Background: Clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine (Colcrys) in an orally administered potent anti-inflammatory that is currently used to treat gout and pericarditis.

The primary endpoint occurred in 5.5% of patients in the colchicine group and 7.1% of those in the placebo group (hazard ratio, 0.77). This was largely because of a decreased incidence of stroke in the colchicine group compared to placebo (0.2% vs 0.8%) and decreased urgent hospitalizations for unstable angina leading to revascularization (1.1% vs 2.1%).

Nausea was more common in the colchicine group as well as pneumonia which was reported as a serious adverse event (0.9% compared to 0.4% in placebo).

Limitations included short follow-­up and significant exclusion criteria.

Bottom line: In patients following a recent myocardial infraction, the use of low-dose colchicine at 0.5 mg daily led to a significantly lower percentage of ischemic cardiovascular events compared to placebo.

Citation: Tardif JC et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019 Dec 26;381:2497-505.

Dr. Qazi is assistant professor in the division of hospital medicine, Loyola University Medical Center, Maywood, Ill.

Background: Clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine (Colcrys) in an orally administered potent anti-inflammatory that is currently used to treat gout and pericarditis.

The primary endpoint occurred in 5.5% of patients in the colchicine group and 7.1% of those in the placebo group (hazard ratio, 0.77). This was largely because of a decreased incidence of stroke in the colchicine group compared to placebo (0.2% vs 0.8%) and decreased urgent hospitalizations for unstable angina leading to revascularization (1.1% vs 2.1%).

Nausea was more common in the colchicine group as well as pneumonia which was reported as a serious adverse event (0.9% compared to 0.4% in placebo).

Limitations included short follow-­up and significant exclusion criteria.

Bottom line: In patients following a recent myocardial infraction, the use of low-dose colchicine at 0.5 mg daily led to a significantly lower percentage of ischemic cardiovascular events compared to placebo.

Citation: Tardif JC et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019 Dec 26;381:2497-505.

Dr. Qazi is assistant professor in the division of hospital medicine, Loyola University Medical Center, Maywood, Ill.

Background: Clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine (Colcrys) in an orally administered potent anti-inflammatory that is currently used to treat gout and pericarditis.

The primary endpoint occurred in 5.5% of patients in the colchicine group and 7.1% of those in the placebo group (hazard ratio, 0.77). This was largely because of a decreased incidence of stroke in the colchicine group compared to placebo (0.2% vs 0.8%) and decreased urgent hospitalizations for unstable angina leading to revascularization (1.1% vs 2.1%).

Nausea was more common in the colchicine group as well as pneumonia which was reported as a serious adverse event (0.9% compared to 0.4% in placebo).

Limitations included short follow-­up and significant exclusion criteria.

Bottom line: In patients following a recent myocardial infraction, the use of low-dose colchicine at 0.5 mg daily led to a significantly lower percentage of ischemic cardiovascular events compared to placebo.

Citation: Tardif JC et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019 Dec 26;381:2497-505.

Dr. Qazi is assistant professor in the division of hospital medicine, Loyola University Medical Center, Maywood, Ill.

”Good evening,“ said the little prince politely.

”Good evening,“ said the snake.

”What planet have I fallen on?“ asked the little prince.

”On the planet Earth, in Africa,“ replied the snake.

”Oh… Then there are no people on Earth?”

”This is the desert. There are no people in the desert. The Earth is big,“ said the snake.

The little prince sat down on a stone and looked up at the sky.

”I wonder,“ he said, “if the stars are lit up so that each of us can find his own star again. Look at my planet. It is right above us… But how far away is it?” ¹

Le Petit Prince is one of the twentieth century’s most widely read fables.¹ Written in 1943 by the French aviator and novelist Antoine de Saint-Exupéry, it tells the story of a young prince who inhabits a small planet in outer space with his muse, a fragile and dainty rose. The prince loves his rose and goes to great lengths to protect her, but her constant needs prove too much for him to bear. One day he decides to leave her and sets out on a journey across the universe. Along the way he stops at several different planets and interacts with their sole inhabitants, each of whom performs a bizarre and arguably pointless activity. The prince leaves each planet confused and despondent—for no place or person has proven more inspiring than his own planet or rose—until he arrives on Earth, where he meets a snake, a fox, and the novel’s unnamed narrator. Their company is a welcome relief for the travel-weary prince, who learns important lessons about love, friendship, and “matters of consequence.” Toward the novel’s end, the snake promises to deliver the little prince home if he allows himself to be bitten. The prince obliges in order to be with his rose, and he soon disappears. The story concludes with the narrator looking up at the stars, wondering if the prince is somewhere among them.

One interpretation of Le Petit Prince is that life is more beautiful when the things that give it meaning are recognized and cherished, but there is a heavy irony behind this theme. The story was published during one of the lowest points in the Second World War, when France was still in the grips of its German oppressors. Saint-Exupéry himself had fled to the United States years earlier and composed Le Petit Prince during a time of personal upheaval. In short, nothing about the context of the book’s birth seemed to inspire its rosy message.   

Now, almost 80 years after the first publication of Le Petit Prince, we find ourselves in a similarly jarring and unpredictable time. As calamitous global events unfold around us, it is difficult not to feel overwhelmed. For healthcare workers, the crush of patient care has made us feel vulnerable—first to a virus that might infect us and our loved ones, and second, to the overwhelming sense of despair when caring for patients who ultimately die despite our best efforts. Pandemics are a time of physical and social disruption, and while it has been 100 years since we experienced one like this, they are a repeated part of the history of life on our planet. What would the little prince see if he landed in our clinics, hospitals, nursing homes, testing centers, or vaccination facilities today? Would he observe patients saying good-bye to family members on tablets and cell phones because their loved ones are not allowed to visit in person? Would he see healthcare workers struggling to resuscitate dying patients in a crowded emergency department or intensive care unit? Would he see long lines of cars filled with people waiting for tests or vaccines? Would he see government officials and public health workers agonizing over decisions about steps that could reduce spread but impose economic hardship on many?

There has been much debate about whether Le Petit Prince is a children’s story or a message for adults disguised as a children’s fable. Perhaps the answer is that it is both, for many children’s stories were actually written for adults. Despite the fragility and delicacy of the book, there is clearly a haunting and deep irony inherent in what it is, in effect, a most savage critique of the world at war.

Two themes that emerge in the novel resonate widely now: isolation and death. Each character the little prince meets is alone, mirroring the long periods of social distancing we have experienced over the past year. And while death is never explicitly mentioned in the book, it seems to be lurking throughout, especially when the prince disappears from Earth after being bitten by the snake. Currently, we have almost become numb to the reported daily death counts—each one alone would have evoked outrage in more usual times. One might imagine that Saint-Exupéry wrote this fable in part to help people cope with the deaths of their loved ones.

And when you are comforted (time soothes all sorrows) you will be happy to have known me. You will always be my friend. You will want to laugh with me. And from time to time you will open your window, so, just for the pleasure of it ... And your friends will be astonished to see you laughing whilst gazing at the sky! And so you will say to them, “Yes, stars always make me laugh!”

Over the past year, both authors of this essay have seen people turn to Le Petit Prince to cope with death. One of us observed a daughter reading the book to her mother at her intensive care bedside on the day she died. The other received a copy as thanks from the wife of a young man who died after 18 months of punishing chemotherapy for sarcoma. Inside the cover was a picture of her husband and the inscription, “Please share this book with someone you love—it’s meant to be read out loud—and remember James.” And so I did, with my grandson Sebastian, who listened to the story with the imagination, wonder, and curiosity of a 6-year-old—he had many questions.

Perhaps the fable that has comforted our patients and their families during their time of despair can do the same for us. Like the prince, who returns to his rose after a difficult journey, we might find solace in the people and things that give our lives their deepest meaning. Thereafter, we might return, rejuvenated, to the clinics, emergency departments, and inpatient wards where our daily work must continue. While the scale of the problems around us makes it feel like any step we take towards preserving our hope will be moot, Le Petit Prince teaches us there is value in making the effort. And there is even a chance that we will find, to our surprise, and against our more cynical judgment, a small rose pushing itself up towards the light.  

The authors thank Rita Charon (Columbia University), Pam Hartzband (Harvard University), Raphael Rush (University of Toronto), and Emily Silverman (University of California San Francisco) for their comments on earlier versions of this essay. None were compensated. We thank Sebastian, James’ wife, and our other patient’s daughter for giving permission to include them in the story.

”Good evening,“ said the little prince politely.

”Good evening,“ said the snake.

”What planet have I fallen on?“ asked the little prince.

”On the planet Earth, in Africa,“ replied the snake.

”Oh… Then there are no people on Earth?”

”This is the desert. There are no people in the desert. The Earth is big,“ said the snake.

The little prince sat down on a stone and looked up at the sky.

”I wonder,“ he said, “if the stars are lit up so that each of us can find his own star again. Look at my planet. It is right above us… But how far away is it?” ¹

Le Petit Prince is one of the twentieth century’s most widely read fables.¹ Written in 1943 by the French aviator and novelist Antoine de Saint-Exupéry, it tells the story of a young prince who inhabits a small planet in outer space with his muse, a fragile and dainty rose. The prince loves his rose and goes to great lengths to protect her, but her constant needs prove too much for him to bear. One day he decides to leave her and sets out on a journey across the universe. Along the way he stops at several different planets and interacts with their sole inhabitants, each of whom performs a bizarre and arguably pointless activity. The prince leaves each planet confused and despondent—for no place or person has proven more inspiring than his own planet or rose—until he arrives on Earth, where he meets a snake, a fox, and the novel’s unnamed narrator. Their company is a welcome relief for the travel-weary prince, who learns important lessons about love, friendship, and “matters of consequence.” Toward the novel’s end, the snake promises to deliver the little prince home if he allows himself to be bitten. The prince obliges in order to be with his rose, and he soon disappears. The story concludes with the narrator looking up at the stars, wondering if the prince is somewhere among them.

One interpretation of Le Petit Prince is that life is more beautiful when the things that give it meaning are recognized and cherished, but there is a heavy irony behind this theme. The story was published during one of the lowest points in the Second World War, when France was still in the grips of its German oppressors. Saint-Exupéry himself had fled to the United States years earlier and composed Le Petit Prince during a time of personal upheaval. In short, nothing about the context of the book’s birth seemed to inspire its rosy message.   

Now, almost 80 years after the first publication of Le Petit Prince, we find ourselves in a similarly jarring and unpredictable time. As calamitous global events unfold around us, it is difficult not to feel overwhelmed. For healthcare workers, the crush of patient care has made us feel vulnerable—first to a virus that might infect us and our loved ones, and second, to the overwhelming sense of despair when caring for patients who ultimately die despite our best efforts. Pandemics are a time of physical and social disruption, and while it has been 100 years since we experienced one like this, they are a repeated part of the history of life on our planet. What would the little prince see if he landed in our clinics, hospitals, nursing homes, testing centers, or vaccination facilities today? Would he observe patients saying good-bye to family members on tablets and cell phones because their loved ones are not allowed to visit in person? Would he see healthcare workers struggling to resuscitate dying patients in a crowded emergency department or intensive care unit? Would he see long lines of cars filled with people waiting for tests or vaccines? Would he see government officials and public health workers agonizing over decisions about steps that could reduce spread but impose economic hardship on many?

There has been much debate about whether Le Petit Prince is a children’s story or a message for adults disguised as a children’s fable. Perhaps the answer is that it is both, for many children’s stories were actually written for adults. Despite the fragility and delicacy of the book, there is clearly a haunting and deep irony inherent in what it is, in effect, a most savage critique of the world at war.

Two themes that emerge in the novel resonate widely now: isolation and death. Each character the little prince meets is alone, mirroring the long periods of social distancing we have experienced over the past year. And while death is never explicitly mentioned in the book, it seems to be lurking throughout, especially when the prince disappears from Earth after being bitten by the snake. Currently, we have almost become numb to the reported daily death counts—each one alone would have evoked outrage in more usual times. One might imagine that Saint-Exupéry wrote this fable in part to help people cope with the deaths of their loved ones.

And when you are comforted (time soothes all sorrows) you will be happy to have known me. You will always be my friend. You will want to laugh with me. And from time to time you will open your window, so, just for the pleasure of it ... And your friends will be astonished to see you laughing whilst gazing at the sky! And so you will say to them, “Yes, stars always make me laugh!”

Over the past year, both authors of this essay have seen people turn to Le Petit Prince to cope with death. One of us observed a daughter reading the book to her mother at her intensive care bedside on the day she died. The other received a copy as thanks from the wife of a young man who died after 18 months of punishing chemotherapy for sarcoma. Inside the cover was a picture of her husband and the inscription, “Please share this book with someone you love—it’s meant to be read out loud—and remember James.” And so I did, with my grandson Sebastian, who listened to the story with the imagination, wonder, and curiosity of a 6-year-old—he had many questions.

Perhaps the fable that has comforted our patients and their families during their time of despair can do the same for us. Like the prince, who returns to his rose after a difficult journey, we might find solace in the people and things that give our lives their deepest meaning. Thereafter, we might return, rejuvenated, to the clinics, emergency departments, and inpatient wards where our daily work must continue. While the scale of the problems around us makes it feel like any step we take towards preserving our hope will be moot, Le Petit Prince teaches us there is value in making the effort. And there is even a chance that we will find, to our surprise, and against our more cynical judgment, a small rose pushing itself up towards the light.  

The authors thank Rita Charon (Columbia University), Pam Hartzband (Harvard University), Raphael Rush (University of Toronto), and Emily Silverman (University of California San Francisco) for their comments on earlier versions of this essay. None were compensated. We thank Sebastian, James’ wife, and our other patient’s daughter for giving permission to include them in the story.

”Good evening,“ said the little prince politely.

”Good evening,“ said the snake.

”What planet have I fallen on?“ asked the little prince.

”On the planet Earth, in Africa,“ replied the snake.

”Oh… Then there are no people on Earth?”

”This is the desert. There are no people in the desert. The Earth is big,“ said the snake.

The little prince sat down on a stone and looked up at the sky.

”I wonder,“ he said, “if the stars are lit up so that each of us can find his own star again. Look at my planet. It is right above us… But how far away is it?” ¹

Le Petit Prince is one of the twentieth century’s most widely read fables.¹ Written in 1943 by the French aviator and novelist Antoine de Saint-Exupéry, it tells the story of a young prince who inhabits a small planet in outer space with his muse, a fragile and dainty rose. The prince loves his rose and goes to great lengths to protect her, but her constant needs prove too much for him to bear. One day he decides to leave her and sets out on a journey across the universe. Along the way he stops at several different planets and interacts with their sole inhabitants, each of whom performs a bizarre and arguably pointless activity. The prince leaves each planet confused and despondent—for no place or person has proven more inspiring than his own planet or rose—until he arrives on Earth, where he meets a snake, a fox, and the novel’s unnamed narrator. Their company is a welcome relief for the travel-weary prince, who learns important lessons about love, friendship, and “matters of consequence.” Toward the novel’s end, the snake promises to deliver the little prince home if he allows himself to be bitten. The prince obliges in order to be with his rose, and he soon disappears. The story concludes with the narrator looking up at the stars, wondering if the prince is somewhere among them.

One interpretation of Le Petit Prince is that life is more beautiful when the things that give it meaning are recognized and cherished, but there is a heavy irony behind this theme. The story was published during one of the lowest points in the Second World War, when France was still in the grips of its German oppressors. Saint-Exupéry himself had fled to the United States years earlier and composed Le Petit Prince during a time of personal upheaval. In short, nothing about the context of the book’s birth seemed to inspire its rosy message.   

Now, almost 80 years after the first publication of Le Petit Prince, we find ourselves in a similarly jarring and unpredictable time. As calamitous global events unfold around us, it is difficult not to feel overwhelmed. For healthcare workers, the crush of patient care has made us feel vulnerable—first to a virus that might infect us and our loved ones, and second, to the overwhelming sense of despair when caring for patients who ultimately die despite our best efforts. Pandemics are a time of physical and social disruption, and while it has been 100 years since we experienced one like this, they are a repeated part of the history of life on our planet. What would the little prince see if he landed in our clinics, hospitals, nursing homes, testing centers, or vaccination facilities today? Would he observe patients saying good-bye to family members on tablets and cell phones because their loved ones are not allowed to visit in person? Would he see healthcare workers struggling to resuscitate dying patients in a crowded emergency department or intensive care unit? Would he see long lines of cars filled with people waiting for tests or vaccines? Would he see government officials and public health workers agonizing over decisions about steps that could reduce spread but impose economic hardship on many?

There has been much debate about whether Le Petit Prince is a children’s story or a message for adults disguised as a children’s fable. Perhaps the answer is that it is both, for many children’s stories were actually written for adults. Despite the fragility and delicacy of the book, there is clearly a haunting and deep irony inherent in what it is, in effect, a most savage critique of the world at war.

Two themes that emerge in the novel resonate widely now: isolation and death. Each character the little prince meets is alone, mirroring the long periods of social distancing we have experienced over the past year. And while death is never explicitly mentioned in the book, it seems to be lurking throughout, especially when the prince disappears from Earth after being bitten by the snake. Currently, we have almost become numb to the reported daily death counts—each one alone would have evoked outrage in more usual times. One might imagine that Saint-Exupéry wrote this fable in part to help people cope with the deaths of their loved ones.

And when you are comforted (time soothes all sorrows) you will be happy to have known me. You will always be my friend. You will want to laugh with me. And from time to time you will open your window, so, just for the pleasure of it ... And your friends will be astonished to see you laughing whilst gazing at the sky! And so you will say to them, “Yes, stars always make me laugh!”

Over the past year, both authors of this essay have seen people turn to Le Petit Prince to cope with death. One of us observed a daughter reading the book to her mother at her intensive care bedside on the day she died. The other received a copy as thanks from the wife of a young man who died after 18 months of punishing chemotherapy for sarcoma. Inside the cover was a picture of her husband and the inscription, “Please share this book with someone you love—it’s meant to be read out loud—and remember James.” And so I did, with my grandson Sebastian, who listened to the story with the imagination, wonder, and curiosity of a 6-year-old—he had many questions.

Perhaps the fable that has comforted our patients and their families during their time of despair can do the same for us. Like the prince, who returns to his rose after a difficult journey, we might find solace in the people and things that give our lives their deepest meaning. Thereafter, we might return, rejuvenated, to the clinics, emergency departments, and inpatient wards where our daily work must continue. While the scale of the problems around us makes it feel like any step we take towards preserving our hope will be moot, Le Petit Prince teaches us there is value in making the effort. And there is even a chance that we will find, to our surprise, and against our more cynical judgment, a small rose pushing itself up towards the light.  

The authors thank Rita Charon (Columbia University), Pam Hartzband (Harvard University), Raphael Rush (University of Toronto), and Emily Silverman (University of California San Francisco) for their comments on earlier versions of this essay. None were compensated. We thank Sebastian, James’ wife, and our other patient’s daughter for giving permission to include them in the story.

REFERENCES

1. American Academy of Family Physicians. Lung cancer: lung cancer screening in adults. AAFP Clinical Preventive Service Recommendations. Accessed April 26, 2021. www.aafp.org/family-physician/patient-care/clinical-recommendations/all-clinical-recommendations/lung-cancer.html
2. USPSTF. Screening for lung cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:962-970. doi:10.1001/jama.2021.1117
3. Jonas DE, Reuland DS, Reddy, SM, et al. Screening for lung cancer with low-dose computed tomography: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2021;325:971-987. doi:10.1001/jama.2021.0377
4. Henderson LM, Rivera MP, Basch E. Broadened eligibility for lung cancer screening: challenges and uncertainty for implementation and equity. JAMA. 2021;325:939-941. doi:10.1001/jama.2020.26422
5. Meza R, Jeon J, Toumazis I, et al. Evaluation of the benefits and harms of lung cancer screening with low-dose computed tomography: modeling study for the US Preventive Services Task Force. JAMA. 2021;325:988-997. doi:10.1001/jama.2021.1077

REFERENCES

1. American Academy of Family Physicians. Lung cancer: lung cancer screening in adults. AAFP Clinical Preventive Service Recommendations. Accessed April 26, 2021. www.aafp.org/family-physician/patient-care/clinical-recommendations/all-clinical-recommendations/lung-cancer.html
2. USPSTF. Screening for lung cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:962-970. doi:10.1001/jama.2021.1117
3. Jonas DE, Reuland DS, Reddy, SM, et al. Screening for lung cancer with low-dose computed tomography: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2021;325:971-987. doi:10.1001/jama.2021.0377
4. Henderson LM, Rivera MP, Basch E. Broadened eligibility for lung cancer screening: challenges and uncertainty for implementation and equity. JAMA. 2021;325:939-941. doi:10.1001/jama.2020.26422
5. Meza R, Jeon J, Toumazis I, et al. Evaluation of the benefits and harms of lung cancer screening with low-dose computed tomography: modeling study for the US Preventive Services Task Force. JAMA. 2021;325:988-997. doi:10.1001/jama.2021.1077

REFERENCES

1. American Academy of Family Physicians. Lung cancer: lung cancer screening in adults. AAFP Clinical Preventive Service Recommendations. Accessed April 26, 2021. www.aafp.org/family-physician/patient-care/clinical-recommendations/all-clinical-recommendations/lung-cancer.html
2. USPSTF. Screening for lung cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:962-970. doi:10.1001/jama.2021.1117
3. Jonas DE, Reuland DS, Reddy, SM, et al. Screening for lung cancer with low-dose computed tomography: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2021;325:971-987. doi:10.1001/jama.2021.0377
4. Henderson LM, Rivera MP, Basch E. Broadened eligibility for lung cancer screening: challenges and uncertainty for implementation and equity. JAMA. 2021;325:939-941. doi:10.1001/jama.2020.26422
5. Meza R, Jeon J, Toumazis I, et al. Evaluation of the benefits and harms of lung cancer screening with low-dose computed tomography: modeling study for the US Preventive Services Task Force. JAMA. 2021;325:988-997. doi:10.1001/jama.2021.1077

Deep brain stimulation (DBS) significantly improves motor function in patients with Parkinson’s disease over the long term, regardless of the therapeutic target, new research shows. In the longest follow-up study comparing the subthalamic nucleus (STN) or the globus pallidus (GPi) as treatment targets for Parkinson’s disease, investigators found DBS was effective at 10 years regardless of which of these two brain regions were treated.

“Both STN and GPi DBS maintained motor benefit out to 10 years, with improvements seen in tremor and rigidity, greater than bradykinesia,” said study author Jill L. Ostrem, MD, medical director and division chief at the University of California, San Francisco Movement Disorders and Neuromodulation Center.

“Less medication was required, and patients had fewer motor fluctuations and less dyskinesia,” she added. But nonmotor symptoms and other symptoms that are less responsive to DBS progress led to worsening disability over time.

The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
 

Advanced patients  

Many studies have examined the GPi and STN as targets for deep brain stimulation in Parkinson’s disease. Some research has compared outcomes between the two targets, but no prospective, randomized trials have evaluated outcomes beyond 3 years of treatment.

For the study, investigators examined data from Study 468, a multicenter, randomized, controlled trial conducted by the U.S. Veterans Affairs (VA) Cooperative Study Program and the National Institute of Neurological Disorders and Stroke (NINDS). In this study, a subset of patients who had been randomly assigned to deep brain stimulation of the GPi or STN were followed for up to 10 years.

Participants were examined at 2 years, 7 years, and 10 years. Eighty-five participants assigned to GPi and 70 assigned to STN completed the visit at 2 years. At 7 years, 68 GPi patients and 49 STN patients completed the visit. Forty-nine patients assigned to GPi and 28 assigned to STN completed the visit at 10 years.

The study’s primary outcome was change in the Unified Parkinson Disease Rating Scale (UPDRS) motor subscale score while off medication and on stimulation between targets. Secondary outcomes included tremor, rigidity, and bradykinesia.

The two groups of patients had comparable baseline characteristics. Mean age was approximately 59 years in both groups. The proportion of male patients was 87% in the GPi group and 83% in the STN group. White patients predominated in the GPi (98%) and STN (94%) groups.

Average disease duration was approximately 11 years, and more than 10% of patients in each group were older than 70 years, indicating a “somewhat more advanced patient cohort,” said Dr. Ostrem.

Although the study’s dropout rate was high, the researchers found no difference in baseline characteristics between patients who did and did not complete the study.
 

Consistent motor improvement

Motor function improved at all timepoints for patients in both study arms. Baseline UPDRS motor subscale score was 43.2 for patients assigned to GPi stimulation. This score changed to 25.8 at 2 years (P < .001), 35.4 at 7 years (P < .001), and 34.0 at 10 years (P = .10).

Baseline UPDRS motor subscale score also was 43.2 for patients assigned to STN stimulation. This score changed to 27.7 at 2 years (P < .001), 34.4 at 7 years (P < .001), and 28.3 at 10 years (P < .001). Improvements were similar between groups but tended to be greater in the STN group.

Among the study’s secondary outcomes, tremor subscales showed the greatest improvement over time, followed by rigidity subscores. Compared with GPi DBS, STN DBS was associated with greater improvement in bradykinesia subscores at 7 and 10 years (P = .03).

In addition, UPDRS I, II, and IV scores, as recorded in motor diaries, showed significant long-term improvement in both study groups. Part I (which reflects mentation and mood) and part II (which reflects activities of daily living) tended to worsen at 7 and 10 years. There were no differences between groups.

Total score on the Parkinson’s Disease Questionnaire-39 (PDQ-39), which measures function in daily living, no longer showed improvement at 7 or 10 years for either target. Rather, it showed worsening, compared with baseline.

“Cognitive impairment and gait and balance issues result in more issues with quality of life and independence,” said Dr. Ostrem.

Stimulation of both targets reduced medication use significantly. There was no difference between targets for this outcome.

The rate of device-related complications in this cohort was comparatively low, said Dr. Ostrem. In the overall study complication, the rate of DBS malfunction was 7.7%, and the rate of DBS infection was 5.8%.

The finding that both targets had similar long-term sustainability of motor benefit provides reassurance that either target is a reasonable choice, said Dr. Ostrem. “I would suggest target choice be determined by a multidisciplinary team, where individual patient signs and symptoms and goals can be considered.”

Other large DBS trials with shorter follow-up durations have suggested differences between the targets. These data can guide the choice of target, said Dr. Ostrem.

“The field of DBS research has never been more exciting,” she added. Newer systems that include improved hardware and software and can record neurophysiologic data from the implanted brain leads could provide improved outcomes of DBS treatment. 

“With modern DBS methods and approaches, we are learning more about Parkinson’s disease and other brain diseases, which I believe will help us to find more treatments and other interventions to slow the progression or minimize symptoms,” Dr. Ostrem concluded.
 

Selection bias?

Commenting on the study, Alfonso Fasano, MD, PhD, chair in neuromodulation and multidisciplinary care at University of Toronto, noted that “these are the first long-term findings resulting from a randomized trial, overall supporting the early notion that STN DBS is superior to GPi DBS in terms of bradykinesia improvement, especially in the long-run.”

The findings reflect the clinical practice of considering STN deep brain stimulation for young patients who face a longer disease duration. Younger patients might tolerate the procedure better than older patients. They also may achieve medication reduction, better motor control, and the possibility of increasing medication when side effects make increased stimulation undesirable.

“It’s interesting to note that even GPi DBS maintained an overall good outcome over time,” said Dr. Fasano. This finding contrasts with that of previous studies, but the latter were limited by selection bias, he added. “Older and frail patients were more likely to be treated with GPi DBS.”

Two factors limit the study’s findings, said Dr. Fasano. During the long study duration, many patients dropped out or were lost to follow-up. “Thus, it is conceivable that the study only enrolled the best responders in each group,” said Dr. Fasano.

In addition, the results of the trial that the current investigators analyzed are not necessarily generalizable, as those who conducted it soon recognized. The study by the VA and NINDS did not detect differences between targets, mainly because of a surprisingly low effect of STN deep brain stimulation. The researchers determined that this finding was related to the study’s inclusion criteria.

“The lack of improvement [on the PDQ-39] clearly indicates that simply treating the motor problems of Parkinson’s disease patients is not enough,” said Dr. Fasano. It also emphasizes that DBS is a symptomatic therapy with little or no effect on the disease’s natural history.

“It will be also important to see how the new data reported by Dr. Ostrem compare to the long-term outcome of the other major STN versus GPi trial from Europe,” said Dr. Fasano, referring to the NSTAPS trial.

He added that it will also be interesting to follow these cohorts for at least 5 more years in order to identify possible differences in terms of disease milestones such as dementia and survival. Previous studies have shown a reduction in survival with targets other than STN, but this finding likely reflects selection bias, he concluded.

The study was funded by the National Institute of Neurological Disorders and Stroke and the U.S. Department of Veterans Affairs. Dr. Ostrem previously has accepted consulting funds from Medtronic and Abbott. She receives grant support from Medtronic and Boston Scientific for fellowship training and clinical trial support. These companies were not involved in the study. Dr. Fasano received honoraria and research support and honoraria from Abbott, Boston Scientific, Brainlab, Ceregate, Inbrain, and Medtronic.

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

Deep brain stimulation (DBS) significantly improves motor function in patients with Parkinson’s disease over the long term, regardless of the therapeutic target, new research shows. In the longest follow-up study comparing the subthalamic nucleus (STN) or the globus pallidus (GPi) as treatment targets for Parkinson’s disease, investigators found DBS was effective at 10 years regardless of which of these two brain regions were treated.

“Both STN and GPi DBS maintained motor benefit out to 10 years, with improvements seen in tremor and rigidity, greater than bradykinesia,” said study author Jill L. Ostrem, MD, medical director and division chief at the University of California, San Francisco Movement Disorders and Neuromodulation Center.

“Less medication was required, and patients had fewer motor fluctuations and less dyskinesia,” she added. But nonmotor symptoms and other symptoms that are less responsive to DBS progress led to worsening disability over time.

The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
 

Advanced patients  

Many studies have examined the GPi and STN as targets for deep brain stimulation in Parkinson’s disease. Some research has compared outcomes between the two targets, but no prospective, randomized trials have evaluated outcomes beyond 3 years of treatment.

For the study, investigators examined data from Study 468, a multicenter, randomized, controlled trial conducted by the U.S. Veterans Affairs (VA) Cooperative Study Program and the National Institute of Neurological Disorders and Stroke (NINDS). In this study, a subset of patients who had been randomly assigned to deep brain stimulation of the GPi or STN were followed for up to 10 years.

Participants were examined at 2 years, 7 years, and 10 years. Eighty-five participants assigned to GPi and 70 assigned to STN completed the visit at 2 years. At 7 years, 68 GPi patients and 49 STN patients completed the visit. Forty-nine patients assigned to GPi and 28 assigned to STN completed the visit at 10 years.

The study’s primary outcome was change in the Unified Parkinson Disease Rating Scale (UPDRS) motor subscale score while off medication and on stimulation between targets. Secondary outcomes included tremor, rigidity, and bradykinesia.

The two groups of patients had comparable baseline characteristics. Mean age was approximately 59 years in both groups. The proportion of male patients was 87% in the GPi group and 83% in the STN group. White patients predominated in the GPi (98%) and STN (94%) groups.

Average disease duration was approximately 11 years, and more than 10% of patients in each group were older than 70 years, indicating a “somewhat more advanced patient cohort,” said Dr. Ostrem.

Although the study’s dropout rate was high, the researchers found no difference in baseline characteristics between patients who did and did not complete the study.
 

Consistent motor improvement

Motor function improved at all timepoints for patients in both study arms. Baseline UPDRS motor subscale score was 43.2 for patients assigned to GPi stimulation. This score changed to 25.8 at 2 years (P < .001), 35.4 at 7 years (P < .001), and 34.0 at 10 years (P = .10).

Baseline UPDRS motor subscale score also was 43.2 for patients assigned to STN stimulation. This score changed to 27.7 at 2 years (P < .001), 34.4 at 7 years (P < .001), and 28.3 at 10 years (P < .001). Improvements were similar between groups but tended to be greater in the STN group.

Among the study’s secondary outcomes, tremor subscales showed the greatest improvement over time, followed by rigidity subscores. Compared with GPi DBS, STN DBS was associated with greater improvement in bradykinesia subscores at 7 and 10 years (P = .03).

In addition, UPDRS I, II, and IV scores, as recorded in motor diaries, showed significant long-term improvement in both study groups. Part I (which reflects mentation and mood) and part II (which reflects activities of daily living) tended to worsen at 7 and 10 years. There were no differences between groups.

Total score on the Parkinson’s Disease Questionnaire-39 (PDQ-39), which measures function in daily living, no longer showed improvement at 7 or 10 years for either target. Rather, it showed worsening, compared with baseline.

“Cognitive impairment and gait and balance issues result in more issues with quality of life and independence,” said Dr. Ostrem.

Stimulation of both targets reduced medication use significantly. There was no difference between targets for this outcome.

The rate of device-related complications in this cohort was comparatively low, said Dr. Ostrem. In the overall study complication, the rate of DBS malfunction was 7.7%, and the rate of DBS infection was 5.8%.

The finding that both targets had similar long-term sustainability of motor benefit provides reassurance that either target is a reasonable choice, said Dr. Ostrem. “I would suggest target choice be determined by a multidisciplinary team, where individual patient signs and symptoms and goals can be considered.”

Other large DBS trials with shorter follow-up durations have suggested differences between the targets. These data can guide the choice of target, said Dr. Ostrem.

“The field of DBS research has never been more exciting,” she added. Newer systems that include improved hardware and software and can record neurophysiologic data from the implanted brain leads could provide improved outcomes of DBS treatment. 

“With modern DBS methods and approaches, we are learning more about Parkinson’s disease and other brain diseases, which I believe will help us to find more treatments and other interventions to slow the progression or minimize symptoms,” Dr. Ostrem concluded.
 

Selection bias?

Commenting on the study, Alfonso Fasano, MD, PhD, chair in neuromodulation and multidisciplinary care at University of Toronto, noted that “these are the first long-term findings resulting from a randomized trial, overall supporting the early notion that STN DBS is superior to GPi DBS in terms of bradykinesia improvement, especially in the long-run.”

The findings reflect the clinical practice of considering STN deep brain stimulation for young patients who face a longer disease duration. Younger patients might tolerate the procedure better than older patients. They also may achieve medication reduction, better motor control, and the possibility of increasing medication when side effects make increased stimulation undesirable.

“It’s interesting to note that even GPi DBS maintained an overall good outcome over time,” said Dr. Fasano. This finding contrasts with that of previous studies, but the latter were limited by selection bias, he added. “Older and frail patients were more likely to be treated with GPi DBS.”

Two factors limit the study’s findings, said Dr. Fasano. During the long study duration, many patients dropped out or were lost to follow-up. “Thus, it is conceivable that the study only enrolled the best responders in each group,” said Dr. Fasano.

In addition, the results of the trial that the current investigators analyzed are not necessarily generalizable, as those who conducted it soon recognized. The study by the VA and NINDS did not detect differences between targets, mainly because of a surprisingly low effect of STN deep brain stimulation. The researchers determined that this finding was related to the study’s inclusion criteria.

“The lack of improvement [on the PDQ-39] clearly indicates that simply treating the motor problems of Parkinson’s disease patients is not enough,” said Dr. Fasano. It also emphasizes that DBS is a symptomatic therapy with little or no effect on the disease’s natural history.

“It will be also important to see how the new data reported by Dr. Ostrem compare to the long-term outcome of the other major STN versus GPi trial from Europe,” said Dr. Fasano, referring to the NSTAPS trial.

He added that it will also be interesting to follow these cohorts for at least 5 more years in order to identify possible differences in terms of disease milestones such as dementia and survival. Previous studies have shown a reduction in survival with targets other than STN, but this finding likely reflects selection bias, he concluded.

The study was funded by the National Institute of Neurological Disorders and Stroke and the U.S. Department of Veterans Affairs. Dr. Ostrem previously has accepted consulting funds from Medtronic and Abbott. She receives grant support from Medtronic and Boston Scientific for fellowship training and clinical trial support. These companies were not involved in the study. Dr. Fasano received honoraria and research support and honoraria from Abbott, Boston Scientific, Brainlab, Ceregate, Inbrain, and Medtronic.

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

Deep brain stimulation (DBS) significantly improves motor function in patients with Parkinson’s disease over the long term, regardless of the therapeutic target, new research shows. In the longest follow-up study comparing the subthalamic nucleus (STN) or the globus pallidus (GPi) as treatment targets for Parkinson’s disease, investigators found DBS was effective at 10 years regardless of which of these two brain regions were treated.

“Both STN and GPi DBS maintained motor benefit out to 10 years, with improvements seen in tremor and rigidity, greater than bradykinesia,” said study author Jill L. Ostrem, MD, medical director and division chief at the University of California, San Francisco Movement Disorders and Neuromodulation Center.

“Less medication was required, and patients had fewer motor fluctuations and less dyskinesia,” she added. But nonmotor symptoms and other symptoms that are less responsive to DBS progress led to worsening disability over time.

The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
 

Advanced patients  

Many studies have examined the GPi and STN as targets for deep brain stimulation in Parkinson’s disease. Some research has compared outcomes between the two targets, but no prospective, randomized trials have evaluated outcomes beyond 3 years of treatment.

For the study, investigators examined data from Study 468, a multicenter, randomized, controlled trial conducted by the U.S. Veterans Affairs (VA) Cooperative Study Program and the National Institute of Neurological Disorders and Stroke (NINDS). In this study, a subset of patients who had been randomly assigned to deep brain stimulation of the GPi or STN were followed for up to 10 years.

Participants were examined at 2 years, 7 years, and 10 years. Eighty-five participants assigned to GPi and 70 assigned to STN completed the visit at 2 years. At 7 years, 68 GPi patients and 49 STN patients completed the visit. Forty-nine patients assigned to GPi and 28 assigned to STN completed the visit at 10 years.

The study’s primary outcome was change in the Unified Parkinson Disease Rating Scale (UPDRS) motor subscale score while off medication and on stimulation between targets. Secondary outcomes included tremor, rigidity, and bradykinesia.

The two groups of patients had comparable baseline characteristics. Mean age was approximately 59 years in both groups. The proportion of male patients was 87% in the GPi group and 83% in the STN group. White patients predominated in the GPi (98%) and STN (94%) groups.

Average disease duration was approximately 11 years, and more than 10% of patients in each group were older than 70 years, indicating a “somewhat more advanced patient cohort,” said Dr. Ostrem.

Although the study’s dropout rate was high, the researchers found no difference in baseline characteristics between patients who did and did not complete the study.
 

Consistent motor improvement

Motor function improved at all timepoints for patients in both study arms. Baseline UPDRS motor subscale score was 43.2 for patients assigned to GPi stimulation. This score changed to 25.8 at 2 years (P < .001), 35.4 at 7 years (P < .001), and 34.0 at 10 years (P = .10).

Baseline UPDRS motor subscale score also was 43.2 for patients assigned to STN stimulation. This score changed to 27.7 at 2 years (P < .001), 34.4 at 7 years (P < .001), and 28.3 at 10 years (P < .001). Improvements were similar between groups but tended to be greater in the STN group.

Among the study’s secondary outcomes, tremor subscales showed the greatest improvement over time, followed by rigidity subscores. Compared with GPi DBS, STN DBS was associated with greater improvement in bradykinesia subscores at 7 and 10 years (P = .03).

In addition, UPDRS I, II, and IV scores, as recorded in motor diaries, showed significant long-term improvement in both study groups. Part I (which reflects mentation and mood) and part II (which reflects activities of daily living) tended to worsen at 7 and 10 years. There were no differences between groups.

Total score on the Parkinson’s Disease Questionnaire-39 (PDQ-39), which measures function in daily living, no longer showed improvement at 7 or 10 years for either target. Rather, it showed worsening, compared with baseline.

“Cognitive impairment and gait and balance issues result in more issues with quality of life and independence,” said Dr. Ostrem.

Stimulation of both targets reduced medication use significantly. There was no difference between targets for this outcome.

The rate of device-related complications in this cohort was comparatively low, said Dr. Ostrem. In the overall study complication, the rate of DBS malfunction was 7.7%, and the rate of DBS infection was 5.8%.

The finding that both targets had similar long-term sustainability of motor benefit provides reassurance that either target is a reasonable choice, said Dr. Ostrem. “I would suggest target choice be determined by a multidisciplinary team, where individual patient signs and symptoms and goals can be considered.”

Other large DBS trials with shorter follow-up durations have suggested differences between the targets. These data can guide the choice of target, said Dr. Ostrem.

“The field of DBS research has never been more exciting,” she added. Newer systems that include improved hardware and software and can record neurophysiologic data from the implanted brain leads could provide improved outcomes of DBS treatment. 

“With modern DBS methods and approaches, we are learning more about Parkinson’s disease and other brain diseases, which I believe will help us to find more treatments and other interventions to slow the progression or minimize symptoms,” Dr. Ostrem concluded.
 

Selection bias?

Commenting on the study, Alfonso Fasano, MD, PhD, chair in neuromodulation and multidisciplinary care at University of Toronto, noted that “these are the first long-term findings resulting from a randomized trial, overall supporting the early notion that STN DBS is superior to GPi DBS in terms of bradykinesia improvement, especially in the long-run.”

The findings reflect the clinical practice of considering STN deep brain stimulation for young patients who face a longer disease duration. Younger patients might tolerate the procedure better than older patients. They also may achieve medication reduction, better motor control, and the possibility of increasing medication when side effects make increased stimulation undesirable.

“It’s interesting to note that even GPi DBS maintained an overall good outcome over time,” said Dr. Fasano. This finding contrasts with that of previous studies, but the latter were limited by selection bias, he added. “Older and frail patients were more likely to be treated with GPi DBS.”

Two factors limit the study’s findings, said Dr. Fasano. During the long study duration, many patients dropped out or were lost to follow-up. “Thus, it is conceivable that the study only enrolled the best responders in each group,” said Dr. Fasano.

In addition, the results of the trial that the current investigators analyzed are not necessarily generalizable, as those who conducted it soon recognized. The study by the VA and NINDS did not detect differences between targets, mainly because of a surprisingly low effect of STN deep brain stimulation. The researchers determined that this finding was related to the study’s inclusion criteria.

“The lack of improvement [on the PDQ-39] clearly indicates that simply treating the motor problems of Parkinson’s disease patients is not enough,” said Dr. Fasano. It also emphasizes that DBS is a symptomatic therapy with little or no effect on the disease’s natural history.

“It will be also important to see how the new data reported by Dr. Ostrem compare to the long-term outcome of the other major STN versus GPi trial from Europe,” said Dr. Fasano, referring to the NSTAPS trial.

He added that it will also be interesting to follow these cohorts for at least 5 more years in order to identify possible differences in terms of disease milestones such as dementia and survival. Previous studies have shown a reduction in survival with targets other than STN, but this finding likely reflects selection bias, he concluded.

The study was funded by the National Institute of Neurological Disorders and Stroke and the U.S. Department of Veterans Affairs. Dr. Ostrem previously has accepted consulting funds from Medtronic and Abbott. She receives grant support from Medtronic and Boston Scientific for fellowship training and clinical trial support. These companies were not involved in the study. Dr. Fasano received honoraria and research support and honoraria from Abbott, Boston Scientific, Brainlab, Ceregate, Inbrain, and Medtronic.

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

Two new phase 2 studies show encouraging findings with the investigational once-weekly basal insulin analogue icodec (Novo Nordisk) for people with type 2 diabetes who require insulin.

Sara Freeman/MDedge News

Insulin icodec works by reversibly binding to albumin, which slows the release of the active insulin analogue. It has a half-life of about 1 week. The glucose-lowering effect is distributed nearly evenly over the course of that week.

Ildiko Lingvay, MD, of the University of Texas Southwestern Medical Center, Dallas, who is an author of both new articles, said: “A weekly insulin is a game changer that will decrease the treatment burden for patients while also improving compliance.”

She noted that these studies demonstrate optimal approaches to initiating treatment with icodec and serve “as the steppingstones for a large phase 3 clinical trial program that is currently ongoing ... which is designed to evaluate the efficacy of once-weekly insulin administration in patients with either type 1 or type 2 diabetes.”

Another advantage of the formulation, Dr. Lingvay pointed out in a press release from her institution, is that it could decrease the burden on caregivers of patients with diabetes who require insulin.

“For example, for patients who need help injecting, those living in long-term care facilities, and those with memory problems, a once-weekly insulin will facilitate treatment and decrease the burden on the care providers,” she explained.
 

Titration balances glycemic control with hypoglycemic risk reduction

The first phase 2 trial, published online April 19, 2021, in Diabetes Care, was an open-label, 16-week, treat-to-target study that involved 205 insulin-naive adults with type 2 diabetes whose hemoglobin A1c levels were 7%-10% while using oral glucose-lowering medications.

They were randomly assigned to one of three once-weekly icodec titration groups:

• Group A – Fasting glucose target of 80-130 mg/dL with adjustments ±21 units/wk
• Group B – Fasting glucose target of 80-130 mg/dL with ±28 units/wk
• Group C – Fasting glucose target of 70-108 mg/dL, adjusting by ±28 units/wk or to once-daily glargine U100 with a fasting glucose target of 80-130 mg/dL with adjustments of ±4 units/d

The percentage of time in the ideal glucose range of 70-180 mg/dL, assessed by continuous glucose monitoring during weeks 15-16, improved from baseline levels of 57.0%, 55.2%, 51.0% for groups A, B, and C, respectively, and from 55.3% for glargine to 76.6%, 83.0%, 80.9%, and 75.9%, respectively.

There were no unexpected safety problems. Hypoglycemia episodes of glucose levels <54 mg/dL occurred in 0.05, 0.15, 0.38, and 0.00 per patient-year for the four groups, respectively. None were severe (i.e., required assistance).

The titration for patients in group A (80-130 mg/dL, ±21 units/wk) yielded the best balance between glycemic control and risk for hypoglycemia, Dr. Lingvay and colleagues said.
 

Use of loading dose when switching to icodec improves time in range

In the other phase 2 trial, also published online April 19 in Diabetes Care, Harpreet S. Bajaj, MD, of Mount Sinai Hospital, Toronto, and colleagues, with Dr. Lingvay as a coauthor, examined two methods of switching to icodec. This multicenter, open-label, treat-to-target study included 154 patients with A1c levels of 7-10% who were already receiving basal insulin daily and at least one oral glucose-lowering medication.

Patients were randomly assigned to one of three treatment approaches: a 100% loading dose of icodec (only the first dose was doubled), no loading dose, or once-daily glargine.

The primary endpoint was time in range (70-180 mg/dL) during weeks 15 and 16. This was achieved with 72.9% of patients receiving the icodec loading dose, 66.0% of patients receiving icodec without the loading dose, and 65.0% of patients receiving daily glargine. The difference between the icodec loading-dose method and glargine was significant, Dr. Bajaj and colleagues reported.

The mean A1c level was reduced from an overall average of 7.9% at baseline to 7.1% in the icodec loading dose group and to 7.4% in both the no-loading-dose and glargine groups.

Rates of adverse events and hypoglycemic episodes did not differ significantly among the groups.

Previous phase 2 data showing that the efficacy and safety of icodec were comparable with that of once-daily insulin glargine U100 in 247 insulin-naive patients with type 2 diabetes were published in November 2020 in the New England Journal of Medicine and were presented at the European Association for the Study of Diabetes (EASD) 2020 Annual Meeting, as reported by this news organization.

Both studies were funded by Novo Nordisk. Dr. Lingvey has received research funding, advisory/consulting fees, or other support from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Boehringer Ingelheim, Janssen, Intercept, Intarcia, Target RWE, Merck, Pfizer, Novartis, GI Dynamics, Mylan, Mannkind, Valeritas, Bayer, and Zealand Pharma. Dr. Bajaj has received speaking fees from AstraZeneca, Eli Lilly, Janssen Pharmaceuticals, Merck, and Novo Nordisk and research funding paid to LMC Healthcare for serving as principal investigator on clinical trials from Amgen, AstraZeneca Boehringer Ingelheim, Ceapro Inc, Eli Lilly, Gilead Sciences, Janssen Pharmaceuticals, Kowa Pharmaceuticals, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Sanofi, and Tricida.

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

Two new phase 2 studies show encouraging findings with the investigational once-weekly basal insulin analogue icodec (Novo Nordisk) for people with type 2 diabetes who require insulin.

Sara Freeman/MDedge News

Insulin icodec works by reversibly binding to albumin, which slows the release of the active insulin analogue. It has a half-life of about 1 week. The glucose-lowering effect is distributed nearly evenly over the course of that week.

Ildiko Lingvay, MD, of the University of Texas Southwestern Medical Center, Dallas, who is an author of both new articles, said: “A weekly insulin is a game changer that will decrease the treatment burden for patients while also improving compliance.”

She noted that these studies demonstrate optimal approaches to initiating treatment with icodec and serve “as the steppingstones for a large phase 3 clinical trial program that is currently ongoing ... which is designed to evaluate the efficacy of once-weekly insulin administration in patients with either type 1 or type 2 diabetes.”

Another advantage of the formulation, Dr. Lingvay pointed out in a press release from her institution, is that it could decrease the burden on caregivers of patients with diabetes who require insulin.

“For example, for patients who need help injecting, those living in long-term care facilities, and those with memory problems, a once-weekly insulin will facilitate treatment and decrease the burden on the care providers,” she explained.
 

Titration balances glycemic control with hypoglycemic risk reduction

The first phase 2 trial, published online April 19, 2021, in Diabetes Care, was an open-label, 16-week, treat-to-target study that involved 205 insulin-naive adults with type 2 diabetes whose hemoglobin A1c levels were 7%-10% while using oral glucose-lowering medications.

They were randomly assigned to one of three once-weekly icodec titration groups:

• Group A – Fasting glucose target of 80-130 mg/dL with adjustments ±21 units/wk
• Group B – Fasting glucose target of 80-130 mg/dL with ±28 units/wk
• Group C – Fasting glucose target of 70-108 mg/dL, adjusting by ±28 units/wk or to once-daily glargine U100 with a fasting glucose target of 80-130 mg/dL with adjustments of ±4 units/d

The percentage of time in the ideal glucose range of 70-180 mg/dL, assessed by continuous glucose monitoring during weeks 15-16, improved from baseline levels of 57.0%, 55.2%, 51.0% for groups A, B, and C, respectively, and from 55.3% for glargine to 76.6%, 83.0%, 80.9%, and 75.9%, respectively.

There were no unexpected safety problems. Hypoglycemia episodes of glucose levels <54 mg/dL occurred in 0.05, 0.15, 0.38, and 0.00 per patient-year for the four groups, respectively. None were severe (i.e., required assistance).

The titration for patients in group A (80-130 mg/dL, ±21 units/wk) yielded the best balance between glycemic control and risk for hypoglycemia, Dr. Lingvay and colleagues said.
 

Use of loading dose when switching to icodec improves time in range

In the other phase 2 trial, also published online April 19 in Diabetes Care, Harpreet S. Bajaj, MD, of Mount Sinai Hospital, Toronto, and colleagues, with Dr. Lingvay as a coauthor, examined two methods of switching to icodec. This multicenter, open-label, treat-to-target study included 154 patients with A1c levels of 7-10% who were already receiving basal insulin daily and at least one oral glucose-lowering medication.

Patients were randomly assigned to one of three treatment approaches: a 100% loading dose of icodec (only the first dose was doubled), no loading dose, or once-daily glargine.

The primary endpoint was time in range (70-180 mg/dL) during weeks 15 and 16. This was achieved with 72.9% of patients receiving the icodec loading dose, 66.0% of patients receiving icodec without the loading dose, and 65.0% of patients receiving daily glargine. The difference between the icodec loading-dose method and glargine was significant, Dr. Bajaj and colleagues reported.

The mean A1c level was reduced from an overall average of 7.9% at baseline to 7.1% in the icodec loading dose group and to 7.4% in both the no-loading-dose and glargine groups.

Rates of adverse events and hypoglycemic episodes did not differ significantly among the groups.

Previous phase 2 data showing that the efficacy and safety of icodec were comparable with that of once-daily insulin glargine U100 in 247 insulin-naive patients with type 2 diabetes were published in November 2020 in the New England Journal of Medicine and were presented at the European Association for the Study of Diabetes (EASD) 2020 Annual Meeting, as reported by this news organization.

Both studies were funded by Novo Nordisk. Dr. Lingvey has received research funding, advisory/consulting fees, or other support from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Boehringer Ingelheim, Janssen, Intercept, Intarcia, Target RWE, Merck, Pfizer, Novartis, GI Dynamics, Mylan, Mannkind, Valeritas, Bayer, and Zealand Pharma. Dr. Bajaj has received speaking fees from AstraZeneca, Eli Lilly, Janssen Pharmaceuticals, Merck, and Novo Nordisk and research funding paid to LMC Healthcare for serving as principal investigator on clinical trials from Amgen, AstraZeneca Boehringer Ingelheim, Ceapro Inc, Eli Lilly, Gilead Sciences, Janssen Pharmaceuticals, Kowa Pharmaceuticals, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Sanofi, and Tricida.

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

Two new phase 2 studies show encouraging findings with the investigational once-weekly basal insulin analogue icodec (Novo Nordisk) for people with type 2 diabetes who require insulin.

Sara Freeman/MDedge News

Insulin icodec works by reversibly binding to albumin, which slows the release of the active insulin analogue. It has a half-life of about 1 week. The glucose-lowering effect is distributed nearly evenly over the course of that week.

Ildiko Lingvay, MD, of the University of Texas Southwestern Medical Center, Dallas, who is an author of both new articles, said: “A weekly insulin is a game changer that will decrease the treatment burden for patients while also improving compliance.”

She noted that these studies demonstrate optimal approaches to initiating treatment with icodec and serve “as the steppingstones for a large phase 3 clinical trial program that is currently ongoing ... which is designed to evaluate the efficacy of once-weekly insulin administration in patients with either type 1 or type 2 diabetes.”

Another advantage of the formulation, Dr. Lingvay pointed out in a press release from her institution, is that it could decrease the burden on caregivers of patients with diabetes who require insulin.

“For example, for patients who need help injecting, those living in long-term care facilities, and those with memory problems, a once-weekly insulin will facilitate treatment and decrease the burden on the care providers,” she explained.
 

Titration balances glycemic control with hypoglycemic risk reduction

The first phase 2 trial, published online April 19, 2021, in Diabetes Care, was an open-label, 16-week, treat-to-target study that involved 205 insulin-naive adults with type 2 diabetes whose hemoglobin A1c levels were 7%-10% while using oral glucose-lowering medications.

They were randomly assigned to one of three once-weekly icodec titration groups:

• Group A – Fasting glucose target of 80-130 mg/dL with adjustments ±21 units/wk
• Group B – Fasting glucose target of 80-130 mg/dL with ±28 units/wk
• Group C – Fasting glucose target of 70-108 mg/dL, adjusting by ±28 units/wk or to once-daily glargine U100 with a fasting glucose target of 80-130 mg/dL with adjustments of ±4 units/d

The percentage of time in the ideal glucose range of 70-180 mg/dL, assessed by continuous glucose monitoring during weeks 15-16, improved from baseline levels of 57.0%, 55.2%, 51.0% for groups A, B, and C, respectively, and from 55.3% for glargine to 76.6%, 83.0%, 80.9%, and 75.9%, respectively.

There were no unexpected safety problems. Hypoglycemia episodes of glucose levels <54 mg/dL occurred in 0.05, 0.15, 0.38, and 0.00 per patient-year for the four groups, respectively. None were severe (i.e., required assistance).

The titration for patients in group A (80-130 mg/dL, ±21 units/wk) yielded the best balance between glycemic control and risk for hypoglycemia, Dr. Lingvay and colleagues said.
 

Use of loading dose when switching to icodec improves time in range

In the other phase 2 trial, also published online April 19 in Diabetes Care, Harpreet S. Bajaj, MD, of Mount Sinai Hospital, Toronto, and colleagues, with Dr. Lingvay as a coauthor, examined two methods of switching to icodec. This multicenter, open-label, treat-to-target study included 154 patients with A1c levels of 7-10% who were already receiving basal insulin daily and at least one oral glucose-lowering medication.

Patients were randomly assigned to one of three treatment approaches: a 100% loading dose of icodec (only the first dose was doubled), no loading dose, or once-daily glargine.

The primary endpoint was time in range (70-180 mg/dL) during weeks 15 and 16. This was achieved with 72.9% of patients receiving the icodec loading dose, 66.0% of patients receiving icodec without the loading dose, and 65.0% of patients receiving daily glargine. The difference between the icodec loading-dose method and glargine was significant, Dr. Bajaj and colleagues reported.

The mean A1c level was reduced from an overall average of 7.9% at baseline to 7.1% in the icodec loading dose group and to 7.4% in both the no-loading-dose and glargine groups.

Rates of adverse events and hypoglycemic episodes did not differ significantly among the groups.

Previous phase 2 data showing that the efficacy and safety of icodec were comparable with that of once-daily insulin glargine U100 in 247 insulin-naive patients with type 2 diabetes were published in November 2020 in the New England Journal of Medicine and were presented at the European Association for the Study of Diabetes (EASD) 2020 Annual Meeting, as reported by this news organization.

Both studies were funded by Novo Nordisk. Dr. Lingvey has received research funding, advisory/consulting fees, or other support from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Boehringer Ingelheim, Janssen, Intercept, Intarcia, Target RWE, Merck, Pfizer, Novartis, GI Dynamics, Mylan, Mannkind, Valeritas, Bayer, and Zealand Pharma. Dr. Bajaj has received speaking fees from AstraZeneca, Eli Lilly, Janssen Pharmaceuticals, Merck, and Novo Nordisk and research funding paid to LMC Healthcare for serving as principal investigator on clinical trials from Amgen, AstraZeneca Boehringer Ingelheim, Ceapro Inc, Eli Lilly, Gilead Sciences, Janssen Pharmaceuticals, Kowa Pharmaceuticals, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Sanofi, and Tricida.

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

Poor continuity of care may lead to worse outcomes among patients with active inflammatory bowel disease (IBD), according to data from more than 20,000 veterans.

Even in the Veterans Health Administration health care system, which “may provide the ideal environment for care coordination,” patients with active IBD had “substantial variation” in dispersion of care, leading to more frequent surgical interventions, corticosteroid use, and hospitalizations, reported lead author Shirley Cohen-Mekelburg, MD, MS, of the University of Michigan, Ann Arbor, and colleagues.

“Health care in the United States is marked by substantial fragmentation, with patients pursuing and receiving care from multiple clinicians, often at different institutions,” the investigators wrote in JAMA Network Open. “Fragmented care has been associated with poor chronic disease outcomes, higher health care use, duplication in testing, and increased costs of care.”

In the VHA, these issues prompted creation of the Patient Aligned Care Team (PACT), a medical home model in which primary care physicians coordinate clinical teams of specialists and other health care practitioners. But coordination can be challenging with chronic medical conditions like IBD, according to Dr. Cohen-Mekelburg and colleagues.

“High-quality care for IBD includes not only disease-specific management of symptoms but also disease-specific preventive care, such as immunizations and cancer screening, to prevent associated adverse outcomes,” the investigators wrote. “Identifying which physician is responsible for managing each aspect of care requires some degree of coordination and makes patients with IBD vulnerable to care fragmentation.”
 

Worse outcomes tied to poor first-year continuity

To evaluate care fragmentation within the VHA, the investigators identified 20,079 veterans with IBD who had at least one outpatient encounter with the system between the beginning of 2002 and the end of 2014. Continuity of care (COC) was calculated with the Bice-Boxerman COC index, which measures how much a patient’s care is connected with a distinct physician. The investigators used the first year COC as the primary independent variable.

SDI Productions/E+/Getty Images

In the first year of care, the median COC index was 0.24 (interquartile range, 0.13-0.46). The investigators noted that this figure was lower than reported by previous studies involving patients with several other chronic conditions, including IBD.

After controlling for covariates and adjusting for facility-related clustering, the investigators found a lower COC index in the first year was associated with a higher rate of worse outcomes in the subsequent 2 years, including surgical interventions (adjusted hazard ratio, 1.72; 95% confidence interval, 1.43-2.07), hospitalizations (aHR, 1.25; 95% CI, 1.06-1.47), and outpatient flares requiring corticosteroids (aHR, 1.11; 95% CI, 1.01-1.22). Conversely, improving COC index score by 0.1 reduced risk of outpatient flare (aHR, 0.69; 95%CI, 0.58-0.82), hospitalization (aHR, 0.57; 95%CI, 0.41-0.79), and surgical intervention (aHR, 0.25; 95% CI, 0.16-0.38).

Further analyses showed that the relationship between lower COC and worse outcomes carried across measures such as baseline use of an immunomodulator or biological agent, as well as subgroups such as patients with nonsevere IBD and nonsurgical patients.

Among those treated by a VHA gastroenterologist, a lower level of COC was associated with a higher rate of surgical interventions, but not hospitalizations or outpatient flares. Physician-specific COC index scores were highest for primary care providers (0.54), followed by gastroenterologists (0.25) and surgeons (0.17). However, lower physician-specific COC scores did not translate to worse IBD outcomes.

“The level of COC among patients with IBD in the present VHA cohort was ... lower than the values described in previous studies of veterans in the VHA system, including a study of VHA-Medicare dual enrollees who were especially prone to fragmented care because of their ability to seek care both inside and outside of the VHA system,” the investigators wrote, referring to a 2018 study. “The difference in COC among patients with IBD vs. patients without IBD is likely multifactorial and may be associated with confusion about physician accountability and lack of focus on coordination in IBD multidisciplinary care. Patients with IBD require care by primary care providers, gastroenterologists, and surgeons, but the delineation of responsibility by physician is often unclear.”
 

‘Better care, not just more care,’ is needed

“These outcomes cannot be improved with a more robust treatment armamentarium alone,” according to Jason K. Hou, MD, MS, AGAF, FACG, interim chief of gastroenterology and hepatology at Michael E. DeBakey VA Medical Center and associate professor of medicine at Baylor College of Medicine, Houston, who cowrote a simultaneously published editorial, which was also authored by David I. Fudman, MD.

“Examples exist of improving care coordination and outcomes through patient-aligned care teams in primary care and medical specialty homes for IBD,” Dr. Hou said in an interview. “However, significant barriers to widespread implementation remain.”

Dr. Hou offered several possible approaches to overcome these barriers.

“We need improved methods to identify and follow high-risk patients most likely to have complications and health care utilization,” he said. “We need an investment by payers and health care systems on care coordination so the identified high-risk patients can receive timely testing, referral, and treatment. These changes require reevaluation of how the health care system incentivizes health care to provide better care, not just more care.”

The investigators reported grants from the U.S. Department of Veterans Affairs and the National Institutes of Health and financial relationships with AbbVie, UCB, and Takeda. Dr. Hou reported no conflicts of interest.

Poor continuity of care may lead to worse outcomes among patients with active inflammatory bowel disease (IBD), according to data from more than 20,000 veterans.

Even in the Veterans Health Administration health care system, which “may provide the ideal environment for care coordination,” patients with active IBD had “substantial variation” in dispersion of care, leading to more frequent surgical interventions, corticosteroid use, and hospitalizations, reported lead author Shirley Cohen-Mekelburg, MD, MS, of the University of Michigan, Ann Arbor, and colleagues.

“Health care in the United States is marked by substantial fragmentation, with patients pursuing and receiving care from multiple clinicians, often at different institutions,” the investigators wrote in JAMA Network Open. “Fragmented care has been associated with poor chronic disease outcomes, higher health care use, duplication in testing, and increased costs of care.”

In the VHA, these issues prompted creation of the Patient Aligned Care Team (PACT), a medical home model in which primary care physicians coordinate clinical teams of specialists and other health care practitioners. But coordination can be challenging with chronic medical conditions like IBD, according to Dr. Cohen-Mekelburg and colleagues.

“High-quality care for IBD includes not only disease-specific management of symptoms but also disease-specific preventive care, such as immunizations and cancer screening, to prevent associated adverse outcomes,” the investigators wrote. “Identifying which physician is responsible for managing each aspect of care requires some degree of coordination and makes patients with IBD vulnerable to care fragmentation.”
 

Worse outcomes tied to poor first-year continuity

To evaluate care fragmentation within the VHA, the investigators identified 20,079 veterans with IBD who had at least one outpatient encounter with the system between the beginning of 2002 and the end of 2014. Continuity of care (COC) was calculated with the Bice-Boxerman COC index, which measures how much a patient’s care is connected with a distinct physician. The investigators used the first year COC as the primary independent variable.

SDI Productions/E+/Getty Images

In the first year of care, the median COC index was 0.24 (interquartile range, 0.13-0.46). The investigators noted that this figure was lower than reported by previous studies involving patients with several other chronic conditions, including IBD.

After controlling for covariates and adjusting for facility-related clustering, the investigators found a lower COC index in the first year was associated with a higher rate of worse outcomes in the subsequent 2 years, including surgical interventions (adjusted hazard ratio, 1.72; 95% confidence interval, 1.43-2.07), hospitalizations (aHR, 1.25; 95% CI, 1.06-1.47), and outpatient flares requiring corticosteroids (aHR, 1.11; 95% CI, 1.01-1.22). Conversely, improving COC index score by 0.1 reduced risk of outpatient flare (aHR, 0.69; 95%CI, 0.58-0.82), hospitalization (aHR, 0.57; 95%CI, 0.41-0.79), and surgical intervention (aHR, 0.25; 95% CI, 0.16-0.38).

Further analyses showed that the relationship between lower COC and worse outcomes carried across measures such as baseline use of an immunomodulator or biological agent, as well as subgroups such as patients with nonsevere IBD and nonsurgical patients.

Among those treated by a VHA gastroenterologist, a lower level of COC was associated with a higher rate of surgical interventions, but not hospitalizations or outpatient flares. Physician-specific COC index scores were highest for primary care providers (0.54), followed by gastroenterologists (0.25) and surgeons (0.17). However, lower physician-specific COC scores did not translate to worse IBD outcomes.

“The level of COC among patients with IBD in the present VHA cohort was ... lower than the values described in previous studies of veterans in the VHA system, including a study of VHA-Medicare dual enrollees who were especially prone to fragmented care because of their ability to seek care both inside and outside of the VHA system,” the investigators wrote, referring to a 2018 study. “The difference in COC among patients with IBD vs. patients without IBD is likely multifactorial and may be associated with confusion about physician accountability and lack of focus on coordination in IBD multidisciplinary care. Patients with IBD require care by primary care providers, gastroenterologists, and surgeons, but the delineation of responsibility by physician is often unclear.”
 

‘Better care, not just more care,’ is needed

“These outcomes cannot be improved with a more robust treatment armamentarium alone,” according to Jason K. Hou, MD, MS, AGAF, FACG, interim chief of gastroenterology and hepatology at Michael E. DeBakey VA Medical Center and associate professor of medicine at Baylor College of Medicine, Houston, who cowrote a simultaneously published editorial, which was also authored by David I. Fudman, MD.

“Examples exist of improving care coordination and outcomes through patient-aligned care teams in primary care and medical specialty homes for IBD,” Dr. Hou said in an interview. “However, significant barriers to widespread implementation remain.”

Dr. Hou offered several possible approaches to overcome these barriers.

“We need improved methods to identify and follow high-risk patients most likely to have complications and health care utilization,” he said. “We need an investment by payers and health care systems on care coordination so the identified high-risk patients can receive timely testing, referral, and treatment. These changes require reevaluation of how the health care system incentivizes health care to provide better care, not just more care.”

The investigators reported grants from the U.S. Department of Veterans Affairs and the National Institutes of Health and financial relationships with AbbVie, UCB, and Takeda. Dr. Hou reported no conflicts of interest.

Poor continuity of care may lead to worse outcomes among patients with active inflammatory bowel disease (IBD), according to data from more than 20,000 veterans.

Even in the Veterans Health Administration health care system, which “may provide the ideal environment for care coordination,” patients with active IBD had “substantial variation” in dispersion of care, leading to more frequent surgical interventions, corticosteroid use, and hospitalizations, reported lead author Shirley Cohen-Mekelburg, MD, MS, of the University of Michigan, Ann Arbor, and colleagues.

“Health care in the United States is marked by substantial fragmentation, with patients pursuing and receiving care from multiple clinicians, often at different institutions,” the investigators wrote in JAMA Network Open. “Fragmented care has been associated with poor chronic disease outcomes, higher health care use, duplication in testing, and increased costs of care.”

In the VHA, these issues prompted creation of the Patient Aligned Care Team (PACT), a medical home model in which primary care physicians coordinate clinical teams of specialists and other health care practitioners. But coordination can be challenging with chronic medical conditions like IBD, according to Dr. Cohen-Mekelburg and colleagues.

“High-quality care for IBD includes not only disease-specific management of symptoms but also disease-specific preventive care, such as immunizations and cancer screening, to prevent associated adverse outcomes,” the investigators wrote. “Identifying which physician is responsible for managing each aspect of care requires some degree of coordination and makes patients with IBD vulnerable to care fragmentation.”
 

Worse outcomes tied to poor first-year continuity

To evaluate care fragmentation within the VHA, the investigators identified 20,079 veterans with IBD who had at least one outpatient encounter with the system between the beginning of 2002 and the end of 2014. Continuity of care (COC) was calculated with the Bice-Boxerman COC index, which measures how much a patient’s care is connected with a distinct physician. The investigators used the first year COC as the primary independent variable.

SDI Productions/E+/Getty Images

In the first year of care, the median COC index was 0.24 (interquartile range, 0.13-0.46). The investigators noted that this figure was lower than reported by previous studies involving patients with several other chronic conditions, including IBD.

After controlling for covariates and adjusting for facility-related clustering, the investigators found a lower COC index in the first year was associated with a higher rate of worse outcomes in the subsequent 2 years, including surgical interventions (adjusted hazard ratio, 1.72; 95% confidence interval, 1.43-2.07), hospitalizations (aHR, 1.25; 95% CI, 1.06-1.47), and outpatient flares requiring corticosteroids (aHR, 1.11; 95% CI, 1.01-1.22). Conversely, improving COC index score by 0.1 reduced risk of outpatient flare (aHR, 0.69; 95%CI, 0.58-0.82), hospitalization (aHR, 0.57; 95%CI, 0.41-0.79), and surgical intervention (aHR, 0.25; 95% CI, 0.16-0.38).

Further analyses showed that the relationship between lower COC and worse outcomes carried across measures such as baseline use of an immunomodulator or biological agent, as well as subgroups such as patients with nonsevere IBD and nonsurgical patients.

Among those treated by a VHA gastroenterologist, a lower level of COC was associated with a higher rate of surgical interventions, but not hospitalizations or outpatient flares. Physician-specific COC index scores were highest for primary care providers (0.54), followed by gastroenterologists (0.25) and surgeons (0.17). However, lower physician-specific COC scores did not translate to worse IBD outcomes.

“The level of COC among patients with IBD in the present VHA cohort was ... lower than the values described in previous studies of veterans in the VHA system, including a study of VHA-Medicare dual enrollees who were especially prone to fragmented care because of their ability to seek care both inside and outside of the VHA system,” the investigators wrote, referring to a 2018 study. “The difference in COC among patients with IBD vs. patients without IBD is likely multifactorial and may be associated with confusion about physician accountability and lack of focus on coordination in IBD multidisciplinary care. Patients with IBD require care by primary care providers, gastroenterologists, and surgeons, but the delineation of responsibility by physician is often unclear.”
 

‘Better care, not just more care,’ is needed

“These outcomes cannot be improved with a more robust treatment armamentarium alone,” according to Jason K. Hou, MD, MS, AGAF, FACG, interim chief of gastroenterology and hepatology at Michael E. DeBakey VA Medical Center and associate professor of medicine at Baylor College of Medicine, Houston, who cowrote a simultaneously published editorial, which was also authored by David I. Fudman, MD.

“Examples exist of improving care coordination and outcomes through patient-aligned care teams in primary care and medical specialty homes for IBD,” Dr. Hou said in an interview. “However, significant barriers to widespread implementation remain.”

Dr. Hou offered several possible approaches to overcome these barriers.

“We need improved methods to identify and follow high-risk patients most likely to have complications and health care utilization,” he said. “We need an investment by payers and health care systems on care coordination so the identified high-risk patients can receive timely testing, referral, and treatment. These changes require reevaluation of how the health care system incentivizes health care to provide better care, not just more care.”

The investigators reported grants from the U.S. Department of Veterans Affairs and the National Institutes of Health and financial relationships with AbbVie, UCB, and Takeda. Dr. Hou reported no conflicts of interest.

COVID-19 is linked to novel seizures and subsequent adverse outcomes, including death, in patients without a previous history of epilepsy, new research shows. In a retrospective study of more than 900 patients admitted to the hospital with COVID-19, those without a known history of epilepsy had three times greater odds of experiencing novel seizures than those with a known history of epilepsy.

In addition, among patients with new-onset seizures, hospital stays were about 15 days longer – and mortality rates were significantly higher.

“We’re finding that there are many neurological consequences that can happen with COVID-19 infections, and it’s important for clinicians to keep that in mind as they monitor people long term,” said study investigator Neeraj Singh, MD, neurologist and epileptologist with Northwell Health System, Great Neck, New York.

Dr. Singh noted that although seizures “might not be the most common thing we see in people with COVID-19, they seem to be new seizures and not just a seizure we knew would happen in someone with epilepsy.”

“So there’s definitely a need now for more prospective research and following people over time to fully understand all the different things that might be newly a problem for them in the long term,” he added.

Dr. Singh and Hardik Bhaskar, an undergraduate student at Hunter College, New York, presented the study findings at the American Academy of Neurology’s 2021 annual meeting.
 

Largest sample to date

“This study explores the relationship between the incidences of COVID-19 infections and [novel] epileptic seizures in the largest sample to date in a single New York–based hospital system,” the investigators noted. Novel seizures included both new-onset and breakthrough seizures.

Dr. Singh told meeting attendees that the “early epicenter” of the COVID pandemic was in New York and occurred from Feb. 29, 2020 to June 1, 2020. Patients with COVID-19 “had multiple neurological sequelae, including seizures, strokes, and encephalopathy,” he said.

However, the effects of COVID-19 on individuals with epilepsy “remain unclear,” Dr. Singh said.

For their study, the researchers assessed 917 patients in 13 New York City metropolitan hospitals. All participants had received a confirmed positive test result on PCR for COVID and had received an antiepileptic medication upon admission. The patients were admitted between Feb. 14 and June 14, 2020.

For the study, the patients were first divided into two groups: those with a history of epilepsy (n = 451), and those without such a history (n = 466).

The first group was further divided on the basis of those who presented with breakthrough seizures and those who presented without them. The second group was further divided on the basis of those who presented with new-onset seizures and those who presented without them.
 

Significant adverse outcomes

Results showed that 27% of the patients without a history of epilepsy experienced a novel/new-onset seizure and that 11% of the patients with a history of epilepsy experienced a novel/breakthrough seizure (odds ratio, 3.15; P < .0001).

In addition, participants with new-onset seizures had a longer stay in the hospital (mean, 26.9 days) than the subgroup with a history of epilepsy and no breakthrough seizures (10.9 days) and the subgroup with a history of epilepsy who did experience breakthrough seizures (12.8 days; P < .0001 for both comparisons).

In the group of patients with a history of epilepsy, there were no significant differences in lengths of stay between those with and those without breakthrough seizures (P = .68).

Although mortality rates did not differ significantly between the full group with a history of epilepsy versus the full group without epilepsy (23% vs. 25%; OR, 0.9), the mortality rate was significantly higher among patients who experienced novel seizures than among those who did not experience such seizures (29% vs. 23%; OR, 1.4; P = .045).

Mr. Bhaskar noted that there are “many hypotheses for the mechanism by which COVID-19 might cause seizures.” Those mechanisms include proinflammatory cytokine storms, which may increase the rate of apoptosis, neuronal necrosis, and glutamate concentrations and may disrupt the blood-brain barrier. Another hypothesis is that SARS-CoV-2 infection may lead to hypoxia and abnormal coagulation, resulting in stroke and a subsequent increase in the risk for seizures.

Interestingly, “the presence of antiepileptic medications in patients with epilepsy may confer a protective effect against breakthrough seizures,” Dr. Singh said. “However, some subclinical seizures may be misdiagnosed as encephalopathy when patients present with COVID-19 infections.”

He added that further research is needed into the mechanisms linking these infections and new-onset seizures and to “identify subclinical seizures in encephalopathic patients.”

Asked during the question-and-answer session whether the investigators had assessed differences by demographics, such as age or sex, Dr. Singh said, “We have not subdivided them that way yet,” but he said he would like to do so in the future. He also plans to look further into which specific medications were used by the participants.

The investigators have reported no relevant financial relationships.

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

COVID-19 is linked to novel seizures and subsequent adverse outcomes, including death, in patients without a previous history of epilepsy, new research shows. In a retrospective study of more than 900 patients admitted to the hospital with COVID-19, those without a known history of epilepsy had three times greater odds of experiencing novel seizures than those with a known history of epilepsy.

In addition, among patients with new-onset seizures, hospital stays were about 15 days longer – and mortality rates were significantly higher.

“We’re finding that there are many neurological consequences that can happen with COVID-19 infections, and it’s important for clinicians to keep that in mind as they monitor people long term,” said study investigator Neeraj Singh, MD, neurologist and epileptologist with Northwell Health System, Great Neck, New York.

Dr. Singh noted that although seizures “might not be the most common thing we see in people with COVID-19, they seem to be new seizures and not just a seizure we knew would happen in someone with epilepsy.”

“So there’s definitely a need now for more prospective research and following people over time to fully understand all the different things that might be newly a problem for them in the long term,” he added.

Dr. Singh and Hardik Bhaskar, an undergraduate student at Hunter College, New York, presented the study findings at the American Academy of Neurology’s 2021 annual meeting.
 

Largest sample to date

“This study explores the relationship between the incidences of COVID-19 infections and [novel] epileptic seizures in the largest sample to date in a single New York–based hospital system,” the investigators noted. Novel seizures included both new-onset and breakthrough seizures.

Dr. Singh told meeting attendees that the “early epicenter” of the COVID pandemic was in New York and occurred from Feb. 29, 2020 to June 1, 2020. Patients with COVID-19 “had multiple neurological sequelae, including seizures, strokes, and encephalopathy,” he said.

However, the effects of COVID-19 on individuals with epilepsy “remain unclear,” Dr. Singh said.

For their study, the researchers assessed 917 patients in 13 New York City metropolitan hospitals. All participants had received a confirmed positive test result on PCR for COVID and had received an antiepileptic medication upon admission. The patients were admitted between Feb. 14 and June 14, 2020.

For the study, the patients were first divided into two groups: those with a history of epilepsy (n = 451), and those without such a history (n = 466).

The first group was further divided on the basis of those who presented with breakthrough seizures and those who presented without them. The second group was further divided on the basis of those who presented with new-onset seizures and those who presented without them.
 

Significant adverse outcomes

Results showed that 27% of the patients without a history of epilepsy experienced a novel/new-onset seizure and that 11% of the patients with a history of epilepsy experienced a novel/breakthrough seizure (odds ratio, 3.15; P < .0001).

In addition, participants with new-onset seizures had a longer stay in the hospital (mean, 26.9 days) than the subgroup with a history of epilepsy and no breakthrough seizures (10.9 days) and the subgroup with a history of epilepsy who did experience breakthrough seizures (12.8 days; P < .0001 for both comparisons).

In the group of patients with a history of epilepsy, there were no significant differences in lengths of stay between those with and those without breakthrough seizures (P = .68).

Although mortality rates did not differ significantly between the full group with a history of epilepsy versus the full group without epilepsy (23% vs. 25%; OR, 0.9), the mortality rate was significantly higher among patients who experienced novel seizures than among those who did not experience such seizures (29% vs. 23%; OR, 1.4; P = .045).

Mr. Bhaskar noted that there are “many hypotheses for the mechanism by which COVID-19 might cause seizures.” Those mechanisms include proinflammatory cytokine storms, which may increase the rate of apoptosis, neuronal necrosis, and glutamate concentrations and may disrupt the blood-brain barrier. Another hypothesis is that SARS-CoV-2 infection may lead to hypoxia and abnormal coagulation, resulting in stroke and a subsequent increase in the risk for seizures.

Interestingly, “the presence of antiepileptic medications in patients with epilepsy may confer a protective effect against breakthrough seizures,” Dr. Singh said. “However, some subclinical seizures may be misdiagnosed as encephalopathy when patients present with COVID-19 infections.”

He added that further research is needed into the mechanisms linking these infections and new-onset seizures and to “identify subclinical seizures in encephalopathic patients.”

Asked during the question-and-answer session whether the investigators had assessed differences by demographics, such as age or sex, Dr. Singh said, “We have not subdivided them that way yet,” but he said he would like to do so in the future. He also plans to look further into which specific medications were used by the participants.

The investigators have reported no relevant financial relationships.

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

COVID-19 is linked to novel seizures and subsequent adverse outcomes, including death, in patients without a previous history of epilepsy, new research shows. In a retrospective study of more than 900 patients admitted to the hospital with COVID-19, those without a known history of epilepsy had three times greater odds of experiencing novel seizures than those with a known history of epilepsy.

In addition, among patients with new-onset seizures, hospital stays were about 15 days longer – and mortality rates were significantly higher.

“We’re finding that there are many neurological consequences that can happen with COVID-19 infections, and it’s important for clinicians to keep that in mind as they monitor people long term,” said study investigator Neeraj Singh, MD, neurologist and epileptologist with Northwell Health System, Great Neck, New York.

Dr. Singh noted that although seizures “might not be the most common thing we see in people with COVID-19, they seem to be new seizures and not just a seizure we knew would happen in someone with epilepsy.”

“So there’s definitely a need now for more prospective research and following people over time to fully understand all the different things that might be newly a problem for them in the long term,” he added.

Dr. Singh and Hardik Bhaskar, an undergraduate student at Hunter College, New York, presented the study findings at the American Academy of Neurology’s 2021 annual meeting.
 

Largest sample to date

“This study explores the relationship between the incidences of COVID-19 infections and [novel] epileptic seizures in the largest sample to date in a single New York–based hospital system,” the investigators noted. Novel seizures included both new-onset and breakthrough seizures.

Dr. Singh told meeting attendees that the “early epicenter” of the COVID pandemic was in New York and occurred from Feb. 29, 2020 to June 1, 2020. Patients with COVID-19 “had multiple neurological sequelae, including seizures, strokes, and encephalopathy,” he said.

However, the effects of COVID-19 on individuals with epilepsy “remain unclear,” Dr. Singh said.

For their study, the researchers assessed 917 patients in 13 New York City metropolitan hospitals. All participants had received a confirmed positive test result on PCR for COVID and had received an antiepileptic medication upon admission. The patients were admitted between Feb. 14 and June 14, 2020.

For the study, the patients were first divided into two groups: those with a history of epilepsy (n = 451), and those without such a history (n = 466).

The first group was further divided on the basis of those who presented with breakthrough seizures and those who presented without them. The second group was further divided on the basis of those who presented with new-onset seizures and those who presented without them.
 

Significant adverse outcomes

Results showed that 27% of the patients without a history of epilepsy experienced a novel/new-onset seizure and that 11% of the patients with a history of epilepsy experienced a novel/breakthrough seizure (odds ratio, 3.15; P < .0001).

In addition, participants with new-onset seizures had a longer stay in the hospital (mean, 26.9 days) than the subgroup with a history of epilepsy and no breakthrough seizures (10.9 days) and the subgroup with a history of epilepsy who did experience breakthrough seizures (12.8 days; P < .0001 for both comparisons).

In the group of patients with a history of epilepsy, there were no significant differences in lengths of stay between those with and those without breakthrough seizures (P = .68).

Although mortality rates did not differ significantly between the full group with a history of epilepsy versus the full group without epilepsy (23% vs. 25%; OR, 0.9), the mortality rate was significantly higher among patients who experienced novel seizures than among those who did not experience such seizures (29% vs. 23%; OR, 1.4; P = .045).

Mr. Bhaskar noted that there are “many hypotheses for the mechanism by which COVID-19 might cause seizures.” Those mechanisms include proinflammatory cytokine storms, which may increase the rate of apoptosis, neuronal necrosis, and glutamate concentrations and may disrupt the blood-brain barrier. Another hypothesis is that SARS-CoV-2 infection may lead to hypoxia and abnormal coagulation, resulting in stroke and a subsequent increase in the risk for seizures.

Interestingly, “the presence of antiepileptic medications in patients with epilepsy may confer a protective effect against breakthrough seizures,” Dr. Singh said. “However, some subclinical seizures may be misdiagnosed as encephalopathy when patients present with COVID-19 infections.”

He added that further research is needed into the mechanisms linking these infections and new-onset seizures and to “identify subclinical seizures in encephalopathic patients.”

Asked during the question-and-answer session whether the investigators had assessed differences by demographics, such as age or sex, Dr. Singh said, “We have not subdivided them that way yet,” but he said he would like to do so in the future. He also plans to look further into which specific medications were used by the participants.

The investigators have reported no relevant financial relationships.

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

Nivolumab continues to demonstrate a substantial survival benefit over docetaxel at 5 years in advanced non-small cell lung cancer (NSCLC) patients who progressed on platinum-based therapies, according to a pooled analysis of two phase 3 trials published in the Journal of Clinical Oncology.

Across the two studies – CheckMate 017 and 057 – 854 patients were randomized 1:1 following progression on platinum therapy to either nivolumab at 3 mg/kg once every 2 weeks or docetaxel at 75 mg/m² once every 3 weeks until further progression or unacceptable toxicity. Previously reported overall survival (OS) outcomes favored nivolumab.

At a minimum follow-up of 5.4 years, 50 nivolumab-treated patients and 9 docetaxel-treated patients were still alive.

The 5-year OS rates were 13.4% in the nivolumab arm and 2.6% in the docetaxel arm. The 5-year progression-free survival (PFS) rates were 8% and 0%, respectively.

There were no new safety signals with nivolumab, and there was no evidence of select late-onset grade 3-4 adverse events.

According to the study authors, this analysis is the longest phase 3 follow-up to date of a PD-1 inhibitor in previously treated, advanced NSCLC, and it suggests that “long-term survival beyond 5 years may ... be possible in NSCLC.”

“The results indicate that some patients with NSCLC can have long-lasting benefit from checkpoint inhibitors. We have seen similar results in terms of long-term OS with pembrolizumab,” said investigator Hossein Borghaei, DO, chief of thoracic medical oncology at the Fox Chase Cancer Center in Philadelphia.

Dr. Borghaei said the question now is “how to identify the population that really benefits from these treatments. We think PD-L1–high [patients] have a better chance, [as do patients with] tumors that have a higher percentage of tumor-infiltrating lymphocytes, but there’s nothing concrete beyond that.”

No baseline clinical or tumor factors emerged to distinguish between long-and short-term survivors, but the 5-year OS rate was 18.3% among nivolumab-treated patients with PD-L1 expression at or above 1% versus 8% among patients with expression below 1%.

The optimal duration of nivolumab treatment beyond 1 year is also uncertain.

The median duration of therapy was 36.9 months in the 5-year survivors treated with nivolumab, and 36% of patients (18/50) were still on nivolumab at the 5-year mark.

The median duration of time off treatment was 41.9 months among patients who discontinued nivolumab. Five patients (10%) were off treatment with no subsequent therapy and had not progressed at 5 years, “suggesting benefit even for patients who stopped nivolumab treatment,” the researchers wrote.

They also found that nivolumab-treated patients who remained alive at 3 years appeared to stabilize and plateau thereafter, with early response suggesting better long-term outcomes. The majority of patients without disease progression at 2, 3, and 4 years, for instance, remained progression free at 5 years. Nearly one-third of patients who achieved an objective response with nivolumab – but none of the patients who responded to docetaxel – had ongoing responses at 5 years.

Similarly, nivolumab-treated patients without disease progression at 2 years and 3 years had an 82% and 93% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression free at 5 years.

This research was funded by Bristol-Myers Squibb. Dr. Borghaei and coauthors disclosed numerous ties to the company, including employment.

[email protected]

Nivolumab continues to demonstrate a substantial survival benefit over docetaxel at 5 years in advanced non-small cell lung cancer (NSCLC) patients who progressed on platinum-based therapies, according to a pooled analysis of two phase 3 trials published in the Journal of Clinical Oncology.

Across the two studies – CheckMate 017 and 057 – 854 patients were randomized 1:1 following progression on platinum therapy to either nivolumab at 3 mg/kg once every 2 weeks or docetaxel at 75 mg/m² once every 3 weeks until further progression or unacceptable toxicity. Previously reported overall survival (OS) outcomes favored nivolumab.

At a minimum follow-up of 5.4 years, 50 nivolumab-treated patients and 9 docetaxel-treated patients were still alive.

The 5-year OS rates were 13.4% in the nivolumab arm and 2.6% in the docetaxel arm. The 5-year progression-free survival (PFS) rates were 8% and 0%, respectively.

There were no new safety signals with nivolumab, and there was no evidence of select late-onset grade 3-4 adverse events.

According to the study authors, this analysis is the longest phase 3 follow-up to date of a PD-1 inhibitor in previously treated, advanced NSCLC, and it suggests that “long-term survival beyond 5 years may ... be possible in NSCLC.”

“The results indicate that some patients with NSCLC can have long-lasting benefit from checkpoint inhibitors. We have seen similar results in terms of long-term OS with pembrolizumab,” said investigator Hossein Borghaei, DO, chief of thoracic medical oncology at the Fox Chase Cancer Center in Philadelphia.

Dr. Borghaei said the question now is “how to identify the population that really benefits from these treatments. We think PD-L1–high [patients] have a better chance, [as do patients with] tumors that have a higher percentage of tumor-infiltrating lymphocytes, but there’s nothing concrete beyond that.”

No baseline clinical or tumor factors emerged to distinguish between long-and short-term survivors, but the 5-year OS rate was 18.3% among nivolumab-treated patients with PD-L1 expression at or above 1% versus 8% among patients with expression below 1%.

The optimal duration of nivolumab treatment beyond 1 year is also uncertain.

The median duration of therapy was 36.9 months in the 5-year survivors treated with nivolumab, and 36% of patients (18/50) were still on nivolumab at the 5-year mark.

The median duration of time off treatment was 41.9 months among patients who discontinued nivolumab. Five patients (10%) were off treatment with no subsequent therapy and had not progressed at 5 years, “suggesting benefit even for patients who stopped nivolumab treatment,” the researchers wrote.

They also found that nivolumab-treated patients who remained alive at 3 years appeared to stabilize and plateau thereafter, with early response suggesting better long-term outcomes. The majority of patients without disease progression at 2, 3, and 4 years, for instance, remained progression free at 5 years. Nearly one-third of patients who achieved an objective response with nivolumab – but none of the patients who responded to docetaxel – had ongoing responses at 5 years.

Similarly, nivolumab-treated patients without disease progression at 2 years and 3 years had an 82% and 93% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression free at 5 years.

This research was funded by Bristol-Myers Squibb. Dr. Borghaei and coauthors disclosed numerous ties to the company, including employment.

[email protected]

Nivolumab continues to demonstrate a substantial survival benefit over docetaxel at 5 years in advanced non-small cell lung cancer (NSCLC) patients who progressed on platinum-based therapies, according to a pooled analysis of two phase 3 trials published in the Journal of Clinical Oncology.

Across the two studies – CheckMate 017 and 057 – 854 patients were randomized 1:1 following progression on platinum therapy to either nivolumab at 3 mg/kg once every 2 weeks or docetaxel at 75 mg/m² once every 3 weeks until further progression or unacceptable toxicity. Previously reported overall survival (OS) outcomes favored nivolumab.

At a minimum follow-up of 5.4 years, 50 nivolumab-treated patients and 9 docetaxel-treated patients were still alive.

The 5-year OS rates were 13.4% in the nivolumab arm and 2.6% in the docetaxel arm. The 5-year progression-free survival (PFS) rates were 8% and 0%, respectively.

There were no new safety signals with nivolumab, and there was no evidence of select late-onset grade 3-4 adverse events.

According to the study authors, this analysis is the longest phase 3 follow-up to date of a PD-1 inhibitor in previously treated, advanced NSCLC, and it suggests that “long-term survival beyond 5 years may ... be possible in NSCLC.”

“The results indicate that some patients with NSCLC can have long-lasting benefit from checkpoint inhibitors. We have seen similar results in terms of long-term OS with pembrolizumab,” said investigator Hossein Borghaei, DO, chief of thoracic medical oncology at the Fox Chase Cancer Center in Philadelphia.

Dr. Borghaei said the question now is “how to identify the population that really benefits from these treatments. We think PD-L1–high [patients] have a better chance, [as do patients with] tumors that have a higher percentage of tumor-infiltrating lymphocytes, but there’s nothing concrete beyond that.”

No baseline clinical or tumor factors emerged to distinguish between long-and short-term survivors, but the 5-year OS rate was 18.3% among nivolumab-treated patients with PD-L1 expression at or above 1% versus 8% among patients with expression below 1%.

The optimal duration of nivolumab treatment beyond 1 year is also uncertain.

The median duration of therapy was 36.9 months in the 5-year survivors treated with nivolumab, and 36% of patients (18/50) were still on nivolumab at the 5-year mark.

The median duration of time off treatment was 41.9 months among patients who discontinued nivolumab. Five patients (10%) were off treatment with no subsequent therapy and had not progressed at 5 years, “suggesting benefit even for patients who stopped nivolumab treatment,” the researchers wrote.

They also found that nivolumab-treated patients who remained alive at 3 years appeared to stabilize and plateau thereafter, with early response suggesting better long-term outcomes. The majority of patients without disease progression at 2, 3, and 4 years, for instance, remained progression free at 5 years. Nearly one-third of patients who achieved an objective response with nivolumab – but none of the patients who responded to docetaxel – had ongoing responses at 5 years.

Similarly, nivolumab-treated patients without disease progression at 2 years and 3 years had an 82% and 93% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression free at 5 years.

This research was funded by Bristol-Myers Squibb. Dr. Borghaei and coauthors disclosed numerous ties to the company, including employment.

[email protected]

The remarkable efficacy of biologics for moderate to severe psoriasis has led some to ask if biologics should be used for milder cases.

The issue was tackled in a debate at the American Academy of Dermatology Virtual Meeting Experience.

Taking the con side, Kenneth Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee, argued that, with the high cost of biologics, availability of many alternatives, and other issues, “we should just say no. ... There is no good reason that we need to expand the use of biologics in patients with limited disease.”

On the pro side, Richard Langley, MD, professor of dermatology at Dalhousie University Halifax, N.S, argued for a nuanced approach. He noted that patients with smaller patches of disease can be just as miserable as patients who hit traditional benchmarks of increased severity, such as high body surface area involvement – especially if those small areas are in sensitive locations like the scalp, palms, or genitals.

The decision to use a biologic should hinge on how badly patients and their quality of life are affected, not on “some artificial and limiting definition” of severity, Dr. Langley said.

Dr. Gordon didn’t disagree, noting that current use criteria include objective measures as well as disease in sensitive areas and failure of alternative treatments.

Rather, he was concerned about “expanding the definition of who is eligible beyond these criteria ... to chase every last bit of” disease. “I don’t think we have” a good rationale for that approach, he said.

Cost is the most important issue, Dr. Gordon said.

With more biologics on the way and prices continuing to go up, “there is going to a be a huge challenge to our use of these expensive medicines over the next few years” from payers. “It is important that we use them smartly in order to make sure we are able to use them for people with severe disease” who really need them. If “we start using biologics for all our patients with psoriasis,” it will be a “cost disaster,” Dr. Gordon said.

In addition, topicals and home phototherapy can be effective as long as patients adhere to them, as can alternative systemic agents, such as methotrexate and apremilast.

Often with biologics, “the issue is mainly convenience” rather than a fundamental problem with the alternatives, and despite the good safety record in trials, “chasing the last bit” of psoriasis with a biologic “is not necessarily” without risk for the patient, Dr. Gordon said.

Still, there can be a “pretty significant disconnect” between how patients perceive their psoriasis and “what physicians are thinking and prescribing” for it based on objective measures, Dr. Langley noted. Sometimes patients who have limited disease but are in significant distress aren’t even receiving treatment or are only given another cream to add to their collection of ones that haven’t worked.

One problem with traditional severity classifications is that they don’t generally take patients’ subjective experience into account, he added. There’s also been a lack of standardization to the point that dermatologists, researchers, and payers can sometimes disagree over severity in a given patient.

There’s movement toward better incorporation of patient experience into severity considerations, but for now at least, a designation of mild psoriasis can underestimate the true severity of disease, Dr. Langley said.

Dr. Gordon and Dr. Langley reported receiving honoraria and/or research support from many pharmaceutical companies, including AbbVie, Pfizer, and Lilly.

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

The remarkable efficacy of biologics for moderate to severe psoriasis has led some to ask if biologics should be used for milder cases.

The issue was tackled in a debate at the American Academy of Dermatology Virtual Meeting Experience.

Taking the con side, Kenneth Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee, argued that, with the high cost of biologics, availability of many alternatives, and other issues, “we should just say no. ... There is no good reason that we need to expand the use of biologics in patients with limited disease.”

On the pro side, Richard Langley, MD, professor of dermatology at Dalhousie University Halifax, N.S, argued for a nuanced approach. He noted that patients with smaller patches of disease can be just as miserable as patients who hit traditional benchmarks of increased severity, such as high body surface area involvement – especially if those small areas are in sensitive locations like the scalp, palms, or genitals.

The decision to use a biologic should hinge on how badly patients and their quality of life are affected, not on “some artificial and limiting definition” of severity, Dr. Langley said.

Dr. Gordon didn’t disagree, noting that current use criteria include objective measures as well as disease in sensitive areas and failure of alternative treatments.

Rather, he was concerned about “expanding the definition of who is eligible beyond these criteria ... to chase every last bit of” disease. “I don’t think we have” a good rationale for that approach, he said.

Cost is the most important issue, Dr. Gordon said.

With more biologics on the way and prices continuing to go up, “there is going to a be a huge challenge to our use of these expensive medicines over the next few years” from payers. “It is important that we use them smartly in order to make sure we are able to use them for people with severe disease” who really need them. If “we start using biologics for all our patients with psoriasis,” it will be a “cost disaster,” Dr. Gordon said.

In addition, topicals and home phototherapy can be effective as long as patients adhere to them, as can alternative systemic agents, such as methotrexate and apremilast.

Often with biologics, “the issue is mainly convenience” rather than a fundamental problem with the alternatives, and despite the good safety record in trials, “chasing the last bit” of psoriasis with a biologic “is not necessarily” without risk for the patient, Dr. Gordon said.

Still, there can be a “pretty significant disconnect” between how patients perceive their psoriasis and “what physicians are thinking and prescribing” for it based on objective measures, Dr. Langley noted. Sometimes patients who have limited disease but are in significant distress aren’t even receiving treatment or are only given another cream to add to their collection of ones that haven’t worked.

One problem with traditional severity classifications is that they don’t generally take patients’ subjective experience into account, he added. There’s also been a lack of standardization to the point that dermatologists, researchers, and payers can sometimes disagree over severity in a given patient.

There’s movement toward better incorporation of patient experience into severity considerations, but for now at least, a designation of mild psoriasis can underestimate the true severity of disease, Dr. Langley said.

Dr. Gordon and Dr. Langley reported receiving honoraria and/or research support from many pharmaceutical companies, including AbbVie, Pfizer, and Lilly.

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

The remarkable efficacy of biologics for moderate to severe psoriasis has led some to ask if biologics should be used for milder cases.

The issue was tackled in a debate at the American Academy of Dermatology Virtual Meeting Experience.

Taking the con side, Kenneth Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee, argued that, with the high cost of biologics, availability of many alternatives, and other issues, “we should just say no. ... There is no good reason that we need to expand the use of biologics in patients with limited disease.”

On the pro side, Richard Langley, MD, professor of dermatology at Dalhousie University Halifax, N.S, argued for a nuanced approach. He noted that patients with smaller patches of disease can be just as miserable as patients who hit traditional benchmarks of increased severity, such as high body surface area involvement – especially if those small areas are in sensitive locations like the scalp, palms, or genitals.

The decision to use a biologic should hinge on how badly patients and their quality of life are affected, not on “some artificial and limiting definition” of severity, Dr. Langley said.

Dr. Gordon didn’t disagree, noting that current use criteria include objective measures as well as disease in sensitive areas and failure of alternative treatments.

Rather, he was concerned about “expanding the definition of who is eligible beyond these criteria ... to chase every last bit of” disease. “I don’t think we have” a good rationale for that approach, he said.

Cost is the most important issue, Dr. Gordon said.

With more biologics on the way and prices continuing to go up, “there is going to a be a huge challenge to our use of these expensive medicines over the next few years” from payers. “It is important that we use them smartly in order to make sure we are able to use them for people with severe disease” who really need them. If “we start using biologics for all our patients with psoriasis,” it will be a “cost disaster,” Dr. Gordon said.

In addition, topicals and home phototherapy can be effective as long as patients adhere to them, as can alternative systemic agents, such as methotrexate and apremilast.

Often with biologics, “the issue is mainly convenience” rather than a fundamental problem with the alternatives, and despite the good safety record in trials, “chasing the last bit” of psoriasis with a biologic “is not necessarily” without risk for the patient, Dr. Gordon said.

Still, there can be a “pretty significant disconnect” between how patients perceive their psoriasis and “what physicians are thinking and prescribing” for it based on objective measures, Dr. Langley noted. Sometimes patients who have limited disease but are in significant distress aren’t even receiving treatment or are only given another cream to add to their collection of ones that haven’t worked.

One problem with traditional severity classifications is that they don’t generally take patients’ subjective experience into account, he added. There’s also been a lack of standardization to the point that dermatologists, researchers, and payers can sometimes disagree over severity in a given patient.

There’s movement toward better incorporation of patient experience into severity considerations, but for now at least, a designation of mild psoriasis can underestimate the true severity of disease, Dr. Langley said.

Dr. Gordon and Dr. Langley reported receiving honoraria and/or research support from many pharmaceutical companies, including AbbVie, Pfizer, and Lilly.

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

Researchers are reporting impressive results in a small, open-label trial of the JAK inhibitor tofacitinib in cutaneous sarcoidosis: 6 of 10 patients improved so much that they reached a disease activity level of zero, and all patients improved by an average of 83% via a scoring system.

“Not only did patients get better, but they were in many cases able to come off their baseline immunosuppressive regimen, including prednisone and methotrexate. They’d get off prednisone entirely or, in some cases, decrease it substantially,” study investigator William Damsky, MD, PhD, reported at the American Academy of Dermatology Virtual Meeting Experience.

Sarcoidosis is a common disease that affects an estimated 1 in 25 Black women and is believed to contribute to the deaths of about 4,000 people in the United States each year, noted Dr. Damsky of the department of dermatology, Yale University, New Haven, Conn. One famous patient is comedian Bernie Mac, who died from the condition in 2008.

“Approximately one third of patients have cutaneous involvement,” Dr. Damsky said, and skin may be the only manifestation of the disease. There is no Food and Drug Administration-approved therapy for cutaneous sarcoidosis, he added. Prednisone, the first-line therapy in skin manifestations, is approved only for pulmonary sarcoidosis.


“Oftentimes, there’s an attempt to transition either partially or fully to other therapies, including methotrexate and TNF-alpha blockers. But there’s been mixed success in doing that,” he said. This is not always possible, “so a lot of patients end up on prednisone.”

Earlier, a team at Yale prescribed 5 mg tofacitinib (Xeljanz) for several patients with severe cutaneous sarcoidosis and saw impressive results, Dr. Damsky said, including a patient with pulmonary sarcoidosis that also improved. He noted that there are case reports in the medical literature with similar findings.

Those positive results inspired the new study. Researchers recruited 10 patients with cutaneous sarcoidosis (9 with internal organ involvement) with a Cutaneous Sarcoidosis Activity and Morphology Instrument ( CSAMI ) score of 10 or higher. Nine patients were in their 50s, one was aged 63 years, and five were men. Skin colors of the patients ranged from Fitzpatrick skin types I to VI, and all had been taking at least two medications, typically methotrexate and prednisone.

The patients received 5 mg of tofacitinib twice a day for 6 months. “Everyone got better during the study, and six patients had a complete response, which we defined as a CSAMI score of zero activity,” Dr. Damsky said. “It’s really quite remarkable to see that.” Overall, the patients saw an 83% improvement in CSAMI scores.

In regard to safety, “all patients completed the study,” he said. “Tofacitinib was well tolerated, and there were no serious adverse effects or events.”

Tofacitinib is approved for treating rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis.

A month’s supply of twice-daily 5 mg tofacitinib pills would cost $4,900-$5,100 with free coupons, according to information accessed on April 24, 2021, on GoodRx.com. Generics are not available.

In an interview, Sotonye Imadojemu, MD, of the department of dermatology, Brigham and Women’s Hospital, Boston, praised the study, and said “tofacitinib is a reasonable treatment for treatment-refractory or extensive cutaneous sarcoidosis,” although it will be helpful to get results from randomized-controlled trials.

She cautioned that the drug “is a powerful immunosuppressant, so the risk of infection must be discussed with patients before prescribing. Screening for chronic infections such as viral hepatitis, tuberculosis, and HIV should be completed prior to treatment initiation. Blood counts, liver function, and lipid panels should be regularly monitored. The vaccines necessary for those who are immunosuppressed should be administered as able, and age-appropriate cancer screening must be kept up to date.”

The study was funded by Pfizer, the Dermatology Foundation, and the Yale Department of Dermatology. Dr. Damsky disclosed research support (Pfizer), consulting fees (Eli Lilly, Pfizer, TWi Biotechnology), and licensing fees (EMD Millipore/MillporeSigma). Dr. Imadojemu has no disclosures.

This article was updated 5/5/21.

Researchers are reporting impressive results in a small, open-label trial of the JAK inhibitor tofacitinib in cutaneous sarcoidosis: 6 of 10 patients improved so much that they reached a disease activity level of zero, and all patients improved by an average of 83% via a scoring system.

“Not only did patients get better, but they were in many cases able to come off their baseline immunosuppressive regimen, including prednisone and methotrexate. They’d get off prednisone entirely or, in some cases, decrease it substantially,” study investigator William Damsky, MD, PhD, reported at the American Academy of Dermatology Virtual Meeting Experience.

Sarcoidosis is a common disease that affects an estimated 1 in 25 Black women and is believed to contribute to the deaths of about 4,000 people in the United States each year, noted Dr. Damsky of the department of dermatology, Yale University, New Haven, Conn. One famous patient is comedian Bernie Mac, who died from the condition in 2008.

“Approximately one third of patients have cutaneous involvement,” Dr. Damsky said, and skin may be the only manifestation of the disease. There is no Food and Drug Administration-approved therapy for cutaneous sarcoidosis, he added. Prednisone, the first-line therapy in skin manifestations, is approved only for pulmonary sarcoidosis.


“Oftentimes, there’s an attempt to transition either partially or fully to other therapies, including methotrexate and TNF-alpha blockers. But there’s been mixed success in doing that,” he said. This is not always possible, “so a lot of patients end up on prednisone.”

Earlier, a team at Yale prescribed 5 mg tofacitinib (Xeljanz) for several patients with severe cutaneous sarcoidosis and saw impressive results, Dr. Damsky said, including a patient with pulmonary sarcoidosis that also improved. He noted that there are case reports in the medical literature with similar findings.

Those positive results inspired the new study. Researchers recruited 10 patients with cutaneous sarcoidosis (9 with internal organ involvement) with a Cutaneous Sarcoidosis Activity and Morphology Instrument ( CSAMI ) score of 10 or higher. Nine patients were in their 50s, one was aged 63 years, and five were men. Skin colors of the patients ranged from Fitzpatrick skin types I to VI, and all had been taking at least two medications, typically methotrexate and prednisone.

The patients received 5 mg of tofacitinib twice a day for 6 months. “Everyone got better during the study, and six patients had a complete response, which we defined as a CSAMI score of zero activity,” Dr. Damsky said. “It’s really quite remarkable to see that.” Overall, the patients saw an 83% improvement in CSAMI scores.

In regard to safety, “all patients completed the study,” he said. “Tofacitinib was well tolerated, and there were no serious adverse effects or events.”

Tofacitinib is approved for treating rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis.

A month’s supply of twice-daily 5 mg tofacitinib pills would cost $4,900-$5,100 with free coupons, according to information accessed on April 24, 2021, on GoodRx.com. Generics are not available.

In an interview, Sotonye Imadojemu, MD, of the department of dermatology, Brigham and Women’s Hospital, Boston, praised the study, and said “tofacitinib is a reasonable treatment for treatment-refractory or extensive cutaneous sarcoidosis,” although it will be helpful to get results from randomized-controlled trials.

She cautioned that the drug “is a powerful immunosuppressant, so the risk of infection must be discussed with patients before prescribing. Screening for chronic infections such as viral hepatitis, tuberculosis, and HIV should be completed prior to treatment initiation. Blood counts, liver function, and lipid panels should be regularly monitored. The vaccines necessary for those who are immunosuppressed should be administered as able, and age-appropriate cancer screening must be kept up to date.”

The study was funded by Pfizer, the Dermatology Foundation, and the Yale Department of Dermatology. Dr. Damsky disclosed research support (Pfizer), consulting fees (Eli Lilly, Pfizer, TWi Biotechnology), and licensing fees (EMD Millipore/MillporeSigma). Dr. Imadojemu has no disclosures.

This article was updated 5/5/21.

Researchers are reporting impressive results in a small, open-label trial of the JAK inhibitor tofacitinib in cutaneous sarcoidosis: 6 of 10 patients improved so much that they reached a disease activity level of zero, and all patients improved by an average of 83% via a scoring system.

“Not only did patients get better, but they were in many cases able to come off their baseline immunosuppressive regimen, including prednisone and methotrexate. They’d get off prednisone entirely or, in some cases, decrease it substantially,” study investigator William Damsky, MD, PhD, reported at the American Academy of Dermatology Virtual Meeting Experience.

Sarcoidosis is a common disease that affects an estimated 1 in 25 Black women and is believed to contribute to the deaths of about 4,000 people in the United States each year, noted Dr. Damsky of the department of dermatology, Yale University, New Haven, Conn. One famous patient is comedian Bernie Mac, who died from the condition in 2008.

“Approximately one third of patients have cutaneous involvement,” Dr. Damsky said, and skin may be the only manifestation of the disease. There is no Food and Drug Administration-approved therapy for cutaneous sarcoidosis, he added. Prednisone, the first-line therapy in skin manifestations, is approved only for pulmonary sarcoidosis.


“Oftentimes, there’s an attempt to transition either partially or fully to other therapies, including methotrexate and TNF-alpha blockers. But there’s been mixed success in doing that,” he said. This is not always possible, “so a lot of patients end up on prednisone.”

Earlier, a team at Yale prescribed 5 mg tofacitinib (Xeljanz) for several patients with severe cutaneous sarcoidosis and saw impressive results, Dr. Damsky said, including a patient with pulmonary sarcoidosis that also improved. He noted that there are case reports in the medical literature with similar findings.

Those positive results inspired the new study. Researchers recruited 10 patients with cutaneous sarcoidosis (9 with internal organ involvement) with a Cutaneous Sarcoidosis Activity and Morphology Instrument ( CSAMI ) score of 10 or higher. Nine patients were in their 50s, one was aged 63 years, and five were men. Skin colors of the patients ranged from Fitzpatrick skin types I to VI, and all had been taking at least two medications, typically methotrexate and prednisone.

The patients received 5 mg of tofacitinib twice a day for 6 months. “Everyone got better during the study, and six patients had a complete response, which we defined as a CSAMI score of zero activity,” Dr. Damsky said. “It’s really quite remarkable to see that.” Overall, the patients saw an 83% improvement in CSAMI scores.

In regard to safety, “all patients completed the study,” he said. “Tofacitinib was well tolerated, and there were no serious adverse effects or events.”

Tofacitinib is approved for treating rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis.

A month’s supply of twice-daily 5 mg tofacitinib pills would cost $4,900-$5,100 with free coupons, according to information accessed on April 24, 2021, on GoodRx.com. Generics are not available.

In an interview, Sotonye Imadojemu, MD, of the department of dermatology, Brigham and Women’s Hospital, Boston, praised the study, and said “tofacitinib is a reasonable treatment for treatment-refractory or extensive cutaneous sarcoidosis,” although it will be helpful to get results from randomized-controlled trials.

She cautioned that the drug “is a powerful immunosuppressant, so the risk of infection must be discussed with patients before prescribing. Screening for chronic infections such as viral hepatitis, tuberculosis, and HIV should be completed prior to treatment initiation. Blood counts, liver function, and lipid panels should be regularly monitored. The vaccines necessary for those who are immunosuppressed should be administered as able, and age-appropriate cancer screening must be kept up to date.”

The study was funded by Pfizer, the Dermatology Foundation, and the Yale Department of Dermatology. Dr. Damsky disclosed research support (Pfizer), consulting fees (Eli Lilly, Pfizer, TWi Biotechnology), and licensing fees (EMD Millipore/MillporeSigma). Dr. Imadojemu has no disclosures.

This article was updated 5/5/21.