, and as we talked about, they might be quite uncommon. We just want people to keep their ears up for any kind of unusual toxicity we see. We all know that the presentation of efficacy data is not adequate for education.

Dr. Cardoso: When we present a new treatment, we focus usually on efficacy, right? Then we say a few things about safety, particularly if there is a new or a severe side effect, but we don’t go through details on how to best manage this in clinical practice.

Anecdotally, I remember that I contacted you because I was going to start using a new treatment and you had some experience. I asked, “What about nausea and vomiting? What do you do for prophylaxis?” I couldn’t find it anywhere in the manuscripts or the presentations. I think we need to focus a little bit more on practical tips. If you are about to start this new treatment, what you should think about and not just the very severe and rare side effects?

Of course, as health care professionals, we need to keep this in our minds. For example, with immunotherapy, side effects can often occur even after stopping the treatment. For other types of new treatments, we need to gain knowledge about endocrinology, for example, which is something that oncologists wouldn’t have to deal with that often in the past. Now, new skills are needed.

It’s also what makes our profession so exciting. There’s always something new to learn, and I like to look at it from that perspective. It’s not boring at all. We are always learning new things.

Dr. Rugo: Indeed. Certainly, you and I have worked together on trying to encourage our pharmaceutical colleagues to publish these papers alongside their urgency of distributing the efficacy data and publishing the papers on efficacy, and also to do a nitty-gritty review of safety and talk about management strategies. I’m really pleased that there seems to be a little more focus on that earlier now in the drug process – although still not early enough – but it’s getting there. That’s a good thing.

Ms. Pettiford: Julia, you mentioned earlier how important it is for the individual patient’s quality of life to understand how these side effects can affect them. It really is one of those things in which we have to make personal decisions. What might be good for one person in terms of what happens with side effects, and their ability to function might not work with someone else.

If you are a person who’s dealing with metastatic disease who has children, a household, a dog, and a cat to take care of, what I can handle being that I’m a single person is not what they can handle. That’s all a part of the education piece. That’s all part of the teamwork. That’s all part of the communication process. It all comes into play.

Dr. Rugo: That’s such an incredibly important point. As we’re wrapping up, it would be great if everybody had some points to make that pulled together some of our conversation. Julia, do you want to start?

Ms. Maués: Yes, I was going to add specifically about the topic you were just discussing, with all that an oncologist’s team has to know and all the different areas of our health being affected by these new treatments. One tip for patients and their teams is that the other providers around the patients may not be as informed about the disease and the treatments they are on. Sometimes we patients end up getting information that isn’t up to date with the latest drugs and things like that.

When we do talk with someone about our issues, make sure they are informed about the new drugs. For example, we often have skin issues. There are dermatologists that work with cancer patients often, and they’re very informed about the side effects that come with these drugs. There are others who never see these sorts of issues and may assume it’s something completely different.

I usually just go to doctors that my oncologist’s team collaborates with and gets referrals from because they send their patients to these doctors often. These are doctors that see cancer patients. We’re a very unique group.

Dr. Rugo: That’s a really good point. I have the same thing. We all have a little stable of people we refer to for various issues that we can reach on speed dial.
 

The importance of diversity in clinical trials to obtain the most useful outcomes

Fatima, there’s recently been, appropriately so, more of a push to try and evaluate side effects by racial and ethnic subgroups. I think we’re still pretty crummy at it, but we are making some progress. How important is that to you when you think about patients and managing them?

Dr. Cardoso: I think this is quite important. One area of research that is underused, really, is all the new genomics and sequencing technologies to understand why people react differently to the same treatment. Why is it that for some people, either for ethnic or other reasons, you have a different metabolism or something else that justifies a very high rate of side effects from a certain treatment, whereas in other regions of the world this doesn’t happen?

Not to go into these new drugs, but when using a very old drug like a taxane, I found a difference in reaction between the Portuguese patients and the Belgian patients, the two countries where I’ve worked. I even found that the cause might be genetic because the Portuguese living in Belgium reacted differently than the Belgians themselves.

Maybe there is something in the genetics that justifies the type of side effects that you have. I make a plea also for us to dedicate research to understanding why certain side effects are related to race and others are related to maybe some other types of genetic alterations that will lead to an increased side effect.

Dr. Rugo: Sheila, comments?

Ms. Pettiford: That is just excellent. It’s excellent to even consider it because it is so obvious. To me, it’s an obvious situation because there are things that are underneath the skin that we don’t understand. We have to take that into consideration when we are dealing with all these wonderful – I call them miracle – drugs that have come about in the last 20 years.

There still is much more to be done, and I try to participate in any type of organization that’s encouraging diversity in clinical trials because you need to have people of all different ethnicities in order for us to get to these answers. It’s fascinating that you found this out, doctor.
 

The patient-centered dosing initiative

Ms. Maués: I have the pleasure of being a member of a patient-led initiative called the Patient-Centered Dosing Initiative (PCDI). We are highlighting the discussion around dosages of drugs, especially in the metastatic setting. Metastatic breast cancer is what we’re focusing on, although it could apply to any type of cancer. We are advised by a number of wonderful, world-renowned physicians, Dr. Rugo being one of them. Anne Loeser, the leader of our group, has spoken at ASCO about this topic of dosage. What we’re seeing is that the dosage determination for oncology drugs is still done in the same way it used to be done decades ago and mostly with the curative intent of early-stage disease — metastatic cancer patients back then really didn’t live long at all. What we’re seeing right now is people with metastatic breast cancer that are able to, in some cases, live a long life managing their disease.

Patients are put on doses that are too high for them to be able to manage the side effects, and then they end up having to go off the drug, which means they have lost one of the tools in their toolbox. So, what we like to say about dosing is that, for metastatic cancer patients, it’s a marathon and not a sprint. If we throw all the poison at the patient from the very beginning, they won’t be able to take this for a very long time. And in the metastatic setting, the goal is to stay on each therapy for as long as possible. If we burn one of the cards early on, you have to move on to the next one. This is finite because at some point, there are not enough drugs that can help a particular patient. The PCDI is really getting a lot of visibility with the FDA and experts. People are talking more about dosages, and the FDA is now providing guidance for pharmaceutical companies to study different dosages in the clinical trials from the very beginning. This initiative is almost 3 years old, and we have made a tremendous impact since then.

Dr. Rugo: I think this is an incredibly important area moving forward, and thankfully, there’s so much interest now in not only promoting diversity, enrollment in trials, and education to promote diversity but also in looking at differences in efficacy and side effects.

I’ll just thank everybody for your contributions and amazing perspectives in this incredibly important area. As we move forward with better agents, we need to also make sure we’re understanding what the side effects are, managing them, and hearing the voices of our patients. Thanks very much.

Ms. Pettiford: Thank you so much.

Dr. Cardoso: Thank you.

Ms. Maués: Thank you.
 

Editor’s note: Our panelists would like to highlight these points:

• The patient and the health care team must build trust with each other. 
• African Americans have historical reasons for not trusting the health care industry. Much outreach is still needed. 
• Inform and educate before the start of treatment and during the treatment.
• Be balanced and do not underestimate common side effects or overestimate rare ones. Adapt the amount and the detail of the information to the wishes of the individual patient. Offer various methods of delivery (e.g., videos, pamphlets, fact sheets).
• Patients will research their condition and treatments online. Instead of trying to stop this, help them find the best sources.
• Patients will connect with others in the patient community and learn from each other’s experiences. Keep in mind that everyone is different, and decisions should always be made together with the medical team.
• Monitor patients regularly, especially during the first few treatment cycles.
• Use different forms of communication between the patient and health care providers (e.g., apps, digital charts, oncology nurses/nurse navigators, responsive oncologists, different forms of telemedicine), but don’t forget to speak directly with the patient.
• The use of new PRO apps can be very useful to help patients differentiate between urgent and nonurgent signs and symptoms.
• As much as possible, use preventive/prophylactic measures, namely for nausea, vomiting, diarrhea/constipation, and mucositis.
• Be aware of late side effects, especially with immunotherapy.
• Don’t forget that grade 1-2 side effects can substantially impact quality of life, particularly if they are persistent.
• Consider quality-of-life issues for each patient. What is acceptable for one patient may not be for another.
• Learn how to manage new and specific side effects (e.g., endocrine, skin related, pneumonitis).
• Keep an open dialogue about treatment and side effects. Things can change, and there are different ways to address issues such as medications for side effects and dosing changes.
• Listen to your patient and respond in a timely fashion.
• Ethnicity and genetics should be studied as a factor for individual side effects. Standard industry dosages of a new anticancer medication might not be as effective in one ethnic group as another due to the lack of diversity in clinical trials.
• Medications with hard-to-manage or dangerous side effects may be counterproductive regardless of effectiveness.
• Cancer treatment varies vastly depending on region and type of treatment facility. There are many unmet needs in rural areas because of lack of oncology personnel, finances, transportation, etc.

Dr. Rugo is a professor in the department of medicine, University of California San Francisco Comprehensive Cancer Center; director, Breast Oncology and Clinical Trials Education, Cancer Infusion Services, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco. Dr. Cardoso is director, breast unit, Champalimaud Clinical Centre, Lisbon. Financial disclosures for both Dr. Rugo and Dr. Cardoso are available on Medscape.com, where this article first appeared. Julia Maués is a patient in Washington. She has disclosed no relevant financial relationships. Sheila Pettiford is a patient in Middletown, Del. She has disclosed no relevant financial relationships.

Atypical anxiety in adults with Parkinson’s disease ranged from 15% to 51% in a systematic review of 60 studies.

Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.

Courtesy University of Queensland

In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).

Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.

Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.

The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.

The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.

Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.

The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.

The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.

However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.

Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.

Atypical anxiety in adults with Parkinson’s disease ranged from 15% to 51% in a systematic review of 60 studies.

Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.

Courtesy University of Queensland

In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).

Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.

Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.

The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.

The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.

Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.

The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.

The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.

However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.

Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.

Atypical anxiety in adults with Parkinson’s disease ranged from 15% to 51% in a systematic review of 60 studies.

Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.

Courtesy University of Queensland

In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).

Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.

Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.

The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.

The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.

Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.

The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.

The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.

However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.

Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.

Suicidal behaviors are common in older adults – and especially older women, new research suggests.

In a meta-analysis that included 20 studies and more than 3 million total individuals living in long-term care (LTC), the prevalence rate for suicidal behavior was more than 6%. In addition, the most common of these behaviors was suicidal ideation.

The prevalence was much higher in women than in men.

These high rates underline the need for clinicians to exercise “extra caution” when assessing elderly people living in a long-term care facility, coinvestigator Syeda Beenish Bareeqa, MBBS, clinical researcher, Jinnah Medical and Dental College, Karachi, Pakistan, and research observer, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Missed diagnoses or undertreatment in this population can lead to deleterious health outcomes,” Dr. Bareeqa said.

The findings were presented at the annual meeting of the American Association for Geriatric Psychiatry.
 

Underdiagnosed, undertreated

In the United States, about 42% of adults 70 years and older will live in LTC, either in an assisted care facility or a nursing home, Dr. Bareeqa noted.

Although many LTC residents have a mood disorder, previous research shows that fewer than 25% of cases are diagnosed and treated, she said.

Dr. Bareeqa added that suicide – and its association with factors such as the COVID-19 pandemic, depression, and cyberbullying – is a topic of increasing interest to researchers. She and her colleagues wanted to investigate suicidal behaviors in the setting of LTC.

The researchers conducted a literature search for studies of suicidal behavior among LTC residents over aged 60 years. They examined general suicidal behavior and the most common subtypes: suicide ideation, suicide attempts, completed suicide, self-destructive behavior, and nonsuicidal self-injury.

The analysis included 20 studies and 3 million individuals living in LTC. The majority of the studies were conducted in the United States (n = 5) and Australia (n = 4).

Results showed an estimated suicidal behavior prevalence rate of 6.4% (.064; 95% confidence interval, .057 to .070), or 64 per 100,000 persons.

A rate this high is “alarming and unexpected,” said Dr. Bareeqa. She noted most of the studies included in the analysis were conducted in developed countries with advanced health care systems.

The World Health Organization reports the suicide rate per 100,000 older adults (aged 75 years and older) is 50 for men and 16 for women, but this is not stratified by living settings, Dr. Bareeqa noted.
 

Higher rates in women

In the current analysis, 5 of the 20 studies had low risk of bias, 14 had moderate risk, and 1 had high risk, Dr. Bareeqa reported.

In subgroup analyses, the researchers found much of the suicidal behavior was driven by studies out of Australia, where the prevalence of suicidal behaviors was 36.9% (95% CI, 9.2-64.7) vs. 1.4% in the U.S. (95% CI, 1.0-1.8).

Another surprising finding was the prevalence of suicidal behaviors among women (15.8%), which was much higher than among men (7.9%). “Male gender is a well-established risk factor for suicide in the medical literature but this is not the case in our study,” said Dr. Bareeqa.

In addition, the analysis showed suicidal ideation was the most common type of suicidal behavior. In a pooled population of around 2 million people in eight studies, the prevalence of suicidal ideation was 12%.

For psychiatric illnesses accompanying suicidal behavior, the prevalence of depression alone was 14.4%, which was much higher than the rate of 5.1% for multiple comorbidities – including depression, anxiety, obsessive-compulsive disorder, psychotic disorder, history of previous suicide attempt, delusion, delirium, and hallucination.

Although depression and other psychiatric conditions may help explain suicidal behavior in older adults, Dr. Bareeqa said physical illness also plays a major role.

“Illnesses like cancer or end-stage organ failure, which are quite common with advancing age, are debilitating and in some instances incurable. These medical problems create a breeding ground for mental health problems and can eventually lead to devastating outcomes such as suicide,” she said.

She noted the importance of a “multipronged approach” to prevent suicide among older people in LTC facilities.

In addition, her research team aims to assess the quality of care provided by LTC facilities. “Maybe we can get to the root of this problem and devise strategies to improve it,” she said.
 

‘Not uncommon’

In an interview with this news organization Rajesh R. Tampi, MBBS, professor and chairman, department of psychiatry, Creighton University and Catholic Health Initiatives Health Behavioral Health Services, Omaha, Neb., said the results suggest that, despite the risk for bias among the included studies, “suicidal behaviors are not uncommon among older adults in LTC.”

The analysis describes only associations “but does not indicate causality,” said Dr. Tampi, past president of the AAGP. He was not involved with the research.

Additional subgroup analyses should yield information on possible risk factors for suicidal behaviors in LTC, such as depression, anxiety, and chronic pain, he added.

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

Suicidal behaviors are common in older adults – and especially older women, new research suggests.

In a meta-analysis that included 20 studies and more than 3 million total individuals living in long-term care (LTC), the prevalence rate for suicidal behavior was more than 6%. In addition, the most common of these behaviors was suicidal ideation.

The prevalence was much higher in women than in men.

These high rates underline the need for clinicians to exercise “extra caution” when assessing elderly people living in a long-term care facility, coinvestigator Syeda Beenish Bareeqa, MBBS, clinical researcher, Jinnah Medical and Dental College, Karachi, Pakistan, and research observer, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Missed diagnoses or undertreatment in this population can lead to deleterious health outcomes,” Dr. Bareeqa said.

The findings were presented at the annual meeting of the American Association for Geriatric Psychiatry.
 

Underdiagnosed, undertreated

In the United States, about 42% of adults 70 years and older will live in LTC, either in an assisted care facility or a nursing home, Dr. Bareeqa noted.

Although many LTC residents have a mood disorder, previous research shows that fewer than 25% of cases are diagnosed and treated, she said.

Dr. Bareeqa added that suicide – and its association with factors such as the COVID-19 pandemic, depression, and cyberbullying – is a topic of increasing interest to researchers. She and her colleagues wanted to investigate suicidal behaviors in the setting of LTC.

The researchers conducted a literature search for studies of suicidal behavior among LTC residents over aged 60 years. They examined general suicidal behavior and the most common subtypes: suicide ideation, suicide attempts, completed suicide, self-destructive behavior, and nonsuicidal self-injury.

The analysis included 20 studies and 3 million individuals living in LTC. The majority of the studies were conducted in the United States (n = 5) and Australia (n = 4).

Results showed an estimated suicidal behavior prevalence rate of 6.4% (.064; 95% confidence interval, .057 to .070), or 64 per 100,000 persons.

A rate this high is “alarming and unexpected,” said Dr. Bareeqa. She noted most of the studies included in the analysis were conducted in developed countries with advanced health care systems.

The World Health Organization reports the suicide rate per 100,000 older adults (aged 75 years and older) is 50 for men and 16 for women, but this is not stratified by living settings, Dr. Bareeqa noted.
 

Higher rates in women

In the current analysis, 5 of the 20 studies had low risk of bias, 14 had moderate risk, and 1 had high risk, Dr. Bareeqa reported.

In subgroup analyses, the researchers found much of the suicidal behavior was driven by studies out of Australia, where the prevalence of suicidal behaviors was 36.9% (95% CI, 9.2-64.7) vs. 1.4% in the U.S. (95% CI, 1.0-1.8).

Another surprising finding was the prevalence of suicidal behaviors among women (15.8%), which was much higher than among men (7.9%). “Male gender is a well-established risk factor for suicide in the medical literature but this is not the case in our study,” said Dr. Bareeqa.

In addition, the analysis showed suicidal ideation was the most common type of suicidal behavior. In a pooled population of around 2 million people in eight studies, the prevalence of suicidal ideation was 12%.

For psychiatric illnesses accompanying suicidal behavior, the prevalence of depression alone was 14.4%, which was much higher than the rate of 5.1% for multiple comorbidities – including depression, anxiety, obsessive-compulsive disorder, psychotic disorder, history of previous suicide attempt, delusion, delirium, and hallucination.

Although depression and other psychiatric conditions may help explain suicidal behavior in older adults, Dr. Bareeqa said physical illness also plays a major role.

“Illnesses like cancer or end-stage organ failure, which are quite common with advancing age, are debilitating and in some instances incurable. These medical problems create a breeding ground for mental health problems and can eventually lead to devastating outcomes such as suicide,” she said.

She noted the importance of a “multipronged approach” to prevent suicide among older people in LTC facilities.

In addition, her research team aims to assess the quality of care provided by LTC facilities. “Maybe we can get to the root of this problem and devise strategies to improve it,” she said.
 

‘Not uncommon’

In an interview with this news organization Rajesh R. Tampi, MBBS, professor and chairman, department of psychiatry, Creighton University and Catholic Health Initiatives Health Behavioral Health Services, Omaha, Neb., said the results suggest that, despite the risk for bias among the included studies, “suicidal behaviors are not uncommon among older adults in LTC.”

The analysis describes only associations “but does not indicate causality,” said Dr. Tampi, past president of the AAGP. He was not involved with the research.

Additional subgroup analyses should yield information on possible risk factors for suicidal behaviors in LTC, such as depression, anxiety, and chronic pain, he added.

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

Suicidal behaviors are common in older adults – and especially older women, new research suggests.

In a meta-analysis that included 20 studies and more than 3 million total individuals living in long-term care (LTC), the prevalence rate for suicidal behavior was more than 6%. In addition, the most common of these behaviors was suicidal ideation.

The prevalence was much higher in women than in men.

These high rates underline the need for clinicians to exercise “extra caution” when assessing elderly people living in a long-term care facility, coinvestigator Syeda Beenish Bareeqa, MBBS, clinical researcher, Jinnah Medical and Dental College, Karachi, Pakistan, and research observer, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Missed diagnoses or undertreatment in this population can lead to deleterious health outcomes,” Dr. Bareeqa said.

The findings were presented at the annual meeting of the American Association for Geriatric Psychiatry.
 

Underdiagnosed, undertreated

In the United States, about 42% of adults 70 years and older will live in LTC, either in an assisted care facility or a nursing home, Dr. Bareeqa noted.

Although many LTC residents have a mood disorder, previous research shows that fewer than 25% of cases are diagnosed and treated, she said.

Dr. Bareeqa added that suicide – and its association with factors such as the COVID-19 pandemic, depression, and cyberbullying – is a topic of increasing interest to researchers. She and her colleagues wanted to investigate suicidal behaviors in the setting of LTC.

The researchers conducted a literature search for studies of suicidal behavior among LTC residents over aged 60 years. They examined general suicidal behavior and the most common subtypes: suicide ideation, suicide attempts, completed suicide, self-destructive behavior, and nonsuicidal self-injury.

The analysis included 20 studies and 3 million individuals living in LTC. The majority of the studies were conducted in the United States (n = 5) and Australia (n = 4).

Results showed an estimated suicidal behavior prevalence rate of 6.4% (.064; 95% confidence interval, .057 to .070), or 64 per 100,000 persons.

A rate this high is “alarming and unexpected,” said Dr. Bareeqa. She noted most of the studies included in the analysis were conducted in developed countries with advanced health care systems.

The World Health Organization reports the suicide rate per 100,000 older adults (aged 75 years and older) is 50 for men and 16 for women, but this is not stratified by living settings, Dr. Bareeqa noted.
 

Higher rates in women

In the current analysis, 5 of the 20 studies had low risk of bias, 14 had moderate risk, and 1 had high risk, Dr. Bareeqa reported.

In subgroup analyses, the researchers found much of the suicidal behavior was driven by studies out of Australia, where the prevalence of suicidal behaviors was 36.9% (95% CI, 9.2-64.7) vs. 1.4% in the U.S. (95% CI, 1.0-1.8).

Another surprising finding was the prevalence of suicidal behaviors among women (15.8%), which was much higher than among men (7.9%). “Male gender is a well-established risk factor for suicide in the medical literature but this is not the case in our study,” said Dr. Bareeqa.

In addition, the analysis showed suicidal ideation was the most common type of suicidal behavior. In a pooled population of around 2 million people in eight studies, the prevalence of suicidal ideation was 12%.

For psychiatric illnesses accompanying suicidal behavior, the prevalence of depression alone was 14.4%, which was much higher than the rate of 5.1% for multiple comorbidities – including depression, anxiety, obsessive-compulsive disorder, psychotic disorder, history of previous suicide attempt, delusion, delirium, and hallucination.

Although depression and other psychiatric conditions may help explain suicidal behavior in older adults, Dr. Bareeqa said physical illness also plays a major role.

“Illnesses like cancer or end-stage organ failure, which are quite common with advancing age, are debilitating and in some instances incurable. These medical problems create a breeding ground for mental health problems and can eventually lead to devastating outcomes such as suicide,” she said.

She noted the importance of a “multipronged approach” to prevent suicide among older people in LTC facilities.

In addition, her research team aims to assess the quality of care provided by LTC facilities. “Maybe we can get to the root of this problem and devise strategies to improve it,” she said.
 

‘Not uncommon’

In an interview with this news organization Rajesh R. Tampi, MBBS, professor and chairman, department of psychiatry, Creighton University and Catholic Health Initiatives Health Behavioral Health Services, Omaha, Neb., said the results suggest that, despite the risk for bias among the included studies, “suicidal behaviors are not uncommon among older adults in LTC.”

The analysis describes only associations “but does not indicate causality,” said Dr. Tampi, past president of the AAGP. He was not involved with the research.

Additional subgroup analyses should yield information on possible risk factors for suicidal behaviors in LTC, such as depression, anxiety, and chronic pain, he added.

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

On his last shift in the last hockey game of the regular season, our 14-year-old grandson broke his arm. Although this was his first fracture, the rest of the nuclear family has had ample experience with orthopedic trauma over the last year, both planned and unplanned.

As I drove Peter and my daughter-in-law to his first postsetting and casting appointment I told him how sorry I was that he had been told “no contact sports for the next 3 months.” This was a tough pill for a kid eager to begin his first high school lacrosse season. Then I asked him what the doctor had told him he could do in the way of activity.

Based on personal and professional experience I was not surprised when he told me that no one had suggested things he could be doing. In fact, being a cautious and thoughtful kid, he was concerned about what he should be doing around the house let alone any athletic activities. It turns out he wasn’t even lifting his laptop computer with two hands because some nurse had told him not to lift anything over 2 pounds.

I told him “Peter, even some of the most experienced doctors focus on the ‘can’ts’ and forget to tell you the ‘cans’ and ‘shoulds.’ While you’re in the waiting room make up a mental list of what you would like to be doing that you aren’t.”

As he climbed back in the car for the ride home I asked how the visit went. The x-ray showed good alignment and the doctor was pleased. But, as I predicted, they were already on the launch pad to the receptionist to make a follow-up appointment without the physician uttering a single word about what activities he could resume. Always a very coachable kid, Peter piped up with the list he had created in the waiting room and was relieved to hear that he could do anything as long as it didn’t hurt. In fact, the doctor encouraged him to use his fingers because it might speed the healing.

Not every patient, regardless of age, is as cautious as my grandson and in some circumstances the physician must err on the side of emphasizing the “don’ts.” However, in my experience, too many physicians forget to include a generous list of “can do’s” in their visit closing discussions. This oversight is a mistake for several reasons.

First, and maybe most importantly, even a brief discussion of “can do’s” can soften the depressing message that the patient will not be able to do things he or she enjoys. I can’t quote the references but I am sure there is plenty of evidence that depression slows the healing process.

Second, and this is particularly true in older patients with orthopedic problems – failure to include a plan for return to activity can hinder recovery. I can recall more than a few patients who were seen in the emergency department and diagnosed with sprains but not given even the simplest instructions on how to begin moving the injured joint. When they finally returned to see me we had to begin the painful and unnecessary project of thawing a frozen joint.

Fortunately, we have evolved past the era when best rest was near the top of the list of our recommended remedies. However, there still remains a bias against activity in some situations. The most recent example is the evolving strategies for the management of concussion. There is some evidence that involving the patient in a return to activity plan may shorten the time to recovery. The myth about brain rest has been slow to die.

Finally, providing the patient with a personalized list of “can do’s” makes good business sense because it can head off those time-gobbling call backs that tie up you and your office staff. As an experienced physician, you have probably learned the most frequently asked “Can Jason do ... ?” questions. Make your own list and give the patient your answers. An ounce of anticipatory guidance is worth hours on the telephone or sorting through the email inbox.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

On his last shift in the last hockey game of the regular season, our 14-year-old grandson broke his arm. Although this was his first fracture, the rest of the nuclear family has had ample experience with orthopedic trauma over the last year, both planned and unplanned.

As I drove Peter and my daughter-in-law to his first postsetting and casting appointment I told him how sorry I was that he had been told “no contact sports for the next 3 months.” This was a tough pill for a kid eager to begin his first high school lacrosse season. Then I asked him what the doctor had told him he could do in the way of activity.

Based on personal and professional experience I was not surprised when he told me that no one had suggested things he could be doing. In fact, being a cautious and thoughtful kid, he was concerned about what he should be doing around the house let alone any athletic activities. It turns out he wasn’t even lifting his laptop computer with two hands because some nurse had told him not to lift anything over 2 pounds.

I told him “Peter, even some of the most experienced doctors focus on the ‘can’ts’ and forget to tell you the ‘cans’ and ‘shoulds.’ While you’re in the waiting room make up a mental list of what you would like to be doing that you aren’t.”

As he climbed back in the car for the ride home I asked how the visit went. The x-ray showed good alignment and the doctor was pleased. But, as I predicted, they were already on the launch pad to the receptionist to make a follow-up appointment without the physician uttering a single word about what activities he could resume. Always a very coachable kid, Peter piped up with the list he had created in the waiting room and was relieved to hear that he could do anything as long as it didn’t hurt. In fact, the doctor encouraged him to use his fingers because it might speed the healing.

Not every patient, regardless of age, is as cautious as my grandson and in some circumstances the physician must err on the side of emphasizing the “don’ts.” However, in my experience, too many physicians forget to include a generous list of “can do’s” in their visit closing discussions. This oversight is a mistake for several reasons.

First, and maybe most importantly, even a brief discussion of “can do’s” can soften the depressing message that the patient will not be able to do things he or she enjoys. I can’t quote the references but I am sure there is plenty of evidence that depression slows the healing process.

Second, and this is particularly true in older patients with orthopedic problems – failure to include a plan for return to activity can hinder recovery. I can recall more than a few patients who were seen in the emergency department and diagnosed with sprains but not given even the simplest instructions on how to begin moving the injured joint. When they finally returned to see me we had to begin the painful and unnecessary project of thawing a frozen joint.

Fortunately, we have evolved past the era when best rest was near the top of the list of our recommended remedies. However, there still remains a bias against activity in some situations. The most recent example is the evolving strategies for the management of concussion. There is some evidence that involving the patient in a return to activity plan may shorten the time to recovery. The myth about brain rest has been slow to die.

Finally, providing the patient with a personalized list of “can do’s” makes good business sense because it can head off those time-gobbling call backs that tie up you and your office staff. As an experienced physician, you have probably learned the most frequently asked “Can Jason do ... ?” questions. Make your own list and give the patient your answers. An ounce of anticipatory guidance is worth hours on the telephone or sorting through the email inbox.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

On his last shift in the last hockey game of the regular season, our 14-year-old grandson broke his arm. Although this was his first fracture, the rest of the nuclear family has had ample experience with orthopedic trauma over the last year, both planned and unplanned.

As I drove Peter and my daughter-in-law to his first postsetting and casting appointment I told him how sorry I was that he had been told “no contact sports for the next 3 months.” This was a tough pill for a kid eager to begin his first high school lacrosse season. Then I asked him what the doctor had told him he could do in the way of activity.

Based on personal and professional experience I was not surprised when he told me that no one had suggested things he could be doing. In fact, being a cautious and thoughtful kid, he was concerned about what he should be doing around the house let alone any athletic activities. It turns out he wasn’t even lifting his laptop computer with two hands because some nurse had told him not to lift anything over 2 pounds.

I told him “Peter, even some of the most experienced doctors focus on the ‘can’ts’ and forget to tell you the ‘cans’ and ‘shoulds.’ While you’re in the waiting room make up a mental list of what you would like to be doing that you aren’t.”

As he climbed back in the car for the ride home I asked how the visit went. The x-ray showed good alignment and the doctor was pleased. But, as I predicted, they were already on the launch pad to the receptionist to make a follow-up appointment without the physician uttering a single word about what activities he could resume. Always a very coachable kid, Peter piped up with the list he had created in the waiting room and was relieved to hear that he could do anything as long as it didn’t hurt. In fact, the doctor encouraged him to use his fingers because it might speed the healing.

Not every patient, regardless of age, is as cautious as my grandson and in some circumstances the physician must err on the side of emphasizing the “don’ts.” However, in my experience, too many physicians forget to include a generous list of “can do’s” in their visit closing discussions. This oversight is a mistake for several reasons.

First, and maybe most importantly, even a brief discussion of “can do’s” can soften the depressing message that the patient will not be able to do things he or she enjoys. I can’t quote the references but I am sure there is plenty of evidence that depression slows the healing process.

Second, and this is particularly true in older patients with orthopedic problems – failure to include a plan for return to activity can hinder recovery. I can recall more than a few patients who were seen in the emergency department and diagnosed with sprains but not given even the simplest instructions on how to begin moving the injured joint. When they finally returned to see me we had to begin the painful and unnecessary project of thawing a frozen joint.

Fortunately, we have evolved past the era when best rest was near the top of the list of our recommended remedies. However, there still remains a bias against activity in some situations. The most recent example is the evolving strategies for the management of concussion. There is some evidence that involving the patient in a return to activity plan may shorten the time to recovery. The myth about brain rest has been slow to die.

Finally, providing the patient with a personalized list of “can do’s” makes good business sense because it can head off those time-gobbling call backs that tie up you and your office staff. As an experienced physician, you have probably learned the most frequently asked “Can Jason do ... ?” questions. Make your own list and give the patient your answers. An ounce of anticipatory guidance is worth hours on the telephone or sorting through the email inbox.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Intravenous gentamicin therapy was associated with new laminin 332 – a major component of anchoring filaments in the dermal-epidermal junction – in the skin of five pediatric patients with intermediate or severe junctional epidermolysis bullosa (JEB) caused by nonsense variants.

The newly generated structural protein persisted during the 3-month randomized clinical trial and was associated with significant wound closure – with no signs of ototoxic effects, nephrotoxic effects, or anti–laminin 332 autoantibody induction, investigators recently reported in JAMA Dermatology.

JEB is a rare, autosomal recessive disorder caused mainly by nonsense variants (i.e., mutations) in the LAMA3, LAMB3, or LAMC2 genes that encode laminin, resulting in widespread blisters and erosions of the skin. Current treatment is limited to supportive management and palliative care, and children with its severe subtype are likely to die within the first year of life.

“With data indicating a robust response to short-term gentamicin treatment and the marked stability of laminin 332, we envision that gentamicin could be delivered as a short-term pulse therapy every 2-3 months for patients with JEB caused by nonsense variants,” the researchers wrote.

Of the five patients, ages 3 months to 10 years, three received 7.5 mg/kg IV gentamicin daily for 14 days, and two received 10 mg/kg daily for 24 days at the University of Southern California, Los Angeles.

All had confirmed nonsense variants in LAMA3 or LAMB3 in one or two alleles, and all had minimal laminin 332 expression at baseline as determined by immunofluorescence. After treatment, each of the children had increased, sustained expression of laminin 332.

The researchers monitored three open wounds in each patient. By 1 month, seven of nine wounds in those receiving the lower-dose therapy and all of the wounds in those receiving the higher-dose therapy showed at least 50% closure. By 3 months, eight of nine wounds in the lower-dose group, and all wounds in the higher-dose group showed greater than 85% closure.

In an interview, senior investigators Mei Chen, PhD, professor of dermatology, and David T. Woodley, MD, professor and chair of dermatology, both at USC, emphasized laminin’s long half-life.“Once these skin structural proteins are generated at the dermal-epidermal junction, they are long-lasting structures, which means the therapy can be pulsed rather than continuously delivered, which can obviate some of the known side effects of the medication,” Dr. Woodley said.

Gentamicin, an aminoglycoside, works as a “read-through therapy,” inducing ribosomal read-through of premature termination codons (PTCs) caused by nonsense mutations. The read-through allows translation to proceed and full-length proteins to be generated.

Gentamicin read-through therapy is also being investigated for recessive dystrophic epidermolysis bullosa (RDEB) attributable to nonsense mutations. The culprit mutations in this form of EB occur in a gene that encodes collagen type VII alpha 1, which, like laminin, is responsible for dermal-epidermal adherence. A clinical trial of intravenous gentamicin for RDEB is ongoing at USC, Dr. Chen said.


 

EBS-MD case report

It may also have a role in treating epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), according to investigators in Madrid. Their case report, published in JAMA Dermatology, details how two 14-day courses of infused gentamicin therapy were followed by re-expression of plectin in the skin for 4-5 months and mild improvement in symptoms in one patient, a woman in her 30s, with a homozygous nonsense variant in PLEC1.

In an editorial accompanying the two reports, Anna L. Bruckner, MD, MSCS, professor of dermatology, University of Colorado at Denver, Aurora, and colleagues expressed cautious optimism and said that additional research on the feasibility, possible cumulative toxic effects, risk of microbial resistance, and overall clinical relevance is needed.

Still, the “investigators should be applauded for taking advantage of a readily available systemic treatment to target cutaneous and extracutaneous symptoms of patients who have very limited treatment options at this time,” they wrote. While all forms of EB are considered orphan disorders, JEB and EBS-MD have received less research attention than RDEB.

The JEB study evaluated patients with clinical assessments/quality of life surveys and with a validated clinical score that considers skin and mucosae – the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI). There were small positive changes in EBDASI scores, but data were incomplete and therefore difficult to interpret.

A “noteworthy” finding, the authors wrote, were improvements in emotions and functioning in two of the children who were eligible given their older ages for assessment with the Skindex-16 quality-of-life survey. The improvements suggest “potential psychosocial benefits” of the gentamicin therapy.

The JEB study was supported in part by grants from the EB Research Partnership and EB Medical Research Foundation and an award from the Congressionally Directed Medical Research Program. In addition to the grants, Dr. Woodley and Dr. Chen reported receiving personal fees from Phoenix Tissue Repair outside of the submitted work. For the EBS-MD case report, the authors reported no disclosures. Dr. Bruckner, corresponding author of the editorial, reported grants from several companies outside the submitted work.

Intravenous gentamicin therapy was associated with new laminin 332 – a major component of anchoring filaments in the dermal-epidermal junction – in the skin of five pediatric patients with intermediate or severe junctional epidermolysis bullosa (JEB) caused by nonsense variants.

The newly generated structural protein persisted during the 3-month randomized clinical trial and was associated with significant wound closure – with no signs of ototoxic effects, nephrotoxic effects, or anti–laminin 332 autoantibody induction, investigators recently reported in JAMA Dermatology.

JEB is a rare, autosomal recessive disorder caused mainly by nonsense variants (i.e., mutations) in the LAMA3, LAMB3, or LAMC2 genes that encode laminin, resulting in widespread blisters and erosions of the skin. Current treatment is limited to supportive management and palliative care, and children with its severe subtype are likely to die within the first year of life.

“With data indicating a robust response to short-term gentamicin treatment and the marked stability of laminin 332, we envision that gentamicin could be delivered as a short-term pulse therapy every 2-3 months for patients with JEB caused by nonsense variants,” the researchers wrote.

Of the five patients, ages 3 months to 10 years, three received 7.5 mg/kg IV gentamicin daily for 14 days, and two received 10 mg/kg daily for 24 days at the University of Southern California, Los Angeles.

All had confirmed nonsense variants in LAMA3 or LAMB3 in one or two alleles, and all had minimal laminin 332 expression at baseline as determined by immunofluorescence. After treatment, each of the children had increased, sustained expression of laminin 332.

The researchers monitored three open wounds in each patient. By 1 month, seven of nine wounds in those receiving the lower-dose therapy and all of the wounds in those receiving the higher-dose therapy showed at least 50% closure. By 3 months, eight of nine wounds in the lower-dose group, and all wounds in the higher-dose group showed greater than 85% closure.

In an interview, senior investigators Mei Chen, PhD, professor of dermatology, and David T. Woodley, MD, professor and chair of dermatology, both at USC, emphasized laminin’s long half-life.“Once these skin structural proteins are generated at the dermal-epidermal junction, they are long-lasting structures, which means the therapy can be pulsed rather than continuously delivered, which can obviate some of the known side effects of the medication,” Dr. Woodley said.

Gentamicin, an aminoglycoside, works as a “read-through therapy,” inducing ribosomal read-through of premature termination codons (PTCs) caused by nonsense mutations. The read-through allows translation to proceed and full-length proteins to be generated.

Gentamicin read-through therapy is also being investigated for recessive dystrophic epidermolysis bullosa (RDEB) attributable to nonsense mutations. The culprit mutations in this form of EB occur in a gene that encodes collagen type VII alpha 1, which, like laminin, is responsible for dermal-epidermal adherence. A clinical trial of intravenous gentamicin for RDEB is ongoing at USC, Dr. Chen said.


 

EBS-MD case report

It may also have a role in treating epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), according to investigators in Madrid. Their case report, published in JAMA Dermatology, details how two 14-day courses of infused gentamicin therapy were followed by re-expression of plectin in the skin for 4-5 months and mild improvement in symptoms in one patient, a woman in her 30s, with a homozygous nonsense variant in PLEC1.

In an editorial accompanying the two reports, Anna L. Bruckner, MD, MSCS, professor of dermatology, University of Colorado at Denver, Aurora, and colleagues expressed cautious optimism and said that additional research on the feasibility, possible cumulative toxic effects, risk of microbial resistance, and overall clinical relevance is needed.

Still, the “investigators should be applauded for taking advantage of a readily available systemic treatment to target cutaneous and extracutaneous symptoms of patients who have very limited treatment options at this time,” they wrote. While all forms of EB are considered orphan disorders, JEB and EBS-MD have received less research attention than RDEB.

The JEB study evaluated patients with clinical assessments/quality of life surveys and with a validated clinical score that considers skin and mucosae – the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI). There were small positive changes in EBDASI scores, but data were incomplete and therefore difficult to interpret.

A “noteworthy” finding, the authors wrote, were improvements in emotions and functioning in two of the children who were eligible given their older ages for assessment with the Skindex-16 quality-of-life survey. The improvements suggest “potential psychosocial benefits” of the gentamicin therapy.

The JEB study was supported in part by grants from the EB Research Partnership and EB Medical Research Foundation and an award from the Congressionally Directed Medical Research Program. In addition to the grants, Dr. Woodley and Dr. Chen reported receiving personal fees from Phoenix Tissue Repair outside of the submitted work. For the EBS-MD case report, the authors reported no disclosures. Dr. Bruckner, corresponding author of the editorial, reported grants from several companies outside the submitted work.

Intravenous gentamicin therapy was associated with new laminin 332 – a major component of anchoring filaments in the dermal-epidermal junction – in the skin of five pediatric patients with intermediate or severe junctional epidermolysis bullosa (JEB) caused by nonsense variants.

The newly generated structural protein persisted during the 3-month randomized clinical trial and was associated with significant wound closure – with no signs of ototoxic effects, nephrotoxic effects, or anti–laminin 332 autoantibody induction, investigators recently reported in JAMA Dermatology.

JEB is a rare, autosomal recessive disorder caused mainly by nonsense variants (i.e., mutations) in the LAMA3, LAMB3, or LAMC2 genes that encode laminin, resulting in widespread blisters and erosions of the skin. Current treatment is limited to supportive management and palliative care, and children with its severe subtype are likely to die within the first year of life.

“With data indicating a robust response to short-term gentamicin treatment and the marked stability of laminin 332, we envision that gentamicin could be delivered as a short-term pulse therapy every 2-3 months for patients with JEB caused by nonsense variants,” the researchers wrote.

Of the five patients, ages 3 months to 10 years, three received 7.5 mg/kg IV gentamicin daily for 14 days, and two received 10 mg/kg daily for 24 days at the University of Southern California, Los Angeles.

All had confirmed nonsense variants in LAMA3 or LAMB3 in one or two alleles, and all had minimal laminin 332 expression at baseline as determined by immunofluorescence. After treatment, each of the children had increased, sustained expression of laminin 332.

The researchers monitored three open wounds in each patient. By 1 month, seven of nine wounds in those receiving the lower-dose therapy and all of the wounds in those receiving the higher-dose therapy showed at least 50% closure. By 3 months, eight of nine wounds in the lower-dose group, and all wounds in the higher-dose group showed greater than 85% closure.

In an interview, senior investigators Mei Chen, PhD, professor of dermatology, and David T. Woodley, MD, professor and chair of dermatology, both at USC, emphasized laminin’s long half-life.“Once these skin structural proteins are generated at the dermal-epidermal junction, they are long-lasting structures, which means the therapy can be pulsed rather than continuously delivered, which can obviate some of the known side effects of the medication,” Dr. Woodley said.

Gentamicin, an aminoglycoside, works as a “read-through therapy,” inducing ribosomal read-through of premature termination codons (PTCs) caused by nonsense mutations. The read-through allows translation to proceed and full-length proteins to be generated.

Gentamicin read-through therapy is also being investigated for recessive dystrophic epidermolysis bullosa (RDEB) attributable to nonsense mutations. The culprit mutations in this form of EB occur in a gene that encodes collagen type VII alpha 1, which, like laminin, is responsible for dermal-epidermal adherence. A clinical trial of intravenous gentamicin for RDEB is ongoing at USC, Dr. Chen said.


 

EBS-MD case report

It may also have a role in treating epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), according to investigators in Madrid. Their case report, published in JAMA Dermatology, details how two 14-day courses of infused gentamicin therapy were followed by re-expression of plectin in the skin for 4-5 months and mild improvement in symptoms in one patient, a woman in her 30s, with a homozygous nonsense variant in PLEC1.

In an editorial accompanying the two reports, Anna L. Bruckner, MD, MSCS, professor of dermatology, University of Colorado at Denver, Aurora, and colleagues expressed cautious optimism and said that additional research on the feasibility, possible cumulative toxic effects, risk of microbial resistance, and overall clinical relevance is needed.

Still, the “investigators should be applauded for taking advantage of a readily available systemic treatment to target cutaneous and extracutaneous symptoms of patients who have very limited treatment options at this time,” they wrote. While all forms of EB are considered orphan disorders, JEB and EBS-MD have received less research attention than RDEB.

The JEB study evaluated patients with clinical assessments/quality of life surveys and with a validated clinical score that considers skin and mucosae – the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI). There were small positive changes in EBDASI scores, but data were incomplete and therefore difficult to interpret.

A “noteworthy” finding, the authors wrote, were improvements in emotions and functioning in two of the children who were eligible given their older ages for assessment with the Skindex-16 quality-of-life survey. The improvements suggest “potential psychosocial benefits” of the gentamicin therapy.

The JEB study was supported in part by grants from the EB Research Partnership and EB Medical Research Foundation and an award from the Congressionally Directed Medical Research Program. In addition to the grants, Dr. Woodley and Dr. Chen reported receiving personal fees from Phoenix Tissue Repair outside of the submitted work. For the EBS-MD case report, the authors reported no disclosures. Dr. Bruckner, corresponding author of the editorial, reported grants from several companies outside the submitted work.

Ivermectin, an antiparasitic drug that became popular as an alternative treatment for COVID-19, showed no signs of quelling the disease or reducing patients’ risk of hospitalization, according to results from a large clinical trial published in the New England Journal of Medicine.

The findings pretty much rule out the drug as a treatment for COVID-19, the study authors wrote.

“There’s really no sign of any benefit,” David Boulware, MD, one of the coauthors and an infectious disease specialist at the University of Minnesota, Minneapolis, told the New York Times.

The researchers shared a summary of the results in August 2021 during an online presentation hosted by the National Institutes of Health. The full data hadn’t been published until now.

“Now that people can dive into the details and the data, hopefully that will steer the majority of doctors away from ivermectin toward other therapies,” Dr. Boulware said.

In the trial, the research team compared more than 1,350 people infected with the coronavirus in Brazil who received either ivermectin or a placebo as treatment.

Between March and August 2021, 679 patients received a daily dose of ivermectin over the course of 3 days. The researchers found that ivermectin didn’t reduce the risk that people with COVID-19 would be hospitalized or go to an ED within 28 days after treatment.

In addition, the researchers looked at particular groups to understand if some patients benefited for some reason, such as taking ivermectin sooner after testing positive for COVID-19. But those who took the drug during the first 3 days after a positive coronavirus test ended up doing worse than those in the placebo group. The drug also didn’t help patients recover sooner.

The researchers found “no important effects” of treatment with ivermectin on the number of days people spent in the hospital, the number of days hospitalized people needed mechanical ventilation, or the risk of death.

Ivermectin has become a controversial focal point during the pandemic.

For decades, the drug has been widely used to treat parasitic infections. At the beginning of the pandemic, researchers checked thousands of existing drugs against the coronavirus to determine if a potential treatment already existed. Laboratory experiments on cells suggested that ivermectin might work, the New York Times reported.

But some researchers noted that the experiments worked because a high concentration of ivermectin was used, a much higher dose than would be safe for people. Despite the concerns, some doctors began prescribing ivermectin to patients. After receiving reports of people who needed medical attention, particularly after using formulations intended for livestock, the Food and Drug Administration issued a warning that the drug wasn’t approved to be used for COVID-19.

Researchers around the world have done small clinical trials to understand whether ivermectin treats COVID-19, the newspaper reported. At the end of 2020, Andrew Hill, MD, a virologist at the University of Liverpool in England, reviewed the results from 23 trials and concluded that the drug could lower the risk of death from COVID-19. He published the results in July 2021, but later reports found that many of the studies were flawed, and at least one was fraudulent.

Dr. Hill retracted his original study and began another analysis, which was published in January 2022. In this review, he and his colleagues focused on studies that were least likely to be biased. They found that ivermectin was not helpful.

Recently, Dr. Hill and associates ran another analysis using the new data from the Brazil trial, and once again they saw no benefit.

Several clinical trials are still testing ivermectin as a treatment, the New York Times reported, with results expected in upcoming months. After reviewing the data from the Brazil trial, which tested ivermectin and a variety of other drugs against COVID-19, some infectious disease experts say they’ll likely see more of the same – that ivermectin doesn’t help people with COVID-19.

“I welcome the results of the other clinical trials and will view them with an open mind,” Paul Sax, MD, an infectious disease expert at Brigham and Women’s Hospital, Boston, who has been watching the data on the drug throughout the pandemic, told the New York Times.

“But at some point, it will become a waste of resources to continue studying an unpromising approach,” he said.

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

Ivermectin, an antiparasitic drug that became popular as an alternative treatment for COVID-19, showed no signs of quelling the disease or reducing patients’ risk of hospitalization, according to results from a large clinical trial published in the New England Journal of Medicine.

The findings pretty much rule out the drug as a treatment for COVID-19, the study authors wrote.

“There’s really no sign of any benefit,” David Boulware, MD, one of the coauthors and an infectious disease specialist at the University of Minnesota, Minneapolis, told the New York Times.

The researchers shared a summary of the results in August 2021 during an online presentation hosted by the National Institutes of Health. The full data hadn’t been published until now.

“Now that people can dive into the details and the data, hopefully that will steer the majority of doctors away from ivermectin toward other therapies,” Dr. Boulware said.

In the trial, the research team compared more than 1,350 people infected with the coronavirus in Brazil who received either ivermectin or a placebo as treatment.

Between March and August 2021, 679 patients received a daily dose of ivermectin over the course of 3 days. The researchers found that ivermectin didn’t reduce the risk that people with COVID-19 would be hospitalized or go to an ED within 28 days after treatment.

In addition, the researchers looked at particular groups to understand if some patients benefited for some reason, such as taking ivermectin sooner after testing positive for COVID-19. But those who took the drug during the first 3 days after a positive coronavirus test ended up doing worse than those in the placebo group. The drug also didn’t help patients recover sooner.

The researchers found “no important effects” of treatment with ivermectin on the number of days people spent in the hospital, the number of days hospitalized people needed mechanical ventilation, or the risk of death.

Ivermectin has become a controversial focal point during the pandemic.

For decades, the drug has been widely used to treat parasitic infections. At the beginning of the pandemic, researchers checked thousands of existing drugs against the coronavirus to determine if a potential treatment already existed. Laboratory experiments on cells suggested that ivermectin might work, the New York Times reported.

But some researchers noted that the experiments worked because a high concentration of ivermectin was used, a much higher dose than would be safe for people. Despite the concerns, some doctors began prescribing ivermectin to patients. After receiving reports of people who needed medical attention, particularly after using formulations intended for livestock, the Food and Drug Administration issued a warning that the drug wasn’t approved to be used for COVID-19.

Researchers around the world have done small clinical trials to understand whether ivermectin treats COVID-19, the newspaper reported. At the end of 2020, Andrew Hill, MD, a virologist at the University of Liverpool in England, reviewed the results from 23 trials and concluded that the drug could lower the risk of death from COVID-19. He published the results in July 2021, but later reports found that many of the studies were flawed, and at least one was fraudulent.

Dr. Hill retracted his original study and began another analysis, which was published in January 2022. In this review, he and his colleagues focused on studies that were least likely to be biased. They found that ivermectin was not helpful.

Recently, Dr. Hill and associates ran another analysis using the new data from the Brazil trial, and once again they saw no benefit.

Several clinical trials are still testing ivermectin as a treatment, the New York Times reported, with results expected in upcoming months. After reviewing the data from the Brazil trial, which tested ivermectin and a variety of other drugs against COVID-19, some infectious disease experts say they’ll likely see more of the same – that ivermectin doesn’t help people with COVID-19.

“I welcome the results of the other clinical trials and will view them with an open mind,” Paul Sax, MD, an infectious disease expert at Brigham and Women’s Hospital, Boston, who has been watching the data on the drug throughout the pandemic, told the New York Times.

“But at some point, it will become a waste of resources to continue studying an unpromising approach,” he said.

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

Ivermectin, an antiparasitic drug that became popular as an alternative treatment for COVID-19, showed no signs of quelling the disease or reducing patients’ risk of hospitalization, according to results from a large clinical trial published in the New England Journal of Medicine.

The findings pretty much rule out the drug as a treatment for COVID-19, the study authors wrote.

“There’s really no sign of any benefit,” David Boulware, MD, one of the coauthors and an infectious disease specialist at the University of Minnesota, Minneapolis, told the New York Times.

The researchers shared a summary of the results in August 2021 during an online presentation hosted by the National Institutes of Health. The full data hadn’t been published until now.

“Now that people can dive into the details and the data, hopefully that will steer the majority of doctors away from ivermectin toward other therapies,” Dr. Boulware said.

In the trial, the research team compared more than 1,350 people infected with the coronavirus in Brazil who received either ivermectin or a placebo as treatment.

Between March and August 2021, 679 patients received a daily dose of ivermectin over the course of 3 days. The researchers found that ivermectin didn’t reduce the risk that people with COVID-19 would be hospitalized or go to an ED within 28 days after treatment.

In addition, the researchers looked at particular groups to understand if some patients benefited for some reason, such as taking ivermectin sooner after testing positive for COVID-19. But those who took the drug during the first 3 days after a positive coronavirus test ended up doing worse than those in the placebo group. The drug also didn’t help patients recover sooner.

The researchers found “no important effects” of treatment with ivermectin on the number of days people spent in the hospital, the number of days hospitalized people needed mechanical ventilation, or the risk of death.

Ivermectin has become a controversial focal point during the pandemic.

For decades, the drug has been widely used to treat parasitic infections. At the beginning of the pandemic, researchers checked thousands of existing drugs against the coronavirus to determine if a potential treatment already existed. Laboratory experiments on cells suggested that ivermectin might work, the New York Times reported.

But some researchers noted that the experiments worked because a high concentration of ivermectin was used, a much higher dose than would be safe for people. Despite the concerns, some doctors began prescribing ivermectin to patients. After receiving reports of people who needed medical attention, particularly after using formulations intended for livestock, the Food and Drug Administration issued a warning that the drug wasn’t approved to be used for COVID-19.

Researchers around the world have done small clinical trials to understand whether ivermectin treats COVID-19, the newspaper reported. At the end of 2020, Andrew Hill, MD, a virologist at the University of Liverpool in England, reviewed the results from 23 trials and concluded that the drug could lower the risk of death from COVID-19. He published the results in July 2021, but later reports found that many of the studies were flawed, and at least one was fraudulent.

Dr. Hill retracted his original study and began another analysis, which was published in January 2022. In this review, he and his colleagues focused on studies that were least likely to be biased. They found that ivermectin was not helpful.

Recently, Dr. Hill and associates ran another analysis using the new data from the Brazil trial, and once again they saw no benefit.

Several clinical trials are still testing ivermectin as a treatment, the New York Times reported, with results expected in upcoming months. After reviewing the data from the Brazil trial, which tested ivermectin and a variety of other drugs against COVID-19, some infectious disease experts say they’ll likely see more of the same – that ivermectin doesn’t help people with COVID-19.

“I welcome the results of the other clinical trials and will view them with an open mind,” Paul Sax, MD, an infectious disease expert at Brigham and Women’s Hospital, Boston, who has been watching the data on the drug throughout the pandemic, told the New York Times.

“But at some point, it will become a waste of resources to continue studying an unpromising approach,” he said.

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

What prophylactic antibiotic should be administered intrapartum to a pregnant woman who is colonized with group B streptococci but who has a mild allergy to penicillin?

Continue to the answer...

In this situation, the drug of choice is intravenous cefazolin, 2 g initially then 1 g every 8 hours until delivery. For patients with a severe allergy to penicillin, the drugs of choice are either clindamycin, 900 mg intravenously every 8 hours (if sensitivity of the organism is confirmed), or vancomycin, 20 mg/kg intravenously every 8 hours (maximum of 2 g per single dose).

What prophylactic antibiotic should be administered intrapartum to a pregnant woman who is colonized with group B streptococci but who has a mild allergy to penicillin?

Continue to the answer...

In this situation, the drug of choice is intravenous cefazolin, 2 g initially then 1 g every 8 hours until delivery. For patients with a severe allergy to penicillin, the drugs of choice are either clindamycin, 900 mg intravenously every 8 hours (if sensitivity of the organism is confirmed), or vancomycin, 20 mg/kg intravenously every 8 hours (maximum of 2 g per single dose).

What prophylactic antibiotic should be administered intrapartum to a pregnant woman who is colonized with group B streptococci but who has a mild allergy to penicillin?

Continue to the answer...

In this situation, the drug of choice is intravenous cefazolin, 2 g initially then 1 g every 8 hours until delivery. For patients with a severe allergy to penicillin, the drugs of choice are either clindamycin, 900 mg intravenously every 8 hours (if sensitivity of the organism is confirmed), or vancomycin, 20 mg/kg intravenously every 8 hours (maximum of 2 g per single dose).

BOSTON – For patients presenting with moderate to severe pemphigus, the choice of initial therapy has been distilled to a single agent: rituximab. This drug is more rapidly effective, more likely to provide sustained remission, better tolerated, and lowers health care costs, according to an expert summary at the annual meeting of the American Academy of Dermatology.

With rituximab “we are not only able to offer better efficacy, earlier and longer remissions, less side effects, less risk of relapse after a response, but it is actually cheaper,” reported Erin X. Wei, MD, director of the Bullous Diseases Clinic at Brigham and Women’s Hospital, Boston.

There are many treatments that reduce the inflammatory component of pemphigus. Corticosteroids, doxycycline, mycophenolate mofetil, azathioprine, and methotrexate are among those options commonly considered in the early control of this rare and potentially fatal autoimmune blistering disease of the skin, mouth, and other tissues.

Not all of these options have been compared directly in controlled trials, but Dr. Wei indicated that the preponderance of evidence is now on the side of rituximab as a first-line choice. For example, in the multicenter Ritux 3 trial, which compared a tapered regimen of prednisone alone to rituximab combined with a shorter and lower-dose prednisone taper in patients with pemphigus, complete response rates off therapy at 2 years were 89% in the rituximab group versus 34% in the group that received prednisone alone.

“This was quite a remarkable difference,” said Dr. Wei, who noted that remissions overall occurred faster in the rituximab group and were more durable once achieved.

No other treatment option has demonstrated this degree of relative benefit over corticosteroids, according to Dr. Wei. She said there is evidence that mycophenolate mofetil acts more rapidly, but it has not been shown to be superior for sustained complete response. Nor has azathioprine provided a clear advantage over steroids. There are no well-conducted comparisons of methotrexate and prednisone, according to Dr. Wei, assistant professor at Harvard Medical School, Boston.

Corticosteroids, doxycycline, and immunomodulators have been characterized as mainstays of early treatment in pemphigus, but Dr. Wei argued that the evidence supports starting with the most effective therapy first. There are many advantages to suppressing disease activity “as soon as possible” after diagnosis.

Early control “is associated with a more sustained remission, lower overall steroid use, and better quality of life,” said Dr. Wei, listing the hazards of starting with less effective therapy, and explaining why she has moved to rituximab as a first-line choice. According to her, there are data to support these advantages.

“Several studies have observed that rituximab, within the first 6 months of disease onset, is associated with a higher rate of complete response and a longer duration of complete response,” Dr. Wei said.

Intravenous immunoglobulin (IVIG) therapy is effective in many patients but less reliable, and it has other disadvantages relative to rituximab as a first-line therapy.

“IVIG in pemphigus works quickly when it works, but it is more expensive and it is more of an ongoing therapy relative to rituximab,” said Dr. Wei, referring to the lower likelihood of IVIG to provide sustained remissions.

The price of rituximab is high relative to prednisone or other immunomodulators, but management costs are ultimately reduced because of better disease control, according to Dr. Wei. She cited a Canadian study published several years ago in which health care costs in the 6 months prior to rituximab were compared to costs over 6 months after it was initiated.

In this cohort of 89 patients with pemphigus or pemphigoid, the average cost per patient for 6 months of care prior to starting rituximab was $42,231 in Canadian dollars. After treatment was started, the cost fell to $29,423, a 30% reduction, over the next 6 months.

“It takes rituximab up to 3 months or sometimes even longer to achieve its greatest benefit, making these results even more impressive,” Dr. Wei said.

The activity of rituximab to suppress autoreactive B-cells can be monitored with antidesmoglein autoantibody levels and by measuring CD20-positive cell percentages. Unlike severity of disease at baseline, which Dr. Wei said is not a reliable predictor of relapse risk, these can guide steroid tapering.

“If the patient is not making new autoantibodies, then tapering steroids can be considered safe,” Dr. Wei said.

One small case series cited by Dr. Wei has suggested that rituximab might be effectively employed as a maintenance therapy for pemphigus. The maintenance treatment, which initially consisted of 1 g of rituximab every 6 months, was evaluated in 11 patients with a history of severe and frequent relapses.

In this group, rituximab was first employed to achieve a complete response. The maintenance was initiated when patients were in remission. In some patients, the maintenance dose interval was extended to once every 12 months over time. During a mean follow-up of 4 years, all 11 patients remained in complete remission.

“This was a remarkable result,” said Dr. Wei, who noted that there were no serious adverse events associated with rituximab maintenance over this period. This cannot be considered a routine strategy without a large patient experience, according to Dr. Wei, but it does provide another piece of evidence that rituximab is effective and well tolerated.

There are no guidelines from a major organization that establish an evidence-based treatment algorithm for pemphigus, but Dr. Wei is not alone in considering early initiation of the most effective therapy as the best approach to sustained control.

“I agree that rituximab is a good first-line option for pemphigus patients,” said Kara Heelan, MBBCh, MD, a consultant dermatologist at the Royal Marsden and Lister Hospital, London. She was the first author of the cost-effectiveness study that Dr. Wei cited. The study was published when she was an associate in the division of dermatology at the University of Toronto.

By calling rituximab “a good” option rather than a potential standard, Dr. Heelan appeared to be more circumspect than Dr. Wei about its central role in the care of pemphigus, but she did agree in an interview that this agent “has been shown to be cost-effective.” In her study, this was an advantage attributed to relative efficacy and safety that reduced use of health care resources.
 

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

BOSTON – For patients presenting with moderate to severe pemphigus, the choice of initial therapy has been distilled to a single agent: rituximab. This drug is more rapidly effective, more likely to provide sustained remission, better tolerated, and lowers health care costs, according to an expert summary at the annual meeting of the American Academy of Dermatology.

With rituximab “we are not only able to offer better efficacy, earlier and longer remissions, less side effects, less risk of relapse after a response, but it is actually cheaper,” reported Erin X. Wei, MD, director of the Bullous Diseases Clinic at Brigham and Women’s Hospital, Boston.

There are many treatments that reduce the inflammatory component of pemphigus. Corticosteroids, doxycycline, mycophenolate mofetil, azathioprine, and methotrexate are among those options commonly considered in the early control of this rare and potentially fatal autoimmune blistering disease of the skin, mouth, and other tissues.

Not all of these options have been compared directly in controlled trials, but Dr. Wei indicated that the preponderance of evidence is now on the side of rituximab as a first-line choice. For example, in the multicenter Ritux 3 trial, which compared a tapered regimen of prednisone alone to rituximab combined with a shorter and lower-dose prednisone taper in patients with pemphigus, complete response rates off therapy at 2 years were 89% in the rituximab group versus 34% in the group that received prednisone alone.

“This was quite a remarkable difference,” said Dr. Wei, who noted that remissions overall occurred faster in the rituximab group and were more durable once achieved.

No other treatment option has demonstrated this degree of relative benefit over corticosteroids, according to Dr. Wei. She said there is evidence that mycophenolate mofetil acts more rapidly, but it has not been shown to be superior for sustained complete response. Nor has azathioprine provided a clear advantage over steroids. There are no well-conducted comparisons of methotrexate and prednisone, according to Dr. Wei, assistant professor at Harvard Medical School, Boston.

Corticosteroids, doxycycline, and immunomodulators have been characterized as mainstays of early treatment in pemphigus, but Dr. Wei argued that the evidence supports starting with the most effective therapy first. There are many advantages to suppressing disease activity “as soon as possible” after diagnosis.

Early control “is associated with a more sustained remission, lower overall steroid use, and better quality of life,” said Dr. Wei, listing the hazards of starting with less effective therapy, and explaining why she has moved to rituximab as a first-line choice. According to her, there are data to support these advantages.

“Several studies have observed that rituximab, within the first 6 months of disease onset, is associated with a higher rate of complete response and a longer duration of complete response,” Dr. Wei said.

Intravenous immunoglobulin (IVIG) therapy is effective in many patients but less reliable, and it has other disadvantages relative to rituximab as a first-line therapy.

“IVIG in pemphigus works quickly when it works, but it is more expensive and it is more of an ongoing therapy relative to rituximab,” said Dr. Wei, referring to the lower likelihood of IVIG to provide sustained remissions.

The price of rituximab is high relative to prednisone or other immunomodulators, but management costs are ultimately reduced because of better disease control, according to Dr. Wei. She cited a Canadian study published several years ago in which health care costs in the 6 months prior to rituximab were compared to costs over 6 months after it was initiated.

In this cohort of 89 patients with pemphigus or pemphigoid, the average cost per patient for 6 months of care prior to starting rituximab was $42,231 in Canadian dollars. After treatment was started, the cost fell to $29,423, a 30% reduction, over the next 6 months.

“It takes rituximab up to 3 months or sometimes even longer to achieve its greatest benefit, making these results even more impressive,” Dr. Wei said.

The activity of rituximab to suppress autoreactive B-cells can be monitored with antidesmoglein autoantibody levels and by measuring CD20-positive cell percentages. Unlike severity of disease at baseline, which Dr. Wei said is not a reliable predictor of relapse risk, these can guide steroid tapering.

“If the patient is not making new autoantibodies, then tapering steroids can be considered safe,” Dr. Wei said.

One small case series cited by Dr. Wei has suggested that rituximab might be effectively employed as a maintenance therapy for pemphigus. The maintenance treatment, which initially consisted of 1 g of rituximab every 6 months, was evaluated in 11 patients with a history of severe and frequent relapses.

In this group, rituximab was first employed to achieve a complete response. The maintenance was initiated when patients were in remission. In some patients, the maintenance dose interval was extended to once every 12 months over time. During a mean follow-up of 4 years, all 11 patients remained in complete remission.

“This was a remarkable result,” said Dr. Wei, who noted that there were no serious adverse events associated with rituximab maintenance over this period. This cannot be considered a routine strategy without a large patient experience, according to Dr. Wei, but it does provide another piece of evidence that rituximab is effective and well tolerated.

There are no guidelines from a major organization that establish an evidence-based treatment algorithm for pemphigus, but Dr. Wei is not alone in considering early initiation of the most effective therapy as the best approach to sustained control.

“I agree that rituximab is a good first-line option for pemphigus patients,” said Kara Heelan, MBBCh, MD, a consultant dermatologist at the Royal Marsden and Lister Hospital, London. She was the first author of the cost-effectiveness study that Dr. Wei cited. The study was published when she was an associate in the division of dermatology at the University of Toronto.

By calling rituximab “a good” option rather than a potential standard, Dr. Heelan appeared to be more circumspect than Dr. Wei about its central role in the care of pemphigus, but she did agree in an interview that this agent “has been shown to be cost-effective.” In her study, this was an advantage attributed to relative efficacy and safety that reduced use of health care resources.
 

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

BOSTON – For patients presenting with moderate to severe pemphigus, the choice of initial therapy has been distilled to a single agent: rituximab. This drug is more rapidly effective, more likely to provide sustained remission, better tolerated, and lowers health care costs, according to an expert summary at the annual meeting of the American Academy of Dermatology.

With rituximab “we are not only able to offer better efficacy, earlier and longer remissions, less side effects, less risk of relapse after a response, but it is actually cheaper,” reported Erin X. Wei, MD, director of the Bullous Diseases Clinic at Brigham and Women’s Hospital, Boston.

There are many treatments that reduce the inflammatory component of pemphigus. Corticosteroids, doxycycline, mycophenolate mofetil, azathioprine, and methotrexate are among those options commonly considered in the early control of this rare and potentially fatal autoimmune blistering disease of the skin, mouth, and other tissues.

Not all of these options have been compared directly in controlled trials, but Dr. Wei indicated that the preponderance of evidence is now on the side of rituximab as a first-line choice. For example, in the multicenter Ritux 3 trial, which compared a tapered regimen of prednisone alone to rituximab combined with a shorter and lower-dose prednisone taper in patients with pemphigus, complete response rates off therapy at 2 years were 89% in the rituximab group versus 34% in the group that received prednisone alone.

“This was quite a remarkable difference,” said Dr. Wei, who noted that remissions overall occurred faster in the rituximab group and were more durable once achieved.

No other treatment option has demonstrated this degree of relative benefit over corticosteroids, according to Dr. Wei. She said there is evidence that mycophenolate mofetil acts more rapidly, but it has not been shown to be superior for sustained complete response. Nor has azathioprine provided a clear advantage over steroids. There are no well-conducted comparisons of methotrexate and prednisone, according to Dr. Wei, assistant professor at Harvard Medical School, Boston.

Corticosteroids, doxycycline, and immunomodulators have been characterized as mainstays of early treatment in pemphigus, but Dr. Wei argued that the evidence supports starting with the most effective therapy first. There are many advantages to suppressing disease activity “as soon as possible” after diagnosis.

Early control “is associated with a more sustained remission, lower overall steroid use, and better quality of life,” said Dr. Wei, listing the hazards of starting with less effective therapy, and explaining why she has moved to rituximab as a first-line choice. According to her, there are data to support these advantages.

“Several studies have observed that rituximab, within the first 6 months of disease onset, is associated with a higher rate of complete response and a longer duration of complete response,” Dr. Wei said.

Intravenous immunoglobulin (IVIG) therapy is effective in many patients but less reliable, and it has other disadvantages relative to rituximab as a first-line therapy.

“IVIG in pemphigus works quickly when it works, but it is more expensive and it is more of an ongoing therapy relative to rituximab,” said Dr. Wei, referring to the lower likelihood of IVIG to provide sustained remissions.

The price of rituximab is high relative to prednisone or other immunomodulators, but management costs are ultimately reduced because of better disease control, according to Dr. Wei. She cited a Canadian study published several years ago in which health care costs in the 6 months prior to rituximab were compared to costs over 6 months after it was initiated.

In this cohort of 89 patients with pemphigus or pemphigoid, the average cost per patient for 6 months of care prior to starting rituximab was $42,231 in Canadian dollars. After treatment was started, the cost fell to $29,423, a 30% reduction, over the next 6 months.

“It takes rituximab up to 3 months or sometimes even longer to achieve its greatest benefit, making these results even more impressive,” Dr. Wei said.

The activity of rituximab to suppress autoreactive B-cells can be monitored with antidesmoglein autoantibody levels and by measuring CD20-positive cell percentages. Unlike severity of disease at baseline, which Dr. Wei said is not a reliable predictor of relapse risk, these can guide steroid tapering.

“If the patient is not making new autoantibodies, then tapering steroids can be considered safe,” Dr. Wei said.

One small case series cited by Dr. Wei has suggested that rituximab might be effectively employed as a maintenance therapy for pemphigus. The maintenance treatment, which initially consisted of 1 g of rituximab every 6 months, was evaluated in 11 patients with a history of severe and frequent relapses.

In this group, rituximab was first employed to achieve a complete response. The maintenance was initiated when patients were in remission. In some patients, the maintenance dose interval was extended to once every 12 months over time. During a mean follow-up of 4 years, all 11 patients remained in complete remission.

“This was a remarkable result,” said Dr. Wei, who noted that there were no serious adverse events associated with rituximab maintenance over this period. This cannot be considered a routine strategy without a large patient experience, according to Dr. Wei, but it does provide another piece of evidence that rituximab is effective and well tolerated.

There are no guidelines from a major organization that establish an evidence-based treatment algorithm for pemphigus, but Dr. Wei is not alone in considering early initiation of the most effective therapy as the best approach to sustained control.

“I agree that rituximab is a good first-line option for pemphigus patients,” said Kara Heelan, MBBCh, MD, a consultant dermatologist at the Royal Marsden and Lister Hospital, London. She was the first author of the cost-effectiveness study that Dr. Wei cited. The study was published when she was an associate in the division of dermatology at the University of Toronto.

By calling rituximab “a good” option rather than a potential standard, Dr. Heelan appeared to be more circumspect than Dr. Wei about its central role in the care of pemphigus, but she did agree in an interview that this agent “has been shown to be cost-effective.” In her study, this was an advantage attributed to relative efficacy and safety that reduced use of health care resources.
 

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

Treatment with the human monoclonal antibody guselkumab over 12 weeks was shown to be safe and more effective than placebo in patients with moderate to severe Crohn’s disease, according to phase 2 trial data

Conventional first-line therapies for Crohn’s disease (CD) often are not effective for maintaining clinical remission and are associated with significant toxicity concerns, wrote study investigator William J. Sandborn, MD, of the University of California, San Diego, and colleagues. Guselkumab is a human monoclonal antibody that selectively inhibits the p19 subunit of interleukin 23, a cytokine that plays an important role in gut inflammation, the researchers wrote. Their report was published online Feb. 5 in Gastroenterology.

In the phase 2 GALAXI-1 study, Dr. Sandborn and colleagues evaluated the safety and efficacy of guselkumab in 309 patients with moderate to severe CD for at least 3 months. All patients previously had experienced either an inadequate response or intolerance to convention treatment or biologic agents.

Patients were randomly assigned to either placebo (n = 61); intravenous guselkumab at doses of 200 mg (n = 61), 600 mg (n = 63), or 1,200 mg at weeks 0, 4, and 8 (n = 61); or a reference arm comprising ustekinumab approximately 6 mg/kg IV at week 0 and subcutaneous 90 mg at week 8 (n = 63).

The study’s primary endpoint included the change from baseline to 12 weeks in the CD Activity Index score. The mean age of the population was 38.8 years and the mean duration of CD was 8.8 years.

There were patients in the primary efficacy analysis set who discontinued the study through week 12. At one point the study was paused to assess a serious adverse event of toxic hepatitis in a guselkumab-treated patient. Fifty-one patients were discontinued from the study because their induction treatment was paused during the adverse event evaluation; however, these patients were included in the safety analyses.

At the 12-week follow-up assessment, patients assigned to all doses of guselkumab experienced significantly greater reductions in the CD Activity Index from baseline when compared with placebo (least squares mean: 200 mg: –160.4; 600 mg: –138.9; and 1,200 mg: –144.9 vs. placebo: –36.2; all P < .05). In addition, a significantly greater proportion of patients in each guselkumab arm achieved clinical remission compared with the placebo group (CD Activity Index < 150; 57.4%, 55.6%, and 45.9% vs. 16.4%; all P < .05).

Among the patients who had an inadequate response or intolerance to prior biologic therapy, 47.5% of those in the combined guselkumab arm and 10.0% in the placebo arm met the criteria for clinical remission at 12 weeks. In addition, 62.4% of patients in the combined guselkumab group and 20% in the placebo group within the prior biologic therapy subgroup achieved clinical response at week 12.

Of patients with inadequate response or intolerance to prior conventional therapy, approximately 60% treated with guselkumab at all doses vs. 22.6% of the placebo group had clinical remission by 12 weeks. Also within this subgroup, 70.2% of patients in the combined guselkumab arm and 29% in the placebo arm had clinical response.

Finally, among the 360 patients in the safety analysis set, the proportions of patients with at least one adverse event were similar across the treatment groups during the treatment period (60% for placebo; 45.7% for guselkumab combined; 50.7% for ustekinumab).

There was no observable relationship between the dose of guselkumab and the proportion of patients with adverse events. Infection rates were 21.4% in the placebo arm, 15.1% in the combined guselkumab group, and 12.7% in the ustekinumab arm. Approximately 3.7% of patients in the combined guselkumab arm, 5.7% of patients in the placebo arm, and 5.6% of patients in the ustekinumab arm experienced at least one serious adverse event.

Greater proportions of patients receiving guselkumab achieved clinical response, Patient Reported Outcomes–2 remission, clinical-biomarker response, and endoscopic response at week 12 vs. placebo. Efficacy of ustekinumab vs. placebo was demonstrated. Safety event rates were generally similar across treatment groups.

Limitations of the study included the small number of patients in the overall dataset and the relatively short treatment period of 12 weeks. The researchers noted that phase 3 studies of guselkumab for the treatment of Crohn’s disease are underway.

Several of the researchers reported conflicts of interest with the pharmaceutical industry. The study received funding from Janssen Research & Development, LLC.

Treatment with the human monoclonal antibody guselkumab over 12 weeks was shown to be safe and more effective than placebo in patients with moderate to severe Crohn’s disease, according to phase 2 trial data

Conventional first-line therapies for Crohn’s disease (CD) often are not effective for maintaining clinical remission and are associated with significant toxicity concerns, wrote study investigator William J. Sandborn, MD, of the University of California, San Diego, and colleagues. Guselkumab is a human monoclonal antibody that selectively inhibits the p19 subunit of interleukin 23, a cytokine that plays an important role in gut inflammation, the researchers wrote. Their report was published online Feb. 5 in Gastroenterology.

In the phase 2 GALAXI-1 study, Dr. Sandborn and colleagues evaluated the safety and efficacy of guselkumab in 309 patients with moderate to severe CD for at least 3 months. All patients previously had experienced either an inadequate response or intolerance to convention treatment or biologic agents.

Patients were randomly assigned to either placebo (n = 61); intravenous guselkumab at doses of 200 mg (n = 61), 600 mg (n = 63), or 1,200 mg at weeks 0, 4, and 8 (n = 61); or a reference arm comprising ustekinumab approximately 6 mg/kg IV at week 0 and subcutaneous 90 mg at week 8 (n = 63).

The study’s primary endpoint included the change from baseline to 12 weeks in the CD Activity Index score. The mean age of the population was 38.8 years and the mean duration of CD was 8.8 years.

There were patients in the primary efficacy analysis set who discontinued the study through week 12. At one point the study was paused to assess a serious adverse event of toxic hepatitis in a guselkumab-treated patient. Fifty-one patients were discontinued from the study because their induction treatment was paused during the adverse event evaluation; however, these patients were included in the safety analyses.

At the 12-week follow-up assessment, patients assigned to all doses of guselkumab experienced significantly greater reductions in the CD Activity Index from baseline when compared with placebo (least squares mean: 200 mg: –160.4; 600 mg: –138.9; and 1,200 mg: –144.9 vs. placebo: –36.2; all P < .05). In addition, a significantly greater proportion of patients in each guselkumab arm achieved clinical remission compared with the placebo group (CD Activity Index < 150; 57.4%, 55.6%, and 45.9% vs. 16.4%; all P < .05).

Among the patients who had an inadequate response or intolerance to prior biologic therapy, 47.5% of those in the combined guselkumab arm and 10.0% in the placebo arm met the criteria for clinical remission at 12 weeks. In addition, 62.4% of patients in the combined guselkumab group and 20% in the placebo group within the prior biologic therapy subgroup achieved clinical response at week 12.

Of patients with inadequate response or intolerance to prior conventional therapy, approximately 60% treated with guselkumab at all doses vs. 22.6% of the placebo group had clinical remission by 12 weeks. Also within this subgroup, 70.2% of patients in the combined guselkumab arm and 29% in the placebo arm had clinical response.

Finally, among the 360 patients in the safety analysis set, the proportions of patients with at least one adverse event were similar across the treatment groups during the treatment period (60% for placebo; 45.7% for guselkumab combined; 50.7% for ustekinumab).

There was no observable relationship between the dose of guselkumab and the proportion of patients with adverse events. Infection rates were 21.4% in the placebo arm, 15.1% in the combined guselkumab group, and 12.7% in the ustekinumab arm. Approximately 3.7% of patients in the combined guselkumab arm, 5.7% of patients in the placebo arm, and 5.6% of patients in the ustekinumab arm experienced at least one serious adverse event.

Greater proportions of patients receiving guselkumab achieved clinical response, Patient Reported Outcomes–2 remission, clinical-biomarker response, and endoscopic response at week 12 vs. placebo. Efficacy of ustekinumab vs. placebo was demonstrated. Safety event rates were generally similar across treatment groups.

Limitations of the study included the small number of patients in the overall dataset and the relatively short treatment period of 12 weeks. The researchers noted that phase 3 studies of guselkumab for the treatment of Crohn’s disease are underway.

Several of the researchers reported conflicts of interest with the pharmaceutical industry. The study received funding from Janssen Research & Development, LLC.

Treatment with the human monoclonal antibody guselkumab over 12 weeks was shown to be safe and more effective than placebo in patients with moderate to severe Crohn’s disease, according to phase 2 trial data

Conventional first-line therapies for Crohn’s disease (CD) often are not effective for maintaining clinical remission and are associated with significant toxicity concerns, wrote study investigator William J. Sandborn, MD, of the University of California, San Diego, and colleagues. Guselkumab is a human monoclonal antibody that selectively inhibits the p19 subunit of interleukin 23, a cytokine that plays an important role in gut inflammation, the researchers wrote. Their report was published online Feb. 5 in Gastroenterology.

In the phase 2 GALAXI-1 study, Dr. Sandborn and colleagues evaluated the safety and efficacy of guselkumab in 309 patients with moderate to severe CD for at least 3 months. All patients previously had experienced either an inadequate response or intolerance to convention treatment or biologic agents.

Patients were randomly assigned to either placebo (n = 61); intravenous guselkumab at doses of 200 mg (n = 61), 600 mg (n = 63), or 1,200 mg at weeks 0, 4, and 8 (n = 61); or a reference arm comprising ustekinumab approximately 6 mg/kg IV at week 0 and subcutaneous 90 mg at week 8 (n = 63).

The study’s primary endpoint included the change from baseline to 12 weeks in the CD Activity Index score. The mean age of the population was 38.8 years and the mean duration of CD was 8.8 years.

There were patients in the primary efficacy analysis set who discontinued the study through week 12. At one point the study was paused to assess a serious adverse event of toxic hepatitis in a guselkumab-treated patient. Fifty-one patients were discontinued from the study because their induction treatment was paused during the adverse event evaluation; however, these patients were included in the safety analyses.

At the 12-week follow-up assessment, patients assigned to all doses of guselkumab experienced significantly greater reductions in the CD Activity Index from baseline when compared with placebo (least squares mean: 200 mg: –160.4; 600 mg: –138.9; and 1,200 mg: –144.9 vs. placebo: –36.2; all P < .05). In addition, a significantly greater proportion of patients in each guselkumab arm achieved clinical remission compared with the placebo group (CD Activity Index < 150; 57.4%, 55.6%, and 45.9% vs. 16.4%; all P < .05).

Among the patients who had an inadequate response or intolerance to prior biologic therapy, 47.5% of those in the combined guselkumab arm and 10.0% in the placebo arm met the criteria for clinical remission at 12 weeks. In addition, 62.4% of patients in the combined guselkumab group and 20% in the placebo group within the prior biologic therapy subgroup achieved clinical response at week 12.

Of patients with inadequate response or intolerance to prior conventional therapy, approximately 60% treated with guselkumab at all doses vs. 22.6% of the placebo group had clinical remission by 12 weeks. Also within this subgroup, 70.2% of patients in the combined guselkumab arm and 29% in the placebo arm had clinical response.

Finally, among the 360 patients in the safety analysis set, the proportions of patients with at least one adverse event were similar across the treatment groups during the treatment period (60% for placebo; 45.7% for guselkumab combined; 50.7% for ustekinumab).

There was no observable relationship between the dose of guselkumab and the proportion of patients with adverse events. Infection rates were 21.4% in the placebo arm, 15.1% in the combined guselkumab group, and 12.7% in the ustekinumab arm. Approximately 3.7% of patients in the combined guselkumab arm, 5.7% of patients in the placebo arm, and 5.6% of patients in the ustekinumab arm experienced at least one serious adverse event.

Greater proportions of patients receiving guselkumab achieved clinical response, Patient Reported Outcomes–2 remission, clinical-biomarker response, and endoscopic response at week 12 vs. placebo. Efficacy of ustekinumab vs. placebo was demonstrated. Safety event rates were generally similar across treatment groups.

Limitations of the study included the small number of patients in the overall dataset and the relatively short treatment period of 12 weeks. The researchers noted that phase 3 studies of guselkumab for the treatment of Crohn’s disease are underway.

Several of the researchers reported conflicts of interest with the pharmaceutical industry. The study received funding from Janssen Research & Development, LLC.