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Biosimilars and patients: Discussions should address safety, cost, and anxiety about change
Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.
“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.
The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”
He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”
The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.
It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.
Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
Insurance often drives the conversation
The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.
Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.
Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.
Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”
However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.
This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.
But not all physicians are quick to prescribe biosimilars.
Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”
Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
Conversations about cost
Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.
If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.
Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.
Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”
Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.
“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.
Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”
For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.
Biosimilars 101: Familiarizing patients
Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.
Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.
Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar. 
As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.
When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.
Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.
In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
A village approach to education
When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.
The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar.
This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”
Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”
Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.
No consensus on interchangeability
Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.
If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.
The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.
In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).
“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.
Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”
Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.
“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
Resources for physicians, patients
The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.
The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.
Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.
“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.
Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.
Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.
A version of this article originally appeared on Medscape.com.
Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.
“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.
The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”
He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”
The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.
It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.
Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
Insurance often drives the conversation
The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.
Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.
Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.
Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”
However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.
This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.
But not all physicians are quick to prescribe biosimilars.
Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”
Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
Conversations about cost
Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.
If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.
Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.
Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”
Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.
“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.
Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”
For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.
Biosimilars 101: Familiarizing patients
Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.
Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.
Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar.
As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.
When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.
Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.
In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
A village approach to education
When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.
The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar.
This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”
Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”
Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.
No consensus on interchangeability
Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.
If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.
The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.
In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).
“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.
Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”
Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.
“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
Resources for physicians, patients
The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.
The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.
Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.
“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.
Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.
Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.
A version of this article originally appeared on Medscape.com.
Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.
“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.
The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”
He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”
The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.
It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.
Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
Insurance often drives the conversation
The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.
Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.
Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.
Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”
However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.
This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.
But not all physicians are quick to prescribe biosimilars.
Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”
Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
Conversations about cost
Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.
If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.
Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.
Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”
Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.
“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.
Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”
For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.
Biosimilars 101: Familiarizing patients
Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.
Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.
Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar.
As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.
When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.
Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.
In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
A village approach to education
When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.
The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar.
This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”
Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”
Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.
No consensus on interchangeability
Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.
If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.
The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.
In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).
“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.
Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”
Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.
“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
Resources for physicians, patients
The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.
The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.
Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.
“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.
Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.
Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.
A version of this article originally appeared on Medscape.com.
Could a baby’s gut health be an early predictor of future type 1 diabetes?
Microbial biomarkers for type 1 diabetes may be present in infants as young as 12 months old, suggesting the potential to mitigate disease onset by nurturing a healthy gut microbiome early, show data from the Swedish general population.
“Our findings indicate that the gut of infants who go on to develop type 1 diabetes is notably different from healthy babies,” said Malin Bélteky, MD, from the Crown Princess Victoria’s Children’s Hospital, Linköping, Sweden, who jointly led the work, which was recently published in Diabetologia, alongside Patricia L. Milletich, PhD candidate, from the University of Florida, Gainesville.
“This discovery could be used to help identity infants at [the] highest risk of developing type 1 diabetes before or during the first stage of disease and could offer the opportunity to bolster a healthy gut microbiome to prevent the disease from becoming established,” added Dr. Bélteky.
Currently, beta-cell autoantibodies are used to predict disease, which are usually only identifiable between 9 and 36 months of age.
Marian Rewers, MD, PhD, professor of pediatrics & medicine, University of Colorado, Denver, and principal investigator of The Environmental Determinants of Diabetes in the Young (TEDDY) study, welcomed the findings, saying it is a well-designed study from a strong group of investigators.
“While the effective number of cases was very small [n = 16], the results were apparently adjusted for multiple comparisons, and significant differences were noted in the microbiome of cases versus controls at 1 year of age. This was 12 years prior to the average age of type 1 diabetes diagnosis in the cases,” he said.
“The differences in diversity and abundances of specific bacteria need to be interpreted with caution; however, the study results are consistent with several previous reports,” he noted.
Differences in microbial diversity and function
Data were drawn from children participating in the longitudinal, general population All Babies In Southeast Sweden (ABIS) study. Microbiota from stool samples, taken at age 1 year, were sequenced and analyzed to establish diversity, abundance, and functional status of the component bacteria. Questionnaires were completed at birth and at 1 year of age, allowing for the study of environmental factors that might influence the microbiota or type 1 diabetes risk independently. Parent diaries provided information on pregnancy, nutrition, and lifestyle factors.
Of the cohort of 167 children who developed type 1 diabetes by 2020, stool samples were available for 16 of these participants, which were compared with 268 healthy controls. The microbiomes of the 16 infants who later developed type 1 diabetes were compared with 100 iterations of 32 matched control infants (matched by geographical region, siblings at birth, residence type, duration of breastfeeding, and month of stool collection) who didn’t develop type 1 diabetes by the age of 20.
Specific bacteria found in greater abundance in children who later developed type 1 diabetes, compared with those who didn’t, included Firmicutes (Enterococcus, Gemella, and Hungatella), as well as Bacteroides (Bacteroides and Porphyromonas), known to promote inflammation and be involved in the immune response.
Bacteria with greater abundance in children who didn’t develop type 1 diabetes, compared with those who did, were Firmicutes (Anaerostipes, Flavonifractor, and Ruminococcaceae UBA1819, and Eubacterium). These species help maintain metabolic and immune health and produce butyrate, an important short-chain fatty acid that helps prevent inflammation and fuels the cells of the gut lining.
Alistipes were more abundant in infants who didn’t develop type 1 diabetes, and various abundances of Fusicatenibacter were the strongest factors for differentiating future type 1 diabetes, reported the researchers.
“Gut microbial biomarkers at 12 months would benefit the prediction opportunity well before the onset of multiple autoantibodies,” write the authors.
The youngest age at type 1 diabetes diagnosis was aged 1 year, 4 months, and the oldest was aged 21 years, 4 months. The mean age at diagnosis was 13.3 years.
The microbial differences found between infants who go on to develop type 1 diabetes and those who don’t also shed light on interactions between the developing immune system and short-chain fatty acid production and metabolism in childhood autoimmunity, write the authors.
Prior studies have found fewer short-chain fatty acid–producing microbiota in the gut of children with early-onset autoantibody development. This study confirmed these data, finding a decrease in butyrate-producing bacteria (Anaerostipes, Flavonifractor, Ruminococcaceae UBA1819, and Eubacterium) in infants who went on to develop type 1 diabetes. Likewise, a reduction in pyruvate fermentation was found in those infants with future disease.
According to coauthor Eric Triplett, PhD, from the University of Florida, Gainesville: “The autoimmune processes usually begin long before any clinical signs of disease appear, highlighting how differences in the makeup of the infant gut microbiome could shed important light on the complex interaction between the developing immune system, environmental exposures in childhood, and autoimmunity. Studies with much larger cohorts of prospectively traced individuals will be required to establish which are the strongest biomarkers and how effectively they can predict disease.”
The authors and Dr. Rewers have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Microbial biomarkers for type 1 diabetes may be present in infants as young as 12 months old, suggesting the potential to mitigate disease onset by nurturing a healthy gut microbiome early, show data from the Swedish general population.
“Our findings indicate that the gut of infants who go on to develop type 1 diabetes is notably different from healthy babies,” said Malin Bélteky, MD, from the Crown Princess Victoria’s Children’s Hospital, Linköping, Sweden, who jointly led the work, which was recently published in Diabetologia, alongside Patricia L. Milletich, PhD candidate, from the University of Florida, Gainesville.
“This discovery could be used to help identity infants at [the] highest risk of developing type 1 diabetes before or during the first stage of disease and could offer the opportunity to bolster a healthy gut microbiome to prevent the disease from becoming established,” added Dr. Bélteky.
Currently, beta-cell autoantibodies are used to predict disease, which are usually only identifiable between 9 and 36 months of age.
Marian Rewers, MD, PhD, professor of pediatrics & medicine, University of Colorado, Denver, and principal investigator of The Environmental Determinants of Diabetes in the Young (TEDDY) study, welcomed the findings, saying it is a well-designed study from a strong group of investigators.
“While the effective number of cases was very small [n = 16], the results were apparently adjusted for multiple comparisons, and significant differences were noted in the microbiome of cases versus controls at 1 year of age. This was 12 years prior to the average age of type 1 diabetes diagnosis in the cases,” he said.
“The differences in diversity and abundances of specific bacteria need to be interpreted with caution; however, the study results are consistent with several previous reports,” he noted.
Differences in microbial diversity and function
Data were drawn from children participating in the longitudinal, general population All Babies In Southeast Sweden (ABIS) study. Microbiota from stool samples, taken at age 1 year, were sequenced and analyzed to establish diversity, abundance, and functional status of the component bacteria. Questionnaires were completed at birth and at 1 year of age, allowing for the study of environmental factors that might influence the microbiota or type 1 diabetes risk independently. Parent diaries provided information on pregnancy, nutrition, and lifestyle factors.
Of the cohort of 167 children who developed type 1 diabetes by 2020, stool samples were available for 16 of these participants, which were compared with 268 healthy controls. The microbiomes of the 16 infants who later developed type 1 diabetes were compared with 100 iterations of 32 matched control infants (matched by geographical region, siblings at birth, residence type, duration of breastfeeding, and month of stool collection) who didn’t develop type 1 diabetes by the age of 20.
Specific bacteria found in greater abundance in children who later developed type 1 diabetes, compared with those who didn’t, included Firmicutes (Enterococcus, Gemella, and Hungatella), as well as Bacteroides (Bacteroides and Porphyromonas), known to promote inflammation and be involved in the immune response.
Bacteria with greater abundance in children who didn’t develop type 1 diabetes, compared with those who did, were Firmicutes (Anaerostipes, Flavonifractor, and Ruminococcaceae UBA1819, and Eubacterium). These species help maintain metabolic and immune health and produce butyrate, an important short-chain fatty acid that helps prevent inflammation and fuels the cells of the gut lining.
Alistipes were more abundant in infants who didn’t develop type 1 diabetes, and various abundances of Fusicatenibacter were the strongest factors for differentiating future type 1 diabetes, reported the researchers.
“Gut microbial biomarkers at 12 months would benefit the prediction opportunity well before the onset of multiple autoantibodies,” write the authors.
The youngest age at type 1 diabetes diagnosis was aged 1 year, 4 months, and the oldest was aged 21 years, 4 months. The mean age at diagnosis was 13.3 years.
The microbial differences found between infants who go on to develop type 1 diabetes and those who don’t also shed light on interactions between the developing immune system and short-chain fatty acid production and metabolism in childhood autoimmunity, write the authors.
Prior studies have found fewer short-chain fatty acid–producing microbiota in the gut of children with early-onset autoantibody development. This study confirmed these data, finding a decrease in butyrate-producing bacteria (Anaerostipes, Flavonifractor, Ruminococcaceae UBA1819, and Eubacterium) in infants who went on to develop type 1 diabetes. Likewise, a reduction in pyruvate fermentation was found in those infants with future disease.
According to coauthor Eric Triplett, PhD, from the University of Florida, Gainesville: “The autoimmune processes usually begin long before any clinical signs of disease appear, highlighting how differences in the makeup of the infant gut microbiome could shed important light on the complex interaction between the developing immune system, environmental exposures in childhood, and autoimmunity. Studies with much larger cohorts of prospectively traced individuals will be required to establish which are the strongest biomarkers and how effectively they can predict disease.”
The authors and Dr. Rewers have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Microbial biomarkers for type 1 diabetes may be present in infants as young as 12 months old, suggesting the potential to mitigate disease onset by nurturing a healthy gut microbiome early, show data from the Swedish general population.
“Our findings indicate that the gut of infants who go on to develop type 1 diabetes is notably different from healthy babies,” said Malin Bélteky, MD, from the Crown Princess Victoria’s Children’s Hospital, Linköping, Sweden, who jointly led the work, which was recently published in Diabetologia, alongside Patricia L. Milletich, PhD candidate, from the University of Florida, Gainesville.
“This discovery could be used to help identity infants at [the] highest risk of developing type 1 diabetes before or during the first stage of disease and could offer the opportunity to bolster a healthy gut microbiome to prevent the disease from becoming established,” added Dr. Bélteky.
Currently, beta-cell autoantibodies are used to predict disease, which are usually only identifiable between 9 and 36 months of age.
Marian Rewers, MD, PhD, professor of pediatrics & medicine, University of Colorado, Denver, and principal investigator of The Environmental Determinants of Diabetes in the Young (TEDDY) study, welcomed the findings, saying it is a well-designed study from a strong group of investigators.
“While the effective number of cases was very small [n = 16], the results were apparently adjusted for multiple comparisons, and significant differences were noted in the microbiome of cases versus controls at 1 year of age. This was 12 years prior to the average age of type 1 diabetes diagnosis in the cases,” he said.
“The differences in diversity and abundances of specific bacteria need to be interpreted with caution; however, the study results are consistent with several previous reports,” he noted.
Differences in microbial diversity and function
Data were drawn from children participating in the longitudinal, general population All Babies In Southeast Sweden (ABIS) study. Microbiota from stool samples, taken at age 1 year, were sequenced and analyzed to establish diversity, abundance, and functional status of the component bacteria. Questionnaires were completed at birth and at 1 year of age, allowing for the study of environmental factors that might influence the microbiota or type 1 diabetes risk independently. Parent diaries provided information on pregnancy, nutrition, and lifestyle factors.
Of the cohort of 167 children who developed type 1 diabetes by 2020, stool samples were available for 16 of these participants, which were compared with 268 healthy controls. The microbiomes of the 16 infants who later developed type 1 diabetes were compared with 100 iterations of 32 matched control infants (matched by geographical region, siblings at birth, residence type, duration of breastfeeding, and month of stool collection) who didn’t develop type 1 diabetes by the age of 20.
Specific bacteria found in greater abundance in children who later developed type 1 diabetes, compared with those who didn’t, included Firmicutes (Enterococcus, Gemella, and Hungatella), as well as Bacteroides (Bacteroides and Porphyromonas), known to promote inflammation and be involved in the immune response.
Bacteria with greater abundance in children who didn’t develop type 1 diabetes, compared with those who did, were Firmicutes (Anaerostipes, Flavonifractor, and Ruminococcaceae UBA1819, and Eubacterium). These species help maintain metabolic and immune health and produce butyrate, an important short-chain fatty acid that helps prevent inflammation and fuels the cells of the gut lining.
Alistipes were more abundant in infants who didn’t develop type 1 diabetes, and various abundances of Fusicatenibacter were the strongest factors for differentiating future type 1 diabetes, reported the researchers.
“Gut microbial biomarkers at 12 months would benefit the prediction opportunity well before the onset of multiple autoantibodies,” write the authors.
The youngest age at type 1 diabetes diagnosis was aged 1 year, 4 months, and the oldest was aged 21 years, 4 months. The mean age at diagnosis was 13.3 years.
The microbial differences found between infants who go on to develop type 1 diabetes and those who don’t also shed light on interactions between the developing immune system and short-chain fatty acid production and metabolism in childhood autoimmunity, write the authors.
Prior studies have found fewer short-chain fatty acid–producing microbiota in the gut of children with early-onset autoantibody development. This study confirmed these data, finding a decrease in butyrate-producing bacteria (Anaerostipes, Flavonifractor, Ruminococcaceae UBA1819, and Eubacterium) in infants who went on to develop type 1 diabetes. Likewise, a reduction in pyruvate fermentation was found in those infants with future disease.
According to coauthor Eric Triplett, PhD, from the University of Florida, Gainesville: “The autoimmune processes usually begin long before any clinical signs of disease appear, highlighting how differences in the makeup of the infant gut microbiome could shed important light on the complex interaction between the developing immune system, environmental exposures in childhood, and autoimmunity. Studies with much larger cohorts of prospectively traced individuals will be required to establish which are the strongest biomarkers and how effectively they can predict disease.”
The authors and Dr. Rewers have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA panels vote to modify isotretinoin iPLEDGE REMS
At a joint meeting of a drug for severe, nodular acne that is highly teratogenic.
The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.
Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.
Listed options and the number of votes for each were:
- Only with the first prescription as part of patient enrollment (10)
- Monthly (1)
- Every 120 days (6)
- Some other frequency (5)
For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.
Lack of data
On both questions, several advisory committee members cited a lack of data on which they could base their decision.
On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.
“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”
The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.
The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.
They were also tasked with discussing other REMS requirements without taking a vote on each topic.
Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.
The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
A version of this article first appeared on Medscape.com.
At a joint meeting of a drug for severe, nodular acne that is highly teratogenic.
The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.
Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.
Listed options and the number of votes for each were:
- Only with the first prescription as part of patient enrollment (10)
- Monthly (1)
- Every 120 days (6)
- Some other frequency (5)
For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.
Lack of data
On both questions, several advisory committee members cited a lack of data on which they could base their decision.
On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.
“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”
The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.
The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.
They were also tasked with discussing other REMS requirements without taking a vote on each topic.
Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.
The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
A version of this article first appeared on Medscape.com.
At a joint meeting of a drug for severe, nodular acne that is highly teratogenic.
The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.
Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.
Listed options and the number of votes for each were:
- Only with the first prescription as part of patient enrollment (10)
- Monthly (1)
- Every 120 days (6)
- Some other frequency (5)
For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.
Lack of data
On both questions, several advisory committee members cited a lack of data on which they could base their decision.
On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.
“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”
The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.
The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.
They were also tasked with discussing other REMS requirements without taking a vote on each topic.
Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.
The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
A version of this article first appeared on Medscape.com.
Melatonin: A new way to reduce self-harm?
. However, at least one expert has some concerns about the strength of the evidence.
The results suggest improving sleep hygiene in this population may reduce self-injury, study investigator Sarah E. Bergen, PhD, associate professor, department of medical epidemiology and biostatistics, Karolinska Institute, Stockholm, said in an interview.
In addition, she noted, for “pediatric patients who are experiencing sleep problems, melatonin is a safe and effective way to help them.”
Dr. Bergen believes clinicians should recommend melatonin to all teens because “there’s little harm that could come from it and possibly a lot of benefit.”
The findings were published online in the Journal of Child Psychology and Psychiatry.
Few treatments available
Research shows sleep disorders like insomnia are common in youth, particularly among those with psychiatric disorders. Sleep disorders can significantly affect daytime functioning, cognition, emotional regulation, and behavior, and can be a risk factor for unintentional injuries such as falls and vehicular accidents, as well as for intentional self-harm.
The lifetime prevalence of self-harm in youth is estimated to be 17%, but this varies across study designs. There are few treatments for self-harm in youth, although psychosocial treatments appear promising.
Melatonin is a naturally occurring hormone secreted primarily by the pineal gland in response to darkness. It helps promote and maintain the normal sleep-wake cycle and is involved in other biological functions.
In Sweden, melatonin is the most commonly prescribed drug for sleep disturbances in children and adolescents. Prior to 2020, during the course of the study, it was only available by prescription.
The study, which used linked national databases, included 25,575 children and adolescents, 58.2% of them male, who initiated a melatonin treatment between the ages of 6 and 18 years.
Researchers estimated the risks of self-harm, including poisoning (57%) and cutting (34%). The fact that poisoning was more common than cutting was somewhat surprising, said Dr. Bergen. “I would have thought the opposite would be true; that cutting was more prevalent.”
The study examined the risk of self-harm in individual participants by comparing the last unmedicated month with the 12 months after initiating melatonin treatment. In this way, they accounted for potential confounders such as genetics, sleep disorder severity, and psychiatric disorders.
The median age at first melatonin prescription was 13 years for males and 15 years for females.
While there were no statistically significant changes in relative risk for body injuries, falls, and transport accidents, the relative risk for self-injury was statistically significantly lower during the months following melatonin treatment initiation.
The incidence rate ratio in the month following treatment was 0.58 (95% confidence interval, 0.46-0.73) for self-harm and 0.59 (95% CI, 0.45-0.78) for poisoning.
Higher risks in females
The relative risk of self-harm was higher in females than males. This, said Dr. Bergen, is possibly because self-harm is more common in adolescence than in childhood. Female study participants were older than their male counterparts.
Melatonin may help male teens, too, she said. “It’s just that the problem is not that great in males to begin with, so a decrease is not very dramatic after melatonin initiation.”
About 87.2% of participants treated with melatonin were diagnosed with at least one psychiatric disorder. Attention-deficit hyperactivity disorder, the most common comorbidity, was diagnosed in more than 50% of new melatonin users. This isn’t surprising, because sleep disturbances are associated with this psychiatric condition and are frequent side effects of ADHD medications.
After ADHD, anxiety and depression were the next most common psychiatric disorders among study subjects. The analysis found risks for self-harm and poisoning were largely driven by patients suffering from one or both of these disorders, particularly among females.
The IRR in the month following melatonin treatment initiation was 0.46 (95% CI, 0.27-0.76] among adolescent females with psychiatric disorders, after excluding antidepressant users.
Melatonin may reduce the risk of self-harm by treating sleep problems related to psychiatric comorbidities, especially anxiety and depression. It could also decrease pain sensitivity experienced by adolescents who self-harm.
Other factors could play a role in treating sleep problems and/or preventing self-harm in these patients. For example, increased clinician awareness and monitoring, behavioral interventions, a placebo effect, and concurrent use of other medications.
When researchers ran an analysis that excluded individuals taking an antidepressant, “surprisingly, there wasn’t much difference,” said Dr. Bergen. “We thought antidepressants might be causing some of the effect we observed, but when we removed antidepressant users, we saw a very similar pattern of intentional self-harm rates following melatonin use, which suggests melatonin is causal, but we can’t prove that.”
Other sleep medications such as sedatives could also affect self-harm rates by improving sleep. However, these are not typically prescribed to children because of their side effects and overdose potential, said Dr. Bergen.
“Melatonin is extremely safe and side effects are rare; it’s impossible to overdose, and people really can’t hurt themselves with it.”
More research needed
Adrian Jacques Ambrose, MD, medical director, Columbia University Irving Medical Center, and assistant professor of psychiatry, Columbia University, New York, pointed out some evidence in the study is relatively weak.
“When the authors separated out the on- and off-melatonin groups, it looks like there wasn’t a statistically significant difference [in IRRs] between the two groups – for example, in any injury, self-harm, or poisoning – and this weakens their argument that melatonin is associated with self-harm and poisoning.”
Given the current youth mental health crisis, more research “would absolutely be indicated” to better explore possible additional variables, said Dr. Ambrose.
“For example, some additional follow-up studies may add on covariates in conjunction with melatonin usage, such as the number of medical appointments, the presence of psychotherapeutic interventions, dosage of melatonin, or even the sleepiness scale, to evaluate whether the symptoms of sleep disturbances are more directly correlated with the self-harm behaviors.”
The study was supported by the European Union’s Horizon 2020 Research and Innovation Programme. Dr. Bergen and Dr. Ambrose report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
. However, at least one expert has some concerns about the strength of the evidence.
The results suggest improving sleep hygiene in this population may reduce self-injury, study investigator Sarah E. Bergen, PhD, associate professor, department of medical epidemiology and biostatistics, Karolinska Institute, Stockholm, said in an interview.
In addition, she noted, for “pediatric patients who are experiencing sleep problems, melatonin is a safe and effective way to help them.”
Dr. Bergen believes clinicians should recommend melatonin to all teens because “there’s little harm that could come from it and possibly a lot of benefit.”
The findings were published online in the Journal of Child Psychology and Psychiatry.
Few treatments available
Research shows sleep disorders like insomnia are common in youth, particularly among those with psychiatric disorders. Sleep disorders can significantly affect daytime functioning, cognition, emotional regulation, and behavior, and can be a risk factor for unintentional injuries such as falls and vehicular accidents, as well as for intentional self-harm.
The lifetime prevalence of self-harm in youth is estimated to be 17%, but this varies across study designs. There are few treatments for self-harm in youth, although psychosocial treatments appear promising.
Melatonin is a naturally occurring hormone secreted primarily by the pineal gland in response to darkness. It helps promote and maintain the normal sleep-wake cycle and is involved in other biological functions.
In Sweden, melatonin is the most commonly prescribed drug for sleep disturbances in children and adolescents. Prior to 2020, during the course of the study, it was only available by prescription.
The study, which used linked national databases, included 25,575 children and adolescents, 58.2% of them male, who initiated a melatonin treatment between the ages of 6 and 18 years.
Researchers estimated the risks of self-harm, including poisoning (57%) and cutting (34%). The fact that poisoning was more common than cutting was somewhat surprising, said Dr. Bergen. “I would have thought the opposite would be true; that cutting was more prevalent.”
The study examined the risk of self-harm in individual participants by comparing the last unmedicated month with the 12 months after initiating melatonin treatment. In this way, they accounted for potential confounders such as genetics, sleep disorder severity, and psychiatric disorders.
The median age at first melatonin prescription was 13 years for males and 15 years for females.
While there were no statistically significant changes in relative risk for body injuries, falls, and transport accidents, the relative risk for self-injury was statistically significantly lower during the months following melatonin treatment initiation.
The incidence rate ratio in the month following treatment was 0.58 (95% confidence interval, 0.46-0.73) for self-harm and 0.59 (95% CI, 0.45-0.78) for poisoning.
Higher risks in females
The relative risk of self-harm was higher in females than males. This, said Dr. Bergen, is possibly because self-harm is more common in adolescence than in childhood. Female study participants were older than their male counterparts.
Melatonin may help male teens, too, she said. “It’s just that the problem is not that great in males to begin with, so a decrease is not very dramatic after melatonin initiation.”
About 87.2% of participants treated with melatonin were diagnosed with at least one psychiatric disorder. Attention-deficit hyperactivity disorder, the most common comorbidity, was diagnosed in more than 50% of new melatonin users. This isn’t surprising, because sleep disturbances are associated with this psychiatric condition and are frequent side effects of ADHD medications.
After ADHD, anxiety and depression were the next most common psychiatric disorders among study subjects. The analysis found risks for self-harm and poisoning were largely driven by patients suffering from one or both of these disorders, particularly among females.
The IRR in the month following melatonin treatment initiation was 0.46 (95% CI, 0.27-0.76] among adolescent females with psychiatric disorders, after excluding antidepressant users.
Melatonin may reduce the risk of self-harm by treating sleep problems related to psychiatric comorbidities, especially anxiety and depression. It could also decrease pain sensitivity experienced by adolescents who self-harm.
Other factors could play a role in treating sleep problems and/or preventing self-harm in these patients. For example, increased clinician awareness and monitoring, behavioral interventions, a placebo effect, and concurrent use of other medications.
When researchers ran an analysis that excluded individuals taking an antidepressant, “surprisingly, there wasn’t much difference,” said Dr. Bergen. “We thought antidepressants might be causing some of the effect we observed, but when we removed antidepressant users, we saw a very similar pattern of intentional self-harm rates following melatonin use, which suggests melatonin is causal, but we can’t prove that.”
Other sleep medications such as sedatives could also affect self-harm rates by improving sleep. However, these are not typically prescribed to children because of their side effects and overdose potential, said Dr. Bergen.
“Melatonin is extremely safe and side effects are rare; it’s impossible to overdose, and people really can’t hurt themselves with it.”
More research needed
Adrian Jacques Ambrose, MD, medical director, Columbia University Irving Medical Center, and assistant professor of psychiatry, Columbia University, New York, pointed out some evidence in the study is relatively weak.
“When the authors separated out the on- and off-melatonin groups, it looks like there wasn’t a statistically significant difference [in IRRs] between the two groups – for example, in any injury, self-harm, or poisoning – and this weakens their argument that melatonin is associated with self-harm and poisoning.”
Given the current youth mental health crisis, more research “would absolutely be indicated” to better explore possible additional variables, said Dr. Ambrose.
“For example, some additional follow-up studies may add on covariates in conjunction with melatonin usage, such as the number of medical appointments, the presence of psychotherapeutic interventions, dosage of melatonin, or even the sleepiness scale, to evaluate whether the symptoms of sleep disturbances are more directly correlated with the self-harm behaviors.”
The study was supported by the European Union’s Horizon 2020 Research and Innovation Programme. Dr. Bergen and Dr. Ambrose report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
. However, at least one expert has some concerns about the strength of the evidence.
The results suggest improving sleep hygiene in this population may reduce self-injury, study investigator Sarah E. Bergen, PhD, associate professor, department of medical epidemiology and biostatistics, Karolinska Institute, Stockholm, said in an interview.
In addition, she noted, for “pediatric patients who are experiencing sleep problems, melatonin is a safe and effective way to help them.”
Dr. Bergen believes clinicians should recommend melatonin to all teens because “there’s little harm that could come from it and possibly a lot of benefit.”
The findings were published online in the Journal of Child Psychology and Psychiatry.
Few treatments available
Research shows sleep disorders like insomnia are common in youth, particularly among those with psychiatric disorders. Sleep disorders can significantly affect daytime functioning, cognition, emotional regulation, and behavior, and can be a risk factor for unintentional injuries such as falls and vehicular accidents, as well as for intentional self-harm.
The lifetime prevalence of self-harm in youth is estimated to be 17%, but this varies across study designs. There are few treatments for self-harm in youth, although psychosocial treatments appear promising.
Melatonin is a naturally occurring hormone secreted primarily by the pineal gland in response to darkness. It helps promote and maintain the normal sleep-wake cycle and is involved in other biological functions.
In Sweden, melatonin is the most commonly prescribed drug for sleep disturbances in children and adolescents. Prior to 2020, during the course of the study, it was only available by prescription.
The study, which used linked national databases, included 25,575 children and adolescents, 58.2% of them male, who initiated a melatonin treatment between the ages of 6 and 18 years.
Researchers estimated the risks of self-harm, including poisoning (57%) and cutting (34%). The fact that poisoning was more common than cutting was somewhat surprising, said Dr. Bergen. “I would have thought the opposite would be true; that cutting was more prevalent.”
The study examined the risk of self-harm in individual participants by comparing the last unmedicated month with the 12 months after initiating melatonin treatment. In this way, they accounted for potential confounders such as genetics, sleep disorder severity, and psychiatric disorders.
The median age at first melatonin prescription was 13 years for males and 15 years for females.
While there were no statistically significant changes in relative risk for body injuries, falls, and transport accidents, the relative risk for self-injury was statistically significantly lower during the months following melatonin treatment initiation.
The incidence rate ratio in the month following treatment was 0.58 (95% confidence interval, 0.46-0.73) for self-harm and 0.59 (95% CI, 0.45-0.78) for poisoning.
Higher risks in females
The relative risk of self-harm was higher in females than males. This, said Dr. Bergen, is possibly because self-harm is more common in adolescence than in childhood. Female study participants were older than their male counterparts.
Melatonin may help male teens, too, she said. “It’s just that the problem is not that great in males to begin with, so a decrease is not very dramatic after melatonin initiation.”
About 87.2% of participants treated with melatonin were diagnosed with at least one psychiatric disorder. Attention-deficit hyperactivity disorder, the most common comorbidity, was diagnosed in more than 50% of new melatonin users. This isn’t surprising, because sleep disturbances are associated with this psychiatric condition and are frequent side effects of ADHD medications.
After ADHD, anxiety and depression were the next most common psychiatric disorders among study subjects. The analysis found risks for self-harm and poisoning were largely driven by patients suffering from one or both of these disorders, particularly among females.
The IRR in the month following melatonin treatment initiation was 0.46 (95% CI, 0.27-0.76] among adolescent females with psychiatric disorders, after excluding antidepressant users.
Melatonin may reduce the risk of self-harm by treating sleep problems related to psychiatric comorbidities, especially anxiety and depression. It could also decrease pain sensitivity experienced by adolescents who self-harm.
Other factors could play a role in treating sleep problems and/or preventing self-harm in these patients. For example, increased clinician awareness and monitoring, behavioral interventions, a placebo effect, and concurrent use of other medications.
When researchers ran an analysis that excluded individuals taking an antidepressant, “surprisingly, there wasn’t much difference,” said Dr. Bergen. “We thought antidepressants might be causing some of the effect we observed, but when we removed antidepressant users, we saw a very similar pattern of intentional self-harm rates following melatonin use, which suggests melatonin is causal, but we can’t prove that.”
Other sleep medications such as sedatives could also affect self-harm rates by improving sleep. However, these are not typically prescribed to children because of their side effects and overdose potential, said Dr. Bergen.
“Melatonin is extremely safe and side effects are rare; it’s impossible to overdose, and people really can’t hurt themselves with it.”
More research needed
Adrian Jacques Ambrose, MD, medical director, Columbia University Irving Medical Center, and assistant professor of psychiatry, Columbia University, New York, pointed out some evidence in the study is relatively weak.
“When the authors separated out the on- and off-melatonin groups, it looks like there wasn’t a statistically significant difference [in IRRs] between the two groups – for example, in any injury, self-harm, or poisoning – and this weakens their argument that melatonin is associated with self-harm and poisoning.”
Given the current youth mental health crisis, more research “would absolutely be indicated” to better explore possible additional variables, said Dr. Ambrose.
“For example, some additional follow-up studies may add on covariates in conjunction with melatonin usage, such as the number of medical appointments, the presence of psychotherapeutic interventions, dosage of melatonin, or even the sleepiness scale, to evaluate whether the symptoms of sleep disturbances are more directly correlated with the self-harm behaviors.”
The study was supported by the European Union’s Horizon 2020 Research and Innovation Programme. Dr. Bergen and Dr. Ambrose report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
Retinopathy ‘emerging decades earlier’ in kids with type 2 diabetes than in adults
Nearly one in four children diagnosed with type 2 diabetes for 5 years or more develop diabetic retinopathy, according to a new report.
The global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes is about 7%, which appears to increase with age.
“In our clinical practice, we have seen an increase in children presenting with type 2 diabetes over the past few years. These patients present with multiple simultaneous comorbidities and complications like hypertension, fatty liver, and other conditions,” senior author M. Constantine Samaan, MD, told this news organization.
“The exact scale of diabetes-related eye disease was not clear, and we decided to quantify it,” said Dr. Samaan, associate professor of pediatrics at McMaster University and pediatric endocrinologist at McMaster Children’s Hospital in Hamilton, Ont.
“What we found was that in pediatric patients with type 2 diabetes, diabetic retinopathy is present in 1 in 14 youth. The risk of retinopathy increased significantly 5 years after diagnosis to almost one in four,” he noted.
“While we acknowledged that the number of diabetic retinopathy cases was relatively small and there was heterogeneity in studies, we were surprised that retinopathy rates rose so fast in the first few years after diabetes diagnosis,” Dr. Samaan indicated.
The findings signal that the increase in the prevalence of diabetic retinopathy is emerging decades earlier among children compared with adults with type 2 diabetes, the authors wrote in their article published online in JAMA Network Open.
“While the guidelines for eye care in children with type 2 diabetes recommend screening at diagnosis and annually afterward, these recommendations are not followed in almost half of these patients,” Dr. Samaan said. “There is a need to ensure that patients get screened to try and prevent or delay retinopathy onset and progression.”
Analyzing prevalence rates
Diabetic retinopathy is the leading cause of blindness in patients with type 2 diabetes. Between 21% and 39% of adults have diabetic retinopathy at diagnosis, with rates subsequently increasing, the authors wrote.
Dr. Samaan and colleagues conducted a systematic review and meta-analysis to estimate the global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes. They included studies that had a study population of at least 10 participants diagnosed at age 21 and younger, an observational study design, and prevalence data on diabetic retinopathy.
Among the 29 studies included, 6 were cross-sectional, 13 had a retrospective cohort design, and 10 had a prospective cohort design. Patients were diagnosed between age 6.5 and 21 years, and the diabetes duration ranged from 0 to 15 years after diagnosis.
The overall global prevalence of diabetic retinopathy in 5,924 pediatric patients was 7.0%. Prevalence varied by study design, ranging from 1.1% in cross-sectional studies to 6.5% in prospective cohort studies and 11.3% in retrospective cohort studies.
In the nine studies that reported diabetic retinopathy classification based on criteria, the prevalence of minimal-to-moderate nonproliferative diabetic retinopathy was 11.2%, the prevalence of severe nonproliferative diabetic retinopathy was 2.6%, the prevalence of proliferative diabetic retinopathy was 2.4%, and the prevalence of macular edema was 3.1%.
In the five studies that reported diabetic retinopathy diagnosis using fundoscopy, the prevalence was 0.5%. In the four studies that used 7-field stereoscopic fundus photography, the prevalence was 13.6%.
In the pooled analysis of 27 studies, the prevalence of diabetic retinopathy was 1.8% less than 2.5 years after diabetes diagnosis but more than doubled to 5.1% in years 2.5 to 5 and jumped to 28.8% more than 5 years after diagnosis.
Differences by sex, ethnicity
“We were also surprised that there was very limited evidence to understand the sex and race differences in retinopathy risk,” said Dr. Samaan. “Further research is warranted, considering that more girls develop type 2 diabetes than boys, and the risk of type 2 diabetes is higher in some racial groups.”
In addition, older age, longer diabetes duration, and higher hypertension prevalence were associated with diabetic retinopathy prevalence. There were no associations with obesity prevalence or mean age at diabetes diagnosis. However, patients who developed diabetic retinopathy had a higher mean A1c level of 1.4% compared to those without retinopathy.
Dr. Samaan and colleagues are continuing to research the comorbidities and complications that children with type 2 diabetes face as well as mechanisms that drive diabetes outcomes among children and adolescents.
For now, the findings highlight the importance of retinopathy screening and personalized diabetes treatment to protect vision, Dr. Samaan reiterated.
No funding source for the study was reported. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Nearly one in four children diagnosed with type 2 diabetes for 5 years or more develop diabetic retinopathy, according to a new report.
The global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes is about 7%, which appears to increase with age.
“In our clinical practice, we have seen an increase in children presenting with type 2 diabetes over the past few years. These patients present with multiple simultaneous comorbidities and complications like hypertension, fatty liver, and other conditions,” senior author M. Constantine Samaan, MD, told this news organization.
“The exact scale of diabetes-related eye disease was not clear, and we decided to quantify it,” said Dr. Samaan, associate professor of pediatrics at McMaster University and pediatric endocrinologist at McMaster Children’s Hospital in Hamilton, Ont.
“What we found was that in pediatric patients with type 2 diabetes, diabetic retinopathy is present in 1 in 14 youth. The risk of retinopathy increased significantly 5 years after diagnosis to almost one in four,” he noted.
“While we acknowledged that the number of diabetic retinopathy cases was relatively small and there was heterogeneity in studies, we were surprised that retinopathy rates rose so fast in the first few years after diabetes diagnosis,” Dr. Samaan indicated.
The findings signal that the increase in the prevalence of diabetic retinopathy is emerging decades earlier among children compared with adults with type 2 diabetes, the authors wrote in their article published online in JAMA Network Open.
“While the guidelines for eye care in children with type 2 diabetes recommend screening at diagnosis and annually afterward, these recommendations are not followed in almost half of these patients,” Dr. Samaan said. “There is a need to ensure that patients get screened to try and prevent or delay retinopathy onset and progression.”
Analyzing prevalence rates
Diabetic retinopathy is the leading cause of blindness in patients with type 2 diabetes. Between 21% and 39% of adults have diabetic retinopathy at diagnosis, with rates subsequently increasing, the authors wrote.
Dr. Samaan and colleagues conducted a systematic review and meta-analysis to estimate the global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes. They included studies that had a study population of at least 10 participants diagnosed at age 21 and younger, an observational study design, and prevalence data on diabetic retinopathy.
Among the 29 studies included, 6 were cross-sectional, 13 had a retrospective cohort design, and 10 had a prospective cohort design. Patients were diagnosed between age 6.5 and 21 years, and the diabetes duration ranged from 0 to 15 years after diagnosis.
The overall global prevalence of diabetic retinopathy in 5,924 pediatric patients was 7.0%. Prevalence varied by study design, ranging from 1.1% in cross-sectional studies to 6.5% in prospective cohort studies and 11.3% in retrospective cohort studies.
In the nine studies that reported diabetic retinopathy classification based on criteria, the prevalence of minimal-to-moderate nonproliferative diabetic retinopathy was 11.2%, the prevalence of severe nonproliferative diabetic retinopathy was 2.6%, the prevalence of proliferative diabetic retinopathy was 2.4%, and the prevalence of macular edema was 3.1%.
In the five studies that reported diabetic retinopathy diagnosis using fundoscopy, the prevalence was 0.5%. In the four studies that used 7-field stereoscopic fundus photography, the prevalence was 13.6%.
In the pooled analysis of 27 studies, the prevalence of diabetic retinopathy was 1.8% less than 2.5 years after diabetes diagnosis but more than doubled to 5.1% in years 2.5 to 5 and jumped to 28.8% more than 5 years after diagnosis.
Differences by sex, ethnicity
“We were also surprised that there was very limited evidence to understand the sex and race differences in retinopathy risk,” said Dr. Samaan. “Further research is warranted, considering that more girls develop type 2 diabetes than boys, and the risk of type 2 diabetes is higher in some racial groups.”
In addition, older age, longer diabetes duration, and higher hypertension prevalence were associated with diabetic retinopathy prevalence. There were no associations with obesity prevalence or mean age at diabetes diagnosis. However, patients who developed diabetic retinopathy had a higher mean A1c level of 1.4% compared to those without retinopathy.
Dr. Samaan and colleagues are continuing to research the comorbidities and complications that children with type 2 diabetes face as well as mechanisms that drive diabetes outcomes among children and adolescents.
For now, the findings highlight the importance of retinopathy screening and personalized diabetes treatment to protect vision, Dr. Samaan reiterated.
No funding source for the study was reported. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Nearly one in four children diagnosed with type 2 diabetes for 5 years or more develop diabetic retinopathy, according to a new report.
The global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes is about 7%, which appears to increase with age.
“In our clinical practice, we have seen an increase in children presenting with type 2 diabetes over the past few years. These patients present with multiple simultaneous comorbidities and complications like hypertension, fatty liver, and other conditions,” senior author M. Constantine Samaan, MD, told this news organization.
“The exact scale of diabetes-related eye disease was not clear, and we decided to quantify it,” said Dr. Samaan, associate professor of pediatrics at McMaster University and pediatric endocrinologist at McMaster Children’s Hospital in Hamilton, Ont.
“What we found was that in pediatric patients with type 2 diabetes, diabetic retinopathy is present in 1 in 14 youth. The risk of retinopathy increased significantly 5 years after diagnosis to almost one in four,” he noted.
“While we acknowledged that the number of diabetic retinopathy cases was relatively small and there was heterogeneity in studies, we were surprised that retinopathy rates rose so fast in the first few years after diabetes diagnosis,” Dr. Samaan indicated.
The findings signal that the increase in the prevalence of diabetic retinopathy is emerging decades earlier among children compared with adults with type 2 diabetes, the authors wrote in their article published online in JAMA Network Open.
“While the guidelines for eye care in children with type 2 diabetes recommend screening at diagnosis and annually afterward, these recommendations are not followed in almost half of these patients,” Dr. Samaan said. “There is a need to ensure that patients get screened to try and prevent or delay retinopathy onset and progression.”
Analyzing prevalence rates
Diabetic retinopathy is the leading cause of blindness in patients with type 2 diabetes. Between 21% and 39% of adults have diabetic retinopathy at diagnosis, with rates subsequently increasing, the authors wrote.
Dr. Samaan and colleagues conducted a systematic review and meta-analysis to estimate the global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes. They included studies that had a study population of at least 10 participants diagnosed at age 21 and younger, an observational study design, and prevalence data on diabetic retinopathy.
Among the 29 studies included, 6 were cross-sectional, 13 had a retrospective cohort design, and 10 had a prospective cohort design. Patients were diagnosed between age 6.5 and 21 years, and the diabetes duration ranged from 0 to 15 years after diagnosis.
The overall global prevalence of diabetic retinopathy in 5,924 pediatric patients was 7.0%. Prevalence varied by study design, ranging from 1.1% in cross-sectional studies to 6.5% in prospective cohort studies and 11.3% in retrospective cohort studies.
In the nine studies that reported diabetic retinopathy classification based on criteria, the prevalence of minimal-to-moderate nonproliferative diabetic retinopathy was 11.2%, the prevalence of severe nonproliferative diabetic retinopathy was 2.6%, the prevalence of proliferative diabetic retinopathy was 2.4%, and the prevalence of macular edema was 3.1%.
In the five studies that reported diabetic retinopathy diagnosis using fundoscopy, the prevalence was 0.5%. In the four studies that used 7-field stereoscopic fundus photography, the prevalence was 13.6%.
In the pooled analysis of 27 studies, the prevalence of diabetic retinopathy was 1.8% less than 2.5 years after diabetes diagnosis but more than doubled to 5.1% in years 2.5 to 5 and jumped to 28.8% more than 5 years after diagnosis.
Differences by sex, ethnicity
“We were also surprised that there was very limited evidence to understand the sex and race differences in retinopathy risk,” said Dr. Samaan. “Further research is warranted, considering that more girls develop type 2 diabetes than boys, and the risk of type 2 diabetes is higher in some racial groups.”
In addition, older age, longer diabetes duration, and higher hypertension prevalence were associated with diabetic retinopathy prevalence. There were no associations with obesity prevalence or mean age at diabetes diagnosis. However, patients who developed diabetic retinopathy had a higher mean A1c level of 1.4% compared to those without retinopathy.
Dr. Samaan and colleagues are continuing to research the comorbidities and complications that children with type 2 diabetes face as well as mechanisms that drive diabetes outcomes among children and adolescents.
For now, the findings highlight the importance of retinopathy screening and personalized diabetes treatment to protect vision, Dr. Samaan reiterated.
No funding source for the study was reported. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Autism rates trending upwards, CDC reports
Childhood autism rates have ticked up once again, according to the latest data from Centers for Disease Control and Prevention.
According to the CDC, 1 in 36 (2.8%) 8-year-old children have been identified with autism spectrum disorder (ASD) – up from the previous 2018 estimate of 1 in 44 (2.3%).
The updated data come from 11 communities in the Autism and Developmental Disabilities Monitoring (ADDM) network and were published online in Morbidity and Mortality Weekly Report.
A separate report in the MMWR on 4-year-old children in the same 11 communities highlights the impact of COVID-19, showing disruptions in progress in early autism detection.
In the early months of the pandemic, 4-year-old children were less likely to have an evaluation or be identified with ASD than 8-year-old children when they were the same age. This coincides with interruptions in childcare and health care services during the COVID-19 pandemic.
“Disruptions due to the pandemic in the timely evaluation of children and delays in connecting children to the services and support they need could have long-lasting effects,” Karen Remley, MD, director of CDC’s National Center on Birth Defects and Developmental Disabilities, said in a statement.
“The data in this report can help communities better understand how the pandemic impacted early identification of autism in young children and anticipate future needs as these children get older,” Dr. Remley noted.
Shifting demographics
The latest data also show that ASD prevalence among Asian, Black, and Hispanic children was at least 30% higher in 2020 than in 2018, and ASD prevalence among White children was 14.6% higher than in 2018.
For the first time, according to the CDC, the percentage of 8-year-old Asian/Pacific Islander (3.3%), Hispanic (3.2%) and Black (2.9%) children identified with autism was higher than the percentage of 8-year-old White children (2.4%).
This is the opposite of racial and ethnic differences seen in previous ADDM reports for 8-year-olds. These shifts may reflect improved screening, awareness, and access to services among historically underserved groups, the CDC said.
Disparities for co-occurring intellectual disability have also persisted, with a higher percentage of Black children with autism identified with intellectual disability compared with White, Hispanic, or Asian/Pacific Islander children with autism. These differences could relate in part to access to services that diagnose and support children with autism, the CDC noted.
Overall, autism prevalence within the 11 ADDM communities was nearly four times higher for boys than girls. However, it’s the first time that the prevalence of autism among 8-year-old girls has topped 1%.
Community differences
Autism prevalence in the 11 ADDM communities ranged from 1 in 43 (2.3%) children in Maryland to 1 in 22 (4.5%) in California – variations that could be due to how communities identify children with autism.
This variability affords an opportunity to compare local policies and models for delivering diagnostic and interventional services that could enhance autism identification and provide more comprehensive support to people with autism, the CDC said.
A version of this article first appeared on Medscape.com.
Childhood autism rates have ticked up once again, according to the latest data from Centers for Disease Control and Prevention.
According to the CDC, 1 in 36 (2.8%) 8-year-old children have been identified with autism spectrum disorder (ASD) – up from the previous 2018 estimate of 1 in 44 (2.3%).
The updated data come from 11 communities in the Autism and Developmental Disabilities Monitoring (ADDM) network and were published online in Morbidity and Mortality Weekly Report.
A separate report in the MMWR on 4-year-old children in the same 11 communities highlights the impact of COVID-19, showing disruptions in progress in early autism detection.
In the early months of the pandemic, 4-year-old children were less likely to have an evaluation or be identified with ASD than 8-year-old children when they were the same age. This coincides with interruptions in childcare and health care services during the COVID-19 pandemic.
“Disruptions due to the pandemic in the timely evaluation of children and delays in connecting children to the services and support they need could have long-lasting effects,” Karen Remley, MD, director of CDC’s National Center on Birth Defects and Developmental Disabilities, said in a statement.
“The data in this report can help communities better understand how the pandemic impacted early identification of autism in young children and anticipate future needs as these children get older,” Dr. Remley noted.
Shifting demographics
The latest data also show that ASD prevalence among Asian, Black, and Hispanic children was at least 30% higher in 2020 than in 2018, and ASD prevalence among White children was 14.6% higher than in 2018.
For the first time, according to the CDC, the percentage of 8-year-old Asian/Pacific Islander (3.3%), Hispanic (3.2%) and Black (2.9%) children identified with autism was higher than the percentage of 8-year-old White children (2.4%).
This is the opposite of racial and ethnic differences seen in previous ADDM reports for 8-year-olds. These shifts may reflect improved screening, awareness, and access to services among historically underserved groups, the CDC said.
Disparities for co-occurring intellectual disability have also persisted, with a higher percentage of Black children with autism identified with intellectual disability compared with White, Hispanic, or Asian/Pacific Islander children with autism. These differences could relate in part to access to services that diagnose and support children with autism, the CDC noted.
Overall, autism prevalence within the 11 ADDM communities was nearly four times higher for boys than girls. However, it’s the first time that the prevalence of autism among 8-year-old girls has topped 1%.
Community differences
Autism prevalence in the 11 ADDM communities ranged from 1 in 43 (2.3%) children in Maryland to 1 in 22 (4.5%) in California – variations that could be due to how communities identify children with autism.
This variability affords an opportunity to compare local policies and models for delivering diagnostic and interventional services that could enhance autism identification and provide more comprehensive support to people with autism, the CDC said.
A version of this article first appeared on Medscape.com.
Childhood autism rates have ticked up once again, according to the latest data from Centers for Disease Control and Prevention.
According to the CDC, 1 in 36 (2.8%) 8-year-old children have been identified with autism spectrum disorder (ASD) – up from the previous 2018 estimate of 1 in 44 (2.3%).
The updated data come from 11 communities in the Autism and Developmental Disabilities Monitoring (ADDM) network and were published online in Morbidity and Mortality Weekly Report.
A separate report in the MMWR on 4-year-old children in the same 11 communities highlights the impact of COVID-19, showing disruptions in progress in early autism detection.
In the early months of the pandemic, 4-year-old children were less likely to have an evaluation or be identified with ASD than 8-year-old children when they were the same age. This coincides with interruptions in childcare and health care services during the COVID-19 pandemic.
“Disruptions due to the pandemic in the timely evaluation of children and delays in connecting children to the services and support they need could have long-lasting effects,” Karen Remley, MD, director of CDC’s National Center on Birth Defects and Developmental Disabilities, said in a statement.
“The data in this report can help communities better understand how the pandemic impacted early identification of autism in young children and anticipate future needs as these children get older,” Dr. Remley noted.
Shifting demographics
The latest data also show that ASD prevalence among Asian, Black, and Hispanic children was at least 30% higher in 2020 than in 2018, and ASD prevalence among White children was 14.6% higher than in 2018.
For the first time, according to the CDC, the percentage of 8-year-old Asian/Pacific Islander (3.3%), Hispanic (3.2%) and Black (2.9%) children identified with autism was higher than the percentage of 8-year-old White children (2.4%).
This is the opposite of racial and ethnic differences seen in previous ADDM reports for 8-year-olds. These shifts may reflect improved screening, awareness, and access to services among historically underserved groups, the CDC said.
Disparities for co-occurring intellectual disability have also persisted, with a higher percentage of Black children with autism identified with intellectual disability compared with White, Hispanic, or Asian/Pacific Islander children with autism. These differences could relate in part to access to services that diagnose and support children with autism, the CDC noted.
Overall, autism prevalence within the 11 ADDM communities was nearly four times higher for boys than girls. However, it’s the first time that the prevalence of autism among 8-year-old girls has topped 1%.
Community differences
Autism prevalence in the 11 ADDM communities ranged from 1 in 43 (2.3%) children in Maryland to 1 in 22 (4.5%) in California – variations that could be due to how communities identify children with autism.
This variability affords an opportunity to compare local policies and models for delivering diagnostic and interventional services that could enhance autism identification and provide more comprehensive support to people with autism, the CDC said.
A version of this article first appeared on Medscape.com.
Air pollution may be causing eczema
The finding points scientists toward how to better treat the skin ailment. There are now more than three times as many eczema cases as there were in the 1970s, and it now affects as many as 20% of children and 10% of adults.
“I think these authors are spot-on in recognizing that the incidence of allergic conditions is increasing concurrently with how different pollutants are increasing in our environment,” said Denver-based pediatric allergist and immunologist Jessica Hui, MD, according to NBC News. “We’re finally understanding more about why people are getting eczema.”
Some people get eczema because of genetics, but the new research built on the previous understanding of how chemicals called diisocyanates can trigger the eczema symptoms of severe itching, skin redness, and oozing or painful rashes. An experiment on mice showed that exposure to a specific part of diisocyanates, called isocyanates, disrupted oil production that the skin needs to stay healthy.
Researchers at the National Institutes of Health “found that when bacteria that live on healthy skin are exposed to isocyanate, they must adapt to survive,” the agency summarized in a news release. “When they adapt, these bacteria shift their metabolism away from making the lipids, or oils, that skin needs to stay healthy. This finding suggests that eczema may be treatable by replacing the modified skin bacteria with healthy bacteria.”
The study was published in the journal Science Advances.
The chemicals also trigger a message to the brain that causes skin inflammation and itching, lead researcher Ian Myles, MD, told NBC News. Dr. Myles is also chief of the Epithelial Research Unit in the National Institute of Allergy and Infectious Diseases Laboratory of Clinical Immunology and Microbiology.
“So much of this is out of our control. I mean, you can’t shut the highways down,” he said of the environmental sources.
Previous research that explored attempting to restore healthy skin bacteria called Roseomonas mucosa to treat eczema symptoms had mixed results. The NIH says it has made the bacteria available “for commercial, nontherapeutic development ... as a potentially beneficial probiotic.”
A version of this article first appeared on WebMD.com.
The finding points scientists toward how to better treat the skin ailment. There are now more than three times as many eczema cases as there were in the 1970s, and it now affects as many as 20% of children and 10% of adults.
“I think these authors are spot-on in recognizing that the incidence of allergic conditions is increasing concurrently with how different pollutants are increasing in our environment,” said Denver-based pediatric allergist and immunologist Jessica Hui, MD, according to NBC News. “We’re finally understanding more about why people are getting eczema.”
Some people get eczema because of genetics, but the new research built on the previous understanding of how chemicals called diisocyanates can trigger the eczema symptoms of severe itching, skin redness, and oozing or painful rashes. An experiment on mice showed that exposure to a specific part of diisocyanates, called isocyanates, disrupted oil production that the skin needs to stay healthy.
Researchers at the National Institutes of Health “found that when bacteria that live on healthy skin are exposed to isocyanate, they must adapt to survive,” the agency summarized in a news release. “When they adapt, these bacteria shift their metabolism away from making the lipids, or oils, that skin needs to stay healthy. This finding suggests that eczema may be treatable by replacing the modified skin bacteria with healthy bacteria.”
The study was published in the journal Science Advances.
The chemicals also trigger a message to the brain that causes skin inflammation and itching, lead researcher Ian Myles, MD, told NBC News. Dr. Myles is also chief of the Epithelial Research Unit in the National Institute of Allergy and Infectious Diseases Laboratory of Clinical Immunology and Microbiology.
“So much of this is out of our control. I mean, you can’t shut the highways down,” he said of the environmental sources.
Previous research that explored attempting to restore healthy skin bacteria called Roseomonas mucosa to treat eczema symptoms had mixed results. The NIH says it has made the bacteria available “for commercial, nontherapeutic development ... as a potentially beneficial probiotic.”
A version of this article first appeared on WebMD.com.
The finding points scientists toward how to better treat the skin ailment. There are now more than three times as many eczema cases as there were in the 1970s, and it now affects as many as 20% of children and 10% of adults.
“I think these authors are spot-on in recognizing that the incidence of allergic conditions is increasing concurrently with how different pollutants are increasing in our environment,” said Denver-based pediatric allergist and immunologist Jessica Hui, MD, according to NBC News. “We’re finally understanding more about why people are getting eczema.”
Some people get eczema because of genetics, but the new research built on the previous understanding of how chemicals called diisocyanates can trigger the eczema symptoms of severe itching, skin redness, and oozing or painful rashes. An experiment on mice showed that exposure to a specific part of diisocyanates, called isocyanates, disrupted oil production that the skin needs to stay healthy.
Researchers at the National Institutes of Health “found that when bacteria that live on healthy skin are exposed to isocyanate, they must adapt to survive,” the agency summarized in a news release. “When they adapt, these bacteria shift their metabolism away from making the lipids, or oils, that skin needs to stay healthy. This finding suggests that eczema may be treatable by replacing the modified skin bacteria with healthy bacteria.”
The study was published in the journal Science Advances.
The chemicals also trigger a message to the brain that causes skin inflammation and itching, lead researcher Ian Myles, MD, told NBC News. Dr. Myles is also chief of the Epithelial Research Unit in the National Institute of Allergy and Infectious Diseases Laboratory of Clinical Immunology and Microbiology.
“So much of this is out of our control. I mean, you can’t shut the highways down,” he said of the environmental sources.
Previous research that explored attempting to restore healthy skin bacteria called Roseomonas mucosa to treat eczema symptoms had mixed results. The NIH says it has made the bacteria available “for commercial, nontherapeutic development ... as a potentially beneficial probiotic.”
A version of this article first appeared on WebMD.com.
FROM SCIENCE ADVANCES
FDA approves new formulation of Hyrimoz adalimumab biosimilar
The Food and Drug Administration has approved a citrate-free, 100 mg/mL formulation of the biosimilar adalimumab-adaz (Hyrimoz), according to a statement from manufacturer Sandoz.
Hyrimoz, a tumor necrosis factor (TNF) blocker that is biosimilar to its reference product Humira, was approved by the FDA in 2018 at a concentration of 50 mg/mL for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis. The high-concentration formula is indicated for these same conditions.
Sandoz said that it intends to launch the citrate-free formulation in the United States on July 1. It will be one of up to nine other adalimumab biosimilars that are expected to launch in July. On January 31, Amjevita (adalimumab-atto) became the first adalimumab biosimilar to launch in the United States.
The current label for Hyrimoz contains a black box warning emphasizing certain risks, notably the increased risk for serious infections, such as tuberculosis or sepsis, and an increased risk of malignancy, particularly lymphomas.
Adverse effects associated with Hyrimoz with an incidence greater than 10% include upper respiratory infections and sinusitis, injection-site reactions, headache, and rash.
The approval for the high-concentration formulation was based on data from a phase 1 pharmacokinetics bridging study that compared Hyrimoz 50 mg/mL and citrate-free Hyrimoz 100 mg/mL.
“This study met all of the primary objectives, demonstrating comparable pharmacokinetics and showing similar safety and immunogenicity of the Hyrimoz 50 mg/mL and Hyrimoz [100 mg/mL],” according to Sandoz, a division of Novartis.
The approval for Hyrimoz 50 mg/mL in 2018 was based on preclinical and clinical research comparing Hyrimoz and Humira. In a phase 3 trial published in the British Journal of Dermatology, which included adults with clinically stable but active moderate to severe chronic plaque psoriasis, Hyrimoz and Humira showed a similar percentage of patients met the primary endpoint of a 75% reduction or more in Psoriasis Area and Severity Index (PASI 75) score at 16 weeks, compared with baseline (66.8% and 65%, respectively).
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration has approved a citrate-free, 100 mg/mL formulation of the biosimilar adalimumab-adaz (Hyrimoz), according to a statement from manufacturer Sandoz.
Hyrimoz, a tumor necrosis factor (TNF) blocker that is biosimilar to its reference product Humira, was approved by the FDA in 2018 at a concentration of 50 mg/mL for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis. The high-concentration formula is indicated for these same conditions.
Sandoz said that it intends to launch the citrate-free formulation in the United States on July 1. It will be one of up to nine other adalimumab biosimilars that are expected to launch in July. On January 31, Amjevita (adalimumab-atto) became the first adalimumab biosimilar to launch in the United States.
The current label for Hyrimoz contains a black box warning emphasizing certain risks, notably the increased risk for serious infections, such as tuberculosis or sepsis, and an increased risk of malignancy, particularly lymphomas.
Adverse effects associated with Hyrimoz with an incidence greater than 10% include upper respiratory infections and sinusitis, injection-site reactions, headache, and rash.
The approval for the high-concentration formulation was based on data from a phase 1 pharmacokinetics bridging study that compared Hyrimoz 50 mg/mL and citrate-free Hyrimoz 100 mg/mL.
“This study met all of the primary objectives, demonstrating comparable pharmacokinetics and showing similar safety and immunogenicity of the Hyrimoz 50 mg/mL and Hyrimoz [100 mg/mL],” according to Sandoz, a division of Novartis.
The approval for Hyrimoz 50 mg/mL in 2018 was based on preclinical and clinical research comparing Hyrimoz and Humira. In a phase 3 trial published in the British Journal of Dermatology, which included adults with clinically stable but active moderate to severe chronic plaque psoriasis, Hyrimoz and Humira showed a similar percentage of patients met the primary endpoint of a 75% reduction or more in Psoriasis Area and Severity Index (PASI 75) score at 16 weeks, compared with baseline (66.8% and 65%, respectively).
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration has approved a citrate-free, 100 mg/mL formulation of the biosimilar adalimumab-adaz (Hyrimoz), according to a statement from manufacturer Sandoz.
Hyrimoz, a tumor necrosis factor (TNF) blocker that is biosimilar to its reference product Humira, was approved by the FDA in 2018 at a concentration of 50 mg/mL for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis. The high-concentration formula is indicated for these same conditions.
Sandoz said that it intends to launch the citrate-free formulation in the United States on July 1. It will be one of up to nine other adalimumab biosimilars that are expected to launch in July. On January 31, Amjevita (adalimumab-atto) became the first adalimumab biosimilar to launch in the United States.
The current label for Hyrimoz contains a black box warning emphasizing certain risks, notably the increased risk for serious infections, such as tuberculosis or sepsis, and an increased risk of malignancy, particularly lymphomas.
Adverse effects associated with Hyrimoz with an incidence greater than 10% include upper respiratory infections and sinusitis, injection-site reactions, headache, and rash.
The approval for the high-concentration formulation was based on data from a phase 1 pharmacokinetics bridging study that compared Hyrimoz 50 mg/mL and citrate-free Hyrimoz 100 mg/mL.
“This study met all of the primary objectives, demonstrating comparable pharmacokinetics and showing similar safety and immunogenicity of the Hyrimoz 50 mg/mL and Hyrimoz [100 mg/mL],” according to Sandoz, a division of Novartis.
The approval for Hyrimoz 50 mg/mL in 2018 was based on preclinical and clinical research comparing Hyrimoz and Humira. In a phase 3 trial published in the British Journal of Dermatology, which included adults with clinically stable but active moderate to severe chronic plaque psoriasis, Hyrimoz and Humira showed a similar percentage of patients met the primary endpoint of a 75% reduction or more in Psoriasis Area and Severity Index (PASI 75) score at 16 weeks, compared with baseline (66.8% and 65%, respectively).
A version of this article originally appeared on Medscape.com.
COVID in pregnancy may affect boys’ neurodevelopment: Study
Boys born to mothers infected with SARS‐CoV‐2 during pregnancy may be more likely to receive a diagnosis of a neurodevelopmental disorder by age 12 months, according to new research.
Andrea G. Edlow, MD, MSc, with Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues examined data from 18,355 births between March 1, 2020, and May 31, 2021, at eight hospitals across two health systems in Massachusetts.
Of these births, 883 (4.8%) were to individuals who tested positive for SARS‐CoV‐2 during pregnancy. Among the children exposed to SARS‐CoV‐2 in the womb, 26 (3%) received a neurodevelopmental diagnosis, including disorders of motor function, speech and language, and psychological development, by age 1 year. In the group unexposed to the virus, 1.8% received such a diagnosis.
After adjusting for factors such as race, insurance, maternal age, and preterm birth, Dr. Edlow’s group found that a positive test for SARS-CoV-2 during pregnancy was associated with an increased risk for neurodevelopmental diagnoses at 12 months among boys (adjusted odds ratio, 1.94; 95% confidence interval, 1.12-3.17; P = .01), but not among girls.
In a subset of children with data available at 18 months, the correlation among boys at that age was less pronounced and not statistically significant (aOR, 1.42; 95% CI, 0.92-2.11; P = .10).
The findings were published online in JAMA Network Open
Prior epidemiological research has suggested that maternal infection during pregnancy is associated with heightened risk for a range of neurodevelopmental disorders, including autism and schizophrenia, in offspring, the authors wrote.
“The neurodevelopmental risk associated with maternal SARS-CoV-2 infection was disproportionately high in male infants, consistent with the known increased vulnerability of males in the face of prenatal adverse exposures,” Dr. Edlow said in a news release about the findings.
Larger studies and longer follow‐up are needed to confirm and reliably estimate the risk, the researchers said.
“It is not clear that the changes we can detect at 12 and 18 months will be indicative of persistent risks for disorders such as autism spectrum disorder, intellectual disability, or schizophrenia,” they write.
New data published online by the Centers for Disease Control and Prevention show that in 11 communities in 2020, 1 in 36 (2.8%) 8-year-old children had been identified with autism spectrum disorder, an increase from 2.3% in 2018. The data also show that the early months of the pandemic may have disrupted autism detection efforts among 4-year-olds.
The investigators were supported by grants from the National Institutes of Health and the Simons Foundation Autism Research Initiative. Coauthors disclosed consulting for or receiving personal fees from biotechnology and pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Boys born to mothers infected with SARS‐CoV‐2 during pregnancy may be more likely to receive a diagnosis of a neurodevelopmental disorder by age 12 months, according to new research.
Andrea G. Edlow, MD, MSc, with Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues examined data from 18,355 births between March 1, 2020, and May 31, 2021, at eight hospitals across two health systems in Massachusetts.
Of these births, 883 (4.8%) were to individuals who tested positive for SARS‐CoV‐2 during pregnancy. Among the children exposed to SARS‐CoV‐2 in the womb, 26 (3%) received a neurodevelopmental diagnosis, including disorders of motor function, speech and language, and psychological development, by age 1 year. In the group unexposed to the virus, 1.8% received such a diagnosis.
After adjusting for factors such as race, insurance, maternal age, and preterm birth, Dr. Edlow’s group found that a positive test for SARS-CoV-2 during pregnancy was associated with an increased risk for neurodevelopmental diagnoses at 12 months among boys (adjusted odds ratio, 1.94; 95% confidence interval, 1.12-3.17; P = .01), but not among girls.
In a subset of children with data available at 18 months, the correlation among boys at that age was less pronounced and not statistically significant (aOR, 1.42; 95% CI, 0.92-2.11; P = .10).
The findings were published online in JAMA Network Open
Prior epidemiological research has suggested that maternal infection during pregnancy is associated with heightened risk for a range of neurodevelopmental disorders, including autism and schizophrenia, in offspring, the authors wrote.
“The neurodevelopmental risk associated with maternal SARS-CoV-2 infection was disproportionately high in male infants, consistent with the known increased vulnerability of males in the face of prenatal adverse exposures,” Dr. Edlow said in a news release about the findings.
Larger studies and longer follow‐up are needed to confirm and reliably estimate the risk, the researchers said.
“It is not clear that the changes we can detect at 12 and 18 months will be indicative of persistent risks for disorders such as autism spectrum disorder, intellectual disability, or schizophrenia,” they write.
New data published online by the Centers for Disease Control and Prevention show that in 11 communities in 2020, 1 in 36 (2.8%) 8-year-old children had been identified with autism spectrum disorder, an increase from 2.3% in 2018. The data also show that the early months of the pandemic may have disrupted autism detection efforts among 4-year-olds.
The investigators were supported by grants from the National Institutes of Health and the Simons Foundation Autism Research Initiative. Coauthors disclosed consulting for or receiving personal fees from biotechnology and pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Boys born to mothers infected with SARS‐CoV‐2 during pregnancy may be more likely to receive a diagnosis of a neurodevelopmental disorder by age 12 months, according to new research.
Andrea G. Edlow, MD, MSc, with Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues examined data from 18,355 births between March 1, 2020, and May 31, 2021, at eight hospitals across two health systems in Massachusetts.
Of these births, 883 (4.8%) were to individuals who tested positive for SARS‐CoV‐2 during pregnancy. Among the children exposed to SARS‐CoV‐2 in the womb, 26 (3%) received a neurodevelopmental diagnosis, including disorders of motor function, speech and language, and psychological development, by age 1 year. In the group unexposed to the virus, 1.8% received such a diagnosis.
After adjusting for factors such as race, insurance, maternal age, and preterm birth, Dr. Edlow’s group found that a positive test for SARS-CoV-2 during pregnancy was associated with an increased risk for neurodevelopmental diagnoses at 12 months among boys (adjusted odds ratio, 1.94; 95% confidence interval, 1.12-3.17; P = .01), but not among girls.
In a subset of children with data available at 18 months, the correlation among boys at that age was less pronounced and not statistically significant (aOR, 1.42; 95% CI, 0.92-2.11; P = .10).
The findings were published online in JAMA Network Open
Prior epidemiological research has suggested that maternal infection during pregnancy is associated with heightened risk for a range of neurodevelopmental disorders, including autism and schizophrenia, in offspring, the authors wrote.
“The neurodevelopmental risk associated with maternal SARS-CoV-2 infection was disproportionately high in male infants, consistent with the known increased vulnerability of males in the face of prenatal adverse exposures,” Dr. Edlow said in a news release about the findings.
Larger studies and longer follow‐up are needed to confirm and reliably estimate the risk, the researchers said.
“It is not clear that the changes we can detect at 12 and 18 months will be indicative of persistent risks for disorders such as autism spectrum disorder, intellectual disability, or schizophrenia,” they write.
New data published online by the Centers for Disease Control and Prevention show that in 11 communities in 2020, 1 in 36 (2.8%) 8-year-old children had been identified with autism spectrum disorder, an increase from 2.3% in 2018. The data also show that the early months of the pandemic may have disrupted autism detection efforts among 4-year-olds.
The investigators were supported by grants from the National Institutes of Health and the Simons Foundation Autism Research Initiative. Coauthors disclosed consulting for or receiving personal fees from biotechnology and pharmaceutical companies.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Like mother, like daughter? Moms pass obesity risk to girls
Girls between 4 and 9 years old were more likely to have high fat mass and a high body mass index if their mothers had excess adiposity – but this relationship was not seen between mothers and sons, or between fathers and sons or daughters, in a new study.
The researchers measured fat mass, lean mass, and BMI in the sons and daughters when they were age 4 (before a phenomenon known as “adiposity rebound”), ages 6-7 (around the adiposity rebound), and ages 8-9 (before or at the onset of puberty).
They also obtained measurements from the mothers and fathers when the offspring were ages 8-9.
The group found “a strong association between the fat mass of mothers and their daughters but not their sons,” Rebecca J. Moon, BM, PhD, and colleagues report.
“It would be important to establish persistence through puberty,” according to the researchers, “but nonetheless, these findings are clinically important, highlighting girls who are born to mothers with high BMI and excess adiposity are at high risk of themselves of becoming overweight/obese or having unfavorable body composition early in childhood.”
The mother-daughter relationship for fat mass appears to be established by age 4 years, note Dr. Moon, of the MRC Lifecourse Epidemiology Centre, University of Southampton (England), and colleagues.
Therefore, “early awareness and intervention is needed in mothers with excess adiposity, and potentially beginning even in the periconception and in utero period.”
Because 97% of the mothers and fathers were White, the findings may not be generalizable to other populations, they caution.
The results, from the Southampton Women’s Survey prospective cohort study, were published online in the Journal of Clinical Endocrinology & Metabolism.
One of the first studies to look at fat mass, not just BMI
Children with overweight or obesity are more likely to have excess weight in adulthood that puts them at risk of developing type 2 diabetes, cardiovascular disease, cancer, and osteoarthritis. Previous research has reported that children with overweight or obesity were more likely to have mothers with adiposity.
However, most prior studies have looked at BMI alone and did not measure fat mass, and it was not known how a father’s obesity might affect offspring or how risk may differ in boy versus girl children.
Researchers analyzed data from a subset of participants in the Southampton Women’s Survey of 3,158 women who were aged 20-34 in 1998-2002 and delivered a liveborn infant.
The current study included 240 mother-father-offspring trios who had data for BMI and dual-energy X-ray absorptiometry (DXA) scans (whole body less head).
Mothers were a mean age of 31 years at delivery and had a median pre-pregnancy BMI of 23.7 kg/m2.
The offspring were 129 boys (54%) and 111 girls.
The offspring had DXA scans at ages 4, 6-7, and 8-9 years, and the mothers and fathers had a DXA scan at the last time point.
At ages 6-7 and ages 8-9, BMI and fat mass of the girls reflected that of their mothers (a significant association).
At age 4, BMI and fat mass of the daughters tended to be associated with that of their mothers, but the 95% confidence interval crossed zero.
There were no significant mother-son, father-son, or father-daughter associations for BMI or fat mass at each of the three studied ages.
The study received funding from the Medical Research Council, the British Heart Foundation, the National Institute for Health and Care Research Southampton Biomedical Research Centre, the NIHR Oxford Biomedical Research Centre, the Seventh Framework Program, the Biotechnology and Biological Sciences Research Council, the Horizon 2020 Framework Program, and the National Institute on Aging. Dr. Moon has reported receiving travel bursaries from Kyowa Kirin unrelated to the current study. Disclosures for the other authors are listed with the article.
A version of this article originally appeared on Medscape.com.
Girls between 4 and 9 years old were more likely to have high fat mass and a high body mass index if their mothers had excess adiposity – but this relationship was not seen between mothers and sons, or between fathers and sons or daughters, in a new study.
The researchers measured fat mass, lean mass, and BMI in the sons and daughters when they were age 4 (before a phenomenon known as “adiposity rebound”), ages 6-7 (around the adiposity rebound), and ages 8-9 (before or at the onset of puberty).
They also obtained measurements from the mothers and fathers when the offspring were ages 8-9.
The group found “a strong association between the fat mass of mothers and their daughters but not their sons,” Rebecca J. Moon, BM, PhD, and colleagues report.
“It would be important to establish persistence through puberty,” according to the researchers, “but nonetheless, these findings are clinically important, highlighting girls who are born to mothers with high BMI and excess adiposity are at high risk of themselves of becoming overweight/obese or having unfavorable body composition early in childhood.”
The mother-daughter relationship for fat mass appears to be established by age 4 years, note Dr. Moon, of the MRC Lifecourse Epidemiology Centre, University of Southampton (England), and colleagues.
Therefore, “early awareness and intervention is needed in mothers with excess adiposity, and potentially beginning even in the periconception and in utero period.”
Because 97% of the mothers and fathers were White, the findings may not be generalizable to other populations, they caution.
The results, from the Southampton Women’s Survey prospective cohort study, were published online in the Journal of Clinical Endocrinology & Metabolism.
One of the first studies to look at fat mass, not just BMI
Children with overweight or obesity are more likely to have excess weight in adulthood that puts them at risk of developing type 2 diabetes, cardiovascular disease, cancer, and osteoarthritis. Previous research has reported that children with overweight or obesity were more likely to have mothers with adiposity.
However, most prior studies have looked at BMI alone and did not measure fat mass, and it was not known how a father’s obesity might affect offspring or how risk may differ in boy versus girl children.
Researchers analyzed data from a subset of participants in the Southampton Women’s Survey of 3,158 women who were aged 20-34 in 1998-2002 and delivered a liveborn infant.
The current study included 240 mother-father-offspring trios who had data for BMI and dual-energy X-ray absorptiometry (DXA) scans (whole body less head).
Mothers were a mean age of 31 years at delivery and had a median pre-pregnancy BMI of 23.7 kg/m2.
The offspring were 129 boys (54%) and 111 girls.
The offspring had DXA scans at ages 4, 6-7, and 8-9 years, and the mothers and fathers had a DXA scan at the last time point.
At ages 6-7 and ages 8-9, BMI and fat mass of the girls reflected that of their mothers (a significant association).
At age 4, BMI and fat mass of the daughters tended to be associated with that of their mothers, but the 95% confidence interval crossed zero.
There were no significant mother-son, father-son, or father-daughter associations for BMI or fat mass at each of the three studied ages.
The study received funding from the Medical Research Council, the British Heart Foundation, the National Institute for Health and Care Research Southampton Biomedical Research Centre, the NIHR Oxford Biomedical Research Centre, the Seventh Framework Program, the Biotechnology and Biological Sciences Research Council, the Horizon 2020 Framework Program, and the National Institute on Aging. Dr. Moon has reported receiving travel bursaries from Kyowa Kirin unrelated to the current study. Disclosures for the other authors are listed with the article.
A version of this article originally appeared on Medscape.com.
Girls between 4 and 9 years old were more likely to have high fat mass and a high body mass index if their mothers had excess adiposity – but this relationship was not seen between mothers and sons, or between fathers and sons or daughters, in a new study.
The researchers measured fat mass, lean mass, and BMI in the sons and daughters when they were age 4 (before a phenomenon known as “adiposity rebound”), ages 6-7 (around the adiposity rebound), and ages 8-9 (before or at the onset of puberty).
They also obtained measurements from the mothers and fathers when the offspring were ages 8-9.
The group found “a strong association between the fat mass of mothers and their daughters but not their sons,” Rebecca J. Moon, BM, PhD, and colleagues report.
“It would be important to establish persistence through puberty,” according to the researchers, “but nonetheless, these findings are clinically important, highlighting girls who are born to mothers with high BMI and excess adiposity are at high risk of themselves of becoming overweight/obese or having unfavorable body composition early in childhood.”
The mother-daughter relationship for fat mass appears to be established by age 4 years, note Dr. Moon, of the MRC Lifecourse Epidemiology Centre, University of Southampton (England), and colleagues.
Therefore, “early awareness and intervention is needed in mothers with excess adiposity, and potentially beginning even in the periconception and in utero period.”
Because 97% of the mothers and fathers were White, the findings may not be generalizable to other populations, they caution.
The results, from the Southampton Women’s Survey prospective cohort study, were published online in the Journal of Clinical Endocrinology & Metabolism.
One of the first studies to look at fat mass, not just BMI
Children with overweight or obesity are more likely to have excess weight in adulthood that puts them at risk of developing type 2 diabetes, cardiovascular disease, cancer, and osteoarthritis. Previous research has reported that children with overweight or obesity were more likely to have mothers with adiposity.
However, most prior studies have looked at BMI alone and did not measure fat mass, and it was not known how a father’s obesity might affect offspring or how risk may differ in boy versus girl children.
Researchers analyzed data from a subset of participants in the Southampton Women’s Survey of 3,158 women who were aged 20-34 in 1998-2002 and delivered a liveborn infant.
The current study included 240 mother-father-offspring trios who had data for BMI and dual-energy X-ray absorptiometry (DXA) scans (whole body less head).
Mothers were a mean age of 31 years at delivery and had a median pre-pregnancy BMI of 23.7 kg/m2.
The offspring were 129 boys (54%) and 111 girls.
The offspring had DXA scans at ages 4, 6-7, and 8-9 years, and the mothers and fathers had a DXA scan at the last time point.
At ages 6-7 and ages 8-9, BMI and fat mass of the girls reflected that of their mothers (a significant association).
At age 4, BMI and fat mass of the daughters tended to be associated with that of their mothers, but the 95% confidence interval crossed zero.
There were no significant mother-son, father-son, or father-daughter associations for BMI or fat mass at each of the three studied ages.
The study received funding from the Medical Research Council, the British Heart Foundation, the National Institute for Health and Care Research Southampton Biomedical Research Centre, the NIHR Oxford Biomedical Research Centre, the Seventh Framework Program, the Biotechnology and Biological Sciences Research Council, the Horizon 2020 Framework Program, and the National Institute on Aging. Dr. Moon has reported receiving travel bursaries from Kyowa Kirin unrelated to the current study. Disclosures for the other authors are listed with the article.
A version of this article originally appeared on Medscape.com.