Conference Coverage

With chronic pain common among people with multiple sclerosis (MS), approximately 20% of patients report opioid use - despite warnings that the drugs are generally not recommended for the management of chronic pain and ongoing concerns of addiction, new research shows.

“This high level of opioid use supports that better pain management treatment options, including nonpharmacological options, are needed for people with MS and pain,” wrote the authors of the study, which was presented at ACTRIMS Forum 2021, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Previous research has shown that more than 50% of people with MS report chronic pain that is serious enough to interfere with daily activities, employment, and quality of life. Many with MS report that pain is one of their worst symptoms, the authors noted.

With surprisingly few studies evaluating opioid use in the MS population, Cinda L. Hugos, PT, associate professor of neurology with the VA Portland Health Care System and the department of neurology, Oregon Health and Science University, Portland, and colleagues investigated the issue in a sample of patients participating in a U.S. multisite MS fatigue management trial conducted between 2013 and 2014.

Of the 281 participants with MS in the study, 58 patients (20.6%) reported using prescription opioids. Among them, most – 44 (76%) – reported regular daily use, 10 (17%) reported using the drugs only as needed, 3 (5%) reported only short-term use, including after recent injury or dental surgery, and 1 provided incomplete information.

Those who reported opioid use had significantly worse fatigue scores on the Modified Fatigue Impact Scale (P = .015) and worse pain scores (P < .0001).

There were no significant differences in terms of age (mean age, 53 years), gender (69% were female), or race (in both groups, about 76% were White). No significant differences were seen in disability or depression scores in the opioid users versus nonusers.

“In this sample of people with multiple sclerosis who self-reported fatigue and volunteered to join an MS fatigue management research study, more than one in five reported using prescription opioids and nearly one in six used opioids daily,” the authors wrote. “Opioid users had more pain and fatigue than nonusers.”

Commenting on the study, Jeffrey Cohen, MD, president of ACTRIMS, said that the findings are consistent with his observations that “in the general population, opioids often are used to treat chronic pain in people with MS.”

But they’re not getting the drugs from his clinic. “We do not prescribe opioids in our clinic, referring such patients to a chronic pain program,” Dr. Cohen said. “However, there clearly is need for better treatment options.”

A previous study on opioid use by people with MS, published in 2015, found even higher rates – 42% reported having ever used opioids, and 38% reported currently using opioids.

Although reports of opioid use by patients with MS have been lacking, more has been published on the emerging use of cannabis-related products. One recent study showed that nearly half of people with MS reported using a cannabis-based therapy for nerve-based pain and sleep disturbances.

Although cannabis is considered safer than opioids, the authors noted that it has its own significant drawback – a “paucity of provider guidance.”

“The range of perceived benefits and potential differential effects of THC and cannabinoid highlight the need for personalized, evidence-based guidelines regarding cannabinoid use,” they wrote.
 

Stretching program for spasticity shows benefits

With spasticity representing a key contributor to MS pain and affecting more than 80% of people with MS, Ms. Hugos and colleagues are developing an alternative to medication – a nonpharmacologic stretching regimen called Spasticity: Take Control” (STC).

Based on evidence-based strategies for the treatment of spasticity in MS, the program involves exercises with daily routines of 15-20 minutes over 6 months.

In a pilot study of 66 patients, also presented at the ACTRIMS meeting, the investigators reported that the program showed significant reductions in pain severity and interference, measured with the Brief Pain Inventory–Short Form, compared with a control consisting of range of motion instruction over 6 months.

The study also offered insights on the specific areas of pain. Among those who reported chronic pain (42% in the STC group and 63.3% in the range-of-motion group), the pain was most frequently reported in the lower back (74.3%), legs (68.6%), or lower back and legs (88.6%).

Ms. Hugos noted that the findings suggest a potentially important nonpharmacologic alternative to spasticity-related pain in MS.

“Stretching is the cornerstone treatment for spasticity from all causes, but there is very little information on stretching exercises in MS or any other conditions,” Ms. Hugos said. “[Our] pilot study is the first and only study using a standardized, daily stretching exercise program to treat MS spasticity,” she said.

“A fully powered study is needed to better understand the impact of different types of exercise on pain severity and interference in multiple sclerosis,” she noted.

Ms. Hugos has received consulting fees from Greenwich Biosciences, Evidera, and Techspert.io. Dr. Cohen has received personal compensation for consulting for Adamas, Atara, Bristol-Myers Squibb, Convelo, MedDay, and Mylan.

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

With chronic pain common among people with multiple sclerosis (MS), approximately 20% of patients report opioid use - despite warnings that the drugs are generally not recommended for the management of chronic pain and ongoing concerns of addiction, new research shows.

“This high level of opioid use supports that better pain management treatment options, including nonpharmacological options, are needed for people with MS and pain,” wrote the authors of the study, which was presented at ACTRIMS Forum 2021, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Previous research has shown that more than 50% of people with MS report chronic pain that is serious enough to interfere with daily activities, employment, and quality of life. Many with MS report that pain is one of their worst symptoms, the authors noted.

With surprisingly few studies evaluating opioid use in the MS population, Cinda L. Hugos, PT, associate professor of neurology with the VA Portland Health Care System and the department of neurology, Oregon Health and Science University, Portland, and colleagues investigated the issue in a sample of patients participating in a U.S. multisite MS fatigue management trial conducted between 2013 and 2014.

Of the 281 participants with MS in the study, 58 patients (20.6%) reported using prescription opioids. Among them, most – 44 (76%) – reported regular daily use, 10 (17%) reported using the drugs only as needed, 3 (5%) reported only short-term use, including after recent injury or dental surgery, and 1 provided incomplete information.

Those who reported opioid use had significantly worse fatigue scores on the Modified Fatigue Impact Scale (P = .015) and worse pain scores (P < .0001).

There were no significant differences in terms of age (mean age, 53 years), gender (69% were female), or race (in both groups, about 76% were White). No significant differences were seen in disability or depression scores in the opioid users versus nonusers.

“In this sample of people with multiple sclerosis who self-reported fatigue and volunteered to join an MS fatigue management research study, more than one in five reported using prescription opioids and nearly one in six used opioids daily,” the authors wrote. “Opioid users had more pain and fatigue than nonusers.”

Commenting on the study, Jeffrey Cohen, MD, president of ACTRIMS, said that the findings are consistent with his observations that “in the general population, opioids often are used to treat chronic pain in people with MS.”

But they’re not getting the drugs from his clinic. “We do not prescribe opioids in our clinic, referring such patients to a chronic pain program,” Dr. Cohen said. “However, there clearly is need for better treatment options.”

A previous study on opioid use by people with MS, published in 2015, found even higher rates – 42% reported having ever used opioids, and 38% reported currently using opioids.

Although reports of opioid use by patients with MS have been lacking, more has been published on the emerging use of cannabis-related products. One recent study showed that nearly half of people with MS reported using a cannabis-based therapy for nerve-based pain and sleep disturbances.

Although cannabis is considered safer than opioids, the authors noted that it has its own significant drawback – a “paucity of provider guidance.”

“The range of perceived benefits and potential differential effects of THC and cannabinoid highlight the need for personalized, evidence-based guidelines regarding cannabinoid use,” they wrote.
 

Stretching program for spasticity shows benefits

With spasticity representing a key contributor to MS pain and affecting more than 80% of people with MS, Ms. Hugos and colleagues are developing an alternative to medication – a nonpharmacologic stretching regimen called Spasticity: Take Control” (STC).

Based on evidence-based strategies for the treatment of spasticity in MS, the program involves exercises with daily routines of 15-20 minutes over 6 months.

In a pilot study of 66 patients, also presented at the ACTRIMS meeting, the investigators reported that the program showed significant reductions in pain severity and interference, measured with the Brief Pain Inventory–Short Form, compared with a control consisting of range of motion instruction over 6 months.

The study also offered insights on the specific areas of pain. Among those who reported chronic pain (42% in the STC group and 63.3% in the range-of-motion group), the pain was most frequently reported in the lower back (74.3%), legs (68.6%), or lower back and legs (88.6%).

Ms. Hugos noted that the findings suggest a potentially important nonpharmacologic alternative to spasticity-related pain in MS.

“Stretching is the cornerstone treatment for spasticity from all causes, but there is very little information on stretching exercises in MS or any other conditions,” Ms. Hugos said. “[Our] pilot study is the first and only study using a standardized, daily stretching exercise program to treat MS spasticity,” she said.

“A fully powered study is needed to better understand the impact of different types of exercise on pain severity and interference in multiple sclerosis,” she noted.

Ms. Hugos has received consulting fees from Greenwich Biosciences, Evidera, and Techspert.io. Dr. Cohen has received personal compensation for consulting for Adamas, Atara, Bristol-Myers Squibb, Convelo, MedDay, and Mylan.

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

With chronic pain common among people with multiple sclerosis (MS), approximately 20% of patients report opioid use - despite warnings that the drugs are generally not recommended for the management of chronic pain and ongoing concerns of addiction, new research shows.

“This high level of opioid use supports that better pain management treatment options, including nonpharmacological options, are needed for people with MS and pain,” wrote the authors of the study, which was presented at ACTRIMS Forum 2021, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Previous research has shown that more than 50% of people with MS report chronic pain that is serious enough to interfere with daily activities, employment, and quality of life. Many with MS report that pain is one of their worst symptoms, the authors noted.

With surprisingly few studies evaluating opioid use in the MS population, Cinda L. Hugos, PT, associate professor of neurology with the VA Portland Health Care System and the department of neurology, Oregon Health and Science University, Portland, and colleagues investigated the issue in a sample of patients participating in a U.S. multisite MS fatigue management trial conducted between 2013 and 2014.

Of the 281 participants with MS in the study, 58 patients (20.6%) reported using prescription opioids. Among them, most – 44 (76%) – reported regular daily use, 10 (17%) reported using the drugs only as needed, 3 (5%) reported only short-term use, including after recent injury or dental surgery, and 1 provided incomplete information.

Those who reported opioid use had significantly worse fatigue scores on the Modified Fatigue Impact Scale (P = .015) and worse pain scores (P < .0001).

There were no significant differences in terms of age (mean age, 53 years), gender (69% were female), or race (in both groups, about 76% were White). No significant differences were seen in disability or depression scores in the opioid users versus nonusers.

“In this sample of people with multiple sclerosis who self-reported fatigue and volunteered to join an MS fatigue management research study, more than one in five reported using prescription opioids and nearly one in six used opioids daily,” the authors wrote. “Opioid users had more pain and fatigue than nonusers.”

Commenting on the study, Jeffrey Cohen, MD, president of ACTRIMS, said that the findings are consistent with his observations that “in the general population, opioids often are used to treat chronic pain in people with MS.”

But they’re not getting the drugs from his clinic. “We do not prescribe opioids in our clinic, referring such patients to a chronic pain program,” Dr. Cohen said. “However, there clearly is need for better treatment options.”

A previous study on opioid use by people with MS, published in 2015, found even higher rates – 42% reported having ever used opioids, and 38% reported currently using opioids.

Although reports of opioid use by patients with MS have been lacking, more has been published on the emerging use of cannabis-related products. One recent study showed that nearly half of people with MS reported using a cannabis-based therapy for nerve-based pain and sleep disturbances.

Although cannabis is considered safer than opioids, the authors noted that it has its own significant drawback – a “paucity of provider guidance.”

“The range of perceived benefits and potential differential effects of THC and cannabinoid highlight the need for personalized, evidence-based guidelines regarding cannabinoid use,” they wrote.
 

Stretching program for spasticity shows benefits

With spasticity representing a key contributor to MS pain and affecting more than 80% of people with MS, Ms. Hugos and colleagues are developing an alternative to medication – a nonpharmacologic stretching regimen called Spasticity: Take Control” (STC).

Based on evidence-based strategies for the treatment of spasticity in MS, the program involves exercises with daily routines of 15-20 minutes over 6 months.

In a pilot study of 66 patients, also presented at the ACTRIMS meeting, the investigators reported that the program showed significant reductions in pain severity and interference, measured with the Brief Pain Inventory–Short Form, compared with a control consisting of range of motion instruction over 6 months.

The study also offered insights on the specific areas of pain. Among those who reported chronic pain (42% in the STC group and 63.3% in the range-of-motion group), the pain was most frequently reported in the lower back (74.3%), legs (68.6%), or lower back and legs (88.6%).

Ms. Hugos noted that the findings suggest a potentially important nonpharmacologic alternative to spasticity-related pain in MS.

“Stretching is the cornerstone treatment for spasticity from all causes, but there is very little information on stretching exercises in MS or any other conditions,” Ms. Hugos said. “[Our] pilot study is the first and only study using a standardized, daily stretching exercise program to treat MS spasticity,” she said.

“A fully powered study is needed to better understand the impact of different types of exercise on pain severity and interference in multiple sclerosis,” she noted.

Ms. Hugos has received consulting fees from Greenwich Biosciences, Evidera, and Techspert.io. Dr. Cohen has received personal compensation for consulting for Adamas, Atara, Bristol-Myers Squibb, Convelo, MedDay, and Mylan.

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

Among individuals with asthma and allergies who use cannabis, more than half said they aren’t willing to discuss their use of cannabis with their doctor and their doctor doesn’t ask, according to recent research at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

VladK213/Getty Images

In an online survey of respondents with asthma and allergies in the Allergy & Asthma Network, 88 of 489 (18.0%) reported cannabis use. Of these respondents, 37.5% said they wanted to discuss their cannabis use with their doctor, 51.1% said they would not want to, and 11.4% reported they were unsure. In addition, 40.9% of respondents said their doctor inquired about cannabis use, while 51.1% said their doctor did not bring up cannabis use at all, either through a verbal discussion or on an intake form.

To date, there has not been much research on use of cannabis among patients with allergies and asthma, Joanna S. Zeiger, MS, PhD, of the Canna Research Foundation in Boulder, Colo., said in her presentation. “This is a group with whom route of administration could have broad adverse effects. Smoking or vaping cannabis in this population could lead to increased symptoms of cough and wheeze, as well as increased use of asthma medications and exacerbations of their disease.”

Dr. Zeiger and colleagues recruited 489 respondents for the AAN Pain, Exercise, and Cannabis Experience Survey study through social media channels between May 2020 and September 2020. In the survey, the researchers asked questions about the nature of the respondent’s cannabis use (medical, recreational, or both), the types of cannabinoids used (tetrahydrocannabinol [THC], cannabidiol [CBD], or both), the route of administration (capsule, edible, oil/tincture, smoke, spray, topical, or vaporizer), and subjective effects. Most of the respondents reported using both THC and CBD, with smoking, edibles, and vaping being the most comment route of administration.

Of the 88 respondents who said they currently used cannabis, 60.2% were aged less than 50 years, 72.4% were women, and 71.6% were White. A majority of respondents had been using cannabis for 3 or more years (54.5%) , used it less than one time per day (60.2%), and used it for pain (68.2%). Current asthma was reported in 51 respondents (58.0%), and 39.2% had uncontrolled asthma. Half of those respondents with uncontrolled asthma reported smoking cannabis, and 25.0% reported coughing because of cannabis. Both THC and CBD were used by 47.7% of respondents; 33% reported THC use alone, while 19.3% used CBD alone.

Reported effects of cannabis use

The most common positive effects of using cannabis reported among respondents were that it helped with sleep (66 respondents), calmed them down (60 respondents), reduced pain (60 respondents), or decreased anxiety (59 respondents). Many respondents who reported positive effects were using both THC and CBD. For example, respondents who reported using cannabinoids for calming, 46.7% reported using both, compared with 36.7% who used THC only and 16.7% who used CBD only. Among respondents who reported that cannabis helped them sleep, 51.5% used both THC and CBD.

Regarding adverse effects, there were no significant differences based on use of THC or CBD, but 31.9% of respondents who said they smoked cannabis and 4.9% of respondents who used cannabis through a route of administration that wasn’t smoking reported they coughed with their cannabis use (P < .001). No respondents reported anaphyalaxis, although, among individuals who did not use cannabis, 2.5% reported a cannabis allergy.
 

‘Cannabis allergy is real’

Commenting on the research, Gordon L. Sussman MD, allergist, clinical immunologist, and clinical professor of medicine at the University of Toronto, said the survey is a thorough questionnaire that is likely representative of attitudes about cannabis in the United States and countries where cannabis is not broadly legalized.

Cannabis allergy, however, is not uncommon, and “is something that people should be aware of,” he said. “Cannabis IgE allergy is real, is probably fairly common, and is something that [clinicians] should be asking about routinely.”

One limitation of the research was not knowing the number of people who declined to answer the survey, as there may be a bias in the results toward people who want to answer the questions, compared with those who did not want to answer. “When you do a survey, only a certain number of people are going to answer, and [you also want input from] people that don’t answer,” Dr. Sussman said.

Dr. Sussman acknowledged it can be difficult to get patients to admit cannabis use, even in countries like Canada where it is legal. Surveys like the one administered by Dr. Zeiger and colleagues are “the first step” to getting updated assessments of cannabis attitudes and recommendations. “The next step is doing an international survey, so you get different countries’ viewpoints and perspectives,” he said.

This study was supported by the Allergy & Asthma Network and the Canna Research Foundation. Three authors are affiliated with the Canna Research Foundation. Dr. Sussman reported no financial conflicts of interest. Dr. Sussman participates in the International Cannabis Allergy KAP Collaboration, a group founded by one of the coauthors, William Silvers, MD, but Dr. Sussman was not involved with this study.

Among individuals with asthma and allergies who use cannabis, more than half said they aren’t willing to discuss their use of cannabis with their doctor and their doctor doesn’t ask, according to recent research at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

VladK213/Getty Images

In an online survey of respondents with asthma and allergies in the Allergy & Asthma Network, 88 of 489 (18.0%) reported cannabis use. Of these respondents, 37.5% said they wanted to discuss their cannabis use with their doctor, 51.1% said they would not want to, and 11.4% reported they were unsure. In addition, 40.9% of respondents said their doctor inquired about cannabis use, while 51.1% said their doctor did not bring up cannabis use at all, either through a verbal discussion or on an intake form.

To date, there has not been much research on use of cannabis among patients with allergies and asthma, Joanna S. Zeiger, MS, PhD, of the Canna Research Foundation in Boulder, Colo., said in her presentation. “This is a group with whom route of administration could have broad adverse effects. Smoking or vaping cannabis in this population could lead to increased symptoms of cough and wheeze, as well as increased use of asthma medications and exacerbations of their disease.”

Dr. Zeiger and colleagues recruited 489 respondents for the AAN Pain, Exercise, and Cannabis Experience Survey study through social media channels between May 2020 and September 2020. In the survey, the researchers asked questions about the nature of the respondent’s cannabis use (medical, recreational, or both), the types of cannabinoids used (tetrahydrocannabinol [THC], cannabidiol [CBD], or both), the route of administration (capsule, edible, oil/tincture, smoke, spray, topical, or vaporizer), and subjective effects. Most of the respondents reported using both THC and CBD, with smoking, edibles, and vaping being the most comment route of administration.

Of the 88 respondents who said they currently used cannabis, 60.2% were aged less than 50 years, 72.4% were women, and 71.6% were White. A majority of respondents had been using cannabis for 3 or more years (54.5%) , used it less than one time per day (60.2%), and used it for pain (68.2%). Current asthma was reported in 51 respondents (58.0%), and 39.2% had uncontrolled asthma. Half of those respondents with uncontrolled asthma reported smoking cannabis, and 25.0% reported coughing because of cannabis. Both THC and CBD were used by 47.7% of respondents; 33% reported THC use alone, while 19.3% used CBD alone.

Reported effects of cannabis use

The most common positive effects of using cannabis reported among respondents were that it helped with sleep (66 respondents), calmed them down (60 respondents), reduced pain (60 respondents), or decreased anxiety (59 respondents). Many respondents who reported positive effects were using both THC and CBD. For example, respondents who reported using cannabinoids for calming, 46.7% reported using both, compared with 36.7% who used THC only and 16.7% who used CBD only. Among respondents who reported that cannabis helped them sleep, 51.5% used both THC and CBD.

Regarding adverse effects, there were no significant differences based on use of THC or CBD, but 31.9% of respondents who said they smoked cannabis and 4.9% of respondents who used cannabis through a route of administration that wasn’t smoking reported they coughed with their cannabis use (P < .001). No respondents reported anaphyalaxis, although, among individuals who did not use cannabis, 2.5% reported a cannabis allergy.
 

‘Cannabis allergy is real’

Commenting on the research, Gordon L. Sussman MD, allergist, clinical immunologist, and clinical professor of medicine at the University of Toronto, said the survey is a thorough questionnaire that is likely representative of attitudes about cannabis in the United States and countries where cannabis is not broadly legalized.

Cannabis allergy, however, is not uncommon, and “is something that people should be aware of,” he said. “Cannabis IgE allergy is real, is probably fairly common, and is something that [clinicians] should be asking about routinely.”

One limitation of the research was not knowing the number of people who declined to answer the survey, as there may be a bias in the results toward people who want to answer the questions, compared with those who did not want to answer. “When you do a survey, only a certain number of people are going to answer, and [you also want input from] people that don’t answer,” Dr. Sussman said.

Dr. Sussman acknowledged it can be difficult to get patients to admit cannabis use, even in countries like Canada where it is legal. Surveys like the one administered by Dr. Zeiger and colleagues are “the first step” to getting updated assessments of cannabis attitudes and recommendations. “The next step is doing an international survey, so you get different countries’ viewpoints and perspectives,” he said.

This study was supported by the Allergy & Asthma Network and the Canna Research Foundation. Three authors are affiliated with the Canna Research Foundation. Dr. Sussman reported no financial conflicts of interest. Dr. Sussman participates in the International Cannabis Allergy KAP Collaboration, a group founded by one of the coauthors, William Silvers, MD, but Dr. Sussman was not involved with this study.

Among individuals with asthma and allergies who use cannabis, more than half said they aren’t willing to discuss their use of cannabis with their doctor and their doctor doesn’t ask, according to recent research at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

VladK213/Getty Images

In an online survey of respondents with asthma and allergies in the Allergy & Asthma Network, 88 of 489 (18.0%) reported cannabis use. Of these respondents, 37.5% said they wanted to discuss their cannabis use with their doctor, 51.1% said they would not want to, and 11.4% reported they were unsure. In addition, 40.9% of respondents said their doctor inquired about cannabis use, while 51.1% said their doctor did not bring up cannabis use at all, either through a verbal discussion or on an intake form.

To date, there has not been much research on use of cannabis among patients with allergies and asthma, Joanna S. Zeiger, MS, PhD, of the Canna Research Foundation in Boulder, Colo., said in her presentation. “This is a group with whom route of administration could have broad adverse effects. Smoking or vaping cannabis in this population could lead to increased symptoms of cough and wheeze, as well as increased use of asthma medications and exacerbations of their disease.”

Dr. Zeiger and colleagues recruited 489 respondents for the AAN Pain, Exercise, and Cannabis Experience Survey study through social media channels between May 2020 and September 2020. In the survey, the researchers asked questions about the nature of the respondent’s cannabis use (medical, recreational, or both), the types of cannabinoids used (tetrahydrocannabinol [THC], cannabidiol [CBD], or both), the route of administration (capsule, edible, oil/tincture, smoke, spray, topical, or vaporizer), and subjective effects. Most of the respondents reported using both THC and CBD, with smoking, edibles, and vaping being the most comment route of administration.

Of the 88 respondents who said they currently used cannabis, 60.2% were aged less than 50 years, 72.4% were women, and 71.6% were White. A majority of respondents had been using cannabis for 3 or more years (54.5%) , used it less than one time per day (60.2%), and used it for pain (68.2%). Current asthma was reported in 51 respondents (58.0%), and 39.2% had uncontrolled asthma. Half of those respondents with uncontrolled asthma reported smoking cannabis, and 25.0% reported coughing because of cannabis. Both THC and CBD were used by 47.7% of respondents; 33% reported THC use alone, while 19.3% used CBD alone.

Reported effects of cannabis use

The most common positive effects of using cannabis reported among respondents were that it helped with sleep (66 respondents), calmed them down (60 respondents), reduced pain (60 respondents), or decreased anxiety (59 respondents). Many respondents who reported positive effects were using both THC and CBD. For example, respondents who reported using cannabinoids for calming, 46.7% reported using both, compared with 36.7% who used THC only and 16.7% who used CBD only. Among respondents who reported that cannabis helped them sleep, 51.5% used both THC and CBD.

Regarding adverse effects, there were no significant differences based on use of THC or CBD, but 31.9% of respondents who said they smoked cannabis and 4.9% of respondents who used cannabis through a route of administration that wasn’t smoking reported they coughed with their cannabis use (P < .001). No respondents reported anaphyalaxis, although, among individuals who did not use cannabis, 2.5% reported a cannabis allergy.
 

‘Cannabis allergy is real’

Commenting on the research, Gordon L. Sussman MD, allergist, clinical immunologist, and clinical professor of medicine at the University of Toronto, said the survey is a thorough questionnaire that is likely representative of attitudes about cannabis in the United States and countries where cannabis is not broadly legalized.

Cannabis allergy, however, is not uncommon, and “is something that people should be aware of,” he said. “Cannabis IgE allergy is real, is probably fairly common, and is something that [clinicians] should be asking about routinely.”

One limitation of the research was not knowing the number of people who declined to answer the survey, as there may be a bias in the results toward people who want to answer the questions, compared with those who did not want to answer. “When you do a survey, only a certain number of people are going to answer, and [you also want input from] people that don’t answer,” Dr. Sussman said.

Dr. Sussman acknowledged it can be difficult to get patients to admit cannabis use, even in countries like Canada where it is legal. Surveys like the one administered by Dr. Zeiger and colleagues are “the first step” to getting updated assessments of cannabis attitudes and recommendations. “The next step is doing an international survey, so you get different countries’ viewpoints and perspectives,” he said.

This study was supported by the Allergy & Asthma Network and the Canna Research Foundation. Three authors are affiliated with the Canna Research Foundation. Dr. Sussman reported no financial conflicts of interest. Dr. Sussman participates in the International Cannabis Allergy KAP Collaboration, a group founded by one of the coauthors, William Silvers, MD, but Dr. Sussman was not involved with this study.

Sublingual immunotherapy for the treatment of peanut allergy is safe and effective, even in children as young as age 1 year.

In a double-blind, placebo-controlled, food challenge (DBPCFC) of some 36 peanut-allergic children (mean age 2.2 years, range 1-4 years), those who were randomly assigned to receive peanut sublingual immunotherapy (PNSLIT) showed significant desensitization compared with those who received placebo.

In addition, there was a “strong potential” for sustained unresponsiveness at 3 months for the toddlers who received the active treatment.

The findings were presented in a late breaking oral abstract session at the 2021 American Academy of Allergy, Asthma & Immunology virtual annual meeting (Abstract L2).

“A year ago, the Food and Drug Administration approved the oral agent Palforzia (peanut allergen powder) for the treatment of peanut allergy in children 4 and older, and it is a great option, but I think what we have learned over time is that this approach is not for everybody,” Edwin H. Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, said in an interview.

Palforzia is a powder that is mixed in food like yogurt or pudding which the child then eats daily, according to a rigorous schedule. But Palforzia treatment presents some difficulties.

“Palforzia requires getting the powder dose, mixing it with food, like pudding or apple sauce, then eating it, which can take up to 30 minutes depending on age and kids’ cooperation. It tastes and smells like peanut which can cause aversion. Kids have to refrain from exercise or strenuous activity for at least 30 minutes before and after dosing and have to be observed for up to 2 hours post dose for symptoms,” Dr. Kim said.

“It’s a great drug, but the treatment could be overly difficult for certain families to be able to do, and in some cases the side effects may be more than certain patients are able or willing to handle, so there is a real urgent need for alternative approaches,” Dr. Kim said. “SLIT is several drops under the tongue, held for 2 minutes, swallowed and done.”

In the current placebo-controlled study, he and his group tested the feasibility, efficacy, and safety of the sublingual approach to peanut allergy in children age 4 years and younger.

Both groups were similar with regard to gender, race, ethnicity, atopic history, peanut skin prick test, and qualifying DBPCFC, and all children were previously allergic with positive blood and skin tests, with a positive reaction during baseline food challenge, thus proving the allergy and establishing the baseline threshold.

“We have learned from some studies, for instance the DEVIL and LEAP studies, that strongly suggest that the immune systems in younger patients may be more amenable to change, and there may be some justification for early intervention,” he said.

“Based on both of those ideas, we wanted to take our sublingual approach, which we have shown to have a pretty good efficacy in older children, and bring it down to this younger group and see if it still could have the same efficacy and also maintain what seems to be a very good safety signal.”

The researchers randomly assigned the children to receive PNSLIT at a daily maintenance dose of 4 mg peanut protein (n = 19) or to receive placebo (n = 17) for 36 months.

“There was a 5- to 6-month buildup period where the SLIT dose was increased every 1-2 weeks up to the target dose of 4 mg, and then the final dose of 4 mg was continued through to the end of the study,” Dr. Kim noted.

Over a total of 20,593 potential dosing days, the children took 91.2% of SLIT doses and 93.5% of placebo doses.

At the end of the 3-year study period, the children were challenged by DBPCFC with up to 4,333 mg of peanut protein.

Sustained unresponsiveness was assessed by an identical DBPCFC after discontinuation of the immunotherapy for 3 months.

Cumulative tolerated dose increased from a median of 143 mg to 4,443 mg in the PNSLIT group, compared with a median of 43 mg to 143 mg in the placebo group (P < .0001).

Fourteen of the children receiving PNSLIT, and none of the children receiving placebo, passed the desensitization food challenge. Twelve of the children receiving PNSLIT and two of the children receiving placebo passed the sustained unresponsiveness challenge.

Children who underwent the immunotherapy saw a decrease in their peanut skin prick test from 10 mm to 3.25 mm, compared to an increase from 11.5 mm to 12 mm with placebo (P < .0001).

The most common side effect reported was itching or irritation in the mouth. Most side effects resolved on their own, although some patients used an antihistamine. Getting children as young as 1 to hold the dose under their tongue was a challenge in some instances, but it eventually worked out, Dr. Kim said.

“It took a lot of work from the parents as well as from our research coordinators in trying to train these young kids to, first of all, allow us to put the peanut medication in the mouth and then to try as best as possible to keep it in their mouth for up to 2 minutes, but the families involved in our study were very dedicated and so we were able to get through that,” he said.
 

Study merits larger numbers

“Among the 36 who completed the 3 years of therapy, the authors report significant rates of desensitization among treated children compared with those receiving placebo. Furthermore, this effect was persistent for at least 3 months after stopping therapy in a subgroup of the children,” said Leonard B. Bacharier, MD, director of the Center for Pediatric Asthma, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tenn.

“Overall, these findings suggest the promise of peanut SLIT, which should be studied in larger numbers of preschool children,” Dr. Bacharier, who was not part of the study, said in an interview.

Jonathan A. Bernstein, MD, professor of medicine, University of Cincinnati, agreed.

“It’s a well-designed study, it’s small, but it’s promising,” Dr. Bernstein, who was not involved with the study, said in an interview.

“They did show that most of the patients who got the sublingual therapy were able to get to the target dose and develop tolerance, so I think it’s promising. We know that this stuff works. This is just more data from a well-controlled study in a younger population,” he said.

“We do OIT [oral immunotherapy] and sublingual but we don’t do it in such young children in our practice. The youngest is 3 years old, because they have to understand what is going on and cooperate. If they don’t cooperate it’s not possible.”

Dr. Kim reported financial relationships with DBV Technologies, Kenota Health, Ukko, Aimmune Therapeutics, ALK, AllerGenis, Belhaven Pharma, Duke Clinical Research Institute, Nutricia, NIH/NIAID, NIH/NCCIH, NIH/Immune Tolerance Network, FARE, and the Wallace Foundation. Dr. Bacharier and Dr. Bernstein have disclosed no relevant financial relationships.

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

Sublingual immunotherapy for the treatment of peanut allergy is safe and effective, even in children as young as age 1 year.

In a double-blind, placebo-controlled, food challenge (DBPCFC) of some 36 peanut-allergic children (mean age 2.2 years, range 1-4 years), those who were randomly assigned to receive peanut sublingual immunotherapy (PNSLIT) showed significant desensitization compared with those who received placebo.

In addition, there was a “strong potential” for sustained unresponsiveness at 3 months for the toddlers who received the active treatment.

The findings were presented in a late breaking oral abstract session at the 2021 American Academy of Allergy, Asthma & Immunology virtual annual meeting (Abstract L2).

“A year ago, the Food and Drug Administration approved the oral agent Palforzia (peanut allergen powder) for the treatment of peanut allergy in children 4 and older, and it is a great option, but I think what we have learned over time is that this approach is not for everybody,” Edwin H. Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, said in an interview.

Palforzia is a powder that is mixed in food like yogurt or pudding which the child then eats daily, according to a rigorous schedule. But Palforzia treatment presents some difficulties.

“Palforzia requires getting the powder dose, mixing it with food, like pudding or apple sauce, then eating it, which can take up to 30 minutes depending on age and kids’ cooperation. It tastes and smells like peanut which can cause aversion. Kids have to refrain from exercise or strenuous activity for at least 30 minutes before and after dosing and have to be observed for up to 2 hours post dose for symptoms,” Dr. Kim said.

“It’s a great drug, but the treatment could be overly difficult for certain families to be able to do, and in some cases the side effects may be more than certain patients are able or willing to handle, so there is a real urgent need for alternative approaches,” Dr. Kim said. “SLIT is several drops under the tongue, held for 2 minutes, swallowed and done.”

In the current placebo-controlled study, he and his group tested the feasibility, efficacy, and safety of the sublingual approach to peanut allergy in children age 4 years and younger.

Both groups were similar with regard to gender, race, ethnicity, atopic history, peanut skin prick test, and qualifying DBPCFC, and all children were previously allergic with positive blood and skin tests, with a positive reaction during baseline food challenge, thus proving the allergy and establishing the baseline threshold.

“We have learned from some studies, for instance the DEVIL and LEAP studies, that strongly suggest that the immune systems in younger patients may be more amenable to change, and there may be some justification for early intervention,” he said.

“Based on both of those ideas, we wanted to take our sublingual approach, which we have shown to have a pretty good efficacy in older children, and bring it down to this younger group and see if it still could have the same efficacy and also maintain what seems to be a very good safety signal.”

The researchers randomly assigned the children to receive PNSLIT at a daily maintenance dose of 4 mg peanut protein (n = 19) or to receive placebo (n = 17) for 36 months.

“There was a 5- to 6-month buildup period where the SLIT dose was increased every 1-2 weeks up to the target dose of 4 mg, and then the final dose of 4 mg was continued through to the end of the study,” Dr. Kim noted.

Over a total of 20,593 potential dosing days, the children took 91.2% of SLIT doses and 93.5% of placebo doses.

At the end of the 3-year study period, the children were challenged by DBPCFC with up to 4,333 mg of peanut protein.

Sustained unresponsiveness was assessed by an identical DBPCFC after discontinuation of the immunotherapy for 3 months.

Cumulative tolerated dose increased from a median of 143 mg to 4,443 mg in the PNSLIT group, compared with a median of 43 mg to 143 mg in the placebo group (P < .0001).

Fourteen of the children receiving PNSLIT, and none of the children receiving placebo, passed the desensitization food challenge. Twelve of the children receiving PNSLIT and two of the children receiving placebo passed the sustained unresponsiveness challenge.

Children who underwent the immunotherapy saw a decrease in their peanut skin prick test from 10 mm to 3.25 mm, compared to an increase from 11.5 mm to 12 mm with placebo (P < .0001).

The most common side effect reported was itching or irritation in the mouth. Most side effects resolved on their own, although some patients used an antihistamine. Getting children as young as 1 to hold the dose under their tongue was a challenge in some instances, but it eventually worked out, Dr. Kim said.

“It took a lot of work from the parents as well as from our research coordinators in trying to train these young kids to, first of all, allow us to put the peanut medication in the mouth and then to try as best as possible to keep it in their mouth for up to 2 minutes, but the families involved in our study were very dedicated and so we were able to get through that,” he said.
 

Study merits larger numbers

“Among the 36 who completed the 3 years of therapy, the authors report significant rates of desensitization among treated children compared with those receiving placebo. Furthermore, this effect was persistent for at least 3 months after stopping therapy in a subgroup of the children,” said Leonard B. Bacharier, MD, director of the Center for Pediatric Asthma, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tenn.

“Overall, these findings suggest the promise of peanut SLIT, which should be studied in larger numbers of preschool children,” Dr. Bacharier, who was not part of the study, said in an interview.

Jonathan A. Bernstein, MD, professor of medicine, University of Cincinnati, agreed.

“It’s a well-designed study, it’s small, but it’s promising,” Dr. Bernstein, who was not involved with the study, said in an interview.

“They did show that most of the patients who got the sublingual therapy were able to get to the target dose and develop tolerance, so I think it’s promising. We know that this stuff works. This is just more data from a well-controlled study in a younger population,” he said.

“We do OIT [oral immunotherapy] and sublingual but we don’t do it in such young children in our practice. The youngest is 3 years old, because they have to understand what is going on and cooperate. If they don’t cooperate it’s not possible.”

Dr. Kim reported financial relationships with DBV Technologies, Kenota Health, Ukko, Aimmune Therapeutics, ALK, AllerGenis, Belhaven Pharma, Duke Clinical Research Institute, Nutricia, NIH/NIAID, NIH/NCCIH, NIH/Immune Tolerance Network, FARE, and the Wallace Foundation. Dr. Bacharier and Dr. Bernstein have disclosed no relevant financial relationships.

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

Sublingual immunotherapy for the treatment of peanut allergy is safe and effective, even in children as young as age 1 year.

In a double-blind, placebo-controlled, food challenge (DBPCFC) of some 36 peanut-allergic children (mean age 2.2 years, range 1-4 years), those who were randomly assigned to receive peanut sublingual immunotherapy (PNSLIT) showed significant desensitization compared with those who received placebo.

In addition, there was a “strong potential” for sustained unresponsiveness at 3 months for the toddlers who received the active treatment.

The findings were presented in a late breaking oral abstract session at the 2021 American Academy of Allergy, Asthma & Immunology virtual annual meeting (Abstract L2).

“A year ago, the Food and Drug Administration approved the oral agent Palforzia (peanut allergen powder) for the treatment of peanut allergy in children 4 and older, and it is a great option, but I think what we have learned over time is that this approach is not for everybody,” Edwin H. Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, said in an interview.

Palforzia is a powder that is mixed in food like yogurt or pudding which the child then eats daily, according to a rigorous schedule. But Palforzia treatment presents some difficulties.

“Palforzia requires getting the powder dose, mixing it with food, like pudding or apple sauce, then eating it, which can take up to 30 minutes depending on age and kids’ cooperation. It tastes and smells like peanut which can cause aversion. Kids have to refrain from exercise or strenuous activity for at least 30 minutes before and after dosing and have to be observed for up to 2 hours post dose for symptoms,” Dr. Kim said.

“It’s a great drug, but the treatment could be overly difficult for certain families to be able to do, and in some cases the side effects may be more than certain patients are able or willing to handle, so there is a real urgent need for alternative approaches,” Dr. Kim said. “SLIT is several drops under the tongue, held for 2 minutes, swallowed and done.”

In the current placebo-controlled study, he and his group tested the feasibility, efficacy, and safety of the sublingual approach to peanut allergy in children age 4 years and younger.

Both groups were similar with regard to gender, race, ethnicity, atopic history, peanut skin prick test, and qualifying DBPCFC, and all children were previously allergic with positive blood and skin tests, with a positive reaction during baseline food challenge, thus proving the allergy and establishing the baseline threshold.

“We have learned from some studies, for instance the DEVIL and LEAP studies, that strongly suggest that the immune systems in younger patients may be more amenable to change, and there may be some justification for early intervention,” he said.

“Based on both of those ideas, we wanted to take our sublingual approach, which we have shown to have a pretty good efficacy in older children, and bring it down to this younger group and see if it still could have the same efficacy and also maintain what seems to be a very good safety signal.”

The researchers randomly assigned the children to receive PNSLIT at a daily maintenance dose of 4 mg peanut protein (n = 19) or to receive placebo (n = 17) for 36 months.

“There was a 5- to 6-month buildup period where the SLIT dose was increased every 1-2 weeks up to the target dose of 4 mg, and then the final dose of 4 mg was continued through to the end of the study,” Dr. Kim noted.

Over a total of 20,593 potential dosing days, the children took 91.2% of SLIT doses and 93.5% of placebo doses.

At the end of the 3-year study period, the children were challenged by DBPCFC with up to 4,333 mg of peanut protein.

Sustained unresponsiveness was assessed by an identical DBPCFC after discontinuation of the immunotherapy for 3 months.

Cumulative tolerated dose increased from a median of 143 mg to 4,443 mg in the PNSLIT group, compared with a median of 43 mg to 143 mg in the placebo group (P < .0001).

Fourteen of the children receiving PNSLIT, and none of the children receiving placebo, passed the desensitization food challenge. Twelve of the children receiving PNSLIT and two of the children receiving placebo passed the sustained unresponsiveness challenge.

Children who underwent the immunotherapy saw a decrease in their peanut skin prick test from 10 mm to 3.25 mm, compared to an increase from 11.5 mm to 12 mm with placebo (P < .0001).

The most common side effect reported was itching or irritation in the mouth. Most side effects resolved on their own, although some patients used an antihistamine. Getting children as young as 1 to hold the dose under their tongue was a challenge in some instances, but it eventually worked out, Dr. Kim said.

“It took a lot of work from the parents as well as from our research coordinators in trying to train these young kids to, first of all, allow us to put the peanut medication in the mouth and then to try as best as possible to keep it in their mouth for up to 2 minutes, but the families involved in our study were very dedicated and so we were able to get through that,” he said.
 

Study merits larger numbers

“Among the 36 who completed the 3 years of therapy, the authors report significant rates of desensitization among treated children compared with those receiving placebo. Furthermore, this effect was persistent for at least 3 months after stopping therapy in a subgroup of the children,” said Leonard B. Bacharier, MD, director of the Center for Pediatric Asthma, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tenn.

“Overall, these findings suggest the promise of peanut SLIT, which should be studied in larger numbers of preschool children,” Dr. Bacharier, who was not part of the study, said in an interview.

Jonathan A. Bernstein, MD, professor of medicine, University of Cincinnati, agreed.

“It’s a well-designed study, it’s small, but it’s promising,” Dr. Bernstein, who was not involved with the study, said in an interview.

“They did show that most of the patients who got the sublingual therapy were able to get to the target dose and develop tolerance, so I think it’s promising. We know that this stuff works. This is just more data from a well-controlled study in a younger population,” he said.

“We do OIT [oral immunotherapy] and sublingual but we don’t do it in such young children in our practice. The youngest is 3 years old, because they have to understand what is going on and cooperate. If they don’t cooperate it’s not possible.”

Dr. Kim reported financial relationships with DBV Technologies, Kenota Health, Ukko, Aimmune Therapeutics, ALK, AllerGenis, Belhaven Pharma, Duke Clinical Research Institute, Nutricia, NIH/NIAID, NIH/NCCIH, NIH/Immune Tolerance Network, FARE, and the Wallace Foundation. Dr. Bacharier and Dr. Bernstein have disclosed no relevant financial relationships.

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

The antibody-drug conjugate enfortumab vedotin is superior to chemotherapy in patients with previously treated advanced urothelial carcinoma, primary results of the EV-301 trial show.

Findings were reported at the 2021 Genitourinary Cancers Symposium (Abstract 393).

“Treatment after platinum-based chemotherapy and immune checkpoint inhibitors is challenging. Overall survival is short, and therapeutic options are also limited,” noted first author Thomas Powles, MD, a professor of genitourinary oncology and director of the Barts Cancer Centre, Queen Mary University of London. “Chemotherapy is being used as the global standard of care, but randomized trials supporting these treatment choices are actually lacking. In this setting, new therapeutic agents supported by randomized trials are needed.”

Patients enrolled in EV-301 (NCT03474107), an international open-label, phase 3 trial, had locally advanced or metastatic urothelial carcinoma, had received platinum-based chemotherapy, and had experienced progression during or after immune checkpoint inhibitor therapy (anti–PD1/PD-L1 therapy).

The trial met its primary endpoint, showing that, relative to chemotherapy, enfortumab vedotin reduced the risk of death by 30%, giving patients nearly 4 additional months of life. The toxicity profile was similar to that seen in earlier trials and was manageable.

“Enfortumab vedotin is the first drug, beyond chemotherapy and immunotherapy, to show a significant survival advantage in previously treated urothelial cancer. This is a big step in the right direction for patients with advanced urothelial cancer, where treatment options remain quite limited,” Dr. Powles maintained.

The drug is also showing promising activity when used in the immunotherapy-treated but cisplatin-ineligible patients in the second cohort of the predecessor EV-201 trial, reported at the symposium as well (Abstract 394), he noted. “I hope that, as we move it earlier, we will show better efficacy.”

The Food and Drug Administration granted enfortumab vedotin accelerated approval as third-line therapy in 2019 on the basis of data from the EV-201 trial’s first cohort. With these new data from both trials, the manufacturers have submitted applications to convert the accelerated approval to regular approval, and to expand the current label to include cisplatin-ineligible patients.
 

Trial details

In EV-301, a total of 608 patients were randomized evenly to enfortumab vedotin (an antibody-drug conjugate that targets nectin-4, a cell-adhesion molecule highly expressed in urothelial carcinoma) or the physician’s choice among three standard chemotherapy options having similar efficacy (docetaxel, paclitaxel, or vinflunine).

“None of these chemotherapy drugs have spectacular response rates, and the overall survival is best described as modest,” Dr. Powles said.

He reported results of the trial’s planned interim analysis, which became the primary analysis because the primary endpoint was positive. Specifically, median overall survival was 12.9 months with enfortumab vedotin and 9.0 months with chemotherapy (hazard ratio, 0.70; P = .00142). Benefit was similar across most patient subgroups.

The enfortumab vedotin group also had a better median progression-free survival (5.6 vs. 3.7 months; HR, 0.62; P < .00001) and investigator-assessed overall response rate (40.6% vs. 17.9%; P < .001).

The rate of grade 3 or worse treatment-related adverse events was 51% with enfortumab vedotin and 50% with chemotherapy. The former was associated with a higher rate of grade 3 or worse maculopapular rash (7% vs. 0%), whereas the latter was associated with higher rates of grade 3 or worse decreased neutrophil count (13% vs. 6%), decreased white blood cell count (7% vs. 1%), and febrile neutropenia (6% vs. 1%).

Regarding events of special interest, enfortumab vedotin led to more grade 3 or worse skin reactions of any type (15% vs. 1%), peripheral neuropathy (5% vs. 2%), and hyperglycemia (4% vs. 0%). However, the majority of all treatment-related adverse events of special interest were mild to moderate in severity and consistent with those previously reported.

“There is a skill associated with the management of toxicity, and there is going to be a learning curve for people who haven’t used the drug before,” Dr. Powles acknowledged. “But my experience is, it’s a manageable drug, and delays and dose interruptions actually make it a relatively straightforward drug to give in the context of the profile that we’ve seen today.”
 

Level 1 evidence

“We now know that enfortumab vedotin is here to stay in the armamentarium for the treatment of urothelial cancer, adding its name to the ranks of others which have shown level 1 evidence, proof of a survival benefit in metastatic urothelial carcinoma,” commented invited discussant Arlene O. Siefker-Radtke, MD, a professor in the department of genitourinary medical oncology, University of Texas MD Anderson Cancer Center, Houston.

“I’ve been impressed not only by the activity of enfortumab vedotin in visceral and liver metastases, but also by the impact in patients with bone metastases as this appears very helpful in controlling bone pain in many patients,” she noted.

Preventing and managing toxicity requires appropriate patient selection, careful monitoring, and dose modifications, with knowledge of the agent’s adverse event profile and of factors conferring elevated risk for events, Dr. Siefker-Radtke said.

“The early evidence for enfortumab vedotin in the postimmunotherapy, platinum-ineligible group suggests that this can help treat patients with an unmet need due to their inability to receive platinum-based therapy,” she concluded. “And while it’s currently approved in the third-line setting, we are all eagerly awaiting the outcomes of the frontline studies of enfortumab vedotin combined with pembrolizumab, which showed such a promising objective response rate, as has been presented at earlier meetings.”

The trial was sponsored by Astellas Pharma and Seagen. Dr. Powles disclosed relationships with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, and numerous other pharmaceutical and biotechnology companies. Dr. Siefker-Radtke disclosed relationships with AstraZeneca, Bavarian Nordic, Bristol-Myers Squibb, and a variety of other pharmaceutical and biotechnology companies, as well as patents, royalties, and/or other intellectual property pertaining to methods of characterizing and treating molecular subsets of muscle-invasive bladder cancer.

The antibody-drug conjugate enfortumab vedotin is superior to chemotherapy in patients with previously treated advanced urothelial carcinoma, primary results of the EV-301 trial show.

Findings were reported at the 2021 Genitourinary Cancers Symposium (Abstract 393).

“Treatment after platinum-based chemotherapy and immune checkpoint inhibitors is challenging. Overall survival is short, and therapeutic options are also limited,” noted first author Thomas Powles, MD, a professor of genitourinary oncology and director of the Barts Cancer Centre, Queen Mary University of London. “Chemotherapy is being used as the global standard of care, but randomized trials supporting these treatment choices are actually lacking. In this setting, new therapeutic agents supported by randomized trials are needed.”

Patients enrolled in EV-301 (NCT03474107), an international open-label, phase 3 trial, had locally advanced or metastatic urothelial carcinoma, had received platinum-based chemotherapy, and had experienced progression during or after immune checkpoint inhibitor therapy (anti–PD1/PD-L1 therapy).

The trial met its primary endpoint, showing that, relative to chemotherapy, enfortumab vedotin reduced the risk of death by 30%, giving patients nearly 4 additional months of life. The toxicity profile was similar to that seen in earlier trials and was manageable.

“Enfortumab vedotin is the first drug, beyond chemotherapy and immunotherapy, to show a significant survival advantage in previously treated urothelial cancer. This is a big step in the right direction for patients with advanced urothelial cancer, where treatment options remain quite limited,” Dr. Powles maintained.

The drug is also showing promising activity when used in the immunotherapy-treated but cisplatin-ineligible patients in the second cohort of the predecessor EV-201 trial, reported at the symposium as well (Abstract 394), he noted. “I hope that, as we move it earlier, we will show better efficacy.”

The Food and Drug Administration granted enfortumab vedotin accelerated approval as third-line therapy in 2019 on the basis of data from the EV-201 trial’s first cohort. With these new data from both trials, the manufacturers have submitted applications to convert the accelerated approval to regular approval, and to expand the current label to include cisplatin-ineligible patients.
 

Trial details

In EV-301, a total of 608 patients were randomized evenly to enfortumab vedotin (an antibody-drug conjugate that targets nectin-4, a cell-adhesion molecule highly expressed in urothelial carcinoma) or the physician’s choice among three standard chemotherapy options having similar efficacy (docetaxel, paclitaxel, or vinflunine).

“None of these chemotherapy drugs have spectacular response rates, and the overall survival is best described as modest,” Dr. Powles said.

He reported results of the trial’s planned interim analysis, which became the primary analysis because the primary endpoint was positive. Specifically, median overall survival was 12.9 months with enfortumab vedotin and 9.0 months with chemotherapy (hazard ratio, 0.70; P = .00142). Benefit was similar across most patient subgroups.

The enfortumab vedotin group also had a better median progression-free survival (5.6 vs. 3.7 months; HR, 0.62; P < .00001) and investigator-assessed overall response rate (40.6% vs. 17.9%; P < .001).

The rate of grade 3 or worse treatment-related adverse events was 51% with enfortumab vedotin and 50% with chemotherapy. The former was associated with a higher rate of grade 3 or worse maculopapular rash (7% vs. 0%), whereas the latter was associated with higher rates of grade 3 or worse decreased neutrophil count (13% vs. 6%), decreased white blood cell count (7% vs. 1%), and febrile neutropenia (6% vs. 1%).

Regarding events of special interest, enfortumab vedotin led to more grade 3 or worse skin reactions of any type (15% vs. 1%), peripheral neuropathy (5% vs. 2%), and hyperglycemia (4% vs. 0%). However, the majority of all treatment-related adverse events of special interest were mild to moderate in severity and consistent with those previously reported.

“There is a skill associated with the management of toxicity, and there is going to be a learning curve for people who haven’t used the drug before,” Dr. Powles acknowledged. “But my experience is, it’s a manageable drug, and delays and dose interruptions actually make it a relatively straightforward drug to give in the context of the profile that we’ve seen today.”
 

Level 1 evidence

“We now know that enfortumab vedotin is here to stay in the armamentarium for the treatment of urothelial cancer, adding its name to the ranks of others which have shown level 1 evidence, proof of a survival benefit in metastatic urothelial carcinoma,” commented invited discussant Arlene O. Siefker-Radtke, MD, a professor in the department of genitourinary medical oncology, University of Texas MD Anderson Cancer Center, Houston.

“I’ve been impressed not only by the activity of enfortumab vedotin in visceral and liver metastases, but also by the impact in patients with bone metastases as this appears very helpful in controlling bone pain in many patients,” she noted.

Preventing and managing toxicity requires appropriate patient selection, careful monitoring, and dose modifications, with knowledge of the agent’s adverse event profile and of factors conferring elevated risk for events, Dr. Siefker-Radtke said.

“The early evidence for enfortumab vedotin in the postimmunotherapy, platinum-ineligible group suggests that this can help treat patients with an unmet need due to their inability to receive platinum-based therapy,” she concluded. “And while it’s currently approved in the third-line setting, we are all eagerly awaiting the outcomes of the frontline studies of enfortumab vedotin combined with pembrolizumab, which showed such a promising objective response rate, as has been presented at earlier meetings.”

The trial was sponsored by Astellas Pharma and Seagen. Dr. Powles disclosed relationships with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, and numerous other pharmaceutical and biotechnology companies. Dr. Siefker-Radtke disclosed relationships with AstraZeneca, Bavarian Nordic, Bristol-Myers Squibb, and a variety of other pharmaceutical and biotechnology companies, as well as patents, royalties, and/or other intellectual property pertaining to methods of characterizing and treating molecular subsets of muscle-invasive bladder cancer.

The antibody-drug conjugate enfortumab vedotin is superior to chemotherapy in patients with previously treated advanced urothelial carcinoma, primary results of the EV-301 trial show.

Findings were reported at the 2021 Genitourinary Cancers Symposium (Abstract 393).

“Treatment after platinum-based chemotherapy and immune checkpoint inhibitors is challenging. Overall survival is short, and therapeutic options are also limited,” noted first author Thomas Powles, MD, a professor of genitourinary oncology and director of the Barts Cancer Centre, Queen Mary University of London. “Chemotherapy is being used as the global standard of care, but randomized trials supporting these treatment choices are actually lacking. In this setting, new therapeutic agents supported by randomized trials are needed.”

Patients enrolled in EV-301 (NCT03474107), an international open-label, phase 3 trial, had locally advanced or metastatic urothelial carcinoma, had received platinum-based chemotherapy, and had experienced progression during or after immune checkpoint inhibitor therapy (anti–PD1/PD-L1 therapy).

The trial met its primary endpoint, showing that, relative to chemotherapy, enfortumab vedotin reduced the risk of death by 30%, giving patients nearly 4 additional months of life. The toxicity profile was similar to that seen in earlier trials and was manageable.

“Enfortumab vedotin is the first drug, beyond chemotherapy and immunotherapy, to show a significant survival advantage in previously treated urothelial cancer. This is a big step in the right direction for patients with advanced urothelial cancer, where treatment options remain quite limited,” Dr. Powles maintained.

The drug is also showing promising activity when used in the immunotherapy-treated but cisplatin-ineligible patients in the second cohort of the predecessor EV-201 trial, reported at the symposium as well (Abstract 394), he noted. “I hope that, as we move it earlier, we will show better efficacy.”

The Food and Drug Administration granted enfortumab vedotin accelerated approval as third-line therapy in 2019 on the basis of data from the EV-201 trial’s first cohort. With these new data from both trials, the manufacturers have submitted applications to convert the accelerated approval to regular approval, and to expand the current label to include cisplatin-ineligible patients.
 

Trial details

In EV-301, a total of 608 patients were randomized evenly to enfortumab vedotin (an antibody-drug conjugate that targets nectin-4, a cell-adhesion molecule highly expressed in urothelial carcinoma) or the physician’s choice among three standard chemotherapy options having similar efficacy (docetaxel, paclitaxel, or vinflunine).

“None of these chemotherapy drugs have spectacular response rates, and the overall survival is best described as modest,” Dr. Powles said.

He reported results of the trial’s planned interim analysis, which became the primary analysis because the primary endpoint was positive. Specifically, median overall survival was 12.9 months with enfortumab vedotin and 9.0 months with chemotherapy (hazard ratio, 0.70; P = .00142). Benefit was similar across most patient subgroups.

The enfortumab vedotin group also had a better median progression-free survival (5.6 vs. 3.7 months; HR, 0.62; P < .00001) and investigator-assessed overall response rate (40.6% vs. 17.9%; P < .001).

The rate of grade 3 or worse treatment-related adverse events was 51% with enfortumab vedotin and 50% with chemotherapy. The former was associated with a higher rate of grade 3 or worse maculopapular rash (7% vs. 0%), whereas the latter was associated with higher rates of grade 3 or worse decreased neutrophil count (13% vs. 6%), decreased white blood cell count (7% vs. 1%), and febrile neutropenia (6% vs. 1%).

Regarding events of special interest, enfortumab vedotin led to more grade 3 or worse skin reactions of any type (15% vs. 1%), peripheral neuropathy (5% vs. 2%), and hyperglycemia (4% vs. 0%). However, the majority of all treatment-related adverse events of special interest were mild to moderate in severity and consistent with those previously reported.

“There is a skill associated with the management of toxicity, and there is going to be a learning curve for people who haven’t used the drug before,” Dr. Powles acknowledged. “But my experience is, it’s a manageable drug, and delays and dose interruptions actually make it a relatively straightforward drug to give in the context of the profile that we’ve seen today.”
 

Level 1 evidence

“We now know that enfortumab vedotin is here to stay in the armamentarium for the treatment of urothelial cancer, adding its name to the ranks of others which have shown level 1 evidence, proof of a survival benefit in metastatic urothelial carcinoma,” commented invited discussant Arlene O. Siefker-Radtke, MD, a professor in the department of genitourinary medical oncology, University of Texas MD Anderson Cancer Center, Houston.

“I’ve been impressed not only by the activity of enfortumab vedotin in visceral and liver metastases, but also by the impact in patients with bone metastases as this appears very helpful in controlling bone pain in many patients,” she noted.

Preventing and managing toxicity requires appropriate patient selection, careful monitoring, and dose modifications, with knowledge of the agent’s adverse event profile and of factors conferring elevated risk for events, Dr. Siefker-Radtke said.

“The early evidence for enfortumab vedotin in the postimmunotherapy, platinum-ineligible group suggests that this can help treat patients with an unmet need due to their inability to receive platinum-based therapy,” she concluded. “And while it’s currently approved in the third-line setting, we are all eagerly awaiting the outcomes of the frontline studies of enfortumab vedotin combined with pembrolizumab, which showed such a promising objective response rate, as has been presented at earlier meetings.”

The trial was sponsored by Astellas Pharma and Seagen. Dr. Powles disclosed relationships with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, and numerous other pharmaceutical and biotechnology companies. Dr. Siefker-Radtke disclosed relationships with AstraZeneca, Bavarian Nordic, Bristol-Myers Squibb, and a variety of other pharmaceutical and biotechnology companies, as well as patents, royalties, and/or other intellectual property pertaining to methods of characterizing and treating molecular subsets of muscle-invasive bladder cancer.

Asthma is not an independent risk factor for more severe disease or hospitalization due to COVID-19, according to recent research presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“In our cohort of patients tested for SARS-CoV-2 at Stanford between March and September, asthma was not an independent risk factor in and of itself for hospitalization or more severe disease from COVID,” Lauren E. Eggert, MD, of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University, said in a poster presentation at the meeting. “What’s more, allergic asthma actually decreased the risk of hospitalization by nearly half.”

Dr. Eggert noted that there have been conflicting data on whether comorbid asthma is or is not a risk factor for more severe COVID-19. “The general thought at the beginning of the pandemic was that because COVID-19 is predominantly a viral respiratory illness, and viral illnesses are known to cause asthma exacerbations, that patients with asthma may be at higher risk if they got COVID infection,” she explained. “But some of the data also showed that Th2 inflammation downregulates ACE2 receptor [expression], which has been shown to be the port of entry for the SARS-CoV-2 virus, so maybe allergy might have a protective effect.”

The researchers at Stanford University identified 168,190 patients at Stanford Health Care who had a positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between March and September 2020 and collected data from their electronic medical records on their history of asthma, if they were hospitalized, comorbid conditions, and laboratory values. Patients who had no other data available except for a positive SARS-CoV-2 result, or were younger than 28 days, were excluded from the study. Dr. Eggert and colleagues used COVID-19 treatment guidelines from the National Institutes of Health to assess disease severity, which grades COVID-19 severity as asymptomatic or presymptomatic infection, mild illness, moderate illness, severe illness, and critical illness.

In total, the researchers analyzed 5,596 patients who were SARS-CoV-2 positive, with 605 patients (10.8%) hospitalized within 14 days of receiving a positive test. Of these, 100 patients (16.5%) were patients with asthma. There were no significant differences between groups hospitalized and not hospitalized due to COVID-19 in patients with asthma and with no asthma.

Among patients with asthma and COVID-19, 28.0% had asymptomatic illness, 19.0% had moderate disease, 33.0% had severe disease, and 20.0% had critical COVID-19, compared with 36.0% of patients without asthma who had asymptomatic illness, 12.0% with moderate disease, 30.0% with severe disease, and 21.0% with critical COVID-19. Dr. Eggert and colleagues performed a univariate analysis, which showed a significant association between asthma and COVID-19 related hospitalization (odds ratio, 1.53; 95% confidence interval, 1.2-1.93; P < .001), but when adjusting for factors such as diabetes, obesity coronary heart disease, and hypertension, they found there was not a significant association between asthma and hospitalization due to COVID-19 (OR, 1.12; 95% CI, 0.86-1.45; P < .40).

In a univariate analysis, asthma was associated with more severe disease in patients hospitalized for COVID-19, but the results were not significant (OR, 1.21; 95% CI, 0.8-1.85; P = .37). When analyzing allergic asthma alone in a univariate analysis, the researchers found a significant association between allergic asthma and lower hospitalization risk, compared with patients who had nonallergic asthma (OR, 0.55; 95% CI, 0.31-0.92; P = .029), and this association remained after they performed a multivariate analysis as well.

“When we stratified by allergic asthma versus nonallergic asthma, we found that having a diagnosis of allergic asthma actually conferred a protective effect, and there was almost half the risk of hospitalization in asthmatics with allergic asthma as compared to others, which we thought was very interesting,” Dr. Eggert said.

“Eosinophil levels during hospitalization, even when adjusted for systemic steroid use – and we followed patients out through September, when dexamethasone was standard of care – also correlated with better outcomes,” she explained. “This is independent of asthmatic status.”

Asthma is not an independent risk factor for more severe disease or hospitalization due to COVID-19, according to recent research presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“In our cohort of patients tested for SARS-CoV-2 at Stanford between March and September, asthma was not an independent risk factor in and of itself for hospitalization or more severe disease from COVID,” Lauren E. Eggert, MD, of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University, said in a poster presentation at the meeting. “What’s more, allergic asthma actually decreased the risk of hospitalization by nearly half.”

Dr. Eggert noted that there have been conflicting data on whether comorbid asthma is or is not a risk factor for more severe COVID-19. “The general thought at the beginning of the pandemic was that because COVID-19 is predominantly a viral respiratory illness, and viral illnesses are known to cause asthma exacerbations, that patients with asthma may be at higher risk if they got COVID infection,” she explained. “But some of the data also showed that Th2 inflammation downregulates ACE2 receptor [expression], which has been shown to be the port of entry for the SARS-CoV-2 virus, so maybe allergy might have a protective effect.”

The researchers at Stanford University identified 168,190 patients at Stanford Health Care who had a positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between March and September 2020 and collected data from their electronic medical records on their history of asthma, if they were hospitalized, comorbid conditions, and laboratory values. Patients who had no other data available except for a positive SARS-CoV-2 result, or were younger than 28 days, were excluded from the study. Dr. Eggert and colleagues used COVID-19 treatment guidelines from the National Institutes of Health to assess disease severity, which grades COVID-19 severity as asymptomatic or presymptomatic infection, mild illness, moderate illness, severe illness, and critical illness.

In total, the researchers analyzed 5,596 patients who were SARS-CoV-2 positive, with 605 patients (10.8%) hospitalized within 14 days of receiving a positive test. Of these, 100 patients (16.5%) were patients with asthma. There were no significant differences between groups hospitalized and not hospitalized due to COVID-19 in patients with asthma and with no asthma.

Among patients with asthma and COVID-19, 28.0% had asymptomatic illness, 19.0% had moderate disease, 33.0% had severe disease, and 20.0% had critical COVID-19, compared with 36.0% of patients without asthma who had asymptomatic illness, 12.0% with moderate disease, 30.0% with severe disease, and 21.0% with critical COVID-19. Dr. Eggert and colleagues performed a univariate analysis, which showed a significant association between asthma and COVID-19 related hospitalization (odds ratio, 1.53; 95% confidence interval, 1.2-1.93; P < .001), but when adjusting for factors such as diabetes, obesity coronary heart disease, and hypertension, they found there was not a significant association between asthma and hospitalization due to COVID-19 (OR, 1.12; 95% CI, 0.86-1.45; P < .40).

In a univariate analysis, asthma was associated with more severe disease in patients hospitalized for COVID-19, but the results were not significant (OR, 1.21; 95% CI, 0.8-1.85; P = .37). When analyzing allergic asthma alone in a univariate analysis, the researchers found a significant association between allergic asthma and lower hospitalization risk, compared with patients who had nonallergic asthma (OR, 0.55; 95% CI, 0.31-0.92; P = .029), and this association remained after they performed a multivariate analysis as well.

“When we stratified by allergic asthma versus nonallergic asthma, we found that having a diagnosis of allergic asthma actually conferred a protective effect, and there was almost half the risk of hospitalization in asthmatics with allergic asthma as compared to others, which we thought was very interesting,” Dr. Eggert said.

“Eosinophil levels during hospitalization, even when adjusted for systemic steroid use – and we followed patients out through September, when dexamethasone was standard of care – also correlated with better outcomes,” she explained. “This is independent of asthmatic status.”

Asthma is not an independent risk factor for more severe disease or hospitalization due to COVID-19, according to recent research presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“In our cohort of patients tested for SARS-CoV-2 at Stanford between March and September, asthma was not an independent risk factor in and of itself for hospitalization or more severe disease from COVID,” Lauren E. Eggert, MD, of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University, said in a poster presentation at the meeting. “What’s more, allergic asthma actually decreased the risk of hospitalization by nearly half.”

Dr. Eggert noted that there have been conflicting data on whether comorbid asthma is or is not a risk factor for more severe COVID-19. “The general thought at the beginning of the pandemic was that because COVID-19 is predominantly a viral respiratory illness, and viral illnesses are known to cause asthma exacerbations, that patients with asthma may be at higher risk if they got COVID infection,” she explained. “But some of the data also showed that Th2 inflammation downregulates ACE2 receptor [expression], which has been shown to be the port of entry for the SARS-CoV-2 virus, so maybe allergy might have a protective effect.”

The researchers at Stanford University identified 168,190 patients at Stanford Health Care who had a positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between March and September 2020 and collected data from their electronic medical records on their history of asthma, if they were hospitalized, comorbid conditions, and laboratory values. Patients who had no other data available except for a positive SARS-CoV-2 result, or were younger than 28 days, were excluded from the study. Dr. Eggert and colleagues used COVID-19 treatment guidelines from the National Institutes of Health to assess disease severity, which grades COVID-19 severity as asymptomatic or presymptomatic infection, mild illness, moderate illness, severe illness, and critical illness.

In total, the researchers analyzed 5,596 patients who were SARS-CoV-2 positive, with 605 patients (10.8%) hospitalized within 14 days of receiving a positive test. Of these, 100 patients (16.5%) were patients with asthma. There were no significant differences between groups hospitalized and not hospitalized due to COVID-19 in patients with asthma and with no asthma.

Among patients with asthma and COVID-19, 28.0% had asymptomatic illness, 19.0% had moderate disease, 33.0% had severe disease, and 20.0% had critical COVID-19, compared with 36.0% of patients without asthma who had asymptomatic illness, 12.0% with moderate disease, 30.0% with severe disease, and 21.0% with critical COVID-19. Dr. Eggert and colleagues performed a univariate analysis, which showed a significant association between asthma and COVID-19 related hospitalization (odds ratio, 1.53; 95% confidence interval, 1.2-1.93; P < .001), but when adjusting for factors such as diabetes, obesity coronary heart disease, and hypertension, they found there was not a significant association between asthma and hospitalization due to COVID-19 (OR, 1.12; 95% CI, 0.86-1.45; P < .40).

In a univariate analysis, asthma was associated with more severe disease in patients hospitalized for COVID-19, but the results were not significant (OR, 1.21; 95% CI, 0.8-1.85; P = .37). When analyzing allergic asthma alone in a univariate analysis, the researchers found a significant association between allergic asthma and lower hospitalization risk, compared with patients who had nonallergic asthma (OR, 0.55; 95% CI, 0.31-0.92; P = .029), and this association remained after they performed a multivariate analysis as well.

“When we stratified by allergic asthma versus nonallergic asthma, we found that having a diagnosis of allergic asthma actually conferred a protective effect, and there was almost half the risk of hospitalization in asthmatics with allergic asthma as compared to others, which we thought was very interesting,” Dr. Eggert said.

“Eosinophil levels during hospitalization, even when adjusted for systemic steroid use – and we followed patients out through September, when dexamethasone was standard of care – also correlated with better outcomes,” she explained. “This is independent of asthmatic status.”

While most commercially insured patients with asthma have good disease control, some patients may not, according to a recent review of U.S. administrative claims data.

The results of the retrospective analysis, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year, showed some patients with asthma had two or more refills for prescribed systemic corticosteroids (SCS) or short-acting beta agonists (SABA) within a period of 12 months.

“Frequent prescription of systemic corticosteroids and short-acting beta agonists is often indicative of poor asthma disease control,” Randall Brown, MD, MPH, pulmonologist and senior director of Global Respiratory Medical Affairs at Teva Pharmaceuticals in West Chester, Penn., said in a presentation at the meeting. “Understanding the extent of systemic steroid and SABA prescriptions among patients with asthma and the distribution of those prescriptions across disease severity can be useful in determining the degree of disease control.”

Global Initiative for Asthma (GINA) guidelines consider factors such as symptom control and risk of exacerbation when determining asthma severity, but uncontrolled asthma can still be difficult to assess. Dr. Brown and colleagues set out to determine the prevalence of uncontrolled asthma for patients in the IBM/Watson MarketScan U.S. claims database as well as the rate of uncontrolled asthma by GINA classification. In total, 597,955 patients who had an asthma diagnosis between 12 months before or up to 3 months after the index data of filling a SABA prescription were included for analysis. Patients were at least 12 years old with commercial insurance for at least 12 months, and had no other respiratory diseases other than asthma during the 12 months prior to the index date and during the study period.

The researchers then measured each patient’s 2018 GINA classification of asthma severity based on the number of SCS and SABA prescription claims made between January and December 2017. Overall, 54.3% patients were GINA Step 1, 14.6% were Step 2, 10.2% were Step 3, 19.8% were Step 4, and 1.1% were Step 5.

Dr. Brown and colleagues found that, regardless of GINA disease severity, 18.8% of patients filled two or more SCS prescriptions in 1 year, 27.4% filled three or more SABA prescriptions in 1 year, and 38.7% filled two or more SCS and/or three or more SABA prescriptions in 1 year. “[A] large proportion of these patients did not meet the GINA goal of disease control,” Dr. Brown said.

The researchers found 13% of patients with uncontrolled asthma categorized as GINA Step 1, 20% of patients categorized as GINA Step 2, 19% of patients who were GINA Step 3, 31% of patients who were GINA Step 4, and 54% of patients categorized as GINA Step 5 filled two or more two or more SCS prescriptions per year.

The proportion of patients with uncontrolled asthma who filled three or more SABA prescriptions per year included 19% in GINA Step 1, 29% in GINA Step 2, 35% in GINA Step 3, 44% in GINA Step 4, and 57% in GINA Step 5 groups. For patients who filled both two or more SCS and/or three or more SABA prescriptions per year, the proportion of patients with uncontrolled asthma by GINA category was 29% in GINA Step 1, 42% in GINA Step 2, 46% in GINA Step 3, 58% in GINA Step 4, and 76% of patients in GINA Step 5.

While “poor control was seen across all of the GINA disease severity classifications, the greatest proportion of uncontrolled disease was seen at the highest disease severity, which was also true when we used a stricter definition of uncontrolled disease,” Dr. Brown said. When the researchers applied stricter criteria for patients categorized as GINA Step 5, 39% of patients filled three or more SCS, 41% filled four or more SABA, and 60% filled three or more SCS and/or four or more SABA prescriptions over 12 months.

Dr. Brown said that the analysis “highlights the need for improved asthma management strategies within each of the asthma GINA classification steps.”

“While this population that was studied may be reflective of the wider insured U.S. population, the proportions of uncontrolled asthma may be even greater in non–commercially insured patients within the United States,” he said. “Updates to GINA guidelines incorporate recent consensus [and] recent scientific information and therapies, but many patients in the U.S. are not meeting the GINA goal of disease control. Newer paradigms for systemic corticosteroid-free asthma control as a target of disease ‘remission’ are becoming more commonplace. Such changes and goals may lead to improved asthma management strategies and advancement in treatment.”

This study was funded in part by Teva Branded Pharmaceutical Products R&D, which also provided funding for medical writing assistance from Ashfield MedComms. The authors report being employees of Teva Pharmaceuticals.

While most commercially insured patients with asthma have good disease control, some patients may not, according to a recent review of U.S. administrative claims data.

The results of the retrospective analysis, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year, showed some patients with asthma had two or more refills for prescribed systemic corticosteroids (SCS) or short-acting beta agonists (SABA) within a period of 12 months.

“Frequent prescription of systemic corticosteroids and short-acting beta agonists is often indicative of poor asthma disease control,” Randall Brown, MD, MPH, pulmonologist and senior director of Global Respiratory Medical Affairs at Teva Pharmaceuticals in West Chester, Penn., said in a presentation at the meeting. “Understanding the extent of systemic steroid and SABA prescriptions among patients with asthma and the distribution of those prescriptions across disease severity can be useful in determining the degree of disease control.”

Global Initiative for Asthma (GINA) guidelines consider factors such as symptom control and risk of exacerbation when determining asthma severity, but uncontrolled asthma can still be difficult to assess. Dr. Brown and colleagues set out to determine the prevalence of uncontrolled asthma for patients in the IBM/Watson MarketScan U.S. claims database as well as the rate of uncontrolled asthma by GINA classification. In total, 597,955 patients who had an asthma diagnosis between 12 months before or up to 3 months after the index data of filling a SABA prescription were included for analysis. Patients were at least 12 years old with commercial insurance for at least 12 months, and had no other respiratory diseases other than asthma during the 12 months prior to the index date and during the study period.

The researchers then measured each patient’s 2018 GINA classification of asthma severity based on the number of SCS and SABA prescription claims made between January and December 2017. Overall, 54.3% patients were GINA Step 1, 14.6% were Step 2, 10.2% were Step 3, 19.8% were Step 4, and 1.1% were Step 5.

Dr. Brown and colleagues found that, regardless of GINA disease severity, 18.8% of patients filled two or more SCS prescriptions in 1 year, 27.4% filled three or more SABA prescriptions in 1 year, and 38.7% filled two or more SCS and/or three or more SABA prescriptions in 1 year. “[A] large proportion of these patients did not meet the GINA goal of disease control,” Dr. Brown said.

The researchers found 13% of patients with uncontrolled asthma categorized as GINA Step 1, 20% of patients categorized as GINA Step 2, 19% of patients who were GINA Step 3, 31% of patients who were GINA Step 4, and 54% of patients categorized as GINA Step 5 filled two or more two or more SCS prescriptions per year.

The proportion of patients with uncontrolled asthma who filled three or more SABA prescriptions per year included 19% in GINA Step 1, 29% in GINA Step 2, 35% in GINA Step 3, 44% in GINA Step 4, and 57% in GINA Step 5 groups. For patients who filled both two or more SCS and/or three or more SABA prescriptions per year, the proportion of patients with uncontrolled asthma by GINA category was 29% in GINA Step 1, 42% in GINA Step 2, 46% in GINA Step 3, 58% in GINA Step 4, and 76% of patients in GINA Step 5.

While “poor control was seen across all of the GINA disease severity classifications, the greatest proportion of uncontrolled disease was seen at the highest disease severity, which was also true when we used a stricter definition of uncontrolled disease,” Dr. Brown said. When the researchers applied stricter criteria for patients categorized as GINA Step 5, 39% of patients filled three or more SCS, 41% filled four or more SABA, and 60% filled three or more SCS and/or four or more SABA prescriptions over 12 months.

Dr. Brown said that the analysis “highlights the need for improved asthma management strategies within each of the asthma GINA classification steps.”

“While this population that was studied may be reflective of the wider insured U.S. population, the proportions of uncontrolled asthma may be even greater in non–commercially insured patients within the United States,” he said. “Updates to GINA guidelines incorporate recent consensus [and] recent scientific information and therapies, but many patients in the U.S. are not meeting the GINA goal of disease control. Newer paradigms for systemic corticosteroid-free asthma control as a target of disease ‘remission’ are becoming more commonplace. Such changes and goals may lead to improved asthma management strategies and advancement in treatment.”

This study was funded in part by Teva Branded Pharmaceutical Products R&D, which also provided funding for medical writing assistance from Ashfield MedComms. The authors report being employees of Teva Pharmaceuticals.

While most commercially insured patients with asthma have good disease control, some patients may not, according to a recent review of U.S. administrative claims data.

The results of the retrospective analysis, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year, showed some patients with asthma had two or more refills for prescribed systemic corticosteroids (SCS) or short-acting beta agonists (SABA) within a period of 12 months.

“Frequent prescription of systemic corticosteroids and short-acting beta agonists is often indicative of poor asthma disease control,” Randall Brown, MD, MPH, pulmonologist and senior director of Global Respiratory Medical Affairs at Teva Pharmaceuticals in West Chester, Penn., said in a presentation at the meeting. “Understanding the extent of systemic steroid and SABA prescriptions among patients with asthma and the distribution of those prescriptions across disease severity can be useful in determining the degree of disease control.”

Global Initiative for Asthma (GINA) guidelines consider factors such as symptom control and risk of exacerbation when determining asthma severity, but uncontrolled asthma can still be difficult to assess. Dr. Brown and colleagues set out to determine the prevalence of uncontrolled asthma for patients in the IBM/Watson MarketScan U.S. claims database as well as the rate of uncontrolled asthma by GINA classification. In total, 597,955 patients who had an asthma diagnosis between 12 months before or up to 3 months after the index data of filling a SABA prescription were included for analysis. Patients were at least 12 years old with commercial insurance for at least 12 months, and had no other respiratory diseases other than asthma during the 12 months prior to the index date and during the study period.

The researchers then measured each patient’s 2018 GINA classification of asthma severity based on the number of SCS and SABA prescription claims made between January and December 2017. Overall, 54.3% patients were GINA Step 1, 14.6% were Step 2, 10.2% were Step 3, 19.8% were Step 4, and 1.1% were Step 5.

Dr. Brown and colleagues found that, regardless of GINA disease severity, 18.8% of patients filled two or more SCS prescriptions in 1 year, 27.4% filled three or more SABA prescriptions in 1 year, and 38.7% filled two or more SCS and/or three or more SABA prescriptions in 1 year. “[A] large proportion of these patients did not meet the GINA goal of disease control,” Dr. Brown said.

The researchers found 13% of patients with uncontrolled asthma categorized as GINA Step 1, 20% of patients categorized as GINA Step 2, 19% of patients who were GINA Step 3, 31% of patients who were GINA Step 4, and 54% of patients categorized as GINA Step 5 filled two or more two or more SCS prescriptions per year.

The proportion of patients with uncontrolled asthma who filled three or more SABA prescriptions per year included 19% in GINA Step 1, 29% in GINA Step 2, 35% in GINA Step 3, 44% in GINA Step 4, and 57% in GINA Step 5 groups. For patients who filled both two or more SCS and/or three or more SABA prescriptions per year, the proportion of patients with uncontrolled asthma by GINA category was 29% in GINA Step 1, 42% in GINA Step 2, 46% in GINA Step 3, 58% in GINA Step 4, and 76% of patients in GINA Step 5.

While “poor control was seen across all of the GINA disease severity classifications, the greatest proportion of uncontrolled disease was seen at the highest disease severity, which was also true when we used a stricter definition of uncontrolled disease,” Dr. Brown said. When the researchers applied stricter criteria for patients categorized as GINA Step 5, 39% of patients filled three or more SCS, 41% filled four or more SABA, and 60% filled three or more SCS and/or four or more SABA prescriptions over 12 months.

Dr. Brown said that the analysis “highlights the need for improved asthma management strategies within each of the asthma GINA classification steps.”

“While this population that was studied may be reflective of the wider insured U.S. population, the proportions of uncontrolled asthma may be even greater in non–commercially insured patients within the United States,” he said. “Updates to GINA guidelines incorporate recent consensus [and] recent scientific information and therapies, but many patients in the U.S. are not meeting the GINA goal of disease control. Newer paradigms for systemic corticosteroid-free asthma control as a target of disease ‘remission’ are becoming more commonplace. Such changes and goals may lead to improved asthma management strategies and advancement in treatment.”

This study was funded in part by Teva Branded Pharmaceutical Products R&D, which also provided funding for medical writing assistance from Ashfield MedComms. The authors report being employees of Teva Pharmaceuticals.

Wearing a mask to protect against transmission of COVID-19 does not decrease oxygen saturation, according to a new study.

Oxygen saturation did not decline in more than 200 mask-wearing individuals attending an asthma and allergy clinic, regardless of the type of mask they were wearing and how long they had been wearing the mask.

The study was presented in a late breaking poster session by Marisa Hodges, MD, University of Michigan, Ann Arbor, at the virtual annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“In patients with or without asthma, wearing a mask does not decrease your oxygen level,” coauthor Alan P. Baptist, MD, MPH, director of the University of Michigan Comprehensive Asthma Program, said in an interview.

“Some of my asthma patients had called me requesting an exemption from wearing a mask because they feared that their oxygen intake may be affected, and that got me thinking,” said Malika Gupta, MD, assistant professor, division of allergy and immunology, University of Michigan, Ann Arbor, and the study’s lead investigator.

“We say masks are safe, but I couldn’t find any data to support that statement, and we wanted to provide them with evidence, so they could feel comfortable about wearing their masks,” Dr. Gupta added.

The study collected 223 surveys from adult and pediatric patients presenting to the University of Michigan Medicine Allergy Clinic between Sept. 10 and Oct. 23, 2020.

The patients were asked whether they had a diagnosis of asthma, their degree of perceived control if they did have asthma, the type of mask they were wearing, and how long they had been wearing it.

Investigators obtained resting pulse oximetry readings to measure oxygen saturation (SpO₂) from all study participants.

Forty percent of the participants were male, 46% reported having asthma, and 27% were age 19 years or younger.

Overall, the mean SpO₂ was 98% (range, 93%-100%) in both asthma and nonasthma groups.

The study also looked at SpO₂ with 3 different types of masks: fabric, surgical, and N95.

The mean SpO₂ for a fabric mask was 98% (119 patients), for a surgical mask it was also 98% (83 patients), and for the N95 mask it was 99% (3 patients).

Similar results were found with duration of mask use, with the mean SpO₂ 98% in those wearing a mask for 1 hour or less and 99% in those wearing a mask for 1 hour or longer.

People with asthma who reported they were well controlled showed similar mean SpO₂ levels (98%) compared with those who reported they were not well controlled (96.5%)

“No effect on oxygen saturation was noted in any patients, whether they had asthma or not, whether it was well controlled or not, and this was also true regardless of what masks they wore and how long they wore the masks for. So our data reinforce that wearing a mask, whether it be a surgical mask, cloth mask, or N95, is completely safe,” Dr. Baptist said.

“We know wearing a mask is an essential step we can all take to reduce the spread of COVID-19, and we hope these data will give peace of mind to individuals who fear that wearing a mask will adversely affect their oxygen levels,” Dr. Gupta added.

Leonard B. Bacharier, MD, professor of pediatrics and director of the Center for Pediatric Asthma, Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, Tenn., agreed with the investigators’ conclusions.

“The authors found no differences in oxygen saturations between asthmatic and nonasthmatic patients, nor was there a difference based upon mask use or type,” Dr. Bacharier, who was not part of the study, said in an interview.

“These findings provide reassurance that patients, including those with stable asthma, do not experience impaired oxygenation while wearing a mask.”

Dr. Hodges, Dr. Baptist, and Dr. Bacharier have disclosed no relevant financial relationships.

This article was updated 3/11/21.

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

Wearing a mask to protect against transmission of COVID-19 does not decrease oxygen saturation, according to a new study.

Oxygen saturation did not decline in more than 200 mask-wearing individuals attending an asthma and allergy clinic, regardless of the type of mask they were wearing and how long they had been wearing the mask.

The study was presented in a late breaking poster session by Marisa Hodges, MD, University of Michigan, Ann Arbor, at the virtual annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“In patients with or without asthma, wearing a mask does not decrease your oxygen level,” coauthor Alan P. Baptist, MD, MPH, director of the University of Michigan Comprehensive Asthma Program, said in an interview.

“Some of my asthma patients had called me requesting an exemption from wearing a mask because they feared that their oxygen intake may be affected, and that got me thinking,” said Malika Gupta, MD, assistant professor, division of allergy and immunology, University of Michigan, Ann Arbor, and the study’s lead investigator.

“We say masks are safe, but I couldn’t find any data to support that statement, and we wanted to provide them with evidence, so they could feel comfortable about wearing their masks,” Dr. Gupta added.

The study collected 223 surveys from adult and pediatric patients presenting to the University of Michigan Medicine Allergy Clinic between Sept. 10 and Oct. 23, 2020.

The patients were asked whether they had a diagnosis of asthma, their degree of perceived control if they did have asthma, the type of mask they were wearing, and how long they had been wearing it.

Investigators obtained resting pulse oximetry readings to measure oxygen saturation (SpO₂) from all study participants.

Forty percent of the participants were male, 46% reported having asthma, and 27% were age 19 years or younger.

Overall, the mean SpO₂ was 98% (range, 93%-100%) in both asthma and nonasthma groups.

The study also looked at SpO₂ with 3 different types of masks: fabric, surgical, and N95.

The mean SpO₂ for a fabric mask was 98% (119 patients), for a surgical mask it was also 98% (83 patients), and for the N95 mask it was 99% (3 patients).

Similar results were found with duration of mask use, with the mean SpO₂ 98% in those wearing a mask for 1 hour or less and 99% in those wearing a mask for 1 hour or longer.

People with asthma who reported they were well controlled showed similar mean SpO₂ levels (98%) compared with those who reported they were not well controlled (96.5%)

“No effect on oxygen saturation was noted in any patients, whether they had asthma or not, whether it was well controlled or not, and this was also true regardless of what masks they wore and how long they wore the masks for. So our data reinforce that wearing a mask, whether it be a surgical mask, cloth mask, or N95, is completely safe,” Dr. Baptist said.

“We know wearing a mask is an essential step we can all take to reduce the spread of COVID-19, and we hope these data will give peace of mind to individuals who fear that wearing a mask will adversely affect their oxygen levels,” Dr. Gupta added.

Leonard B. Bacharier, MD, professor of pediatrics and director of the Center for Pediatric Asthma, Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, Tenn., agreed with the investigators’ conclusions.

“The authors found no differences in oxygen saturations between asthmatic and nonasthmatic patients, nor was there a difference based upon mask use or type,” Dr. Bacharier, who was not part of the study, said in an interview.

“These findings provide reassurance that patients, including those with stable asthma, do not experience impaired oxygenation while wearing a mask.”

Dr. Hodges, Dr. Baptist, and Dr. Bacharier have disclosed no relevant financial relationships.

This article was updated 3/11/21.

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

Wearing a mask to protect against transmission of COVID-19 does not decrease oxygen saturation, according to a new study.

Oxygen saturation did not decline in more than 200 mask-wearing individuals attending an asthma and allergy clinic, regardless of the type of mask they were wearing and how long they had been wearing the mask.

The study was presented in a late breaking poster session by Marisa Hodges, MD, University of Michigan, Ann Arbor, at the virtual annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“In patients with or without asthma, wearing a mask does not decrease your oxygen level,” coauthor Alan P. Baptist, MD, MPH, director of the University of Michigan Comprehensive Asthma Program, said in an interview.

“Some of my asthma patients had called me requesting an exemption from wearing a mask because they feared that their oxygen intake may be affected, and that got me thinking,” said Malika Gupta, MD, assistant professor, division of allergy and immunology, University of Michigan, Ann Arbor, and the study’s lead investigator.

“We say masks are safe, but I couldn’t find any data to support that statement, and we wanted to provide them with evidence, so they could feel comfortable about wearing their masks,” Dr. Gupta added.

The study collected 223 surveys from adult and pediatric patients presenting to the University of Michigan Medicine Allergy Clinic between Sept. 10 and Oct. 23, 2020.

The patients were asked whether they had a diagnosis of asthma, their degree of perceived control if they did have asthma, the type of mask they were wearing, and how long they had been wearing it.

Investigators obtained resting pulse oximetry readings to measure oxygen saturation (SpO₂) from all study participants.

Forty percent of the participants were male, 46% reported having asthma, and 27% were age 19 years or younger.

Overall, the mean SpO₂ was 98% (range, 93%-100%) in both asthma and nonasthma groups.

The study also looked at SpO₂ with 3 different types of masks: fabric, surgical, and N95.

The mean SpO₂ for a fabric mask was 98% (119 patients), for a surgical mask it was also 98% (83 patients), and for the N95 mask it was 99% (3 patients).

Similar results were found with duration of mask use, with the mean SpO₂ 98% in those wearing a mask for 1 hour or less and 99% in those wearing a mask for 1 hour or longer.

People with asthma who reported they were well controlled showed similar mean SpO₂ levels (98%) compared with those who reported they were not well controlled (96.5%)

“No effect on oxygen saturation was noted in any patients, whether they had asthma or not, whether it was well controlled or not, and this was also true regardless of what masks they wore and how long they wore the masks for. So our data reinforce that wearing a mask, whether it be a surgical mask, cloth mask, or N95, is completely safe,” Dr. Baptist said.

“We know wearing a mask is an essential step we can all take to reduce the spread of COVID-19, and we hope these data will give peace of mind to individuals who fear that wearing a mask will adversely affect their oxygen levels,” Dr. Gupta added.

Leonard B. Bacharier, MD, professor of pediatrics and director of the Center for Pediatric Asthma, Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, Tenn., agreed with the investigators’ conclusions.

“The authors found no differences in oxygen saturations between asthmatic and nonasthmatic patients, nor was there a difference based upon mask use or type,” Dr. Bacharier, who was not part of the study, said in an interview.

“These findings provide reassurance that patients, including those with stable asthma, do not experience impaired oxygenation while wearing a mask.”

Dr. Hodges, Dr. Baptist, and Dr. Bacharier have disclosed no relevant financial relationships.

This article was updated 3/11/21.

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

Approximately half of all patients with locally advanced or metastatic urothelial cancer (la/mUC) are ineligible to receive cisplatin-based chemotherapy. They face poor outlooks and extremely limited treatment options.

A new study indicates that enfortumab vedotin (EV) can cause major, prolonged responses in most patients in that unfortunate setting.
 

EV is an antibody-drug conjugate directed against nectin-4, an immunoglobulin-like cell adhesion molecule that is highly expressed in UC, obviating the need for testing prior to treatment. It is internalized in malignant cells, with release of the active moiety (monomethyl auristatin E; MMAE). MMAE causes microtubule disruption, with resultant cell-cycle arrest and apoptosis.

EV received accelerated approval from the Food and Drug Administration in December 2019 after publication of the results from cohort 1 of the open-label, single-arm, phase 2 EV-201 study.

Arjun V. Balar, MD, of the Perlmutter Cancer Center at New York University Langone Health, presented results from cohort 2 of EV-201 – the cisplatin-ineligible cohort – at the 2021 Genitourinary Cancer Symposium (Abstract 394).
 

EV in patients ineligible for platinum-based therapy

Patients in cohort 2 of EV-201 had received immune checkpoint inhibitor therapy for la/mUC. They received EV in the FDA-approved dose for cohort 1: 1.25 mg/kg EV on days 1, 8, and 15 of a 28-day cycle.

Patients experienced disease progression during or following their most recent treatment. Patients with more than two neuropathies, active central nervous system metastases, and uncontrolled diabetes mellitus were excluded.

“Platinum ineligible” was defined as a creatinine clearance between 30-59 cm³/min, Eastern Cooperative Oncology Group performance status (ECOG PS) 2, or hearing loss of grade 2 or greater.

The primary endpoint for cohort 2 was confirmed overall response rate (ORR) per RECIST 1.1 by blinded independent central review. Secondary endpoints were duration of response, progression-free survival, overall survival, and safety.

There were 91 patients enrolled. Two patients never received EV treatment because of deterioration after registration. The median treatment duration among the remaining 89 patients was 6.0 months (range, 0.3-24.6).

Impressive results in poor-risk patients

The patients in EV-201 cohort 2 were elderly (median age, 75 years; range, 49-90) with comorbidities. The primary reasons for platinum-ineligibility were creatinine clearance less than 60 mL/min (66%), grade 2 or greater hearing loss (15%), and ECOG PS 2 (7%); 12% of patients met more than one criterion for platinum ineligibility.

The primary tumor site was in the upper urinary tract in 43% of patients, and 79% had visceral metastases, including 24% with liver involvement.

The confirmed ORR was 52% (95% confidence interval, 40.8-62.4), with 20% complete responses. There were responses in all subgroups, including patients with primary tumor sites in the upper tract (ORR, 61%), those with liver metastasis (ORR, 48%), and patients who had not responded to immune checkpoint inhibitors (ORR, 48%).

A total of 88% of patients had some decrease in measurable tumor diameters, generally within a few weeks of treatment initiation (median time to response, 1.8 months). The rapid response to treatment was especially important to patients having cancer-associated pain.

The median progression-free and overall survival durations were 5.8 months (95% CI, 5.0-8.3) and 14.7 months (95% CI, 10.5-18.2), respectively. The median response duration was 10.9 months (95% CI, 5.78-NR). More than 25% of responses extended beyond 12 months.

About 82% of patients in cohort 2 discontinued treatment, most commonly because of disease progression (51%). The second most common reason was the development of treatment-related adverse events (TRAE; 24%).
 

Drilling down on treatment-related adverse events

As might be expected for cisplatin-ineligible patients, adverse events were higher for patients in cohort 2 than for cohort 1 and led to treatment discontinuation in 16% of patients overall.

TRAEs over grade 3 occurred in 55% of patients. TRAEs of special interest included rash (61% overall; 17% ≥ grade 3), peripheral neuropathy (54% overall; 8% ≥ grade 3), and hyperglycemia (10% overall; 6% ≥ grade 3). Dose reductions, interruptions, and physical therapy were helpful.

Twenty percent of patients with TRAE hyperglycemia had hyperglycemia at baseline, and 30% of TRAEs were in patients with high body mass index (BMI).

There were four treatment-related deaths, all in patients 75 years or older with multiple comorbidities. Three of the four deaths occurred within 30 days of first EV dose in patients with BMI of 30 or greater (acute kidney injury, metabolic acidosis, and multiple organ dysfunction syndrome). The remaining death occurred more than 30 days after the last dose (pneumonitis).
 

Context and caution

The authors concluded that EV produced durable responses in platinum-ineligible patients with la/mUC, including 20% complete responses. Safety was felt to be as expected, given the known toxicities of the agent and the compromised medical condition of the patients studied.

The study discussant, Arlene O. Siefker-Radtke, MD, of the University of Texas MD Anderson Cancer Center, Houston, agreed that EV fills an unmet need, showing impressive responses in patients with visceral, liver, and bone metastases. She agreed that EV should be investigated across the spectrum of urothelial cancer.

Dr. Siefker-Radtke reminded attendees that the FDA package insert for EV described a 48% increase in the area under the concentration-time curve concentration of the MMAE active moiety in patients with mild hepatic impairment and that EV use should be avoided entirely in patients with moderate to severe liver disease.

She speculated whether augmented toxicity in patients with a high BMI could be attributable to clinically occult impaired hepatic function from fatty liver infiltration.

She indicated that clinicians should monitor closely patients with higher BMI and grade 3-4 hyperglycemia or elevated hemoglobin A1c levels and advised holding EV in patients who develop:

• Glucose levels above 250 mg/dL
• Peeling skin or bullous skin lesions. These lesions can be heralded by a diffuse erythematous or papillary rash in the preceding weeks.
• Grade 3 diarrhea or mucosal membrane toxicity of other types.

Notwithstanding concerns about toxicity and the need for monitoring, EV merits continued study in combination with other agents and in additional settings in the clinical spectrum of urothelial cancer. It is an important new option for oncologists caring for patients with urothelial cancer.

The EV-201 study was funded by Seagen. Dr. Balar and Dr. Siefker-Radtke disclosed relationships with Seagen and many other companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Approximately half of all patients with locally advanced or metastatic urothelial cancer (la/mUC) are ineligible to receive cisplatin-based chemotherapy. They face poor outlooks and extremely limited treatment options.

A new study indicates that enfortumab vedotin (EV) can cause major, prolonged responses in most patients in that unfortunate setting.
 

EV is an antibody-drug conjugate directed against nectin-4, an immunoglobulin-like cell adhesion molecule that is highly expressed in UC, obviating the need for testing prior to treatment. It is internalized in malignant cells, with release of the active moiety (monomethyl auristatin E; MMAE). MMAE causes microtubule disruption, with resultant cell-cycle arrest and apoptosis.

EV received accelerated approval from the Food and Drug Administration in December 2019 after publication of the results from cohort 1 of the open-label, single-arm, phase 2 EV-201 study.

Arjun V. Balar, MD, of the Perlmutter Cancer Center at New York University Langone Health, presented results from cohort 2 of EV-201 – the cisplatin-ineligible cohort – at the 2021 Genitourinary Cancer Symposium (Abstract 394).
 

EV in patients ineligible for platinum-based therapy

Patients in cohort 2 of EV-201 had received immune checkpoint inhibitor therapy for la/mUC. They received EV in the FDA-approved dose for cohort 1: 1.25 mg/kg EV on days 1, 8, and 15 of a 28-day cycle.

Patients experienced disease progression during or following their most recent treatment. Patients with more than two neuropathies, active central nervous system metastases, and uncontrolled diabetes mellitus were excluded.

“Platinum ineligible” was defined as a creatinine clearance between 30-59 cm³/min, Eastern Cooperative Oncology Group performance status (ECOG PS) 2, or hearing loss of grade 2 or greater.

The primary endpoint for cohort 2 was confirmed overall response rate (ORR) per RECIST 1.1 by blinded independent central review. Secondary endpoints were duration of response, progression-free survival, overall survival, and safety.

There were 91 patients enrolled. Two patients never received EV treatment because of deterioration after registration. The median treatment duration among the remaining 89 patients was 6.0 months (range, 0.3-24.6).

Impressive results in poor-risk patients

The patients in EV-201 cohort 2 were elderly (median age, 75 years; range, 49-90) with comorbidities. The primary reasons for platinum-ineligibility were creatinine clearance less than 60 mL/min (66%), grade 2 or greater hearing loss (15%), and ECOG PS 2 (7%); 12% of patients met more than one criterion for platinum ineligibility.

The primary tumor site was in the upper urinary tract in 43% of patients, and 79% had visceral metastases, including 24% with liver involvement.

The confirmed ORR was 52% (95% confidence interval, 40.8-62.4), with 20% complete responses. There were responses in all subgroups, including patients with primary tumor sites in the upper tract (ORR, 61%), those with liver metastasis (ORR, 48%), and patients who had not responded to immune checkpoint inhibitors (ORR, 48%).

A total of 88% of patients had some decrease in measurable tumor diameters, generally within a few weeks of treatment initiation (median time to response, 1.8 months). The rapid response to treatment was especially important to patients having cancer-associated pain.

The median progression-free and overall survival durations were 5.8 months (95% CI, 5.0-8.3) and 14.7 months (95% CI, 10.5-18.2), respectively. The median response duration was 10.9 months (95% CI, 5.78-NR). More than 25% of responses extended beyond 12 months.

About 82% of patients in cohort 2 discontinued treatment, most commonly because of disease progression (51%). The second most common reason was the development of treatment-related adverse events (TRAE; 24%).
 

Drilling down on treatment-related adverse events

As might be expected for cisplatin-ineligible patients, adverse events were higher for patients in cohort 2 than for cohort 1 and led to treatment discontinuation in 16% of patients overall.

TRAEs over grade 3 occurred in 55% of patients. TRAEs of special interest included rash (61% overall; 17% ≥ grade 3), peripheral neuropathy (54% overall; 8% ≥ grade 3), and hyperglycemia (10% overall; 6% ≥ grade 3). Dose reductions, interruptions, and physical therapy were helpful.

Twenty percent of patients with TRAE hyperglycemia had hyperglycemia at baseline, and 30% of TRAEs were in patients with high body mass index (BMI).

There were four treatment-related deaths, all in patients 75 years or older with multiple comorbidities. Three of the four deaths occurred within 30 days of first EV dose in patients with BMI of 30 or greater (acute kidney injury, metabolic acidosis, and multiple organ dysfunction syndrome). The remaining death occurred more than 30 days after the last dose (pneumonitis).
 

Context and caution

The authors concluded that EV produced durable responses in platinum-ineligible patients with la/mUC, including 20% complete responses. Safety was felt to be as expected, given the known toxicities of the agent and the compromised medical condition of the patients studied.

The study discussant, Arlene O. Siefker-Radtke, MD, of the University of Texas MD Anderson Cancer Center, Houston, agreed that EV fills an unmet need, showing impressive responses in patients with visceral, liver, and bone metastases. She agreed that EV should be investigated across the spectrum of urothelial cancer.

Dr. Siefker-Radtke reminded attendees that the FDA package insert for EV described a 48% increase in the area under the concentration-time curve concentration of the MMAE active moiety in patients with mild hepatic impairment and that EV use should be avoided entirely in patients with moderate to severe liver disease.

She speculated whether augmented toxicity in patients with a high BMI could be attributable to clinically occult impaired hepatic function from fatty liver infiltration.

She indicated that clinicians should monitor closely patients with higher BMI and grade 3-4 hyperglycemia or elevated hemoglobin A1c levels and advised holding EV in patients who develop:

• Glucose levels above 250 mg/dL
• Peeling skin or bullous skin lesions. These lesions can be heralded by a diffuse erythematous or papillary rash in the preceding weeks.
• Grade 3 diarrhea or mucosal membrane toxicity of other types.

Notwithstanding concerns about toxicity and the need for monitoring, EV merits continued study in combination with other agents and in additional settings in the clinical spectrum of urothelial cancer. It is an important new option for oncologists caring for patients with urothelial cancer.

The EV-201 study was funded by Seagen. Dr. Balar and Dr. Siefker-Radtke disclosed relationships with Seagen and many other companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Approximately half of all patients with locally advanced or metastatic urothelial cancer (la/mUC) are ineligible to receive cisplatin-based chemotherapy. They face poor outlooks and extremely limited treatment options.

A new study indicates that enfortumab vedotin (EV) can cause major, prolonged responses in most patients in that unfortunate setting.
 

EV is an antibody-drug conjugate directed against nectin-4, an immunoglobulin-like cell adhesion molecule that is highly expressed in UC, obviating the need for testing prior to treatment. It is internalized in malignant cells, with release of the active moiety (monomethyl auristatin E; MMAE). MMAE causes microtubule disruption, with resultant cell-cycle arrest and apoptosis.

EV received accelerated approval from the Food and Drug Administration in December 2019 after publication of the results from cohort 1 of the open-label, single-arm, phase 2 EV-201 study.

Arjun V. Balar, MD, of the Perlmutter Cancer Center at New York University Langone Health, presented results from cohort 2 of EV-201 – the cisplatin-ineligible cohort – at the 2021 Genitourinary Cancer Symposium (Abstract 394).
 

EV in patients ineligible for platinum-based therapy

Patients in cohort 2 of EV-201 had received immune checkpoint inhibitor therapy for la/mUC. They received EV in the FDA-approved dose for cohort 1: 1.25 mg/kg EV on days 1, 8, and 15 of a 28-day cycle.

Patients experienced disease progression during or following their most recent treatment. Patients with more than two neuropathies, active central nervous system metastases, and uncontrolled diabetes mellitus were excluded.

“Platinum ineligible” was defined as a creatinine clearance between 30-59 cm³/min, Eastern Cooperative Oncology Group performance status (ECOG PS) 2, or hearing loss of grade 2 or greater.

The primary endpoint for cohort 2 was confirmed overall response rate (ORR) per RECIST 1.1 by blinded independent central review. Secondary endpoints were duration of response, progression-free survival, overall survival, and safety.

There were 91 patients enrolled. Two patients never received EV treatment because of deterioration after registration. The median treatment duration among the remaining 89 patients was 6.0 months (range, 0.3-24.6).

Impressive results in poor-risk patients

The patients in EV-201 cohort 2 were elderly (median age, 75 years; range, 49-90) with comorbidities. The primary reasons for platinum-ineligibility were creatinine clearance less than 60 mL/min (66%), grade 2 or greater hearing loss (15%), and ECOG PS 2 (7%); 12% of patients met more than one criterion for platinum ineligibility.

The primary tumor site was in the upper urinary tract in 43% of patients, and 79% had visceral metastases, including 24% with liver involvement.

The confirmed ORR was 52% (95% confidence interval, 40.8-62.4), with 20% complete responses. There were responses in all subgroups, including patients with primary tumor sites in the upper tract (ORR, 61%), those with liver metastasis (ORR, 48%), and patients who had not responded to immune checkpoint inhibitors (ORR, 48%).

A total of 88% of patients had some decrease in measurable tumor diameters, generally within a few weeks of treatment initiation (median time to response, 1.8 months). The rapid response to treatment was especially important to patients having cancer-associated pain.

The median progression-free and overall survival durations were 5.8 months (95% CI, 5.0-8.3) and 14.7 months (95% CI, 10.5-18.2), respectively. The median response duration was 10.9 months (95% CI, 5.78-NR). More than 25% of responses extended beyond 12 months.

About 82% of patients in cohort 2 discontinued treatment, most commonly because of disease progression (51%). The second most common reason was the development of treatment-related adverse events (TRAE; 24%).
 

Drilling down on treatment-related adverse events

As might be expected for cisplatin-ineligible patients, adverse events were higher for patients in cohort 2 than for cohort 1 and led to treatment discontinuation in 16% of patients overall.

TRAEs over grade 3 occurred in 55% of patients. TRAEs of special interest included rash (61% overall; 17% ≥ grade 3), peripheral neuropathy (54% overall; 8% ≥ grade 3), and hyperglycemia (10% overall; 6% ≥ grade 3). Dose reductions, interruptions, and physical therapy were helpful.

Twenty percent of patients with TRAE hyperglycemia had hyperglycemia at baseline, and 30% of TRAEs were in patients with high body mass index (BMI).

There were four treatment-related deaths, all in patients 75 years or older with multiple comorbidities. Three of the four deaths occurred within 30 days of first EV dose in patients with BMI of 30 or greater (acute kidney injury, metabolic acidosis, and multiple organ dysfunction syndrome). The remaining death occurred more than 30 days after the last dose (pneumonitis).
 

Context and caution

The authors concluded that EV produced durable responses in platinum-ineligible patients with la/mUC, including 20% complete responses. Safety was felt to be as expected, given the known toxicities of the agent and the compromised medical condition of the patients studied.

The study discussant, Arlene O. Siefker-Radtke, MD, of the University of Texas MD Anderson Cancer Center, Houston, agreed that EV fills an unmet need, showing impressive responses in patients with visceral, liver, and bone metastases. She agreed that EV should be investigated across the spectrum of urothelial cancer.

Dr. Siefker-Radtke reminded attendees that the FDA package insert for EV described a 48% increase in the area under the concentration-time curve concentration of the MMAE active moiety in patients with mild hepatic impairment and that EV use should be avoided entirely in patients with moderate to severe liver disease.

She speculated whether augmented toxicity in patients with a high BMI could be attributable to clinically occult impaired hepatic function from fatty liver infiltration.

She indicated that clinicians should monitor closely patients with higher BMI and grade 3-4 hyperglycemia or elevated hemoglobin A1c levels and advised holding EV in patients who develop:

• Glucose levels above 250 mg/dL
• Peeling skin or bullous skin lesions. These lesions can be heralded by a diffuse erythematous or papillary rash in the preceding weeks.
• Grade 3 diarrhea or mucosal membrane toxicity of other types.

Notwithstanding concerns about toxicity and the need for monitoring, EV merits continued study in combination with other agents and in additional settings in the clinical spectrum of urothelial cancer. It is an important new option for oncologists caring for patients with urothelial cancer.

The EV-201 study was funded by Seagen. Dr. Balar and Dr. Siefker-Radtke disclosed relationships with Seagen and many other companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Loss-of-function mutations in the FLG gene are the strongest known genetic risk factor for developing atopic dermatitis (AD), according to Zelma Chiesa Fuxench, MD.

This gene codes for profilaggrin, a protein, which is then cleaved to form filaggrin, which helps to organize the cytoskeleton of the skin and is an important structural component of the skin. The understanding is that patients who have filaggrin mutations tend to have earlier onset and more persistent disease, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said during the Revolutionizing Atopic Dermatitis virtual symposium.

“Prior studies have shown that mutations in the FLG gene can confer a risk of developed AD that is two- to sevenfold with variants R501X and the 22804del4 frequently described. It is important to note that most of these findings have been described primarily in populations of European descent, with other variants being found in populations of African nation descent, and seem to be more prevalent in populations with early onset disease.”
 

Environmental factors

Other AD-related risk factors that have been previously described in the literature include environmental factors such as climate, diet, breastfeeding, obesity, pollution, tobacco smoke, pet ownership, and microbiome or gut microflora. “The list of culprits is ever increasing,” she said. “However, it’s important to recognize that data to support some of these associations are lacking, and oftentimes, a lot of the results are contradictory.”

As part of the International Study of Asthma and Allergies in Childhood, researchers evaluated the association between climate factors with the 12-month period prevalence rates of symptoms of atopic eczema in children. They found that patients who lived at higher latitudes and those who lived in areas where there were lower mean outdoor temperatures tended to have a higher prevalence of eczema symptoms. Worldwide, they found that symptoms of eczema were also prevalent in areas where there was lower indoor humidity.

“The authors concluded that they can’t really demonstrate a cause and effect, and that while latitude and temperature changes appear to affect the prevalence of eczema, they may do so indirectly, perhaps to changes in behavior and differences in sun exposure,” said Dr. Chiesa Fuxench, who was not involved with the study. “For example, we know that vitamin D is a protective risk factor for AD. Low vitamin D has been associated with more severe disease in some studies. We also know that UV exposure leads to the conversion of filaggrin degradation products such as trans-urocanic acid into cis-urocanic acid, which has been demonstrated to have immunosuppressive effects.”

A systematic review and meta-analysis of nine articles found small associations, which were significant, between being born in the winter (odds ratio, 1.15) and fall (OR, 1.16) and the risk of developing AD, compared with being born in the spring and summer. However, an analysis of satellite-derived data on air temperature across the United States from 1993 to 2011 found that as ambient air temperature increases, so did the risk for an ambulatory visit for AD to physicians from the National Ambulatory Medical Care Survey.

In all areas but the south, the largest number of AD visits occur in the spring. In the south, more AD visits occur in the summer. “This raises the point that we don’t really know everything when it comes to the influence of temperature and climate change on AD,” Dr. Chiesa Fuxench said.

Several maternal and neonatal risk factors for AD have been described in the literature, including the effect of prenatal exposure to antibiotics. In one large analysis, investigators assessed the association among 18-month-old children in the Danish National Birth Cohort, which included 62,560 mother-child pairs. They found that prenatal antibiotic use was associated with an increased odds of AD among children born to atopic mothers but only when used during all three trimesters (adjusted OR, 1.45). When they further stratified these analyses by type of birth (vaginal versus C-section), the association persisted in both groups, but was stronger among those delivered by C-section.

 

Probiotics

The role of probiotics to reduce the risk for AD has also been investigated. “We do know that probiotics could potentially be helpful, and it is often a readily available intervention,” Dr. Chiesa Fuxench said. “But the question still is how and when to supplement.”

In a systematic review and meta-analysis, researchers examined supplementation with probiotics given to breastfeeding mothers, pregnant mothers, or directly given to infants, and the risk of developing AD up to 18 months of age. They found that overall, probiotic exposure resulted in decreased risk of developing AD. In stratified analyses, the strongest association was observed for those who received probiotics during their pregnancy, during breastfeeding, and as an infant, which conferred about a 25% reduced risk.
 

Antibiotic exposure

What about early-life exposure to antibiotics on one’s risk for developing AD? A meta-analysis of 22 studies found that children who had been exposed to antibiotics during the first 2 years of life had an increased risk of eczema (OR, 1.26), compared with children who had not been exposed during the same period of time. “Interesting hypotheses can be generated from this study,” she said. “Perhaps future steps should focus on the impact of antibiotic exposure, the gut microbiome, and maternal risk factors for AD.”

In a separate study that supported these findings, researchers evaluated the association between the use of acid-suppressive medications and antibiotics during infancy and the development of allergic disease in early childhood. They found that exposure to either of these medications during the first six months of infancy resulted in a mild increased risk of developing AD, and concluded that they should be used during infancy only in situations of clear clinical benefit. “We should be good stewards of antibiotic use, in particular due to concern for antibiotic resistance in the population overall,” Dr. Chiesa Fuxench said.
 

Prevention strategies

Several AD prevention strategies have also been described in the medical literature, including the use of daily emollients during infancy. In a multicenter trial carried out in the United Kingdom, researchers tested whether daily use of emollient in the first year of life could prevent eczema in high-risk children, which was defined as having at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma. The primary outcome was eczema at age 2 years. The researchers found no evidence to suggest that daily emollient use during the first year of life prevents eczema.

Another study, the PreventADALL trial of 2,397 infants, consisted of four treatment arms: a control group advised to follow national guidelines on infant nutrition; a skin intervention group that was asked to use skin emollients, a food intervention group with early introduction of peanut, cow’s milk, wheat, and egg, and a combined skin and food intervention. The investigators found no difference in the risk reduction of developing AD among patients who were treated with skin emollients or early complementary feeding, and concluded that these types of interventions should not be considered as interventions to prevent AD in this cohort of patients.

However, Dr. Chiesa Fuxench emphasized that emollients and moisturizers are an important part of the treatment regimen for AD patients. A Cochrane systematic review of nearly 80 randomized, controlled trials evaluating the use of emollients in eczema found that most moisturizers showed some beneficial effects in addition to active treatment, including prolonging the time to flare, reducing the number of flares, and reducing the amount of topical corticosteroids used.

For treatment, Dr. Chiesa Fuxench recommends a proactive approach focused on short-term induction therapy with intensive topical anti-inflammatories until the affected area is almost healed, followed by maintenance therapy that involves use of a long-term, low- to mid-potency steroid or a topical calcineurin inhibitor to previously affected areas. “These interventions have been shown to decrease the risk of recurrence and can shorten the treatment duration in the event of a flare,” she said.

She also favors a time-contingent approach to treating patients with AD. “As physicians, we tend to do our visits more as symptom contingent, which means when a patient is flaring. This reinforces the view that this is a difficult disease to treat, and that there is no hope,” she pointed out. But for chronic diseases, she added, “a time-contingent approach with appointments at set intervals leads to a different perception. It can result in better compliance, because skin care might be performed more regularly. It’s analogous to when you know you’re going to see the dentist so you floss more regularly the week before your appointment. There also seems to be less pressure on physicians and patients because you are seeing each other more frequently; you can talk more openly about what’s working and what’s not.”

Dr. Chiesa Fuxench reported having no disclosures relevant to her presentation.

dbrunk@mdedge.com

Loss-of-function mutations in the FLG gene are the strongest known genetic risk factor for developing atopic dermatitis (AD), according to Zelma Chiesa Fuxench, MD.

This gene codes for profilaggrin, a protein, which is then cleaved to form filaggrin, which helps to organize the cytoskeleton of the skin and is an important structural component of the skin. The understanding is that patients who have filaggrin mutations tend to have earlier onset and more persistent disease, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said during the Revolutionizing Atopic Dermatitis virtual symposium.

“Prior studies have shown that mutations in the FLG gene can confer a risk of developed AD that is two- to sevenfold with variants R501X and the 22804del4 frequently described. It is important to note that most of these findings have been described primarily in populations of European descent, with other variants being found in populations of African nation descent, and seem to be more prevalent in populations with early onset disease.”
 

Environmental factors

Other AD-related risk factors that have been previously described in the literature include environmental factors such as climate, diet, breastfeeding, obesity, pollution, tobacco smoke, pet ownership, and microbiome or gut microflora. “The list of culprits is ever increasing,” she said. “However, it’s important to recognize that data to support some of these associations are lacking, and oftentimes, a lot of the results are contradictory.”

As part of the International Study of Asthma and Allergies in Childhood, researchers evaluated the association between climate factors with the 12-month period prevalence rates of symptoms of atopic eczema in children. They found that patients who lived at higher latitudes and those who lived in areas where there were lower mean outdoor temperatures tended to have a higher prevalence of eczema symptoms. Worldwide, they found that symptoms of eczema were also prevalent in areas where there was lower indoor humidity.

“The authors concluded that they can’t really demonstrate a cause and effect, and that while latitude and temperature changes appear to affect the prevalence of eczema, they may do so indirectly, perhaps to changes in behavior and differences in sun exposure,” said Dr. Chiesa Fuxench, who was not involved with the study. “For example, we know that vitamin D is a protective risk factor for AD. Low vitamin D has been associated with more severe disease in some studies. We also know that UV exposure leads to the conversion of filaggrin degradation products such as trans-urocanic acid into cis-urocanic acid, which has been demonstrated to have immunosuppressive effects.”

A systematic review and meta-analysis of nine articles found small associations, which were significant, between being born in the winter (odds ratio, 1.15) and fall (OR, 1.16) and the risk of developing AD, compared with being born in the spring and summer. However, an analysis of satellite-derived data on air temperature across the United States from 1993 to 2011 found that as ambient air temperature increases, so did the risk for an ambulatory visit for AD to physicians from the National Ambulatory Medical Care Survey.

In all areas but the south, the largest number of AD visits occur in the spring. In the south, more AD visits occur in the summer. “This raises the point that we don’t really know everything when it comes to the influence of temperature and climate change on AD,” Dr. Chiesa Fuxench said.

Several maternal and neonatal risk factors for AD have been described in the literature, including the effect of prenatal exposure to antibiotics. In one large analysis, investigators assessed the association among 18-month-old children in the Danish National Birth Cohort, which included 62,560 mother-child pairs. They found that prenatal antibiotic use was associated with an increased odds of AD among children born to atopic mothers but only when used during all three trimesters (adjusted OR, 1.45). When they further stratified these analyses by type of birth (vaginal versus C-section), the association persisted in both groups, but was stronger among those delivered by C-section.

 

Probiotics

The role of probiotics to reduce the risk for AD has also been investigated. “We do know that probiotics could potentially be helpful, and it is often a readily available intervention,” Dr. Chiesa Fuxench said. “But the question still is how and when to supplement.”

In a systematic review and meta-analysis, researchers examined supplementation with probiotics given to breastfeeding mothers, pregnant mothers, or directly given to infants, and the risk of developing AD up to 18 months of age. They found that overall, probiotic exposure resulted in decreased risk of developing AD. In stratified analyses, the strongest association was observed for those who received probiotics during their pregnancy, during breastfeeding, and as an infant, which conferred about a 25% reduced risk.
 

Antibiotic exposure

What about early-life exposure to antibiotics on one’s risk for developing AD? A meta-analysis of 22 studies found that children who had been exposed to antibiotics during the first 2 years of life had an increased risk of eczema (OR, 1.26), compared with children who had not been exposed during the same period of time. “Interesting hypotheses can be generated from this study,” she said. “Perhaps future steps should focus on the impact of antibiotic exposure, the gut microbiome, and maternal risk factors for AD.”

In a separate study that supported these findings, researchers evaluated the association between the use of acid-suppressive medications and antibiotics during infancy and the development of allergic disease in early childhood. They found that exposure to either of these medications during the first six months of infancy resulted in a mild increased risk of developing AD, and concluded that they should be used during infancy only in situations of clear clinical benefit. “We should be good stewards of antibiotic use, in particular due to concern for antibiotic resistance in the population overall,” Dr. Chiesa Fuxench said.
 

Prevention strategies

Several AD prevention strategies have also been described in the medical literature, including the use of daily emollients during infancy. In a multicenter trial carried out in the United Kingdom, researchers tested whether daily use of emollient in the first year of life could prevent eczema in high-risk children, which was defined as having at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma. The primary outcome was eczema at age 2 years. The researchers found no evidence to suggest that daily emollient use during the first year of life prevents eczema.

Another study, the PreventADALL trial of 2,397 infants, consisted of four treatment arms: a control group advised to follow national guidelines on infant nutrition; a skin intervention group that was asked to use skin emollients, a food intervention group with early introduction of peanut, cow’s milk, wheat, and egg, and a combined skin and food intervention. The investigators found no difference in the risk reduction of developing AD among patients who were treated with skin emollients or early complementary feeding, and concluded that these types of interventions should not be considered as interventions to prevent AD in this cohort of patients.

However, Dr. Chiesa Fuxench emphasized that emollients and moisturizers are an important part of the treatment regimen for AD patients. A Cochrane systematic review of nearly 80 randomized, controlled trials evaluating the use of emollients in eczema found that most moisturizers showed some beneficial effects in addition to active treatment, including prolonging the time to flare, reducing the number of flares, and reducing the amount of topical corticosteroids used.

For treatment, Dr. Chiesa Fuxench recommends a proactive approach focused on short-term induction therapy with intensive topical anti-inflammatories until the affected area is almost healed, followed by maintenance therapy that involves use of a long-term, low- to mid-potency steroid or a topical calcineurin inhibitor to previously affected areas. “These interventions have been shown to decrease the risk of recurrence and can shorten the treatment duration in the event of a flare,” she said.

She also favors a time-contingent approach to treating patients with AD. “As physicians, we tend to do our visits more as symptom contingent, which means when a patient is flaring. This reinforces the view that this is a difficult disease to treat, and that there is no hope,” she pointed out. But for chronic diseases, she added, “a time-contingent approach with appointments at set intervals leads to a different perception. It can result in better compliance, because skin care might be performed more regularly. It’s analogous to when you know you’re going to see the dentist so you floss more regularly the week before your appointment. There also seems to be less pressure on physicians and patients because you are seeing each other more frequently; you can talk more openly about what’s working and what’s not.”

Dr. Chiesa Fuxench reported having no disclosures relevant to her presentation.

dbrunk@mdedge.com

Loss-of-function mutations in the FLG gene are the strongest known genetic risk factor for developing atopic dermatitis (AD), according to Zelma Chiesa Fuxench, MD.

This gene codes for profilaggrin, a protein, which is then cleaved to form filaggrin, which helps to organize the cytoskeleton of the skin and is an important structural component of the skin. The understanding is that patients who have filaggrin mutations tend to have earlier onset and more persistent disease, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said during the Revolutionizing Atopic Dermatitis virtual symposium.

“Prior studies have shown that mutations in the FLG gene can confer a risk of developed AD that is two- to sevenfold with variants R501X and the 22804del4 frequently described. It is important to note that most of these findings have been described primarily in populations of European descent, with other variants being found in populations of African nation descent, and seem to be more prevalent in populations with early onset disease.”
 

Environmental factors

Other AD-related risk factors that have been previously described in the literature include environmental factors such as climate, diet, breastfeeding, obesity, pollution, tobacco smoke, pet ownership, and microbiome or gut microflora. “The list of culprits is ever increasing,” she said. “However, it’s important to recognize that data to support some of these associations are lacking, and oftentimes, a lot of the results are contradictory.”

As part of the International Study of Asthma and Allergies in Childhood, researchers evaluated the association between climate factors with the 12-month period prevalence rates of symptoms of atopic eczema in children. They found that patients who lived at higher latitudes and those who lived in areas where there were lower mean outdoor temperatures tended to have a higher prevalence of eczema symptoms. Worldwide, they found that symptoms of eczema were also prevalent in areas where there was lower indoor humidity.

“The authors concluded that they can’t really demonstrate a cause and effect, and that while latitude and temperature changes appear to affect the prevalence of eczema, they may do so indirectly, perhaps to changes in behavior and differences in sun exposure,” said Dr. Chiesa Fuxench, who was not involved with the study. “For example, we know that vitamin D is a protective risk factor for AD. Low vitamin D has been associated with more severe disease in some studies. We also know that UV exposure leads to the conversion of filaggrin degradation products such as trans-urocanic acid into cis-urocanic acid, which has been demonstrated to have immunosuppressive effects.”

A systematic review and meta-analysis of nine articles found small associations, which were significant, between being born in the winter (odds ratio, 1.15) and fall (OR, 1.16) and the risk of developing AD, compared with being born in the spring and summer. However, an analysis of satellite-derived data on air temperature across the United States from 1993 to 2011 found that as ambient air temperature increases, so did the risk for an ambulatory visit for AD to physicians from the National Ambulatory Medical Care Survey.

In all areas but the south, the largest number of AD visits occur in the spring. In the south, more AD visits occur in the summer. “This raises the point that we don’t really know everything when it comes to the influence of temperature and climate change on AD,” Dr. Chiesa Fuxench said.

Several maternal and neonatal risk factors for AD have been described in the literature, including the effect of prenatal exposure to antibiotics. In one large analysis, investigators assessed the association among 18-month-old children in the Danish National Birth Cohort, which included 62,560 mother-child pairs. They found that prenatal antibiotic use was associated with an increased odds of AD among children born to atopic mothers but only when used during all three trimesters (adjusted OR, 1.45). When they further stratified these analyses by type of birth (vaginal versus C-section), the association persisted in both groups, but was stronger among those delivered by C-section.

 

Probiotics

The role of probiotics to reduce the risk for AD has also been investigated. “We do know that probiotics could potentially be helpful, and it is often a readily available intervention,” Dr. Chiesa Fuxench said. “But the question still is how and when to supplement.”

In a systematic review and meta-analysis, researchers examined supplementation with probiotics given to breastfeeding mothers, pregnant mothers, or directly given to infants, and the risk of developing AD up to 18 months of age. They found that overall, probiotic exposure resulted in decreased risk of developing AD. In stratified analyses, the strongest association was observed for those who received probiotics during their pregnancy, during breastfeeding, and as an infant, which conferred about a 25% reduced risk.
 

Antibiotic exposure

What about early-life exposure to antibiotics on one’s risk for developing AD? A meta-analysis of 22 studies found that children who had been exposed to antibiotics during the first 2 years of life had an increased risk of eczema (OR, 1.26), compared with children who had not been exposed during the same period of time. “Interesting hypotheses can be generated from this study,” she said. “Perhaps future steps should focus on the impact of antibiotic exposure, the gut microbiome, and maternal risk factors for AD.”

In a separate study that supported these findings, researchers evaluated the association between the use of acid-suppressive medications and antibiotics during infancy and the development of allergic disease in early childhood. They found that exposure to either of these medications during the first six months of infancy resulted in a mild increased risk of developing AD, and concluded that they should be used during infancy only in situations of clear clinical benefit. “We should be good stewards of antibiotic use, in particular due to concern for antibiotic resistance in the population overall,” Dr. Chiesa Fuxench said.
 

Prevention strategies

Several AD prevention strategies have also been described in the medical literature, including the use of daily emollients during infancy. In a multicenter trial carried out in the United Kingdom, researchers tested whether daily use of emollient in the first year of life could prevent eczema in high-risk children, which was defined as having at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma. The primary outcome was eczema at age 2 years. The researchers found no evidence to suggest that daily emollient use during the first year of life prevents eczema.

Another study, the PreventADALL trial of 2,397 infants, consisted of four treatment arms: a control group advised to follow national guidelines on infant nutrition; a skin intervention group that was asked to use skin emollients, a food intervention group with early introduction of peanut, cow’s milk, wheat, and egg, and a combined skin and food intervention. The investigators found no difference in the risk reduction of developing AD among patients who were treated with skin emollients or early complementary feeding, and concluded that these types of interventions should not be considered as interventions to prevent AD in this cohort of patients.

However, Dr. Chiesa Fuxench emphasized that emollients and moisturizers are an important part of the treatment regimen for AD patients. A Cochrane systematic review of nearly 80 randomized, controlled trials evaluating the use of emollients in eczema found that most moisturizers showed some beneficial effects in addition to active treatment, including prolonging the time to flare, reducing the number of flares, and reducing the amount of topical corticosteroids used.

For treatment, Dr. Chiesa Fuxench recommends a proactive approach focused on short-term induction therapy with intensive topical anti-inflammatories until the affected area is almost healed, followed by maintenance therapy that involves use of a long-term, low- to mid-potency steroid or a topical calcineurin inhibitor to previously affected areas. “These interventions have been shown to decrease the risk of recurrence and can shorten the treatment duration in the event of a flare,” she said.

She also favors a time-contingent approach to treating patients with AD. “As physicians, we tend to do our visits more as symptom contingent, which means when a patient is flaring. This reinforces the view that this is a difficult disease to treat, and that there is no hope,” she pointed out. But for chronic diseases, she added, “a time-contingent approach with appointments at set intervals leads to a different perception. It can result in better compliance, because skin care might be performed more regularly. It’s analogous to when you know you’re going to see the dentist so you floss more regularly the week before your appointment. There also seems to be less pressure on physicians and patients because you are seeing each other more frequently; you can talk more openly about what’s working and what’s not.”

Dr. Chiesa Fuxench reported having no disclosures relevant to her presentation.

dbrunk@mdedge.com

A novel educational and personalized physical therapy program is showing signs that it may help people to mitigate their risk of developing knee osteoarthritis after an injury.

Speaking at the Canadian Arthritis Research Conference: Research with Impact, Jackie Whittaker, PhD, observed that initial work from the Stop Osteoarthritis (SOAR) program showed that meaningful improvements in knee-related quality of life and improvement in participants’ perceived self-management could be achieved.

Further feasibility work is ongoing and a proof-of-concept and phase 3 study need to follow, but the research suggests the approach could potentially help to reduce the substantial burden of managing people who develop posttraumatic OA (PTOA) of the knee.
 

Understanding the post–knee injury period

“Despite the progress that we’ve made in preventing injuries, and reducing disability in people with osteoarthritis, we lack good evidence about what should be done in the period between joint injury and the onset of osteoarthritis to delay or halt that onset,” Dr. Whittaker said at the virtual meeting, which was sponsored by the Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Musculoskeletal Health and Arthritis.

That’s where the SOAR program comes in. For the past 8 years, Dr. Whittaker, an assistant professor in the department of physical therapy at the University of British Columbia in Vancouver and affiliated to Arthritis Research Canada, and collaborators have been looking into the post–knee injury period with the aim of developing an intervention that could potentially reduce the risk of OA further down the line.

Much work has gone into understanding the burden and risk factors for PTOA of the knee in order to know who exactly to target with the intervention and what the risk factors may be for the subsequent development of OA .

This research suggests that knee injuries are most commonly seen in people aged between 15 and 35 years who participated in sporting or other physical activities, so this is the target population for the SOAR intervention.

Broadly speaking, sustaining any knee injury is associated with a sixfold increased risk for subsequent PTOA, Dr. Whittaker observed.

“Despite the fact that ACL [anterior cruciate ligament] and meniscal tears get all the press, collateral ligament injury are still associated with about a fivefold increased risk of osteoarthritis, and therefore maybe shouldn’t be so easily dismissed as an important target,” Dr. Whittaker said.

Postinjury risk factors for OA

“Basically, what all prevention comes down to is our understanding of risk factors and our ability to be able to modify them,” she said.

KatarzynaBialasiewicz/Thinkstock

Previous joint injury is one of the strongest and most established modifiable risk factors for developing knee OA, and Dr. Whittaker and associates have performed two small but “mighty” cohort studies comparing people who have and have not had a knee injury. These two studies have looked at different time periods following injury to see if they could first identify the risk factors for developing OA some 3-10 years later, and then to look more closely at some of those risk factors in first 2 years after injury with a view to targeting these with an intervention.

Data analysis of the latter study is still ongoing but have shown that, among injured subjects, there is a fear of movement and reinjury, knee strength is weaker in both injured and uninjured knees, and they are perhaps less physically active than those who have not been injured.

“Going into those two studies, we knew that this group of people already [had an] increased risk for osteoarthritis because they had an injury. However, what we found is that it looks like this risk may be compounded through adiposity [and] deficits in muscle strength and physical inactivity, which are associated with pain, stiffness, lack of confidence, and at times, unrealistic expectations and poor pacing,” Dr. Whittaker said.

She added: “It also looks like some of these additional factors and particular adiposity or fat gain may develop after injury, which would then give us a concrete target for delaying or halting the onset of osteoarthritis in the segment of the population.”
 

SOAR program components

The SOAR program intervention is an 8-week, physiotherapist-led program that targets people aged 15-35 years who have had a sport-related knee injury and received formal care. All of this is conducted via videoconferencing software and starts off with a 2-hour group education session or “knee camp.” This is followed by a one-on-one assessment with a physiotherapist and setting exercise and physical activity goals for the week.

Participants then undertake their personalized exercise and physical activity programs at home and track their progress using an activity monitor. They can participate in an optional weekly group exercise class and receive weekly one-on-one physiotherapy counseling where goals can be modified and any issues participants might be experiencing solved.

According to Dr. Whittaker, “this program really aims to increase participants capacity to manage their elevated risk for osteoarthritis, and we’re doing this by also optimizing their knee muscle function and their physical activity participation.”

While the knee camp enables a therapeutic alliance to be formed between participants and their physiotherapists, the weekly group classes provide social support and an opportunity to interact with others.

“Brief action planning builds self-efficacy [and] promotes autonomous health behaviors, while goal setting and tracking provide accountability, feedback about progress, and facilitated adherence,” she said.

And finally, regular communication with a physiotherapist in the program ensures timely support to learn how to navigate obstacles and helps participants to learn how to deal with their own knee health.

Testing the feasibility of the SOAR program intervention

“Currently we are smack in the middle of our feasibility study,” Dr. Whittaker said. So far, four physiotherapists have been trained to deliver an abridged, 4-week version of the program, and 25 of a planned 30 participants have been enrolled.

Results seem promising so far. No participants have dropped out of the program to date and attendance is at 100%.

“Based on data from the first 12 participants who completed the program, we are meeting all of our ‘a priori’ program benchmarks,” Dr. Whittaker said.

“It is very early days,” she emphasized, but “we are excited to see clinically important improvements in both knee-related quality of life and perceived self-management.

“This gives us some confidence that maybe all this time that we’ve put into developing our intervention is paying off, but obviously time will tell if we’re headed in the right direction,” she said. “Perhaps in time, we may be able to look at whether or not the individuals that participated in that program have fewer symptoms of OA disease. But that will obviously take us a few years before we’ll be able to get to that point.”

Dr. Whittaker acknowledged receiving funding for the SOAR program from the Arthritis Society, the Michael Smith Foundation for Health Research, BC SUPPORT Unit, and the Canadian Musculoskeletal Rehab Network.

A novel educational and personalized physical therapy program is showing signs that it may help people to mitigate their risk of developing knee osteoarthritis after an injury.

Speaking at the Canadian Arthritis Research Conference: Research with Impact, Jackie Whittaker, PhD, observed that initial work from the Stop Osteoarthritis (SOAR) program showed that meaningful improvements in knee-related quality of life and improvement in participants’ perceived self-management could be achieved.

Further feasibility work is ongoing and a proof-of-concept and phase 3 study need to follow, but the research suggests the approach could potentially help to reduce the substantial burden of managing people who develop posttraumatic OA (PTOA) of the knee.
 

Understanding the post–knee injury period

“Despite the progress that we’ve made in preventing injuries, and reducing disability in people with osteoarthritis, we lack good evidence about what should be done in the period between joint injury and the onset of osteoarthritis to delay or halt that onset,” Dr. Whittaker said at the virtual meeting, which was sponsored by the Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Musculoskeletal Health and Arthritis.

That’s where the SOAR program comes in. For the past 8 years, Dr. Whittaker, an assistant professor in the department of physical therapy at the University of British Columbia in Vancouver and affiliated to Arthritis Research Canada, and collaborators have been looking into the post–knee injury period with the aim of developing an intervention that could potentially reduce the risk of OA further down the line.

Much work has gone into understanding the burden and risk factors for PTOA of the knee in order to know who exactly to target with the intervention and what the risk factors may be for the subsequent development of OA .

This research suggests that knee injuries are most commonly seen in people aged between 15 and 35 years who participated in sporting or other physical activities, so this is the target population for the SOAR intervention.

Broadly speaking, sustaining any knee injury is associated with a sixfold increased risk for subsequent PTOA, Dr. Whittaker observed.

“Despite the fact that ACL [anterior cruciate ligament] and meniscal tears get all the press, collateral ligament injury are still associated with about a fivefold increased risk of osteoarthritis, and therefore maybe shouldn’t be so easily dismissed as an important target,” Dr. Whittaker said.

Postinjury risk factors for OA

“Basically, what all prevention comes down to is our understanding of risk factors and our ability to be able to modify them,” she said.

KatarzynaBialasiewicz/Thinkstock

Previous joint injury is one of the strongest and most established modifiable risk factors for developing knee OA, and Dr. Whittaker and associates have performed two small but “mighty” cohort studies comparing people who have and have not had a knee injury. These two studies have looked at different time periods following injury to see if they could first identify the risk factors for developing OA some 3-10 years later, and then to look more closely at some of those risk factors in first 2 years after injury with a view to targeting these with an intervention.

Data analysis of the latter study is still ongoing but have shown that, among injured subjects, there is a fear of movement and reinjury, knee strength is weaker in both injured and uninjured knees, and they are perhaps less physically active than those who have not been injured.

“Going into those two studies, we knew that this group of people already [had an] increased risk for osteoarthritis because they had an injury. However, what we found is that it looks like this risk may be compounded through adiposity [and] deficits in muscle strength and physical inactivity, which are associated with pain, stiffness, lack of confidence, and at times, unrealistic expectations and poor pacing,” Dr. Whittaker said.

She added: “It also looks like some of these additional factors and particular adiposity or fat gain may develop after injury, which would then give us a concrete target for delaying or halting the onset of osteoarthritis in the segment of the population.”
 

SOAR program components

The SOAR program intervention is an 8-week, physiotherapist-led program that targets people aged 15-35 years who have had a sport-related knee injury and received formal care. All of this is conducted via videoconferencing software and starts off with a 2-hour group education session or “knee camp.” This is followed by a one-on-one assessment with a physiotherapist and setting exercise and physical activity goals for the week.

Participants then undertake their personalized exercise and physical activity programs at home and track their progress using an activity monitor. They can participate in an optional weekly group exercise class and receive weekly one-on-one physiotherapy counseling where goals can be modified and any issues participants might be experiencing solved.

According to Dr. Whittaker, “this program really aims to increase participants capacity to manage their elevated risk for osteoarthritis, and we’re doing this by also optimizing their knee muscle function and their physical activity participation.”

While the knee camp enables a therapeutic alliance to be formed between participants and their physiotherapists, the weekly group classes provide social support and an opportunity to interact with others.

“Brief action planning builds self-efficacy [and] promotes autonomous health behaviors, while goal setting and tracking provide accountability, feedback about progress, and facilitated adherence,” she said.

And finally, regular communication with a physiotherapist in the program ensures timely support to learn how to navigate obstacles and helps participants to learn how to deal with their own knee health.

Testing the feasibility of the SOAR program intervention

“Currently we are smack in the middle of our feasibility study,” Dr. Whittaker said. So far, four physiotherapists have been trained to deliver an abridged, 4-week version of the program, and 25 of a planned 30 participants have been enrolled.

Results seem promising so far. No participants have dropped out of the program to date and attendance is at 100%.

“Based on data from the first 12 participants who completed the program, we are meeting all of our ‘a priori’ program benchmarks,” Dr. Whittaker said.

“It is very early days,” she emphasized, but “we are excited to see clinically important improvements in both knee-related quality of life and perceived self-management.

“This gives us some confidence that maybe all this time that we’ve put into developing our intervention is paying off, but obviously time will tell if we’re headed in the right direction,” she said. “Perhaps in time, we may be able to look at whether or not the individuals that participated in that program have fewer symptoms of OA disease. But that will obviously take us a few years before we’ll be able to get to that point.”

Dr. Whittaker acknowledged receiving funding for the SOAR program from the Arthritis Society, the Michael Smith Foundation for Health Research, BC SUPPORT Unit, and the Canadian Musculoskeletal Rehab Network.

A novel educational and personalized physical therapy program is showing signs that it may help people to mitigate their risk of developing knee osteoarthritis after an injury.

Speaking at the Canadian Arthritis Research Conference: Research with Impact, Jackie Whittaker, PhD, observed that initial work from the Stop Osteoarthritis (SOAR) program showed that meaningful improvements in knee-related quality of life and improvement in participants’ perceived self-management could be achieved.

Further feasibility work is ongoing and a proof-of-concept and phase 3 study need to follow, but the research suggests the approach could potentially help to reduce the substantial burden of managing people who develop posttraumatic OA (PTOA) of the knee.
 

Understanding the post–knee injury period

“Despite the progress that we’ve made in preventing injuries, and reducing disability in people with osteoarthritis, we lack good evidence about what should be done in the period between joint injury and the onset of osteoarthritis to delay or halt that onset,” Dr. Whittaker said at the virtual meeting, which was sponsored by the Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Musculoskeletal Health and Arthritis.

That’s where the SOAR program comes in. For the past 8 years, Dr. Whittaker, an assistant professor in the department of physical therapy at the University of British Columbia in Vancouver and affiliated to Arthritis Research Canada, and collaborators have been looking into the post–knee injury period with the aim of developing an intervention that could potentially reduce the risk of OA further down the line.

Much work has gone into understanding the burden and risk factors for PTOA of the knee in order to know who exactly to target with the intervention and what the risk factors may be for the subsequent development of OA .

This research suggests that knee injuries are most commonly seen in people aged between 15 and 35 years who participated in sporting or other physical activities, so this is the target population for the SOAR intervention.

Broadly speaking, sustaining any knee injury is associated with a sixfold increased risk for subsequent PTOA, Dr. Whittaker observed.

“Despite the fact that ACL [anterior cruciate ligament] and meniscal tears get all the press, collateral ligament injury are still associated with about a fivefold increased risk of osteoarthritis, and therefore maybe shouldn’t be so easily dismissed as an important target,” Dr. Whittaker said.

Postinjury risk factors for OA

“Basically, what all prevention comes down to is our understanding of risk factors and our ability to be able to modify them,” she said.

KatarzynaBialasiewicz/Thinkstock

Previous joint injury is one of the strongest and most established modifiable risk factors for developing knee OA, and Dr. Whittaker and associates have performed two small but “mighty” cohort studies comparing people who have and have not had a knee injury. These two studies have looked at different time periods following injury to see if they could first identify the risk factors for developing OA some 3-10 years later, and then to look more closely at some of those risk factors in first 2 years after injury with a view to targeting these with an intervention.

Data analysis of the latter study is still ongoing but have shown that, among injured subjects, there is a fear of movement and reinjury, knee strength is weaker in both injured and uninjured knees, and they are perhaps less physically active than those who have not been injured.

“Going into those two studies, we knew that this group of people already [had an] increased risk for osteoarthritis because they had an injury. However, what we found is that it looks like this risk may be compounded through adiposity [and] deficits in muscle strength and physical inactivity, which are associated with pain, stiffness, lack of confidence, and at times, unrealistic expectations and poor pacing,” Dr. Whittaker said.

She added: “It also looks like some of these additional factors and particular adiposity or fat gain may develop after injury, which would then give us a concrete target for delaying or halting the onset of osteoarthritis in the segment of the population.”
 

SOAR program components

The SOAR program intervention is an 8-week, physiotherapist-led program that targets people aged 15-35 years who have had a sport-related knee injury and received formal care. All of this is conducted via videoconferencing software and starts off with a 2-hour group education session or “knee camp.” This is followed by a one-on-one assessment with a physiotherapist and setting exercise and physical activity goals for the week.

Participants then undertake their personalized exercise and physical activity programs at home and track their progress using an activity monitor. They can participate in an optional weekly group exercise class and receive weekly one-on-one physiotherapy counseling where goals can be modified and any issues participants might be experiencing solved.

According to Dr. Whittaker, “this program really aims to increase participants capacity to manage their elevated risk for osteoarthritis, and we’re doing this by also optimizing their knee muscle function and their physical activity participation.”

While the knee camp enables a therapeutic alliance to be formed between participants and their physiotherapists, the weekly group classes provide social support and an opportunity to interact with others.

“Brief action planning builds self-efficacy [and] promotes autonomous health behaviors, while goal setting and tracking provide accountability, feedback about progress, and facilitated adherence,” she said.

And finally, regular communication with a physiotherapist in the program ensures timely support to learn how to navigate obstacles and helps participants to learn how to deal with their own knee health.

Testing the feasibility of the SOAR program intervention

“Currently we are smack in the middle of our feasibility study,” Dr. Whittaker said. So far, four physiotherapists have been trained to deliver an abridged, 4-week version of the program, and 25 of a planned 30 participants have been enrolled.

Results seem promising so far. No participants have dropped out of the program to date and attendance is at 100%.

“Based on data from the first 12 participants who completed the program, we are meeting all of our ‘a priori’ program benchmarks,” Dr. Whittaker said.

“It is very early days,” she emphasized, but “we are excited to see clinically important improvements in both knee-related quality of life and perceived self-management.

“This gives us some confidence that maybe all this time that we’ve put into developing our intervention is paying off, but obviously time will tell if we’re headed in the right direction,” she said. “Perhaps in time, we may be able to look at whether or not the individuals that participated in that program have fewer symptoms of OA disease. But that will obviously take us a few years before we’ll be able to get to that point.”

Dr. Whittaker acknowledged receiving funding for the SOAR program from the Arthritis Society, the Michael Smith Foundation for Health Research, BC SUPPORT Unit, and the Canadian Musculoskeletal Rehab Network.